7 15 672 https://www.nal.usda.gov/exhibits/speccoll/files/original/9fb3db86d5bc7d4267471cb6ea35f6ce.pdf 3c8832d6604c55e424c73dc491f693fa PDF Text Text ItemD Number °5257 AuthOT Costle, Douglas M. Corporate Author Report/Article TItto Typescript: Decision and Emergency Order Suspending Registrations for the Forest, Rights-of-way, and Pasture Uses of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) Journal/Book Title Year Month/Day February 28 Color D Number of Imagos 95 Descrlpton Notes Friday, March 01, 2002 Page 5257 of 5263 �I. Decision and Emergency Order Suspending Registrations for the Forest, Rights-of-way, and Pasture Uses of 2,4,5-Trichlorophenoxyacetic Acid C2,4,5--n INTRODUCTION During the past ten months, the Agency has been gathering information about 2,4,5-T through its Rebuttable Presumption Against Registration I RPAR) process in order to decide whether registration of this pesticide should be continued-l 43 FR 17116, April 21, 1978) . This review was prompted by studies showing that 2,4,5-T and/or its dioxin */ contaminant, 2 , 3 , 7 , 8-tetrachlorodibenzo-p-dioxin f f "{ TCDD) — , caused reproductive and oncogenic effects in test animals. During the public debate initiated by the 2,4,5-T RPAR, the Agency received reports that women living in the vicinity of Alsea, Oregon, had miscarriages shortly after 2,4,5-T was sprayed in the forest areas where they reside. The Agency investigated the circumstances surrounding these reported ^/ Current methods for manufacturing 2,4,5-T produce TCDD as a by-product of the manufacturing process. Although 2,4,5-T manufacturers attempt to remove this contaminant, TCDD cannot be completely removed. An EPA contract laboratory has measured the TCDD content in 16 recently produced commercial samples of technical grade 2,4,5-T from five different manufacturers. The contractor reported that the TCDD content in these samples ranged from not detectable to 0.025 ppm=(J'limit of detection: 0.01 ppm) [excluding higher values that the contractor reported as doubtful]. Therefore, because TCDD is present as a low-level contaminant in commercial samples of 2,4,5-T, references in this document to "2,4,5-T" or the "pesticide product" mean 2,4,5-T that is contaminated with TCDD. -1- �miscarriages and compared the frequency of miscarriage in the Alsea area with comparable data from a control area. The Agency has concluded that the use of 2,4,5-T over a six-year period in the Alsea area was related to a statistically significant increase in the frequency of miscarriages by women residents of the area, and that these miscarriages occurred shortly after the use of 2,4,5-T in the area where these women lived. Based on this and other information detailed below, I am ordering several emergency suspensions under FIFRA Section 6(c). These emergency suspensions immediately halt the distribution, sale/ and use of 2,4,5-T for forestry, rights-of-way, and pastures until the completion of further **/ administrative proceedings.— I am ordering emergency suspen- sion of these uses because I find that they pose an "imminent hazard" to humans and because I also find that an "emergency" exists because there is not enough time to complete a suspension hearing before the next spraying season. **/ Pasture is defined as land producing forage for animal consumption, harvested by grazing, which has annual or more frequent cultivation, seeding, fertilization, irrigation, pesticide application and other similar practices applied to it. Fencerows enclosing pastures are included as part of the pasture. -2- �II. LEGAL AUTHORITY A. Standards for Maintaining a Registration In order to obtain a registration for a pesticide under the Federal Insecticide, Fungicide, and Rodenticide Act£FIFRA) [7. U.S.C. 136 et seq.], a manufacturer must demonstrate that the pesticide satisfies the statutory standard for registration* That standard requires 1 among other things) that the pesticide perform its intended function without "unreasonable adverse effects" on the environment [FIFRA Section 3( c) f 5) ] . "Unreasonable adverse effect on the environment" means "any unreasonable risk to man or the environment/ taking into account the economic, social and environmental costs and benefits of the use of any pesticide" [FIFRA Section < bb) ] . In effect, this standard requires a finding that the benefits of each use of the pesticide exceed the risks of the use* The burden of proving that a pesticide satisfies the registration standard rests with the registrant and continues for as long as the registration remains in effect [Environmental Defense Fund v. Environmental Protection Agency, 510 F.2d 1292.1297 [ CADC, 1975) ; Environmental Defense Fund v. Environmental Protection Agency, 465 F.2d 528, 532 I CADC, 1972)]. Under Section 6 of FIFRA, the Administrator is required to cancel the registration, or change the classification, of a pesticide whenever he determines that the pesticide no longer satisfies the statutory standard for registration. -3- �B. Purpose and Standard for Suspending a Pesticide The suspension provisions in Section 61(c) of the statute give the Administrator authority to take interim action until completion of the time-consuming procedures required to reach final cancellation decisions. Under this Section/ the Administrator may suspend the registrations of a product and prohibit its distribution, sale, or use during cancellation proceedings upon a finding that the pesticide poses an "imminent hazard" to humans or the environment. "Imminent hazard" is defined by the statute to mean that: The continued use of a pesticide during the time required for cancellation proceedings would be likely to result in unreasonable adverse effects on the environment or will involve unreasonable hazard to the survival of a species declared endangered by the Secretary of the Interior under Public Law 94-135. As discussed above, "unreasonable adverse effects on the environment" means that the risks from use of a pesticide outweigh the benefits of its use. Thus, in order to find an imminent hazard, it is necessary to find that the risks of use during the period likely to be required for cancellation proceedings appear to outweigh the benefits. The Administrator may not suspend a pesticide without -4- �having issued a notice of his intention to cancel the registration/ or to change the classification, of the pesticide• Suspension is the Administrator's tool for quickly correcting a situation which endangers public health. The courts have repeatedly held that "the function of a suspension decision is to make a preliminary assessment of evidence/ and probabilities/ not an ultimate resolution of difficult issues" [Environmental Defense Fund v. Environmental Protection Agency, supra, 510 F2d at 1298]. "It is enough if there is a substantial likelihood [emphasis in original] that serious harm will be experienced during the year or two required in any realistic proj ection of the administrative '*• cancellation) process" [Environmental Defense Fund, Inc. v. Environmental Protection Agency/ 510 F2d 1292, 1297, I D . C . Cir. 1975) quoting from Environmental Defense Fund, Inc. v. Environmental Protection Agency, supra, 465 F2d 540< D.C. Cir. 1972)]. Moreover/ the registrant bears the burden of proof during a suspension proceeding because, as indicated above, the burden of proof under FIFRA always resides with the proponent of registration throughout the life of a registration, t See, e.g., Environmental Defense Fund v. Environmental Protection Agency, 510 F2d at 1297; Environmental Defense Fund v. Environmental Protection Agency/ supra, 465 F2d at 532.) -5- �C. Types of Suspension Proceedings In this order, I have begun emergency suspension proceedings. This is not the only type of suspension provided in FIFRA. Section 6(c) provides for two kinds of suspension proceedings: ordinary suspensions [FIFRA Section 6(c)(2)] and emergency suspensions 6(c)(3)]. [FIFRA Section I have chosen to discuss both kinds of suspension because the procedures applicable to each action are intertwined and because of the complexity of the suspension provision as a whole. (1) Ordinary Suspensions The Administrator may begin an ordinary suspension when he finds that action is required to prevent an "imminent hazard." An ordinary suspension is not effective immediately; instead, the Administrator is required to give registrants notice of his intent to suspend and to allow five days for them to request a hearing. hearing. Only a registrant may request a If a hearing is not requested within five days, the suspension order becomes final and is not reviewable by a court. If a hearing is requested, the Administrator is required to convene an expedited proceeding at which other interested persons can intervene. The sole issue at a hearing is whether an imminent hazard in fact exists. The procedures for conducting the hearing, with limited exceptions -6- �discussed below/ parallel the hearing procedures for an emergency suspension. The Administrator decides whether to affirm his imminent hazard determination at the conclusion of the hearing; if he does, he issues a suspension order. This order is accompanied by a notice of intent to cancel the registration, or to change the classification, of a j pesticide (if one has not previously been issued). A final order on suspension following a hearing is reviewable in the Court of Appeals. (2) Emergency Suspensions Before issuing an emergency suspension order, the Administrator is required to make two findings: (1) that the pesticide poses an "imminent hazard" and (2) that an "emergency" exists. An "emergency" exists when the situation "does not permit [the Administrator] to hold a hearing before suspending" [FIFRA Section 6(c)(3), 7 U.S.C. 136d(c)(3)]. The Agency interprets this statutory provision to mean that, if the threat of harm to humans and to the environment is so immediate that the continuation of a pesticide use is likely to result in unreasonable adverse effects - i.e. the risks outweigh the benefits - during a suspension hearing, the registration of any product for that use may be suspended -7- �*/ immediately— . An emergency suspension order is issued without prior notice to registrants and takes effect immediately; it remains in effect until the cancellation decision if no expedited hearing is requested. If an expedited hearing is requested on the issue of imminent hazard, the emergency order continues in effect until the issuance of a final suspension order. Registrants are given five days to request an expedited hearing. The hearing stage is to begin within five days of the Agency's receipt of the hearing request. Unlike the ordinary suspension situation, no party other than the registrant and the Agency may participate in the expedited hearing on the emergency order, except to file briefs. The procedures for conducting the hearing are otherwise the same as in an ordinary suspension. For both types of suspension, the hearing is to be conducted in accordance with 5 U.S.C. Sections 554,.556, and 557 except that ^/ The term "emergency" is not defined by FIFRA, and the statute in the emergency suspension section does not specifically require the Agency to balance benefits against health and environmental risk of pesticide use. An alternative reading would be that an emergency should issue whenever a risk could result from pesticide use during the time for conducting a suspension hearing. However, for the purpose of this proceeding I have decided to consider the risks and benefits in ordering an emergency suspension, just as I balance risks and benefits in deciding whether to register a pesticide or to take the pesticide off the market through a cancellation or ordinary suspension order. FIFRA is a risk/benefit statute, and I see no reason to depart from this balancing test in issuing emergency suspension orders. -8- �the presiding officer need not be a certified hearing examiner. For both types of suspension, the presiding officer shall have ten days from the conclusion of the presentation of evidence to submit recommended findings and conclusions to the Administrator• The Administrator shall then have seven days to issue a final order on the issue of suspension. FIFRA provides for a special appeal of an emergency suspension order to the District Court. If an administrative hearing is requested, an emergency suspension order is subject to immediate review in District Court by the registrant or by other interested persons with the registrant's consent. On the other hand, if no request for a hearing before the Agency is made, the emergency order becomes final and is not reviewable by any court [FIFRA Section 6(c)(2), 6(c)(3)]> The District Court action may occur simultaneously with the suspension proceeding before the Administrator. The District Court reviews only whether the emergency finding is supported. The standard for review by the District Court is very narrow--whether the order of suspension is "arbitrary, capricious, or an abuse of discretion, or whether the order was issued in accordance with the procedures established by law" [FIFRA Section 6(c)(4)]. -9- If the District �Court finds against the Agency, it may stay the suspension order until completion of the expedited suspension hearing. The District Court order may be appealed to the Appellate Court by either the Agency or the registrant, depending on the outcome. A final order on suspension, after a hearing before the Agency, may be reviewed in the Court of Appeals on an expedited basis even though related cancellation proceedings may not have been completed. III. SUMMARY OF FINDINGS A. Summary of Findings on Risks Numerous studies have clearly demonstrated that TCDD and/or 2,4,5-T contaminated with TCDDD can produce fetotoxic, teratogenic, and carcinogenic effects in experimental animals which have been exposed to these chemicals. I find that the occurrence of these effects in test animals indicates that humans who are exposed to TCDD and/or 2,4,5-T may experience comparable effects. A recent epidemiological study reported that women living in the vicinity of Alsea, Oregon ( an area where 2,4,5-T is used for forest management) , have a statistically significant higher incidence of spontaneous abortions (miscarriages) than women living in a control area. Specifically, the study shows that: -10- �( 1) The spontaneous abortion index for the Alsea study area where 2,4,5-T is used is significiantly higher than the index for urban or rural control areas where there is no known use of 2,4,5-T. () 2 There is a significant increase in the sponta- neous abortion index in the study area relative to the control area in the months of June and July: this increase follows by approximately two months a period in March and April when 2,4,5-T was used to control vegetation in the forested areas in which these women live. C 3) Statistical analyses of these data indicate that there is a significant correlation between the amounts of 2,4,5-T used in the study area during the spraying season and the subsequent increase in the spontaneous abortion index in the study area. This relationship between exposure to 2,4,5-T spraying and an increased incidence of miscarriages in humans is not surprising. This is the same relationship that has been demonstrated to exist in test animals through numerous animal studies. While there are uncertainties concerning the amount of 2,4,5-T and/or TCDO to which the study area women may have been exposed and concerning the precise route I or routes) of human exposure, the statistically significant incidence of miscarriages described above makes -1 1- �it reasonable for the Agency to conclude that these women in the Alsea Study area were exposed to 2,4,5-T. The Agency concludes that it is also reasonable to assume that individuals may be exposed to 2,4,5-T and/or TCDD who frequent or live in areas where 2,4,5-T is used in ways and under conditions which may cause them to experience exposure opportunities qualitatively similar to that experienced by the Study area women. The Agency has concluded that 2,4,5-T use patterns involving exposure opportunities qualitatively similar to those experienced by the Study area women are the forestry, rights-of-way, and pasture uses of 2,4,5-T. The Agency has identified pesticide applicators and persons involved in pesticide application support activities, and persons living in or frequenting areas of 2,4,5-T use as the principal groups of individuals who may be exposed as a result of the forestry, rights-of-way, and pasture uses of 2,4,5-T. Based upon the animal test data and other information, including the Alsea study, the Agency has concluded that individuals exposed to 2,4,5-T and/or TCDD may experience adverse reproductive effects and cancer. Accordingly, the Agency concludes that it is prudent to regard individuals who may experience exposures qualitatively similar to those experienced by the Study area women as a result of the forestry, rights-of-way, and pasture uses, as -12- �individuals who may suffer adverse reproductive effects or cancer as a result of these uses of 2,4,5-T. B. Benefits of 2,4,5-T Use During the Cancellation Proceedings The suspended uses J forestry/ rights-of-way, and pastures) comprise about 74% of the estimated 9.3 million pounds of 2,4,5-T used annually in the United States. 2,4,5-T controls a wide variety of weeds at relatively low cost • I estimate that the economic impact of this suspension action will be small* considerations* This finding is based on several The inherent flexibility in the treatment schedules permits delays in treatment during an estimated two-year suspension period. Alternative chemical, mechanical, and manual control treatments are available and are being used. The availability of these alternatives will minimize the impacts of suspension on those acres which require treatment during the suspension period. ^ 1) The Forestry Use The forestry use comprises 28% of 2,4,5-T use. 2,4,5-T's advantage is its ability to control a wide sprectrum of weeds without damaging the treated trees. -13- �Forest managers take measures to control weeds on softwood forests on two maj or occasions during the approximately 50-year life of a commercial forest: ( 1) the preparation stage designed to clear a site of potentially damaging vegetation prior to planting, and 1 2) the release stage designed to free young trees I 3 to 10 years old) from weed and hardwood competition in order to promote extensive growth. I have found that the use of 2,4,5-T is not necessary for site preparation* time. 2,4,5-T is used only 20% of the Other chemicals, mechanical or manual, clearing methods, or burning can be equally effective in giving newly-planted trees the opportunity to grow. The alternatives are more expensive. A two-year suspension of 2,4,5-T use for release treatments would have no serious effect because the treatments could be delayed for two years without impairing tree growth. Alternatives are generally available where weed growth makes treatment necessary. Finally, the impact on consumers of wood products is likely to be small. t 3) The Rights-of-Way Use 2,4,5-T is used to control woody and herbaceous plants on railroads, highways, electric transmission lines, and pipelines. The rights-of-way use covers 41% of total 2,4,5-T usage. -14- �Chemical, mechanical, and manual methods of control are also used on righta-of-way acreage. more than one method is common practice. Use of The cost of 2,4,5-T is less than chemical alternatives for some methods of application, more expensive for others. Many rights-of-way managers who have scheduled 2,4,5-T use during the suspension period are likely to postpone treatment entirely. Managers will likely use alternatives when plant growth is rapid. Even if all acres were treated with alternatives, I estimate that the additional cost of treatment on rights-of-way during suspension would not have a significant impact on users' revenues or operating costs. -•£ 4) The Pasture Use Weed control in pastures is now practiced on only about 1.0 million out of about 101 million acres of pastureland. There are effective chemical and/or mechanical control alternatives for all weed species in all regions. The maj or result of suspension on pastureland would be a delay in treatment on much of the acreage scheduled for treatment due to the inherent flexibility of decisions whether to treat. The economic impacts of a two-year suspension would be of little or no consequence. -15- �C. Summary of Findings on Imminent Hazard =Q 1) The Forestry Use In order to find an imminent hazard, I must find that the risks of use during the period likely to be required for cancellation proceedings appear to outweigh the benefits* The Alsea study, establishing a correla- tion between use of 2,4,5-T in forest management and miscarriages in humans, coupled with animal studies showing similar effects, indicates that there is a substantial likelihood that serious harm could result to persons with qualitatively similar exposures from the forestry use of 2,4,5-T. Aerial application, a major forest treatment method, may result in drift and increased exposure potential* This hazard to human health clearly outweighs the benefits of 2,4,5-T use during the cancellation period. The economic impacts of suspension are small because of the flexibility of treatment schedules and the availability of alternatives. Hence, I find that an imminent hazard exists for the forestry use of 2,4,5-T. 1 2) The Rights-of-Way Use For the reasons discussed below, the use patterns of the rights-of-way use create the same, or greater, potential for human exposure as the forestry use. In broad terms, considerable exposure potential exists due to the -16- �large numbers of persons living near rights-of-way and the likelihood of drift from the widespread use of aerial application. Hence/ the rights-of-way use results in a hazard to human health which in my j udgment outweighs the corresponding benefits. Although rights-of-way is the biggest 2,4,5-T use, a use moratorium during the cancellation proceedings would not have a significant economic impact because many rights-of-way managers are likely to postpone treatment entirely during the suspension proceedings; if they do treat/ alternatives are available. Therefore, I find that an imminent hazard exists for the rights-of-way use during the cancellation proceedings. I 3) The Pasture Use For the reasons discussed below, the application of 2,4,5-T on pastures presents exposures qualitatively similar to the forestry use, and hence the risk posed by 2,4,5-T use to human health is of concern. The exposure risk may be lower than for forests and rights-of-way. The principal application technique is spot spraying with knapsack equipment, which has less drift potential than aerial application. The benefits, however, are marginal at most. Weed control is practiced on less than 2% of pasture acreage, showing the relative unimportance of chemical or other treatments. Treatment can ordinarily be delayed or -17- �dispensed with entirely. In any case, there are effective chemical and/or mechanical control alternatives for all species in all regions of the United States. Thus, while the risks to human health from the pasture use appear to be lower than from the rights-of-way and forest uses, the economic impact of two-year suspension of the pasture use is of little or no consequence. I find that an imminent hazard exists for 2,4,5-T usage on pastures because the risks outweigh the benefits of use during the cancellation proceedings. D. Summary of Findings on Emergency As previously discussed, I have interpreted the statutory provision on emergency suspensions [FIFRA Section 6( c)( 3) ] to require a preliminary balancing of risks against benefits of use during the time for holding a suspension hearing. Hence, an emergency finding involves two issues: ( 1) immediate intervention is required because there is no time to hold a suspension hearing before the next period of pesticide use; and I 2) the risks outweigh the benefits during the time for holding the suspension hearing. At the end of the suspension proceeding, I have discretion to affirm, modify, or reverse my suspension order. -18- �C 1) The Forestry Use There is not enough time to hold a hearing before the next forest spraying season. Much of the year's treatment generally occurs between March and May. I am advised that in some parts of the Pacific Northwest, spraying is about to begin or has already begun. Hence, assuming 2,4,5-T use on forests poses unreasonable adverse effects, immediate action is required to stop 2,4,5-T use. The risks posed by 2,4,5-T forestry use clearly outweigh the benefits of use during the suspension proceeding. The Alsea epidemiological study suggests that persons in the vicinity of forest spray are being exposed to the potential dangers of 2,4,5-T use. These people are about to be exposed to almost one year's dose of 2,4,5-T applications in the next two months. The emergency suspen- sion proceeding is anticipated to run from March through June I see discussion in Section V) . Hence, by the time the suspension hearing is over, it will be too late to halt much of this year's spraying. Considering benefits, the economic consequences from a three-month delay for the completion of suspension proceedings are very small. Much of the scheduled treatment can readily be deferred for this short a period of time. -19- �In any case, alternatives are generally available to prevent reductions in tree growth where treatment is considered essential. Accordingly, I find that an emergency exists for the forestry uses of 2,4,5-T. Therefore, I am ordering immediate suspension of all 2,4,5-T registrations for these uses of 2,4,5-T. ( 2) Rights-of-Way Use 2,4,5-T is applied on rights-of-way I railways, highways, electric transmission lines, and pipelines) during the spring growing season, which starts in March in some parts of the country. Additionally, some methods of application on rights-of-way may be year-round. Hence, there is not enough time to hold a hearing before humans are exposed to the risks to their health presented by this chemical. The risks of 2,4,5-T use far outweigh the benefits during the time for holding a suspension hearing. The potential for human exposure from the rights-of-way use during this period is not inconsiderable even though the use season is not limited to the March-June suspension proceeding period. Large numbers of people live near rights-of-way areas, and aerial application is an important application method. On the other hand, little economic -20- �harm will result from a three-month use moratorium. Use on rights-of-way can generally be deferred for this short period of time* At any rate/ alternatives are available* Chemical alternatives are cheaper than 2,4,5-T for some application methods, including aerial application. Accordingly, I find that an emergency exists for the rights-of-way use of 2,4,5-T. Therefore, I am ordering an immediate suspension of all 2,4,5-T registrations for the use of 2,4,5-T on rights-of-way. C 3) Pasture Use The application of 2,4,5-T to restrict weed growth on pastures is expected to occur in March in some parts of the country and in even more areas before the anticipated completion of the suspension proceeding in June. Hence, emergency measures are required since I believe that the pasture use poses the risk of unreasonable adverse effects to human health during the suspension hearing. The pasture use presents the risk of exposing innocent bystanders because residences are scattered pastureland areas. throughout The risk to humans from 2,4,5-T use on pastures may be lower than from use on forests and rights-of-way, because aerial application is used on forests and rights-ofway and not on pastureland. On the other hand, the benefits -21- �of use during the 3 to virtually nil. 4 month suspension period are Treatment can most certainly be postponed during this short period. In any case, there are effective chemical and/or mechanical control alternatives for all weed species in all regions of the country. Accordingly, I find that an emergency exists for the pasture use of 2,4,5-T. I am therefore ordering an immediate suspension of all 2,4,5-T registrations for the use of 2,4,5-T on pastures. IV. BASIS FOR FINDINGS CONCERNING IMMINENT HAZARD AND EMERGENCY In Section III of this notice, I have presented a summary of my findings that an imminent hazard and emergency exist for the forestry, pasture, and rights-of-way uses of 2,4,5-T. The data, information, and analyses upon which these findings are based are detailed below. A. Findings Relating to Adverse Effects in Test Animals (1) Adverse Reproductive Effects in Test Animals This section presents the test animal data upon which I relied in finding that exposure to TCDD and/or 2,4,5-T is likely to result in adverse reproductive effects in humans. Except as specified below, these data were derived from studies in which pregnant rodents were orally exposed to -22- �TCDD and 2,4,5-T during the second trimester of gestation by daily gavage or in which primates were chronically exposed before mating. The pregnant rodents were sacrificed shortly before the scheduled birth of the offspring, and the fetuses were examined for abnormalities. The Agency has extracted key data for presentation in this report of findings. Experimental details and descriptions of the underlying data are presented in the 2,4,5-T RPAR notice and in the published literature. C *0 Exposure of Test Animals to TCDD TCDD produces fetotoxic effects such as death and reduced fetal size; skeletal deformities such as cleft palate and clubfoot; injury to internal organs such as intestinal bleeding, intestinal lesions, and abnormal kidneys; and post-partum effects such as reduced survival. These effects appear in several different rodent strains and species, occur in all of the litters in some dose groups, and occur at doses at least as low as 0.01 ug TCDD/kg. The repeated and regular appearance of several different forms of damage to test animals of several different strains and species -23- �indicates that TCDD is a teratogenic and fetotoxic agent in mammals. (A) Fetotoxic and Embryolethal Effects Fetotoxic and embryolethal effects have been reported for at least three different mouse strains, two different rat strains, and one strain of subhuman primates exposed to TCDD during gestation. For example, in studies using generally low-dose regimens of TCDD, Neubert and Dillmann reported that resorption sites (resorbed or dead embryos) occurred in 54% (7/13) of the litters at 0.3 ug/kg and in 100% (3/3) of the litters at 9.0 ug/kg for NMRI mice, compared to 24-32% (23/95 and 24/65) of litters exhibiting resorptions in control animals which had not been exposed to TCDD. Sparschu et al. reported resorption of 100% (110/110) of the fetuses in Sprague-Dawley rats exposed to 8 ug TCDD/kg, compared to 20% resorption (63/309) of the fetuses from the control animals. Khera and Ruddick reported 100% (77/77) resorption of fetuses at 4 ug/kg and 36% (56/153) at exposures of 1 ug/kg in Wistar rats, compared to 2-7% (3/152 and 10/127) in the control animals. Smith et al. reported resorptions in 95% (18/19) of the litters of CF-1 mice exposed to 1.0 ug/kg, compared to 74% (25/34) in the control animals; despite the high control incidence of resorptions in this study, the increased incidence in the experimental -24- �animals was statistically significant. In an abstract of a current study, Schantz et al. 1979) reported 57% ( 4/7) of pregnant monkeys aborted and one delivered a stillbirth. Two others on the 50-ppt diet failed to conceive, and two delivered normally. control animals all delivered normal infants. The eight Maternal toxicity was observed in some dose groups in some of these studies. Similar effects have been reported at higher dose levels of TCDD. Neubert and Dillmann reported that a single dose of 45 ug/kg to NMRI mice on day 6 produced resorptions in 100% ( 3/3) of the viable litters, compared to resorptions in 24% ( 23/95) of the control litters. Courtney reported an average of 87% mortality in 6 litters of CD-1 mice orally exposed to 200 ug/kg, compared to an average mortality of 6% in 15 vehicle control litters. This investigator also reported an average of 76% mortality in 6 litters of CD-1 mice exposed subcutaneously to 200 ug TCDD, compared to 14% in the six litters of control animals. Some of these studies also describe statistically significant weight depression in the surviving embryos I e.g., Sparschu et al.) . These and other studies also report that TCDD had no measureable adverse effects at some dose levels in some strains* For example, Khera and Ruddick report no fetotoxic effects at 0.125 ug/kg in Wistar rats, and Neubert and -25- �Dillmann report no teratogenic effects at 0.3 ug/kg in NMRI mice. Courtney and Moore reported that TCDD had no effect on fetal weight or embryonic mortality at 0.5 ug/kg in CD rats, and Sparschu et al. reported no effect at 0.03 ug/kg in Sprague-Dawley rats. Dow Chemical Company, a 2,4,5-T registrant, has recently completed a study of the effects of TCDD on reproduction in Sprague-Dawley rats exposed to low dose-levels of this chemical for three generations. The registrant concluded that "impairment of reproduction was clearly evident among rats ingesting 0.01 or 0.1 ug TCDD/kg per day. Significant decreases were observed in fertility, litter size, gestation survival, post-natal survival, and postnatal body weight." In addition, exposure to 0.001 ug TCDD/kg per day, the lowest level tested in this study, resulted in statistically significant increases in the percentage of pups dead at birth and/or dying before the */ end of three weeks of life in some generations.— ±/ Dow Chemical Company has claimed that the results of this study are "trade secret" or "confidential." An injunction issued on April 4, 1978, in the case of Dow Chemical Co. v. Costle, Civil Action No. 76-10087, U.S. District Court for the Eastern District of Michigan =•". Northern Division) , arguably precludes EPA from disclosing the data from this study at the present time. Although the relevant provisions of FIFRA have since been amended to allow disclosure of data such as this [see, e.g., FIFRA Sections 1GC(d) and 10( g) ] , the injunction has not yet been modified. EPA intends to promptly request the Court to modify the injunction, but until this has been done the Agency will not publicly disclose the data from the study. The summary presented in the text of this Order does not, in EPA's opinion, constitute disclosure of the allegedly "trade secret" data submitted by Dow and would not cause any harm to Dow 1 s legitimate competitive interests. The data from the study may be made available to any party in a suspension or cancellation proceeding under an appropriate protective arrangement. -26- �Although the experimental protocols and strains differ for the several studies cited, in each case TCDD significantly increased the incidence of resorbed embryos or stillborn animals relative to the rate observed in control animals not exposed to TCDD. The regular occurrence of embryonic death in studies by different investigators in primates and in different rodent strains indicates that exposure to TCDD during mammalian gestation may result in the death of the embryos and related maternal reproductive failure• { ii) Skeletal Anomalies Skeletal defects appear in six studies involving four different mouse strains. Courtney and Moore report the following incidences of cleft palate in the indicated strains exposed to 3 ug/kg TCDD: 71% ( 5/7) C57BL/6 mice, compared to none I 0/23) ( 2/9) in litters of in the controls; 22% in litters of DBA/2 mice compared to none ( 0/23) in the controls; and 30% ( 3/10) for CD-1 mice, compared to none (0/9) in the controls. Neubert and Dillmann, also using 3 ug TCDD/kg, reported 29% ( 7/24) of the viable litters had fetuses with cleft palate for NMRI mice compared to 6% ( 10/160) of the control litters. Smith et al. reported cleft palate in 71% I 10/14) of CF-1 mouse litters at 3 ug/kg, compared to none (0/34) in the controls. -27- �In exposures of shorter duration, Moore et al. reported cleft palate in 86% (12/14) of C57BL/6 mouse litters exposed on days 10-13 to 3 ug/kg, compared to none (0/27) in the control litters. Neubert and Dillmann reported cleft palate in 71% (10/14) of litters of NMRI mice exposed to a single 45 ug/kg dose on day 11, compared to 6% (6/95) of litters in the controls. Courtney and Moore reported no cleft palate in any of the litters in CD rats exposed to 0.5 ug/kg. Similarly, Khera and Ruddick, using Wistar rats, reported that the occurrence of the skeletal anomalies in the fetuses exposed to 2.0 ug/kg was comparable to the rate for the untreated animals. (iii) Injury to Internal Organs Exposure to TCDD produced injury to the kidneys and intestinal tracts of at least five different mouse and rat strains. Smith et al. reported 28% (4/14) of litters with kidney anomalies at 3 ug/kg in CF-1 mice, compared to none (0/34) in the controls. Moore et al. reported 100% (14/14) of litters with kidney anomalies in C57BL/6 mice exposed to 3 ug/kg on days 10-13, compared to none (0/27) in the control litters. Courtney and Moore reported kidney anomalies in 100% (10/10) of the litters of CD-1 mice at 3 ug/kg, compared to 33% (3/9) in the controls, and 67% (4/6) -28- litters �with abnormal kidneys in the CD rat at 0.5 ug/kg as compared to none (0/9) in the control litters* Sparschu et al. reported hemorrhages or lesions of the intestine of 36% (36/99) of the fetuses of Sprague-Dawley rats exposed to 0.5 ug/kg, compared to none (0/246) in the control fetuses. (b) Exposure of Test Animals to 2,4,5-T Cleft palate, high incidences of fetal mortality, reduced fetal weight, and other indicators of injury to the developing fetus have been reported in several studies in which test animals were exposed to 2,4,5-T contaminated with varying levels of dioxin. Some of these effects have been reported in test rodents at maternal doses as low as 10 mg/kg 2,4,5-T containing no detectable TCDD (limit of detection: 0.5 ppb). For example, Neubert and Dillman (1972) studied the effects of 2,4,5-T contaminated with dioxin in NMRI mice. Using 2,4,5-T with 0.05 ppm TCDD, these investigators reported resorptions in 57% of the litters and cleft palate in 71% of the litters at 60 mg 2,4,5-T/kg, compared to 24-32% resporptions and 6% cleft palate in the controls. -29- �Similarly/ Courtney and Moore t 1971) reported that oral exposure of CD rats to 80 mg/kg 2,4,5-T containing 0.5 ppm TCDD led to 52% fetal mortality per litter, compared to 3.4% in the controls. At this dose, kidney anomalies were observed in 50% of the litters, compared to none in the controls, but none of the fetuses had cleft palate at any dose. However, subcutaneous injection of 100 mg/kg 2,4,5-T containing 0.05 ppm TCDD led to cleft palate in 40% of the litters of CD-1 mice, compared to none in the controls. The Dow Chemical Company, a 2,4,5-T registrant, has recently completed a study I Smith et al. 1978) of the effects of 2,4,5-T {.containing less than 0.5 ppb TCDD) on reproduction in Sprague-Dawley rats exposed to 2,4,5-T for three generations. The registrant reports that exposure of these animals to 10 and/or 30 mg 2,4,5-T/kg per day resulted in statistically significant increases in the frequency of stillborn rat pups, and/or decreased */ survival of the pups that were born alive.— ^/ Dow Chemical Co. has also requested confidentiality for the results of this study. The discussion in the footnote in Section IV. A fX1 XXa) J i) also applies to these data. -30- �(c) Other Effects in Test Animals Recently/ Highman et al. showed that impaired fetal kidney development followed maternal treatment with 120 mg/kg of 2,4,5-T on days 6-14 of gestation. The im- paired development was associated with a significant reduction in cellular alkaline phosphatase. TCDD has been found to induce delta aminolevulenic acid synthetase (ALA) in chick embryos with as little as 1.5 ng/egg, and Goldstein et al. found a two-fold induction of ALA in C57BL/6 mice as a significant 2,000-fold accumulation of porphyrins in the liver occurred when compared to controls after treatment with 25 ug/kg of TCDD. Abnormal porphyrin synthesis occurred in female rats when treated in a chronic study at 0.01 ug TCDD/kg per day (Kociba et al. 1977). Alkaline phosphatase and gamma glutamyl transferase levels in female rats on 0.1 ug/kg significantly increased when compared to controls. (2) Oncogenic Effects in Test Animals (a) Exposure of Test Animals to TCDD The Carcinogen Assessment Group (CAG) has concluded that TCDD induces carcinogenic responses in mice and rats at exceedingly low dose levels and that these effects, together with data showing that TCDD is mutagenic, constitute substantial evidence that TCDD is likely to be a human carcinogen. -31- �Oow Chemical Company, a 2,4,5-T registrant, studied the effects of TCDD on male and female Sprague-Dawley rats exposed to 0.022, 0.220, or 2.2 ppb TCDD. CAG agrees with the registrant's conclusion that there is a statistically significant increase in the incidence of heapatocellular carcinoma in female rats exposed to 2.2 ppb TCDD. In another study using Sprague-Dawley rats, Van Miller reported that 1 ppb and 5 ppb TCDD produced a carcinogenic response in the livers of male Sprague-Dawley rats. These observations tend to confirm the registrant's observations that TCDD produces an oncogenic response in the livers */ of male Sprague-Dawley rats.— Further, a preliminary report of a not-yet-completed National C.ancer Institute study tends to confirm these observations of a carcinogenic response in rats. A contractor for the National Cancer Institute has reported that TCDD is carcinogenic in the rats and mice used in that study. CAG also emphasized that, at low levels, TCDD is a potent inducer of arylhydrocarbon hydroxylase, an enzyme system that contains an enzyme that is known to mediate the formation of epoxides, compounds which are potentially active carcinogenic metabolites. V The CAG and an EPA audit found that this study had major shortcomings in design and conduct that limited the reliability of the data developed at dose levels lower than 1 ppb. -32- �GAG also reported that TCDD is mutagenic in the Ames test without the metabolic activation system. Its mutagenic activity is exhibited by frameshift mutations caused by intercalation between base-pairs of DNA. (b) Exposure of Test Animals to 2,4,5-T On the basis of its review of 10 chronic toxicity studies, eight using mice and two using rats, CAG has concluded that there is no significant evidence in the completed studies that 2,4,5-T is carcinogenic in these species* Specifically, CAG reported that exposure to 3, 10, or 30 mg 2,4,5-T/kg (TCDD not detectable at detection limits ranging from 0.12 to 0.33 ppb) does not have carcinogenic effects in Sprague-Dawley rats. Preliminary data from a rat study in progress are also negative. Nonetheless, these findings do not negate the cancer-causing potential of 2,4,5-T as commercially produced since it contains the TCDD contaminant. CAG's review of the design and conduct of other studies disclosed that testing in mice is inadequate because the maximum tolerated dose may not have been used in some of the studies in which mice showed no carcinogenic response, and because there were significant defects in the design and execution of a study for which the authors -33- �initially reported a statistically significant increase in tumors in female mice. B. Findings Relating to Risk to Humans (1) (a) Study of Miscarriages in Alsea, Oregon General Discussion In response to the 2,4,5-T RPAR notice, a group of eight women informed the Agency that they lived within 12 miles of Alsea, Oregon, where 2,4,5-T is used in forest management and that they had experienced a total' of 13 miscarriages between 1972 to 1977. In their letter, the women presented information showing that most of their miscarriages occurred eight to ten weeks after conception and followed by four or six weeks the date of the spring application of 2,4,5-T in the forest areas in which these women reside. The women indicated their belief that this information suggested that the unusually high number of miscarriages in their group was related to the use of 2,4,5-T. The effects which these women reported were comparable to the embryolethal and fetotoxic effects observed in test animals that have been exposed to 2,4,5-T and/or TCDD. Moreover, because embryos are particularly susceptible to the harmful or lethal effects of fetotoxic or teratogenic agents during the early stages of pregnancy, the occurrence of these miscarriages within approximately two months of the use -34- �of 2,4,5-T in the Alsea area suggested a possible relationship between the use of the pesticide and the miscarriages reported for this group of women. For these reasons/ the Agency began an epidemiological study to determine if the occurrence of the spontaneous abortions in the entire Alsea area1', parts of three counties comprising about 1/600 square miles) bore any relation to the use of 2,4,5-T in the area. To answer this question, the Agency gathered informa- tion and data from hospitals on the occurrence of spontaneous abortions in the Alsea Study area and compared these data to comparable data from a rural area where there was little or no known use of 2,4,5-T or other dioxin-contaminated phenoxy herbicides 1 Control area) • Data on spontaneous abortions from an Urban area near Alsea were also reviewed for the study. The Agency1 s preliminary analysis of the data generated through this study indicates that: */ ( 1) The spontaneous abortion index— \ hospitalized miscarriages per 1,000 births) for the Alsea Study area where 2,4,5-T was used was significantly greater than the index for the Urban and Control areas where there was little or no known use of 2,4,5-T; ^/ The investigators determined the spontaneous abortion index by relating the number of hospitalized spontaneous abortions to the number of live births, corresponding to month of conception. The ratio derived in this way is expressed as abortions/1,000 births, related to month of conception, and permits comparison between areas of different total population size. The index is based on a five-month moving average for births to correspond with monthly miscarriages for terms up to 20 weeks £ about five months) . -35- �(2) There was a dramatic increase in the spontaneous abortion index for the Study area relative to the Urban and Control areas in the months of June and July; this increase followed, by approximately two months, a period in March and April when 2,4,5-T was used to control vegetation in the forested Study area; and (3) Statistical anlyses of these data indicate that there was a significant correlation between the amounts of 2,4,5-T used in the Study area during the spraying season and the subsequent increase in the spontaneous abortion index in the Study area. In conclusion, the Agency's systematic survey of the occurrence of spontaneous abortions in an area of 2,4,5-T use indicates that there was an unusually high number of spontaneous abortions in the area, and that the incidence of spontaneous abortions may reasonably be related to the use of 2,4,5-T in the area. The data further indicate that the miscarriage experiences which the eight Alsea women reported to the Agency were representative of the experiences of the larger population of women living in the Study area. The data and information which provide the basis for these conclusions are summarized below. (b) Results and Analysis Comparison of the spontaneous abortion indices for the Study, Urban, and Control areas for the period from -36- �1972 through 1977 shows that women living in the Study area where 2,4,5-T is used were more likely to experience spontaneous abortions than women living in either the Urban or Control areas (Table 1). abortion index averaged 80.8 The six-year spontaneous for the Study area, compared to averages of 43*8 and 65.4 for the Urban and Control areas/ respectively. In addition to this general elevation in the Study area spontaneous abortion index, there was a striking increase in the Study area index for the months of June and July. During June, the index in the Study area was 130.4, compared to 44.9 respectively. and 46.0 in the Urban and Control areas, For July, the indices were 105.4 for the Study area, compared to 14.6 and 55.3 for the Urban and Control areas, respectively. These data are presented graphically in Figure A. The increased spontaneous abortion indices in the Study area during June and July are particularly significant when viewed in terms of data on the use of 2,4,5-T in the -37- �*/ Study area.— Spraying records for the Alsea area for the study period indicate that 2,4,5-T use occurs primarily between March 1 and April 30; substantially lower amounts of the pesticide are used during May and still lower amounts are used during July and August ^Figure B) . Examination of this information on the use of 2,4,5-T in light of data on the increased incidence of spontaneous abortions reveals ^/ The preliminary report inadvertently included 3,530 pounds of silvex as 2,4,5-T in the estimates of usage in the Study area. Conceptually, this flaw is not significant: 1) since its effect would merely modify slightly the very significant correlation coefficient between herbicide use and miscarriages; 2) the nature of the relationship between time of application and the miscarriages is expected to remain unchanged; and silvex contains TCDD and could be expected to result in the same effect. Nonetheless, the Agency immediately had the analysis rerun to determine whether specific change in numerical estimates result. Corrected 2,4,5-T use remained significantly correlated with miscarriages occurring 2-3 months laterC r».72; p<.01) . Combined silvex and 2,4,5-T spray data were also correlated with miscarriages since both compounds could be hypothesized to cause the observed effect due to a common TCDD contaminant. This analysis also showed strong correlation.between use of herbicides containing TCDD and miscarriages as would be expected on the basis of animal studies f r-.69; p<.02) . The relative insensitivity of the correlation to changes in quantity further demonstrates the inherent strength of the relationship between the basic use pattern and miscarriages occurring approximately 2 months later. -38- �Table 1. Monthly Spontaneous Abortion Index for the Study, , anAJTpirETo-i^Areas (Oregon, 1972-1977) Month ^StuoTy AreaS"' Lerban~ffr^a CorftrUl Are"^, Average 1 148.1 13^9 &2.Q 68.0 January February 82.2— March 93.8 April ' -"28. 1 53.2 43.9 48.1 61.9 61.9 47.0 97.5 68.8 89.9 50.8 63.2 68.0 130.4 44.9 46.0 73.8 .£0574} 14.6 55.3 58.4 August 88.1 31.8 79.8 66.6 September 46.0 49.6 85.3 60.3 October 76.2 54.8 50.5 60.5 November 76.7 19.6 54.3 50.2 December 70.3 45.6 94 . 5x 70.1 <130^1} 43.8 (6574) --^ 63.3 JteY fJune 1 1 July (Average -—49.3 -39- | 1 | 1 �Figure A. Plot of Monthly Spontaneous Abortion Index for the Study, Urban, and Control Areas Study Area Urban Area 130 . Control Area 120 110 100 . 90 x £ 80 . c H s 70 J o u 60 4 o J3 * 50 40 30 - 20 . 10 - o> 6. a. < « c 9 ••< 9 JC Month -40- a o (A o o > o o o O �Figure B. Pounds of 2,4,5-T Sprayed in Alsea Basin Accumulated by Respective Month, 1972 through 1977, Compared with Abortion Index for the Same Period Pounds Sprayed 9- — -* Abortion index 130 . 120 / A\ \ / \ / 110 - xA X £ c 80 f - H t! 60 . o A < 50 - 1-1 \ i \ \ \ 1 t \ 1 V •H \ Ift (J \ 1 \ . 4 x -u c \ 1 I e 70 o o o \ / 90 . 0 \ / 100 . - 5 1 0) M \ D> / \ N - 3 / \ I ^ •H -U U f^ / \/ I « a) \ V f Q CO 40 - C 3 O 30 - cu - 1 20 -f" 10 1 i ' e 1 .a M M i >i i C ^ O» 14 ^ h X * X >0 fa « «n Month -41- o o o z S o �that this increase occurs approximately two months after the period of annual application of 2,4,5-T in the Alsea area. More refined analysis of these data on total abortions and total 2,4,5-T use by month during the period from 1972 to 1977 indicates that there was a statistically significant correlation between the abortion index in the Study area and the amount of 2,4,5-T used there* That is, when the increased spontaneous abortion index was compared to the amount of 2,4,5-T used each month in the areas where the women resided, the peak in the abortion index followed the peak in the spray pattern by approximately two months. This two-month lag time corresponds to the time predicted on the basis of the initial reports from the eight Alsea women. Because this correlation is statistically significant (p<0.01), there is strong reason to suspect that the spontaneous abortion increase was related to the use of 2,4,5-T. In view of the laboratory data establishing that 2,4,5-T and its contaminant TCDD have embryolethal effects in test animals and the susceptibility of the young embryo to fetotoxic and teratogenic agents, the increased spontaneous abortion index in an area of 2,4,5-T use may reasonably be interpreted to be a consequence of the exposure of women residents of the area to the 2,4,5-T used for forest -42- �*/ management.—' (2) (a) Seveso (Italy) and Vietnam Seveso, Italy On July 10, 1976, an accident at the ICMESA chemical plant in the Seveso region of Italy released 2 to 10 pounds of TCDD over a wide area. Hundreds of animals died, many area residents reported skin disorders, and an area of 110 hectares was evacuated. The most pertinent reports on this incident are provided by Reggiani (1977), Tuchman-Duplessis (1977), and Whiteside (1977; 1978). There is an apparent consensus that the reproductive epidemiology of Seveso, as presented, does not provide firm evidence of increased risk of spontaneous abortions or congenital malformations following the explosion. The ^/ The Alsea experience may not be an isolated incident. Reports of people adversely affected by exposure to phenoxy herbicides and/or TCDD have frequently appeared in medical and scientific journals. Recent summaries appear in IARC, NRCC, and U.S. Air Force documents on phenoxy herbicides and dioxins. Further, as a result of the 2,4,5-T RPAR, the Agency recently received numerous accounts of human health effects attributed to phenoxy herbicides and/or TCDD. These have been summarized in a document included in the record. The cumulative effect of these reported incidents suggests that people who live and/or work in areas of 2,4,5-T use may experience adverse health effects. -43- �Agency does not believe, however, that those investigations provide sufficient evidence of the absence of increased teratogenic risk in humans, either for dioxin in general or among the women of Seveso in particular. reasons for this conclusion: There are three (1) deficiencies in the available data; (2) methodologic deficiencies in the treatment and interpretation of the data which are available; and (3) suggestive indications in the available data that there may actually have been an increase in teratogenic risk in the area after the incident. Major points which illustrate deficiencies in the available data include: reproductive data in the area "either do not exist or are deliberately underreported" (Reggiani 1977); baseline rates for spontaneous abortions and congenital malformations in the area prior to the incident are not available; less than complete cooperation was obtained from local physcians and less than complete registration of pregnant women was attained (623 pregnant women were registered, but 2,513 deliveries were recorded in the area for July 1976 to May 1977; registration was thus about 25%); while 34 women obtained therapeutic abortions in the area, it is estimated that more than 2 times that number obtained them legally or illegally elsewhere (Whiteside estimates the number to be 4 times as many); and the conventional pitfalls of reproductive epidemiology could not -44- �be avoided 1 e.g., dependence on hospitalized spontaneous abortions for numerators and hospitalized births for denominators and different gestational cohorts for spontaneous abortions and births occurring in the same calendar period) . Maj or points which illustrate methodologic deficiencies in the treatment and interpretation of the available data include: estimates of the total amount of dioxin released ranged from 650 g^Reggiani 1977) to 11 kg tWhiteside) , to 130 kg;> Nature 11/28/76) ; estimates of exposure per person 2 2 varied from 29 ug/m ( Tuchman-Duplessis) to 5,620 ug/m ( Reggiani 1977); exposure was characterized by geographic zones, but reproductive data were gathered by geographic districts raising questions whether the zones were contiguous with the districts; spontaneous abortion rates were grouped in 6-month intervals, but congenital malformation rates for 1976 were grouped in 12-month intervals which could have masked an effect expected to be relatively acute or with a 2-3 month lag period; and the rates listed as "totals" for the two groups of districts in Table 13 ( in Reggiani 1977) appear to be averages of the district rates and as such are invalid and cannot be interpreted; the lack of chromosomal abnormalities in the products of therapeutic abortions is overemphasized since dioxin could conceivably produce a teratogenic effect without producing a concomitant mutagenic -45- �effect; and the wide interspecies variation seen in lethality studies should not automatically be applied to teratoqenic effects because it is known that very low doses are teratogenic in the rat I e.g., 0.01 ug/kg) and dioxin doses which caused teratogenic effects in rhesus monkeys were apparently as low as 2.5, 50, and 500 nanograms/kg. Suggestive indications of a possible teratogenic effect in humans, from the available data, includes the congenital malformation rate increased by 570% ( about 7-fold) between 1976 and the first five months of 1977 I Table 14, 0.13 to 0.87 per 100 live births) I in Reggiani 1977). The birth rate dropped "sharply" following the explosion and cows aborted and produced malformed offspring following the explosion. ! Whiteside) . A local doctor noted a "marked increase" in convulsions among infants. I convulsions could be delayed effects of neurotoxicity j.n utero) . [Whiteside]) . Cb) Vietnam A large amount of TCDD- contaminated herbicides were used in Vietnam during 1962-1971. Possible health effects have been reported upon retrospectively by groups entering Vietnam. Tung et al. charged that 2,4,5-T was responsible for much of the Down's Syndrome seen in -46- �[South] Vietnam. Crummer was quoted by Honoroff as having observed high incidences of children with Down's Syndrome. Tung et al. also noted a very significant increase in the Hanoi hospitals in hepatic carcinomas in the period 1962-1968 [1790/7911 cancer cases (10%), compared to 159/5492 (2.9%) for the period 1955-1961], It should be remembered that most of the accidents reported here were retrospective accounts. In the cases of Seveso and Vietnam, reporting was (and still is) at best piecemeal. The exposed populations contained numbers of highly mobile persons who could not be accounted for adequately. ( 3) (a) Exposure Analysis General Considerations There are two components to any pesticide-related risk: (1) the toxicological properties of a chemical, and (2) exposure to the chemical. The risk assessment is a summation of the conclusions in each of these areas. A highly toxic chemical may pose high risk even if exposure is low; conversely, a compound of low to moderate toxicity may pose high risks if exposure is high. Estimating probable exposure is difficult for a -47- �number of reasons. While it would be inappropriate to attempt a definitive discussion of these problems here, it is useful to note a few examples. First/ empirical data on exposure is less available than is toxicology data. Second, there are a number of exposure pathways which require consideration (e.g., inhalation, dermal absorption, ingestion of food residues, and ingestion of water residues). Third, the inherent complexities of the dynamics of a chemical's movement through the environment create formidable obstacles to describing any given exposure pathway. For example, the chemical may behave differently in various media depending upon a number of environmental factors which can vary at any one application site. Thus, even when some empirical data on a given route of exposure is available, there are often uncertainties concerning the applicability of the data to situations involving conditions which vary from those which obtained at the study site. The inherent difficulties of exposure assessment always create a troublesome problem for decision makers. These problems are of great concern in situations involving chemicals which appear to pose risks even at very low levels of exposure. As discussed above, the TCOD contaminant in 2,4,5-T is clearly such a chemical. For example, TCDD is carcinogenic in rats at doses as low as 1 ppb and fetotoxic in mice at doses as low as 0.01 ug/kg/day. -48- �Moreover, the complexities of exposure assessment are also amplified in situations involving persistent chemicals. This is because the length of time a chemical persists in the environment can increase the opportunities for movement of the chemical and confound attempts to eliminate pathways as pathways of concern. Time increases the possibilities of variation in enviromental factors affecting chemical mobility. The environmental persistence of 2,4,5-T is relatively short due to physical, chemical, and biological degradation processes. On the other hand, the contaminant TCDD has a much longer persistence in soil and is known to bioaccumulate in fish (Hatsumura and Benezet, 1973; Kearney et al., 1973). Generally, exposure assessments involve attempts at modeling the likely exposure potential through several pathways which are identified as pathways of principal concern. The exposure assessment typically will involve attempts to describe the movement of the chemical from the site of application to persons potentially at risk, using such empirical data as are available on the presence of the chemical at various intermediate points in the critical path. conservative assumptions based upon such things as knowledge about the behavior of similar chemicals, typical environmental conditions affecting the use site, and -49- �the like, are used to bridge inevitable gaps in the empirical data. The objective, however, is a simple one: to obtain a qualitative and (if possible) quantitative description of the likelihood that a given chemical will move from where it is applied to a given group of potentially exposed individuals• Since 2,4,5-T first surfaced as a subject of regulatory concern, determining potential exposure has been the critical issue on the risk side of the regulatory equation. Uncertainties about exposure resulted in suspension of regulatory action in 1974, and the launching of an ambitious project to generate exposure data (the "Dioxin Implementation Plan" or "DIP"). Primarily because of great difficulties encountered in developing analytical methodologies with sufficient sensitivity to measure the extremely low levels of TCDD which are of biological concern, the progress of the DIP has been disappointing. To date, it has yielded only fragmentary information. In my judgment, the information which has recently come to my attention as a result of the Alsea study constitutes a dramatic and troubling new point of departure for analysis of TCDD exposure concerns. As indicated above, these data show a striking relationship between 2,4,5-T use and increased incidences of spontaneous abortions among -50- �women residing in the use area. As further developed above, this effect is an effect which one would have predicted as a likely outcome of human exposure, based upon a body of animal data of almost unprecedented conclusiveness* The Alsea study, to be sure, contained no data showing actual exposure. However, concern for the health of humans who may be exposed to 2,4,5-T and its contaminant, TCDD, is heightened because scientists have not demonstrated that there is a level of exposure that has no adverse effects in */ humans.— Thus, in the face of the highly significant relationship which the study showed, and the animal data, I conclude it is reasonable and in the public interest to assume ** / that the women in the Alsea study were exposed to TCDD.—' ^/ A committe of the National Research Council of Canada recently agreed with the authors of the World Health Organization's monograph on TCDD that "for TCDD a no-effect level for man could not be established" (NRCC 1978). **/ I have found it prudent to suspend because data from the Alsea Epidemiological Study indicates that women experiencing adverse reproductive effects may have been exposed to 2,4,5-T. Information of this kind concerning a chemical's effects on human populations is rarely available. Before the Alsea Study was completed, Agency scientists developed preliminary exposure analyses for 2,4,5-T based on use information, assumptions, and modeling. Since I have information of adverse human effects correlating with the use of 2,4,5-T, I have chosen to rely on this correlation as a basis for regulatory action, rather than on exposure analyses based exclusively on use information and modeling. -51- �Moreover/ I also conclude that it is prudent to assume that individuals who frequent or live in areas where 2,4,5-T is used may be exposed to TCDD in ways and under conditions which may cause these individuals to be exposed in ways qualitatively similar to those experienced by the Study area women. As developed below, I find that 2,4,5-T use patterns likely to cause exposure opportunities similar to the exposure experienced by the Study area women are the forestry, rights-of-way, and pasture uses of 2,4,5-T. The Agency has identified pesticide applicators and persons involved in pesticide application support activities, and persons living in or frequenting areas of 2,4,5-T use as the principal groups of individuals who may be exposed as a result of the forestry, rights.-of-way, and pasture uses of 2,4,5-T. (b) The Alsea Study Area (i) Description of Area The Alsea Study Area comprises approximately 1,600 square miles of Oregon's forested Coastal Range centered around the "Alsea basin," an area of approximately 400 square miles. It is bounded on the west by approximately 70 miles of the Pacific Coast and extends inland for distances ranging from 10 to 35 miles. The Study area includes all but -52- �the northern and southern reaches of the Suislaw National Forest. Numerous commercially owned and Bureau of Land Management forested acreages are interspersed throughout this region. Mountain elevations of approximately 1,000 feet are not uncommon; peak elevation is slightly more than 4,000 feet. The principal rivers are the Siletz, Alsa, Yaquina and the Suislaw. Eastern fringes of the area drain eastward into the Willamette Valley. Maximum runoff is reached generally during the winter months as the result of storms off the Pacific occurring usually as rain. The Study area is predominantly rural. The four largest towns have a total population of 14,450. All other towns/villages have populations of less than 1,700. Alsea has a population of 400 (1970 census). In addition, many residences are scattered througout the forest areas. All of the nine women who were identified in the first phase of the investigation resided, at the time of pregnancy, in rural residences located within 12 miles of Alsea. (ii) Use Pattern 2,4,5-T is applied to the forests in the Alsea area almost exclusively by helicopter for control of undesirable vegetation such as red alder, vine maple, salmonberry, and thimbleberry. In general, the compound is used in the -53- �spring fMarch, April, or May) with a second application made, if needed, in middle to late summer ( July or August) . Over the six-year study period, 10,000 pounds of 2,4,5-T was distributed over a total area of approximately 7,000 acres. The usual practice was to treat any particular site approximately once every five years. However, contiguous stands could be treated in succeeding years. The spray program spans only a few days' time, with the duration depending on the number of acres to be treated and the weather conditions. To avoid contamination of water sources prior to 1978, the general application policy was to avoid spraying near homes and to provide for a single swath of 30 to 60 feet on each side of any maj or stream. In September 1978, the Oregon Forest Practices Act created guidelines which prohibited spraying within 500 feet of an inhabited residence or within 200 feet on either side of streams with fish and/or ones that are used for domestic water supplies. However, drift and runoff could contaminate surface waters. f iii) Population Exposed to the Herbicide Population of the Alsea Region is clustered in several small towns; there are also isolated homes and farmsteads in the forest area. Groups which may be traversing the forests of the Alsea Region include residents, workers engaged in forest management, incidental travelers, hikers, students, surveyors, and delivery persons. -54- �£ iv) Modes of Exposure The major method of dispensing 2,4,5-T in the Alsea Forest Region is by helicopters. Although the Oregon Forest Practices Act prohibits spraying near homes or streams, there appears a likelihood that residents and travelers of the Alsea Region might be directly exposed to 2,4,5-T during periods of application as a result of drift* Drift from a helicopter flying over a forest canopy can produce drift of the herbicide spray at significant distances from the path of the aircraft* Residents or travelers in the path of the spray might be doused with the pesticide spray. Exposure to the population from drift and direct contact is by the dermal'( exposed skin) and inhalation routes* Resident populations may also incur exposure to 2,4,5-T and TCDD subsequent to application. Waterborne residues are a possible route of exposure; other possible exposure routes include fish, wildlife, and other foods produced or found in the area* The fact that TCDD is somewhat persistent and bioaccumulative may enhance exposure possibilities. Furthermore, pesticide mixers, loaders, applicators, and other workers may be exposed to the pesticide -55- �\c () Comparison Between Presumed Exposure in The Alsea Study Area and Possible Exposure in Other Use Situations The Alsea Study shows a significant correlation between the use of 2,4,5-T in the Alsea area and increased incidence of spontaneous abortions within approximately two months after application* The Agency believes that it is prudent to assume that the women studied were exposed to 2,4,5-T. While the Agency cannot determine the actual routes of exposure, information about how 2,4,5-T is applied, population densities, and proximity of Study area residents to spray areas provides a basis for making assumptions about possible chances for exposure. That 2,4,5-T was applied by helicopter rather than by ground application methods in Alsea, enhanced the potential for exposure to 2,4,5-T from drift. Aerial application is a principal method for applying 2,4,5-T. A substantial amount of the 2,4,5-T applied in forests and on rights-of-way is applied aerially. In contrast, in pastures, application of 2,4,5-T usually is by spot treatment with knapsack spraying equipment. This method, causing less spray distribution than aerial application, lessens potential exposure from drift. -56- �Alsea inhabitants Live in towns and residences scattered throughout forests in which 2,4,5-T was applied* Effects occurred even though application near residences and streams was prohibited. The Study area women who experienced spontaneous abortions were residents of the area. Their exposure to 2,4,5-T may have occurred either while they were at home or while they were in nearby forest areas. Bystanders, workers engaged in forest management, people visiting the forests for recreational purposes, and others would have exposure potential similar to the exposure potential of the Study area women away from their homes. Because TCDD persists in the environment, such non-residents may have been exposed to 2,4,5-T and TCDD during or for some unknown length of time after application had occurred. The Study area women may have been exposed to 2,4,5-T or TCDD through ingestion of drinking water, fish, and wildlife. Residents are more likely to be exposed through this route than infrequent visitors to the spray area. Frequent visitors or workers in the area would have exposure potential similar to that of residents. All other forest areas in which 2,4,5-T is used are most obviously */ similar to the Study area.— ^/ Commercial forests are defined as those lands not withdrawn for non-timber purposes which are capable of growing 20 cubic feet of wood per year of desirable species. -57- �The use of 2,4,5-T to maintain rights-of-way involves exposure potential similar to the exposure potential of the Study area women: residents of the application area and workers and visitors who frequent the area may be exposed. The Agency estimates that a considerable number of people may be exposed to 2,4,5-T and TCDD as a result of the use of 2,4,5-T in non-urban areas to maintain rights-of-way. Rights-of-way uses include highways, railway lines, electric power lines, and pipelines. A principal method of applying 2,4,5-T is by aircraft, which was the method of application in the Alsea, Oregon area. The population that is most likely to be exposed are people who live in the path of the spray or in the area of */ drift.— A large potential exposure group would be comprised of people living along railroad tracks and along _V Factors which affect drift include wind direction and velocity, turbulence, relative humidity and air temperature, atmospheric stability, pesticide formulation, application equipment, and spray volume. For purposes of this analysis, the Agency conservatively estimated possible pesticide drift at 1/2 mile. The Agency notes, however, that pesticides could drift farther depending on the variables listed above. Some pesticide drift has been reported as far as 22 miles from target (EPA DRAFT: "Report to Congress/Study - ULV," p. 95). In addition, this same draft report estimates that percent of pesticide drift over 1,000 feet from the target variously ranges from a low of 10% to a high of 90%. -58- �highways* Other groups that may be exposed are those that live in forests or plains along power lines and pipelines. The residents may be exposed to TCDD through the diet for longer periods of time due to low levels of TCDD contamination in water and food. An additional potentially exposed group are people working in, or traveling through, the treated area. Exposure from the use of 2,4,5-T in pastures is **/ likely to be lower than the Study area*— Pastures are likely to be near farmhouses and small towns. The populations which may be exposed to 2,4,5-T include farm families, other rural residents, and workers in rural occupations. The predominant method of application for controlling brush in pastures is spot treatment with knapsack spraying equipment. The distribution of 2,4,5-T from this technique is lower than that from forestry and rights-of-way use, because this technique produces only short-range drift. Indirect exposure due to residues in food is possible. Generally, persons involved in applying pesticides have greater exposure to the chemicals than do residents of **/ Pasture is defined as land producing forage for animal consumption, harvested by grazing, which has annual or more frequent cultivation, seeding, fertilization, irrigation, pesticide application, and other similar practices applied to it. Fencerows enclosing pastures are included as part of the pasture. -59- �the area in which the pesticides are used. There is no reason to believe that this would not be true of 2,4,5-T. Therefore, the Agency is concerned about potential exposure to pilots, ground spray crews, mixers and loaders, and flaggers, all of whom are exposed to 2,4,5-T in the applica*/ tion process." For aerial application, the ground crew, including mixers and loaders of the aircraft, is the group with the highest potential for exposure by both dermal and inhalation routes, because they handle the concentrated formulations up to 41% of 2,4,5-T acid by weight) . The flaggers on the ground are exposed mainly by drift of the diluted spray deposited on their exposed skin, and to a lesser degree by inhalation. The pilots are expected to be exposed to smaller amounts of 2,4,5-T by dermal and inhalation routes because they sit in the enclosed cabin of the helicopter while applying the diluted herbicide spray. For the ground application techniques, the applicators and mixers are the workers running exposure risk. Inhalation exposure may be more significant when fine mist sprayers^ for example, ^/ In response to the 2,4,5-T RPAR, the American Paper Institute and the National Forest Products Association recently submitted a detailed study of aplicator exposure to 2,4,5-T during both areial and ground applications ; {2,4,5-T RPAR submission #1023H - 30000/26) . The results of this study indicate that workers who handled the pesticide concentrate had the highest exposure, followed by knapsack sprayer applicators, mist blower drivers, helicopter pilots, supervisors, and flagmen* -60- �spraying with a coarse spray. The reason for this is that smaller spray droplets are more readily absorbed through the lungs. C. Determination of Benefits The Agency has evaluated the potential economic impacts of suspending the forestry, pasture/ and rights-of-way */ uses of 2,4,5-T during 1979 and 1980.— The consideration of economic impacts stemming from a suspension is limited to a two-year period because the maximum proj ected length of a cancellation proceeding would be two years. A suspension order remains in effect only during a cancellation proceeding. Thus, only the impacts which would arise during this period would be at issue in a suspension. Any impacts which would be caused by a suspension, but which would be felt after **/ this period, are also considered.— ^/ The emergency suspension order will take effect immediately upon issuance of this Notice and remain in effect during any subsequent emergency suspension hearings. At the conclusion of the hearings, a decision will be made whether to continue or remove the suspension order during the ensuing cancellation proceedings. Ecomonic impacts are therefore separately evaluated for the 3 1/2 month period allocated for an emergency suspension proceeding as well as for the two years which may be required for a cancellation proceeding. **/ The Agency's analysis is based on information from a number of sources including RPAR rebuttal comments received by the Agency from registrants, users and other parties during the RPAR process; and the USDA-States-EPA 2,4,5-T RPAR Assessment Report^February 15, 19791 as well as other relevant data. Although the 2,4,5-T Report attributes a role to EPA, the final report has neither been completely reviewed nor approved by EPA. Therefore, although the Agency has relied on some portions of the report, it cannot and does not wish to adopt all portions of the report as reflecting the Agency position on matters discussed therein. -61- �2,4,5-T is registered for control of woody and herbaceous plants on rights-of-way, forestry, range, pasture/ and rice. The suspended uses ( rights-of-way, forestry, and pasture) comprise about 74% of the estimated 9.3 million pounds of 2,4,5-T active ingredient used annually in the U.S. Rights-of-way usage f3.8 million pounds) is the single largest use, comprising an estimated 41% of total annual usage; forestry f2.6 million pounds) and pasture usage t" 500,000 pounds) account for about 28 and 5%, respectively, of annual 2,4,5-T usage. Economic impacts of suspending forestry, pasture, and rights-of-way usage of 2,4,5-T during 1979 and 1980 were evaluated assuming all registered alternatives are available, except silvex which is also subject to suspension. The analysis often provides qualitative estimates of impacts due to a lack of data to support precise quantitative estimates. Economic impacts during 1979 and 1980 would depend upon the treatment options actually selected by users. For many, use of alternatives to 2,4,5-T during 1979 and 1980 would be optional ="{ i. e., could be delayed to a later year) • Other users might choose to use alternatives immediately. It is not possible to predict with precision which option may be selected by the many potential users of -62- �2,4,5-T during the suspension period. The Agency's analysis indicates that the suspension of 2,4,5-T (and silvex) for forestry, rights-of-way, and pasture uses during 1979/80 would not signficantly affect U.S. production or prices of major commodities and services from these sectors. Impacts on productivity and costs during the two years would generally be regional in nature but insignificant on the national level. Industry impacts would be nominal within the context of year-to-year variations in economic activity due to interaction of normal supply and demand forces, as affected by weather, general monetary and fiscal policies, international economic developments, etc . Economic impacts during the 3 1/2 month emergency suspension proceeding would negligible. The only noteworthy impact would involve the forestry use in which spring applications predominate in the Northwest. Even then, the impacts are nominal during the 3 1/2 month suspension proceeding. -63- �The minimal nature of the overall economic impacts follows from: ( a) the inherent flexibility of treatment schedules, permitting delays in treatment to ameliorate negative economic impacts of suspension; ( b) the existence of chemical, mechanical, or manual alternatives { or combinations) which are currently being used on these sites, even though they are not generally as cost-effective as 2,4,5-T; andr( c) the 2,4,5-T usage which normally would have occurred on the suspended sites represents a small fraction of the overall industry acreage { e.g., 0.2 percent of forestry acreage in the U.S.) ; concentrated acreages needing treatment with alternatives during the suspension period would occur only at the regional and local level. Each of the suspended uses is examined in detail in the following discussion. "( 1) Forestry Use There are about 500,000,000 acres of commercial -64- �*/ - in the U.S. of which 1.16 million acres (0.23%) are forests treated annually with 2,4,5-T. This herbicide can be used * */ at either or both of two stages in the p r o d u c t i o n — o f conifers (softwoods): (1) preparing sites for reforestation and (2) releasing young trees from hardwood competition. Each operation is undertaken once in the 50 year cycle of a softwood stand. 2,4,5-T as well as other chemical and non-chemical control methods may be used individually or in combination for site preparation and release. Use of 2,4,5-T for site preparation is not critical although it is cost effective. Several other chemical as well as non-chemical methods are also effective for site preparation. Picloram and 2,4-D, sometimes combined, are the most effective substitute chemicals. 2,4-D costs less than 2,4,5-T but controls a more limited spectrum of weeds. Because the release (weeding) operation is conducted after the seedling trees are in place, a selective herbicide which will not harm the seedlings is preferred. This is particularly true for pine; only 2,4,5-T provides control of ^/ Commercial forests are defined as those lands not withdrawn for non-timber purposes which are capable of growing 20 cubic feet of wood per year of desirable species. 5*V 2,4,5-T is sometimes used for other forestry herbicide operations, including rehabilitation or species conversion, fuel break maintenance, and timber stand improvement. The major forestry uses of 2,4,5-T are site preparation and release, which are the focus of this analysis. -65- �the wide variety of competing hardwoods without damaging the sensitive seedling pine. This often critical operation is most effective when performed two to ten years after establishment of the stand. If competing hardwoods are not suppressed, the seedlings may be overtopped, and stand growth and density may be decreased. The benefits of weed control for release and site preparation of conifer crops are increased yields at harvest time. For stands receiving no weed control for site preparation or release, annual growth can be substantially reduced on the most productive sites. Approximately 2 million acres of forests currently receive site preparation while approximately 1.5 million acres receive release treatments. 2,4,5-T is used for about 20% of the site preparation (1.16 million pounds on 414,370 acres) and about 51% of release treatments (1.48 million pounds on 749,320 acres). Other chemicals are often used for both practices, as well as hand, mechanical, and prescribed burning treatment. Herbicides are applied by broadcast foliage spray (aerial and ground) and by individual stem applications. Because it is selective and does not injure conifers, 2,4,5-T is the only herbicide widely applied by broadcast methods. Broadcast foliar applications account for 89%, and -66- �the remainding 11% are individual stem treatments* Other registered chemicals are applied almost entirely by stem treatments since they are damaging to conifers. Site preparation with other chemicals generally costs $20-50/acre, which is somewhat more than with 2,4,5-T treatment. Mechanical methods may range from $45-$200/acre. Prescribed burning is effective at $3-$14/acre in the East. In the Pacific Northwest/ burning costs $85-$225/acre, is very risky and hard to control/ and may be restricted because of smoke management regulations. Severe sprouting after fires requires 1-2 release treatments in nearly all cases. Mechanical or combination methods provide the best sites for reforestation. They are limited, however, to gentle terrain and may cause erosion on sloping lands. They can sometimes be incorporated with logging slash cleanup on western forests, reducing the costs of new stand establishment. Release of young conifer stands from hardwood competition can be accomplished only by chemical or hand methods. Chemicals, principally 2,4,5-T, provide some control of sprouting which manual methods do not. Thus, manual weeding may require two or more treatments in severe cases. Only two other chemicals, fosamine and glyphosate (registered only in Washington and Oregon), provide this -67- �selective control. Their costs are $30-$250/acre. Aerial applications of 2,4,5-T cost $ 10-$20/acre in the South and $10-$75 in the West* Hand methods may be used to a limited extent where labor is available, at costs of $30-$200/acre or more depending on density and size of hardwoods* No chemical other than 2,4,5-T is presently available in the eastern U.S. where 67% of the acreage of the 2,4,5-T for release work is accomplished. Intensive management of young confier stands is practiced primarily by public agency managers or timber companies, rarely by small owners. Site preparation is normally tied to harvest cutting which in turn is dependent upon marketing commitments (e.g., U.S. Forest Service) or company raw material needs (industry). Where current site preparation plans include 2,4,5-T, some alternative method will likely be used. Costs may increase from 20-200% for most alternatives now available. If budgets are inflexible, harvest cutting may be reduced (USFS or state agencies) in order not to accumulate acres */ needing site preparation.— Industry owners are more likely to continue planned harvests and absorb the increased site preparation costs. ^ / The U.S Forest Service is required to reforest havested [ acres within three years under the National Forest Management Act of 1976. -68- �Release activities are less dependent on other activities and can ordinarily be postponed for a few years, at the increasing sacrifice of some future production. If budgets are relatively fixed, some of the more productive acres will be treated in 1979-80 where alternatives are not too costly. Because of the lack of a selective herbicide other than 2,4,5-1 for use on pine stands (especially in the South and North), it is anticipated that approximately 60-70% of these stands in need of release will go without treatment during 1979-80. In the West, about 3/4 of needed release will be scheduled using other herbicides, although full adjustments may be delayed to the second year. Immediate impacts on users would occur in two forms: increased costs and reduced future productivity. Cost increases for site preparation would range from $20-$200/acre depending on the method chosen. For the first year, release costs would go up in the West by $ 10-$200/acre on those acres where young stands are threatened with imminent loss to weeds, possibly 20% of the 246,000 acres currently released with 2,4,5-T. The second year could see the use of substi- tutes on the entire 1/4 million acres, as budgets are adjusted to new costs. Current total release costs in the South would drop as many acres (65%) are left without treatment. However, there would be increased release costs -69- �as release is attempted at a later time, as well as productivity losses in the future. Reduced future productivity may be reflected in harvest cut adjustments where budgets cannot accomodate the increased costs of alternate methods. The U.S. Forest Service is presently considering proposals for about 34,000 acres of 2,4,5-T applications on National Forests for 1979 (USFS 1979a). Because of recent policies on the use of 2,4,5-T, these proposals are to cover situations where no alternative weed control appears feasible. The loss of 2,4,5-T for these situations could conceivably cause a reduction of FY 79/80 timber sale offerings to avoid accumulations of future problem areas. However, it is not likely to do so, as discussed below. Since weed control occurs early in the life of forest stands, the economic consequences of reduced control are delayed until harvest time 30-125 years in the future. However, substained yield management (as required on National Forests by the Multiple Use-Sustained Yield Act of 1960) requires a matching of harvest to anticipated growth of the entire forest. Any loss in productivity due to decreased weed control would, on National Forests, be reflected in reduced harvests. Obviously this effect would accumulate for each succeeding year of reduced weed control. -70- These adjust- �ments are normally made at 10-year intervals for most National Forests, and may not be reflected in immediate harvest reductions during a one or two year suspension. Private industry would likely accept the losses in ultimate harvest as they occur in the future, with no immediate reduction in harvest schedules (API/NFPA rebuttal to the RPAR on 2,4,5-T, 1978). Suspension would increase annual control costs by $13.5 million if all 1.16 million acres now treated with 2,4,5-T were treated with alternatives (USDA/States/EPA, Feb. 15, 1979). acre. This is an increase of $11.64 per treatment For site preparation, the increase in cost would average less than this, e.g., $5-$10 per acre; for release, it would be generally much higher due to increased use of the more costly manual methods, e.g., $30-$200 per acre in many cases. No overall average cost impact can be computed on a percentage basis with current information. It is unlikely that alternative control plans would be in full effect until the second year of suspension. The first year effects would likely be 50 to 70% of these costs($7-$10 million), with added spending in later years to make up for operations postponed the first year. These added control costs due to suspension would be -71- �in addition to the value of any actual growth losses associated with delayed or less effective site preparation and/or release treatments. A minor yield loss is projected for loss the first year of suspension ( less than 0.2 percent of U.S. softwood production) . This would increase in the second year to about 0.5 percent. These losses in yield, if realized would have an estimated reduction on forestry income of $9.6 million the first year of suspension and about three times this amount the second year ($29 million) under the assumptions of the USDA/ State/EPA 2,4,5-T Assessment Team Report [USDA/States/EPA, Feb. 15, 1979]. The total impact, including both increased control cost ( $7 to $10 million) and yield losses, if realized (up to $9.6 million) would be in the range of $10 to $17 million, (if all 2,4,5-T acres were treated with alternatives, which is unlikely, the total impact would be about $21.3 million the first year.) For the second year, the combined impact would be more, totalling $36 to $39 million ($7-$10 million plus $29 million in eventual yield losses) . While significant, these impacts are rather nominal within the context of overall forestry industry of the U.S. Effects on wood product prices would only occur if a decision were made by the U.S. Forest Service to curtail timber sales in the near future. -72- The limited �impacts of suspension on production would not necessitate a significant increase in wood product prices. The economic impacts of suspension of the forestry use for 3 1/2 months during emergency proceedings would be nominal even though conifer release treatments in the Pacific Northwest, are generally applied in the spring, before bud break which occurs by March. Some such treatments may have already been made and delay of others for two to four months during a suspension proceeding is of little significance. (2) Rights-of-Way 2,4,5-T is used to control woody and herbaceous plants on rights-of-way (railroad, highway, electric transmission, and pipeline) which could interfere with the functioning of the system (e.g., weed encroachment on highways), threaten the system's equipment, and/or interfere with inspection and maintenance of the system. 2,4,5-T is considered to provide longer control of pest plants than other control methods without harming grass and other vegetation desirable for erosion control, wildlife shelter, and aesthetics. Chemical, manual, and mechanical methods of control are used in various combinations on rights-of-way acres, depending on the terrain, availability of labor, type of -73- �equipment and species type and density. Combining control methods is a common practice on rights-of-way acreage. A relatively large number of acres apparently receive no vegetation management. Only about one-fourth of electric utilities, railroads, pipelines, and highway departments have all acres in management programs. For highways and pipelines, mechanical methods are used on more acres than any other method. Manual is used on most acres of electric acreage and is frequently employed as follow-up treatment to supplement chemical control. Somewhat less than 1/3 of all rights-of-way acreage are estimated to be treated by manual methods. Chemicals other than 2,4,5-T are more common on railroad acreage. Acres treated with chemicals are most likely to be acres where mechanical control is difficult and where other alternatives are expensive or relatively ineffective. About 683,000 rights-of-way acres are treated with 2,4,5-T on the average of once every four years, or 2.7 million acres total. An estimated 3.8 million pounds a.e. are used annually. Only a small percentage of rights-of-way vegetated acres are treated: 6.6% of railroad (127,000 acres), 9.4% of electric (465,000 acres), 4% of pipeline (22,000 acres), and 0.8% of highway (68,000 acres). Usage is believed to be mainly in the eastern and far northwestern parts of the continental U.S. -74- �Other chemicals are also currently used on many rights-of-way acres/ including dicamba, 2,4-D, dichlorprop, and picloram. Almost 13% of the highway, 25% of electric utilities/ 45% of railroad, and 5% of pipeline acreage is treated annually with other chemicals (which may include some non-herbicides). 2,4,5-T is $1.00 to $3.00 more expensive per application than other chemicals, for aerial, selective basal, and stump spray, which account for about 65% of annual acreage treated. For ground broadcast or selective foliar treatment, 2,4,5-T is cheaper ($2.00 to $19.00 in one case). The major economic advantage of 2,4,5-T is in the longer period of control it is said to provide. Generally, mechanical and manual methods are much more expensive than chemical methods. With use of 2,4,5-T suspended, rights-of-way managers would be faced with two main choices: (1) use alternative chemicals on acres scheduled for treatment or (2) postpone any treatment to see if 2,4,5-T would be available the next year. They would most likely use alternatives on at least some acres, in the Southeast and Pacific Northwest, where plant growth is rapid. The percentage of acres treated with alternatives would vary by right-of-way type and would probably be lower for railroads and highways, since they appear to be more flexible in treatment schedules. -75- �If some acres are not treated during the first year following suspension, they would probably be added to scheduled treatments in the second or third year. It can be assumed that many managers would continue treating acres each year as scheduled with alternative herbicides because of increases in size and density of pest plants. If so, annual costs for vegetation management for highways and railroads would increase by about $133,000 and $1,845,000, respectively, if they treat all acres with alternative herbicides. Costs for electric and pipeline rights-of-way would temporarily decrease by an estimated $680,000 and $28,000, respectively, each year during suspension, mainly because of the high proportion of aerial and selective basal applications• These applications are lower in cost than 2,4,5-T but must be repeated more often. There would be a net cost increase over time due to suspension only if 2,4,5-T is not available after the suspension period, i.e., if it is cancelled. The overall net cost increase for all rights-of-way types due to suspension only would be about $1.3 million per year during the 1979-1980 period. These changes in vegetation management costs are not expected to impact industry net revenue or operating costs significantly. Increased vegeta- tion management costs due to suspension would be less than 0.1 percent of operating expenditures for highways and railroads. -76- �Impacts at the consumer level due to suspension of highway and railroad uses are estimated at less than $0.03 per household per year* This is based upon the annual cost impacts noted above ($2*0 million) and the number of households in affected regions* No significant macro-economic impacts would be expected from suspension of 2,4,5-T on rights-of-way. In view of the limited economic impacts from a two-year suspension period, economic impacts during the 3 1/2 months required for a suspension proceeding would be of no economic significance on rights-of-way. (3) Pasture 2,4,5-T is used to control a wide variety of wood */ and herbaceous weeds in pastures— throughout the U.S. Weed control in pastures is economically sound where the cost of control is exceeded by the value of increased forage yield due to suppression of competitive non-forage vegetation. It is also practiced for reasons of long-term pasture maintenance and cheaper fence maintenance. Weed */ Pasture is defined as land producing forage for animal consumption, harvested by grazing, which has annual or more frequent cultivation, seeding, fertilization, irrigation, pesticide application and other similar practices applied to it. Fencerows enclosing pastures are included as part of the pasture. -77- �control by means of 2,4,5-T is now practiced annually on about 1% of U.S. pasture acreage (1.0 million of the estimated 101 million acres of pastureland in the U.S (48 states)). This use includes approximately ingredient of 2,4,5-T annually. 500,000 pounds of active Generally, 2,4,5-T is applied in pastures as a spot treatment with backpack or hand-held sprayers, although some broadcast treatments are also used. ** / In contrast to range—, little 2,4,5-T is aerially applied to pastures because landowners rarely allow weed infestations to become sufficiently dense to justify aerial application. There appear to be effective chemical, manual, and/or mechanical control alternatives for all species in all regions, although no single set of alternatives can be used on all weed species or in all parts of the country. Thus, alternatives such as picloram, dicamba, undiluted 2,4-D, and hand labor can generally provide the same level of control as 2,4,5-T, although at higher rates of application and/or higher expense. Since equally effective alternatives are available, no yield impacts are expected during the 2-year **/ Range is non-pasture grazing land on which forage is produced through native species, or on which introduced species are managed as native species. This precludes land on which regular cultural practices of the nature contained in the pasture definition. -78- �suspension period. On those acres where the conditions and type of weed permit use of an alternative which is not more expensive than 2,4,5-T, it is likely that these alternatives will be fully employed. Here no negative economic impact would be experienced. On those acres where the use of alternatives will cost more than scheduled 2,4,5-T treatments, treatment may be delayed, dispensed with entirely, or the more expensive alternative employed. Since treatments with 2,4,5-T are generally effective for 5 to 10 years, the timing of control is largely voluntary. Therefore, delay during the suspension period may be practical on much of the acreage scheduled for treatment. Treatment may be entirely dispensed with on acres scheduled for 2,4,5-T treatment which only marginally require such treatments. Presently the chemical costs of 2,4,5-T treatments are about $2.00 per acre (or about $2.0 million on 1.0 million acres). The chemical cost of alternatives is estimated at about $6.00 per acre. Thus, for each acre treated with alternatives during suspension, the cost impact would be $4.00. If all 1.0 million acres were treated, the cost impact would be $4.0 million. Since treatment is a given year is quite optional during the 5 to 10 year treatment cycle on pasture, as many as one-half to one-fourth might defer treatment in 1979/1980. This would reduce the impact to $2.0 to $3.0 million per year during suspension. -79- �The economic impacts of a two-year suspension of the pasture use of 2,4,5-T would be of no consequence on a national basis. It would be of significance to the individual owners or operators whose pastures are due for immediate treatment and on which more expensive alternatives must be used. These impacts would be of limited local/regional concern. In view of the limited economic impacts of a two-year suspension, the economic impacts during the 3 1/2 months required for a suspension proceeding would be of no economic significance. V. PROCEDURAL MATTERS This order directs the emergency suspension of the forestry, rights-of-way, and pasture uses of 2,4,5-T. Registrants affected by emergency suspension actions may request an expedited hearing before the Agency. This section explains how to request an expedited hearing, the consequences of requesting or not requesting an expedited hearing, and the procedures which govern an expedited hearing in the event one is requested. -80- �A « Procedures for Requesting a Hearing (1) Who May Request a Hearing and When the Request Should Be Made Registrants of 2,4,5-T products registered for the forestry, pasture/ or rights-of-way uses of 2,4,5-T may request a hearing on these specific registered uses of 2,4,5-T within five days after receipt of this opinion and order. (2) How to Request a Hearing Registrants who request a hearing must follow the Agency's Rules of Practice Governing Hearings (40 CFR, Part 164)• These procedures specify, among other things: (1) that all requests for a hearing must be accompanied by objections that are specific for each use for which a hearing is requested [40 CFR 164.121(a) and 164.123(b)] and (2) that all requests must be filed with the Office of the Hearing Clerk within the applicable five (5) days [40 CFR 164.121(a)]. Failure to comply with these requirements will automatically result in denial of the request for a hearing. Requests for hearings must be submitted to: Hearing Clerk (A-110) U.S. Environmental Protection Agency 401 M Street, S.W. Washington, D.C. 20460 -81- �B. Consequences of Filing a Hearing Request Under PIPRA Section 6( c) I 3) the emergency suspension order becomes effective immediately and, unless stayed/ continues in effect until completion of the expedited hearing and issuance of a final order of suspension* The statute provides that where an administrative hearing is requested, the emergency order is subject to District Court review on the emergency finding. The final suspension order issued by the Administrator after a hearing may keep the suspension in effect, modify it, or terminate it. A final suspension order issued following a hearing is then reviewable in the Court of Appeals. The statute provides that if a hearing is requested on the Administrator's emergency suspension actions regarding 2,4,5-T before the end of the five-day notice period, the hearing stage is to begin within five days after receipt of the request, unless the registrant and the Agency agree that it shall begin at a later time. No party, other than the registrant and the Agency, is to participate, except that any person adversely affected may file briefs within the time allowed by the Agency's rule. Hearings on emergency suspension, like hearings on ordinary suspension, are subj ect to the provisions of subchapters II of Title 5 of the United States Code, except that the presiding -82- �officer need not be a certified hearing examiner. The presiding officer has ten days from the conclusion of the presentation of evidence to submit recommendations to the Administrator, who in turn has seven days to issue a final order on the issue of suspension. C. Consequences of Not Filing a Hearing Request Under the statutory scheme, if there is no request for a hearing on the Administrator's suspension actions within the five-day notice period, the emergency suspension order becomes a final suspension order, which remains in effect until the conclusion of the cancellation proceedings, unless modified or vacated sooner (40CFR 164.130). Court review of an emergency suspension order, including the special review before the District Court discussed in Part II is available only if an administrative hearing has been requested within the applicable five-day period [FIFRA Section 6(c)(2), 6(c)(3)]. D. Supplementary Procedures EPA's rules of procedures for expedited hearings are set forth at 40 CFR Part 164, Subpart C. I do not know if a hearing will be requested on these suspensions. If it is, however, I am establishing the following procedures to supplement the existing regulations in governing its conduct* -83- �1. A deadline is being established for the comple- tion of all hearing procedures and the rendering of a recommended decision under 40 CFR 164.121(j). That dead- line is 90 calendar days from the first prehearing conference, which shall be held in accordance with the time requirements described below. 2. I am naming certain EPA employees to serve as a hearing panel in any hearing arising out of this notice (see Appendix A)• I am naming certain additional persons to be available to provide technical advice and staff support to the hearing panel (see also Appendix A). If questions arise at the hearing which persons in this category are uniquely qualified to assess, they may be called on to serve on the panel either in addition to, or in substitution for, the three panel members named above. The panel will conduct the hearing and submit a recommended decision to me under 40 CFR Section 164.121(j). None of the persons named above is subject in the normal course of their duties to the supervision or direction of any employee or agent of EPA who is a member of the Agency trial staff named below. 554(d)(2). -84- See 5 U.S.C. Section �Since 5 U.S.C. Section 554( dH 1) provides that those presiding at adj udicatory hearings may not "consult a person or party on a fact in issue [in the course of preparing their decision] unless on notice and opportunity for all parties to participate," neither myself nor my appellate staff will consult with the panel or its supporting staff on any matters involving this case from the date of notice until a recommended decision is issued. Members of my appellate staff are also listed in Appendix A. We will conduct an independent review of the questions presented on appeal of any recommended decision• However, in doing this we will feel free to consult with the hearing panel and the support panel, since they will have conducted the initial proceedings and brought expert knowledge to evaluating the record. The following Agency bureaus or divisions, and their staffs, are designated to perform all investigative and prosecutorial functions in this case: Office of */ the Deputy Administrator— , Office of Toxic Substances, the Office of General Counsel, and the Office of Enforcement. ^_/ The Deputy Administrator may properly be included in the trial staff since the prohibitions of 5 U.S.C. Section 55<(d) do not apply to "the agency". Her inclusion is necessary if guidance on general policy matters is to be available to the trial staff and, to free a high agency official to talk to outside interested persons about the questions involved without the constrains otherwise imposed by the ex parte provisions of the APA and the Government in the Sunshine Act. The Deputy Administrator will take no part in the detailed work of preparing and presenting the Agency's case. -85- �From the date of this notice until any final decision, no member of the hearing panel, its support staff, my appellate staff, or myself, shall have any ex parte contact with any trial staff employees, or any other interested person not employed by EPA, on any of the issues involved in this proceeding. However, persons interested in this case should feel free to contact any other EPA employee, including both trial staff and persons not explicitly named as panel members or assistants, with any questions they may have. 3. I am directing the hearing panel to proceed as follows to streamline proceedings in this case. a. My findings on imminent hazard and emergency for suspended uses of 2,4,5-T together with supporting information are in my opinion and order, which is available for inspection in the Office of the Hearing Clerk. Additional supporting information, including references cited in the opinion and orders, is also available for inspection in the Office of the Hearing Clerk. Together these documents **/ constitute the Agency record in this m a t t e r . — E P A has also attempted to put this information in perspective through a narrative summary and analysis. **/ Some of the documents in the record may be entitled to confidential treatment under FIFRA Section 10, as amended. Parties to the hearing may have access to such documents if appropriate protective arrangements are made. See also the footnote to this Order concerning confidentiality of data [in Section IV.A.i 1H aK i) ] . -86- �b. The scheduling of any hearing, particularly in its earlier stages, involves a balancing between the need to conduct an expeditious hearing and a concern that the hearing not proceed too far before the identity of those registrants requesting a hearing is established. In arranging for the first prehearing conference, I have attempted to accommodate both interests. The hearing panel shall convene the first prehearing conference within five days after receipt of the last request for a hearing by a registrant or 15 days after the issuance of my opinion and order, whichever comes earlier. The 15 day maximum should ensure that all registrants wishing to participate in the hearing have been given ample time to file a hearing request after receiving notification of my suspension actions. c. Within ten days from the first prehearing conference, any person requesting a hearing shall submit focused written comments on this opinion and order consisting of a counterstatement of proposed findings on the issue of imminent hazard presented by 2,4,5-T together with supporting information. A narrative summary explaining its bearing on the case should also be included. d. The Agency trial staff shall have seven days thereafter to file supplemental information and comments• -87- �e. Within five calender days from the filing of any supplemental information by the Agency staff, the panel shall convene a second prehearing conference* At this conference all parties shall appear prepared to present arguments on the signficiance and relevance of the material already presented. This prehearing conference shall also hear all requests for oral presentation of direct evidence and crossexamination, and the reasons supporting them. At this time each party shall present the names of witnesses available for cross-examination on the matters the party is putting into issue. The party may list documents (or portions thereof) on which the potential witness is available for cross-examination in lieu of filing a formal witness f. statement. Within five days after the prehearing conference is over/ the panel shall issue a hearing order setting the schedule for oral presentation of witnesses and cross-examination. ( 1) Requests for oral presentation of direct testimony shall be granted only if it is demonstrated that the testimony can be presented meaningfully only in that form; in all other cases/ direct testimony shall be in writing. -88- �(2) Requests for cross-examination shall be granted only if all of the following showings are made: i. The request concerns factual matters* Cross- examination will not be granted on matters of policy or law. ii. The factual matters are legitimately in dispute in light of the record. iii. The factual matters are material to the decision to be made. iv. Cross-examination is the most efficient way of resolving the dispute over these factual matters (as opposed to such alternatives as production of further information, or informal conferences). v. There is a reasonable expectation that crossexamination will resolve the issue of material fact in a way likely to influence the final decision. g. The testimonial phase of the hearing shall begin three days after issuance of the order setting the hearing schedule. At the hearing, the panel shall take an active role in the development of the record through questioning of witnesses and by issuing procedural orders where necessary. -89- �h. At the end of the initial testimonial phase, the hearing panel may permit the introduction of additional information designed to rebut the contentions made by opposing parties. i. The panel may revise any of the procedural provisions of this notice other than the overall 90-day deadline for rendering .- a recommended decision.the time for which starts running after the first pre-hearing conference. A discussion of some aspects of these procedures follows: ( 1) Deadlines Deadlines for completing proceedings under FIFRA have been twice endorsed by the National Academy of Sciences [National Academy of Sciences, Decision Making in the Environmental Protection Agency, Vol. II, p. 84 ( 1977) ; National Academy of Sciences, Decision Making for Regulating Chemicals in the Environment, p. 30 [ 1975)]. In addition, Congress has demonstrated a concern for speedy action where suspensions based on a potential threat to human health are concerned. It has required a hearing on such a suspension to begin five days after it is -90- �*/ requested— , and has allowed ten and seven days respectively for preparation of the initial and final decisions once the hearing is over [FIFRA Section $ c) I 2) ] . FIFRA was amended in 1975 to require consultation by EPA with the Department of Agriculture and a scientific advisory panel before taking action in many cases; suspensions based on human health grounds, however, were exempted from those requirements to allow speedy action where speedy action was desirable [121 Cong. Rec. H 9895-96 ( daily ed. Oct. 9, 1975); 121 Cong. Rec. Section 19820-21 I daily ed. Nov. 12, 1975)]. Deadlines for completing the hearing have been imposed in prior suspensions. See, e.g., In re; Vesicol Chemical Co., et al., 41 F.R.7552, 7553 (Feb. 19, 1976) [Notice of Intent to Suspend Heptachlor and Chlordane], and In re; Dibromochloropropane, 42 FR 48915 ( Sept. 26, 1977) . [Notice of intent to suspend and conditionally suspend registrations of pesticide products]. The requirements set forth in this order simply carry forward that practice. ±/ I do not regard the procedures set forth below as inconsistent with this directive. What concerned Congress was plainly that the hearing stage of Agency decisionmaking begin promptly, not that the oral hearing itself start unconditionally in less than a week. To interpret the law otherwise would forbid the use of such accepted aids to efficient decisions as prehearing conferences in precisely the cases where efficiency is most required. -91- �(2) Use of a Panel Despite the need for speedy action, the issues involved in suspension are complex* Under the statute, a judgement of "imminent hazard" must be based on consideration of costs and risks of all types [FIFRA Sections 2(1), 2(bb)]. Given the necessary time constraints and the preliminary nature of suspension as a remedy, factual certainty may be elusive* "[T]he function of the suspension decision is to make a preliminary assessment of evidence, and probabilities, not any ultimate resolution of difficult issues" [Environmental Defense Fund, Inc• v. EPA, 510 F.2d. 1292, 1298 (D.C. Cir. 1975), quoting from Environmental Defense Fund, Inc. v. EPA, 465 F.2d. 528, 537 (D.C. Cir. 1972)]. Arriving at even such a preliminary assessment can present formidable difficulties. Considering risks, questions can arise concerning the dispersion and persistence of the pesticide in the environment and certain parts of it, the conduct of animal feeding studies, the meaning of those studies for human health, the validity of relevant epidemiological studies, the reliability of using known human exposure from one use pattern as a predictor of potential human exposure in other use patterns, and finally on what the upper and lower boundaries of any risks may be and how firmly they are established. -92- Considering benefits, �questions can be raised about the extent of use/ the availability/ practicality/ and effectiveness of substitutes both now and in the future, and the range of the probable economic impacts of a temporary ban on the pesticide, or some use of it, in the light of all these factors. The job will be easier and better performed, if I am allowed to rely directly on the talents of EPA employees with expert knowledge of the technical fields involved and with the professional ability to assess problems arising in them. I believe it is for this reason that Congress has provided that those presiding over suspension hearings need */ not be hearing examiners— . (3) Conduct of the Hearing Overuse of cross-examination and courtroom formalities, I believe, has made many FIFRA proceedings than was consistent with any rational purpose. far longer The overwhelm- ing bulk of legal analyses by those who have studied the problem, and EPA's own experience demonstrate that scientific and economic issues can be clarified by the exchange of written material far more efficiently th,an through courtroom hearings. I am directing that written submissions be used ^/ The fact that more than one person will preside is of no legal significance. Even when 5 U.S.C. Section 556 requires a hearing to be presided over by an examiner (or a person representing the Agency), it also specifies that "one or more" of those qualified may preside. -93- �here to focus the issues in an attempt to implement those lessons. At the same time/ particularly where Congress has explicitly called for formal hearings, the accompanying rights to reasonable cross-examination and oral presentation must be preserved. All three elements of these supplementary procedures are meant to work together. The use of a panel will ensure that expert knowledge is indeed brought to the task of making a decision. The provision for preliminary written submissions will allow that panel to screen the issues and narrow the formal part of the hearing down to those that are legitimately in dispute and suited to adjudicatory resolution. Finally/ setting a schedule for decision will help ensure that the potential gains in efficiency repres /^l / ted by the first two reforms ara'rearli/zed in Douglae Administrat FEB 2 8 1979 Dated: -94- �APPENDIX A HEARING PANEL Charles Gregg, Chairperson William Brungs Robert Coughlin TECHNICAL SUPPORT PANEL Robert Chapman, M.D. Neil Chernoff Arnold Kuzmack Dr. James Lichtenberg ADMINISTRATIVE APPELLATE PANEL Ronald L. McCallum Charles R. Ford Dr. Edwin H. Clark Ms. Mary Ann Massey Dr. Richard M. Dowd Dr. Stephen J. Gage � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 179 Folder The folder containing the original item. 5257 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Costle, Douglas M. Date A point or period of time associated with an event in the lifecycle of the resource February 28 1979 Title A name given to the resource Typescript: Decision and Emergency Order Suspending Registrations for the Forest, Rights-of-way, and Pasture Uses of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/9e1df2e3ddf72ba748edb1134aec2acc.pdf 7bd626efd57ebfa5ec4d601a7306534b PDF Text Text Item D Number °5258 D Not Scanned Author CorDOratB Author 2,4,5-Trichlorophenol Working Group, U.S. Environment RODOrt/APtiClB TltlB 2,4,5-Trichlorophenol and Its Sodium and Potassium Salts: Position Document 1 Journal/Book Title Year 1979 Month/Day February 28 Color n 82 DOSCrfptOn Notes EPA/SPRD-80/79. P881-103111 Friday, March 01, 2002 Page 5258 of 5263 �—1^ rtt ?*^^£m"™«>T "^ r 6 l 1 ! < l f / 1 i,<V'ir*i f'i »f^»«^BW*>vVt !»l'«^'» ''" '^^^'l^ft^*#^^^''*''** W^'''^ *V ^W'« !V |1H ««,,^w««HS»^.5»^WWwW*a«*^^^S5*™< ,; u-^*,jv~j >-nii'ii.Btf,iAuj'-' »J. >-.(-^rTiLi'.i"<Wtfitf VLi'i '\r - i j'"J™ m^L.-:,j;- >*^ j ft PB81-103111 2,4,5-Trichlorophenol and its Sodium and Potassium Salts: Position Document 1 (U.S.) Environmental Protection Agency Arlington, VA 28 Peb 79 Technical information Service �'^''^^'^Wl^V-'1^!tV?^*',^W'^^,f.v%^»fllWSs'\*^ft'M«'iY^^'''T*'wf'^ <PV"!n,V»f,.'t* w ^ , , . . ^ ^ ^ ^ ^ ^ ^ , ^ , , .,^^, s , ^ , . ^ ,^ ,^ $3)ftMSSSSW49i$W«m«*fiW3*i<EiifflJ<Wrft8^ft^ REPORT DOCUMENTATION ___ PAGE * 3. RecloUiitj* Accession I. REPORT NO. JP_A/S_PRD-_80/7? ^ 4. Title and Subtitle 5. Report 2,4,5-Trichlorophenol end Its Sodium and Potassium Salts: Position Document I 6. 7. Author(l) B. Performing Organteatlufl Rept. No. 9. Performing Organization Name and Address 10. Prolect/Tssk/Work Unit No. Special Pesticide Review Division Environmental Protection Agency Crystal Mall #2 Arlington, VA 22202 11. Contract(C) or Grant(G) No. (0 X (GJ 12. Sponsoring Organisation Name and Address II. Typ« of Report & Period Covered U. S. Environmental Protection AGency 401 M St., S.W. Washington, D.C. 20460 14. IS. Supplementary Notes >«. Abstract (Limit: ZOO words) Preliminary Risk Assessment: Examination of possible unreasonable risks associated with uses of pesticide and a gathering of all available information to determine whether or not this or any other risk does exist. Initiates literature search and evaluates risk data. Limited information on exposure to forecast extent of risk. / 17. Document Analysis a. Descriptor* I 0606,0703,0504 b. ld»ntlll«rs/Open<Ended Terms c. COSATI field/Group I . Availability SIMem»r>: I Release Unlimited I*. Security Claw (This Report, JlnclUSlfJjSd to. Seewliy Clan fthlt Page) See ln<truc(loni an Reverie 21. No. of Pages M. P>tc« OPTIONAL FORM 271 (4-77) (formerly NTIS-Ji) Department el Commerce �P881-1031U 2A5-T81CHLOBOPSEHOL AND US SDDIQM AND POTASSIUM SALTS POSITION 2f^,5-?richloroph8nol Weridag Group Mwy H»«C8, Project Macagar D.S. Errirocaantai Protection Agency trmooucEO it NATIONAL TECHNJCAL INFORMAT1OM SERVICE U.I. KfAKTMCNT Of COMMlfiCI i« �Page Forward I. ,,. 1 Background 2 X. Chendciil and Physical Characteristics B. . Manufacturing Peaces* and Resulting Contaminants 1. Forsulation . « . . . * « . . . . . . . . . . . . . ..•.«..«........... 2. Type* of Dicodns 3* TCCD Content in Fornulattd Pesticides C. Registrations, Uses, and Production D. Tolerances E. Metabolism, Degradation, and Residues 1. soil a. 2,4,5-TC? and Its Salts 2 3 3 4 4 5 7 7 7 7 b. TOD 2. Water * 8 •<> 9 a. 2,4,5-40? and Its Salts b. TCBD 9 , ,. . ... 10 .. 3. Wildlife a. 2,4,5-4X2 and Its Salts b. TCCD iO 10 * 10 1. Terrestrial Eecaystana ii. Aquatic EcosysteBS 4. Plants a. 2,4,5-TC? and Its Salts b. TCCD 5. Anirais a. 2,4,5-TC? and Its Salts b. TOO , „ TCCD b. ,,..„.... 10 10 11 II. Accidental Human Exposure 13 14 14 ; Regulatory History 15 21 Onoogenic Effects in Test AniaaLLs 1. 2,4,5-TC? 2. TCCO a. '/an Miller Study b. Preliminary Report: Dow Chemical Company Study c. Conclusion 14 18 HZ. Sunrary of 'Scientific Evidence Relating to Rebuttzble Presuroticn A. x2 12 12 6. Humans 7. Anifiad. Products a. 2,4,5-TC? and Its Salts F. 1 1 ,... U 21 21 22 22 .. -. 24 24 �Page B. Fetoteodc and Teratogenic Effects in Manrculian Specie* .... 26 ... 1. 2. 3. 2,4,5-TCP TCTO a. Mice b. Rats c. Chide EBbryos Exposure Analyses a. Industrial Cooling Water Syattam b. Paper and Pulp Mills c. Leather Industry d. Hospitals e. ConfUuaicn IV. Evidence not Sufficient to Support a Rebuttabla Presumption A B. C. 27 28 28 34 40 41 43 49 SO 53 ...6 ..5 57 Mutagenic Effects of TCDD in Test Aninala 57 1. Studies Demonstrating the Mutagenic Effects of VXD .. 57 .. 2. Studies in which Mutagenic Effects were not ocaerved .. 59 . Other Effects of TCDD 59 1. Enzynatic Effects 5n 2. Toxic Effects on Humans 60 3. Toxic Effects on Other Manuals 61 4. Miscellaneous Toxic Effects 61 Other Effects of 2,4,5-TC? and Its Salts 62 �FOREWORD All technical and f craniated 2,4,5-trichloropbenol (2,4,5-TC?) products are contaminated in varying degree by & byproduct of the manufacturing procaaa, 2,3,7|8«tetrachloroclibenzi>*£»dioxin (TOO). For this reason all refer-mova to 2,4,5-TC? denote TCDD-contaainatad 2,4,5-TCP. Humarous toxicity studies on purified TCDD are included in this position document. Many of these studies were done in connection with another pesticide, 2,U,5-triehiorcphencDeyacetie acid or 2,4,5-T, whicn ia manufactured frcm 2,4,5-TC?. 2,4,5-T, which is a candidate for rebuttable presumption against registration, is the subject of a separate position �I. Background A. Cjbei^e«l_and..P_^i.ealj;.tjaracteri3tie3 2,i»,5-Trichloropbenol (2,4,5-TCP) and its sodiua (Na-2,4,5-TCP) and potassium OC-2,4,5-TCP) salts are used as fungicides, algicides, and bactarlcides (Weissberg aad Zinld, 1973; Pliomer et ai., 1973). The empirical formulas for 2,4,5-TCP aad its sodium and potassium salts are C H C 1 0 H , C H C l O N a , a B d C H C l C X , respectively. The structural 6 2 3 6 2 3 6 2 3 formulas of these compounds may be found in Figure 1. 2,4,5-TCF Is also known by its trade name, Douicide 2; ths trade name of Na-2,4,5-TC? Is Oovdcide B. Cl Na-2,<»,5-TC? at K-2,4,5-TC? F2GUJH 1. Structural formulas of 2.U<g.7C? " and JM sodium ana potassium; salts 2,U,5-TC? is a fairly weaie acid and is considered to be the least toxic of ti» cnloropnenols (Kirtc-Ctfcmer encyclopedia, 196^). The sodium salt is slightly more toxic. 2,4,5-TCP occurs as gray flakes in subliaed muss with a strong phenolic odor. Although 2,^,5-TC? ii relatively ino soluble in water « 0.2 g/100 g water at 25 C), it is soluble in organic solvents such aa alcohol, ether, and acetone. The sodium salt is more o soluble in water (113 g/100 g water at 25 C). 2,U,5-TC? has a aolecular o o weight of 197.^6 and a specific gravity of 1.678 (25 C/« C). Its o o point is 2f2 C; the melting point is 60-70 C. (2) �8. Manufaetajr^^Pn^aa^a^ 1.' Foraulatign 2,4,5-TCP la produced ccanercially by the alkaline hyrirolysia of 1,2,4,5-tetracnlorobenzene to 2,4,5-TCP. The reaction la carried out o under pressure at 180 C in the presence of aqueous aodlua hydroxide and Mttanal (Kirk-Otaaer Encyclopedia, 1964; F<ahbeiaf 1973)• 2,4,5-TC? can be converted to ita aodium or patasaium aalta by the addition of sodium or potaaaium carbonate. Polychlorinated fMhon^p-^-^i ny^pa JTQ fonsed in *-^ oanufacturicg proceaa of all cnloropnenola. However, tbe aoount formed ia dependent on the degree to vdrteh tne tanperature sad greaaure are controlled during production (Fiahbein^ 1973; Hilnea, 1971; SrhnU, 1968; ff1 ggr!nhottam at al. 1963; Huelder and Shadoff, 1973)' Aa especially toxic <q.«gjnT 2(3i7tS-tetncnlorodibenzo^pj-dioxin (TCDD), ia foraed during tta prcduction of 2,4,5-TC?. Aa can be anticipated, TCPD hg< been ^a«y?gia^yi viltix "i \ syntnetic <i*MC"i?'7rir*? derived frcs 2,4,5-TC? (Kearney et al., 1973)• Thia includes the widely uaed herbicide ana defoliant 2,4,5-T (2,4,5-trichloropnenaxyacetls acid). Tm formation of 2,4,5-TC? and TCDD ia illustrated in Figure 2. a "•o«« Figure 2. Foraulation . of.2,4,5-TC? and TCDD (3) �2* Types, of Dioxins There are many different dioxins; the particular dioxin produced depends OQ the ohlorophsnols present (Poland and itende, 1976). Different ^""' dioxina can be distinguished by the number and position of the chlorines they contain. Chlorine atoms my b« attached at any of eight different positions, creating a theoretical possibility of T5 compounds or isomers (Crosalaod and Shea, 1973; Basra and Roddick, 1973)* The toxicity of a dioxin varies with the position and number of chlorines attached to the aromatic rings. Generally, the toxicity increases with increased chlorine substitution. Those dioxins that have halogens at the 2, 3, and 7 positions are particularly toxic (Burger, 1973)* TCDD, which has.chlorine atoms at the 2, 3* 7, and 8 positions, is considered the most toxic of the diorins (Sparschu et al.t 1971). 3» TCDD_Content in Fora?ilated Pegtieides Although TCDD levels in 2,U,5-TC? have cot been monitored consistently over the years, these levels have been seasured in 2,U,5-T. Different satnufacturers produced 2,4,5-t with various 7C3D contents (Kearney et al., 1 7 ) Samples of 2,4,5-T produced by one manufacturer frca 1966 93. to 1968 often contained more than 10 ppm TCDD (Fiattein, 1973)• Because there vas co^rera about tie extremely toxic effects of TCDD, manufacturing methods wore changed and carefully controlled to minimize its formation. By 1971 industry had reduced the amount of TCDD in commercial samples of 2,4,5-T to less than 1 ppa (Greig et al., 1973; Hussais et al., 1972; Milnes, 1 7 ) Production conditions and the amount of contaminant 91. in th« final product ar« now closely monitored by industry. �2,4,5-TC? is available in both a technical and analytical fora. Technical grade 2,1,5-TCP (Dowicide 2) currently contains 95> active ingredient and 5* inert ingredients in which TOD ia present at a maxLinim of 0.099 ppm. Technical grade Wa-2,H,5-TCP (Dowicide B) contains 855 Ka-2,^,5-TC? and 15* inert ingredients in which TCDD is present at a marianim of 0.099 ppm (Dow Chemical Company Sales Specifications, 1976). The «13ortn content in both of tbas* products does not exceed the limit of 0.1 ppm reconmended by the Advisory Carrel ttee to tbe SPA Administrator on May 7, 1971. To obtain a meaningful assessment of tbe levels of TCDD present in tba environment and to determine tbe amount that could be accumulated in tbe food chain, a sensitive analytical method bad to be developed that could accurately, identify TCDD in parts per trillion. During ths past 10 years coosiderable advances have been made in this regard. Tbe analytical procedure that is currently considered the scat sensitive is. gas-liquid e&romatograpfay coupled with high resolution mass spectrcsetry • (National Academy of Sciences, 1977). C. Registrations, Oaea. and Production The largest u;- cf 2,4,5-TC? is as a starting material in the manuf95cure of a series of industrial and agricultural chemicals, tbe most notable of which is tba herbicide 2,^,5-T and its related products including silver C2-(2,U,5-trichlorophencxy}propionic acid], rcnnel [0_, 2-diaathyl 0-<2,U,5-trichlorophenyL)-pfeaspborothioate], and tfat baotcricide bexachlorophene. (=). �2,4,5-TCP and its salts are used in the textile industry to preserve emulsions used in rayon spinning and silk yarns, in the adhesive induatry to preset*" polyvinyl acetate emulsions, in the leather industry aa a hide preservative, and in tha automotive industry to preserve rubber gasknts. The sodium salt is used as a preservative in adhesives derived from caaaia, as a constituent of natal cutting fluids and foundry core washes to prevent breakdown and spoilage, aa a tactaricide/fungicide in recirculating water in cooling towers, and as an algicide/sliaicide in the pulp/paper manufacturing icduatry. There are some minor uses of 2,4,5-TC? and its salts in disinfectants which are of major Importance relative to h"1*3" exposure. These include use on swimming-pool-related surfaces; household sickroom equipment; food processing plants and equipment: food contact surfaces; hospital rccma; sickroom equipment; and bathrooms (tnelnrting shower stalls, urinals, floors, ,and toilet bowls). 2,4,5-tC? and its salts lave been registered for peaticidal use since 1943. Current EPA records indicate that 42 registrants have 9" Federally-registered products and one State-registered product containing 2,4,5-TCP or its salts. These products are usually fonaulatad as wettable powders, emulsifiable concentrates, dry powders, liquids, or ball briquettes. Dow Oyn1.na] Company is tba major manufacturer of technical grade 2,4,5-TCP (Dowicida 2) and Ha-2,4,5-TCP (Dowicide 3). 2,4,5-TCP and its salts are frequently sixed with other pesticides including pentachlorophenol, tetracslcrcpfcenol, and sodiua pentachlcropbenate. (6) �Stction 7(o) of the Federal Insecticide, Fungicide, and Rodentieide Act (FIFRA) requires asanufaeturers and formula tors to i-jbait to EPA information on the production, sales, and distribution of their products. According to Sections 7(d) and 10 of FIFRA, this information may not be ^" csade available to the public. A confidential memo suonarising this information (Beece, 1977) has been sent to the Deputy Assistant Administrator for Pesticide Programs. D* Tolerances There are no tolerances for 2,*,5-TCF, its salts, or TCSO in or on fool crops. 40 CFR 180.302 does, however, establish a tolerance of 0.05 ppn bexaehloropnene in or on cotton seed (a nonhuaan dietary food itea) and states that technical grade hexschlcropfaene shall not contain more than 0.1 ppm 7C2D. E* Metabolism. DegradatiDn._ and Residues No data baa been found on the nature of the degradation products of 2,4,5-TCP. However, there is evidence that 2,4,5-TC? itself is the metabolite or primary degradation product of a number of pesticides including 2,U,5-7, ailvex, ronnel, lindane, and benzene hexachloride (Watts and Storfcerr, 1973; Crosby and Wong, 1973; Goto et a!., 1972; Leng, 1972). 1. Soil a. 2,t,5-TC? and Its Salts Alexander and Aleea (1961) found that 2,U,5-7C? is persistent because it is resistant to microblal decocpositicn in certain soil populations. They also found that compounds containing a meta-sucstituted chlorine (such as 2,^,5-TC?) were sere persistent than these that did net. (7) �These results were verified by Helling et al.f in 1973. i I b. TCDD Crosby et al. (1973) Irradiated 2,4,5-TCP tad its sodium salt and found that they discolor*! rapidly but did not degrade into dioxins. Kearney et al. (1972) Incubated 2,U,5~TC? in two types of soil for 70 days to determine wnstbar bacterial action might convert the 2,4,5-TC? to TCDD. The fact that no TCDD was detected demonstrated that TCDD vas not foraed under these laboratory conditions. Thus, TCDD is neither foraed indigenously in soil (Kearney et al., 1972) nor produced biosynthetically from soils receiving applications of 2,4,5-T or 2,U,5-TC? (Belling et al., 1973; Kearney et al., 1972; Kearney et al., 1973). TCDD is a remarkably stable ccmpound in biological systems at o temperatures up to 700 C (Grassland and Shea, 1973; Piper et al., 1973). It is also immobile in soil and tends to remain on the surface (Helling, 1971). TCDD degrades slowly in soil; it has. a half-life of 1 year (Kearney et al., 1972; Belling et al., 1973). In 1973, Woolscn et al. investigated the possibility that TCD residues from old, extremely heavy 2,1,5-7 applications night still ycse a threat to wildlife. They analyzed soil samples frca experlcental plots of Ukfla"d sand in Florida that lad received massive doses of 2,^,5-T (947 pounds 2,U,5-T/acre) by aerial application frcm 1962 to 1970. The authors estimated that the- 2,4,5-T used at that time contained between 2 and 50 ppm TCDD. Twenty-five gram samples of 6-lncb increments of a 3-foot cere were taken in 1970. Mo TCCD residues were found in any of the increments; the detection lisit was leas than 1 ppb. The autters (8) �bad estimated that there could be up to 2.1 ppa TCDD present in the soil as a result of the aerial applications. They felt that the absence of daUctable TCDD residues could be explained by jeveral possibilities: 1) the 2,4,5-T applied contained less'than 2 ppm TCDD, 2) the TCDD moved dwper than 36 inches into the soil, 3) the TCDD was decomposed in the soil ptotocaemicaliy or biologically, or 4) wind erosion removed the TCDD frcm the point of application. Bovever, TCDD is immobile in soil and the likelihood of wind erosion or the amount of TCDD present being less than 2 ppm is remote. It Is most Likely that the TCDD photochemically degraded. P11 Timer et al. (1973) found that TCDD is readily photolyzed under certain conditions. Crosby and Wong (1977) found that herbicide foraulations containing TCDD on leares, soil, or glass plates lost most or all of the TCDD in a single day of exposure to sunlight due principally to photochemical dechlcrination. However, Crosby et al. (1971) found that a filffl of "pure* TCDD on glass plates was not photodegraded when exposed to sunlight for 14 days. 2. Water • a. 2.4,5-TC? and Its Salts 2,4,5-TCP is soluble only in organic solvents such as alcohol, ether, or acetone. The sodium salt is more soluble in water but less soluble in organic solvents. However, acne of the uses of 2,4,5-TC? and its salts could feasibly result in their reaching water bodies frcm industrial effluents or fron coding tower water that is not in a closed system. (9) �b. TCDD Becaus« TCDD is roUaively isaobila in soil and soluble in water at only 0.2 ppb, the possibility of ground water contamination ia virtually Bon-«xist<mt and water transport is limited (Belling et •!., 1973; Harvey, 1973). A rteent National Academy of Science report (1977) stated that TCDD has cevor been detected in drinking water; the limit of detection ia the studies cited was in the parts per trillion. The report did note the toxLcity of TCDD and its acceptable daily intake frca water (.0001 ug/kg/ -4 day), and suggested no-adverse-effect levels (7 x 10 ug/kg/day). ' 3. WUdlifer a. 2.U.5-TCP and Its Salts No studies identifying 2,4,5-TCP residues in wildlife were found. b. TCDD i. Terrestrial Eeesystaa To assess the ecolcgisal importance of chlorinated dicrina, Woolson • et al. (1973) examined tissues of 19 bald eagles (Ealiaeetaa leueecaptalua) collected in 15 widely separate States. Ho TCDD residues were found; the liait of detection was 50 ppb. Because eagles are at the top of a food chain, the authors concluded that TCDD residues from past pesticide applications were not available to *-*<-t food chain. tl« Aquatic Ecosystess Isensee and Jones (197?) conducted an expcriaent ia which TCDD was absorbed on three different types of soil at concentrations ranging free 0.001-7.^5 ppa. The soil was then placed in aquatic model eccsys- �tana. TCDD acououlated in all organisms (mosquito fish, daptnid, duckweed, catfish, and snails). The amount of accumulation was directly related to the concentration of TCDD in the water (0.05-1330 ppt). Therefore, the authors concluded that under eertadn conditions TCDD residues oould accumulate in fish or other aquatic organism. Zitco (1972) was unable to detect calorlnaud dibenzodioxin residues in several aquatic animals Area various locations in Canada; the Limit of detection ma 0.01-0.04 ug/g (ppa). The author concluded that there is no detectable contamination of food by chlorinated ios since the species analyzed are in high trophic levels of the aquatic food efaain and serve as good indicators of envirooaratal conuctnation by emulative ccspounds. However, analytical methods have Improved considerably since then and scientists can now detect dioxins in the parts per trillion. Matsufflura and Benezat (1973) found that TCDD pickup (biological transfer) was low in brine sbriap and fish but hlfft in scsquito larvae, which are bottom feeders. This led them to believe that TCD is not Likely to accumulate in aquatic systems due to TCDD 'a lew solubility in water. Eaufhaan aad Meselson (1973) reported the presence cf TCDD is fish acd crustaceans taken free four locations in Vietnam. Concentrations ranged frcn 18 to 810 ppt. 4, Placts a. 2.U.5-TC? and Its Salts So studies identifying 2,4,5-TC? residues is plants were fouftd.- �b. TCDD TOO was not detected la the seeds or mature plants of soybeans or eata sprayed with TCDD or grown on solid contaminated with 60 ppb TCDD. The Halt of detection was laaa than 1 ppb. Researchers concluded tbmt plants do not absorb or tranaloeata TCDD fron aoll or leavos after foliar application (Xsoosee and Jonas, 1971; Matauoura and Berezet, 1973) • Crosby and Hong (1977) found thmt barbicid^ formulations containing known anoints of TCDD tb&t were exposed to natural sunlight on leaves, soil, or glass plataa lost oest or all of their TCDD during a single day. They felt W? uaa due principally to photocneoical dectlcrination. TCDD that la sprayed on leaf surfaces can be readily washed off (Iseosee and Jones, 1971; Helling et al., 1973; Kearney et ai., 1973). MatauBura and Benezet (1973) concluded that any translocates of TCDD in the enrironBest would be H«H»^« to traces of the compound »d» bared to son particles, dispersed hy the wind, or blolcji^ally transferred in aquatic environmnts. • 5* a. 2^.5-TCP and Its Salts Mo studies on t£» metabolism of 2,U,5-7C? in laboratory anlml.i were found. b* TCDD TCDD is •11T*1"«»-^1 frcm biological systeea principally through the feces but also through the urine (Allen et al., 1975; Piper et al., 1973; Vinopal and Caaida, 1973; Kia&rough, 197U). Rose et al. (1976) detected radioactivity only in the fec&s of (125 �14 rats adninistared a single oral dose of X ug/fcg C-labeled TCDO. Liver 14 and fat contained C-TCBO concentrations over 10 tints greater than tbOM in other tissues exaeined 22 days after inge»tion. When oral doses 14 of 0.01, 0.1, or 1 ug C-TCCD kg/day were administered for 13 weeks, the mjor route to excretion was ar^ain via the feces, in2 the half-life of 14 the <MEDD in the rsta was 33.7 days. 14 In Sprsgua-Oawlay cm intubated with C-labeled TOO, only 4.51 of the radioactivity fron a single oral dose was eliminated through the urine in 21 days, A large percentage of the radioactivity remaining in the body at the end of this period was in the liver and over 90% was within the adcmsoral fraction (Allen et * . 1575). 1, In a preliminary feyott of a two-year chronic tcodcity feeding study, Dew Gbeadcal USA (Traynor, 1977) reported the following residue data for rats fed indicztad TOO doses: 24,000 ppt in liver and 8,100 ppt in fat of famalas ingasting 2,200 ppt/d«y; 5,100 ppt in liver and 1,7C3 ppt in fat of feaales ingesting 220 ppt/day; and 540 ppt in liver and fat of fenales ingesting 22 ppt/day. The preliminary report gives no residue data for treated males, or for control of either sex. 5. ntuiWuij the National Huamn Henitoring Program for Pesticides is currently sampling human urine and analyzing theue sacpla* for silvex, ?,,4,5-T, and 2,4,5-TC? through its cooperative arrangement with the EPA Health and Nutritional Examination Survey II (Banes II project). The survey is scheduled for oanpleticn in 1979. Sera preliminary t*sults that relate to 2,4,5-TC? residues in the first 400 of an esti&atad 7,500 sact(13) �pies era available These results are only tentative and of court* subject to change a« further data are received. Of the initial swsqplaa analyzed, 1*66% have shown detectable labels of 2,4,5-TCP with a madman aaount of 32.4 ppb. The arithmetic mean is leas than 1 ppb. In addition, 32.69% of the sanplas hsv* shown trace Mounts (< 5 ppb) of 2,4,5-TCP. Residues of «^ia ccspcund nay also be derived from the metabolism of other pesticides and fcrtn expecure to 2,4,5-TG? that was used as a disinfectant (Kutz, 1 7 ) 97. 7. Animal a. 2,4>s/-TCP and No infonaation is available on the presence of 2,4,5-TG? residues in anianl products, Bcwever, in tests with cattle, sheep, and calves that were fed diets containing 2,4,5-T and allvex, residues of 2,4,5-TC? were detected in th« kidney, liver, tajscl*, fat, and milk (dark et al. 1975; 1976T Bjerke et al. , 1972) . b. Mhen beef fat samples that had been fortified with 2000 ppa 2,4,5o 1C? or its sodium salt were cocked at 500 F for 6-22 hours and analyzed, no TCDD was found in any of the sasples. Th« limit of detection was 0.05 ppa (Watts and Stotherr, 1973) . Eighty-five saqples o£ beef fat were analyzed for TCD content under the auspices of the EFA Dioxin Xvp.\enBntation Plan (see d1 scission p. 20). The beef fat sasples included 18 sascles from ccntroi areas and 67 saoples from areas previously treated with 2,4,5-T. Nona of the 18 control sarplea had detectable amount of TCTO at a detection (14) �of 10 ppt. Of these 67 sasplas from areas previously exposed to 2,4,5-T, one shewed • positive TCDD Isvul of $0 ppt; 2 appeared to have TOCO at 20 ppt; and 5 may have had TOO levels which singed from 5-10 ppt. The values for these 5 staples were at or' talow the lind.ta of detection of 10 ppt. Forty-three beef liver samples were analyzed and showed no TOCO residues at a detection Unit of 10 ppt* F. Accidental Huran Exposure In the cases of human exposure to 2,4,5-TC?, the only adverse effects reported were caused by occupational exposure or accidents that rod during the manufacture of chlcrinatad phenols or producss derived £iun then* In 1949, intersndiary chemicals of the oanufacturing prccess were released in a U.S. 2,4,5-T plant, this accident led to 117 eases of chlcracne aseng exposed worXars (Whitaside, 1 7 ) 97. In 1953 there was? an accident in a Middle Rhine factory manufacturing 2,4,5-TCP from 1,2,4rS-tetrachlorobenzene. In addition to contracting chloracne (Goldman, 1972), aany workers had liver cirrhosis, heart conplaints, and nervous system disorders, and were depressed (Bauer et al., 16) 91. In 1953, 31 esployees of a ganturg, Geraany, plant in which 2,4,5-7 wes made from technical 2,4,5-TC? contracted chlcracne and suffered the physical and psychological syr^tons associated with it (Poland et al., 1971). In 1961 Bauer et al. conclusively identified TCCO as the cause of the chloracne. (15) �An explosion occurred in a 2,4,5-T plant in Aaaterism in 1963. Six Months later, nine of the 18 &en, who were attesting to cacontacinate the plant, developed chloracne. All of the nen had worn deep sea diving suits* and all but one wore face soaks with goggles while working in the plant. Of these nan, three died within 2 years. Tha nan without the face mask or goggles was severely affected. Be was unable to walk and is still undergoing treatment (Whitaside, 1 7 ) 97. In 1964, workers in a 2,4,5-T plant in the United States developed chtocacne from exposure to TCXD (Poland et al., 1 7 ) 91. there was an explosion at the Coalite Ccacany's 2,4,5-TC? plant in Great Britain in 1968. TCCD had aceidently been produced as the result of an exothermic reaction (Milnes, 1971; May, 1973). Seventy-nine cases of chloracne were cayottad; many of then were severe. In 1971 there was an accidental poisoning episcxw L* «!*« United States that affected humans, horses, and other anisals. Waste oil contaminated with TCCD had baen sprayed on a riding arena to control dust.. Later analyses shewed that the arena contained TOT in concentrations of 31.8 to 33.0 ug/g (Carter et al., 1975). Gaorener and Scott (1976) found that the most irportant route of entry of dicxin into the body was the skin. (This dees not preclude the effects of ingesting food contaminated with dioxin from handling.) A 6-year-old girl was the aost severely affected. She had an inflammatory reaction of the kidneys and bladder bleeding fiat was diagncsed as acute heocrrhagic cystitis with signs of focal pyelonephritis. Hisa less severely affected persons developed diarrhea, headaches, nausea, polyarthralgias, and (16) �persistent akin lesions ( . . EPA, 1975). The girl moat affected was US thoroughly reexamined in 1976. Results indicated that all of her artginal symptom hai* completely disappeared. She had grown normally and all tests, including a detailed neurological examination, were normal (Beale et al., 1 7 ) 97. In July 1976, 2-10 pounds of TCDO were accidentally released in the Seveso Region of Italy (Devse, 1 7 ) Host of the inhabitants were 96. adversely affected. Seputia of immediate symptom atd indications of ootiy long-term effects are just becoming available. The first overt reaction was the appearance of nunnrous burn-like lesions on many of the inhabitants, These lesions generally receded. Whiteside ( 9 7 believes 17) that they were probably caused by direct contact with the sodium hydroxide and phenolic ceepcnents in the fallout. However, 2 1/2 months after the explosion, an increasing number "it children and young pecnl* in the zone nest affected began to develop synptoss of chlcrae-* on their faces and bodies, a definite made of diootin poisoning. By Novecber 23 people had of chloracne. This number rose to 38 by Decestoer and to 130 a year after the explosion. A nutcber of the victims exposed underwent a "ccrolcte change of character*; they became extremely nervous, tired, needy, and irritable, and had a oaxfeed loss of appetite. There were a *»ffl*j*r of Seveso woman who were pregnant at the tine of the accident. Whiteside ( 9 7 reported that the total number of 17) legal and illegal abortions performed as a result of the explosion preferably totaled 90. There were 51 spontaneous (as distinct from induced) abortions. A survey conducted by an epideaiological comnissicr. has shewn (17) �that 183 babiaa ware delivered in the 2 Earths following the accident, Eight cues of birth abnoatilitias have been noted anong babies born to woman in the Sevuo area who were pregnant aft the tin* of the explosion. However, Innil physicians have had,,difficulty relating those abnonaalities directly to the explosion because the incidence of birth abnormalities was not significantly higher than the nonanl incidence of abnormal births (Whitsside, 1 7 ) 97. H. Regulatory History The regulation of many polychlorinated ring compounds. has been related to the presence of TOD as a contaminant in the '»'™»K't*\ product. Historically, regulation has focused on 2,4,5-7. In October 1969, Bionetics Research Laboratory, a contractor for the Rational Cancer Institute, released information on their large scale screening of a nuaber of pesticides and industrial chemicals for nutaganicity, caurcinogenicity, and teratogenicLty. They found 2,4,5-7 to be taratogenic in nice when 113 tna/lcg body weight was administered during early pregnancy. Birth defects included cleft palates and cystic kidneys. On later examination researchers ascertained that the 2,4,5-T was contaminated with apptuxlaately 30 ppm TCDD. This and other scientific studies suBcarized in this Section are fully discussed in Sections XU and 1 . 7 On October 29, 1965, the President's Science Adviser responded to the release of the Bionetics' rqxu.S. by announcing that a series cf coordinated actions would be taken by several government agencies to restrict the use of the herbicide 2,4,5-T. (IB) �In early 1970, aniaal experiments confirrad that when the purest «vau'<*ble 2,4,5-T, which contained leas than 0.05 pern TODQ, was fed to pregnant mica in large doses, the offspring would be malformed (Courtney and Koore, 1971). On April 15, 1970, the Secretaries of Agriculture; Eealth, Education and Welfare; &nd Interior announced the suspension of the following registrations of 2,4,5-T: all uses in lakes, ponds, or ditch banks; and liquid femulations for use arcond the hone, recreational areas, and similar sites (USDA-PRD PR 70*1, April 20, 1970). A notice of cancellation of • registration was issued on Hay 1, 1970, for all granular 2,4,5-7 forsulaticns for use around the hone, recreational arena, and sisdlar sites, and all 2,4,5-T uses en crops intended for huean consunpticn (USDA-PRD PR 7013, May 1, 1970). On Septantcr 23, 1570, the Department of Agriculture issued a Pesticide Registration notice stating that all products containing TCT were in violation of FXE3& because they constituted a possible hazard to humans. Th* notice indicated that appropriate regulatory acticn would be taken if TOO were found in any econcadc poison (USDA-PFD PR 70-22, September 28, 1970). On May 5, 1971, the Report of the Advisory Comittee to the S?A Administrator reccseanded that use of 2,4,5-T be peraitted only under certain conditions in forests, ranges, and righta-of-way providing: 1) that a limt of 0.1 pern TCDD be set for all future production of 2,4,5-T; 2) that 2,4,5-7 be applied no acre than once a year (19) �at any one site; and 3) that 2,4,5-T be applied with caution so it will not contaninate other areas where It may cone • into human contact. . « • . , - . . . ' '„•/ - - . - • • • In July 1972 Dm Chemical Company obtained an injunction against EPA. The Court of Appeals for the 8th Circuit overturned this injunc- ' tion in 1S73. EPA withdrew cancellation and information gathering proceedings initiated against 2 4 5 T and related oajgiamJs on June 24, 1974, ,,due to the Agency's inability to monitor food for residues of TCDD with the necessary analytical precision. ' In July 1974 EPA held a Dioxin Planning Conference in Washington, D.C. Participants of the public meeting discussed data analysis, analytical methodology, toxicology, and acnitoring. There was an emphasis on developing analytical methodology for detecting TCDD in parts per trillion. As a result, the Agency promulgated the Pinrin Implementation Plan (DIP) to identify a preferable analytical method to monitor human and environmental samples for TCDD residues in tb« low parts psr trillion (ppt) range. * DIP consisted of a short-tarn monitoring ptojidiu involving beef fat and liver samples and a broad 2- to 5-year research plan. The Environmental Defense Pund, the Departmssnt of Agriculture, and Dew Chemical Ceapany participated in the monitoring program, which utilized iaproved analytical methodology capable of detecting TCDD in the parts per trillion range. . ' . . " .' . . ' ' .. - • On-going TCDD studies under the DIP include: an analytical method validation study to produce statistically defensible data; monitoring for (20) �residues in human milk in the Pacific Northwest; additional beef fat residue studies; additional technical pesticide residue studies; and an «nvinaraasntai monitoring program for TQ3D residues in soil* water/ and biota. IH. Sunggry of Scientific_ Evident RelatJjrvg to Retauttable Presumption A. Cneogenie Effects in Test Animals 40 OR Section 1 2 1 ( ) ( ) U ( ) provides that a rebuttabl* pre6.1a 3()A •waption shall arise if a pesticide's ingredient(s), aetabolite(s}, or . degradation product ( ) . induces oncsgenic effects in experimental mans.. na 1,inn species or in man as a result of oral, inhalation or dermal exposure...* Section 162.3(bb) defines the tarn oncaganie as "the property of a substance or a mixture of substances to produce or induce benign or malignant tuner fewaticn in living animals." 1. 2,4,5-*CP Because all 2,4,5-TC? contains a certain accunt of TCED, any reference to 2,4,5-TC? denotes a product that is contaminated. As a result, all the information used to assess 2,4,5-TC? in relation to Section 162.11 risk criteria is derived frcn studies in which the test substance was 2,4,5-TCP contaminated with TCED. The Agency Knows of no data relating to pure 2,4,5-TC?. The National Cancer Institute tested 2,4,5-TC? for carcincgeniciry (Znnes et al., 1369). Two hybrid strain of mice [(C57BL/&x£2H/Anf)F and 1 (G57BL/6xAKR)F I were given a single subcutaneous injection of 1000 rrn/ 1 Jcg 2,4,5-TCPAg ( 7 pure, contaminant not specified) in corn oil when 9% the mice were approximately 28 days old. Mo significant difference in tumor frequency was found between the 2,4,5-TC? treated groups and the control mice at necrccsy. (21) �In a short-term study on BHC (benzene bexachloride} iscmers and their metabolites including 2,4,5-TCP, Goto en al. (1972) fed twenty 5-veek-old mala XCEKfCL mice a diet containing 600 ppra 2,4,5-TQP (contaminant in 2,4,5-TCP not specified) each day for 6 months. They observed no unusual weight increases in the hearts, kidneys, or livers of treated ode* as compared to the controls. No tumors were noted in the nice fed 2,4,5-TCP although malignant and benign tumors were noted in the livers of mice fed technical BHC, alpha-BHC, beta-SBC, and gacma-ac. The EPA Carcinogen Assessment Group (QG) judged these studies inadequate for assessing the cncscenic potential of 2,4,5-TC?. The Noticing Group concurs. 2. TCP a. Van Miller Study A recent pe?«r by Van Miller et al. (1977) reports the results of a 2-year feeding study with Sprague—-awley rats. Groups cf 10 rats were administered a diet containing TCZD in one of the following csncentra-12 ticns: 0, lf 5, 50, and 500 parts per trillion (ppt, 10 g TCSD/g food), -9 and 1, 5, 50, 500, or 1000 parts per billion (ppb, 10 g TCD/g food). LaparotCBdes were perf orsad on all surviving rats during the 65th week. Biopsies were performed fran all tumors observed. Rats were maintained on the diet for 78 weeks and w-re then placed on the control diet. Surviving rats were killed at 95 vwecs. Complete necropsies were done at this time and tissue samples wers mcrcscspically examined. Special staining methods were used as an "aid in the diagnosis of neoplasms." Food intake was significantly lower in rats that ingested SO, 500, '22: �or 1000 ODD TCDD than U was in the control animals. AH of the rats administered these doses died between the second and fourth weeks of treatment. At the sublethal doses, there were,toxic and tuoorigenie effects. Three of the 10 deaths which occurred in the 5 ppb dose group were at* tributed to aplastic anemia. One aninal in the 500 pot group had severe liver infarction. The overall incidence of neoolasras in the six experimental grouos was 381 (23/60), compared with no lesions or 01 (0/10) in the control group. This difference is statistically significant. Neo- plastic nodules and cholangiocarci nomas of the liver were observed in 4 of 10 rats (40?) that ingested 3 ppb TCDD (two animals had both neoolastic plastic nodules of the liver and cholangiocarcinomas). One rat, (101) in the grouo that ingested 1 ppb had a carcinoma compared to none of the controls. Heoatic tumors were not found in rats administered the other doses (Table 1). I/ TABLE 1. Liver tumors in rats that ingested TCDD" Rats With Neoolastic Modules No. * Rats with 0 0/10 0 0/10 0 0/10 0 1 0/10 0 1/10 10 2/ 2/10 20~ 1/10 10 2/ 4/10 40~ Dose, oob 5 I/ ?/ ~" 4/10 2/ 40" Cholangiocarci nomas NO. * Rats With Nodules plus Carcinomas No. "• Data from Van Miller (1977). Two animals had both neoolastic nodules of the liver and cholangiocarci nomas. (23) �Benign and wlignant tuners developed in rats ttiat ingested 5, 50, or 500 ppt and 1 or 5 ppb TCDD, ccq»ared to none in ttva control rats. Twentytfajree of the rats (46%) in these 5 groups had tuners. Nineteen of these tats (57%) that died in die 6 groups fed subecute level* of TCDD bad nedplastic alterations. Three rats that ingested 5 p$b died of aplastic anemia.. Caretncins were observed in the ear duct, kidney, and liver. Three retrqperitoneal histiocytcnas were described as netastasizing to the lungs, kidney, liver, and skeletal nuscul&ture. Statistically significant increasea in tuners at all sites were found in the rats fed 5, 50, 500, 1000, and 5000 ppt as ccceared with the central animals (p • 0.05) (Table 2). b. Preliminary Reuort: Dow Chfnienl Caneanv Studv The Dew Chemical Coopany has just ceopleted a chronic toxidty study of TCED with 472 Sprague-Cwley rats (Traynor, 1 7 ) Fifty rats 97. of each sex were maintained for 2 years on diets which contained 0.001, 0.01, and 0.1 ug TCSVkg body weicht/day. This dose is equivalent to approximately 22, 210, and 2,200 =pt in the diet. Eighty-six rats of each sex were maintained on a central diet. Table 3 lists the tuners found. c. Conclusion The Working Group has concluded that there is evidence to indicate that TCXD can produce cncogenic effects in rats. Since 2,4,5-TC? contains TCOD (at a nuxirun areunt of 0.099 pent), a rebuttable presunrtion against the registration of 2,4,5-TC? products has arisen because of the cnceeenic effects of its ccnczstLrant, TCTC. (24) �/ T&8LE 2. Benign andrmalignant .tamer* in rata that ingested TCDD" Dose y Ho. Turoca Benign '— Malign*.re Total 0 0 0 Ippt 0 0 Sppt 1 50 ppt Rata with T No. 0 0/10 0 0 0/10 0 5 6 5/10 50 2 1 3 3/10 30 500 ppt 2 2 4 4/10 Ippb 0 5 5 4/10 40 Sffb 8 2 10 7/10 3/ 4/ T/ J/ 7/ 8/ S/ 1 40 70 Data from Van Miller (1977). Rats administered 50, 500, and 1000 peb were all dead within 4 weeks. Fore? mala rats that were ua«d aa controls for anotbar study w«n recaivssd at th« sane tic* a* tha cats in this study and kapt under identical conditions. "Sxty did not haw nacplasat whan '*il'«" at 18 nonths. BITM rata di«d of aplastic anastia. Gm rat had scror* livar infarction. Ona cat had an car duct cardncm and lynphccytic laulcaaia. Ona rat had an adanacareinaBfli (kidnay). Cm cat had a malignant histioe/tona (ratroparitonoal). Ona rat had an angicoarcstn (skin). CM rat had e Laydig call adtncoa (tastis). Qna rat had a fiibroaavcani (nuscla). CM r?it had a aquanous call tumor (skin). OnC' rat had an astirouytcca (brain). Or« rat had a fibroma (striated nuscle). Cna rat had a careinam (skin). One rat had an adenocarcincaa (kidney). One rat had a sclerosing sacdncna (testis). One rat had a cholangiocareinoaa and malignant histiocytoaas (retroperitoneal). Cna rat had an angiosaroana (skin). One rat had a glictxUstcca (brain). One rat had a nalignant histiocytona (retrcceritsneal). One rat had a squancus call tuner (lung) and a nccoXastic nodule (liv«r), TWO rats had cholanqioaurcinanas and necplastic nodules (liver). Three rats had squanous cell tucora (lung). One had a necplastic nodule. (25) �3. Tuners in SprsgueHJewuey rats that intmted TCCP Dose, pet x-"' 0 0 22 0 210 Bepatoctnnlar Modules & Squaaous Call Carcinana Alveolar flyperplasis 3/ Squatnous Cell Carcinoma 2,200 I/ Data from the pgnHnrinary report of tfa« Dew Cbndcal Conpany Stucy, 1377. 2/ Bardjsalat* squaeous dsll cardnams WKPB obscrTvd Ln one fanale rat. 3/ Squaoous coil cardncBU wct« obaKrvod in th« lung/ bart^alate/nasal turSlnatas, or tongu*. B. y»totg»ie arri_?arateg>gue___Egftcas in Maeralian Soteiaa 40 CFR 162.n(a)(3)(ii)(B) provides that a rttbuttabl* tion shall arise if a pesticide's ingredients "...(p)roducea any other chronic or delayed toxic effect in test animals at any dosage up to a lev*!, as determined, by the Administrator, which is substantially higher than that to vni.ch humans can reasonably be anticipated to be exposed, talcing into account arple margins of safety.* Drteyotoxic effects are considered to denote all transient cr n*nt taodc effects induced in an entryo or fetus, regardless of the nechzm-lta of ^action. Ciese effects include teratceenicity, nertal- (26) �,*__ �2. TCDD A number of studies on the embryotoxicity of TCDD indicate that there are two major types of toratogenic effects generally associated with teat animal a receiving doses of TCDD during pregnancy: cleft palates in nice and Iddaay anomalies in rats and nice. TCDD is also fetotoxic in these species. a. Hice The first evidence that TCDD night represent a reproductive hazard to humnn appeared in 1970 in a Bionetica Research Institute study which reported that 2,4,5-T was teratogenic (Courtney et al.t 1970). When a dosage of 113 ng/kg 2,4,5-T was administered to AK nice on days 6 to 15 of pregnancy, 49} of the fetuses were deforced. Cleft palates, cystic kidneys, and fetal mortality were the cannon anomalies found. However, analysis using gas chromatcgraphy later showed that the 2,4,5-T used in the Sianetics study was contaminated with 27 * 8 ppm TCDD. The question of whether dioxin rather than 2,4,5-T caused these adverse effects was raised. Courtney and Moore (1971) studied the enbryotoxic and teratcgenic effects of TCDD in three strains cf pregnant nice (Table 5). Test aniaala were administered 1 and 3 ug TCDD/kg body weight sutcatanecusly in solutions of 100% DMSO (dimethylaulfoxide) an days 6-15 of gestation. DMSC was administered as the control. TCDD produced cleft palates in all three strains of mice. In the CD-1 nice 305 of the litters (3/10) had fetuses witt cleft palates at 3 ug/kg as compared to 05 of the controls (0/9). Seventy-one percent cf the litters cf C5731/6 mice (5/7) had cleft palates at 3 ug/jcg iccy weight as copared t& CS (0/23) of tne ccntrcis. Twenty- �two percent ( / liters) of the DBA/2 nice also bad cleft palates at this 29 sane dosage as compared to OJ ( / 3 of the controls. The authors also 02) found a marked iocrtase in the incidence of IcLtaey anomalies in all mice atralas (Table 5 . There was a dose-related response in the CD-1 mice. ) One strain of inbred mice, C57B1/6, which was'especially sensitive, developed kidney anomalies in all seven 0 0 ) of the litters as compared to 0} 9J ( / 3 in the controls. Although TCDD produced a significant increase 22) in the ratio of maternal liver weight to body weight in the inbred nice strains (C57B1/6 and DBA/?/, the CD-I (randomly bred) mice were not significantly affected. TCDD had no effect on fetal mortality, fetal weights, or maternal weights at the doses administered. In another study in which six dicxlns were administered subcutaneous! y and orally to CD-1 mice, Courtney (1976) found TCSD to be the scat fetotoxic and teratogenic by either route of exposure at all dose levels tasted. On days 7-16 of gestation, TCDD was adaiaistared orally at 2S-WO ug/kg/body weight and subcutaneously at 25-200 ug/lcg/bcdy weight. The results are given in Table 6. Mortality per litter increased with the dose and reached 97* (cral) and 76S (subcutaneous) in the litters administered TCDD, as compared with a mortality of 6 and 14*. in the oral and subcutaneous control groups, respectively. The most common anomalies observed were cleft palates and malformed kidneys. All cf the fetuses in the 200 and 40C ug/kg (cral) and 200 ug/kg (subcutaneous) groups exhibited cleft palates as cccpared to 0* af the controls. Cf the fetuses in the 200 ug/kg (oral) group, ?CC* had Idiney salfunctises as cczparad to '* of the controls. Other (9 2) �M TAIH.fi 5. Smannry of the teratogenlg effects of TCDD In mice and rata Dose, Strain ug/kg l.lttera Affected/ Live Llttera Cleft Palate Kidney Anomalies No. No. \ * Average Fetuses Affected/Live Llttera Kidney Anomalies Cleft Palate No. No. % i NICE CIM DHA/2 C5701/6 0 (DHSO) 0/9 1 1/9 3/10 3 0 11 30 3/9 5/9 10/10 0 (DHSO) 0/23 3 2/29 0 22 0 (DHSO) 0/23 5/7 3 0 71 0 22 100 0/9 2/9 1/10 to 1/9 169 ./ 6.5/10 11 51 65 3/23 8/9 13 69 0/23 1/9 0 11 1/23 1.8/9 * 20 2/23 7/7 9 100 0/23 267 ./ 0 37 1/23 3/7 13 0/9 0/6 0 0 33 56 4 RATS CD 0 (DHSO) 0/9 0/6 05 . 0 0 0/9 1/6 0 67 J/ Data frou Courtney and Moore (1971). (30) 0/9 1.8/6 0 30 �I/ TABLE 6. Fetotoxio and teratogenJo effeota of TCDO in CD-I nice" Dose, ug/kg/day Abncraal Ancaalies/Total Fetuses Average Fetal Average No. Route of Ad- hortality/ Abnoroal Cleft Kidney Ano- Club ministration l.ltter, £ Fotusea/Lltter Palate, % nalies, % Foot, % 25 50 100 200 400 oral oral oral oral oral 6 13 11 87 97 25 50 100 200 subcutaneous subcutaneous subcutaneous subcutaneous 36 56 72 5% antsole com oil oral 1.6 8.1 8.3 1.5 3 19 66 100 subcutaneous 3 7 13 11 01 . too 100 50 6.7 53 58 95 38 17 1 j, 76 3.5 3.1 82 79 85 100 6 0.8 0 11 0.2 0 50 . ( . ml) 01 WISO 3* 72 71 I/ Data froa Courtney (1976). ?/ ItttSO = dimethylsulfoxlde (31) 50 11 0 18 �anomalies observed ware bydrccepbalus, open «ye, and club foot. Edema and patachlae were also observed in f«tus«s administered the high doses* Responses appeared to be dose-related. Subcutan*cus injection produced greater responses than did oral administration. Moore et al. (1973) tlso found that TCDO caused fetotoxio and teratogenic rtspotties in C57B1/6 nice at a dose level as low as 1 ug/kg administered on days 10 through 13 of gestation. Compared with C% incidence (0/27} in the control litters, W (15/16) of the treated litters exhibited kidney anomalies and 195 (3/16) had cleft palates. At 3 ug/'/cg the tnrlrttnra of thes« ancmalies ma 1005 (U/1U) and 365 (12/TO, respectively. Keubert and Dillcann (1972) tasted the ambryotosic and teratcgenic effects of TOD in NMHI mice. In one test pregnant mice wore given varying doses of TCDO (0.3~9 ug/kg) by intubation on da/s 6-15 of gestation. Results are shown in Table 7. Very high eabryomoruiity was observed, as expressed by the percent of fruitful wcmfas shawiMg evidence of resorptions. At 9 ug/kg, all viable litters (3/3) evidenced i-esorptions; 675 (6/9) cf all litters bad total reserptions. Oil control values war« 32 and 05 for litters with resorptions and litters with total resorptions, rsspectiveJLy. Cleft palate was observed in all of the litters and 825 of the fetuses at 9 ug/kg; comparable oil control vaiuis were 6 and 0.75, respectively. Statistically significant (p < 0.01) proportions of the fetuses evidenced cleft palate at 3, *.5, and 9 u^/kg (3, 13, and 825, respectively) when compared with the oil control. In another test in which high doses of TC2D wers given orally or. a (32) �TABLE 7. &tbfwtMo_aBd_taratcg«ale affects of TCDD on NMHI alee 2/ DOM,"" us/kg 0 Oil 0.3 3.0 4.5 9.0 90 .* Litters Affected/Viable Litters Hesorptions Cleft Palate Ho. 2 No. "1 23/95 24 6 21/65 32 7/13 16/24 54 67 6/95 4/65 0/13 7/24 5/12 42 6/12 50 3/3 100 100 3/6 50 3/3 5/6 6 0 29 . 83 1/ Data, froa Seunert and DJ I (92. 17) 2V Dose adaiaistered on days 6-15. J/ Dose adoiniatered on days 9-13. day of gtstation, Heubert and Dillaann (1972) observed tba same type of effects on eaiapynaertality and the incidence of cleft palate. Tie autfcars adndclaterad 23 and 45 ug/kg TCDD on day 6. The nay1,im,an effect on mortality (reaorption in 100} of t£> riabie litters) waa seen in the oice administered 45 ug/icg. tbe highest Incidence of daft palate (71* of viable litters) was noted at 45 ug/kg on day 11. Control values were 24} for litters with rescrpticn and 6} for litters with cleft palates. Sodtn et al. (1976) studied the teratagenicity of TCDD la. C7-1 sice. Dosages of O.C01, C.01, 0.1, 1, ace! 3 ug TC2D/kg bcdy wnigst/cay (23) ' �were administered by gavage on days 6 through 15 of gestation. The percentage of resolutions per iaplantation was significantly higher than It vita in the controls only in the 1 ug/kg group. The incidence of daft palates in tta 1 and 3 us/kg dose groups was significantly higher tfcan it VMS in the controls (Table 8). At 3 ug/kg there was also a significantly greater incidence of litters that had fetuses with bilateral dilated renal pelvlses than there was in the controls. The authors concluded that the no-effect level for taratogenic effects from TCDO was 0.1 ug/kg/d&y. Neubert et al. (1973) found that TCDO was highly embryocoxie and fetotoxic in nice, extrapolating from a dose-response curve, they estimated the E33 for cleft palate in fetuses was 40 ug/kg/day. The co50 effect level during days 6 to 15 of gestation was estimated to be 2 ug/ kg/day for NHRZ mice. No pronounced fetal mortality was observed vtsen 3 ug TCDD/kg body weight was adoisistered on days 6-15 of pregnancy (Table 9); b. Rats Sparschu et al. (1971) studied the teratogsnicity of TCCC in Sprague-Cawley rats. TOD was administered orally in concentrations of 0.03, 0.125, 0.5, 2, and 8 ug/kg/day on days 6-15 of gestation. _ There was a high incidence of fetal mortality. At 8 ug/kg/day all fetuses (100?) were resorted as compared to 63/309 (20%) in the controls. Fetal weights were depressed in the 0.125, 0.5, and 2 ug/kg/day groups. The occurrence of this effect was statistically significant in all groups except the females administered 0.5 ug/kg. Most of the abnormalities *T �_$/ TABLE 8. getptoKJo and toratOBgnto effeota of TCDp in CP-1 Hloa" Dose, ton/kg Incidence. of Cleft Palate in Litters/Live Llttora too. * Lit tens with Reaorbed Fetuaea/ Live Litters No. I 0 0/34 0 25/34 74 0/34 0 001 .0 2/41 5 30/41 73 0/41 0 0.01 0/19 0 17/19 89 0/19 0 01 . 1/17 6 16/17 94 0/17 0 21 21 21 16/19 95 1/19 11/14 78 4/14 1.0 4/19 3.0 10/14 Utters with Dilated Renal Pelviaaa/Liva Littera % No, x 5 aT7 I/ Data from Saith et al. (1976). ?/ Statistically different from the control by the Fishera exact probability teat (p < 0.05 (35) �TABLE 9. Occurrence of cleft palate in offspring of mice fed TCDD Str*m CD-I DBA NMRI C57B1 Dose, ug/lcg 0 3 0 3 0 3 0 3 Cleft Palates/Total Fetuses Examined, % < 0.3 3 <1 4 0.7 3 < 1 22 Affected Litters/ Total Litters NO. % 0/29 0 3/10 30 0/23 2/9 0 22 10/160 7/2U 6 29 0/23 5/7 0 71 I/ Data, from Keubert et al. ( 9 3 . 17) noted were intestinal benorrtagea. No adverse effects were noted in the fetuses whose mothers were fed 0 0 ug/kg/day. Table 10 sbows the dose/ .3 response relatiocship. The authors concluded that TC3D induced a high level of maternal and fetal toxicity and that 0.03 ug/kg/day vaa the noeffect level for fetal and embryotoxic effects in rats. Khera and Huddick (1973) studied the effect of TCDD on reproduction in Vistar rats. In tha first test, rats were orally administered 0.125-1 ug TCDD/kg on days 6-15 of gestation. Observations of visceral lesions showed a dose-response relationship at 0 2 ug/Vcg and above; .5 slight decreases in fetal weight were also seen (Table 11). Postnatal effects of prenatal exposure to TCDD were studied by allowing offspring (36) �10. Intestinal hemorrhages In offsprin of Sraue-Dawley rats fed TOD* — Doa*, ug/k$/day Fetuses Affected/ • Liters Affected/ Fetuses Examined - Litters Exanined % No. i NO. Q (control) 0/246 0.03 0/115 0.125 0.5 20 . 0 0 0/24 0 0/10 0 18/127 14 7/10 70 36/99 4/7 36 57 10/12 83 2/4 50 8.0 - - . - V Data frcn Scarschu et al. (1971). of treated data to bo roared by untreated dams until waning. Reduced survival, body waigbt, and reproductive ability in tba progeny were observed after tfca notters were treated with 0.5 and 1.0 us/kg. Ho fa totoxic effects were observed at 0.125 ug/kg. la a second experiment rats were treated orally with 1-16 ug TCDD/ kg body weight/day on days 6-15 of gnstation. ' Doses of U ug/kg of Qors producod maternal torLcity and 100% eabrycesartalitr/. Fetal weight, nunbar- of live fetuses per litter, and incidence of visceral lesions were all adversely affected by treatment. The incidence of skeletal anon 1! a* was comparable to that in the controls at all dcse levels testad. The authors concluded that oral treatsent of pragnant Wlstar rats with 0.25 ug (or aore)/kg/day on days 6-15 of gestation results in adverse effects �BU& i i. i«rTBl.OPRn.lC BJ:itrcta ATeraga Ho. Liva Fatuaaa/ __ Ltttar Dosa, us/Teg 01 iuuu in NUT•*r rats Fatusaa with Sctlatal Anomalita/ Total No. Examined Av*rag« Fatal Wai£btv S No. TEST T Fatusas with Microaocpic ViscenL Lasiooa/ Total No. Examined J No. % Dntraatad Control lfl.7 4.82 5/107 5 0/13 0 Control 11.0 4.51 21/116 18 o/u 0 0.125 10.6 4.64 3/121 2 0/38 0 0.25 10.9 4.79 6/109 6 1/33 3 0.5 10.5 4.46 10/105 10 3/31 10 1.0 9.3 4.10 6/81 7 3/10 30 7 0/10 0 y . T£5T II Untreated Control 11.5 4.68 Treatad"" Control 9.8 4.77 9/09 10 0/10 0 1.0 6.5 4.17 7/80 9 3/6 50 2.0 6.0 3.31 7/57 12 3/7 43 4,0 0 - - - 8.0 0 - - - 16.0 0 - - - y 8/116 * I/ Data from Khara and Rudclick ( 9 3 . 17) ?/ Anisola - corn oil. (28) �en cat develfifxdent. Courtney and Moore (1971) studied the teratogenicity and anbryotoslcity of TOO in CD cats. TCDO was fldndnitftared stibcutanecusly in solutions of 100% CK50 on days 6-15 of gestation. DSHD was adsdnistarad -w tbr control. Kidney anmaUaa were found in four of the six Utters ($7%) whose dan wore administarad 0.5 ogAg as coopered to Ot (0/9) in tha controls* Results also shewed that TCQD did not causa an incraasa in fatal mortality, fatal weight, or cleft palatas in tha fatusas. Tibia 5 sunorizas tha results of tha study. Dow Qiendcal QSA (Traynor, 19T7) eenducxsd a thpaa ganataduai raproductiTw study OB Spragua-Dawlay cats continuously fad tha aquivalant of 0.001, 0.01, cc 0.1 ug TCDD/Tcg/day. A pealindnary caport dtas caducad fartility and littar survival in f cats as tha raascns for discontinuing 0 -tha 0^ ugAg dcaa Lwalj significantly caducad fertility was also cbMrvad at 0.01 ug/fcg. "Claarly erLcJant" indications of todLcity at 0.01 ugA? ananq f and £ lifetsrs, included «"•"•*• littar size at birth, plus 2 3 dacsaaaad survival and growth of nacnatas. Dilated canal pelvis was ob- served in each of tha three f cats at 0.1 ug/kg which survived to adult1 need. Incraaiwd frequency of this anosaly was also seen acong weanlings at lever doseat howweir, a dose-related or generational cacralaticn could not be nuta. in sunnaxy, Qow concluded that "the reproductive capacity of cats ingesting TCDD was clearly affected at dose levels of 0.01 and 0.1 ugAg per day, but not at 0.001 ugAg par day, through three successive generations." The preliminary ntpcrt did not include the nuoerical data necessary for Agency cvaluaticn. Analysis will continue as these available. (35) �In aunauy, atudiaa how astabliahad that TCED in fietotoxLc and tacatoganie at dQaas aa low m 0.2S uqAq in tha rat {Xhara and Ruddidc, 1973) and at 0.3 ug/k<3 in th* sous* (Ncubaet and BiiiBam, 1972). Tabla 12 lists th« no-*ff act lav«la £cr taxmtogjanicLty in tuba and aioa fiecm 1CDO. Ho tatotoaiie or taxatoganic affacta haw bean obaarvad at doaaa ofi 0.03 aq/log in tats (Sparxlm «t aJL , 1971) and 0.1 ug/kq In ode* (Sadtfa, 1976). c. Chicic Etabtyoa Bui Hoi «t al. (1971) aatablishad that 0.02 ugAq TCED causad Laiau^jmiic affacts in chid? artacyca. Bowaa at al. (1973) and Vatratt (1970) oonfiioBBd thair nwults. TSjay found abnotamlitiaa in tha baaks, ayaa, and faat of chide 12. Summary of jronrff act, leromla for turataganaais ftrem 2,3,7f 8-T Soadm Routa of Adainistrsti.cn ""^SS/daT^' Rat Heum Ran SC sc < 0.2 < 1.0 Oral 0.125 Rat Oral 0.03 tiaubatt and DilLnan (1972) MOUM Oral < 0.3 Smith at al. (1976) Housa Oral 0.1 lijjj^j%^Fl*mBai> •^••jj^ ^•nnv^B (1971) Xhan And Ruddidc (1971) Spatschu at aJL. (1971) SC • Subcutanaeusly (40) �3. Pj^panre Analysis Zn order to datannine whether a rebuttafaie presuBXJtion should be inuad based on reproaucti-ow and fetotoxic effects, pursuant to Section 162.U(a)(3)(UHB), the Mocking Group nat determine whether or not an asple amrqdr. of satat. exists batman th« levels of 2,4,5-TCP or ita salts and/or TCCD which produce reproductive and fatotoxic effects* and thai l«vel(s) to which that pnpuljtim at risk (wocan of child-bearing age) on tmasonably ba anticipatad to b* aaeposad. Social changaa ewer the list few yeaxaf however, have giwi M * wonn the opportunity for aBploynent in axeaa) that were once considered open only to nan. Since wonan of child-bearing age are new employed in all types of occupations, they have beoane part of the pnpnlatlcn «t risk with potaRtisl exposure to 2,4,5-TO», its salts and/or TOD. Zn ociiet" to deteodne whether an aople nsrgin of safety fixists, the Worfcing Group oust first dstaxaine hew auch 2,4,5-TC5 (or salts) & weasm guild be exposed to. Both inhalaticn and desnal exposure routes • were exsBine*i« Fear each of these analyses, the Working Group assumes a woman to weigh 6C kg. de following calcuLiticns are based on an exposure analysis for 2,4,5-TCP, its salts and TCD perfCEaMd by EPA's Criteria and Evaluation Olvislcn. For purposes of this oialysis, the Working Group ccnsidered currently registered uses where the possibility of exposure to 2,4,5TC?, its salts and/or TOO existed. Large quantities of 2,4,S-TC? and its sodiua and potassium salts (41) �arc used in industrial and otbar navHwjriailturil pesticide forsulatians for controlling bacteria and fungi. The following industries ara tha largest UMts of forflulated products containing 2,4,5-TCP and its and potMsiuB salts* axil ing towers; papar and pulp ««4U nystaa*; and leather processing; adscallanaous industrial and institutional uses, disinfactant UM. To « Large extant most of the above industries use the sodivan salt of 2,4,5-TCP because of its higher water solubility. About 10-151 of the ceamereLai products for these uses contain 2,4,5-TO? itself. The aonmer- terrnchlrn-eptianol, and lower Ghlorophenols, as well as other active ingredientsf organic solvents? and eaulsifiers. K contaminant in 2,4,5" TO-c^isaining pesticides is 2,3,7ra-tatrachlorodibanzo-p^iijoxin (TCD) which is currently piasaut up to a "••*l*ftM concentration of 0.1 pen (Crosby et aL,, 1373). To astisBta human expeauri to 2,4,5-TCP or its salts in the above four aejcr use pettecnsr •vsilable piihlithed literature vow ocrrniltrad. It shnald be noted that exoasura data for 2,4,5-TC? or its salts was iimnrjiiyy^ii^ fi''*f tht <v*«->tp»»^i^p* 1 Safety and Heall*^ ^*ftjp^ fLyjtion in the aforementioned industries. However, by making certain aasuroticnif astisataa of potential bunetn ejctxaure to 2,4,5-TC? or its salts and TCTD can be nee. Such estimtea of human exposure in tarsa of derael and inha.lar.1an exposure are described in four sections of this analysis, specifically addressed to the major use patterns. (421 �For the purpose of this analysis, it is assuaed that. the pant" traticn of 2,4,5-TCP or its salts and TCDD into the hunan slcin has a value of about 10%. This is similar to th* p*nttn.ti^t value of several other chlorinatad hydrocarbons which is about 7-15% (Maibach and Feldtaan, 1974). it is also assuped that the TOO oaiLent in omwrcial 2,4,5TC? or its salts is at a neadrua of 0.099 ppa. For the purpose of this analysis a anxisum figure of 0.1 ppn TOGO is used. Lung absorption of TOD by inhalation is a«sunad to be 100%. SOMMKEf this reyuHJ. rtiscosaeii levels of fcunan exposvna to 2,4,5-TC? or its salts end TCDD that can be expected at specific use sites. The estimated values for TCDD darnl and inhalation exposure to wcnen are suBBKEized in Table 13. Table 14 shove the estiseted espcsuxe to 2,4,5TC? and/or its salts. Because of the pnsalMe texutogenic effects frcm TCDD, this analysis is predicated on the basis that the wodcers are wo* oen even though many of the positions that my reiult in exposure are held by sen. Ho eatisBtes of total individuals tiat oey be •xpesed are available at this tiae. a. Exeegure Analyiiia^Jter 2.4, 5-7.C? or...ita_._Salta_in Injuarcelal Cooling viacar .Sv-acagq There are two types of cooling tower water system in industry, one totally enclosed and the other open to the atoospnere. A typical enclosed cooling water system usually contains water storage tanks connected to an application muiifold? watar cirailatfts between a storage reservoir, chiller, «nd open gutters below the point of application such (43) �1'AIUf 13.' Ihimsn «xpcgtiro levels to * Product Niniier Use Site Microtj. a/kq body wt/day NlcrograasAg body wt/day ften..>l Exposure Inhalation Exposure Iniistrial Water System Product B Viper t Pulp Hills Product C feather Product D -6 0 3 x 10 .7 -6 1.4 x 10 Hi 0.2 x 10 -6 4.9 x 10 Hospital- Applicators Product B -6 7 x 10 Cooling Toner Product A -6 2.3 x 10 -6 9.0 x 10 -6 5 5 x 10 . -6 . 0.7 x 10 Non-Industrial - Patients Product B -6 0 8 x 10 .8 -6 0.49 x 10 * Product refers to exasples of cooaercial fonulation discussed in the text of this report under specific use site. Product A Ii C D K t 2,4,5-TCP or Ha 2,4,S~rep 7.2% 85% 15% 17.5% 2.32% (sodium salt) (soditn salt) (tridilorq4ienal) (sodium ^alt) (sodhn salt) (44) �YAJU£ H. ifcgaan exposure levels to 2,4,5-TCP and/or ita salts Use Site Product tiwlier Milligram A 9 body wt/day MllligraieaAg body vt/day Dental Exposure Inhalation Exposure Industrial Cooling Tower Product A 0.0037 0.023 Hater Systems Product 0 0.014 0.0903 Paper i. Pulp Hills Product C 0.092 0.055 leather Product D 0.049 0.087 lloispital- Applicators Product B 0.07 0.009 - Patients Product B 0.005 * Product refers to exanplea of oowerclal fonulation discussed In the text of tliis report under specific use site. ITodiict I 2,4,5-TCP or Ma 2,JfS-TCP A n C 11 7.2% 85% 15% 17.5% (eoditn salt) (sodiu* salt) (tridilorrphenol) (aodiiM salt) K 2.32% (sodium salt) �«* dias, Enl.Ung «LUs, ate. KURD* system uaually contain 20,000100,000 gallons of oaolant. At tha point of application conaidarabla loaaaa occur so make-up watar is constantly pumped from tha watar storage tanks. Tha cooling watar system ara ganarally wry larga Such systems, called "cooling towers", ara found ia heavy industrial BMn ufacturing aitas cSs&linj with mi, 11 tons of gallons of watar. Thasa latga an cSaai^ad eo provide a larga avaporatiw «rrf«ca '*ara watar owtr baat atthangan. Ibay an usually built outsidt of tha producBion hulJtMngs, but natintananoa workacs and cooling tcwar oparatocs mild ba aaqpoaad to this cooling watar. In both situaticnsr ragmrdlaaa of taa siza of th« gaoling watar an naadad ta maintain a dwn syatan. Oan an a larga mmitmr of 'jjitnmi\'r^*1 algicidaJL f^n \n\\im*i*f*tit uxuwnjad for conling tswar acplicatica which contain 2,4,5-TCS or its salts. In some cconsreUl fcoulBticns, it is noted that 2,4,5-TG? and/ car its .adta an the only active ingredients. Fear nest products 2,4,5?G>, or its sndium and potassium salt, is used in conjunction with pentachicrccoenol, tertian and potassium pentachlorcchenate, and other calorophenols. PenttK&lccephenol and its SAlts an used whenever a wood preservative effect is needed in cooling towers. In the gaoling tcwar systaBB, the pesticide- is periodically added to maintain an effective algicidal concentration. Factory workers, in the vicinity of the cooling water systems and the cooling tower, an potentially «*n@ssd ts 2,4,5-TC? or its salts and (46) �its isgurity TOGO by dermal contact or inhalation. Open investigation, it was learned that autcoatic altering davieas an generally used to add thu 2,4,5-'rCP-cctttaifling pesticide, Txo specific pesticide fccaulaticn products an considered fear the purpoMB of estimating th« levels of exposure. According to libel data, the percent concantraticn of tachnical Ka 2,4,5^TCP in th« product and th« conoentrmticn laval of to* product nccnntndad for «ffactivcnass is: of Technical Na 2,4,5-TC? Product \ 7.2% Product B 83% Reconnended Product t'se Concantraticn 300 ppa Q.SS ltos/1000 gal Na 2,4,5TC? Active 22 ppa 87ppa Zt is Humnmd that nsintananca wockazs and cooling ifsmur cpvr cnnld bi •spcaad to soot daead contact with th« coaling watar. It is «timted that possibly 100 ml/day of cooling watar omld com in contact with a person, tta Na 2,4,5-TC? content in each ml of cooling water is «i^»l»»^f and than, based on an assumed skin penetration rat* of 10% for Na 2,4,5-TC?, the desnal* exposure for a 60 fcg woman to this ccnccund is estiSHtad as follows: Product A For Product A the content of Na 2,4,5-TC? in the treated cooling water is 22 ppa or 22 rog/1. Therefore, the 100 ml that might contact the skin per worker per day will contain 2.2 mg of Na 2,4,5-TC?. Since the �penetration of the pattidLda into the bucan body is assumed to be 10%, tba desaal exposure to Ka 2,4,5-TCP can ba estinav.ed to be: 2.2 mg x 10% •f 60 kg • 0.0037 mg/kg/day. Oennal exposure to TCCO will then be 0.00037 -6 -€ ng (Q.0037 ng/fcg/day x 0.1 x 10 ) or 0.37 x 10 ug/fcg tody wt/day. Product B water treated with Prcducr. B contains 87 mg/1 of Ma 2,4,5TC?. Cne hundred ml of this gaoling water, the quantity estimated to contact the skin per worker par day will contain 8.V nsg Ma 2,4,5-TC?. Since tha penetration of tha pesticide into the human body is rated at 10%, the derffltl exposure to Ka 2,4,5-TC? is estiaatad to be 8.7 x 0.1 (10%) r 60 kg • 0.014 agAg/day. Dermal exposure to TCDD will then ba 0.014 axj x 0.1 x -€ -6 10 or 1.4 x 10 ugAg body wt/day. 11* Inhalation _Sxeosure While working in and around cooling towers for apprcxi&ateiy 2 noun a day, workers are subject to inhalation exposure fzcs pesticLdea added to moling water. Because of the high evaporation rate it la assumed that the air a woricar will breathe in the exiling tcwer will have o 2 100% relative huaidity at 20 C. Under these conditions, 1 r*. cf air cantains 17.3 grata of water. It is assumed that the pesticide is carried into the ai^ in proportion to its concentration in the coaling water. Product A If tha Ma 2,4,5-TC? content is 22 cgm or 22 nc/l, and tr.a rreath3 ing rate is 1.8 m hr; then, & 60 kg worker will receive the fciicwing 3 3 exposure 0.0173 I/D x 22 rag/1 x 1.8 m /hr x 2 hrs r 60 kg or C.OZ3 me/' -€ kg/day Ha 2,4,5-TCE>, which iroliea a dose of 0.023 x .1 x 10 cr 2.3 x -3 10 ug TCZD/kg/day. (48) �Product B A« above, the exposure to Product % in calcuiatad as follows: 3 3 0.0173 I/B x 87 ag/1 x 1.8 » /hr^t 2 hrs £ 60 kg or 0.0903 ag/fcg/d»y Na -6 -6 2,4,5-ICP which is equivalent to 0.0903 x 0.1 x 10 or 9.03 x 10 ug TCDD/tog/dsy. Analysis for 2rJ,!HPC? and its Salts in Pulp Induarry Paper and pulp "*n? us« oannsrcial fcmilations containing 2,4,5TCP or its &*ltJ for q»tznll1ng baetati* and fungi. In this walyais products raccomtndad for vfaita water and atoeic svstata of t±e mills, and the onnnarelal products usad in pulpr P^pv,. and papar board natufactoring haw bacn studied. 2b« eyoical caamrrial prcdue: raoaimooJad for the control of bacteria and fungi in tha abova processes contains 15% 2,4,5-TG1 by woight with the cornispcnding TO33 tapurit?. CustOBaarily, the- paaticicii is added directly to the system using a metering device.ELxccsurs Product C (15% 2,4,5-TCP) is added to pulping systaea at the rate of 0.825 lb/1000 gallons under the cost demanding conditions. T&s is equivalent to approxiiatvely 100 ppn of the fomilaticn and therefore, 15 ppm 2,4,5-^rCP. Workers in pulp/paper mi Its periodically take samples to ccnitct the process f cr quality control. Assumirw sailing is done hourly and each tint the worker vwts one hand (10 ml); then, an exposure of 80 al/ day is pcmaible. A 60 Jo? worker could then be exposed to 0.08 I/day x 15 og/1 x 0.1 (ahsc ration) r 60 kg or 0.002 TO 2,4,5-TC?Ag/day. TCC (49) �-6 -6 exposure would then be 0.002 x 0.1 x 10 or 0.2 x 10 ug TODOAg/day. (ii) Inhalation Exposure At the exposed tank areas, open conveyors, and q?an-spurting lo- caticna, tha mill wozkar will bt exposed to ccntaadjiatsd air. It is «•o tuned that conditions of 100% relative humidity and 20 C prevail. In that 3 case tha air would contain 17,3gran water/to . If it is assumed that the pesticide ia present in the sane proportion as the prccorticn in th« process water, then so, inhalation can be ca lariat nd. this would represent a worst case situation as salts at* generally not fdatil*. Using 3 a value of 15 Ffm (15 ngA) and the venter's breathing rate of 1.8 m /hr, 3 3 tho worker would be exposed to 1.8 m /hr x 15 tng/1 t . 1 3 1/te • 0.47 tog 07 It ia reasmaola to atsunt that during an 8-bcur shift, tha wodcmr will be exposed at least 7 hours to mill spray and contaminated air at specific locations. On this oasis, tue inhalation exposure (100% absorbed) to 2,4,5-TC? for tha f=rX«r having a body weight cf 60 to? will be 0.47 mg/hr x 7 hrs ± SO^or O.QbS ngA? tody weight/day. Based on a TOO eentant of 0.1 pern in 2,4,5-TC?, the inhalation of TC2D by the fac-« -€ tory worker is 55 ug x 0.1 x 10 or S.5 x 10 ug TOBAg/day. d. Ettoaure. analysis ...for 2,4,5-<Jg_ in the Leather Industry According to Anderson (li-76> * fungicides and bactericides that contain 2,4,5-TC? or its salts can be used at any stage of operation requiring control of fungi or bacteria: however, it is scat commonly used in the tanning pixoeaa. Open evaluation of all the processes dealing with the preparation of hides and tanning operations, i.e. tanning, soaking, bating, bean house washing, and fleshing and washing, it is evident (50) �that several workers constantly handle wet leather and wash waters used in the leather treating process, which contain anti-bacterial and antifungal agents to cope with the heavy (growth of bacteria and fungi. Data s" on exposure levels of pesticides in tanneries are not available; however, it isCTMonahleto make the following ajuuznpticns. 1. Then is a percentage of workers exposed to pesticide-* containing water. The difference in the exposure is • based on specific tannery operations which nay vary in the- pesticide amaunt and frequency. TJie tanning and fleshing/washing operation appear to provide the neat 2. It has been observed that a person wearing gloves and an apron could possibly get the diluted formulation on exposed skir areas during certain operations. Each time a worker is wet in that manner, approximately 50 ml of water containing small quantities cf organic substances could reach the exposed skin surface. The penetration of 2,4,5-TCP through the skin is assumed to ba 10%. i. Deraal Exposure For the purposes of estimating the decnal exposure of factory era in the leather industry/ a representative pesticide product used in tanneries is considered. This product contains 17.5% of sodium 2,4,5-tridilarcphenata (Product D). The label directions of the product tnd a dilution of the camareial foraulaticn at a rate of 1 pound per 1000 gallons of water. This is equivalent to 0.021 tog/ml of Ha 2,4,5- (51) �TCP in tha procaaa water: 1 lb/1000 gal " 0.454 gn/gal - 454 »9/g*l x 17.5% N* 2,4,5-TCP 7 3,705 nl/gal or 0.021 nn/al !Ia 2,4,S-TO? Baaed on the aaawnption that during the flashing and waahing aper*tion (tba worst case) in tba leather in&istsy, *** wosfcar oanlrt poe*ibly ba exprased to 1400 oil of the process water containing the pair id da par day. Further, baaad on tfaa assumption that tba pamtration of tba Ma 2,4,5-TO ixtta tba buman body ia 10%, Ma 2,4,5-TC? aapoaura ia aatintad to ba 0.1 (10%) x 1400 ml x 0.021 ag/nl - 2.94 nsg Ha 2,4,5-^2/day, Tha avaraga body waight of a woman wotJcar ia aaaumai) ta ba 60 tag, tban a woman taonary wodcar wniLrt raoaiv* a darxoal vxpoaura of 2940 ug * 60 » 49 ug Ka 2,4,5-4CP/1cg body waight/di^'. An additional factor of 0.1 x 10 -6 converts this to tha TOJ} axpoaurax -6 4.9 x 10 ug TCDDA9 body wt/iay. SladlMrly, tba daraal axposur* to tCDD for tba tanning cparation in which aporajdJBatal? 200 ml tnstaad of 1400 ml sight contact a wodcar, -6 rawilts to 0.7 x 10 ugAg tcoo of body wt/day. This ranga of valua*, -6 0.7 to 4.9 x 10 ug ICDD/lcg/day, is ealoilatitd en tha total quantity of traatad water centactad par pataon/day by axpoaura to different typaa of oparationa. ii. Inhnlatlrn Eaxaura In tanneriea, workara will ba expowd to watar vapor from tank* and o orooaaaing wits. If 100% humidity and 20 C conditions prevail, than tha 3 air will contain 17.3 gm/ra . it ia aasuwrf that tha braatbing rata is 3 1.8 m /hr and that tha paaticida ia praaant in tha air in tha satna prcportion aa in tha procaas watar. then, a 60 kg worker could bo exposed to (52) �3 3 17.3 ml/a x 0,021 tsj/tal x 1.8 m /br x 8 hr T 60 leg « 0.087 ng Ha 2,4,5-6 OTAg/day. TOD txpcwm would «qual 0.087 x 0.1 x 10 or 0.0087 x -6 -6 10 »g or 8.7 x 10 vag/kg/day. «. ftqaatun Analyaia foe 2,4 ,5-TCPJ ,08*3 in^Heapltals, (1) jntrodiacdxan Expovun i* wtisntxJ in this walyaia for puticldt footulaticra ufaich ax« UMd aa disinfectants in hospitals. TbtM ccnmiccial products QMd aa dLainfacttantaAacttaclciriM contain 2,4,5-TC? or its salts (sodiua and potaaaiiaa), otiwc activ* ingradiantsf arri imrts. Th«M ccnoarcial product:! ar« concantzatun for whicb ths nanulactumr pnacribas a sp«dgic dlluticn ratio in watar prior to application. To wtinmta quantitatively how mcb TCCD in Ha 2f4r5^TCP may ba t*lsas«d into ttie bos, tfa« usaga pattorn o£ topical connarcial cestidda flanaiUtiona that contain Ha 2,4,5-TC? which an racoamindad tor hospital USA haw hMn ooraidarad. For this purpoM, data on a conDtrcial paaticid* fomilaticn is sucmxizad balow. Pteduct, Product E * Ha 2,4,5^rCP 2.32% • Rftcomwnded Pilaticn Ma 2,4(5-/IC? e?AQO eal 1:123 68.6 gallona of auch a ^JjlAitfd solution will ^ni'iyin 0.78 gallons of product. Sinca Product E contains 2.32% Ita 2,4,5-TC?, 100 gallons will contain 0 0 8 gallons Na 2,4,5-TC?. There ara 3,785 gn/ .1 gal (density o£ 1), and therefore 68.6 grans of Na 2,4,5-TCP an prein 100 gallons. 153) �rs4j �-« TCCO tba exposure would ba O.ff? ng 2 iOOO ug/mg x 0.1 x 10 -6 or 7 x 10 tig tCDO/tog/dsy. Ul« Inhalation hospital workers and patients braatba the air In tba hospital warda and wade area* It is recognized that because of the restful oanditiona of tba patients, they haw* a aonevbat lower breathing rat*, while tba 1 wpital worker nay havt a higher breathing rate. For tba gurpoaaa of estinting tta ralativa- quantity of TC33 ralaaa«, it is aeaumad that SO patianta occupy aaniprivata ttxaa having 3 a ^olianatric spaca of appr09dfflBtaly 60 a /room (20 ft x 10 ft x 10 fit) . tha volumtxic air spaca of tha beapital wing with 10 «ploywta is «a3 tiaatad to b* sppradsaitaly 1800 m which IncluriM tha 25 patiant rccea, 3 3 (1500 a } corridor, and naceasary supj^oct araa (300 m ). For tha size of tba borpital wing and intoanoendad air vantilatica of 1800-2400 ft / 3 tar/pczscn (approxiiaataly 60 n ) (Air Quantitia* for v«ntllatim» 7th ad. ) , tba total ^r*5*!**** air ^oliaa foe an 3-hour pariod «*^'W ba 60 n 3 (ventilation) x 60 (patiants and aBploymM) x 3 (hr/day) or 28,800 a . Of tha 100 gallons of disinfectant applied, about one cop per or 6.25 gallons (100 cups) will ba distributed in the hospital wing interior. Ibis quantity contains 0.043 gm Ma 2,4,5-TCP/cup x 100 -6 cups or 4.3 gm Ma 2,4,5-4C?/lQO cups or 4.3 x (0.1 x 10 ) gm TOE or -6 0.43 gm r 10 gm TCZC/10C Since it i* estirattad that in a water solution, 22% of the TCTO -€ volatilize baton drying, it is assumed that 251 x 0.43 x 10 gm (55) �-6 (ajtsunt of TCEC/100 cups diluted formilation) or 0.108 i 10 ga TCDD is volatilized. Based on the total circulated air volisnt Cor an 8-hour 3 - 6 3 period, 28,800 a , them 3.7 x 10 ug/m would be available. (0.108 -« 3 -12 3 - 6 3 x 10 r 28,800 a • 3.7 x 10 <jm TCCD/m or 3.7 x 10 ug/n . 3 If the breathing rate of the psti«nts is 1.0 a /nr and that of 3 the workers i« assumed to be 1.8 a /hr, then the exposure <n»lrf be: 3 -6 a. Hospital worker (60 kg)* 1.8 a /hr x 8 br x 3.7 x 10 09 3 -6 TCDD/a r 60 tog or 0.88 x 10 ug TGCDAg/day. 3 b. Hospital worker (60 teg)t 1.8 a /hr x 8 hr x 4.3 gm TCP/ 100 cups x 25% volatilization r 28,800 n r 60 kg • 0.00895 ag Ha 2,4f5-TCPAg/<i«y. 3 -€ e. Bospital patient (60 kg): 1.0 a /hr x 8 hr x 3.7 x 10 ug 3 -€ ICCD/m «f 60 kg or 0.49 x 10 ug TCDDAg/8 hrs. 3 d. Bospital patient (60 kg): 1.0 a /hr x 8 hr x 4.3 go TCP/100 cups x 25% volatilization f 28,800 m <? 60 kg • 0.00497 rag Ma 2,4,5-TCP/kg/day. £. Concluaions The sun of the dermal and inhalation exposures to TCDD (per Table 13, page 44) wire compared to the TCCO no-adv«rse-ef£ect level for toratogenicity and fetotoxicLty, 0 0 ugAg body weight/day (Spanchu et al., .3 1 7 ) The difference between this no-adverse effect level and the cal91. culated exposure represents an adequate margin of safety. However, preliminary data (Traynor, 1 7 ) indicates the no-effect level nay be one 97 order of negnitude lass. The dental and inhalation exposures for 2,4,5-TCP or its salts ( e se Table 14, page 45) were also compared to the no-adverse-effect level for (56) �fatotosicity, 0.9 ng/teg beady waight/day (Haubart and Diltaann, 1972) . Since tha diffaranca batuwn this no-advana-stffact laval and tha calculatad axpcBura did not rapraaant an adaquata wargiii of aafaty, tha working Gtccp raceBiaa»da isauanot of a wabuttatole graauoptian againat registration baaart on fatoeoxicity. the Working Gcoup roalizaa that this daciaicn ia baaad on only ona taat paKfcand in 1971. Iba 2,4,5^rO? uaad in thia taat waa spacifiari aa baing of analytical grada frcn a conpany ia Switzarland with no TOX contant apacif iad. iba tachnology for nanufacturirg 2,4,5-TC? vita lev TOD content, aa vmll aa tha capability for tha idantiCicatian a£~lcw Irmla of TQ33, probably waa not aa advancad in 1971/1977 aa it ia today. Tha Working Group nquaats ragiatzanta and othar intarastad par* sons, wbo hava coam«u or relevant data regarding 2,4,5-TOVTCCD, exposura aatdsaataa and nargina of safaty to sutmit suc& inf onoaticn to tha ftqancy.. IV. Evidfnca ttot Sofiicient to Sutxott a Retauttabla PreargPticai &• Mutagenic Sff ecta of TCTD in Tsat 40 CTR 162.11 provides that a rebuttaela preaarption shall arise i£ a paaticida'a ingrBdient(a), netatolite(a), or dagradaticn prcduct(s) "(i)ndocsw outaganic «£2actar aa datanninad by cultitaat •vidanea." lha ganatic affacts of TCTD hava baen studied by aavaral raaaarchers. Sana of tha tasta sutigaat that thia dioxin ia a cutagan. 1, Sj3^riaa.,Dgtu»»trating.i.j±g.ffltaeenic Effects of TCCD Buaaain at al. (1372) evaluated tha mt*r"i4,j activity of TC33 (99% puxa) en thr«a different okrobial taat systns. In tha first study 7CCD (57) �si^nif icartttly increased tba incidanca of reverse nutations in Escherehia. ogli Sd~4 Administered 2 og/ni TCDO from streptonycin dependence to straptonycin indnptndence. Ibis, was the only date at which nutations were clearly cbserwd. No details of toe expertnantal protocol were given and statistical OTtboos were apparently not employed in assessing the data. tttt second test by Hussain studied reverse nutation from histidim dependence to hiatidiia indspendence in. Salmonella tvghiaurium strains T3V 1532 and m 1530. TOT was positive in Sk 1532 but negative in IX 1530. thifl indicates that TOO acts as a franashift nutacen. ld-170 was used an a positive control in the test with TA 1532. Ho positive or iMgatiTO controls were tested in TA 1530. In tho third tast, Bussain observed slight prophaee induction in E^ goli K-39. Hc*ewer, data from this tast were difficult to evaluate becaiVM the solvent used, DMSO, causes «*""l«r effets. A pralintLnary la^otc: en the chrcncscnal analysis of hospital patients exposed to TOD in the accident at the Semaso, Italy, faessry was • ,-^.^ntad at a Departnant of Health, Education, and Welfare tanting on October 12, 1976 (Pertsl, 1 7 ) An increased nutcber of chrcocsomal le97. sions (gaps, cnroratidic and chrcnoscmal braaks and rearrangecatnts) were observed in the somatic cells of the 2- to 28-year-old malts and females testad. Cytogenetic studies of tissues frcm the therapeutic abortions perloanad on woman who were exposed to TCSD during the accident indicated that there was chrcnDsonal damage to e»it* in matamal peripheral blood and placenta! and fatal tissues. Uiese preliminary results wera based on a *"?U nunber of sanplas and no specific data is available at this tis». (53) �.1. Studies, in Whichi Mutagcnie Eff e^ta Wet* ttot Obaetyed and Roddick (1973) conductad dominant lethal tMta in which ode Wiatar rats received TCQD at doaages of 4 and 8 ugAg/day. The studies indicated that ro dominant lethal autaticra KTQM daring the 33 days paattrMtaant. The period examined corresponded to poetneiotic stages of spennetogeneais. A cytoganatic screening stud; of tha effects of TCCD on tha bona narrow calls of nala nilrn-na Murrkil rats wax perfconad by tha Food and Drug Adadnistraticn (Green, 1975) . Two separata axparlnants were perf ecoad. Tha fiat waa a mltiple doaa. test in which 10 ugAg/day was adadnistarad by iAtubaticn daily for S consecutive days. In tha second taatf single deaea of 3, 10, and 15 ugAg ICED were administered intraparitcnaally and 20 ugAg (tha highest cose) waa adsdniatayad orally. Thara waa no evidence firm these studies to indicate tnat 'ru^i produced cftooanatie dneg* in tha bona narrow of these oala rats. Tcodcity, which waa indicatad by a slight weight loss, waa noted in tha rata that received a single dose of 15 or 20 ugAg >;ch« highest dcse levels) . This suggested that the dose level nay have been too lew. Therefore, the Working Group concludes that, although there is sane evidence that TCDD is a nutagen in aicrcbial syatesa, the data is' not sufficient to fora the basis of a rcbuttoble presuocticn. Additional infcrmtian or studies en the nutagenic effects of TGCO should be submitted to the Agency for further review. B. Other Effects cf TC2D 1. \4hether there is a relationship terueen the effects of TCX and (59) �dunical eareinogerasis has bMn the subject o£ ceveral studies. Marquardt et aJU (1974) feund awidenca that aryl hydrocarbon bydrcxylase (ABB) is strongly involved in chattical careinogenesis i^cause nany chaaically nonreactive: oaayounda oust ba metabolized by cellular ewtyines b*f ore they can act as carcinogens. Buu-Boi «t al. (1371) found that even in very lew dona TOO could greatly disturb tba< «Rzynatic chazactar of «n organism «a do CBTtain typical atrcinopnie subatancas (a.g., banco/a/ pyrcna ind p^liitartbylaniinoazobBnzana). In a papar on ME, Kauri at al. (1974) statad that TOO itsalf is not a potant carcinogan in orlca. However, tha txtant to whidi the synargistic action of TO3D and 3^nttbyid5oi«nthr«na (MC) produces cancar in different strains of adea is directly proportional to the increaae in hydroxylase activity and assort at art cytcchroM P-45C content. Tljey raportad that the basal enzyme activity might corraJLata with the enzyme activities that onild be inrtuoid by either TCDD of MC. Ibey found TC2D to ba 40 to 60 tiaea acre potent as a indueer of ABB in coltured human lynphocytas tban was MC. Poland and Glover (1974) &&c*ed that TCED is a^proxinately 30,000 timM itore potent than MC as an inducer of ABE in rat liver. 2. Ttacic Effects on Hunams Thera are several adverse effects that occur in huaans as a result of exposure to TCDD. The nost well known is chloracne, a severe and persistent disease of the skin that is very difficult to cure (S<±ulz, 1957). Porphyria cutanea tarda (PCS) is another disease that is caused by exposure to TCDD and of tan aceenpanies chloracne (Bleiberg, 1964). (60) �PCS is a defect of hepatic prophyri* tagt.abnlisra caaracterijid jy an overproduction of poqphyrins, fragility and ptotosensitivity of the skin* hyptxpigaantaticn, hiraatism, and neurological and intestinal disorders (Poland and Kande, 1976). 3. Toxic Effeeta on Other Mannada MMBMMHMIIMWMMMMnM«M**IMNIM«Mn*M«MiaMMMMMWMM«MMMMrlW* ttw «xtma§ tcaddty of TOO to a variety of animal spades hasbeen well docuuented (Abelaon, 1970; Buu-Boi et aJU, 1971; Jtoee et al., 1976; Farqubwson et aJU> 1958; Uigginbothaa et al., 1968; Milne*, 1971; Spaxscbu et al., 1971). The £0 for TCCD is aa Ian as 0.6 no/kg 50 body weight in tae guinea pig (Table IS). TMLE 15. LD-50 values for TCTD Aniral U>50,uaAq Ref arenas Guinea, pig 0.6 Spvcschu et al. (1971) Babbit 10 Scfaulz (1968) Hat Female Male 22 45 Schwetz et al. (1973) Mouse 114 Vos et al. (1974) Dog 1000 Scfewnts et al. (1973) 4. Miscallaneous Toxic Effects Many wseartAers haw found the-liver to be the main target for the toxic action of TCCD. Liver necrosis (Norbadc and Allan, 1973; Courtney and Moora, 1971), stimulation of hepatic ncLcrracaal enzyir«s (61) �(Piper et al. , 1973; Gupt* «t «!., 1973), and th* formation of nultinuclaate psrenchynel calls (Craig et al* , 1573) an exaspi*s o£ the wry adverse effects also attributed to TOO toposura. Chick edena factor (Eiggenbotham et «Ju, 1263), severe weight lour atrophy of the thywua, and Induction of nenatic and renal micrcsona! drag metabolizing enzymes (Fowler et al, , 1373) art SOD* additional adwcM effacts tiiat haw bean noted* C. Other _Eff8c±3 of . 2, 4, Vrc?_ and, ita Salta Technical gracte 2,4,5-TCP can irritate the eyes, akin, nose, and throat* Depending on the degree of expcoure, ocular damag* nay include burn of the conjunctiva! membrane, severe conjunctiva! swelling, slight to QOderate iritis , and cornea! daaacp. dose exposed to 2,4,5-TC? have ccntractcd chlcracne aad porphyria carda. Hswev«r, these effects were attributed to the presence of fCED as a contaminant (Schulz, 1963). The toxic properties of Na-2,4,5-TCP ars similar to tbose of 2»4f5-TG» but % , are scoewhat uuie The ID for 2,4,5-TO? has been established at ccncentraticns vary 50 ing fircra 820 to 2960 mg/k? body; weight in the cat. No ncnreversible logical changes were noted at the doses cited. The acute feeding studies with both 2,4,5-TCP and its sodlun sale are sunnarized in Table IS. et &L (1961) administered a single dose of 1-3.98 g/ kg 2,4,5-TC? (97-98% pure) by intubation to mala rats. The acute OTA! LD was ^Iml^fH to be 2.96 g/kg/bcdV weight, a finding whidi led the SO authors to conclude that 2,4,5-TC? is low in era! toxicity. In a 3-aonth study *« authors fed rats 0 (cantrol), 0.01, 0.03, (62) �TAM£ 16. Snanaty of acute effects of 2,4,5-TCP and tta sodium gait on rata Chemical Route of Mninistration taq/}f.q bod/ weight Reference 2,4,5-TCP oral 2960 KoColHster et al. (1961) 2C4,5-TCP oral 820 Deiduaarm (1943) 2,4,5-TCP oral 2460-2830 Dow Chealcal Co&pany 2,4,5-TCP oral 620-835 Delchmnn and Mergard (1348) 2,4,5-TCP intraperitoneal injection 355 Fatquharaon et al. (1958) 2,4,5-TCP tuibcutaneous injection 2100-2260 Deichnxcu'A and Mergard (1948; Ma 2,4,5-TCP oraf 1620-1870 Dow Chemical Co0(^any (1976) (63) \ �0,1, 0.3 or 1 9 2,4,5-TCPAg body weight in th« diet for 98 days. Bats •nintainad at the 1 gAg/day level had only alight pathologic changes in the liwr and kidneys, the kidneys showed oodatmtad degenerative changes in the epithelial lining of the convoluted tubules and early proliferation of the interstitial tissue. The effects of 0.3 gAg/day were milder than those at 1 g/fcg/iay. r - adverse effects were noted in either mala or fonale rats naintained at 0.01, 0.03, or 0.1 9/fcg. The authors concluded that 2,4,5-TO? is low in acute oral teaddty to rats when administered in their diet for a period of 13 days. In repeated feeding tests (20 oral doses in 28 days), the authors^ adMRistaxed doses of 2,4,5-TC? ( . 0 , 0.01, 0.1, and 0.5 gAg) to rab001 bits by intubation. There were wry slight kidney changes in rabbits administered 0.1 gAg, and wry alight kidney and liver changes in those given 0.5 gAg. Ho pathologic changes were observed in rabbits in the two lowest dose groups. 2,4,5-TCT and its sortium salt caused no davoal effects en guinea pigs (Dugois and Colcnt, 1957), and oaV a slight reddening of rabbit skin after brief exposure and mild to ooderata chemical burns after longer exposures (Dow Chemical Cowany, 1976). Refined 2,4,5-TO? also did not cause caloracne or other adverse effects in rabbits (Kirxoig and Schulz, 1 5 ) Bather it was the TOD fomad in the alkaline hydrolysis of . 97. 1,2,4,5-tatratilorccenzene into 2,4,5-TCP that produced caloracne. Bladonan et al. (1953) determined that the LD for 2,4,5-TC? on 50 the green water plant (I/cna miror) was 1 6 ag/litar. The authors de.5 fired the ID as xhe concentration which caused chlorosis in 50% of the 50 (64) �plant fronds. Antr and Xli (D74) atudiad th« cytnlr^ical «ffacts of 2,4,5-TG? on th« raicaii, pollan viability^ mi yi*ld of Vleia faba plants that bad bMn t^nyad or wbow laadi had betn.toalod in tte Oiaoicad. 2,4,5- TCP had no significant «££act on tfat pollan noth«r-^alls and no harnful •If act on (65) �� Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5258 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource 2,4,5-Trichlorophenol Working Group, U.S. Environmental Protection Agency Date A point or period of time associated with an event in the lifecycle of the resource February 28 1979 Title A name given to the resource 2,4,5-Trichlorophenol and Its Sodium and Potassium Salts: Position Document 1 ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5259 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Leng, Marguerite L. Description An account of the resource <strong>Corporate Author: </strong>Dow Chemical Company Date A point or period of time associated with an event in the lifecycle of the resource 1979-02-01 Title A name given to the resource Summary of Dow's Response to EPA's Risk Analysis on the Use of 2,4,5-T Herbicide ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5260 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Leng, Marguerite L. Description An account of the resource <strong>Corporate Author: </strong>Dow Chemical Company Date A point or period of time associated with an event in the lifecycle of the resource 1979-02-01 Title A name given to the resource Government Requirements for Pesticide Residue Analyses and Monitoring Studies ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5261 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Date A point or period of time associated with an event in the lifecycle of the resource 1979 Title A name given to the resource Memorandum with attachments: From Joseph J. Merenda, Director, Assessment Division, regarding EPA's Evaluation of Dow's Study Reporting Dioxin Formation as a Result of Combustion, dated February 15, 1979 ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5262 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Schroeter, Rudolf H. Title A name given to the resource Letter from Rudolf H. Schroeter to Alvin L. Young, February 21, 1979 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/0d24b8dedc2ac95fa975a5f243d3fbfd.pdf 3308335f0df63b67f20fd27c5fe1797b PDF Text Text Item D Number °5263 D N0t scanned Author Corporate Author Report/Article TltlB Press Releases, Fact Sheets, and Charts related to the EPA Suspension of 2,4,5-T and Silvex, March 1, 1979 Journal/Book Title Year Month/Day Color D o Descrlpton Notes Tuesday, March 05, 2002 Page 5263 of 5363 �EMERGENCY ACTION TO STOP SPRAYING OF THE HERBICIDES 2,4,5-T AND SILVEX PRESS CONFERENCE STATEMENT BY EPA DEPUTY ADMINISTRATOR BARBARA BLUM THURSDAY, MARCH 1, 1979 WASHINGTON, D. C. Good afternoon. We are taking emergency action today to halt the spring spraying of the herbicide 2,4,5-T on the basis of new information indicating its potential link to human miscarriages. As many of you know, 2,4,5-T has been under intensive review by EPA for over a year due primarily to adverse health effects shown in test animals because of a contaminant known as TCDD or tetra-dioxin. This dioxin, even at very low levels, causes severe reproductive effects — birth defects — miscarriages and and tumors in laboratory animals. We have just received the results of a study which shows a high probability that the herbicide is linked to actual human miscarriages in an area where 2,4,5-T is used regularly. New studies in the Alsea basin area of Oregon, show a high miscarriage rate shortly after the spraying of 2,4,5-T in the forests. This alarming correlation comes at a time when 7 million pounds of 2,4,5-T are about to be used across the Nation to control weeds on power line rights-of-way, to manage forest lands, and to control weeds in pastures. �— 2— The emergency suspension action we are taking today will protect the nearly 4 million people who may be unknowingly and involuntarily exposed as a result of those uses. The potential for significant human exposure, the warning signals from the Alsea study, the preponderance of strong animal test data, and the low short-term economic impact, compel this unusual emergency action. The new study was initiated by EPA because of complaints from women in Alsea reporting that they had experienced miscarriages right after the forest area in which they lived was sprayed with 2,4,5-T. The study was completed by scientists from the Environmental Health Institute of Colorado State University and the University of Miami Medical School, Department of Public Health and Epidemiology. It compared the miscarriages in the Alsea basin area of western Oregon with those of women in a control area in eastern Oregon. These findings, spanning a six year period, were then correlated with the spraying of 2,4,5-T in the State. The Alsea basin is in a national forest area of Oregon which is sprayed each spring with 2,4,5-T. The control group was from a similar rural area in the eastern part of the state which is not sprayed with the herbicide. �-3- Let me show you what we found. First, you see the numbers of pounds of 2,4,5-T used in the area. As you can see, almost all of the herbicide is used in the months of March and April; Second (first overlay) here is a line representing the miscarriages occurring in the study area. Comparing the line with the 2,4,5-T bar graphs, you see that the miscarriage rate appears to be correlated to the amount of 2,4,5-T sprayed. Notice this dramatic peak in June which follows the heaviest use of the herbicide by only 2 months. This peak occurred consistently in each year examined. And third, (second overlay) the June peak is not present for the control group. Indeed, the control group data shows a generally lower rate of miscarriages altogether. Obviously, we are very concerned about the health implications of these findings not only for the residents of Oregon but to all citizens who may be exposed to the herbicide. We estimate that over 4 million people across the Nation may be at risk through the use of the herbicide in forestry, rights-of-way clearance, and pasture uses. �I want to reemphasize four points about today's action: o a^ preponderance of animal test results in several species show adverse reproductive effects! at low levels of exposure; o there is a remarkably high miscarriage rate in June in the Alsea study not seen in :•:}<;.•••;;•; .^the- ooixtroi ..area; . . . . '.JCD.- in:the June peak follows by 2-3 months the -; .spraying of 2,4,5-T in the Alsea area; and OM(I !a:n resitimated A million people are at risk i • • ; • • , ;,.,:.dn-'the, spray season about to begin. Taken together, these facts sound an alarm. They coitlpel-EPAr.to act to stop use until we have a fuller understanding- 'of this phenomenon and its implication for human health.' A<-.V., • : ' • : . < ! . • • • . • • , We are also taking emergency suspension action against related'uses' of /Silvex, another herbicide contaminated by TCDD, .to:preclude similar exposure. Silvex is used primarily for weed control >on suburban lawns and other turf uses, and it could be used as a substitute for 2,4,5-T on forests, rights-of-way,'and pastures. This emergency suspension action is analogous to a temporary restraining order issued by a court. We are not saying that the health effects in humans are positively proven, or that 2,4,5-T should never be used again. What �-5- we are saying is that there is sufficient evidence to stop further exposure to the chemical until the issues can be resolved. The manufacturers of 2,4,5-T have 5 days to appeal the Agency's emergency suspension order. If appealed, EPA will convene a hearing panel to examine all information bearing on the question of whether an emergency exists. The panel will, by law, be required to reach findings and make a recommendation on the emergency suspension issue to the Administrator within 10 days after evidence has been heard. The Administrator would then have 7 days to issue a final order on whether the suspension should continue through the cancellation process. After the suspension issue is decided, the cancellation hearing process will begin to consider the larger issue of the risks and benefits of the herbicide to society. The law requires EPA to balance the benefits of the use of a pesticide against its risks. And, from the information we have already gathered from the Department of Agriculture, the timber industry, power companies, and others, it is clear that the economic benefits of 2,4,5-T. are important to several segments of society. However, �-6- the short-term economic impact of this action — i.e., suspension of uses over the period of the expedited hearing and the cancellation proceedings — should not be serious. This is so because alternatives are available for pasture and rights-of-way uses, and because only a tiny fraction of commercial forest acres are treated in any given year. Moreover, in many cases treatment of forests, rights-of-way, and pastures can be deferred until these proceedings are completed. The long-term economic impacts will be fully evaluated — along with the long-term health risks — in the cancellation proceedings. Thank you. questions. I will be happy to answer your �2,4,5-T Spraying and Miscarriages in Alsea, OR Study 3,280 130 3QQ {iijiiliii JAN FEB PAR APR HAY JUN JUL ' AUG SEP OCT NOV ' DEC JAN �Pasture 2,4,5-T Applications: Major Regions of Treatment and Numbers of Persons Potentially Exposed 100,000 PERSONS //V///: SOUTHEAST/EAST WEST 600 PERSONS 8,000 PERSONS U.S. TOTAL PERSONS: 108,600 ^ Note: No. of persons include rural residents within 1/2 mile of applications; Passers by (equal to 10% of rural residents); and occupational (applicators, etc.) Approximate values. Excludes rangeland �100% Forest Acres Treated in a^ single year = 0.2% of U.S. Total Acres 9-10% "A ?i-i V Total Acres U.S. Commercial Forest 500 million U.S. Commercial Forest Acres Treated During Forest Life (50 yrs. avg.) �Rights-of-Way (Railroad, highway, electric utility and pipeline) 2,4,5-T Applications: Major Regions of Treatment and Numbers of Persons Potentially Exposed NORTHWEST 261,000 PERSONS NORTHEAST 2.0 MILLION PERSONS SOUTHEAST 980,000 PERSONS U. S. TOTAL PERSONS: 3.3 MILLION Note: No. of persons include rural residents within 1/2 mile of applications; Passers by {equal to 10% of rural residents); and occupational (applicators, etc.) Approximate values. �Forestry 2,4,5-T Applications: Major Regions of Treatment and Numbers of Persons Potentially Exposed PACIFIC V —»< 99,000 PERSONS PERSONS PERSONS U.S. TOTAL PERSONS: 900,000 Note: No. of persons include rural residents within 1/2 mile of applications; Passers by (equal to 10% of rural residents); and occupational (applicators', etc.) — Approximate values. �ALTERNATIVES FOR 2,4,5-T FORESTRY - SITE PREPARATION 1. Chemical Amitrole-T 3-amino~l,2,4-triazole and ammonium thiocyanate 2,4-D 2,4-dichlorophenoxyacetic acid Fosamine 2,4-dinitro-6-methylphenol Glyphosate N-phosphonomethyIglycine Picloram 4-atnino-3,5,6-trichloropicolinic acid 2. Non-chemical Manual Mechanical Fire One cannot assume that these alternatives are complete substitutes for 2,4,5T in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR 2,4,5-T FORESTRY - CONIFER RELEASE 1. Chemical Amitrole-T 2,4-D 2,4-dichlorophenoxyacetic acid picamba 3-methoxy-3,6-dichlorobenzoic acid Fosamine 2,4-dinitro-6-methylphenol Glyphosate N-phosphonomethylglycine MSMA monosodium methanearsonate Picloram 2. 3-araino-l,2,4~triazole and ammonium thiocyanate 4-amino-3,5,6-trichloropicolinic acid Non-chemical Manual One cannot assume that these alternatives are complete substitutes for 2,4,5T in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR 2,4,5-T FORESTRY - PCT and TSI 1. Chemical 2,4-D 2,4-dichlorophenoxyacetic acid MSMA monosodium methanearsonate Picloram 4-amino-3>5,6-trichloropicolinic acid 2. Non-chemical Manual Mechanical PCT - Pre-Commercial Thinning TSI - Timber Stand Improvement One cannot assume that these alternatives are complete substitutes for 2,4,5T in respect to hcrbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR 2,4,5-T PASTURES 1. Chemical 2,4-D Dicamba 3-methoxy-3,6-dichlorobenzoic acid Piclorara 2. 2,4-dichlorophenoxyacetic acid 4-amino-3,5,6-trichloropicolinic acid Non-chemical Manual Mechanical One cannot assume that these alternatives are complete substitutes for 2,4,5T in respect to herbicidal effectiveness, means of. application, geographic suitability, or economic considerations. �ALTERNATIVES FOR 2,4,5-T RIGHTS-OF-WAY 1. Chemical Amitrole-T AMS ammonium sulfam.ate 2>4-D 2,4-dichlorophenoxyacetic acid Dicamba 3-methoxy-3,6-dichlorobenzoic acid 2,4-DP 2,4-dichlorophenoxypropionic acid Picloram 2. 3-amino-l,2,4-triazole and ammonium thiocyanate 4-amino-3,5,6-trichloropicolinic acid Non-chemical Manual Mechanical One cannot assume that these alternatives are complete substitutes for 2,4,5T ift respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR SILVEX FORESTRY - SITE PREPARATION 1. Chemical Araitrole-T 3-amino-l,2,4-triazole and ammonium thiocyanate 2,4-D 2,4-dichlorophenoxyacetic acid Fosamine 2,4~dinitro-6-methylphenol Glyphosate N-phosphonomethylglycine Picloram 4-amino-3,5,6-trichloropicolinic acid 2. Non-chemical Manual Mechanical Fire One cannot assume that these alternatives are complete substitutes for silvex in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR SILVEX FORESTRY - CONIFER RELEASE 1. Chemical Amitrole-T 3-amino-l,2,4-triazole and ammonium thiocyanate 2,4-D 2,4-dichlorophenoxyacetic acid Dicamba 3-methoxy-3,6-dichlorobenzoic acid Fosamine 2,4-dinitro-6-methyIphenol Glyphosate N-phosphonomethylglycine MSMA monosodiura methanearsonate Picloram 4-amino-3,5,6-trichloropicolinic acid 2. Non-chemical Manual One cannot assume that these alternatives are complete substitutes for silvex in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR SILVEX FORESTRY - PCT and TSI 1, Chemical 2,4-D 2,4-dichlorophenoxyacetic acid MSMA monosodiutn methanearsonate Picloram 4-amino-3,5,6-trichloropicolinic acid 2. Non-chemical Manual Mechanical PCT - Pre-Commercial Thinning TSI - Timber Stand Improvement One cannot assume that these alternatives are complete substitutes for silvex in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR SILVEX HOME LAWNS AND COMMERCIAL TURF 1 • Chemical 2,4-dichlorophenoxyacetic acid MCPP (Mecoprop)- 2-methoxy-4-chlorophenoxypropionic acid Dicamba— 2-methoxy-3,6-dichlorobenzoic acid 2. Non-chemical Hand weeding Mechanical mowing Cultural practices (optimize fertility, pH and tilth for grass growth) I/ Many formulations contain mixtures of 2 or 3 of the above. One cannot assume that these alternatives are complete substitutes for silvex in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR SILVEX PASTURES 1. Chemical 2,4-D Dicamba 3-methoxy-3,6-dichlorobenzoic acid Picloram 2. 2,4-dichlorophenoxyacetic acid 4-amino-3,5,6-trichloropicolinic acid Non-chemical Manual Mechanical One cannot assume that these alternatives are complete substitutes for silvex in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR SILVEX RIGHTS-OF-WAY 1. Chemical Aoitrole-T AMS ammonium sulfaraate 2,4-D 2,4-dichlorophenoKyacetic acid Dicaraba 3-methoxy-3,6-dichlorobenzoic acid 2,4-DP 2,4-dichlorophenoxypropionic acid Picloram 2. 3-amino~l,2,4~triazole and ammonium thiocyanate 4-amino-3,5,6-trichloropicolinic acid Non-chemical Manual Mechanical One cannot assume that these alternatives are complete substitutes for silvex in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �ALTERNATIVES FOR SILVEX AQUATIC SITES 1. Chemical Alligatorweed control 2,4-D 2,4-dichlorophenoxyacetic acid Emersed weeds 2,4-D Diquat Endothall MCPA 9-, 10-dihydro-8a, 10a-diazoniaphenanthrene-2A 3,6-endoxohexahydrophthalic acid 2-methy1-4-chlorophenoxyacetic acid Submersed weeds 2,4-D Dichlobenil Diquat Endothall 2. 2,6-dichlorobenzonitrile Non-chemical Mechanical Biological One cannot assume that these alternatives are complete substitutes for silvex in respect to herbicidal effectiveness, means of application, geographic suitability, or economic considerations. �UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 FACT SHEET OFFICE OF TOXIC SUBSTANCES WHAT DOES S U S P E N S I O N M E A N ? Under the F e d e r a l P e s t i c i d e L a w , the Federal Insecticide; F u n g i c i d e , and R o d e n t i c i d e Act (FIFRA) 0 , pesticides may be registered by EPA when e v i d e n c e presented by the manufacturer shows that they may be used without posing " u n r e a s o n a b l e adverse effects" to' h u m a n s or the environment. In order, to. a p p l y the " u n r e a s o n a b l e adverse effects" standard the EPA A d m i n i s t r a t o r must b a l a n c e the risks posed by a pesticide against its economic and social benefits. Registration is granted if the b e n e f i t s outweigh the risks. The law places the b u r d e n for s h o w i n g that the pesticide does not pose u n r e a s o n a b l e risks on the proponents of use1, who typically submit experimental information they develop to the government as a b a s i s for e v a l u a t i n g any risks the p e s t i c i d e may pose.. There are times when; because of advances • in- science or when new information becomes a v a i l abl e1,. questions arise about whether a registration s h o u l d remain in effect. There are several procedures EPA can follow in such 1 situations: 1) R e b u t t a b l e P r e s u m p t i o n A g a i n s t R e g i s t r a t i o n ("RPAR") The R P A R process b e g i n s with a notice summarizing e v i d e n c e of potential u n r e a s o n a b l e adverse effects and i n v i t i n g p u b l i c comment on the risks and benefits of the pesticide in question. The RPAR process is characterized by its informal (i.e.; non-adjudieatory) nature. Its purpose is to gather i n f o r m a t i o n and s t i m u l a t e broad p u b l i c debate about whether the seriousness of problems with a pestici.de indicated by "validated tests or other significant evidence" warrants regulatory action. Manufacture and use may continue d u r i n g the process. RPAR leads to a decision to take no action; restrict some or all uses of the pesticide 1 ; or i n i t i a t e cancellation. �-2- 2) C a n c e l l a t i o n Proceedings C a n c e l l a t i o n s b e g i n with a statement of f i n d i n g s by the Administrator of his reasons for b e l i e v i n g that the risks of a p e s t i c i d e outweigh its benefits-, and that its uses should be "cancelled" (i.e.; permanently banned). The notice receives review by the Secretary of A g r i c u l t u r e and i n d e p e n d e n t s c i e n t i f i c review by a s p e c i a l Panel created by the law. Producers and interested parties have 30 days to request a h e a r i n g . If a h e a r i n g is requested',the h e a r i n g w i l l fully explore risks and benefits. This is a formal courtroom-like process before an Administrative Law Judge; expert witnesses are sworn in and1 cross e x a m i n e d * W i t h i n 25 days after the hearing is over , the Judge reports his f i n d i n g s and makes a recommendation to the Administrator. The A d m i n i s t r a t o r has 90 days after the close of the h e a r i n g to issue a f i n a l order. The Final Order may p r o v i d e for c o n t i n u a t i o n of some or a l l uses of the p e s t i c i d e , restrictions on its use, or termination of registration 11 , w h i c h e v e r the A d m i n i s t r a t o r may conclude is supported by the record. Any party adversely affected by the final order may seek review in the Court of Appeals. This may i n c l u d e persons opposed to use of the pesticide', if the Order continues registration, as well as proponents of use if c a n c e l l a t i o n is ordered. C a n c e l l a t i o n h e a r i n g s have t y p i c a l l y taken 2 years or more to complete. The p e s t i c i d e in question may continue to be marketed until and under the terms of the final order issued by the Administrator. 3) S u s p e n s i o n Proceedings Suspension proceedings begin with a f i n d i n g by the A d m i n i s t r a t o r that an "imminent hazard" is posed by a pesticide. An imminent hazard is a situation where the risks from use of a p e s t i c i d e d u r i n g the time required to complete c a n c e l l a t i o n proceedings outweigh the benefits that may be be derived from such use. �-3- The suspension is not effective immediately. Instead', the law affords registrants an opportunity to request an expedited hearing within 5 days of receiving notice from the Administrator that he intends to suspend. If an expedited hearing is not requested'', the Administrator 1may implement the suspension by i s s u i n g an order. However , before issuing the order1, the Administrator must begin .cancellation proceedings if he has not already done so. (This is because suspension is an interim remedy and can be effective only for the duration of cancellation proceedings.) If an expedited hearing is requested 11 , the statute requires that it begin promptly. The sole issue at this hearing is whether an imminent hazard exists. .,. The presiding officer'1, or h e a r i n g panel'1, has 10 days after completion of the hearing to submit findings and a recommendation to the Administrator. The Administrator has 7 days to decide whether to affirm the imminent hazard determination; if he does', a final suspension order is issued. The final suspension order is reviewable in the Court of Appeals. The pesticide(s) in question may be marketed d u r i n g the time it takes to complete the expedited hearing. 4) Emergency Suspension Proceedings This proceeding begins with a f i n d i n g that an imminent hazard exists and that an emergency exists -that the situation is so critical that the Administrator does not have time to hold a hearing before suspending. (In other words', the Administrator finds that unreasonable risks would be posed by continued use of the pesticide during a suspension hearing.) An emergency suspension order is issued without prior notice to registrants and takes effect immediately. The Order must be accompanied by a notice beginning cancellation proceedings, unless they are already in progress �-4- Although they do not.receive advance notice 1 , registrants may s t i l l request an expedited hearing w i t h i n five days to determine whether the suspension order should remain in p l a c e for the duration of the cancellation proceeding. In other words', the emergency order only a p p l i e s during the expedited suspension hearing 1 , if one is requested. The Administrator may lift the emergency order8, modify it, or keep it in place for the duration of the cancellation heari ng. U n l i k e "regular" suspension 11 , only the registrant and the Agency may participate in the expedited hearing; others may present briefs. The presiding officer or hearing panel has 10 days from the conclusion of the hearing to submit findings and recommendations to the Administrator. The Administrator then has 7 days to issue a final order on the issue of suspension. A final order "on suspension after a hearing before the Agency", may be reviewed in the Court of Appeals. Producers may appeal an emergency suspension order to a Federal District Court w h i c h reviews only whether the emergency finding is supported. The District Court order may be appealed to the A p p e l l a t e Court by either the Agency or the registrant. ************************ Suspension 1 , it should be remembered'1, involves a p r e l i m i n a r y assessment of evidence and probabilities', not an u l t i m a t e resolution of the larger question of the risks and benefits of the pesticide to society over the long run. That larger question is addressed in the c a n c e l l a t i o n proceedings. The1 Courts h a v e found in the past that for a suspension action , "It is enough if there is a substantial 1 i k e 1 i h o o d [emphasis in original] that serious harm w i l l be experienced during the year or two required in any realistic projection of the a d m i n i s t r a t i v e (cancellation) process" [Environmental Defense Fund11, Inc. vs. E n v i ronmental Protection Agency; 465 F2d 540 (D.C. Cir 1972)]. �United States Environmental Protection Agency SEPA Office of Public Awareness (A-107) Washington DC 20460 Environmenta Woods 202-755-0344 O'Neill 202-755-0344 Fitzwater (202) 755-0344 FOR I M M E D I A T E R E L E A S E , THURSDAY MARCH 1 , 1979 EPA TAKES E M E R G E N C Y ACTION TO HALT HERBICIDE SPRAYING A c t i n g on s i g n i f i c a n t new e v i d e n c e l i n k i n g the h e r b i c i d e 2,4,5-T w i t h m i s c a r r i a g e s in women in Oregon 1 , the Environmental Protection Agency today halted major uses of the herbicide u n t i l a f u l l review of its impact on h u m a n health and its benefits is completed. The Agency's "emergency suspension" action -- the most drastic measure EPA can take under the law -- was needed because the s p r i n g spray season is only a matter of weeks away. "Stirdies completed only days ago show a h i g h m i s c a r r i a g e rate immediately following the spraying of 2,4,5-T in the forests around Alsqa, Oregon;" said EPA Deputy Administrator Barbara B l u m . "This a l a r m i n g correlation comes at a time when 7 m i l l i o n pounds of 2,4,5^T are about to be used to control weeds on power 1 i n e rights-of-way and in pastures', and to manage forest l a n d s across the Nation." Those uses w i l l be h a l t e d .-.immediately by EPA's order. The remaining legal uses.of 2,4,5-T o/i r a n g e l a n d and rice may c o n t i n u e u n t i l the final decision because they appear at t h i s time not to i n v o l v e human exposure comparable to the suspended uses. �"The emergency s u s p e n s i o n a c t i o n we are t a k i n g w i l l protect the nearly 4 m i l l i o n p e o p l e who may be u n k n o w1i n g l y and i n v o l u n t a r i l y exposed as a result of the forestry , rights-of-way, and pasture uses," B l u m said. "The p o t e n t i a l for s i g n i f i c a n t h u m a n exposure, the w a r n i n g s i g n a l s from the A l s e a study, the strong a n i m a l test data, and the low short term economic benefits compel t h i s u n u s u a l action." The new study was i n i t i a t e d by EPA because of c o m p l a i n t s from women in A l s e a r e p o r t i n g that they had experienced m i s c a r r i a g e s r i g h t after the forest area was sprayed with 2,4,5-T. The study was performed by scientists from the E n v i r o n m e n t a l H e a l t h Institute of Colorado State U n i v e r s i t y and the U n i v e r s i t y of M i a m i M e d i c a l School, Department of P u b l i c H e a l t h and E p i d e m i o l o g y . It compared miscarriages over a 6 year period in the Alsea b a s i n area of western Oregon with a control area in the eastern part of the State. The c o n c l u s i o n s were: The m i s c a r r i a g e rate in the A l s e a area was s i g n i f i c a n t l y h i g h e r than that in a control area in eastern Oregon where no 2,4,5-T is t y p i c a l l y sprayed; The number of m i s c a r r i a g e s peak d r a m a t i c a l l y for the 6 years, and p a r t i c u l a r l y for the last 3 years, in the Alsea area for the month of June. Forest spraying occurs a n n u a l l y in March and A p r i l ; there is a s t a t i s t i c a l l y significant r e l a t i o n s h i p between the spray season and the h i g h m i s c a r r i a g e peak which follows a p p l i c a t i o n of 2,4,5-T by 2-3 months. "It's a remarkable correlation," said B l u m . " W h i l e it is not proof of a cause and effect r e l a t i o n s h i p , it is h i g h l y s u g g e s t i v e , p a r t i c u l a r l y in l i g h t of a n i m a l data, and gives great cause for concern." �-3 - Numerous laboratory tests in several a n i m a l species reveal similar reproductive problems with 2,4,5-T. "There are considerable data on the h e a l t h effects of 2,4,5-T in a n i m a l tests which are p r e d i c t i v e of the same human health effects we are seeing in Alsea," said Blum. 2,4,5-T is contaminated with 2,3,7,8-tetrachlorodibenzo-pd i o x i n (TCDD), which even at very low l e v e l s , produce birth defects, miscarriages, and tumors in laboratory animals. "Taken together, a l l these facts sound an alarm. Prudence dictates EPA to stop use u n t i l we have a fuller u n d e r s t a n d i n g of t h i s phenomenon and its i m p l i c a t i o n for h u m a n h e a l t h , " s a i d Blum. 2,4,5-T was first registered in 1948 as a h e r b i c i d e for control of broadleaf weeds. A c t i n g in 1970 on the basis of the a n i m a l tests, the Federal Government h a l t e d those uses to which there was a h i g h p r o b a b i l i t y of pregnant women b e i n g exposed: home and g a r d e n , recreational area, and a q u a t i c sites. A l l food uses', except for rice which was a p p e a l e d by the manufacturer 11 , were halted as well. Since that t i m e , the h e r b i c i d e has been used against unwanted vegetation primarily in forest management (2.6 m i l l i o n p o u n d s used a n n u a l l y on 1.16 m i l l i o n acres), rights-of-way c l e a r a n c e (3.8 m i l l i o n pounds used a n n u a l l y on' 683,000 acres), p a s t u r e l a n d (500 t h o u s a n d pounds on 1 m i l l i o n acres), r a n g e l a n d (2 m i l l i o n pounds on 1.7 m i l l i o n acres), and rice (300 t h o u s a n d pounds on 300,000 acres). Forresters regard the h e r b i c i d e as a v a l u a b l e tool in reforestation and in encouraging conifer growth (by e l i m i n a t i n g hardwoods w h i c h compete for l i g h t and n u t r i e n t s ) , and in a l l o w i n g m a i n t e n a n c e access to power 1 i nes. There h a v e been years of debate about the safety of these uses of 2,4,5-T. In A p r i l 1978 EPA issued a r e b u t t a b l e p r e s u m p t i o n a g a i n s t r e g i s t r a t i o n (RPAR) on 2,4,5-T, w h i c h s o l i c i t e d p u b l i c i n p u t on the risks and benefits of the h e r b i c i d e . That review of rice and rangeland uses w i l l continue d u r i n g the suspension proceedings. �-4- "This emergency action only suspends use u n t i l the risks and benefits can be more f u l l y evaluated 1 ," said Blum. "We have c o n s i d e r a b l e data on the long term economic benefits' of 2,4,5-T. The extensive analysis and data from the manufacturers and users and the USDA/State/EPA benefits assessment team in the RPAR procedure w i l l be very v a l u a b l e as we continue these d e l i b e r a t i o n s . The groundwork l a i d in the p u b l i c commant period w i l l be 'instrumental in reaching as r a p i d and fair a final c o n c l u s i o n of this d i f f i c u l t question as possible." "The short-term economic impact of this action -- i.e., suspension of uses over the period the expedited hearing and the c a n c e l l a t i o n proceedings -- s h o u l d not be serious. This is so because a l t e r n a t i v e s are a v a i l a b l e for pasture and rights-of-way uses, and because only a tiny fraction of commercial forest acres are treated in any given year. Moreover, in many cases treatment can be deferred u n t i l these proceedings are completed. The long-term economic impacts w i l l be fully e v a l u a t e d -- a l o n g with the long-term health risks -- in the c a n c e l l a t i o n proceedings. In a corollary action, EPA is also s u s p e n d i n g related uses of si"! vex", another h e r b i c i d e contaminated by TCDD, to preclude s i m i l a r exposure^; e s p e c i a l l y since s i l v e x could be used as an a l t e r n a t i v e to the suspended 2,4,5-T uses. S i l v e x is used p r i m a r i l y for weed control on suburban lawns and other turf. Several a l t e r n a t i v e s are a v a i l a b l e for this use. Any sale 1 , d i s t r i b u t i o n , or use of a suspended pesticide d u r i n g the period of its suspension is i l l e g a l and may be p u n i s h e d by s u b s t a n t i a l penalties. The Agency w i l l be issuing Stop Sale, Use", or Removal Orders to a l l registrants and distributor registrants of 2,4',5-T and silvex, as well as to all establishments which produce 2,4,5-T or silvex. EPA is requesting the cooperation of States in assuring that the Suspension Order is followed. Persons who hold q u a n t i t i e s of these products^ must stop any further d i s t r i b u t i o n or use. Stocks should be stored in an out of the way area and in accordance with storage instructions on the products' l a b e l i n g until EPA issues a final order after the cancellation proceedings. �-5- Manufacturers of the herbicides; i n c l u d i n g Dow Chemical Co., 1Rhodia', Inc., Thompson Hayward Chemical Co. and Vertac , Inc.; have 5 days to appeal EPA's emergency suspension order. If it is appealed a s p e c i a l expedited hearing w i l l be convened to consider the Administrator's f i n d i n g that an imminent hazard exists. The hearings w i l l be run by a special p a n e l , which must reach f i n d i n g s and make a recommendation to the Administrator within 10 days after evidence has been heard. The Administrator would then have 7 days to issue a f i n a l order on whether the suspension should continue through the c a n c e l l a t i o n process. After the suspension issue is decided; the c a n c e l l a t i o n hearing process w i l l begin to consider the larger issue of the risks and benefits of the h e r b i c i d e to society over the long run. C a n c e l l a t i o n proceedings usual.ly take between one to two years to complete. ##### � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5263 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Press Releases, Fact Sheets, and Charts related to the EPA Suspension of 2,4,5-T and Silvex, March 1, 1979 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/b48021aba5b402b1fa22001b79d4ec8a.pdf ae5383d0532729eebd9ca88f5f446757 PDF Text Text Item D Number 05264 Author D Deukmejian, George NotSMnnBfl Office of the Attorney General, State of California Report/Article Titlfl Opinion of George Deukmejian, Attorney General, and Clayton P. Roche, Deputy Attorney General; No. CV 78/105, March 2, 1979 Journal/Book Title Year Month/Day Color March 2 D Number of Images ° DeSOrlptOD Notes Opinion on the right of a county board to adopt an ordinance banning the application of phenoxy herbicides. Tuesday, March 05, 2002 Page 5264 of 5363 �OFFICE OF THE ATTORNEY GENERAL • State of California 4+ . * £ ,„ *%% «%..f&>/# .^'A/^ GEORGE DEUKMEJIAN ~\ Attorney General ' OPINION No. CV 78/105 of GEORGE DEUKMEJIAN Attorney General MARCH 2, 1979 CLAYTON P. ROCHE Deputy Attorney General THE HONORABLE JOHN A. DRUMMOND, COUNTY COUNSEL, MENDOCINO COUNTY, has requested an opinion on the following question: May either the Mendocino County Board of Supervisors, or the county voters through the initiative process, adopt an ordinance banning the application of phenoxy herbicides including, but not limited to ".2,4-D", "2,4,5-T" and silvex in Mendo-' cino County, or is such matter goveme'd exclusively by the provision of si_ate. law, specifically section 14001, et seq. of the Food and Agriculture Code? The conclusion is: Neither the Mendocino Co'inty Board of Supervisors nor the county voters through the initiative process may adopt an ordinance banning the application of phenoxy herbicides, including but not limited to "2,4-D", "2,4,5-T" and silvex, in Mendocino County as such matter is governed exclusively by the provisions of section 14001 et seq. of the Food and Agriculture Code and related statutes and regulations. Additionally,-the matter appears to be preempted by federal law insofar as local agencies of the state are concerned. • ' ' ANALYSIS A county has only those powers expressly granted to it by the constitution or the general laws of the state, or those powers which may be necessarily implied therefrom. • (Upton v. City of Antioch (1959) 171. Cal.App.2d 858, 861, and. cases cited 1. �D. Preemption 3y Federal Law The Federal Environmental Pesticide Control Act of 1972 provides for the comprehensive regulation of pesticides, including their registration and use. The legislative history of that act indicates that it did not intend to preempt states from legislating in the same field but it did intend to prohibit local entities of states from doing so. Section 24 of that Act provides (7 U.S.C. 3 136v) : "(a) A State may regulate the sale or use of any pesticide or device in the State, but only if and to the extent the regulation does not permit any sale or use prohibited by this subchapter; "(b) Such State shall not impose or continue in effect any requirements for labeling and packaging in addition to or different from those required pursuant to this subchapter; and "(c) a State may provide registration for pesticides formulated for distribution and use within that State to meet special local needs if that State is certified by the Administrator as capable of exercising adequate controls to assure that such registration will be in accord with the purposes of this subchapter and if registration for such use has not previously been denied, disapproved, or canceled by the Administrator. Such registration shall be deemed registration under section 136a of this title for.all purposes of this subchapter, but shall authorize distribution and use only within such State and shall not be effective for more than .90 days if disapproved by the Administrator within that period." (See also 7 U.S.C. § 136b(a)(2) regarding "state certification" of "state plans." With respect to the 1972 federal law, Senate Report No. 92-838 stated in part: "4. The Senate Committee considered the decision of the House Committee to deprive political subdivisions of States and other local authorities of any authority or jurisdiction over pesticides and concurs with 20. CV 78/105 �the- decision of the House of Representatives. Clearly, the fifty States and the Federal Government provide sufficient jurisdictions to properly regulate pesticides. Moreover, few, if anyr local authorities whether town, counties, villages, or municipalities have the financial wherewithal to provide necessary expert regulation comparable with that provided by the State and Federal Governments. On this basis and on the basis that permitting such regulation would be an extreme burden on interstate commerce, it is the intent that section 24, by not providing any authority to political subdivisions and other local'authorities of or in the States, should be understood as depriving such local authorities and political subdivisions of any and all jurisdiction and authority over pesticides and the regulation of pesticides," (1972 U.S. Code Congr, & Admin. News at pp. 3993, 4008.) (See also further indication of this legislative intent in Senate Report No. 92-970, wherein a proposed amendment is set forth and discussed to give, "local governments the authority to regulate the sale or. use of a pesticide beyond the requirements imposed by State and Federal authorities." The amendment was, of course, not accepted as is evident from the report of the Conference Committee as well 'as the terms of Section 24 of the law as enacted.(See 1972 U.S. Code Congr. & Admin. 'Jews at pp. 4092, 4111, 4128, 4130, 4134.) Accordingly, the legislative history of the Federal Environmental Pesticide Control A it of 1972 indicates virtually conclusively an intent that the federal law should preempt any regulation of pesticides by any local entity of a state. CONCLUSION State and federal law both preempt and preclude Mendocino County, either through its board of supervisors or the electorate, from prohibiting the use, aerial or otherwise, of phenoxy herbicides in the county. "Whether this is or is not wise policy is not for this office to determine but is a question to be directed to the State Director of Agriculture, the State Legislature, the Environmental Protection Agency, and Congress. 13/ 13. We note the news releases this, date to the effect that the Environmental Protection Agency has in fact just used its emergency powers to impose a partial ban upon "2,4,5-?" and silvex, (See, e.g., San Francisco Chronicle, March 2, 1979, p. 4.) PV 7R/10S � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5264 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Deukmejian, George Clayton P. Roche Description An account of the resource <strong>Corporate Author: </strong>Office of the Attorney General, State of California Date A point or period of time associated with an event in the lifecycle of the resource March 2 1979 Title A name given to the resource Opinion of George Deukmejian, Attorney General, and Clayton P. Roche, Deputy Attorney General; No. CV 78/105, March 2, 1979 ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5265 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Smith, Jeffrey Source A related resource from which the described resource is derived Science Date A point or period of time associated with an event in the lifecycle of the resource March 16 1979 Title A name given to the resource EPA Halts Most Use of Herbicide 2,4,5-T ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5266 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Leng, Marguerite L. Description An account of the resource <strong>Corporate Author: </strong>Dow Chemical, U. S. A. Date A point or period of time associated with an event in the lifecycle of the resource February 26 1979 Title A name given to the resource Product Registrations Report ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/7f87f11411c5862d2c09e3d14d0db86c.pdf d95be8356c93635009d4d99a304871cc PDF Text Text item i Number °5267 D Not Scanned Winer, Michael S. CorpOratB Author United States Environmental Protection Agency (EPA) ROUOrt/ArtlClB TitlO Rsbuttal Comments of Respondent Environmental Protection Agency in re: Emergency Suspension Orders for 2,4,5-T and Silvex, April 4, 1979 Journal/Book Title Year Month/Day Color Number of Images A ril 4 P D ° Descripton Notes Tuesday, March 05, 2002 Page 5267 of 5363 �UNITED STATES ENVIRONMENTAL PROTECTION AGENCY In re: Emergency suspension Orders for 2,4,5-T and Silvex ) ) ) FIFRA Docket Nos, 409, 410 REBUTTAL COMMENTS OF RESPONDENT ENVIRONMENTAL PROTECTION AGENCY Michael S. Winer Dorothy E. Patton Patricia A. Roberts Ellen Siegler Kevin M. Lee Timothy D. Backstrom ENVIRONMENTAL PROTECTION AGENCY 401 M Street, S.W. Washington, D.C. 20460 April 4, 1979 �I he:.eby c e r t i f y chat copies of tine foregoing "Rebuttal Comments of Respondent Environmental Protection Agency" were hand-delivered or availed first; class postage p r e p a i d , on April 4, 1979, 10 the following G. K. F r i t h , President Tobacco Scales C h e m i c a l Coraoany , P.O. Box 12045 Lexington, Kentucky 40580 T i mo t h y A t k e s o n 31 e o t o e i J o h n s o n Chevron Chemical Company 1250 Connecticut A v e n u e , N.W. Washington, D.C. 2003S "£. v e!. e t c Meal m a n ? 81 G o r d o n C o r p 300 3 o u ch 3rd Kansas C i t y , K3 55113 Shrikant V. K u l k a r n i , Ph.D. Manager, Pesticide Labeling Vertac Technical Center P.O. Box 941 West Memphis, AR 72301 tiouston G-_*rvais, President Louisiana Pesticide Applicators Assoc Baton Rouce, LA 70303 Ro be r t L . A c ke r 1 y Sellers, Conner & Cunso Counsel f o r L e b a n o n C h e rr, i c -:: .1 C o r p 1525 K Street, H.W. Washington, O.C. 20005 dward ','< , W a r r e n , et al Counsel foi Oov Chemical Company 1775 f. S t r e e t , [•].>/. L a r r y R . Hodges O: A m b l e r , P e n n s y l v a n i a 13002 Gene R. Cur r ie Technical Services Manager M f A Oil C o a p a n y 3 o A -t 2 j - •{ e s t o t n A v e n u e 3 h ~ n a n d o a n , IA 51 o 01 Graham Purcell, Esquire Douo, Purcell, Muntzing & Hansen , Char ter ed 1775 Pennsylvania Ave . , > T . / v . Washington, D.C. 20005 Counsel for R i v e r d a l e Chemical Company, Frank Miller i Sons, Tobacco States Chemical Company, P3I Gordon Corp. , Pueblo Chemical i Supply Company a n d ?1a 11 e Ch e m i c a 1 C o m o a n v Roger A. Shores, President B a r t e i s and Shores Cheir.ica! 1400 St. Louis Avenue K a n s a s City, MO 6 4101 John E. Soltes, General Man I'fSGRO, D i v i s i o n of Old Fort .o �A n c h o n v ? . 3r own Piflsourv, Madison G e n e:: a 1 C o u n 3 .e ]. u n i v e r s a l C o o p e r a t i v e s , Inc. Minneaoolis, MM 5: Sonide Chemical Company 2 ', t u r 2 Yorkville , ;?'/' 13495 F r a n k 3 . 3 c e w a r G , 7 i c e e r e s z. o e n r_ Tne Chas . H. Lilly Company 7237 N". E . X il 1 ingsvor ch ? o r c 1 a n -s , OR 97213 Jon 0 . L o f L , ? r e s i a ent ^" '> f ^-i W ™ *~ O U ™" iC* •. O v«i .. (L -' * '. - „ * _ '"I — '"{ " ,'~T V -J il^ * L -s £j v_/ " Lj '"^ / r; \ j T ^ i~> j. t ; ^ •. P . O . Sox 1 4 5 Bound B r o o k , :JJ 03305 R o n a 1 d A . M e i e r , M a n a-g e r Lawn F e r t i l i s e r D i v i s i o n ' T h e A n d e rs o ns P.O. 3 o x 119 Maumee, OH 43537 MelYin R. Wilcox, III Roberts, H a r b o u r , S m i t h , H a r r French S Ritcer Counsel for T.O. 3ell/dba/?or Unlimited 404 Morch Green S t r e e t Longview, TK 75601 0 . A. Wo1c o c c, Manage r Planning i Technical Services F a r m e r s Union G e n e r a l Exchange, Inc. John J . Sal ardo Corporate Counsel 2727 W a l k e r , M.W. Grand Rapids, MI 49504 Gene R . Cur r ie Technical Services M a n a g e r Imp «:.• ial Inc . Box 423 We 3*. oth Avenue Shenandoah, IA 51501 John R. Diem, Vice Presidenc u the Inc. P.O. Box 213 R i c h a r d deC. H n d s , Esq. C i e a r y , Go^ilieb, 3'een ^ Ha;Tiilcon Counsel for U35 Acr i-Che:r icai D i v i s i o n of United Spates S^eel C o r p o r a t i o n 1250 Connie t ic'-i r_ A v e n u e , II . W . H L o r a n t. for Slack Leaf Lor an. and Lor a n c , ?C P.O. Box 353 Hianland Park , IL 50035 H - r i c a g e Housi P r o d u c t s C o r p o r a t i o n 1025 Northern Boulevard Roslyn, MY 11575 J o n n R . '<-t i r i p Roc'<land C h e m i c a P.O. 3 o x 30 9 West Caldwell, -IJ 07005 �TABLE OF CONTENTS PAGE INTRODUCTION-----------------------------------------------1 REGULATORY HIS TOR Y ----------------------------------------- 4 BURDEN OF PROOF IN SUSPENSION PROCEEDINGS ------------------ 6 ENVIRONMENTAL PROTECTION AGENCY REBUTTAL PCS ITION--------------------------------------------------1 0 I. The Administrator's suspension order is based in large part on animal toxicity data, which corresponds to the effects observed on 'the Alsea stud y — — —-------— ------------------— —— — --— — 1 o A . Introduction--------— ----. — ------------------10 — B. Fetotoxic, teratogenic and carcinogenic effects have occurred in test animals as a result of exposure of 2,4,5-T, silvex a nd /o r T CDD — ———.—. — .-.... — - — ... 1 2 .—-.... ... (1) Spontaneous abortions have occured in non-human primates exposed to 2,4,5-T, silvex and/or TCDD------------------13 (2) Reproductive failure is common in other mammalian species exposed to 2,4,5-T, silvex and/or TCDD — ---—----. — 7 — 1 (3) Exposure to TCDD or 2,4,5-T and/or silvex contaminated with TCDD poses a potential carcinogenic risk to C. Any exposure to TCDD must be regarded as a potential reproductive hazard- ------(1) TCDD is fetotoxic at doses as low as 0.001 mg/kg/d ay------------------------------21 (2) No reproductive no-effect level has been established for TCDD. Therefore, any exposure must be regarded as posing potentially significant risk----------23 �-11PAGE II. The Alsea Study indicates that there is a relationship between the use of 2,4,5-T for forest management in Alsea and spontaneous abortions among Alsea residents------------—28 A. The Alsea Study is* a simple and direct analysis of the relation between the forest use of 2,4,5-T and reproductive failure in humans who live in the area where the pesticide is used—— — - — — —•----- — 31 (1) The spontaneous abortion index was based on hospitalized spontaneous abortions, the most certain means of obtaining a uniform data based for the study and control areas — - — ------• — ----32 (2) The spontaneous abortion, birth and spray data used for 1972-1977, were aggregated to increase the reliability of the rates being estimated—-------35 (3) A statistically significant increase in the overall hospitalized spontaneous abortion index for the study area relative to the control area indicates that such abortions occur more often among women who live in the area where 2,4,5-T is sprayed—----—-----— — -—.-.——- 37 .(4) The statement in the Alsea report that "correlation does not mean causation," re-states a basic principle of statistical analysis and in no way negates the biological significance of the observed relation between the use of 2,4,5-T and miscarriages in the Alsea area—--------—40 (5) There was a statistically significant correlation between the amount of 2,4,5-T used in the Alsea area in March, April and May and the increased incidence of abortions in the study area in June ------------------- 41 �-111- PAGE (6) Dow's argument that there is a June peak of miscarriages in Midland, Michigan actually supports the conclusions of the Alsea Report, and its attempts to discredit the Alsea conclusions by pointing to a June peak in Miami fails because the Miami data is based on induced abortions, not spontaneous abortions-— 42 (7) The results support the hypothesis that the occurrence of spontaneous abortions in Alsea is related to the use of 2,4,5-T 45 E. Valid conclusions concerning human exposure to suspected chemical agents do not depend on the availability of chemicals residue data and are not limited by the lack of such data ———-• ——.——————47 C. In connection with the suspension orders. Alsea I was utilized only to develop the hypothesis, later confirmed through Alsea II, that there was a relation between the use of 2,4,5-T and the occurrence of an excess incidence of miscarriages in Alsea 50 (1) The reviewers inability to find a "causual" relationship between 2,4,5-T and miscarriages in Alsea I is not surprising and has no bearing on the results reported for Alsea II —52 D. The data on the spontaneous abortion index for a neighboring urban area and the spectral analysis -data which were included in the Alsea Report were supplementary in character and were not part of the data used to derive pertinent findings concerning use of 2,4,5-T—————-— 54 (1) The data and analyses relating to' the occurrence of spontaneous abortions in the urban area have no bearing on the differences in the spontaneous abortion indices in the control and study areas 55 �-IV- PAGE (2) The complex spectral analysis in the Alsea Study was performed solely to determine whether or not the June peak in incidence of spontaneous abortions in the Study area could reasonably be attributed to innate periodic variations in the data-------------57 (3) The alternative statistical treatments proposed by Dow do not contradict the basic findings of the Alsea Study----------------------------------59 (a) The alleged "correlation" between monthly spraying of 2,4,5-T in the Study Area and the hospitalized spontaneous abortion index in the Control Area is irrelevant — -------------------60 (b) Even though the suggested use of a Chi-square test to determine whether or not the incidence of hospitalized spontaneous abortions in the Study Area was greater than the incidence of such abortions in the Control Area is of questionable theoretical validity, such a test nevertheless confirms the basic findings of the Alsea Study ------------ 61 III. The Suspended Uses of 2,4,5-T and Silvex result in direct exposure to humans through aerial drift and/or through chemical contamination of vegetation food and water which humans use or consume — - — - — —---—--------.—.-.----53 Introduction B. The Use of 2,4,5-T and/or silvex leads to direct human exposure to these chemicals and to TCDD—---—.—.——— — -----—. ------ — 54 — 1. Use of these pesticides results in direct exposure to bystanders — - — — — ------68 �-vPAGE 2. •3. C. Use of these pesticides results in direct exposure to applicators -------------- 70 Home uses of silvex result in direct exposure to family members------------— — "—73 Use of these pesticides results in contamination of food and water and thereby presents indirect exposure to humans- — - — —•----75 1. Chemical residues of 2,4,5-T» silvex, and/or TCDD are detected in environmental media and human and animal *^"*"^""***** *^ **"w*"™****""^*m*l*"*'w'"™******^"****'—*^"~"""*^""1"^*""*"*^**" / j 2. IV. Contamination of food and water with 2,4,5-T results in indirect exposure to h urn a n s — — — — — — •— — — —---— — 7 7 D . S umm a r y — — —. — — ~ ~ — -- — — — Q Q — The Suspension of the Contested Uses of 2,4,5-T And Silvex Will Not Result in Substantial Adverse Economic Impacts ------------------- -82 A . Introduction — -------------------- — ----•------«•— 82 B . Rights-of-Way—---— — — — ----—• — -— ——84 C. Forestr y — —---— — —---—---—----------------8 7 D . pasture—————— — — — — —- — ———————89 E . Silvex — — — — —---—----- — — — — 9 2 �INTRODUCTION On February 28, 1979, the Administrator issued emergency orders suspending certain uses of the pesticides 2,4,5-T and silvex. The Administrator's decision documents totaled nearly 200 pages.and they were supported by an administrative record approximately 40,000 pages long. The Administrator's orders provided for the filing of counterstatements of position by 2,4,5-T and silvex registrants. On March 26, 1979, the Dow Chemical company filed its comments on the Administrator's emergency suspension orders; several other registrants filed considerably shorter counterstatements. The Administrator's orders also give respondent Environmental Protection Agency an opportunity to file a rebuttal. EPA's rebuttal submission begins with discussions of the regulatory history and of the burden of proof. the rebuttal is divided into four sections. The main body of Section I reaffirms that the suspension orders were based on a vast body of toxicological, medical, and environmental evidence indicating that the uses of 2,4,5-T and silvex pose a serious health threat to */ humans and not just on the Alsea Study. Section I focuses with particular attention on the lack of a reproductive, no-effect level for TCDD and on the primate studies which indicate health effects comparable to those experienced by the Alsea, Oregon, women. V~ Rgport~of Assessment of a_Field Investigation of _Six-Year Spontaneous~Abortion Rates~Tn ThFee 0^egQn_Areas in_~relation t°. ?°-^iIiIlIiiIl5l^§£5Z_l£a.2iiiIs™(hei:e^nafter "Alsea~~II" or Alsea Study"!- This~repoFt was~prompted by letters from eight Oregon women complaining of miscarriages shortly after 2,4,5-T use. The Agency's preliminary assessment of the eight women's experience is referred to as Alsea I. �-2- Section II concerns the validity and significance of the Alsea Study. Although circumstantial evidence of actual and potential adverse human health effects has long existed, the Alsea Study's demonstration of a statistically significant correlation between human miscarriages and the use of 2,4,5-T in the Alsea area provided special new information confirming the predictions of the animal test data and demonstrating that the isolated experiences of individual women occurred in larger groups of women as well. We show in Section II that Dow's analysis of the Alsea Studies is based on unnecessary and unrealistic expectations regarding scientific methods and unsupported claims and erroneous interpretations of the data. Section III deals with Dow's effort to meet its burden of proof by attempting.to show that human exposure to 2,4,5-T is negligible. It should be noted that neither Dow nor other registrants have provided data or other information which refute the Agency's assumption that women who live and work in areas where 2,4,5-T is used may be exposed to the pesticide. Section III presents information developed since the February 28 decisions consisting principally of case histories showing that use of 2,4,5-T may result in the distribution of this chemical (and presumably TCDD) to sites of human habitation and work. The same considerations would, of course, be appli- cable to silvex. Section IV shows that the Administrator adequately assessed the benefits of the suspended 2,4,5-T and silvex uses during the two-year period for cancellation proceedings. We show that �-3- Dow s criticisms of the Agency's analysis is highly speculative and to a considerable degree is marred by misinterpretation of the EPA analyses and by factual or analytical errors. Dow relies heavily on a report entitled "The Biologic and Economic Assessment of 2,4,5-T," which was prepared by the USDA-EPAStates RPAR Assessment Team. That report focused on impacts which could result from a permanent cancellation, not a shortterm suspension. In several instances, Dow has overlooked this important limitation on the Report's pertinence to this case. Moreover, on March 1, 1979, Assistant Secretary of Agriculture Cutler announced cessation of the use of 2,4,5-T for forest management and stated that "the Department fully supported EPA's review of possible risks and benefits associated with the use of 2,4,5-T." The Administrator's findings of relatively minor impacts of the suspended 2,4,5-T and silvex uses are sound. �-4REGULATORY HISTORY During the past 'decade scientific and public concern has steadily mounted over the threat to human health posed by TCDD (a form of dioxin) and by pesticides such as 2,4,5-T and silvex which contain TGDD. In 1969 the Mr.ak Commission, composed of distinguished scientists, issued a report to the Secretary of Health, Education and Welfare recommending that use of 2,4,5-T should be "immediately restricted to prevent risk of human */ exposure." In 1970 the United States Department of Agriculture (which at that time administered the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA)) suspended the registration of 2,4,5-T for aquatic and home uses. As Dow points out, an advisory committee of the National Academy of Sciences did find in a May 1971 report that insufficient evidence of hazard from very low concentrations of TCDD **/ had been established. But the committee went on to note "existing deficiencies in information relative to possible accumulation in the soil and possible magnification in the food chain of the dioxin TCDD. . . . " 67. Advisory Committee Report at And the Committee was sufficiently concerned to recommend that 2,4,5-T formulations used around the home and in recreational areas bear the warning "This compound may be dangerous to pregnant women and animals and its use must be such .as to reduce the possibility of exposure to an absolute minimum." */ Report of the Secretary's Commission on Pesticides and Their Relationship to Environmental Health, U.S. Govt. Printing Office (1969) at 657-58. ^*/ Report of the Advisory Committee on 2,4,5-T to the Administrator of the Environmental Protection Agency (1971) at 64. �-5- Advisory Committee Report at 67. Moreover, it is important to note that studies on animals showing adverse reproductive and carcinogenic effects from TCDD when administered at extremely low dose levels first became available subsequent to issuance of the Advisory Committee Report. For example, the studies showing reproductive and carcinogenic effects at dose levels as low as one_billiqneth of a gram (per kilogram of body weight per day) are very recent. These studies are discussed in some detail later in this memorandum. The Decisions and Emergency Orders are responsive to the new data which has accumulated concerning the toxicity of TCDD at low dose levels in animals and to the very recent Alsea data which indicates a relationship between spraying of 2,4,5-T and incidence of miscarriages. The Administrator has explained why the actions taken are appropriate and candidly set forth the reasons why he has taken these actions now. See Decision and */ Emergency Order (2,4,5-T) at 48-52. As will be explained further below, the decisions that were made were fully in accord with the Administrator's responsibilities and with all applicable requirements of law. */ In Environmental:r Defense Pund_v_._ EPA (Aldrin/Dieldrin), 510 F.2d 1292",~lIF5 ri^~(D.C.""Clr7 T973), plaintiffs charged that EPA's two prior refusals to suspend the registrations of aldrin and dieldrin undermined its decision to take such action subsequently. The court firmly rejected that argument, noting that "what changed here was not EPA s policy but the nature of the evidence." Id. The same is true here. �-6- THE BURDEN OF PROOF IN SUSPENSION PROCEEDINGS The most fundamental principle of FIFRA is that proponents of the use of a pesticide—manufactures and user groups—bear the burden of proof that the benefits of the chemical outweigh the risks which may result as a result of use of the pesticide. Environmental Defense Fund v. EPA, 548 F2d. 998, 1004 (D.C. Cir. 1976); Environmental Defense Fund v. EPA, §10 F2d. 1292, 1297 (D.C. Cir. 1975); Dow Chemical Co. v. Ruckelshaus, 477 F2d. 1317, 1324 (8th Cir. 1973); Stearns Electric Co. v. EPA, 461 F2d. 293, 303 (7th Cir. 1972). The central consequence of this principle and its sound foundation in public policy cannot be grasped without appreciating that chemical regulation is a discipline characterized fundamentally by uncertainty. The statute requires the Agency to balance risks and benefits; however, it.is hardly'ever possible to know, what'the risks and benefits of a pesticide in fact are with the kind of precision which responsible men normally desire to achieve on matters so fundamental and important. This is because the facts are almost always incomplete, the scientific theories unproven, and both the facts and the theories in hot dispute. A few examples are illustrative: a chemical may have been shown to produce liver effects in mice. The chemical is one which is widely used, and as a consequence, a wide varity of groups of people are exposed to the chemical. Leaving aside the questions about the benefits of the chemical (i.e., questions relating to the value of the chemical as a tool to man), the regulation involves, at a minimum, issues about the reliability of the study; whether the animal data is �. a reliable predictor of human illness of man if exposed; what groups of people may be exposed and in what ways and in what amounts? Great uncertainties will be encountered in the attempt to answer each of these questions. The response of an academi- cian to those uncertainties is usually easy to predict—conduct other study, to get more information. While in some situations that answer is an acceptable one, in most situations it is not, for the public policy reasons which are fundamentally sound and reasonable. The reason that "wait and see" is not generally an acceptable answer is precisely because the chemical will continue to be used during any period of further inquiry; con• sequently, the possibility that uncertainties may be resolved after further information gathering in favor of higher, rather than lower, estimates of risk cannot responsibly be ignored. This is not to'say that the regulator must regard risksthat are not known with certainty as infinite; the fundamental point is that responsible regulatory policy will not permit ignoring respectable hypothesis of risk which are consistent with the incomplete information which exists and is relevant to the problem. Thus, the approach which must be taken to risk— and the fundamental meaning of the burden of proof concept under FIFRA—is that the Agency must resolve uncertainties on the risk side of the regulatory equation reasonably in favor of the higher estimates of risk which are consistent with the available data. Registrants and others meet their "burden of proof" by proving that the Agency's assessment of the existing information is flawed, or by performing additional studies to �produce more information which will eliminate or narrow uncertainties, and thereby justify the Agency in acting on the assumption that the chemical to is less risky than it earlier estimated. Risk considerations alone, as we have pointed out before, do not produce decisions under FIFRA; instead, the Agency is required to regulate "unreasonable" risks — which is defined to mean those risks which are found to exceed the economic, social and environmental benefits of use. The burden of proof concept discussed above with respect to risks requires a similar analytical approach to benefits questions. In the end, regula- tory decisions turn on policy laden, legislative decisions on I/ whether the risks exceed the benefits. While there can be considerable disagreement among reasonable men as to how the component parts of a risk/benefit analysis are put together for any given chemical, no one seriously can dispute the fundamental soundness of the approach, or the wisdom of a reasonable allocation of the risks of uncertainty to proponents of the use of a chemical. In summary, this approach is essentially grounded in the judgment that society at large can soundly require people who wish to use a poisonous materal to persuade a regulatory agency that its value as a tool is worth the price which society may have to pay—including the price in injury and illness which can reasonably be hypothesized, if uncertainties in the information available are resolved in V Ethyl Corp. v. EPA., 541 F2d. 124 (D.C. Cir. 1976); Society of Plastics Industry, Inc. v. OSHA 509, F2d. 1301 (2d Cir), cert. denied 421 U.S. 992 (1975). �favor of higher, rather than lower risks. In the context of this decision, this approach boils down to a simple question— are these chemicals valuable enough as tools for man over the two years to justify subjecting people to risks of reproductive failure and cancer which reasonably can be hypothesized to exist, based upon the existing scientific data? The Agency, of course, answers these questions in the negative. The suspension provision is FIFRA's precautionary tool for safeguarding public health before serious harm results. It permits prophylactic action, pending more definitive resolution of the issues. "The function of a suspension decision is to make a preliminary assessment of evidence and probabilities, not an ultimate resolution of difficult issues" Environmental Defense Fund v. EPA, supra, §510 F2d. at 1298. A lesser degree of cer- tainty is required for suspending a pesticide, than for taking it off the market permanently. It is not necessary to find "conclusively" that actual harm to man will occur if the use of the pesticide in question is continued; rather the findings required is that continued use in the cancellation proceedings is "likely" to result in any "unreasonable risk" to man or the environment......[T]he propriety of suspension turns upon an analysis in which the risks are balanced against the benefits, rather than from an analysis of risks or benefits alone... [T]he mere fact that the evidence on either of these issues (risks or benefits) is not complete, or that more evidence may be expected to be developed in the cancellation proceedings, is not a reason to deny suspension. In re Velsicol Chemical Corporation et. al. , Decision of the Administrator on the Suspension of Heptachlor/Chlordane, 41 Fed. Reg. 7552, 7574 (February 19, 1976). �-10ENVIRONMENTAL PROTECTION AGENCY REBUTTAL POSITION I. The Administrator's suspension order is based in large part on animal toxicity data which corresponds to the effects observed in the Alsea Study. A. • Introduction Dow contends that the Administrator's suspension analysis is based almost entirely on the Alsea Study. However/ the exami- • nation of the suspension documents and Administrative Record serves to rebut this contention. These documents unequivocably establish that the decision to suspend was based in part on the studies on animal toxicity and exposure detailed in the notices and listed in the Administrative Record. Specifically, the suspension notices 'open with statements that 2,4,5-T, silvex and TCDD cause reproductive and oncogenic effects in test animals, 2,4,5-T Order at 1, Silvex Order at 1, and continue with the Administrator's finding'that "the occurrence-of [fetotoxic, teratogenic, and carcinogenic] effects in test animals indicates that humans who are exposed to TCDD and/or 2,4,5-T and silvex may experience comparable effects." Order at 2,4,5-T Order at' , Silvex . Further, in the detailed statement of findings, the Notice devotes more than twelve pages to a review of data showing that silvex, 2,4,5-T and/or their common dioxin contaminant, TCDD, produce terotogenic, fetotoxic and carcinogenic effects in test animals. 2,4,5-T Order at 22-34, Silvex Order at 27-36. Further, a discussion of the exposure potential of the uses of 2,4,5-T and silvex fills ten pages of the notice. 2,4,5-T Order at 47-52, 56-61, Silvex Order at 47-52, 54(a)-61. By contrast, �-lithe detailed discussion of the Alsea study occupies six pages. 2,4/5-T Order at 34-42, Silvex Order at 36-43. Thus, although the Alsea study is clearly a crucial element in the decision to suspend these pesticides, the suspension actions were not based exclusively or even primarily on the Alsea study, as Dow contends. Rather, these actions were based on a combination of three interlocking elements which together indicated that the uses of the pesticide presented an imminent hazard to humans who might be exposed to these pesticides if use continued during the coming months. The Alsea study added to the long-standing scientific data and information on the toxic effects and exposure potential of these pesticides, new data showing a correlation between the use of 2,4,5-T in Alsea, Oregon and an excess of spontaneous abortions in that area compared to a control population. Because Dow has chosen to regard the suspension actions as based mainly on the Alsea II study and, notwithstanding the extensive and detailed discussions of other issues in the suspension notices, have based their challenge to these actions almost exclusively on the Alsea study, the Agency responds with corresponding emphasis on the Alsea study in Section II of this memorandum. However, the observed correlation between 2,4,5-T use in the Alsea area and the excess incidence of miscarriages in that area was first investigated and later deemed to be important precisely because the effects observed in the women residents �-12- of Alsea are analagous to the effects observed in test animals. That is, when test animals are exposed to 2,4,5-T, silvex, and/or TCDD, the animals exhibit several different forms of reproductive failure such as fetal death, or animals with birth defects such as cleft palate and abnormal kidneys. 2,4,5-T Order at 22; Silvex Order at 27. Moreover, these fetotoxic and teratogenic effects are observed in test animals at very low dose levels and because no-effect levels for these effects have not been conclusively established,-it is not possible to predict a "safe" level for humans. Thus, the actions suspending 2,4,5-T and silvex were based on animal toxicity data and information on exposure potential, as well as on the Alsea study. The discussion to follow reviews these data in two parts.. Subsection B summarizes the animal toxicity data, referring particularly to the data which tend to be specifically predictive of the adverse reproductive effects observed in the Alsea area residents. Section III reviews information on the potential for biologically significant exposure to humans. B. Fetotoxic teratogenic and carcinogenic effects have occurred in test animals as a result of exposure to 2,4,5-T, silvex and/or TCDD. The Agency's analysis of studies in experimental animals had led to the firm conclusion that maternal exposure to 2,4,5-T, silvex and/or TCDD leads to excess incidences of birth defects, such as cleft palate and abnormal kidneys, stillborn animals and �-13reduced survival among the offspring of these animals. Exposure to these substancies had also resulted in carcinogenic responses. Because of the consistency and reproducibility of these adverse effects, the Agency chose only to cite representative studies in the suspension order documents. are briefly reviewed below. The results of these studies Of special significance are the primate studies, which indicate effects comparable to those seen in the women of Alsea, Oregon. (1) Spontaneous abortions have occurred in non-human primates exposed to 2,4,5-T and/or TCDD. Reproductive studies in rhesus monkeys indicate that V maternal exposure to 2,4,5-T and/or TCDD results in an increased incidence of early spontaneous abortions and reproductive •difficulties. Long-term exposure to' even minute'quantities of ' '. TCDD resulted in a marked increase in the first third of the gestational period even where there was no evidence of maternal toxicity by clinical observation or biomedical testing. Monkeys exposed 50 ppt TCDD (2.5 ng/kg/day) before and during pregnancy had a total fetal loss of 67% (50% by abortion and 17% as stillbirth) and fertility rate of 75%, compared with 0% and 100% in the controls. *7 fn~~TtsTcbimentIT Dow indicates the existence of an unspecified monkey study using silvex. Comments at 28. The Agency is unaware of such a study. *V Total TCDD intake at time of breeding (7 months) was 0.35 ug/kg body weight. It is worth nothing that after 20 months of dietary treatment (total intake - 0.9 ug/kg/ body weight), the females were exhibiting signs of systemic toxicity, indicating that a no NOEL had been established for subchronic toxicity. �-14- Atterapts to re-breed one of the aborters resulted in an additional early abortion. ARI R-9 and personal communications. When animals were treated with a higher dose, the fertility rate dropped to 25%, with one of the two animals aborting in the first third of gestation. Irregularities in menstrual cycles, anovulation, and reduction in the reproductive hormones, progesterone and estrogen, were among the toxic effects seen at the higher dose. The investigators concluded that the reproductive abnormalities were most probably the result of hormone imbalance, and were apparently the result of the TCDD treatment, rather than general toxicity, because the hormonal alterations were observed before the animals became obviously ill (Allen et al., 1977; Barsotti et al., in press). Early abortions have also been observed in monkeys where exposure has only been for a short period of the pregnancy. An accumulated dose of 1 ug/kg (1000 ppt) of TCDD over a 3 week period resulted in a 75% abortion rate, compared with 0% in the controls. All abortions in the treated animals were during the first third of the gestational period and the only evidence of maternal toxicity was slight chloracne in one animal,.observed months later. The viable offspring produced at this dose had abnormal palate develoment, and thre of the four at a lower dose had debatable abnormal development in the same orofacial region. ARI R-39 and personal communications. �-15- Dow regrets that "the agency did not take into consideration the value of primate data prior to the issuance of an emergency cancellation [sic]," and contends that exposure to 2,4,5-T does not result in teratogenic or feto.toxic effects in monkeys, citing two additional studies to support its position. Gehring Affidavit, Appendix (b) (hereinafter "Analyses") at 5. The primate studies using TCDD were discounted because of "significant toxic manifestations" in the pregnant monkeys. Id. at 7. The Agency agrees with Dow's assertion that special emphasis should be placed on the primate studies, because the rhesus monkey is the animal of choice for evaluating the potential V for human reproductive effects. Analyses, Ref. #3; Wilson, 1973. This preference is based upon fundamental similarities between the reproductive systems of man and the monkey. Physically, the monkey uterus, placenta and fetal supportative structures are comparable to those in man; implantation of the ovum and major organogenesis follow similar time courses, occur ing in the first third of the gestational period. In addition, the monkey's hormonal balance of estrogen and progesterone is almost identical to the human system, both in the menstrual cycle and in pregnancy. The ability of the placenta to take over from the ovaries and continue the production of the hormones necessary to maintain pregnancy is common to both. In man, the placenta is able to produce the necessary progesterone and estrogen after the third month, and alteration in maternal levels of these hormones prior �-16- to that time could result in an abortion. Progesterone drops in man have been associated with abortions and the untimely onset I/ of menstruation. The studies cited by Dow were designed to focus primarily on teratogenic effects. In the first, pregnant monkeys were administered 2,4,5-T, containing 0.05 ppm TCDD, "a"t dose levels approximating human exposure." abnormalities were observed. No maternal toxicity or fetal The authors concluded that 2,4,5-T was not teratogenic at the levels tested. However, a close analysis of the study indicates that there may be other evidence of fetotoxicity in the form of increased abortions. In light of the TCDD studies cited above, the apparent doubling of the abortion rate observed in this study should be considered a possible effect. Sufficient experimental details regarding th'e second "study" are not available in the cited reference to allow **/ for an adequate assessment of the s t u d y . H o w e v e r , evidence of abortion, lowered birth weight and incomplete ossification were indicated. In analyzing the TCDD studies, Dow chose to ignore data included in the Record for this action (see above), which demonstrate fetotoxic effects in monkeys at doses where no maternal toxicity was observed prior to the abortion. *7 A~common~coimnent seen among the response to the 2,4,5-T RPAR, Is of women experiencing episodes of untimely vaginal bleeding after reportedly being exposed to spray. See e.g., Responses [30000/26] ##263, 356 and 2187. *V For example, information regarding dioxin contamination of the 2,4,5-T, method of dosing and methods of analysis were not included. �-17- (2) Reproductive failure is common in other mammalian species exposed to 2,4,5-T, silvex and/or TCDD. Studies in rodents have clearly demonstrated that prenatal exposure to 2/4,5-T, silvex and/or TCDD results in toxicity to the offspring of treated animals. Adverse effects from exposure to TCDD have been observed at doses as low as 0.3 ug/kg in mice, 0.01 ug/kg in rats and 2.5 ng/kg in monkeys. The most commonly observed effects are increased fetal mortality and higher incidences of birth defects, such as cleft palate, intestinal bleeding, kidney and cardiovascular anomalies and reduced skeletal ossification. Reduced neonatal survival has also been observed. In all species tested, there is evidence of increased fetal wastage, in the form of resorptions, abortions and stillbirths. 2/4",5-T Order at 22? Silvex Order at 27. Dow contends that "2,4,5-T and TCDD are weakly teratogenic and embryolethal agents which are confined to rodents (primarily mice)...." In support of this contention, Dow claims that the teratogenic effects have only been observed in the mouse which is extremely susceptible to cleft palate, and that other anomalies, such as kidney malformations, are really only retardations in development rathr than true birth defects. The observed fetal lethality is summarily discounted as the result of maternal toxicity, or of a completely different mechanism of action, since rodent fetal death occurs at a different time in pregnancy than the spontaneous abortions observed in Alsea. �-18- Many of Dow's arguments become moot with the realization that for regulatory purposes the important concern is total impact on quality of life, rather than discrete mechanisms of action. Therefore, whether a reproductive failure is the direct result of fetal toxicity or is secondary to maternal toxicity is not a critical determinant for regulation, since the end-result is the same. See Analyses at 3; Comments at 28. This is also true of the distinction made by Dow between studies showing .in-jjtejro death and those showing reduced neonatal survival. Analyses at 4. The important factor is that a life is shortened. Similar reasoning applies to the line drawn by Dow between retardation and "true" teratogenesis. Analyses at 1. The life of an infant born with retarded mental or physical development is certainly disadvantaged and possibly subject to increased risk during his "catch-up" period, even though the handicap may ultimately be overcome. Dow's contention that teratogenicity had only been observed as cleft palate in susceptible strains of mice is unfounded. Cleft palate has also been seen in rats, and palate abnormalities in monkeys. Other types of teratogenic effects which have been observed due to 2,4,5-T, silvex and/or TCDD exposure are cardiovascular anomalies, intestinal disorders and kidney abnormalities, (Some of these observations have been made in Dow sponsored experiments.) Use of a susceptible strain has the advantage of making the experimental system more sensitive. Any baseline �-19- effects due to environmental factors should be nullified through the use of adequate controls. Finally, Dow's argument about time of response does not take into consideration a very basic physiological factor. Dow's Comments at 128-29. The susceptible stages of pregnancy occur at different times in different species. There- fore, the same type of response to a given stimulus could be expected to occur at different times. For example, in mice and i rats, the susceptible period of organogenesis is in the middle third of the gestational period, whereas in man it is early in the first trimester. Therefore, it is reasonable to assume that a toxin which elicits fetal death in the middle third of mouse or rat gestation would be likely to have the same effect in the first trimester of m'an or animals having comparabl'e developmental schemes, such as the rhesus monkey. (3) Exposure to TCDD or 2,4,5-T and/or silvex contaminated with TCDD poses a potential carcinogenic risk for man. Long-term feeding studies have shown that TCDD at very low levels is a carcinogenic agent in mice and rats. TCDD has also been found to be mutagenic in the Ames test without the metabolic activation system. Conversely, there is no significant evidence to indicate that either 2,4,5-T or silvex p_er se is carcinogenic in test species. However, these apparently negative conclusions do not negate the cancer-causing potential of commercially produced 2,4,5-t and silvex, because of their TCDD contamination. �-20- Although Dow "recognizes" that carcinogenic effects from TCDD exposure have been shown in test animals, it contends that human exposure to the TCDD in 2,4,5-T and silvex is so low as to pose no substantial risk. 2,4,5-T or silvex Dow argues that since studies using y have given negative results, the small amount of TCDD they contain cannot be sufficient to pose a significant problem to man. Dow Comments at 31. The Agency's Carcinogen Assessment group (CAG)'concluded that TCDD was carcinogenic at exceedingly low doses; therefore the low amount contained in 2,4,5-T (or silvex) is of concern. The lack of statistically significant tumor incidences from the 2,4,5-T (or silvex) exposure may be attributed to the extremely low levels of TCDD in the product relative to the levels at which it produces observable •carcinogenic effects in rodent bioassays using relatively small numbers of animals. However, since TCDD is a strong carcinogen, 2,4,5-T (or silvex) products containing TCDD at any detectable levels can be considered human carcinogenic hazards. CAG, 1979. Dow argues that a "reproducible carcinogenic effect has been observed only with a higher toxic dose in excess of 1000 ppt (TCDD)." Dow Comments at 30. The CAG has reviewed a recent study conducted by Dow Chemical Company and has concluded that *7 Dow~mentTons~~f"Ive long-term studies in rats or mice using silvex. The Agency is aware of only two of these studies designed to test the oncogenic potential of silvex. However, from the available information, it appears that silvex ge£ se is not carcinogenic in test species. �-21- the combined incidence of hepatocellular carcinoma and hepatocellular hyperplastic nodules in rats is statistically significant at both the 2200 and 220 ppt levels. Also, a recent communication to CAG from the National Cancer Institute indicated that in their as yet incomplete study, TCDD appears to be as carcinogenic and potent as was observed in the Dow study. Dow further alleges that "the negative animal data has [sic] been confirmed by recent and extensive epidemiological studies of humans exposed by phenoxy herbicides." The Agency is unaware of such studies." Finally, Dow contends that it will show that the carcinogenic risk to man from the TCDD in 2,4,5-T and silvex is "considerably less than for . . . eating peanut butter." Since the obvious reference here is to the possibility of exposure to the extremely potent carcinogen, aflatoxin, it seems appropriate to note that recent calculations indicate that TCDD is even more potent as a carcinogen than aflatoxin. C. Any exposure to TCDD must be regarded as a potential reproductive hazard. (1) TCDD is fetotoxic at doses as low as 0.001 ug/kg/day. Dow has also challenged the Agency's failure to adopt the TCDD no-effect level of 0.03 ug/kg/day upon which the RPAR was based as a no-effect level for teratogenic and fetotoxic effects. This challenge ignores, with good reason in terms of Dow's interests, new data, developed in Dow's own laboratories showing �-22- that TCDD has fetotoxic effects effects at doses as low as 0.001 ug/kg/day. After the RPAR was issued in April of 1978, the Agency received new data establishing that TCDD has adverse reproductive effects as doses lower than 0.03 ug/kg/day. Specifically, in the RPAR notice the Agency reported that the Dow Chemfcal Company had submitted a letter summarizing preliminary results from a new study on the effects of TCDD in rats over three generations. Record at R-l, p. 17131. At that time, Dow did not provide the underlying data, but stated'that fetotoxic effects were observed at 0.01 ug/kg/day in some generations. Because Dow described the report as preliminary, and because little data was presented in the letter, the Agency used data from the published literature showing that 0.03 ug/kg/day was a no-effect level, rather than using information from plaintiff's letter. Subsequently, Dow has published an abstract of some of the data and has submitted a data report to the Agency. Record at R-8. In these reports, Dow itself recognized 0.01 ug/kg/day as an effect level. Thus, although Dow's use of the 0.03 ug/kg no-effect level used in the RPAR is understandable, this value would be unsound both as a matter of science and of policy. Moreover, the Agency's review of these data indicates that adverse reproductive effects are observed at 0.001 ug/kg/day. 2,4,5-T Order at 26. Silvex Order at 31. �-23- Thus, the 0.03 ug/kg/day used in the RPAR is not the applicable no-effect level. Because the Agency explained in the emergency orders that "exposure to 0.001 ug/kg/day . . . resulted in statistically significant increases in the percentage of pups dead at birth or dying before the end of three weeks of life in some generations," Id., Dow's statement that the suspension decisions and the RPAR conclusions were based on "virtually identical animal research reports" is totally erroneous. (2) No reproductive no-effect level has been established for TCDD. Therefore, any exposure must be regarded as posing potentially significant risk. The suspension decisions are based in part on a Dow study < showing that TCDD produces adverse reproductive effects in test animal'at doses as low as 0.001 ug/kg/day (.hereinafter''"Dow study"). However/ Dow interprets this data as showing that no effects were observed at 0.001 ug/kg, over three generations. Record at R-8. Action No. Because the injunction in Dow v. Cosjtle, Civil 76-10087, arguably precludes EPA from disclo'sing data from this study, EPA presented a summary, but not the actual data, in the decisions and orders suspending these pesticides. 2,4,5-T Order at 26; Silvex Order at 30. EPA regards this study as critically important to the Agency's determination that an imminent hazard exists, and regrets that the injunction prevents �-24- the disclosure of the data that substantiate and illuminate the basis for the Agency's determination that there are fetotoxic effects at 0.001 ug/kg. the lowest dose tested in any TCDD study. Although the inconsistencies between EPA's and Dow's interpretations of the data can be evaluated only if the actual data can be disclosed, the basis for EPA's position is detailed below. The Dow study shows that adverse reproductive effects occur in test animals exposed to doses of TCDD as low as O.'OOl ug/kg/day. However, Dow's summaries of the data state that there are generally no adverse effects at this dose level, and create the impression that 0.001 is a "no-effect" level. Generally a no-effect level is viewed as a toxicological endpoint, marking a level of exposure in animals which is "safe" */ because there are no observable adverse effects. Toxicologists generally assume that the animal no-effect level can serve as a base for estimating exposure levels which would be "safe" for humans. The "safe" level for humans is set at some level lower than the animal no-effect level to provide a "margin-of-safety" that takes into account differences in senstivities between animals and humans, and differences in sensitivities among humans. This "margin-of-safety" does not represent an infallible *7fhe~dTscuisIon~of "no-effect levels" is irrelevant to the estimation of potential cancer risk. See discussion at , �-25- indicator of potential hazard to humans. Error could be introduced because man is more sensitive than the test species by a greater factor than normally allowed, or by the incorrect choice of a no-effect level. The thalidomide tragedy is probably the best known example of error in predicting human safety from animal data. There, although testing indicated that exposure to the drug produced no abnormal effects in animals, when humans used the drug it became clear that the medically prescribed dose assumed to be safe when considered in terms of the animal test data was, in fact, dangerously toxic to the human fetus. The lowest level at which TCDD has no-observable effects in test animals is crucial to the Agency's determination of the risk potential of 2,4,5-T and silvex. TCDD is present in these pesticides as a low-level contaminant and thus will be present in the environment at low levels whenever and wherever these pesticides are used. If there truly is a no-effect level in animals it is possible at least to begin to estimate a possible "safe" level for humans and to assess the possible risk to humans by relating this assumed "safe" level to the level of pesticide that may be in the environment, if that level is known. Conse- quently, if there is no no-effect level, any use of 2,4,5-T and silvex would result in potentially significant expsure to TCDD, �-26- because there is no minimum level upon which to estimate a V a margin-of-safety. It is the Agency's position that no reproductive no-effect level has been demonstrated for TCDD. In a September 1977 preliminary report to the Agency, Dow described observations in the animals exposed to 0.001 ug/kg/day only in terms that implied that there was no adverse effects at this dose level. Record at R-l. Dow later published an abstract of this study in which it added experimental details and new data, without further elaboration. Specifically, they said: "At 0.001 ug/kg/day, no deleterious effect on fertility was seen in any generation." "Among litters of rats receiving 0.001 ug/kg/day no-effect on litter size at birth or neonatal growth was observed in any generation." "In summary, the reproductive capacity of rats ingesting of 0.01 and O.-l ug/kg/day, but not at 0.001 ug/kg/day, through' three successive generations." "Statistically significant increases and decreases in survival were seen at 0.001 ug/kg/day." Record at R-8. VIt~ls~questlonable whether the traditional margin-of-safety calculation used in establishing tolerances, which uses a factor of 100, would be appropriate for TCDD. The factor of 100 under this approach is derived by assuming that a factor of 10 adequately compensates for possible variation in. susceptibility wJ.thJLn a species, and that a second factor of 10 adequately compensates for differences between species (i.e., between the animal test species and man)7fHere is some reason to doubt whether a safety factor of 10 adequately compensates for the variability in susceptibility of human beings. Even if this were not the case, however, the wide variability in susceptibility of different aruma! species to TCDD raises great doubt as to the justification fol using on_ly_ a factor of 10 to adjust for possible variations in susceptibility between an animal species and man. �-27- In contrast to Dow's descriptions of no effects at 0.001 ug/kg/day, EPA's review of this study indicates that the following adverse reproductive effects were observed at 0.001 ug/kg/day: statistically significant decreases in neonatal survival in the first litter of the first generation at 24 hours, 7 days, and 21 days. a significant decrease in the gestation survival index and the 7 and 14 day survival indices in the second generation literature. Record at R-8, Confidential. These observations mean that there were statistically significant increases in the number of stillborn pups and that a larger than normal proportion of the animals that were born alive did not survive the first two weeks of life. Although EPA acknowledges that adverse effects do not appear in all generations ingesting 0.001 ug/kg/day, it cannot accept the premise that the effects which do appear should be ignored. �--tell. The Alsea Study indicates that there is a relationship between the use of 2,4,5-T for forest management in Alsea and spontaneous abortions among Alsea residents. The Agency's review of the relation between the use of 2,4,5-T and the occurrence of spontaneous abortions in the Alsea area includes three closely related but separate phases. The first phase, or Alsea I in Dow's terminology, was a case history review of the occurrence of miscarriages among a group of eight women who reported an unusually high proportion of miscarriages in their group and that the miscarriages generally followed by approximately two months the annual use of 2,4,5-T in their area. The women questioned whether there might be a relation between the spraying of 2,4,5-T each spring and the occurrence of eight of their miscarriages in June. Alsea I constitutes the Agency's investigation and conclusions relating to the miscarriage experience of these eight women. As the history of this action clearly shows, no regulatory action was taken on the basis of the Alsea I data. Further, except for establishing the initial hypothesis, the examination of these case reports was not utilized to support the decision to suspend these pesticides. Accordingly, the data relating to the eight women have little bearing on the suspension action and Dow's challenges to these data have little relevance. In Alsea II, the Agency investigated the hypothesis which arose from Alsea I and the experimental animal data by studying a large cohort of births and miscarriages among Alsea residents. �Alsea II constitutes the second stage in the Agency's investigation of the relation between the uses of 2,4,5-T and the occurrence of reproductive failure in the Alsea area and it is this study, and only this study, which serves as a basis for the Agency's action suspending 2,4,5-T and silvex. 2,4,5-T Order at 2; Silvex Order at 2. As developed more fully in subsection A below, Alsea II shows that a comparison of the hospitalized spontaneous abortion indices in the Alsea area in relation to a comparable index for women living in areas where 2,4,5-T is not used shows an increased incidence of spontaneous abortions in the Alsea area relative to the control area, that an increase in spontaneous abortions in the study area occurs approximately two months after the area was sprayed with 2,4,5-T and that there is a close correlation between the amount of 2,4,5-T sprayed and the increase in the in the-incidence of abortions by months. The third aspect of the study includes supplementary data on spontaneous abortions in a neighboring urban area and supplementary analyses of the core conclusions by other statistical methods. Each of these supplementary methods was employed to test the validity of the core data or to refine, complete and supplement the basic analyses and conclusions. These supple- mentary aspects were included solely as routine checks on the basic analysis or, as in the case of analyses of the urban area, because the data were generated while gathering data on the study area, and were not used in the explanation of the �basis for the Administrator's action. Accordingly, although the complex supplementary analyses support and confirm the correlation between the use of 2,4,5-T and the occurrence of miscarriages in Alsea, the complexity of these analyses must not be allowed to obscure and complicate the essential simplicity of the study as a whole. Dow contends that the Alsea study is faulty in design, that it does not show an increase in the spontaneous abortion index in the study area in June, and that invalid statistical methods invalidate the study's conclusions. Dow Comments at 16-20, 22-24. In the discussion to follow, we will show that Dow's challenges are based on mistaken, unsupportable, and sometimes unreasonable assumptions which do not withstand simple scientific and logical scrutiny. The discussion is presented in four parts. In subsection A we summarize the Alsea II findings, issues and analyses upon which the decisions to suspend 2,4,5-T and silvex were based. In subsections B, C, and D, we discuss Alsea I and other corrollary data and statistical analyses which relate to the Alsea Study but which are clearly secondary aspects of the suspension decisions. �A. The Alsea Study is a simple and direct analysis of the relation between the forest use of 2,4,5-T and reproductive failure in humans who live in the area where the pesticide is used. The Agency's preliminary analysis of the data generated through the Alsea study indicated that the spontaneous abortion index (hospitalized miscarriages per 1,000 births) for the Alsea Study area where 2,4,5-T was used was significantly greater than the index for the control area where there was little or no known use of 2,4,5-T. A dramatic increase in the spontaneous abortion index for the study area relative to the control area occurred in June and July following, by approximately two or three months, a period in March and April when 2,4,5-T was used to control vegetation in the forested study area. Statistical analyses of these data indicated that there was a significant relationship between the amounts of 2,4,5-T used in the study area and the subsequent increase in the spontaneous abortion index in the study area. Thus, the Agency's systematic survey of the occurrence of spontaneous abortions in an area of 2,4,5-T use indicated that • there was an unusua.lly high number of spontaneous abortions in that area, compared to a representative control area and that the incidence of spontaneous abortions may reasonably be related to the use of 2,4,5-T in the area. The protocol and results, and Dow's challenges to the protocol and results are summarized below. �(1) The spontaneous abortion index was based on hospitalized spontaneous abortions, the most certain means of obtaining a uniform data base for the study and control areas. The validity of any epidemiologic investigation is dependent upon the validity of- information on the event under study. For the Alsea study, data on the occurrence of spontaneous abortions was critical. However, the reporting of spontaneous abortions, particularly those occuring early in pregnancy is influenced by many factors. In the first instance, many women do not know that they have had a spontaneous abortion, interpreting the uterine bleeding simply as delayed menses. In other cases, a woman may seek medical attention for something that both she and her physician interpret as a menstrual problem, not necessarily as a possible abortion. In still other cases, a physician may identify, the problem as a spontaneous abortio'n arid treat the patient in his office. Other patients are hospitalized. The Alsea study is based on hospitalized spontaneous abortions because these data are the most readily available indicators of the occurrence of spontaneous abortions. While it is true that all spontaneous abortions are not hospitalized or even noticed by a woman, it is reasonable to assume that the factors influencing the occurrence, awareness and hospitalization of spontaneous abortions are comparable between the control and study areas. It is also reasonable to assume that these factors are comparable throughout the year within an area. �Dow contends that there would be more hospitalized spontaneous abortion patients in the study area than in the control area and that for this reason the number of hospitalized miscarriages cannot be used as a reliable measure of the total number of miscarriages in a population sample. Dow Comments' at 18. Dow bases this contention in part on the assumption that practices regarding the hospitalization of spontaneous abortion patients differ in the control and study areas. Dow offers no data in support of this assertion that the sample is biased, and miscalculates the data available in the Alsea Report. For example, Dow describes the Alsea Report as stating that "most general practitioners hospitalize over threefourths of the spontaneous abortion cases that they treat as compared with only 10% hospitalization of the cases treated by obstetrical and gynecological specialists." Dow Comments at 18-19. However, contrary to Dow's assertion that "most" general practitioners hospitalize over 75% of their spontaneous abortion patients, in fact only half of the general practitioners referenced in Table 23 of the Alsea report had admission rates in excess of 75%. But more importantly, measurement of the impact of hospitalization on the spontaneous abortion index for the study area must be based on the number of patients who are sent to hospitals, not on the number of physicians who send their patients to hospitals. That, is, the critical information is �the proportion of patients who are treated by general practitioners and who also are hospitalized for spontaneous abortions. Using the data in Table 23 it can be estimated that 57.5% of the spontaneous abortion cases which are seen first by general *j practitioners are hospitalized, not 75% as Dow contends. Furthermore, Dow appears to wrongly assume that none of the study area women were treated by obstetrical specialists at the Corvallis hospitals in the urban area. In fact, 45 of the 188 study area women were treated at the Good Samaritan Hospital — a Corvallis hospital. Indeed, the primary reason for including the hospital in the study was that it was expected that study area women would be treated there. Treatment by the specialists at the hospital would not generally involve hospitalization. The Agency does not dispute Dow's statement that 10% of the spontaneous abortion patients who see specialists in obstetrics and gynecology are hospitalized. To support the contention that there is bias in the reporting of spontaneous abortions, Dow further states that there are eight obstetrical/gynecology specialists in the urban area, one specialist in the control area and none in the study area, and, V This can be estimated from the data in Table 23 by (1) multiplying the proportion of spontaneous abortion cases that are hospitalized by the annual mean number of abortion cases treated for each of the 13 GP's for which both kinds of information are available, and then (2) summing both this product and'the annual mean number of abortion cases treated to obtain 72.3 cases treated annually and 41.6 hospitalized for the 13 GP's. This is an estimate of 41.6/72.3 = 57.5 percent hospitalized among abortion cases seen by GP's. �that the specialist in the control area is responsible for onehalf of the obstetrical care in that area. Dow comments at 19. Accepting for the sake of argument Dow's estimate that half of .the cases in the control area are treated by a specialist, this result does not differ significantly from the Agency'.s estimation that a roughly comparable percentage of the study area women who had abortions were treated by an ob/gyn specialist. The reasons for the Agency's estimate will be developed at the Hearing. Seen in this light, Dow's unsupported claim becomes meaningless. The Agency is aware of no data — and Dow provides none — other than that developed in the Alsea Study which estimates the spontaneous abortion rate for the Alsea area. Absent such data, Dow's change that the hospitalized spontaneous abortions are an "unrepresentative data base,-" 'Dow Comments at 16, is only unsupported speculation. (2) The spontaneous abortion, birth and spray data used for 1972-1977, were aggregated to increase the reliability of the rates being estimated. The statistical analyses underlying the Alsea Study are based in part on aggregated spontaneous abortion data and birth data for the six-year period from 1972-1977. Such aggregation of data over time is a common statistical practice which is used to increase the power of resolution when the event rate is low. This practice is especially necessary for data such as �these where the expected number of miscarriages per month in many of the areas investigated could range from 1 to 4. In this case, even a 20% increase in the rate could not be found in monthy or perhaps even yearly data, but could be found when the data are aggregated over a number of years. Dow characterizes the Agency's use of the sums of all births and all hospitalized spontaneous abortions over aggregated periods as an "improper statistical technique" or "bunching" which obscures annual variation. Dow Comments at 22. Dow's objections suggest familiarity with this basic approach to vital statistics. The data on abortions, births and spraying over a period of years were summed in order to produce the large numbers and more stable results that are essential for the analyst to detect trends in the data and increase the power of statistical tests so that effects that are only moderate can nevertheless be detected. Dow may prefer year-by-year analysis because reducing the sample size can make it virtually impossible to discover a real effect unless that effect is truly overwhelming. Moreover, combining data across years to produce total rates by month, as here, rather than summing across months to produce yearly rates as Dow proposes, Id., is appropriate because the variation in spray pattern between different months is much greater than the variation between different years. Because spraying is a seasonal event, there are seven months with no �sp,raying in any year but there are no years in which spraying did not occur. If Dow's proposal were adopted, the apparent yearly average for the months in which spraying occurred would be reduced by the "zeros" for the months in which there was no spraying. Thus, yearly averages would give lower than actual monthly spray data for the months in which spraying occurred. (3) A statistically significant increase in the overall hospitalized spontaneous abortion index for the study area relative to the control area indicates that such abortions occur more often among women who live in the area where 2/4,5-T is sprayed. The Alsea study was planned to develop data which would allow the Agency to determine whether the miscarriages were related to the use of 2,4,5-T in the area. To test this hypothesis, the Agency gathered data on hospitalized spontaneous abortions occurring in the 1,600 square mile Alsea basin and compared these data to comparable data from a control area where 2,4,5-T was not used. This comparison showed that the overall hospitalized spontaneous abortion index for the study area was greater than that for the control area and that the difference was statistically significant. 2,4,5-T Order at 35; Silvex Order at 39. When the data were analyzed to determine whether the increase in study area spontaneous abortions was insignificant because it was within the normal range of random fluctuation or whether there was a real increase in the incidence of miscarriages among the women residents of the study area in relation to the control area, the difference between the study area and �-35control area was found to be statistically significant when analyzed by several different tests. Report at 46-71. Dow's claim that "there is no statistically significant difference between the overall hositalized spontaneous abortions index" for the study and control areas, Dow Comments at 20, totally disregards the evidence in the record. First, when the mean values for the study and control area are compared by Duncan's Multiple Range Test, the means are significantly different from one another using a two-tailed test (p 0.05). Report at 46. Because the original hypothesis was that exposure to 2,4,5-T increases the isk of miscarriage and because there is no reason to suspect that the pesticide can prevent miscarriages, EPA judges a one-tailed test to be appropriate. Using this test, the result reaches twice the .level of statistical significance'(p .025). Further, the number of abortions occurring in June in the study area is significantly greater than the number that would be expected either on the assumption that the number of abortions were uniform across all months or that the abortion "J index was uniform for all months. Report at 52. '_/ This conclusion is based on the following calculations: number of abortions = 24 number expected on uniform number assumption = 188 = 15.7 12 2 x = 4.39 p = 0.02 (one-tailed) (CONTINUED) �This result confirms the hypothesis by showing a statistically significant increase in the study area spontaneous abortions relative to those occurring in the control area. To test the hypothesis, it was not necessary to show a significant increase in June in the study are compared to the control area since both an overall excess in the study area compared to the control area and an increase in June in the study area above the overall rate in the study area have been shown. However, in the interest of more fully inspecting the available data, the investigators analyzed the data further and showed that women in the control and urban areas do not experience an increased incidence of miscarriages in June. See tables and figures in Report at pp. 42, 44, 45. Moreover, another test contained in the Report confirms this result. This is the test showing a correlation between the monthly pattern of spraying 2,4,5-T in months and the abortion index in the study area two and three months following the spraying. This analysis shows a significant correlation (p .01) between the use of 2,4,5-T and the abortion indices two months and three months after the spraying. *__/ Report at pp. 63, 67. (Footnote continued from previous page) number expected on uniform index assumption = 80.8 X 184 - 14.9 1,000 2 x - 5.56 p = .01 (one-tailed) These would also be significant at .05 on the basis of a two-tailed test. �(4) The statement in the Alsea report that "correlation does not mean causation," re-states a basic principle of statistical analysis and in no way negates the biological significance of the observed relation between the use of 2,4,5,-T and miscarriages in the Alsea area. Philosophers, legal scholars, and scientists have long debated the concept of causality, but few expect conclusively to establish cause and effect relationships. For this reason, thoughtful epidemiologists avoid the term "causal" and seek evidence of association between increases in risk which are temporally and geographically associated with potential exposure to suspected etiologic agents. In particular, descriptive studies such as the Alsea study can and do provide suggestive evidence of increases in risk, but they are not designed to "prove" a "cause and effect" relationship. Dow repeatedly states that the Alsea Report "expressly concedes that this analysis is a correlational analysis, and correlation does not necessarily mean causation." at 15. Dow Comments Dow's characterization of this statement as a concession implies that the Agency itself faults the study on this basis. Again, however, this is simply an honest, scientific appraisal of the meaning of the data, and it is fully consistent with the Agency's conclusion that the data suggests a relationship between the use of 2,4,5-T and miscarriages in the Alsea area. Moreover, correlation between miscarriages and 2,4,5-T is not an isolated observation, a product of statical "manipulation." Dow Critique at 1. Rather, the observed relationship �-ribetween the use of 2,4,5-T and spontaneous abortion is alarmingly consistent with a vast scientific literature which unequivocably demonstrates that when pregnant test animals are exposed to 2,4,5-T, silvex and/or TCDD, dead and damaged offspring are produced. 2,4,5-T Order at 22, Silvex Order at 27. In view of this extremely strong experimental data, the observed correlation as biological as well as statistical significance. Other more complex analyses reinforcing the fundamental conclusions developed using these methods are discussed in Subsection C. (5) There was a statistically significant correlation between the amount of 2,4,5-T used in the Alsea area in March, April and May and the increased incidence of abortions in the study area in June. To test the level of interaction between the spray data and the abortion d.ata, a -cross-correlation was .computed between the abortion index for the study area and the monthly pattern of spraying 2,4,5-T in pounds per month. a statistically significant (p This analysis showed .01) correlation between abortion indices for the study area and the spray pattern after lags of two (r = .70) and three (r = .76) months. Dow acknowledges that the Report at 63. seasonal variations in the abortion index for each of the three areas are possibly common biological phenomena, but cautions that factors other than herbicide spraying account for the variations. Dow Comments at 21. �Because of a concern for factors other than herbicide spraying, the authors of the Alsea Report viewed the cyclic variation as "noise" in the data to be removed, much as seasonal adjustments are made to economic indicators, before comparisons are made. For this reason, an analysis of the cyclic variation was performed, and showed that cyclic trends accounted for nearly all of the variation in the control area but did not remove the seasonal June peak in the study area. Further, the time-course of variation was different in the study area than the control area. Thus, after accounting for cycle variation, the seasonal variation in miscarriages is seen to be quite separate from the remaining variation after removing its effects from the study area data. This residual variation was found to .be associated in time with the level of 2,4,5-T sprayed. (6) Dow's argument that there is a June peak of miscarriages- in Midland, Michigan actually supports the conclusios of the Alsea Report, and its attempts to discredit the Alsea conclusions by pointing to a June peak in Miami fails because the Miami data is based on induced abortions, not spontaneous abortions. The Alsea study demonstrates that there was a statistically significant increase in the incidence of miscarriage among Alsea area women in June and that this increase was correlated with the use of 2,4,5-T in the area for forest management, approximately two months earlier. �Dow contends that the June peak observed in Alsea is comparable to June peaks observed in other urban areas, particularly Midland, Michigan, and Miami, Florida. at 6, i( 15, Gehring Affidavit Dr. Gehring. argues that the finding of June peaks in Miami and Midland "undermines, if not refutes altogether," the Agency's assessment of the Alsea data. Gehring affidavit at 6. Dow's proposal that the Miami and Midland data refute the Alsea data misuses the available information in one case and fails to consider relevant information in the other. First, and quite simply, the Miami data in the Alsea Report, Report at Appendix B, upon which Dow based its conclusion related to therapeutic abortions, not spontaneous abortions. Clearly on increase in elective abortions cannot refute an assessment based on spontaneous abortions. The argument based on the Midland data is similarly unscientific. Dow presents no data or analyses such as those presented in the Alsea Report. Rather, Dow attempts to make its point using only a graph which appears to show a June peak in Midland that is higher than in Alsea. Critique attached to Gehring Affidavit, (hereinafter "Dow Critique" or "Critique") In 1978, Dow submitted three studies on TCDD's to EPA under Section 8(e) of the Toxic Substances Control Act. An EPA status report, concluded that TCDD's "appear to be widespread contaminants of the Tittabawassee and Saginaw Rivers (and �-77-- possibly Saginaw Bay) downstream from Midland." Kover, 1979. Caged rainbow trout accumulated TCDD after 7 days when held in Dow's tertiary waste treatment effluent and after 30 days in flowing waters about six miles downstream of Dow's plant, indicating downstream movement of TGDD from the plant. The status report went on to characterize Dow's plant discharge as "the major (if not the only) source" of TCDD contamination in the area and concluded that "the levels of TCDDs identified in Midland soil and dust samples indicate that this area represents a definite TCDD "hot spot." Data prepared by the Michigan Department of Health showed that the Midland County rate for all malformation was more than twice the rate for the entire state for the period 1970-1974 and in each individual year after 1970. Infante, 1979. In two years, 1972 and 1973, this county's rate was the'highest in the state. Michigan contains at least two other counties where the presence of a university mdeical center, located in Ann Arbor and Detroit, would suggest the identification and recording of anomalies at birth to be at least as thorough and accurate as in Midland County. The Michigan Department of Health also provided data on specific types of malformations and calculated the number of cases of malformation which v/ould be expected for Midland County �I / 'if the rate there were comparable to statewide rates. Infante, 1979. However, when the actual number of malforma- tion cases was compared to the number expected assuming that Midland was like the rest of the state, a clear excess of urogenital abnormalities, cleft lip and palate, and heart defects was found for babies born in Midland County. Bailor, 1967. Whether there is a relationship between the high rates of congenital malformations in Midland County and Dow's monitoring data showing the area to be a TCDD "hot spot" has not been determined. However, cleft lip and palate and urogenital abnormalities are in clear excess in Midland County, as they are among the defects frequently observed in litters of test animals exposed to 2,4,5-T, silvex and/or TCDD during pregnancy, 2,4,5-T Orde.r at 22? Silvex Order at 27. (7) The-results support the hypothesis th-at the occurrence of spontaneous abortions in Alsea is related to the use of 2,4,5-T. The study was planned and conducted to test the suggestion of a relation between miscarriages and the use of 2,4,5-T in the "__/ These data were presented within th context of a discussion of possible reproductive hazards of vinyl chloride exposure. The discussants were careful to avoid attributing an etiologic connection in the absence of exposure data and in light of the knowledge that a number of substances are manufactured or processed at Dow's Midland plant. In 1977, a study published by Dow scientists found little evidence of a teratogenic or fetotoxic effect of vinyl chloride in either of three species: mouse, rat or rabbit. John, 1976. �Alsea area, and the study confirmed that miscarriages were likely to occur there more often than in the control area where 2,4,5-T was not used. Dow's denunciation of the confirmed hypothesis as a "preconceived conclusion," Gehring affidavit at 4, disregards a fundamental principal of the scientific method. To test a hypothesis and to avoid charges of fishing the investigator must know what question he is asking and plan the test accordingly. In the case of the Alsea II study, the eight women had reported that they had experienced what seemed to them to be an unusual number of miscarriages. This obser- vation was then applied to develop the hypothesis that there should be different incidences between the Alsea area and areas where 2,4,5-T was not used, and there should be an increased incidence of miscarriages approximately two months after the annual spring spraying season in the Alsea basin. As developed above these elements of the hypothesis were tested and confirmed in Alsea II. �B. Valid conclusions concerning human exposure to suspected chemical agents do not depend on the availability of chemical residue data and are not limited by the lack of such data. Detection and measurement of chemical residues of a suspected etiologic a g e n t - i n human tissues and fluids are not prerequisites for finding that humans are exposed to the suspected agent. Indeed, most, if not all, of the twenty or so chemicals which are now widely recognized as human carcinogens were confirmed as such through epidemiclogic studies which did not include, much less require, physiologic residue analyses. In studies providing conclu- sive evidence of the carcinogenicity of substances such as asbestos, vinyl chloride, chromium and bis(chloromethy) ether, the only method of confirming human exposure was the simple fact that the exposed group worked at a given * * * ' occupation and the control group did not. • Perhaps the most striking example of an etiologic agent which would not be identified as such if measurement of chemical residues in human tissues were viewed as a sine qua non of exposure is sunlight, an established carcinogenic agent which could not be detected in human tissues by customary chemical analyses. Rather, a key test of epidemiologically established associations is their bi.ologic pluasibility. Part of this plausibility depends on whether the study group was actually exposed to the substance. Depending on the level or cer- tainty needed, evidence of exposure can be as strong as a lung �48 cancer patient's admission that he smoked forty cigarettes a day for twenty years or as speculative as information that a raesothelioma patient lived in the same household as an asbestos worker. In cases where, as here, absolute certainty is not required (See Section —, infra.), the suspect chemical is highly toxic and there is a definite opportunity for exposure, the fact that there is a potential for exposure can reasonably be regarded as adequate evidence of the actual occurrence of exposure to the chemical. Dow contends that the "study is deficient because there are no data establishing any pesticide exposure levels for the women who experienced miscarriages." Dow Comments at 24. Dow further claims that "measurements made elsewhere in humans and animals exposed to 2,4,5-T and TCDD indicate that •the maximum amount of 2,4,5-T and TCDD which could possibly have been absorbed into the body, if any, by the residents of Alsea, Oregon would be far too low to cause any adverse health effects." Gehring Affidavit at 7. Because Dow has supplied no data of any kind or any other information on the measurements to which they refer, the Agency.cannot fully evaluate this statement. However, in view of Dow's criticism of the Agency for failure to provide residue data in support of its finding of probable exposure of the Alsea area residents, it is surprising that Dow itself neither provides the measurements to which they �refer nor any other data showing that human tissue residues are biologically insignificant. Furthermore, even if such data were available, because there is no known no-effect level in humans or animals for fetotoxic or carcinogenic, effect there is no basis for Dow's statement. This inconsistency in Dow's approach to this question illuminates the problem facing both Dow and the Agency. The pesticidal uses of 2,4,5-T and silvex necessarily result in the distribution of these pesticides to the environment and thereby create a potential for human exposure. However, because the available analytical methods can at best detect TCDD only down to 1-10 ppt, if TCDD is present at 1-10 ppt or lower, it would not be detected. As a result, Dow and the Agency can determine that there is no more than --ppt in a particular sample, but neither party can make supportable statements as to the actual residues of TCDD in any environmental or human sample. The Agency's approach, consistent with its obligation to protect the public health, is to view the data on toxicity in animals, and the opportunity for human exposure as indicating that the Alsea residents (and other persons living and working in areas where 2,4,5-T and silvex are used) may be exposed to injurious amounts of the chemical. �C. In connection with the suspension orders, Alsea I was utilized only to develop the hypothesis, later confirmed tnrough Alsea II, that there was a relation between the use of 2,4,5-T and the occurrence of an excess incidence of miscarriages in Alsea. In issuing the suspension order, the Agency explained that eight women residents of Alsea, Oregon had reported that as a group they had experienced an unusually large number of miscarriages and they thought that their miscarriages mights be related to the use of 2,4,5-T because the miscarriages generally followed the annual spring spraying of 2,4,5-T in the forests near their homes. at 34; Silvex Order at 37-8. 2,4,5-T Order EPA conducted a study of these women to determine if there was any validity to their suggestion of a relation between their miscarriages and 2,4,5-T use. A clear distinction must be recognized and maintained uetween the studies now identified as "Alsea I" and Alsea II." Alsea I comprised an intensive, health questionnaire study of nine rural women residing within a 12-mile radius of Alsea, Oregon, who had experienced a total of thirteen miscarriages between 1973 and 1978 which they associated in time and proximity with forest spraying of 2,4,5-T. The questionnaire asked for detailed information on the women's pregnancy and medical histories and on pregnancy outcomes of their sisters. It also included questions on diet, environmental aspects, occupations, household pesticide usage, and educational background. �The purpose of Alsea I was to rspond rapidly to a concerned citizenry to determine hether or not the miscarriages could be explained by causes other than potential exposure to forest herbicides and to examine the degree of association between conception-to-miscarriage of periods and locations, dates and rates of forest herbicide applications. The Alsea I cohort of nine women was recognized as being too small and potentially biased to establish more than the possibility of correlation between forest spraying and miscarriages . Because it was anticipated that medical cause of these miscarriages could not be positively identified, and were not, and because of the apparent seasonal relationship between spray and conception-to-miscarriages of 20 weeks duration or less, the Agency decided to investigate miscarriage ratesin an expanded forest area centered about the Alsea area and in a comparable control area in Oregon, Plans for the expanded investigation were developed prior to the completion of Alsea I, the actual decision to conduct the study being dependent on the outcome of Alsea I. The study of miscarriage rates'in the expanded study area and the comparable control area, reported February 20, 1979, has become identified as Alsea II. It is a retrospective study of records of hospitalized miscarriages in the study and control areas relative to the number of births' in those areas, and compares seasonal miscarriage patterns with 2,4,5-T �spray patterns. It is not a continuation of Alsea I and is virtually independent of that study with the exceptions that the miscarriages of the nine women maybe included in total miscarriages for the entire Alsea area and the spray data assembled for Alsea I were utilized in the Alsea II cross-correlationanalyses. EPA neither took any regulation action nor prepared to take regulatory action based solely on the data from the nine women. Rather, EPA interpreted that data as indicating that there was a possibility that other Alsea area women might also have an unusual incidence of miscarriage and that the data suggested serious enough consequences that further investigation was necessary to determine whether action to protect the public health was necessary. This decision was consistent with the views of the reviewers who, consistent with customary epidemiologic caution, indicated that the data did not indicate a cause and effect relationship but was inconclusive and that further analysis was necessary. (1) The reviewers inability to find a "causual" relationship between 2,4,5-T and miscarriages in Alsea I is not surprising and has no bearing on the results reported for Alsea II. We have previously explained that epidemiologists generally avoid the term "causation" because the of the inexact nature of cause and effect relationships. Alsea I was a retrospective study of the miscarriage experience of a self-selected group of eight women, all personally concerned about those experiences. �53 ^ Scientists would not reasonably expect the study to provide evidence of causation. Despite the obvious limits on finding a cause and effect relationship from this data, Dow repeatedly emphasizes that the specialists who reviewed Alsea I reported that they found "no evidence of a causal relationship." Dow Critique at 2. Cautious interpretation of the Alsea I data, based only on questionnaries and medical records of only nine women, was fully consistent with thgouthtful epidemiologists' careful avoidance of drawing etiological inferences on the basis of case histories alone. Rather, they seek to identify populations and to estimate the relative incidence of death and disability. Thus, the Alsea I reviewers reasonably and responsibly explained that they could find none on the basis of.the information supplied by eight women in reponse to a questionnaire. For this reason, it is difficult to understand plaintiffs' contention that the Agency should have followed the advice of the reviewer who, on the basis of nine case reports, concluded that further study would "be a waste time and fund." To the contrary, the Agency would have been derelict in its statutory obligation to determine whether the use of pesticides may cause unreasonable adverse effects had the Agency not pursue this indication in Alsea I that there was a relation between the use of the pesticide and the increased incidence of miscarriages in areas where the pesticide was used �D. The data on the spontaneous abortion index for a neighboring urban area and the spectral analysis data which were included in the Alsea Report were supplementary in character and were not part of the data used to derive pertinent findings concerning use of 2,4,5-T In Subsection A we isolated and summarized the fundamental objectives, results, and conclusions of the Alsea Study. During the course of the Alsea Study, as in most scientific investigations, the investigators considered infor- mation, methods and analyses that were peripheral to those considerations which formed the center of the study. corollary features included analysis of spontaneous These abortion data from Corvallis, an urban area near Alsea, and use of a statistical technique designed to determine whether the seasonal characteristics of the spontaneous abortion index in the Study area co'uld'be attributed solely to the apparent cyclic variations in each of the areas. In challenging the suspension decisions, Dow has frequently cited alleged defects in these corollary data and analyses as indicators of error or invalidity in the Alsea Study. Dow's emphasis on these features obscures the central nature and strength of the Study and even creates false issues. In this section of the memorandum, we again explain the nature and relevance of each of these corollary features and respond to Dow's changes . �(1) The data and analyses relating to the occurrence of spontaneous abortions in the urban area have no bearing on the differences in the spontaneous abortion indices in the control and study areas. Many of the women residents of the study area use hospitals in Corvallis, an urban area adjacent to the study area. For this reason, Corvallis hospital records were examined to obtain spontaneous abortion data for study area residents who had been treated in the urban area hospitals -at the time of their miscarriages . These records also provided spontaneous abortion data relating to urban area residents and these data were analyzed along with data from the study and control area. The data on miscarriages among urban area women were of interest because 2,4,5-T is not used in the urban area, but they had limited utility because many spontaneous abortions were treated at clinics which had no counterparts in the study and control areas. Because the clinics were not fully investigated, the hospitalized spontaneous abortion index for the urban area under reports the spontaneous abortions for which medical treatment is given. Significantly, if study area women use the urban area clinics as well as urban area hospitals, the spontaneous abortion index for the study area probably under- estimates the abortion rate for the study area because urban clinic abortion data were not included ia the data for the study area. Because there are no such clinics in the control �area, the spontaneous abortion index there .would not be underestimated for that reason. Dow mistakenly treats the data and analyses relating to the spontaneous abortion index in -the urban area as information wnich negates the observations of an increased incidence of spontaneous abortions in the study area. See e.g. Dow Comments at 19. The urban area data in no way influence the Agency's conclusion that there is an increased abortion rate in the study area in the time period following the spray or our conclusion that the abortion rate in the study area exceeds that in the control area. 2,4/5-T Order at 35; Silvex Order at 39 . The urban data are unrelated to the simple and specific . hypothesis which the Alsea II Study was designed to test. The urban area data were carried along in the analysis because the records of the urban area hospital had to be used to provide data on the study area abortions and because, in the event that there was a June increase, the urban area data might be useful in providing a measure of monthly and seasonal trends in abortion frequencies in a nearby area. Report at .19. More specifically, Dow charges that the Alsea Report "capriciously combines the obviously lower values from the urban area with those from the control area for many of the subsequent analyses." Dow Critique at p. 9, �In fact, even a cursory review of the study shows that no such combination of urban and control area data was made in testing the major hpothesis and reaching the conclusion that there was an increased incidence of spontaneous abortions in the study area relative' to the control area.. Rather, consistent with a more thorough testing of the initial results showing a significant June trend, such combinations were made to determine if the observed June peak might be accounted for by seasonal trends. Moreover, whenever the urban and control data were combined for these analyses, the same analysis was conducted for the control area data alone. Report at Therefore, contrary to Dow's contentions, combinations of uroan and control area data did not bias the results. (2) . • The complex spectral analysis in the Alsea Study' was performed solely to determine whether or not the June peak in incidence of spontaneous abortions in the Study area could reasonably be attributed to innate periodic variations in the data. Dow has alleged that the spectral analysis used in the Alsea Study was "a manipulation of the data to devise a desired result." Critique at 13-14, Such a statement reflects a fundamental misunderstanding of the reasons why the spectral analysis was performed. The objective of this complex collateral analysis was not to demonstrate the existence of a June peak in the incidence of spontaneous abortions in the study area, which had already been independently established, but rather to determine whether or not . �th.e observed June peak might simply reflect a cyclical tendency in such data which had never before been reported in the scientific literature or spontaneous abortions. The spectral analysis was designed to test the hypothesis that tne June peak in the abortion index for the Study area merely reflected a cyclic variation of unknown origin which might be common to all the areas studied but which, for equally unknown reasons, might differ between areas in its correspondence to months of the year. To test this highly speculative possibility, an attempt was made to fit the spontaneous abortion data for the Study area with that for the Control Area, in order to determine whether or not a significant similarity between the observed patterns could be established by shifting the phase relationship. Even after apparent cyclic variations in the two areas had been synchronized, the June peak in the Study area remained and could not be reconciled with Control Area data. The spectral analysis was a supplementary evaluation of the basic Alsea data and in no way altered or manipulated the data base upon which che authors of the Study and the Agency ultimately relied. Rather, the spectral analysis demonstrates that the authors of the Alsea Study were sensitive to and considered even highly speculations alternative explanations of the origin of the June peak in the Study area. �(3) The alternative statistical treatments proposed by Dow do not contradict the basic findings of the Alsea S tudy . The petitioner has employed certain alternative statistical approaches which were not utilized by the'authors of the Al-sea Study, in an attempt to demonstrate that the data base does not support the findings of the Alsea Study. Dow alleges that the demonstrated correlations between monthly spraying and the monthly abortion index in the Study area are "correlation" between monthly spraying in the Study area and the monthly hospitalized abortion index in the Control Area. at 23. Dow Comments In addition, Dow suggests that a "simple statistical Chi square test" may be used to demonstrate that there was no statistically significant increase in the hospitalized spontaneous abortion index for the Study Area, as compared to the Control Area. Dow Critique at 9, 12. Both of Dov;' s criticisms are without merit. The allegation of a "correlation" between spraying in the Study Area and abortions in the Control Area comparable to the correlation oetween spraying in the spring and June abortions found in the Study area is•irrelevant. Moreover, even though use of a Chi-square test in the manner suggested by Dow is of questionable theoretical validity, the results of such calculations nevertheless corroborate the basic conclusions of the Alsea Study. �(a) The alleged "correlation" between monthly spraying of 2,4,5-T in the Study Area and the hospitalized spontaneous abortion index in the Control Area is irrelevant. The petitioner's allegation that there is a significant correlation between the amount of 2,4,5-T sprayed on the Study Area and the spontaneous abortion index for the Control Area is of highly questionabel relevance. If Dow is contending that it is possible to find a coincidentally "significant" correlation somewhere if you do enough independent tests using unrelated variables, respondent agrees. However, it is entirely illegitimate to suggest as Dow does that the results of such an abstract experiment can be meaningfully compared to a calculation expressly designed to test the validity of a specific hypothesis. We do-not believe that Dow. intended to test the hypothesis that abortions in the Control Area are related to spraying in the Study Area. Even if a significant 'correlation" could be found between these essentially unrelated variables, this finding would have absolutely no relevance to the reliability of a separate test of a single well-defined hypothesis. No doubt the laws of chance would enable Dow to identify by experimentation many "significant'" correlations between 2,4,5-T spraying and totally unrelated variables, but such data would have no probative value here. Regardless of which figures Dow's allegation is based on, it should be apparent that Dow'3 �selection of a single example from a series of equally implausible alternative hypotheses is a meaningless exercise designed to obfuscate the real issues. (b) Even though the suggested use of a Chisquare test to determine whether or not the incidence of hospitalized spontaneous abortions in the Study Area was greater than the incidence of such abortions in the Control Area is of questionable theoretical validity, such a test nevertheless confirms the basic findings of the Alsea Study. The petitioner alleges that use of a "simple Chi-square statistical test" demonstrates that there is no significant difference between the incidence of spontaneous abortions in the Study Area and the incidence of spontaneous abortions in the Control Area. Since Chi-square represents a type of distribution and may be used in many different ways, Dow's naked assertion does not provide a definitive basic for identification of the exact test Dow used. However, the most reasonaole assumption is that Dow used the Chi-square test for binomial proportions. Use of this Chi-square test involves an implicit assumption that the error variance of the distribution of hospitalized spontaneous abortion indices is binomial variance. This assumption is of questionable validity because the indices are not actually binomial proportions. v V See Chiang, E. L., Standard Error of the Age-Adjusted Death Rate, Vital Statistics Special Reports, Vol. 47, No. 9, for a discussion of this problem. �(flIn contrast, the authors of the Alsea Study estimated the error variance directly by using three-way interaction terms from the available empirical data. Even if we assume that application of a Chi-square test to this type of data is appropriate, the results are consistent with the conclusions of the Alsea Study. The Chi-square test indicaces that the hospitalized spontaneous abortion index in the Study Area is significantly (p .05) greater than the A A / hospitalized spontaneous abortion index in the Control Area. Perhaps Dow concluded that the difference is not significant by use of a two-tailed test. However, since the alternative hypothesis to be tested here is whether or not the spraying was A A f / associated with an increase in spontaneous abortions, the one-tailed test is clearly the more appropraite one. If the validity of the Chi-square method suggested by Bow is accepted, it can also be used to demonstrate that the difference between the June abortion index for two areas is highly significant (p = .01). Thus, corroborates the findings of the Alsea Study. **_/ If the 188/2344 abortion rate in the Study Area is compared to the 109/1666 aoortion rate in the Control Area and Yataes' ccorrection for continuity is applied, x = 2.89 and p = .04 (one-tailed) . '_/_ The Alsea Study was not designed to determine whether or not 2,4,5-T could prevent spontaneous abortions. �III. The Suspended Uses of 2,4,5-1 and Silvex. result in direct exposure to humans through aerial drift and/or through chemical contamination of vegetation food and water which humans use or consume•A. Introduction As the Administrator acknowledged in his 2,4,5-T and Silvex suspension decisions, a chemical cannot pose a risk to human "health if no one is exposed to it. The Administrator then provided to analyze carefully the questions of exposure. He concluded as follows: In my judgment, the information which as recently come to my attention as a result of the Alsea study constitutes a dramatic and troubling new point of departure for analysis of TCDD exposure concerns.. As indicated above, these data show a striking relationship between 2,4,5-T use and increased incidences of spontaneous abortions among women residing in the use area. As further developed above, this effect is an effect w.hich one would have predicted as a likely outcome o'f human exposure, based upon a body of animal data of almost unprecedented conclusiveness. The Alsea study, to be sure, contained no data showing actual exposure. However, concern for the health of humans who may be exposed to TCCD, and therefore, to 2,4,5-T or silvex contaminated with TCDD, is heightened because scientists have not demonstrated that there is a level of exposure that has no adverse effects in humans. Thus, in the face of the highly significant relationship which the study showed, and the animal data, I conclude it is reasonable and in the public interest to assume that the women in Alsea study were exposed to TCDD. Moreover , I also conclude that it is prudent that individuals who frequent or live in areas where 2,4,5-T or silvex ace used may be exposed -co TCDD in vasy and under conditions which may cause these indivicduals to be exposed in ways qualitatively similar to those experienced by the Study area women. 2,4,5-T Order at 50-51; Silvex at 50-51. �As developed above chemical regulation inevitably involves uncertainty which must be dealth with by framing prudent assumptions which are consistent with the available d a t a , and which reflect the situations as it may exist, if the uncertainties were resolved in favor of higher, rather than lower risks. The Agency's position is that the Administrator's exposure assumptions are fully consistent with this approach. We will show below that Dow attempts to meet its burden of proof in this area by rebutting the Administrator's exposure analysis are unpresuasive, and that the Administrator's exposure concerns, as set out in this suspension decisions, remain unanswered. In addition, we will present additional information developed since the Administrator's February 28 decisions which is consistent with, and therefore corroborates, the exposure analysis set out in those decisions. This information consists, for the most p a r t , of case histories showing that uses of 2,4,5-T and silvex result in distribucion of these chemicals (and presumably TCDB as well) to sites of human work and habitation. E. The Use of 2,4,5-T and/or silvex leads to direct human exposure to these chemicals and to TCDD The current methods of application of 2,4,5-T and silvex necessarilly result in the distribution of these chemicasis to the environment. In the first instance, the application methods are specifically designed to direct the pesticide to a site that includes not onlv taraec brush and weeds but also includes a wide �v a r i e t y of non-target organisms and environmental media. That is, any target site necessarily includes in addition to the target .brush and weeds, other non-target vegetation, the soil substrate, surface water and ground water, and, of course, the surrounding air. Thus, the intended and actual use of the pesticide unavoidably and invariably leads to the presence of 2,4,5-T, silvex, and TCDD at each and every site of affication. This \ fact is indisputable and even if none of the facts discussed below influenced the environmental distribution of these chemicals, the use of these chemicals clearly leads to contamination of the living and non-living organisms and materials at the site of application. In addition, although regulations and/or industry practice, generally prohibit use of these chemicals in areas of human work habitation, if persons are present at the site of application, these persons would also be directly exposed to the pesticide. Thus, even assuming full conforming with all regulations in the pare of applicators, the applicators themselves are necessarily present at the place and time of application and therefore are directly exposed. Any other person inadvertently or unknowningly present at an application sita would also be exposed. �F u r t h e r , because normal difffusion though air and w a t e r , as well as wind and currents distributes the pesticide beyond the site of application, any persons, plants and animals, water, soil and other environmental media which lie in the path of chemical-bearing drift or water will aslo be exposed J/ to these chemicals . For example', in a November 1978 letter to the Administrator, the Chief of the Forest service explained contamination of water was unavoidable: Most applications of 2,4,5~T in forest ... situations necessarily involve water to some extent, and although we have vary stringent criteria for preventing unnecessary water contamination, it is not possible to to completely avoid it. We are becoming increasingly aware of this with improvements in analytical detection capabilities. Our go.al in respect to 2,4,5-T residues ' in water has been not to exceed the maximum contaminant level of 10 parts per billion ( ppb ) established for silvex, a very closely related herbicide (40 CFR 141). Almost all of our water samples taken on site immediately after application projects show no 2,4,5-T residues, but some do — usually less than 1 ppb, and in almost every case less than 10 ppb, Together these factors conclusively establish the use of these pesticides leads to exposure of persons, plants and animals, and environmental media to these chemicals. ™ _~™™™_™__,_^ subject of spray drift indicates that exposure due to drift is likely. For e x a m p l e , Oregon State Univerisity staff conducted spraying experiments in an area 20 miles northwest of Alsea , Oregon. They reported that between 60 and 75% of the 2,4,5-T sprayed from aircraft did not reach the target areas. Norris, 1967 . :.-•<;*- �-47Dow contends that c u r r e n t technology permits precise application of 2,4,5-T and silvex, thereby eliminating spray drift as a source of human exposure. Comments at 32. The error of this statement is readily demonstrated through simple discriptions of actual exposure which have been reported to the Agency. incidents Drawing from the Agency's Pesticide Episode Reporting System (FEES), the 2,4,5-T RPAR rebuttal file, and other sources, the Agency has selected several case histories which rebut Dow's contention that the use of the pesticide does not result in exposure. Each case was selected on the basis of the following criteria: 1. 2,4,5-T was the pesticide used, 2. The use resulted in injury or damage to humans, animals, or vegetation. 3. The site of injury was some distance away from the site of application. 4. The incident was the subject of a contemporaneous report. As the discussion to follow demonstrates, the use of these chemicals does lead, directly and indirectly, to human exposure . �1. Use of these pesticides results in direct exposure to bystanders. During the spring of 1976 .the area near the home of Patricia Clary (Candrian) in Milo, Oregon was sprayed with 2,4,5-T as well as other chemicals. Curing this period Ms. Clary suffered from uterine hemorrhaging . Her case was sufficiently severe so as to require transfusions of eight pints of blood and five pints of plasma. Her health returned to normal during the summer after the spraying. The next spring spraying resumed as did Ms. Clary's health problems. She experienced abnormal and heavy "spotting," extremely extended menstrual periods and dizziness and nausea. In September of the same year (1977) spraying with 2,4,5-T was undertaken again, this time within several yards of her home. Analysis of water from a nearby spring by the Oregon Department of Agriculture revealed residues of 2,4,5-T at concentrations of 0.3 ppm . For the week following this spraying incident, Ms. Clary, her husband and two children as well as a visitor suffered drowsiness, nausea, and d i a r r h e a . abnormal. Once again Ms. Clary's menstrual cycle was Finally, in February of 1978 an area 1/2 mile away �from the Clary house was sprayed. Ms. Clary and her son experienced nausea and d i a r r h e a for 4-5 days after the spraying. Ms. Clary's menstrual cycle .was again abnormal. (Exhibit O ) A parallel case history was related by Barbara Eurkett also of Milo , Oregon. During the same spring, 1975 spraying operations described by Ms. Clary, the 16 year old daughter'of Ms. Eurkett also experienced unexplained as severe headaches and backaches. hemorrhaging , as well In September of 1977 the area was again sprayed with 2,445-T. Ms. Eurkett stated, "The drift was heavy enough to bring this spray across highway 227 and onto our property. The spray could be seen, left (sic) and smelt and tasted. At the time of the spraying I received a very sore throat." (Exhibit / ) Eloise Cromwell of Fope, Arkansas, related the following incident, "During the spring of 1972, our immediate neighbors sprayed the chemical 2,4,5-T on land directly above our spring and into our watershed. Since the spraying, there have been seven pregnancies among the women living on our farm. Three of the babies were m i s c a r r i e d , one visibly deformed. One baby died at age three months of crib death, no medical explanation," (See, also, F.FAS rebuttals S139A [3000/26]; $264 [3000/26]; O'Hagan A f f i d a v i t ; Weber Affidavit) (Exhibit a t ) The foregoing incidents demonstrate that spray operations result in direct human exposure. F u r t h e r m o r e , the evidence strongly suggests that these airborne exposures occur at levels �sufficient to cause severe adverse effects in exposed humans. The Agency is'currently collecting mere recorts of incidents similar to those described above. These will be presented in the suspension hearing. 2. Use of these pesticides results in direct exposure to applicators. Pilots, ground spray crews, mixers and loaders of the pesticides, and flaggers are all exposed during the application process See 2,4,5-T Decision and Order at 60; Silvex Decision and Order at 57-58. Their exposure can occur throughout a work day and for succeeding days and weeks during the spray season. These workers inhale pesticide spray, and some of them have direct skin contact with concentrated formulatives or with spray. Moreover, the.spray or .concentrate can adhere to clothing, causing exposure to last during one or several days. Dow contends that applicator exposure is insignificant. They argue that if the Agency had not ignored data submitted by them during the 2,4,5-T SPAR, the Agency would have agreed with them that "exposure to applicators to 2,4,5-T and silvex, with their trace contaminant TCDD, cannot cause the kinds of toxic effects claimed in the Administrator's decisions." 36. Dow's comments at Prom these contentions, Dow constructs the argument that, for the general population, "the margins of safety are of course many orders of magnitude greater." I_d_. �The d a t a which Cow and others claim the Agency failed to consider are the results of a Dow-National Forest Products Association field test to d e t e r m i n e actual exposure of forestry */ applicators exposure to 2,4,5-T and TCDD. These data demonstrate that application workers are exposed to 2,4,5-T in amounts ranging * */ from 0.51 mg per hour to 6,75 mg per hour. Despite the difficulties of detecting TCDD, the NF?A study also reported that two samples contained TCDD. Conceding that actual exposure occurs, Dow's pegs their argument that this level of exposure is safe to the fact that the d a t a from the NFPA Study demonstrates exposure to be substantially lower than no-adverse effect level presented in che 2,4,5-T RPAP . Record at 1. Dow comments p, 35. The flaw in Dow's argument is that it assumes that the Agency's tentative conclusions with respect to a no-effect levelj presented for comment in A p r i l , 1978, were definite conclusions. The probable no-effect level calculated a year ago was based on animal studies available at the time and on the basis of assumed inter-species variations in sensitivity. Since the issuance of Position Document Mo. 1 4 additional animal data and the Alsea V HP A R~ R¥b"u t"t aT~¥l 0 2 3 H . V Exposure data are presented in terras of milligrams per hour of spray operation. Corrections have been made for efficiency of excretion. The estimates presented here are the upper r a n g e figures reported in the study; the Agency believes these are the most appropriate figures. �T2- Study have become a v a i l a b l e ; these new d a c a necessitated revision in the Agency's t e n t a t i v e conclusions with respect to exposure levels that may be deemed to be safe for humans. Animal data, now available show that fetotoxic effects occur in animals at doses of TCDD as low as one hundred millionth of a g r a m , substantially lower than the doses at which effects occurred in the studies previously available. Moreover, the Alsea Study shows the like- lihood that either human exposure is g r e a t e r than either EFA calculations or the NFPA Study indicates, or that human sensitivity to the fetotoxic effects of these chemicals bears a d i f f e r e n t relationship to animal sensitivity than the Agency originally believed. In any event, the new data leads to the conclusion t h a t , even though actual exposure appears to be lower than the Agency had estimated in issuing the SPAR, exposure poses serious fetotoxic risks to humans. In fact, as discussed above, the best evidence now available to the Agency indicates that it is not possible to establish a no-effect level for TCDD-induced fetotoxic effects. Accordingly» although actual exposure appears to be lower than chat originally estimated, the more significant fact is that effects appear to occur at levels of exposure substantially below those that the Agency had believed would cause these effects. ingly, the Agency cannot give credence to Cow's a r g u m e n t , Accord- �which are based on che assumption chat che Agency a d h e r e s co the view that a probable no-effect level exists at the level */ indicated in the RPAR, 3. Home Uses of silvex result in d i r e c t exposure to family m e m b e r s Silvex products are used for weed control on home lawns and gardens, and the application techniques create the potential for exposure to users. Home users apply these products with small tank sprayers , hose-end d i l u t e r s , and aerosol cans for spray applications, and mechanical spreaders for g r a n u l a r formulations. Exposure is likely to result from applications by some or all routes: splashing and low-distance drift of droplets from tank sprayers, hose-end d i l u t e e s , and aerosol _^7~ Cf couTIe, even ""If the data justified adherence co che Agency's position at the beginning of the PFAS process on the "no-effect level" for r e p r o d u c t i v e effects, it still would not follw that the TCDD human exposures which are likely to occur would be "safe." This is because TCCD is a carcinogen, and it is recognized by SPA and other federal regulation agencies involved in protecting public h e a l t h that no level of exposure co a carcinogen can be considered safe. See ^c^, Health Risk and Economic Impact Assessments of Suspected"CaTcinogans , Interim Procedures and Guidelines, 41 FB. 21402 (1975) Dow appears to concede this point, and argues instead that the l^svej.. of risk would be. insignificant. In light of data which has come, to the Agency's attention since the beginning of the RPAP process showing that TCDC is a more potent carcinogen than the Agency originally believed it to be, this assertion is troublesome. (This data show that doses as low as o_rvs b_ilJLj.oneth of a g r a m of TCDD cause marked carcinogenic effects in animals.) In.any e v e n t , as we point out above, a'c^olutje level of risk has no meaning under FIFRA; under FIFPA, decTiTons turn on whether a given level of risk is greater than che economic, social, or e n v i r o n m e n t a l benefits of the use of the cesticice cosine; the r i s k . �74containers; d i r e c t skin contact and dust particle d r i f t from granular application, IV • Persons who are bystanders could also receive exposure to silvex by accidental splashing or d r i f t , or low-level d r i f t of droplets and/or dust particles, Hose-end diluters create a high potential for dermal exposure to both applicators and bystanders because the sprayarising from these devices is dispersed over a wide range. The coarseness of the spray, however, probably precludes any significant inhalation exposure or drift away from the site of treatment . Preparing liquid concentrates for use exposes home users. While the concentrate is diluted with large volumes of w a t e r , the concentrate may spill or splash onto exposed skin. Additional exposure is likely to occur due ing spraying, m i x i n g , and cleanup of equipment. Householders are not likely to exercise the ame caution as the certified experienced operator, and m a y , for example spray upwind, thus receiving an unduly high amount of drift on face, hands, and other unprotected parts of the body. a d d i t i o n , home-users are likely to exceed label instructions in regard to application rates and number of applications. */ Some~horn.e~ar.d~garden applications of silvex are made by lawn care professionals, who work much more extensively with this h e r b i c i d e that would a single homeowner. These professionals are likely to exercise more care curing the use of pesticide chemicals? thus, the risks of d e r m a l exposure, resulting from spills is lower to them than to home users cenerallv. In �C. Use of these pesticides results in contamination of food and water and thereby presents indirect exposure to humans Even in the absence of direct exposure curing application, there are indirect routes through which can be exposed to 2,4,5-1, silvex, and/or TCCD. individuals Cnce a herbicide is a p p l i e d j subsequent environmental factors play an important role in determining its human accessibility. For example, animals used for food may eat the treated foliage, thereby providing a source of d i e t a r y contamination, treated ;' treated soil run-off could contaminate water supplies; and weather conditions favoring persistence of the chemical could prolong possible exposure. Monitoring studies have detected these substances in water and a n i m a l s , indicating a very real source of indirect human exposure and possibly explaining the residues detected in human urine. In the following section, sources of indirect exposure to 2,4,5-T, silvex, and/or TCDD are discussed. 1. Chemical residues of 2,4,5-T, S i l v e x , and/or TCDD are detected in environmental media and human and animal tissues. The EPA and other Federal agencies support numerous programs which monitor 2,4,5-1, Silvex, and TCDD in environmental samples. For example, EPA monitors u r i n e , a i r , surface w a t e r , s e d i m e n t , and soils. Other agencies have similar p r o g r a m s which are a p p r o p r i a t e to their needs, i.e.., the Bureau of Land-management has done water monitoring for Silvex in connection with its h e r b i c i d e sera 1 / croiects on 5LM forested land. �-75aDow contends that environmental monitoring has failed to reveal any significant TCDD residues and that studies fail to demonstrate the presence of TCDD as a residue in the American food supply. They contend that this is because the short half- lives of 2,4,5-T, silvex and TCDD prevent a significant contamination of environmental media. Doubt is cast upon these claims by the evidence. Monitoring studies done by EPA indicate that 2.,4,5-T and/or silvex are present in human urine, ambient air and surface waters. Recent preliminary results from a national urine survey show trace amounts of 2,4,5-T in 3 of 1085 samples, quantifiable silvex residues in 4 samples, and trace amounts of silvex in an additional 13 samples. During the period May, 1976 - August, 1978, 2,4,5-T was detected in 6 of 1350 whole water samples; silvex was detected twice. Ambient air monitoring of agricultural areas from 1970-1971 3 3 shows residues of 2,4,5-T ranging from 0.5 ng/m to 36 ng/m . The U.S. Forest Service has done some limited monitoring studies in connection with herbicide spray projects on National Forest Lands in the Pacific Northwest. Analyses were only done for 2,4,5-T since Silvex is generally not used by the Forest Service. Some of those analyses were positive for 2,4,5-T. The Bureau of Land-Management analyzed a limited number of Oregon water samples for silvex only, since 2,4,5-T is not usually used by the Bureau. Silvex was detected within 72 hours after treatment. Data collected by the U.S. Geological Survey for 1968 - 1971 showed that 2,4,5-T was the most commonly detected herbicide in western streams. �In 1974, the Agency, Dow, United Stages Capartrpent of A g r i c u l t u r e , and the Environmental Defense Fund joined together' to form the Dioxin Implementation Flan, which was organized to develop the analytical methodology for detecting TCDD in the low parts per trillion range (pet), to conduct monitoring for TCDC in environmental samples, and to support research on the toxicological effects of TCDD. Record at E-74. As a part of the Flan, samples of birds and mice from forest areas in Oregon which had been collected in 1973 and analyzed using e a r l i e r , less reliable, techniques, were re-analyzed in 1976 using improved gas chrcmatography/high resolution mass spectroscopy techniques. Three of five samples which had originally been analyzed as positive showed detectable levels of TCCD, although exact qualification varied between laboratories. Therefore, although precise quantification is not a v a i l a b l e , it appears from q u a l i t a t i v e standpoint that TCDD was present in some of the Oregon forest samples collected in 1973. Pecord at H-63 and 73. Three beef fat samples out of 67 collected in 1975 from areas where 2,4,5-T was probably used were also found to be positive (one at 60 ppt and two at 20 ppt') , In addition, some ether samples showed the possibility of TCDD, but levels were at or below the detection limit of 10 ppt. Record at R-65. Studies on the environmental movement of 2,4,5-T and Silvax indicate that run-off from sites of application is a likely means of environmental transport. These herbicides are usually applied �js a dilute spray, forming a chin film on foliage and soil. They are thus accessible to r a i n f a l l that occurs subsequent to application. Both are fairly soluble in water and are trans- ported in run-off largely in solution r a t h e r than by adsorption to suspended run-off sediments. Numerous studies have documented transport of 2,4,5-T under d i f f e r e n t situations. For e x a m p l e » 2,4,5-T levels of at least 7.2 ppb were foundd in a fish hatchery, 4000 feet downstream from a forest treatment days after treatment N o r r i s , 1973 site, six . (Exhibit 7- ). For p a s t u r e and range land use, concentrations of 2,4»5-T from 15 to 3,300 ppb were found in surface run-off waters collected at the edge of the treated plots. In sum, monitoring p r o g r a m s have demonstrated the presence of 2,4,5-T, silvex and TCDD in water, a i r , and foodstuffs. Proof that human exposure is actually taking place is demonstrated by the presence of 2,4,5-T and silvex in u r i n e samples. 2. Contamination of food and water with 2,4,5-T results in indirect exposure to humans Numerous documented incidents establish that, despite inconclusive or apparently negative results in many residue analyses samplings, use of 2,4,5-T results in contamination of food or water at considerable distances for the site of application and that such contamination causes damage and causes indirect h u m a n exposure. Dow contends that the environ- m e n t a l fate of 2,4,5-T is such that "stream c o n t a m i n a t i o n is negligible" and that "Residues of 2,4,5-T r a r e l y occur ir. m e a t , milk and other a g r i c u l t u r a l p r o d u c t s under c u r r e n t r e g i s t r a t i o n s , " (Cow comments, p. 37) Cow also implies -hat TCDC does not �contaminate food and w a t e r : " . . . TCDD is not mobile in soil and residues nave not been found application of 2,4,5-T. in vegetation or water after Significantly, environmental monitoring .has failed to reveal any significant TCCD residues." Id_. Dow'3 position overlooks incidents such as those described below. The selection c r i t e r i a used in collecting these incidents involving indirect exposure are the criteria used for collecting reports of direct exposure. 1. 2,4,5-T was the pesticide used. 2. The use resulted in damage. 3. The iste of injury was some distance away from the site of application 4. The incident was the subject of a contemporaneous report. The incidents selected are d r a w n from RF&R rebuttal submission and FSPS Reports, The Agency is in the process of•collecting . reports of additional incidents for use in the administrative hear ing. In March 1975 , 2,4,5-T was applied by air on timber land near Poseburg, Oregon, at a time when snow was present on the ground. Subsequent melting of the snow caused contamination of a creek that supplies water to residents of the a r e a . analysis for one household revealed Tap water the presence of 0.0003 ppm of 2,4 ,5-T. In M a r c h 1975, 2,4,5-T was applied by equipment to c l e a r brush along a logging road in Lecombe ., Oregon. Contamination of a ditch alongside the unwanted foliage caused d a i r y c a t t l e to become ill. Analyses of milk sampled five and eight days �"after the spraying shewed that 2,4,5-T was present at levels of 0.03 pprn and 0.002 ppm, respectively. Two hundred and forty gallons of milk generated by the sick cows had to be discarded. ( E x h i b i t v5) . In June 1973, 2,4,5-T was applied in a municipal shop maintenance area in West Linn, Oregon, Gardens and surrounding foliage and trees suffered damages including contamination of food crops. (Exhibit £ ). In June 1973,, application of 2,4,5-T along a right-of-way caused damage in a garden 150 yards from the right-of-way. Visible chemical damage occurred on beans, tomatoes, and peas. In the area surrounding the garden , visible damage occurred to grapes, apples, clover and foliage. (Exhibit *J ). In March 1978, 2,435-T was applied along a power line rightof-way in Gandeeville, West Virginia. The owner of property through which the right-of-way ran testified before a local commission chat the spray caused a "brown-out" which damaged vegetation, bushes, fruit trees and a creek in the area near the spray site, (Exhibit <5 ). In September 1977, 2,4,5-T was applied aerially on .3 power right-of-way about 30-40 feet from a school near H e r m i t , West Virginia, just after children had been dismissed from school. The teacher of the school testified in a court proceeding that spray fell both on the schoolyard and on adjacent areas, including a p a s t u r e , where children walk and play. Vegetation including b e r r i e s customarily eaten by the school children, was contaminated. A veil supplying water for che school was close to the spray site and may have been contaminated. (Exhibit '9 ). �• _ -7<Ja- 3. The environmental persistence of TCDD allows for exposure after the actual use-time. While 2,4,5-T and silvex are not environmentally persistent chemicals, TCDD is capable of great persistence. Helling et al. (1973) concluded that this persistence is not surprising since it is an insoluble, non-polar, chlorinated molecule, devoid of biologically labile functional groups. The half-life in soil has been estimated to be about one year in two different soils (Kearney et al., 1972). Of 100 strains of micro- organisms which have the capability to degrade other persistent pesticides, only five showed some ability to degrade TCDD (Matsumura and Benezet, 1973). Matsumura (1978) found that TCDD was stable in lake sediments and had a half-life of about 600 days. TCDD usually first appears in the environment at a very low concentration in a thin film on foliage or soil, as a result of spraying. The extent of its persistence depends upon the current environmental circumstances. Under certain conditions, including principally the presence of a hydrogen-donating solvent and adequate sunlight intensity, photodechlorination of TCDD to lower chlorinated dioxins can take place. Dow contends that TCDD has a short half-life in the environment when "on vegetation in the presence of a hydrogen donor and that photochemical degradation also occurs in soil." at 37. Dow Comments However, these conditions are clearly not always available. As noted by Crosby (1977), breakdown would be expected to be slower in the shade even if efficient hydrogen donors were available. Much of the forest area in the Northwest is subject to long periods �~ So of cloudiness and rain so that sunlight: may not be adequate. TCDD which reaches the soil may not be accessible co s u n l i g h t ; in such a case, the photodegradation process would not.occur. "No actual measurements of dioxin dissipation from he'rbicide treated forast appear to have been made" Crosby, 1977 . In the most intensive case of environmental contamination with TCDD, in Seveso, TCDD was observed to dissipate very slowly even though adequate sunlight was available in this case "effective contact with photochemical H donors was minimal" Crosby, 1977 . Thus,it is clear that, while TCDD photcdegration is po'ssible and might be rapid under certain circumstances, its likelihood of TCDD being destroyed by ths process under actual field conditions is unknown and may be low. D. Summary The implications for human health of the data on animal toxicity and the results of the Alsea study depends on the extent to which humans are esposed to toxicclogically significant levels of 2,4,5-T silvex and/or TCDD. going In view of the data from Alsea and the fore- instances a human e x p o s u r e , Dew's unsupported assertion that "the actual patterns of use in the Alsea basin should not reasonably be expected to produce more than negligible exposure to 2,4,5-T and silvex," Dow Comments at 24, simply cannot stand. The uses of 2,4,5-T and silvex result in distribution of these c h e m i c a l s co sites of human work and habitation. These chemicals and TCCC are present in e n v i r o n m e n t a l media and h u m a n tissues. There are no d a t a establishing a no effect level in a n i m a l s or h u m a n s for fatotcxic e f f e c t s , and even if t h e r e were are no d a t a �- a; - on an acceptable margin of these chemicals, of safecy or actual environmental levels Together these factors indicatae that the uses of these chemicals create an imminent hazard. �- 32-- The Suspension of the Contested Uses of 2,4,5-T And Silvex Will Not Result in Substantial A d v e r s e Economi Impacts A. Introduction In its comments, Dow attempts to demonstrate that where 2,4,5-T and Silvex are used they are essential. Thus, they argue, the suspension of these compounds for the uses at issue here will result in substantial economic losses where alternative control methods are not available or are less economical or efficacious. to these contentions. There are two general answers First, the Agency believes that for every use there is a practical alternative available to replace 2,4,5-T and Silvex. In some cases these alternatives may prove more costly than 2,4,5-T and/or silvex. For these, the/increased cost has been calculated and reported..in the Administrator's Decision and O r d e r . In no instance are these increased cost substantial in the context of the o v e r a l l economy or the particular industry involved. The second response to Dow's argument is that the timing of treatments with 2,4,5-T and Silvex is very flexible, such that.a delay in trea-tment, of 1 to 2 years is often feasible. Hone of the 2,4,5-T uses at issue here involve yearly treatments. cycles. Generally, treatments are spread over 5 to 10 year There is no evidence to indicate that a one or two year delay in treatments will result in substantial impacts eitner immediately or over the 2 year suspension period. Thus, for example, release treatments in conifer forests car, �- 33- be, undertaken quite readily in any year between the second and tenth year after planting. 44 ?R 15333 , This type of flexibility is the rule r a t h e r than the exception for 2,4,5-T and silvex herbicioal treatments. Former users of these compounds not only have the option of using a variety of alternative control methods, but in many instances the users can simply delay treatment during the pendency of the suspension without experiencing substantial adverse economic impacts. Dow bases its analysis entirely upon the document entitled, "The Biologic and Economic Assessment of 2,4,5-T," February 1979 ("USDA Report"). This document was originally intended as a cooperative effort of the USDA, EPA and State officials to be used as a major input into the benefits analysis phase of the RPAR process. In fact, EPA had a very ' V limited role in d r a f t i n g this report. The Agency was never afforded an opportunity to review and aoorove the final . X* / document. There are portions of the document which the */ Cf the 43 members of the Assessment team, only 5 -were from SPA. USDA Report, V-IX, et §eg. **/ A memorandum of Understanding between the USDA and EPA (signed Movernber 26 and December 2, 197-5) and a subsequent supplement (signed October 14 and 13, 1377) established the mechanism f";>: a joint U'SCA, EPA, States benefits analysis. The Memorandum of Understanding provides for a cooperative e f f o r t on an equal basis for all phases of the u n d e r t a k i n g . The supplement at ?. 6 r e q u i r e s that the participants './'ill be afforded an opportunity to r e v i e w and comment on the final document prior to issuance of the report. This provision was not complied with when rJ3GA issued the r e p o r t b e f o r e EPA has an opportunity to r e v i e w and comment upon it. �Agency does not concur w i t h ; accordingly, the Agency has not and cannot adopt, all portions of the r e o o r t as reflecting the * ** / Agency position on the matters discussed therein. There is useful information contained within the 'JSDA Report. However, it must be kept in mind r.hat the USDA Report was designed and directed at assessing the impact of a permanent cancellation of 2,4,5-T and not a short term 2 year suspension. Basic information (e.g., use data reported on a yearly basis)/ in the Report was used by the Agency in assessing short term impacts, however, much care was exercised by Agency staff in identifying and employing these data to avoid using data only applicable to long term impacts. Dow has failed in many instances to exercize similar care in using the data from the USDA Report. As a consequence , many of the citations in Dow's comments are to data which are applicable only to long term economic impacts. In the following discussion these e r r o r s as well the more serious allegations made by Dow and Chevron in their comments are aea11 with in detail. 3. Rights-of-Way The Dow comments on the rights-of-way use attempt to create an impression that 2,4,5-T is an essential tool for maintenance of many rights-of-way acres. In fact, a large number of acres receive no vegetation management of any ***/ .v>r_e Agency used portions of the 'JSDA Report which it felt it could a p p r o p r i a t e l y rely upon. In the context of the emergency conditions s u r r o u n d i n g the p r e p a r a t i o n s and 'promulgation of the Decisions and O r d e r s in this m a t t e r , it was sometimes necessary to rely upon benefits data in the U3DA Report which the Agency may u l t i m a t e l y w a n t to s u p p l a n t �- -X5 typ.e . 44 FR 15839 . For those acres under vegetation management, chemical control is the exception rather than the rule. Id. . The suspension of 2,4,5-1 for rights-of-way use will not cause significant economic impacts because a variety of efficacious alternatives are available, including manual, mechanical and several chemical control Id,, . methods. In some instances, these alternatives are less expensive than 2,4,5-T. Most of the chemicals (Dicamba, 2,4-D, dichloroprop, and piclorarn) are less expensive for a e r i a l , selective basal and stump sprays which account for the majority of annual treatments by acreage. Id . Thus, to the extent that these chemicals might have a shorter active life than 2,4,5~T, they partially, compensate for this with lower initial application costs . The weakness of Dow's position on rights-of-vay uses is f u r t h e r illustrated by their misuse of cited materials. Thus, for example, Dow claims that 2,4,5,-T does not cause adverse environmental effects. Dow Memo/ p. 48 . accompanying citation is to the U3DA Report. The• The C3SDA report does' contain several comments regarding the relative persistence of 2,4,5-T and its alternatives. However, the Report does not state nor infer, as Dow suggests, that no e n v i r o n m e n t a l hazards are posed by use of 2,4,5-T. Perhaps more importantly, the use of the USDA Report to support any statements about environmental impacts must be questioned. The "3DA Report was intended to collect, e v a l u a t e and document data needed by the Agency to evaluate the economic �significance of 2,4,5-T use. It was not designed nor does it d i r e c t itself to an assessment of broad environmental issues . Dow relies on the USDA Report to support its statement that dica.-'oa is less effective than 2,4,5-T for control of several weed species on rights-of-ways. The USDA Report (at 3-50) does suggest that dicarnba is not effective for these pests, 1 but it does not provide any basis for this statement. There is no indication that any form of scientific or formal observation was relied upon as the basis for this conclusion. As such, the Agency properly chose not to rely upon this statement. Dow claims that the annual increased costs of utilizing alternatives in place of 2,4,5-T for rights-of-way use would amount to $32 million per year rather than the §1.3 million estimated by SPA. This is erroneous. The 532 million figure, taken from the USDA Report, is excessive for purposes of assessing the impact arising d u r i n g a 2 year suspension because the USDA figure assumes a p e r m a n e n t cancellation. SPA figure cited by Dow -- 31.3 million — on a two year suspension. The is an estimate based A major reason for the relatively slight short term impact is the substantial flexibility in the timing o£ 2,4,5-T rights-of-way treatments. In fact, on the a v e r a g e , 2,4,5~T is only used onca every four years. 44 £R 15339 . In many cases t r e a t m e n t can be postponed for some time with little or no economic impact. Thus, a 2 year suspension would have a auantitativelv lesser impact �than a permanent suspension. In addition, on those acres for * wnich immediate treatments are desired, treatment can be undertaken wich any one of a number of efficacious and economical alternatives' Ij3. . C. Forestry It is Dow's position that serious economic impacts will be experienced as a result of the suspension of 2,4,5-T for forestry uses. For site preparation activities Dow claims that alternatives are more costly than 2,4,5-T. For release treatments there are no chemical alternatives and the manual alternative is very expensive and often impractical. Thus, for release treatments on those acres where manual methods are feasible there will be a substantial cose increase. Dow further alleges that there will be production losses on chose acres where manual methods are not feasible. */ contentions are incorrect. These The Agency has found that 2,4,5-T is not an essential tool for forest management. 44 FR 15333 . only C.23% of all U.S. commercial acreage. It is used on IcL . This level of use does not suggest that the chemical is essential to the entire industry. of alternatives available Furthermore, there are a variety for site preparations. In addi- tion to manual and mechanical methods there are a variety of efficacious and economical chemicals which are reaistered */ The U3DA agrees with the Agency that the short term economic impacts on forestry management arising from the suspension will ce minor. Thus, the Assistant Secretary of A g r i c u l t u r e , M . Rupert C u t l e r recently stated, " . . . the emergency suspension of 2,4,5-T for forest management uses would have no short-term impacts on the national forest timber h a r v e s t p r o g r a m . " U3DA Mews, "U3DA to ouscend Use of 2,4,5-T in Forest Manarer.ent" 3/1/79. U3DA 494-79. �and available for use this season. * Id. . It is important > to nottf that site p r e p a r a t i o n does not r e q u i r e a selective method of treatment, Selectivity is the primary special q u a l i t y claimed by Dow for 2,4,5-T. R a t h e r , sice preparation involves the suppression of all types of vegetative growth in the site. Thus, a variety of compounds other than 2,4,5-T are widely used for this purpose as well as mechanical clearing techniques. Release treatments require a selective method which will not harm the young conifers. In addition to 2,4,5~T, fosamine and glyohosphate provide selective control of indigenous pest plants and are registered in Washington and Oregon for this use. Manual treatments p r o v i d e the most selective and effective release treatments, albeit at a greater cost. How- e v e r , both Dow and USuA overestimate the cost and underestimate the cost effectiveness of manual release methods. The Agency will adduce evidence in the suspension hearings which will demonstrate that manual treatments are c u r r e n t l y in use in commercial forests. These operations have been successful both economically and biologically. Notwithstanding the availability of a v a r i e t y of alternatives, the Agency believes that for many managers the •most likely course of action during the suspension will be to delay release treatments temporarily. release activities is v e r y flexible. The timing of Release is generally u n d e r t a k e n at almost any time d u r i n g a 2 to 10 year ceriod aft^r p l a n t i n g . I d. . The growth dyanamics of a newly "1 an tec f o r e s t are such that the timina of treatments within �after p l a n t i n g . Id. . The growth dyanamics of a newly • planted forest are such that the tiding of treatments within this 3 year "window" often per~.it delays of a year or two and would, not have rneasureable effects on overall, production. Finally, Dow has assumed tha.t c u r r e n t practices, particularly for release treatments, have been cost effective. There is evidence to indicate that the effectiveness of current 2,4,5-T treatment techniques has 'been substantially overestimated. The Agency intends to present evidence in the hearings which will demonstrate that 2,4,5-T is frequently applied to acres which cannot or do not benefit from its use; that many applications are needless; and that 2,4,5-T can and does have phytotoxic effects on conifers. D. Pasture Dow states that the suspension of 2,4,5-T for pasture weed control will result in "substantial" economic impacts Dow Memo p. 53 . figures. However, there is no mention of actual This is not unexpected in view of the actual figures. Approximately 1% of all range and pasture acres */ w e r e treated with all herbicides in 1975." USDA, ESC3, 1973, p. 7 , Of the total quantity of herbicides used, 2,4-D accounted for 93.3%. Ibid. , p. 12 . All other pesti- cides including those which account for as little as 0.02% of the r e m a i n i n c use were listed; 2,4,5-7 did not e v e n aooear ision and Order at 44 ?R 15390 i n c o r r e c t l y states that 2,4,5-T is used on 1% of all acres. The statement should h -5. v e indicated that all c h e m i c 31 h e r b i c i d e s c o m b i n e d a r e us.-d on only 1% of all acres. �on. the list. Thus, to the e x t e n t that any chemical h e r b i c i d e s are used on pasture acreage, 2,4,5-T a p p e a r s to be one of the least, if not the l e a s t , favored of the a v a i l a b l e m a t e r ials. It cannot be said on the basis Of the foregoing data that the suspension of 2,4,5-T for pasture use will result in "substantial" economic impacts. Dow makes a number of statements, which on closer inspection are without support. Thus, for example, Dow states that, ", . . authorities have estimated as much as 53 of U.S. livestock die each year from grazing on poisonous plants". Dow Memo p, 52 . This statement is footnoted with a reference to 3. Day, "The Pher.oxy Herbicides" published by the Council for A g r i c u l t u r a l Science and Technology (CAST). The CAST report does contain a statement supporting Dow's statement. However, the relied upon CAST allegation is unsupported by reference to any type of documentary or factual support.' It is also unat tr i'outed, thus making it impossible to investigate the source of the claim. It is worthy of note that a similar statement also appears in the USDA Report (at p. 2-113). H-ere too, the statement appears without support OL attribution. In addition, it is explicitly li-mited to Western rangelands, a use not challenged in this proceeding. Tnere is no indication that the same r a t e of poisoning is thought to occur on p a s t u r e acres. In a similar v-in, Cow alleges tha.t, " uncesir .-able vegetation on all g r a z i n g land in the -U.S. causes losses of almost 32 b i l l i o n per year" Cow .'1-mo, o. 52 . This estimate is accarer.tlv drawn from �the "J33A Report at 2-3 where it spaces, "Annual losses from * weeds and brush on. rangeland and cost of control are conservatively estimated at ?1,7 oillicn". In addition to being excessively rounded off, Dow 1 3 use o if the 52 billion figure is inappropriate because the USDA estimate is again limited to rangeland. It does not encompass pasture land, the only c Y?e grazing land at issue in this proceeding. Finally, Dow argues that taken individually the available alternatives are not as broadly effective as 2,4,5-T. Although it nay be true that no single chemical alternative will replace 2,4,5-T in all areas of the country for all uses, there are effective chemical, manual and mechanical methods available to control all of the pest species in all parts of the country. 44 FR 1590 . Picloram, dicamba, 2,4,-D -and hand labor can generally provide the same level of control as 2,4,5-T although at higher r a t e s of application and/or higher cost. On those acres where the use of alternatives will cost more than scheduled 2,4,5-T treatments, treatment may be delayed, dispensed with altogether or the more expensive alternative employed. Since treatments with 2,4,5-T are generally scheduled for 5 to 10 years intervals, the timing of subsequent treatments is largely optional. Therefore, delay during the suspension period may be practical for many of the acres now scheduled for treatment. Treatment may be entirely dispensed '.-/it h on acres s c h e d u 1 e d f o r 2 , 4 , 5 — T treatment w n i c h �The Agency agrees with Dow that, "to the extent that 2,4,5-7 and Silvex are interchangeable in use on rights-ofway, forestry and pastures, the above discussion concerning 2,4,5-T applies" Dow Memo, p. 54 . Similarly, to the extent that Dow has failed to rebut the Agency's positions on 2,4,5-T uses, they have also failed with regard to the same uses of silvex. Chevron is the only Registrant other than Dow which submitted consents on the benefits of either silvex or 2,4,5-T. Chevron's comments were limited solely to the home and garden uses of silvex. Chevron argues that each of the three alter- natives to silvex for this use have limited effectiveness, Thus, they allege that dicarnba can adversely affect nearby shrubs when it is applied to lawns. MC?? is said to be less effective than silvex if it is applied to lawns or gardens during cool periods. Finally, some species of lawn pasts are said to be resistant to 2,4-Q. Hone of these claims are substantiated by Chevron in their submission. However, even if it were assumed, a£g_uendo , t h a t the claims w e r e accurate, Chevron has not succeeded in demonstrating that adequate tt alternatives are not available to replace silvex for lawn and garden use. The alleged limitations of the alternatives are mutually exclusive. A c c o r d i n g l y , at least one of the compounds would be effective in virtually any s i t u a t i o n . Thus, the homeown-• r ~ w*' ^ 1 ^o *~ b^ ^ •? ~ t w^ thou ~ an ^ '•*f ^c t' v^ a 11er ra t *; v^ It follows that t r. e i m o a c 13 3 t e m m i n c from the s j s " e n s i o n of e . •? •= : ?. i c ~j 1 j , �EPA t r i a l counsel w i l l p r e s e n t evidence at: the hearing vnich will show that c o n t i n u e d use of 2,4,5-T and silvex d u r i n g the period required to complete c a n c e l l a t i o n proceedings would result in an imminent h a z a r d . Respectfully submitted, ,-,'• j / ? /(AVVXx"!^ •)' ,\i''vvy<ffi^lj/) Michae 1 3 . "-7_ner Oeouty A3.3oc-.ate Gen-ral Counsel Dorothy S.^Patton P a t r i c i a PC. Roberts Ellen Siecier Kevin M . Lee Tip.othy D. 3ackscror.i L"1 ** 7 V 7 T O t'"> ",T *> '1 r~- "-N T "Tn A T 1 G ol V 1 .c\U IN »'I c* *. i -, A ij -"} .'n i^~> rn w .'"' rn T •_/ i-JT A -sj i %O I t? w 11 ^ ;•• \ *"" i" A c r i l 4 , 1979 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5267 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Winer, Michael S. Dorothy E. Patton Patricia A. Roberts Ellen Siegler Kevin M. Lee Timothy D. Backstrom Description An account of the resource <strong>Corporate Author: </strong>United States Environmental Protection Agency (EPA) Date A point or period of time associated with an event in the lifecycle of the resource April 4 1979 Title A name given to the resource Rebuttal Comments of Respondent Environmental Protection Agency in re: Emergency Suspension Orders for 2,4,5-T and Silvex, April 4, 1979 ao_seriesVIII Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5268 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Creator An entity primarily responsible for making the resource Bergland, Bob Title A name given to the resource Memorandum to Heads of Department Agencies: 2,4,5-T and Silvex Litigation Proceedings, April 5, 1979 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/b1fa6dbaa3acd8cc03ace14a021e44e1.pdf 46c74166a455a35e3917814e4139aa35 PDF Text Text Item D Numb en 05269 D NotScannBfl Author CorpOratB Author United States Environmental Protection Agency (EPA) Roport/Artido TltlB Appendix to Rebuttal Comments of Respondent Environmental Protection Agency in re: Emergency Suspension Order for 2,4,5-T and Silvex, FIFRA Docket Nos. 409-410 Journal/Book Title Year 1979 Month/Day A ril Color Number ofimages P D ° Also includes cover letter from L. Mark Wine of Kirkland and Ellis. Tuesday, March 05,2002 Page 5269 of 5363 �KIRKLAND&. ELLIS Washington Office Area Code 202 857-5000 To Call Writer Direct 202857- 5024 1776 K Street, N.W. Washington, D.C. 20006 April 5, 1979 chlcago ^ Area Code 312 861-2000 Telex 25-4361 200 E. Randolph Drive Chicago,III.60601 Enclosed is a copy of EPA's rebuttal comments which greatly expands its discussion of the data and sets forth the points it intends to prove at the hearing. We must respond as fully as possible to all of these claims both in preparation of Dow's testimony and in crossexamination of EPA witnesses. Sincerely yours/ L. Mark Wine LMW:bac Enclosure �U.S. ENVIRONMENTAL PROTECTION AGENCY in Fe: Emergency Suspension Order for 2.4.5-T and Silvex ) ) FIFFA Docket Nos. 409-410 APPENDIX TO REBUTTAL COMMENTS OF RESPONDENT ENVIRONMENTAL PROTECTION AGENCY Attached herwith are copies of the exhibits cited in "Rebuttal Comments of Respondent Environmental Protection Agency", dated April 4, 1979. Copies of this Appendix have been filed with the Hearing Clerk, the Hearing Panel and Counsel for Dow Chemical Corp. Any active party desiring a copy of the Appendix should contact the Office of General Counsel directly (202-755-2680). �APPENDIX I. Introduction - II. Exhibit 1, cited at p. 3. "USDA to Suspend Use of 2.4.5-T in Forest Management". USDA 1979. Animal Data Exhibit 1, cited at p. 14. "Reproductive Dysfunction. . ."« Barsotti, 1977. - Exhibit 2, cited at p. 14, "Hormonal Alternatives . . ." . Earsotti, 1979. Exhibit 3. cited at p. 15. "Environment and Birth Defects". 1973. - Exhibit 4. cited a p. 14. "TCDD Toxicity in Various Animal Models". Spencer 1979. - Exhibit 5. cited pp. 15-16. "The non-teratogenicity . . ." . Dougherty. 1975. Exhibit 6. cited at p. 16. "Abnormalities of Intrauterine Development . . ". 1971. Wilson. * III. - Exhibit 7. cited at p. 20. "Response to Rebuttal Comments. . ." . Albert. 1979. Alsea Exhibit 1. cited a p. 44. "Status Report". EPA. Feb. 8 . 1979. Exhibit 2, cited at p. 44. "Congential Abnormalities" , Infante. Exhibit 3. cited at p. 45. "Proceedings. Conference on Women in the Workplace. Infante 1976. - Exhibit 4. cited a p. 45. "Significant Factors . . .". Bailar. 1967. - Exhibit 5. cited p. 45. "The Effects of Maternally Inhaled Vinyl Chloride . . .". John. 1977. �-2- IV. Exposure - Exhibit 1. cited p. 66. letter. McGuire to Costle. 11-13-78. - Exhibit la. cited p. 69. Burkett affidavit. 4-3-79. - Exhibit 2. cited p. 68. Clary affadivit. 4-3-79. - Exhibit 3. cited p. 69. Cromwell affidavit. 3-14-74 - Exhibit 4. cited p. 77. "General Review of Environmental Movement of 2.4.5-T and Silvex". - Exhibit 5. cited p. 78. Exposure Report. "Ditch Contamination . - Exhibit 6. cited p. 79. "Soil Application of 2.4.5-T". - Exhibit 7. cited p. 79. "Railroad Rows". - Exhibit 8. cited p. 79. "Testimony of Hal Weber". 3-14-78. Exhibit 9. cited p. 79. "Testimony of Kathleen O'Hagan". 3-14-78. Exhibit 9a» cited p. 79a. "Chlorodioxins in Pesticides. Soils and Plants". Helling. 1973. - Exhibit 11. cited p. 79a. "Studies on Bioaccumulation . . .". Matsumura. 1973. - Exhibit 12. cited p. 79a. "Fate of 2,3.7.8 Tetrachlordibenzo-p-Dioxin. . . "..Ward & Matsumra. 1978. - V. Exhibit 10. cited p. 79a« "Persistence and Metabolism of Chlorodioxins in Soils". Kearney. 1972. Exhibit 13. cited p. 79a, "Conquering the Monster". Crosby. 1977. Benefits - Exhibit 1. cited at p. 83. "Memorandum of Understanding . . .". _- Exhibit-2. cited at p. 87. "USDA to Suspend Use of 2.4.5-T in Forest Management". 3-1-79. �U.S. ENVIRONMENTAL PROTECTION AGENCY ,in Re: Emergency Suspension Order for 2,4,5-T and Silvex ) ) FIFRA Docket Nos. 409-410 ' ERRATA SHEET FOR REBUTTAL COMMENTS OF RESPONDENT ENVIRONMENTAL PROTECTION AGENCY The following corrections should be incorporated into the text of the "Rebuttal Comments of Respondent Environmental Protection Agency," filed April 4, 1979. i 1) p. iii, §B., "chemical residue" not "chemicals residue" 2) p. iii, §(1), "causal" not "causual" 3) p. If line 4, "pages," not "pages" 4) p. 3, line 1, "Dow's" not "Dow s" 5) p. 6, line 2, "manufacturers" not "manufactures" 6) p. 6, line 6, "510 F2d. 1292," not "§10 2d. 1292," 7) p. 6, line 23, "variety" not "varity" 8) p. 7, line 6, "another study," not "other study," 9) p. 7, line 18, "hypotheses" not "nypothesis" 10) p. 8, line 3, delete "to" 11} p. 9, line 14, "510" not "§510" 12) p. 10, line 14, "at 10," not "at 13) p. 10, line 15, "at 10." not "at ," �-2- 14) p. 10, line 18, "teratogenic," not "terotogenic," .15) p. 11, l i n e 8, "pesticides" not "pesticide" ,16) p. 12, heading B . , l i n e 1, "Fetotoxic," not "Fetotoxic" 17) p. 13, l i n e 2, "has" not " h a d " 18) p. 13, **/, delete "a" in last line — NOEL had" 19) p. 14, line 22, "three" not "thre" 20) p. 17, line 19,."rather" not "rathr" 21) p. 21, line 10, "studies." not "studies"" 22) p. 22, line 1, delete second "effects" 23) p. 24, line 3, "ug/kg.," not "ug/kg." 24) p. 24, fn */ "at 19-20," not "at 25) p. 26, third indented paragraph; insert the following should read "that no ," after "ingesting": "TCDD was clearly affected at dose levels" 26) p. 29, line 15, delete second "in the" 27) p. 38, line 4, "hospitalized" not "hositalized" 28) p. 38, line 11, "risk" not "isk" 29) p. 39, 1'ine 5, "study area" not "study are" 30) p. 43, line 11, add "is" after "conclusion" 31) p. 43, line 12, "an" not "on" 32) p. 44, l i n e 17, "medical" not "radeical" 33) p . ' 4 6 , line 7, " f i s h i n g , " not " f i s h i n g " 34) p. 47, line 20, "plausibility." not "pluasibility." 35) p. 48, line 5, "(See, text, supra, at 9.)," not "(See Section , infra.)," �-3- 36) p. 49, line 14 "no more than 1-10 ppt in1- 37) p. 51, line 1, "respond" not "rspond" ,38) p. 51, line 2, "whether" not "nether" 39) p. 52, line 3, "may be" not "maybe" 40) p. 52, line 6, "cross-correlation a n a l y s i s . " not "cross-correlationanalys is." 41) p. 52, line 7, " r e g u l a t o r y " not " r e g u l a t i o n " 42) p. 52, S d ) , f i r s t l i n e , ""causal"" not " " c a u s u a l " " 43) p. 53, l i n e 9, " t h o u g h t f u l " not " t h g o u t h t f u l " 44) p. 53, line 15, "response" not "reponse" 45) p. 53, line 20, "waste of time and f u n d s . " not "waste time a n d f u n d . " 46) p. 53, line 24, "pursued" not "pursue" 47) p. 54, l i n e 20, "charges." not " c h a n g e s . " 48) p. 55, line 16, "uncler-reports" not "under r e p o r t s " 49) p. 56, l i n e 1, delete " t h e r e " 50) p. 57, line 3, "hypothesis" not "hpothesis" 51) .p. 58, line 3, "on" not "or" 52) p. 60, line 4, "questionable" not "questionabel" 53) p. 62, fn. **/, line 3, "correction" not "ccorrection" 54) p. 62, line 15, "Dow" not "Bow" 55) p. 63, 2nd indented paragraph, line 4, "ways" not "wasy" 56) p. 63, 2nd indented paragraph, line 7, "at 50-52;" not "at 50-51;" 57) ,p. 63,_ljLne_ 4, "proceeded" not "provided" �-4- 58) p. 64, line 2, "dealt" not "dealth" .59) p. 64, line 4, "they" not "it" ,60) p. 64, line 11, "unpersuasive," not "unpresuasive," 61) p. 64, line 21, "chemicals" not "chemicasls" 62) p. 65, line 8, "application." not "affication." 63) p. 65, line 16, "and habitation," not "hibitation," 64) p. 65, line 18, "conformance" not "conforming" 65) p. 65, line 19, "on" not "in" 66) p. 65, line 22, "unknowingly" not "unknowningly" 67) p. 66, line, "diffusion" not "difffusion" 68) p. 66, line 1, "through" not "though" 69) p. 66, line 2, delete "and" 70) p. 66, line 5, "also" not "aslo" 71) p. 67, line 5, "descriptions" not "discriptions" 72) p. 73, fn. */, line 4, "follow" not "follw" 73) p. 74, fn. */, line 6, place "generally" after "is" 74) p. 74, line 2, "*/" not "**/" 75) p. 74, line 14, "during" not "dueing" 76) p. 74, line 15, "same" not "ame" 77) p. 75, line 7, delete ", treated" 78) p. 76, line 13, "quantification" not "qualification" 79) p. 76, line 15, "from a qualitative" not "from qualitative" 80) p. 77, line 20, "from" not "for" 81) p. 78, line 11, "site" not "iste" �-5- 82) p. 80, line 19, " o f " not "a" 83) p. 81, line 2, " i n d i c a t e " not " i n d i c a t a e " 84) p. 82, line 16 "costs" not "cost" 85) p. 84, line 11, "exercised" not "exercized" 86) p. 84, line 13, "exercise" not "exercize" 87) p. 85, line 13, delete comma after "partially" 88) p. 87, line 10, insert ", Dow asserts" after "treatment" 89) p. 87, line 13, insert ", Dow claims" after "feasible" �INSERT AFTER P. 75 -75aDow contends that environmental monitoring has failed to reveal any significant TCDD residues and that studies fail to demonstrate the presence of TCDD as a residue in the American food supply. They contend that this is because the short half- lives of 2,4,5-T, silvex and TCDD prevent a significant contamination of environmental media. Doubt is cast upon these claims by the evidence. Monitoring studies done by EPA indicate that 2,4,5-T and/or silvex are present in human urine, ambient air and surface waters. Recent preliminary results from a national urine survey show trace amounts of 2,4,5-T in 3 of 1085 samples, quantifiable silvex residues in 4 samples, and trace amounts of silvex in an additional 13 samples. During the period May, 1976 - August, 1978, 2,4,5-T was detected in 6 of 1350 whole water samples; silvex was detected twice. Ambient air monitoring of agricultural areas from 1970-1971 3 3 shows residues of 2,4,5-T ranging from 0.5 ng/m to 36 ng/m . The U.S. Forest Service has done some limited monitoring studies in connection with herbicide spray projects on National Forest Lands in the Pacific Northwest. Analyses were only done for 2,4,5-T since Silvex is generally not used by the Forest Service. Some of those analyses were positive for 2,4,5-T. The Bureau of Land-Management analyzed a limited number of Oregon water samples for silvex only, since 2,4,5-T is not usually used by the Bureau. Silvex was detected within 72 hours after treatment. Data^collected by the U.S. Geological Survey for 1968 - 1971 showed that 2,4,5-T was the most commonly detected herbicide in western streams. �INSERT AFTER P. 79 -79a3. The environmental persistence of TCDD allows for exposure after the actual use-time. While 2,4,5-T and silvex are not environmentally persistent chemicals, TCDD is capable of great persistence. Helling et al. (1973) concluded that this persistence is not surprising since it is an insoluble, non-polar, chlorinated molecule, devoid of biologically labile functional groups. The half-life in soil has been estimated to be about one year in two different soils (Kearney et al., 1972). Of 100 strains of micro- organisms which have the capability to degrade other persistent pesticides, only five showed some ability to degrade TCDD (Matsumura and Benezet, 1973). Matsumura (1978) found that TCDD was stable in lake sediments and had a half-life of about 600 days. TCDD usually first appears in the environment at a very low concentration spraying. in a thin film on foliage or soil, as a result of The extent of its persistence depends upon the current environmental circumstances. Under certain conditions, including principally the presence of a hydrogen-donating solvent and adequate sunlight intensity, photodechlorination of TCDD to lower chlorinated dioxins can take place. Dow contends that TCDD has a short half-life in the environment when "on vegetation in the presence of a hydrogen donor and that photochemical degradation also occurs in soil." at 37. Dow Comments However, these conditions are clearly not always available. As noted by Crosby (1977), breakdown would be expected to be slower in the shade even if efficient hydrogen donors wore available. Much of the forest area in the Northwest is subject to long periods �CERTIFICATE OF SERVICE I hereby certify that copies of the foregoing "ERRATA Sheet for Rebuttal Comments of Respondent Environmental Protection Agency" and "Appendix to Rebuttal Comment of Respondent of Environmental Protection Agency" were hand-delivered or mailed first class postage prepaid, on April 9, 1979, to the following persons: Timothy Atkeson Steptoe & Johnson Chevron Chemical Company 1250 Connecticut Avenue, N.W, Washington, D.C. 20036 Shrikant V. Kulkarni, Ph. D. Manager, Pesticide Labeling Vertac Technical Center P.O. Box 941 West Memphis, AR 72301 Robert L. Ackerly Sellers, Conner & Cuneo Counsel for Lebanon Chemical Corp, 1625 K Street, N.W. Graham Purcell Doub, Purcell, Muntzing & Hansen Chartered 1775 Pennsylvania Avenue, N.W. Washington, D.C. 20006 Counsel for Riverdale Chemical Company Frank Miller & Sons Tobacco States Chemical Co. PBI Gordon Corp Pueblo Chemical & Supply Co. Plat'te Chemical Co. Roger A. Shores, President Bartels and Shores Chemical Co 1400 St. Louis Avenue Kansas City, HO 64101 Washington, D.C. 20006 Edward W. Warren, et al Kirkland & Ellis Counsel for Dow Chemical Company 1776 K Street, N.W. Washington, D.C. 20006 Gene R. Currie Technical Services Manager Imperial Inc. Box 423 West 6th Avenue Shenandoah, IA 51601 Larry R. Hodges AMCHEM PRODUCTS, Inc. Ambler, Pennsylvania 19002 Anthony P. Brown Pillsbury, Madison & Sutro Chevron Chemical Company P.O. Box 7880 San Francisco, CA 94120 Gene R. Currie Floyd E. Grabiel, II General Counsel Universal Cooperatives, Inc 3001 Metro Drive Minneapolis, MN 55420 Technical Services Manager MFA Oil Company Box 423 West 6th Avenue Shenandoah, IA 51601 �- 2Bonide Chemical Company 2 wurz Yorkviile, New York 13495 Jacqueline Warren Counsel for the Environmental Defense Fund, Inc. 1525 18th Street, W.W. Washington, D.C. 20036 Graham Purcell Doub, Purcell, Muntzing & Hansen Attorneys at Law Counsel for Platte Chemical Company 1775 Pennsylvania Avenue, N.W. Washington, D.C. 20006 Melvin R. Wilcox, III Roberts, Harbour, Smith, Harris French & Ritter Counsel for T.O. Bell/dba/Forage Unlimited 404 North Green Street Longview, Texas 75601 Frank B. Stewart, Vice President The Chas. H. Lilly Company 7237 N.E. Killingsworth Portland, Oregon 97218 John J. Balardo Corporate Counsel 2727 Walker, N.W. Grand Rapids, MI 49504 0. A. Wolcott, Manager Planning & Technical Services Farmers Union Central Exchange, Inc. Box 43089 St. Paul, MM 55164 John R. Diem, Vice President Southern Agricultural Insecticides,- Inc P.O. Box 218 Palmetto, PL 335'61 J. R. McCloud, Manager Specialty Products Smith-Douglass Division of Borden Chemical, Borden, Inc. P.O. Box 419 Norfolk, VA 23501 Richard deC. Hinds, Esq. Cleary, Gottlieb, Steen & Hamilton Counsel for USS Agri-Chemical Division of USS Corporation 1250 Connecticut Avenue, N.W. Washington, D.C. 20036 Bernard H. Lorant Counsel for Black Leaf Products Co. Lorant and Lorant, PC P.O. Box 668 Aldo Blasio, President Farmingdale Garden Labs, Inc. 136 Verdi Street Farmingdale, New York 11735 Highland Park, II 60035 John E. Soltes, General Manager WEGRO, Division of Old Fort Industries, Inc. Grand Rapids, Ohio 43522 Fernando Erazo, President Heritage House Product Corporation 1025 Northern Boulevard Roslyn, New York 11576 �- 3- - Ronald A. Meier, Manager Lawn Fertilizer Division The Andersons P.O. tiox 119 Mauraee, Ohio 43537 John R. Wittpenn, President Rockland Chemical Company, Inc. P.O. Box 809 West Caldwell, New Jersey 07006 Robert w. Cummings Assistant Vice President J. & L. Adikes, Inc. 182-12 93rd Avenue Jamaica, New York 11423 Jon D. Loft, President Lofts Pedigreed Seed, Inc. P.O. Box 146 Bound Brook, New Jersey 08805 JU_1 Kevin Lee April 9, 1979 � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5269 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource <strong>Corporate Author: </strong>United States Environmental Protection Agency (EPA) Date A point or period of time associated with an event in the lifecycle of the resource 1979-04-01 Title A name given to the resource Appendix to Rebuttal Comments of Respondent Environmental Protection Agency in re: Emergency Suspension Order for 2,4,5-T and Silvex, FIFRA Docket Nos. 409-410 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/5bf63a2889a1e3101e4b8bbf4bee4dfb.pdf c16036b1e0894289a2884fdaf5b54a45 PDF Text Text Item D Number 05270 D NotScanned Author CorDOratB Author United States Environmental Protection Agency (EPA) RODOrt/ArtiOlO TitlO Notice and Order in re: Suspension of Registrations for Certain Uses of 2,4,5-T and Silvex, FIFRA Docket Nos. 409 and 410 Journal/Book Title Year Month/Day Color April 4 a Number of Images ° DOSOrlOtOn NOtOS Also includes cover letter from L. Mark Wine of Kirkland and Ellis, and Hand Delivery cover letter from Sonia G. Anderson of the EPA. Tuesday, March 05, 2002 Page 5270 of 5363 �KiRKLANDS, ELLIS Washinflton Office Area Code 202 857-5000 To Call Writer Direct 202857- 5024 1 776 K Street, N.W. Washington, D.C. 20006 CWcago Qffjce Area Code 31 2 861 -2000 Telex 25-4361 200 E. Randolph Drive April 6, Chicago, III. 60601 1979 To: Potential Dow EPA Hearing Witnesses In an order received yesterday, the EPA Hearing Panel established initial dates and procedures for the hearing. I thought each of you would appreciate receiving a copy of the order so that you will have a better idea of the hearing status. As you will see in the enclosed order, testimony will begin on Thursday, April 19. The hearing will be split into two phases, risks and benefits. Although we are not sure how long EPA's case will take, we anticipate that the Dow risk case will begin during the week of April 23 and will take several weeks to complete. We expect benefits testimony to be presented during the week of May 14. Finally, written statements will be required three days before a witness is scheduled to appear. We will keep you advised as the schedule is developed in more detail. Even the dates given above are subject to change. Sincerely yours, L. Mark Wine LMW:bac Enclosure �UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 April 5, 1979 OFFICE OF THE HAND DELIVERY ADMINISTRATOR (See List of Addressees) Subject: In re Emergency Order Suspending 2,4,5-T & Si 1 vex FIFRA Docket Nos. 409 & 410 Dear Sirs or Madams: Enclosed, please find a copy of "Notice and Order" dated April 4, 1979, filed April 5, 1979 in the above-entitled proceeding by Charles N. Gregg, Chairperson, Hearing Panel. Sincerely, Sonia G./Anderson Enclosure �Hand Delivery LIST OF ADDRESSEES Graham Purcell Doub, Purcell, Muntzing & Hansen Counsel for Tobacco States Chemical Co., Frank Miller & Sons, Riverdale Chem. Co., PBI Gordon Corp., Pueblo Chemical & Supply Company & Platte Chemical Company 1775 Pennysi vania Avenue, N.W. Washington, D.C. 20006 Richard deC. Hinds, Esq. Cleary, Gottlieb, Steen & Hamilton Counsel for USS Agri-Chemical Division of United States Steel Corporation 1250 Connecticut Avenue, N.W. Washington, D.C. 20036 Timothy Atkeson Steptoe & Johnson Chevron Chemical Company 1250 Connecticut Avenue, N.W. Washington, D.C. 20036 Robert I. Acker!y Sellers, Conner & Cuneo Counsel for Lebanon Chemical Corp. 1625 K Street, N.W. Washington, D.C. 20006 Edward W. Warren, et al Kirkland & Ellis ' Counsel for Dow Chemical Company 1776 K Street, N.W. Washington, D.C. 20006 Michael S. Winer U. S. Environmental Protection Agency Office of General Counsel (A-132) 401 M Street, S.W. Washington, D.C. 20460 �ENVIRONMENTAL PROTECTION AGENCY Suspension of Registrations for Certain Uses of.2,4,5-T and Silvex PIFRA Docket Nos. 409 and 410 Notice and Order I. Active Parties Any party may be an active party. If parties do not intend to participate in the introduction of evidence or examination of witnesses, they will be considered inactive parties. Inactive parties will not lose the right to file proposed findings and • conclusions and briefs. They will not, however, be entitled to expedited service (See V below), and they will not be served with written witness statements and other papers rel'ating to the introduction of testimony and the conduct of hearings. To be an active party, a party must file a statement to this effect (including a reference to its having-filed and served its statement of intention to introduce evidence and/or cross-examine witnesses as provided in IV, below)with the Hearing Clerk by April 12 and shall serve such statement on all parties by hand delivery or telex by noon, April 13. �2 II. Order of Introduction of_ Evidence Evidence will be introduced in the. following order: o • • The complete evidence on the risk associated with the suspended uses of 2,4,5-T and Silvex will be introduced by all parties before commencement of the introduction of evidence on the benefits of such uses. o The respondent will introduce its complete .. evidence on risk first. The petitioners (pes- ticide registrants) will then introduce their complete evidence on risk. o Following the completion of evidence on risk, the respondent will present its evidence on the benefits of the suspended uses, to be followed by the evidence on benefits of the petitioners. t o » The parties may choose the order of presentation of subject matter in introducing evidence on risk and in introducing evidence on benefits. �3 III. Requirements Regarding Written Witness Statements Except in unusual circumstances, and as approved by the Panel, introduction of direct testimony and documentary evidence and other exhibits shall (in the case of oral direct testimony) be preceded by, and i:; other cases consist of, introduction of a sworn written statement of a witness which shall incorporate his complete direct testimony and/or identify with specificity the documentary evidence and other exhibits to be introduced through him. Such statement shall be filed with the Hearing Panel and served _on active'parties no later than 11:00 a. m. on the third day preceding the day on which it is anticipated that the witness will testify (by 10:00 a. m., Friday, in the case of a Tuesday hearing). Exhibits need not be served on parties, but they shall be filed with the Hearing Panel as provided in V below, except that fewer copies can.be provided in the case of bulky exhibits by arrangement with the Panel. Counsel should attempt to oblige other parties who request copies of exhibits. �4 IV * Schedule and Related Orders The following schedule is established: April 1£ Each party who intends to introduce direct evidence (including documentary and other exhibits) will provide the names of the witnesses whose testimony it will introduce (or through whom exhibits will be introduced); a brief description of each witness1 proposed testimony (including identification of exhibits); a statement whether the testimony will be in writing alone or whether permission to introduce oral direct testimony will also be requested; and in the latter case, the estimated time for such oral testimony and a brief justification for allowing oral testimony in addition to written testimony. This information will be served on every party and will be filed with the Hearing • Panel. Filing and service upon parties in the greater Washington area will be by hand delivery, and service upon other parties by telex (or other guaranteed 24-hour delivery), in each case by close of business April 10. �April 1£ Each party who wishes to cross-examine any listed witness will provide a list of the witnesses it proposes to cross-examine? an estimate of the time needed for cross-examination of each such witness; and a brief statement indicating the likely benefit of such cross-examination. This information will be served and filed, in the same fashion as was the information on direct testimony, by close' of business April 12. April 13, and 1£. . Parties who have indicated an intention to introduce evidence (direct testimony and exhibits) and/or a wish to cross-examine will attempt to allocate among themselves the available hearing time, to include allocations between the risk and benefit aspects of the hearing; within these two « categories, allocation among the respondent, the petitioner Dow Chemical Company and other pesticide registrant petitioners should be attempted. Counsel shall also confer concerning objections to proposed �6 * ' * witnesses. Counsel shall also employ their best efforts to stipulate facts and to narrow the issues for the Panel. Where such agreements cannot be reached, counsel shall attempt to arrive at a useful statement of the differences among the parties and agreed upon statements of major issues. Respondent shall convene a conference for the foregoing purposes on Friday afternoon, April 13, or Monday morning, April 16. All active parties are urged to participate in this conference. Parties should contact Mr. Michael Winer for the time and place of the conference. Following the conference, counsel shall prepare a report or • reports to the Hearing Panel on the results of these attempts to allocate time and stipulate and shall submit requests for allocation of hearing time to the extent agreement was not reached. Such report and requests shall be filed with the Hearing Panel by 4:00 p. m., April 16. « April 1£ The•respondent shall file and serve the written statements of its witnesses who will appear during the week of April 16. �April 17 A prehearing conference will be held at 9:00 a., m., at the Environmental Protection Agency, Crystal Mall Building No. 2, Room 1118B, 1921 Jefferson Davis Highway, Arlington, Virginia, to consider any remaining questions as to the apportionment of hearing time between the risk and benefit aspects of the hearing and among the parties, the scheduling of witnesses, and for other purposes. No party who fails to be present at the prehearing conference, except for good cause shown,'will receive an allocation of hearing* time. . The Panel-will,allocate hearing time among active parties at the prehearing conference or no later than the following day. Time will be allocated on the basis of 22 full days of hearings, April 19 through May 18. The week, of May 21 will be reserved for hearing witnesses recommended by the Hearing Panel and for witnesses unavailable for good cause during the »preceding hearing schedule, or as otherwise provided by the Panel. Whether requests to present oral direct testimony will be granted in the case of individual witnesses and whether requests to cross-examine particular �8 witnesses will be granted will not be made as a part of the allocation of time to parties, but will be addressed.individually either at the prehearing conference, or in most cases, as the hearings progress. April 19^ The first two hearing days for the introduction of evidence (respondent's witnesses on risk) will begin at 9:00 a. m. and will be held in Room 1118B, same address as above. Subsequent hearings are all expected to be held at the same address. - Time of commencement and hearing room numbers for each hearing day will be ; announced at the preceding day's hearing. At all times following the allocation of hearing time, counsel should be prepared to provide the Hearing Panel and other parties their good faith best estimates as to the order in which and expected * times when they .propose to call witnesses and any changes in the witnesses they intend to call. In this connection, counsel shall exert their best efforts to avoid surprise and waste of time and allow counsel and the Hearing Panel to focus on the most important issues. �9 V. Service and Filing Except as otherwise provided in particular cases, service will be made on active parties in the greater Washington area by hand delivery promptly after.filing. Service on active parties outside the Washington area will be made by telex or express mail (or other guaranteed 24-hour delivery). When service on inactive parties is required, it will be by first class mail. When filing a document with the Hearing Panel, an original plus two copies shall be delivered to the Hearing Clerk, and three copies shall be delivered to the offices o.f -the Hearing Panel at Crystal Mall Building No. 2, Room 1003, 1921 Jefferson Davis Highway, Arlington, Virginia. Charles N. G r e g g / / Chairperson, Hearing. Panel ^ r~5 '<S>ii^y<-^g^ Dr. William A. Brungs Member, Hearing Panel April 4, 1979 Robert L. Coughlin <• Member, Hearing Panel 7j � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5270 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource <strong>Corporate Author: </strong>United States Environmental Protection Agency (EPA) Date A point or period of time associated with an event in the lifecycle of the resource April 4 1979 Title A name given to the resource Notice and Order in re: Suspension of Registrations for Certain Uses of 2,4,5-T and Silvex, FIFRA Docket Nos. 409 and 410 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/9b9ccc9fb4994737a0e5412ebd55d05d.pdf 9dd4d5f75af920454e243c275fcc8744 PDF Text Text item D Number °5271 n NotScanneil Author Corporate Author Comptroller General of the United States ROUOrt/ArtiClO Tltlfl ReP°rt bytne Comptroller General of the United States: Health Effects of Exposure to Herbicide Orange in South Vietnam Should be Resolved Journal/Book Title Year Month/Day Color April e D Number of Images ° Descripton Notes CED-79-22 Tuesday, March 05, 2002 Page 5271 of 5363 �DW TUG ALVIN L. YOUKG, Major, USAF UT Consultant, Environmental Science: MIL Comptroller General OF THE UNITED STATES Health Effects Of Exposure To Herbicide Orange In South Vietnam Should Be Resolved Since 1977 Vietnam veterans have been contacting the Veterans Administration about health problems which they believe were caused by exposure to herbicides in Vietnam. Problems in identifying personnel exposed to herbicides and determining the possible health consequences of such exposure have hampered VA efforts to resolve veterans' concerns. This report recommends that the Department of Defense, with the assistance and guidance of an appropriate interagency group, conduct a survey of any long-term medical effects on military personnel who were likely to have been exposed to herbicides in South Vietnam. It also recommends several additional actions VA and DOD should take. CED-79-22 APRIL 6 1979 - �PRIORITY - 3 DELIVERY i» HEChlPT r f! REQUEST NO.: GENERAL ACCOUNTING OFFICE I ' DOCUMENT HANDLING AND INFORMATION SERVICES FACILITY i ! ' I i B O X 6015, GArrHERSBURG, MARYLAND 20760 TeLEPf*ON£-(2Q2) 275-6241 •>*-"•-.• " , •• ' ••« 06886? DOCUMENT NOt h h .X^ED-79-22 S«n fttonte- I'X 7»JI«i i L TOTAUCOST: AMOUNT RECEIVED: CREDIT DUE: AMOUNT DUE GAO: MESSAGE: 'REQUEST NO.: 068867 AMOUNT DUE: AMOUNT REMITTED: PROCESSED DATE, TIME DATE, TIME DATE, TIME BY: , OF DELIVER^ TO REQUESTER: OF DELIVERY TO USPS. • ' OF DELIVERY TO GAO MAIL ROOM: DATE: ' 7/19/79 GAO CHARGE POLICY; Single copies of up to ten titles are free of charge. Multiple copies of any title or single copies of the eleventh (ahd onwards) title cost $1.00 each. PAYMENT IS DUE UPON RECEIPT OF INVOICE RETURN THIS STUB. WITH CHECK OR MONEY ORDER PAYABLE TO: GENERAL ACCOUNTING OFFICE DHISF BOX 6015, GAITHERSBURG, MARYLAND 20760 J �COMPTROLLER GENERAL OF THE UNITED STATES WASHINGTON, D.C. 20548 B-159451 The Honorable Bennett Stewart House of Representatives Dear Mr. Stewart: As agreed on June 28, 1978, with the office of your predecessor, the late Representative Ralph H. Metcalfe, this is the second of the two reports on our review of the Department of Defense's use of herbicides in South Vietnam and veterans' concerns over possible adverse health effects of herbicide exposure. Our interim report (CED-78-158, Aug. 16, 1978) addressed the (1) extent of the Defense's use of herbicides and other chemicals in South Vietnam, (2) number of military and civilian personnel exposed to these chemicals, and (3) Defense-funded studies of the health effects of these chemicals. This report addresses primarily the Veterans Administration's response to veterans' concerns on herbicide exposure in South Vietnam and health effects studies of TCDD, a highly toxic contaminant of 2,4,5-T, a component of Herbicide Orange. As arranged with your office, we will make the report available to other interested parties 2 days after the issue date. Sincer Comptroller General of the United States �COMPTROLLER GENERAL'S REPORT TO THE HONORABLE BENNETT STEWART HOUSE OF REPRESENTATIVES HEALTH EFFECTS OF EXPOSURE TO HERBICIDE ORANGE IN SOUTH VIETNAM SHOULD BE RESOLVED D I G E S T In late 1977, Veterans Administration (VA) regional offices began receiving compensation claims from veterans who felt that some of their medical problems were caused by exposure to herbicides in Vietnam. These problems included such conditions as fatigue, nervousness, cancer, reduced hearing, and birth defects in offspring. Vietnam veterans also began contacting VA health care facilities, expressing concerns over possible herbicide exposure. By September 1978 about 600 veterans had been examined at VA health cate facilities and about 450 had submitted claims to regional offices. The Department of Defense carried out military herbicide operations in South Vietnam from 1962 to 1971. Herbicides were used primarily for —defoliating trees and plants to improve observation and —destroying food crops of hostile forces. Herbicide Orange, a 50:50 mixture of 2,4-D and 2,4,5-T, was the most widely used herbicide. Concentrations of 2,4,5-T used in South Vietnam were heavier than those used in the United States for various purposes. The component, 2,4,5-T, contains a contaminant, TCDD (dioxin), that is highly toxic. TCDD's toxic effects have been reported by researchers investigating the effects of continued occupational exposure to chemicals contaminated by TCDD and also acute exposures resulting from industrial Tear ftheet. Upon removal, the report cover date should be noted hereon. CED-79-22 �accidents. Its effects on laboratory test animals have been studied; however, longterm health effects on humans remain largely unknown. VA's actions have been hampered by this lack of information on long-tern health effects of herbicides. VA has established an interagency advisory group to assist in evaluating the medical aspects of herbicide exposure. (See p. 13.) VA has allowed no compensation claims solely on the basis of herbicide exposure. However, one veteran has received benefits for a skin condition existing while he was in the service which VA believes might be related to herbicide exposure. (See p. 11.) Because there are no specific records on herbicide exposure, VA is having difficulty identifying veterans who were exposed to herbicides. Defense officials believe that those most likely.to have been exposed were herbicide handlers and aircraft crews flying herbicide missions. Defense has identified about 500 of these crew members. (See p. 6.) VA health care facilities have been instructed to examine any veteran concerned about herbicide exposure. Veterans currently being treated in VA facilities and those applying for .care will be asked if they have been exposed to herbicides or other chemicals in Vietnam. The results will be included in a data base compiled by VA. (See pp. 11 and 12.) VA regional offices have been instructed to evaluate herbicide-related claims as they would any other claim for serviceconnected compensation. However, no assurance is made that all veterans submitting such claims to regional offices are being referred to VA health 11 �care facilities for examination. In addition, VA regional offices have not been instructed to ^obtain information from military records concerning the likelihood of an individual veteran's exposure to herbicides (for example, occupational specialty, duties performed, locations, and dates in Vietnam). (See p. 12.) Defense medical facilities may also be receiving patients who are concerned about exposure to herbicides. However, no system exists to determine the extent of these contacts. The Department of the Air Force is the only service to have developed any guidance for its medical facilities to evaluate personnel concerned about herbicide exposure. RECOMMENDATIONS The Department of Defense, with the assistance and guidance of an appropriate interagency group, should conduct a survey of any long-term medical effects on military personnel who were likely to have been exposed to herbicides in South Vietnam. The Secretary should also provide guidance to insure that Air Force, Army, and Navy medical facilities are uniformly monitoring and evaluating possible herbicide-related concerns of personnel who served in Vietnam. In addition, information developed through Defense medical facilities should be coordinated with the VA. The Administrator of Veterans Affairs should provide guidance to insure that: —In evaluating herbicide-related claims, regional offices obtain all information from military records pertaining to a veteran's possible exposure to herbicides in Vietnam. Tear Sheet �—All veterans submitting such claims to regional offices are encouraged to contact VA health care facilities. AGENCY COMMENTS Defense generally agreed with the need to provide guidance to all Defense medical facilities. However, officials doubted that a retrospective epidemiological study of Vietnam veterans would produce reliable results because of various data limitations. GAO recognizes that there would be limitations on a study of Vietnam veterans, but believes it would be desirable to obtain information related to the herbicides as used in Vietnam. (See pp. 27 and 28.) VA agreed that all veterans submitting herbicide-related claims should be referred to VA medical facilities, and, VA regional offices should obtain information on the veterans' possible exposure to herbicides. (See p. 16.) IV �C o n t e n t s DIGEST CHAPTER PERSPECTIVE Military use of herbicides and other chemicals in South Vietnam Personnel exposure to herbicides Current concerns over effects of 2,4,5-T and TCDD FEDERAL RESPONSE TO HERBICIDE CONCERNS OF VIETNAM VETERANS Scope and characteristics of veterans' concerns VA actions on the herbicide issue Defense involvement in the herbicide issue Conclusions Recommendations Agency comments HEALTH EFFECTS STUDIES OF TCDD Toxic effects of TCDD in humans Toxic effects of TCDD in animals Long-range health effects of TCDD in humans have not been determined Recommendation to the Secretary of Defense Agency comments and our evaluation 1 6 9 10 14 14 15 16 17 17 20 24 27 27 APPENDIX The military use of herbicides in South Vietnam II III IV V 29 Applications of herbicides in the Vietnam war 31 Letter from Department of Defense dated February 8, 1979 32 Letter from Veterans Administration dated January 25, 1979 34 Letter from the Environmental Protection Agency dated March 22, 1979 37 �ABBREVIATIONS EPA Environmental Protection Agency GAO General Accounting Office IARC International Agency for Research on Cancer NAS National Academy of Sciences NIEHS National Institute of Environmental Health Sciences iig/kg microgram (chemical) per kilogram body weight (animal) ppb parts per billion ppt parts per trillion VA Veterans Administration �CHAPTER 1 PERSPECTIVE By letter dated April 10, 1978, the late Representative Ralph H. Metcalfe expressed concern about possible longrange adverse health effects on individuals that were exposed to Herbicide Orange. He requested that we examine certain aspects of the Department of Defense's use of herbicides in Vietnam and the Veterans Administration (VA) handling of disability claims submitted by herbicide-exposed Vietnam veterans. As agreed with the Representative's office on June 28, 1978, we issued an interim report (CED-78-158, Aug. 16, 1978) which addressed (1) the extent of the Defense's use of herbicides and other chemicals in South Vietnam, (2) the number of military and civilian personnel exposed to these chemicals, and (3) the Defense-funded studies of the health effects of these chemicals. This report addresses primarily VA's response to veterans' concerns on herbicide exposure in South Vietnam and health effects studies of TCDD. We conducted our review at the Washington, D.C., headquarters offices of the Department of Defense, Environmental Protection Agency (EPA), and VA; and at the VA regional office and Hines Hospital in Chicago, Illinois. We examined pertinent legislation, instructions, studies, reports, and other documents. 'In addition, we talked with officials of Defense, EPA, VA, the National Academy of Sciences (NAS), the National Institute for Occupational Safety and Health, and the National Cancer Institute, MILITARY USE OF HERBICIDES AND OTHER CHEMICALS IN SOUTH VIETNAM Defense field tested herbicides in Vietnam in 1961 and carried out military herbicide operations from 1962 to 1971. The herbicides were used primarily for (1) defoliating trees and plants to improve observation and (2) destroying food crops of hostile forces. The herbicides used were: —Herbicide Orange, a 50:50 mixture of 2,4-D and 2,4,5-T, was the most widely used herbicide in Vietnam. The component 2,4,5-T contains a �contaminant, TCDD (2,3,7,8-tetrachlorodibenzopara-dioxin) which is one of most toxic chemicals known. —Herbicide Purple (a similar mixture of 2,4-D and 2,4,5-T that contained a different form of 2,4,5-T—it was replaced by Herbicide Orange in 1964) . I/ —Herbicide White (a mixture of 2,4-D and Picloram). —Herbicide Blue (cacodylic acid). The military use of herbicides in Vietnam is detailed in appendix I. According to a Defense estimate, about 17.7 million gallons of herbicides were sprayed during the 1962 to 1971 period. From 1965 to 1971, Defense sprayed 10.65 million gallons of Herbicide Orange, 5.63 million gallons of Herbicide White, and 1.14 million gallons of Herbicide Blue. NAS estimated that of the 3.6 million acres sprayed, 66 percent was sprayed once, 22 percent was sprayed twice, 8 percent was sprayed three times, and 4 percent was sprayed four or more times. NAS estimates of the quantities sprayed annually and application rates are summarized in appendix II. Herbicide Orange was sprayed undiluted in Vietnam at the rate of about 3 gallons (containing 12 pounds of 2,4-D and 13.8 pounds of 2,4,5-T) per acre. Civilian applications of this herbicide's components are usually diluted in oil or water. According to industry officials, the civilian application rate of 2,4,5-T varies from 1 to 4 pounds per acre. A Defense official said that the heavier application was needed to assure success of the herbicide operations. Defense officials also stated that due to the dense jungle canopy, the amount of herbicide penetrating the forest floor would have been similar to those normally applied to brush infested ranch land in the United States. _!/ Other herbicides used primarily during the 1962-1964 period included about 130,000 gallons of Herbicides Pink and Green. Both herbicides were formulations containing 2,4,5-T. �In October 1969 Defense restricted the use of Herbicide Orange to areas remote from population. This action was prompted by a National Institutes of Health report that 2,4,5-T could cause malformations and stillbirths in mice. Researchers later attributed similar problems to the contaminant TCDD, which is produced during the manufacture of 2,4,5-T. In April 1970 Defense suspended all use of Herbicide Orange in Vietnam. About the same time, the Department of Agriculture restricted certain domestic uses of 2,4,5-T because of its possible health hazards. In 1971 Defense directed the Air Force to dispose of all remaining stocks of Herbicide Orange. These stocks contained TCDD contaminant levels ranging from less than 0.02 to 47 parts per million and averaging about 1.98 parts per million. \J Current manufacturing standards for 2,4,5-T require TCDD levels to be less than 0.1 part per million. The Air Force reported that Herbicide Orange was disposed of by high temperature incineration at sea in 1977. The fate of TCDD in the environment TCDD has had the reputation of being very stable and persistent except when dissolved in organic solvents, such as methanol and benzene, and exposed to ultraviolet light. An experiment reported in March 1977 concluded, however, that despite the known persistence of pure TCDD, it is not stable as a contaminant in thin herbicide films exposed to outdoor light. According to NAS, TCDD is insoluble in water, slightly soluble in fats, slightly more soluble in hydrocarbons, and somewhat more soluble in chlorinated organic solvents. TCDD is stable to heat, acids, and alkali. Thermal decomposition requires a temperature of at least 1500° Fahrenheit. Studies have indicated that TCDD is immobile in soils and has a halflife in soil of about 1 year. TCDD exerts its biological effects at extremely low concentrations. This has posed serious limitations on analytical work with the substance. VSince Herbicide Orange is a 50:50 mixture of 2,4-D and 2,4,5-T, an average TCDD contaminant level of 2 parts per million would indicate that the 2,4,5-T component, as manufactured, contained TCDD levels averaging about 4 parts per million. �Scientists involved in measuring samples for TCDD have calculated that a sensitivity of about 1 part per trillion (ppt) is required for environmental monitoring of TCDD. Studies at Eglin Air Force Base Reservation in Florida The Air Force sprayed massive amounts of herbicides over approximately 1 square mile at Eglin to test aerial dissemination systems. The testing area was divided into four grids, three of which were sprayed with 2,4,5-T. Grid number one containing 92 acres, was sprayed with about 87,000 pounds of 2,4,5-T (947 pounds per acre) during 196264. Grids two and four were sprayed in 1964-66 and 1968-69, respectively, with substantially lesser amounts of 2,4,5-T per acre of grid area. Between 1973 and 1978, the Air Force collected 54 soil samples from the test grids. It detected levels of TCDD in the range of less than 10 ppt (minimum detection level) to 1,500 ppt. The median concentration was 30 ppt, while the mean was 165 ppt. In an October 1978 report, the Air Force attributed the wide fluctuation in TCDD concentrations to the locations of the actual flight paths on the test grid. The Air Force also said that it was apparent that the herbicides applied during 1962 to 1964 contained very high levels of the TCDD contaminant. The Air Force, in its October 1978 report, noted that its ecological survey documented the presence of more than 123 different plant species, 77 bird species, 71 insect families, 20 fish species, 18 reptile species, 18 mammal species, 12 amphibian species, and 2 mollusk species. At least 170 biological samples were analyzed for TCDD, including 30 species of animals. No TCDD was found of the plant species examined. However, TCDD was found in nine species of animals including two rodent species: beachmice (300 to 1,500 ppt, liver) and hispid cotton rat (less than 10 to 210 ppt, liver); three species of birds: meadowlark (100 to 1,020 ppt, liver) mourning dove (50 ppt, liver) and Savannah sparrows (69 ppt, liver); three species of fish: spotted sunfish (85 ppt, liver), mosquito fish (12 ppt, whole body), and sailfin shiner (12 ppt, whole body); and one reptile, the six-lined racerunner (360-430 ppt, muscle). �Other studies 1. Samples of fish, crustaceans, and human milk from areas of South Vietnam heavily treated with 2,4,5-T in the military herbicide program were analyzed for TCDD. Unconfirmed levels of is to 810 ppt in fish and crustaceans and 40 to 50 ppt in human milk were found in samples collected in 1970 shortly after large scale use of Herbicide Orange was ordered discontinued. (Reported by Dr. Robert Baughman and Matthew Meselson, Harvard University, 1973 and 1975. ) 2. Thin layers of Herbicide Orange containing 15 parts per million of TCDD were exposed to California summer sunlight in glass petri dishes. Identical treatments, masked from sunlight, served as dark controls. Loss of the TCDD was rapid in sunlight, and less than half remained after 6 hours. Herbicide Orange also was applied evenly in droplets over leaves of a rubber plant and on the surface of loam soil and exposed to sunlight. TCDD was lost even more rapidly from the leaf surface than from glass while loss from soil was slower. According to the authors, their measurements indicated sunlight is the principal factor in TCDD disappearance from inert surfaces, plants, and soils treated with TCDDcontaminated pesticides. They also stated that in every experiment, light caused the TCDD content to decline sharply, while dark controls remained virtually unaffected. The authors concluded that there were three requirements for significant TCDD breakdown: dissolution in a light transmitting film; the presence of an organic hydrogen-donor such as solvent or pesticide; and ultraviolet light. According to the authors, all three conditions normally should have been met consistently during the practical application of 2,4,5-T and, consequently, their data ( �suggests environmental residues of TCDD often will be considerably less than previously expected (Donald G. Crosby and Anthony S. Wong, University of California, Davis, 1976). 3. A 1977 study of the distribution, persistence, and mobility of TCDD found that once TCDD volatilized, it degraded in direct sunlight and apparently even in shade outdoors. However, the researchers did not find as rapid degradation on grass as Crosby found on excised leaves. In addition, they found that TCDD degradation in air was considerable but not as great as Crosby's data suggested. (Ralph G. Nash and M. Leroy Beall, Jr., 1977.) Other chemicals used in South Vietnam A Defense official said that malathion and DDT were the other principal pesticides used in Vietnam; they were used throughout the war for mosquito control. Malathion was sprayed by aircraft, and DDT was applied by backpack and paint brush. Defense stated that ground forces were routinely exposed to aerially applied insecticides such as malithion and could have confused this with direct exposure to herbicides. An official said that no information is readily available on the quantities used in Vietnam. Malathion is still used domestically for insect control. However, in 1972 EPA canceled all except public health and quarantine uses of DDT because of its persistence, biomagnification, and toxicological effects. PERSONNEL EXPOSURE TO HERBICIDES A Defense report shows that about 2.6 million military personnel served in South Vietnam from January 1, 1965, to March 31, 1973. Defense records indicate that the number of U.S. civilian personnel employed by Defense in South Vietnam ranged from 49 in March 1965 to 1,522 in September 1969 —cumulative data on civilians is not readily available. Defense has little information, however, on the number of personnel exposed to herbicides in Vietnam. Defense officials stated that (1) no such personnel records were maintained, (2) it would be difficult to estimate meaningful exposure data because the potential for exposure �varied widely among personnel, and (3) only a few military personnel would have been exposed directly to spraying. Some personnel could have been exposed indirectly to low levels of herbicides through ingestion of contaminated drinking water and food and by skin contact. However, Defense stated that indirect exposure through ingestion of food and water was unlikely because subsistence was not generally obtained from local sources. According to Defense, military personnel did not enter areas treated with Herbicide Orange in most instances until 4 to 6 weeks after treatment, thereby greatly minimizing their chances of contacting or inhaling the herbicide. Personnel involved in actual "dedrumming" of the herbicides and spraying missions (particularly crewchiefs and flight mechanics) were more likely to have been exposed than others. Defense has identified about 500 aircraft crew members involved in herbicide missions. CURRENT CONCERNS OVER EFFECTS OF 2,4,5-T and TCDD Extensive adverse health in March 1978, special report media coverage has been given to purported effects of 2,4,5-T and TCDD. For example, a CBS-owned affiliate in Chicago aired a on Herbicide Orange. In late 1977 veterans started making inquiries of the Chicago VA regional office on the possible effects of herbicide exposure. Some filed claims for VA compensation alleging that their medical problems were caused by herbicide exposure in Vietnam. As of September 1978 veterans had filed an estimated 450 claims nationwide, including about 255 at the VA regional office in Chicago. In an April 12, 1978, news release EPA, which has the responsibility for regulating such pesticides as 2,4,5-T, said that about 450 letters had been received from citizens and environmental groups protesting the domestic use of 2,4,5-T. The herbicide 2,4,5-T was used domestically for brush control on livestock grazing land, on right-of-way areas and in forests, and for weed control in rice. Use of 2,4,5-T is prohibited around homes; recreational sites and aquatic areas; and in crops, except rice, used for human consumption. In a Federal Register notice dated April 21, 1978, EPA announced that it was reevaluating the registered uses of pesticides containing 2,4,5-T (43 FR 17116, et seq.). �EPA stated in its announcement that 2,4,5-T and/or its contaminant, TCDD, exceed the risk criteria for oncogenicity (the quality of being able to cause tumor formation) and for teratogenic (causing congenital malformations) and/or fetotoxic (causing harm to fetus) effects as set forth in its regulations. The announcement invited interested parties to submit rebuttals and other information on the findings and to submit any other data on the risks and benefits of this pesticide chemical. On March 1, 1979, EPA announced emergency action to halt the spraying of 2,4,5-T on forests, pastures, and rights-ofway because of new information indicating its potential link to human miscarriages. This emergency suspension action is similar to a temporary restraining order issued by a court. This action reflects EPA's belief that there is sufficient evidence to stop further exposure to 2,4,5-T until health questions can be resolved. �CHAPTER 2 FEDERAL RESPONSE TO HERBICIDE CONCERNS OP VIETNAM VETERANS VA began receiving herbicide-related compensation claims in late 1977. As of October 1978 VA has allowed no compensation claims solely on the basis of herbicide exposure in Vietnam. However, one veteran did receive benefits for a skin condition existing inservice which VA believes may have been related to herbicide exposure. Actions to resolve individual herbicide claims and develop overall policy have been hampered by inconclusive information on the long-term health effects of herbicides and problems in identifying the veterans exposed to chemicals during military service. These medical and exposure uncertainties have made it difficult for VA to define the relationship between chemical exposure in Vietnam and health problems currently experienced by veterans. SCOPE AND CHARACTERISTICS OF VETERANS' CONCERNS Fifty-eight VA regional offices are responsible for receiving and adjudicating service-connected compensation claims. As of September 1978 an estimated 450 herbiciderelated compensation claims had been filed at regional offices within the contiguous United States. Over half of these claims (about 255) originated in the Chicago regional office. The Mew York and Seattle regional offices received the second largest number of claims—about 18 each. We reviewed about 120 of the herbicide-related cases at the Chicago regional office to determine the types of illnesses veterans are associating with herbicide exposure. The most commonly indicated concerns are categorized below as a percentage of total cases reviewed: �Illness Percent Skin conditions Fatigue and/or nervousness Numbness of extremities Vision and/or hearing impairment Birth defects in offspring Reduced libido 50 32 28 17 13 13 Less frequently cited concerns included miscarriages by spouse, impotency, respiratory problems, and gastrointestinal problems. In addition, about six cases associated cancer with herbicide exposure. In about 10 percent of the cases, no specific concerns could be identified. In addition to filing compensation claims at regional offices, veterans have also contacted VA hospitals or other VA health care facilities. As of September 1978 about 600 veterans had been examined by VA health care facilities concerning herbicide exposure. Of the 172 VA hospitals, Mines Hospital in Chicago, Illinois, examined the most veterans—84. Martinez (California) and Chicago Westside examined the second and third highest number—54 and 47, respectively. Officials at Hines Hospital told us that a large number of veterans contacting them about herbicide exposure were concerned about rashes, others were concerned about nervousness, and some said they were experiencing numbness. In addition, some veterans had no specific illness but were interested only in obtaining information on the possible ill effects of herbicide exposure. VA ACTIONS ON THE HERBICIDE ISSUE In response to concerns about herbicide exposure, VA has issued guidelines for its health care facilities and regional offices, initiated internal studies, and established various working groups to study herbicide related illnesses and formulate policy. However, VA action to resolve individual compensation claims and develop overall policy have been hampered by a lack of information in several areas. For example, VA officials stated that little data is available on what the long term health effects are of Herbicide Orange. Another official pointed out that some of the health problems associated with herbicide exposure, such as fatigue, are not unique enough to diagnose the problem's cause. Because of 10 �the medical uncertainties, it becomes difficult for VA to associate current illnesses with herbicide exposure in Vietnam. VA guidance to regional offices and health care facilities reflects these uncertainties and acknowledges that currently the only chronic illness known to be caused by herbicide exposure is a skin condition called chloracne. As with health effects information, little data is available to identify personnel exposed to herbicides in Vietnam. VA has been unable to find specific reference to herbicide exposure in individual military service records. As an alternative, VA is attempting to obtain information on the possibility of an individual veteran's exposure to herbicides in Vietnam. In a September 18, 1978, letter to the Department of Defense, VA requested complete maps of herbicide missions, dates they were carried out, units spraying the herbicides, and units in sprayed area at the time of the mission or entering afterwards. As a result of this request, Defense agreed to provide VA with the names of aircraft crew members involved in herbicide operations, and computer printouts and maps of the spraying missions in South Vietnam. As of October 1978 VA had evaluated about 90 compensation claims for herbicide exposure and awarded benefits in about 8 cases. However, only one of these awards, a service-connected skin condition, was linked to possible herbicide exposure. The remaining claims were awarded for reasons not related to herbicide exposure. Instructions to VA health care facilities Principal guidance for VA hospitals and other health care facilities is contained in a May 1978 teletype and September 1978 circular. VA's general policy is to examine and treat all veterans claiming toxic effects from exposure to herbicides during the Vietnam War. In addition, all veterans who are currently being treated in VA facilities or who apply for care will be asked if they have been exposed to herbicides or other chemicals in Vietnam. These instructions also provide guidance for developing record keeping systems and submitting quarterly reports to VA headquarters. In examining veterans concerned about herbicide exposure, health care facilities have been instructed to pay particular attention to the kidneys, liver, thyroid, 11 �adrenals, gonads, skin, lungs, nervous system, blood-forming system, and immune system. In addition, medical histories are to include information on possible reduced libido, frequent abortions, sterility, congenital deformities among children, neoplasia, chloracne, and repeated infections. The health facilities also will solicit information on the time, place, and extent of possible exposure to chemicals regardless of when it took place. This and other information will be used in a data base being compiled on possible effects of herbicide exposure. VA has also arranged for the Armed Forces Institute of Pathology to receive and store specimens removed at VA medical centers from Vietnam veterans possibly exposed to herbicides. Instructions to VA regional offices In an April 1978 directive, VA instructed its regional offices to evaluate herbicide-related claims in the same manner as other claims for service-connected compensation. In general, disabilities can be service-connected for either immediate or delayed effects that are shown to be a direct result of incurrence while in service. Under current procedures, a herbicide-related compensation claim can be administratively denied for two reasons. One is if the veteran does not claim a disability but is only concerned with possible exposure to herbicides. The second is if a veteran claims genetic damage which VA states is not provided for under the law. VA regional offices have been instructed to send copies of completed ratings of herbicide-related claims to headquarters for review. In addition, regional offices have been instructed to request information from a veteran's service record to verify herbicide exposure. However, service records normally do not contain specific information on chemical exposure. As a result, responses to such requests are neither verified nor denied by military service records' personnel. Currently, VA regional offices have not been instructed to obtain other information from military records which may assist in determining the possibility of exposure to herbicides (e.g. occupational specialty, duties performed, unit, locations, and dates while in Vietnam). 12 �There are no special instructions to regional offices regarding if and when a veteran submitting a herbiciderelated claim should be referred to a VA health care facility. About 33 percent o.f the 50 final ratings we reviewed had no indication of a recent VA physical examination. VA herbicide committees' activities and internal studies The VA has formed three committees to deal with scientific and policy questions related to the herbicide issue. Policy guidance has been provided by an in-house steering committee which first met in June 1978. Assisting them is an interagency group known as the Interagency Committee on Herbicides. It functions as a factfinding, advisory group and was developed to explore: —the potential adverse health effects of defoliants on Vietnam veterans, including symptoms associated with these effects, —methods for diagnosing and treating the adverse health effects of defoliants, and —approaches through which the VA might discover the prevalence of adverse effects of defoliants used in Vietnam on its patient population. VA has requested that an advisory committee composed of Federal and non-Federal members be formally chartered. The interagency committee will be absorbed by the new advisory committee if approval is granted for its establishment. As of January 1979 the group had not been formally chartered. In October 1978 VA established a third committee to evaluate herbicide cases received by VA health care facilities. The committee is composed of specialists in various disciplines, such as internal medicine, neurology, and psychiatry. This committee and the interagency committee report through the steering committee. In addition to committee activities, VA medical officials are reviewing past patient treatment files to determine if there is an increased cancer rate among Vietnam era veterans. As of f>eptember 1978 no conclusions have been 13 �drawn from this review. VA medical officials also plan to examine past records of compensation claims for skin conditions to determine if they may have been related to herbicide exposure in Vietnam. VA also is sponsoring a study to determine if dioxin levels in 10 Vietnam veterans possibly exposed to herbicides are higher than levels found in personnel who were not exposed. This study is not expected to be completed before September 1979. DEFENSE INVOLVEMENT IN THE HERBICIDE ISSUE In October 1978 Defense testified before the Veterans' Affairs Committee of the House of Representatives that there was little or no relationship between many alleged symptoms and past exposure to Herbicide Orange in Vietnam. Its testimony was based on a recent review of the use of herbicides in Vietnam and scientific literature pertaining to the toxicological effects of these herbicides. The results of its review were published in an October 1978 Air Force report entitled "The Toxicology, Environmental Fate, and Human Risk of Herbicide Orange and Its Associated Dioxin." Defense has, however, offered assistance to VA and has representatives on the interagency committee. The Department of the Air Force is the only service to have developed any guidance for its medical facilities regarding the evaluation of military personnel who might be concerned about herbicide exposure. None of the services have monitoring systems for such personnel. As a result, the extent of concern related to possible herbicide exposure among active military personnel is unknown. CONCLUSIONS VA is dealing with a sensitive issue that is complicated by a number of medical uncertainties. It has taken steps toward resolving these questions through analyzing available research information and initiating new research. However, additional measures could be taken to provide VA with a better basis for evaluating the nature of herbicide concerns expressed by veterans. VA has not fully utilized information in military records to determine a veteran's possible exposure to herbicides in Vietnam. Although the records normally do not 14 �contain unequivocal verification of herbicide exposure, they do contain information that may reflect on the likelihood of exposure. However, VA regional offices have been instructed to obtain only verification of exposure from service records and not necessarily information on the likelihood of exposure. In view of the absence of unequivocal verification of herbicide exposure, we believe that VA regional offices should attempt to obtain all information from military records which may reflect on a veteran's likelihood of exposure to herbicides in Vietnam. In addition, under current VA policy, all veterans who contact VA health care facilities regarding possible health complications due to herbicide exposure will be examined, and the results will be included in a data base. However, veterans contacting regional offices in regard to compensation claims may or may not be referred to a VA health care facility. As a result, VA physical examination and inclusion in the data base are partially dependent on whether the veteran contacts a regional office or a health care facility. Similar to VA health care facilities, Defense medical facilities also may be receiving contacts from military personnel concerned about exposure to herbicides in Vietnam. However, there is no system to determine the extent of these contacts. In addition, the Department of the Air Force is the only service to have developed any guidance for its hospitals concerning herbicide related matters. We believe that the medical facilities in all services should receive appropriate guidance, including monitoring instructions for possible herbicide related cases. RECOMMENDATIONS We recommend that the Administrator of Veterans Affairs provide guidance to assure that — in evaluating herbicide related claims, regional offices obtain all military record information pertaining to a veteran's possible exposure to herbicides in Vietnam and —all veterans submitting such claims to VA regional offices are encouraged to contact VA health care facilities. 15 �We also recommend that the Secretary of Defense provide guidance to ensure that Air Force, Army, and Navy medical facilities are uniformly monitoring and evaluating possible herbicide-related concerns of personnel who served in Vietnam. In addition, information developed through Defense medical facilities should be coordinated with VA. AGENCY COMMENTS VA agreed that regional offices should obtain all military record information concerning possible exposure to herbicides in Vietnam. It also agreed that veterans submitting claims of possible herbicide exposure should be encouraged to contact VA health care facilities. Defense generally agreed with the recommendation to provide guidance to all DOD medical facilities. 16 �CHAPTER 3 HEALTH EFFECTS STUDIES. OF TCDD The toxic effects of TCDD have been reported by investigators of chronic occupational exposure in the manufacture of chemicals contaminated by TCDD and acute expo-sure in industrial accidents. Also, many studies of the effects of TCDD have been conducted on animals. The long-range health effects on humans, however, remains largely unknown. TOXIC EFFECTS OF TCDD IN HUMANS In an August 1977 publication, \J the International Agency for Research on Cancer (IARC) of the World Health Organization noted that toxic effects in humans caused by TCDD have been reported after (1) occupational exposure during the industrial production of 2,4,5-trichlorophenol (the precursor of 2,4,5-T) and 2,4,5-T, (2) exposure during accidents at such facilities, and (3) exposure to herbicides and other materials containing TCDD. The exposed individuals developed a wide variety of dermatological, internal, neurological, and psychiatric disorders. The dermatological disorders include: —Chloracne which is probably the best known toxic effect of TCDD. Chloracne has been described by a medical authority 2/ as an eruption of blackheads, usually accompanied by small yellow cysts which, in all but the worst cases, are from pinhead to lentil size. 3/ Mild.cases of Chloracne reportedly clear within months, and after 3 years all but 20 percent of cases are likely to have resolved themselves. The most severe cases, V"IARC Monographs On The Evaluation Of The Carcinogenic Risk Of Chemicals To Man," Vol. 15. 2/Dr. Kenneth Crow, "Chloracne: the chemical disease," New Scientist, Apr. 13, 1978, p. 78. 3/Lentil seeds are about 4 to 6 millimeters in diameter. 17 �however, may still have active skin lesions 15 years after contact with the causative agent has ceased. Chloracne is considered a sign of potential systemic poisoning and an indication of exposure to TCDD or some other chloracnigen. —Porphyria cutanea tarda which is characterized by photosensitivity, skin lesions, and hepatic (liver) dysfunction. —Hyperpigmentation and hirsutism (abnormal hairiness). The internal disorders include: —Liver damage. —Fat metabolism disorders. —Carbohydrate metabolism disorders. —Cardiovascular disorders. —Urinary tract disorders, —Respiratory disorders. —Pancreatic disorders. The neurological disorders include: —Polyneuropathies which are diseases involving several nerves. —Lower extremity weakness. —Sensorial impairments (sight, hearing, smell, and taste). The psychiatric disorders include: —Neurasthenic or depressive syndromes; the neurasthenia was reported to be characterized by altered basic frame of mind, lack of drive and vigor, sleep disorders, emotional instability, such as a tendency to anger or irritability, and diminished libido or potency. 18 �Defense evaluation of Herbicide Orange hunan health effects In its 1978 report, I/ the Air Force reviewed literature involving exposure to 2,4-D, 2,4,5-T, and TCDD. In summary it stated: "The pharmacodynamics and adverse effects of the . phenoxy herbicides, trichlorophenol and TCDD were reviewed, primarily through reports of occupational exposure and accidents as well as reported exposures to the general public. A number of organ systems may be involved if the dose is significantly high with emphasis on the skin, liver, CNS and peripheral nervous system. Adverse effects of 2,4-D and 2,4,5-T should manifest themselves shortly after exposure. Symptoms arising for the first time months to years after the last exposure are probably due to an etiology other than 2,4-D and 2,4,5-T. The hallmark of TCDD is chloracne and its absence makes it unlikely that systemic disorders present are related to TCDD. Asthenic and vegetative symptoms are often present in overexposure but are difficult to interpret. They would normally be expected to clear .with time. There is no conclusive evidence at this time that the phenoxy herbicides or TCDD are mutagenic, teratogenic or carcinogenic in man." National Academy of Sciences study in South Vietnam In a study of the ecological and physiological effects of the military use of herbicides in South Vietnam, NAS reported 2/ in 1974 that its study committee was unable to gather definitive indication of direct damage by herbicides to human health. NAS noted, however, that reports of Highlanders (Montagnards) on death and illness—abdominal pains, diarrhea, vomiting, respiratory symptoms, and rashes—caused by herbicides were so consistent that, despite the lack of medical and toxicological evidence for such effects they could not be dismissed and should be followed as promptly as l/"The Toxicology, Environmental Fate and Human Risk of Herbicide Orange and its Associated Dioxin." Oct. 1978 2/"The Effects of Herbicides in South Vietnam." 19 �possible by intensive studies which should include medical and behavioral sciences approaches. They recognized, however, that such studies would become possible only after peace had been restored in that area. TOXIC EFFECTS OF TCDD IN ANIMALS TCDD has produced a variety of toxic effects in laboratory animals. However, the results of studies on the mutagencity of TCDD have been conflicting and inconclusive. In addition, Air Force studies of mice gathered from an area previously sprayed with massive amounts of 2,4,5-T have indicated that although the mice accumulated TCDD in their livers, they apparently suffered no significant adverse health effects. In its 1974 report, "The Effects of Herbicides in South Vietnam," NAS summarized the clinical signs of TCDD poisoning as follows: H* * * effects include necrotic I/ changes of the liver; gastric hyperplasia 2/ or ulceration; hemorrhages in the gastrointestinal tract and various other organs; atrophy of the kidneys; and atrophy of the thymus and other lymphoid organs and tissues. * * * [These] changes appear to be the most commonly observed ones and may lead to reduced immunoresponses and thus a decrease in the animal's chemical defense mechanism. But whether any of the above changes are related to the primary toxic action of TCDD is not clear." The authors did not specify whether these were acute or chronic effects. The NAS also noted in its 1974 report that the teratogenicity 3/ of TCDD in mice is well established, although in rhesus monkeys no teratological effects had yet been found. ^/Pertaining to the death or decay of tissue. 2/The abnormal increase of normal cells in the stomach. agent or chemical is considered as teratogenic when it causes developmental disturbances in the enbryo resulting in congenital malformations. 20 �In its 1978 report, the Air Force stated: "Subacute and chronic doses of TCDD produced a variety of toxic effects, including hepatic necrosis in mice, rats and rabbits; thymic atrophy in mice, rats and guinea piqs with adrenal gland hemorrhages and depletion of lymphoid organs -also being seen in guinea pigs. Repeated oral doses of 0.001-to 10 yg/kg TCDD for four to 13 weeks did not significantly affect weight gain nor were signs of toxicity noted in mice and rats. Suppressed immune responses and changes in liver enzymes were noted, however, in mice. Repeated doses of TCDD as low as 1 yg/kg caused guinea pigs to become moribund and repeated doses of 0.04 yg/kg decreased lymphocyte counts. Rabbits developed acne of increasing severity when doses of 0.04 to 400 yg/kg were applied repeatedly to the internal surface of the ear. A total oral dose of 2-3 yg/kg over a nine month period produced severe hematological changes and death in rhesus monkeys." EPA's 2,4,5-T working group concluded that there is sufficient evidence to indicate that 2,4,5-Tf containing TCDD at levels as low as 0.05 parts per million, and TCDD alone can produce oncogenic I/ effects in mamallian species (43 FR 17128, Apr. 21, 1978). The working group supported its conclusion with summaries of several studies. For example: —A 95-week feeding study was conducted with male rats. Ten groups of 10 animals per group were fed ground food containing 0, 1, 5, 50, or 500 ppt TCDD, or 1, 5, 50, 500, or 1,000 parts per billion (ppb) TCDD. All rats receiving the three highest dose levels (50, 500, or 1,000 ppb TCDD) died between the 2d and 4th week of treatment. Tumors developed in 46 percent (23/50) of the rats ingesting 5, 50, or 500 ppt and 1 or 5 ppb TCDD compared to none in the control group or the group fed 1 ppt TCDD; carcinomas (cancerous growths) were observed in the ear duct, kidney, and liver. Also, neoplasms (any new or abnormal growth) were observed in 38 percent (23/60) of the six lowest dose groups compared with none in the control group. I/Giving rise to tumors or causing tumor formation. 21 �—In another study, fenale rhesus monkeys were fed diets containing 500 ppt TCDD for 9 months. Anemia, thrombocytopenia (decrease in the number of blood platelets), and leukopenia (reduction in the number of leukocytes _!/ in the blood) were the most debilitating changes. The altered lymphopoiesis (development of lymphatic tissue) could be associated with immune suppression. The authors reported widespread hypertrophy (enlargement or overgrowth of an organ), hyperplasia (abnormal increase in the number of normal cells in normal arrangement in a tissue), and metaplasia (abnormal change in the type of adult cells in a tissue) in the epithelium (the covering of internal and external surfaces of the body) of monkeys exposed to TCDD, and related this to data showing increased tumor frequency in TCDD-fed rats. Potential mutagenicity of TCDD has not been determined The mutagenicity of a pesticide is one of the hazards which EPA evaluates in determining whether a pesticide can be handled and used safely and whether the public is protected from injury. Although several studies have been conducted, the results have been conflicting and inconclusive. Mutagenicity studies are designed to determine if a substance causes mutations. A mutation is any heritable change, such as a chemical transformation of an individual gene which may alter its functions, or a rearrangement of the structure of or a gain or loss of parts of a chromosome. Mutations may cause abortion, genetic disease, shorter life span, infertility, mental retardation, senility, and cancer. EPA's 2,4,5-T working group concluded on the basis of a review of available studies "that there is a data gap on mutagenic effects and that further evidence and testing is needed on the mutagenicity of 2,4,5-T and TCDD." A study entitled "A Review of the Genetic Toxicology of Chlorinated Dibenzo-p-Dioxins" sponsored in part by the National Institute of Environmental Health Sciences (NIEHS) _l/Small colorless cells which are important in the body's defense against infection. 22 �reached the same conclusion as EPA's 2,4,5-T working group. The February 1978 study report stated that: "Data available for assessing the rautagenic potential of TCDD are conflicting and scarce. Differences in testing results reported in these studies could be attributed to solubility problems with the test chemical, treatment • protocols, purity of test samples, or toxicity. Because there are conflicting data, additional experiments are needed before the mutagenic potential of TCDD and other dioxins can be determined. Studies exploring the promoting effect of dioxins on the mutagenicity of other compounds are also recommended because experiments have shown TCDD to be an extremely active liver enzyme inducing agent that enhances the mutagenicity of certain polycyclic hydrocarbons such as 3-methylcholanthrene in vitro." Air Force study at Eglin Air Force Base Reservation in Florida From 1962 to 1970 the Air Force sprayed 346,117 pounds of herbicides (including 160,948 pounds of 2,4,5-T) on a 1 square mile test area at the Eglin Air Force Base Reservation to test aerial spray equipment. Subsequently, the Department of Chemistry and Biological Sciences, U.S. Air Force Academy, initiated studies on Herbicide Orange and TCDD in 1972 to (1) investigate soil incorporation/biodegradation as a disposal method for Herbicide Orange, (2) investigate the ecological effects associated with past uses of Herbicide Orange, and (3) investigate the soil persistence and food chain accumulation of TCDD. In an October 1978 presentation to the American Society for Testing Materials, Air Force officials reported on the results of field investigations at the Eglin Air Force Base test area. They reported no evidence that the herbicides produced any adverse, long-term health effects in the field species examined. Specifically, they reported that: "Gross pathology was done on all species collected for TCDD residue analyses. Histopathological JL/ I/Pertaining to the study of changes in tissues caused by disease. 23 �examinations were performed on over 300 beachnice or hispid cotton rats from the test area and a control field site. Examinations were performed on the heart, lungs, trachea, salivary glands, thymus, liver, kidneys, stomach, pancreas, adrenals, large and small intestine, spleen, genital organs, bone, bone marrow, skin and brain. Initially, the tissues were examined on a random basis without the knowledge of whether the animal was from a control or test area. All microscopic changes were recorded including those interpreted as minor or insignificant. The tissues were then reexamined on a control and test basis, which demonstrated that the test and control mice could not be distinguished histopathologically. Similar histopathological studies were conducted on the fish and racerunner, and again no significant abnormalities were found." LONG-RANGE HEALTH EFFECTS OF TCDD ON HUMANS HAVE NOT BEEN DETERMINED Although TCDD is one of the most toxic compounds known, the long-term human health effects of TCDD exposure are virtually unknown. IARC concluded in its 1977 publication (see p. 17) that insufficient data is available to evaluate the carcinogenicity of 2,4,5-T and TCDD to man. IARC stated, with respect to TCDD: "A number of cases of cancer have been reported in workers exposed to TCDD, but no adequate epidemiological studies were available. An increased proportion of liver cancers has been reported in Hanoi, after the spraying of herbicides (2,4-D and 2,4,5-T) containing TCDD in South Vietnam. The significance of these observations cannot be assessed because not enough details were reported. More details of the reported cases and more extensive observation of the exposed people are needed before an evaluation of the carcinogenicity of chlorinated dibenzodioxins to man can be made." The authors of the NIEHS-sponsored study (see p. 22) observed that the importance of understanding the hazards to human health from dioxin compounds, including TCDD, and 24 �the insufficient data available to properly evaluate their long-term health risks have generated several research projects. In January 1978 a joint NIEHS/IARC ad hoc working group was convened to consider the feasibility of coordinating epidemiological studies on the long-term health hazards associated with dioxin compounds and certain other structurally related compounds. The working group noted in a June 1978 report I/ that a need had become clear for (1) better coordination of ongoing and projected epidemiological efforts and (2) a worldwide action plan for harmonizing the various activities already in progress or in preparatory stages. The NIEHS/IARC working group included in its report comments and recommendations concerning followup of accidentexposed individuals in five countries. The working group also recommended —Development of a system for an international exchange of information and research coordination on the health effects of dioxins and other structurally related compounds. —Development of common protocols (plans) for clinical examinations and, in particular, design of a protocol for basic core information. —Development of an international registry of exposed persons to serve as a basis for longterm followup. This was considered especially important because the relatively small size populations involved in individual exposure episodes are an obstacle to risk assessment. Therefore, pooling of data is almost a necessity. In its 1978 report, the Air Force stated that "The long-term effects of large acute doses of TCDD or small intermittent or chronic exposures are not known." l/"Long-Term Hazards of Polychlorinated Dibenzodioxins and Polychlorinated Dibenzofurans" 25 �Need for study of health risks to herbicideexposed personnel in South Vietnam Because of (1) the very high toxicity of dioxin to animals, (2) the presence of this substance in Herbicide Orange, (3) preliminary reports of TCDD in fish in Vietnam, and (4) the lack of data permitting assessment of TCDD effects on humans, NAS recommended in its 1974 report on "The Effects of Herbicides in South Vietnam" that long-term studies be made for assessing the potential harmful effects of TCDD on man. Among other specific recommendations, NAS strongly urged a comprehensive medical study of the approximately 50 Vietnamese military personnel who were heavily exposed as handlers of herbicides in the defoliation program, if they could be located, as compared with an appropriate "control" group. The authors noted that this group of personnel, which was identified near the end of the studies in South Vietnam, had been handling herbicides—transferring them from the containers in which they arrived, to other containers and to the aircraft—for many years and therefore appeared to represent a population uniquely suited for studies of any long-term medical effects. We believe that the proposed study of the Vietnamese herbicide handlers could have provided important data on the potential long-term medical effects on personnel exposed to Herbicide Orange. Since such a study could not be done because of U.S. withdrawal from Vietnam, however, we believe a survey of military personnel identified as most likely to have been exposed to herbicides, might also provide data on any long-term medical effects. This survey could be performed by trying to locate those personnel most likely to have been exposed to herbicides and taking a medical history of these individuals since the time of exposure in an effort to ascertain whether this history reveals evidence of disease that could be related to herbicide exposure. Such a survey is needed because: —Data is lacking on any long-term medical effects of Herbicide Orange and TCDD. Without such information, VA action to deal with concern over herbicide exposure .is handicapped. 26 �—The survey could provide data related to the effects of exposure to Herb'icide Orange and other chemicals as used in South Vietnam. Any data developed by investigations of 2,4,5-T as currently manufactured and used in the United States would not necessarily be applicable to the use of Herbicide Orange in South Vietnam because of differences in the contaminant levels. —The continuing public and veterans' concerns over the alleged health risks attributed to herbicides need to be resolved. As noted on page 7, Defense has identified about 500 aircraft crew members involved in herbicide spraying missions. If it is determined that these crew members were the personnel most likely to have been exposed to herbicides they could serve as the nucleus of a systematic followup survey. We believe that Defense should conduct such a survey with the assistance and guidance of an interagency group composed of knowledgeable representatives from interested agencies, such as Department of Health, Education, and Welfare; VA; and EPA. An effective interagency group could provide the expertise needed to help insure that the survey is properly planned and carried out and could serve to minimize possible criticism of the findings and conclusions. RECOMMENDATION TO THE SECRETARY OF DEFENSE The Department of Defense, with the assistance and guidance of an appropriate interagency group, should conduct a survey of any long-term medical effects on military personnel who were likely to have been exposed to herbicides in South Vietnam. Agency Comments and Our Evaluation Defense doubted that a retrospective epidemiological study would produce reliable results because (1) 17 years had elapsed from the beginning of herbicide operations in Vietnam, during which time any number of other influences on health could have taken place, (2) generally, there is no data on exposure concentrations and times, and (3) identifying an appropriate control group would be virtually impossible. Defense said, however, that a study of an 27 �appropriate group would be valuable to determine the longterm health effects of TCDD. In this regard, it pointed out that it was supporting an NAS study being developed to assist in determining the health effects of the release of large amounts of TCDD into the environment from an industrial accident in Seveso, Italy. We agree that there would be limitations on a study of Vietnam veterans and that the Seveso accident might provide more scientifically valid study results. However, we believe that it would be desirable to obtain information specifically related to the herbicides as used in Vietnam because the results of the Seveso study may not be entirely applicable to Vietnam. For example, scientists told us that the toxicological effects of the same chemical may vary due to (1) environmental/climatic differences, (2) differences in the degree and duration of exposure, and (3) interaction with other chemicals. Although a study of Vietnam may have limitations in terms of scientifically associating specific health effects with individual chemicals, it could provide information on the general health of those most likely to have been affected by herbicides. This, in turn, would help provide an indication of general problems, if any, that may be related to the herbicides as used in Vietnam. We believe that this information would be valuable to VA and others concerned with determining if there is a basic health problem among personnel who served in Vietnam. 28 �APPENDIX I APPENDIX I THE MILITARY USE OF HERBICIDES IN SOUTH VIETNAM I/ Military herbicide operations began in South Vietnam in early 1962 and were phased out in 1971. After a relatively slow buildup from 1962 to 1965, the operations increased rapidly to a peak in 1967; declined, but only slightly, in 1968 and 1969; and dropped sharply in 1970. According to information from Defense, the last herbicide spraying by fixed-wing aircraft occurred on January 7, 1971. After this, herbicide operations were limited to spraying around fire base perimeters, on enemy cache sites, and along land and water communication routes; all were carried out by helicopter or on the ground. The last helicopter spraying operation under U.S. control was flown on October 31, 1971. THE HERBICIDAL AGENTS USED The herbicidal agents used in South Vietnam were identified by code names that referred to the color of bands painted on the containers of the chemicals: Orange, White, Blue, and Purple. Agent Orange is a 50:50 mixture of the n-butyl esters of 2,4-D ([2,4-dichlorophenoxy] acetic acid) and 2,4,5-T ([2,4,5-trichlorophenoxy] acetic acid). Each gallon of Orange contains 4 pounds of 2,4-D and 4.6 pounds of 2,4,5-T on an acid equivalent basis. 2/ Agent Orange was used most extensively in Vietnam until its use was terminated on April 15, 1970, because of concerns of its possible teratogenicity and its contamination with the highly toxic TCDD. I/Information excerpted from "The Effects of Herbicides in South Vietnam," NAS, Feb. 1974. 2/Acid equivalent is the weight of the acid form of the chemical. This is used because the weights of various ester or amine formulations vary. Expression in terms of acid equivalents provides a uniform basis for comparison of different formulations. 29 �APPENDIX I APPENDIX I Agent Purple is a 50:30:20 mixture of the n-butyl ester of 2,4-D, and n-butyl and isobutyl esters of 2,4,5-T. It was used only until 1964 and was then replaced by Agent Orange. Agent White is a mixture containing 2 pounds of 2,4-D and 0.54 pounds of picloram (4-amino-3,5,6-trichloropicolinic acid) per gallon on an acid-equivalent basis. It is a formulated product containing 2,4-D and picloram as the triisopropanolamine salts, with the addition of surfactants and water. Agent Blue is formulated as the sodium salt of cacodylic acid (hydroxydimethylarsine oxide). It contains a minimum of 21-percent sodium cacodylate with additional free cacodylic acid for a total dimethylarsinic acid equivalent of not less than 26 percent on a weight basis, or 3.1 pounds of cacodylic acid and about 1.7 pounds of arsenic per gallon with 5-percent surfactant and 0.5-percent antifoam agent. All agents were for use at a rate of 3 gallons per acre (28 liters per hectare), except that in the earlier operations and on rare occasions thereafter only half of this dose was used. The herbicides were applied by fixed-wing aircraft (UC-123), helicopter (UH-1), from trucks, from riverboats, and from backpacks. Aircraft were outfitted with special spraying equipment consisting essentially of a container and a spray boom with nozzles. The container of the plane spray system had a 1,000-gallon capacity and normally flew at 150 feet with a delivery speed of 130 to 140 knots. The spray-on time of 3-1/2 to 4 minutes permitted approximately 950 gallons of herbicide to be distributed at the rate of 3 gallons per acre. The capacity of the helicopter spray system container was 200 gallons, but the helicopter could carry only 100 gallons because of weight limitations. Herbicide spraying from tanker trucks used 50-gallon or 100-gallon drums. Spraying by riverboats was done directly from the agents original 55-gallon drums; backpack sprayers had 3-gallon drums. The great majority of the herbicides were sprayed by plane—at least into the later part of 1970, from which time helicopter herbicide operations increased and gradually became the only aerial means of herbicide delivery. 30 �APPENDIX II APPENDIX II APPLICATION OF HERBICIDES IN THF VIETNAM WAR (note a) 1962 to July Aug1965 Dec. (note b) 1965 1966 1967 1968 1969 1970 1971 Total Agent •(millions of gallons)Orange White Blue - TOTAL 1.27 0.37 1.64 3.17 2.22 3.25 0.57 11.22 0.53 1.33 2.13 1.02 0.22 0.01 5.24 0.02 0.38 0.28 0.26 0.18 1.12 0.37 2.19 4.88 4.63 4.53 0.97 0.01 18.85 b/Detail by type of herbicide not available HERBICIDES USED IN SOUTH VIETNAM 1965 TO 1971 Active chemical Agent Military application Millions of gallpns to components rate (lb./acr«») used, Aug. 1965 1971 Orange 2,4-D 2,4,5-T 12.00 13.80 11.22 White 2,4-D Picloram 6.00 1.62 5.24 Cacodylic acid 9.30 1.12 Blue TOTAL 17.58 Source: "The Effects of Herbicides in South Vietnam," MAS, Feb. 1974. a/Defense statistics on herbicide use shown on p. 2 and MAS statistics on herbicide use differ because Defense used procurement records only while MAS used procurement records and estimates. 31 �APPENDIX III APPENDIX III ASSISTANT SECRETARY OF DEFENSE WASHINGTON. D. C. 20301 MANPOWER, RESERVE AFFAIRS AND LOGISTICS O ctTD 1070 OTLD W J Mr. Henry Eschwege Director, Community and Economic Development Division U. S. General Accounting Office (GAO) Washington, D. C. 20548 Dear Mr. Eschwege: This is in response to your letter of November 22, 1978, to the Secretary of Defense concerning a draft GAO proposed report entitled "Need to Determine Long-Term Health Effects of Exposure to the Herbicide Agent Orange in South Vietnam" (OSD Case #^992A) (Code 08766). The report is generally well written and comprehensive. We do recommend, however, that the enclosed comments be considered for accuracy and completeness. There also is a lack of recognition and inadequate attention to the very comprehensive Air Force report published in October 1978, OEHL TR-78-92, "The Toxicology, Environmental Fate and Human Risk of Herbicide Orange and its Associated Dioxin." This report was provided to the Subcommittee on Medical Facilities and Benefits of the Veterans Affairs Committee of the House of Representatives on October 11, 1978. The report supports the Department of Defense (DoD) position presented in testimony that there is little or no relationship between many alleged symptoms and past exposure to herbicide orange in Vietnam. We agree with the recommendation that the Secretary of Defense provide guidance to ensure that all DoD medical facilities are aware of possible herbicide orange health effects. We do not agree, however, with the recommendation that the DoD undertake a comprehensive interagency study of the long-term medical effects on military personnel who might have been exposed to herbicide orange in Vietnam. It is extremely doubtful that a retrospective epidemiological study of that population would produce reliable results because: • Approximately 17 years have elapsed since the beginning of herbicide operations in Vietnam. Djring this interim, any number of other 32 �APPENDIX III APPENDIX III Influences on health may have supervened. Thus, ft would be virtually Impossible to assure that the results of the study were not confounded by variables other than the variable of Interest, viz., herbicide orange exposure, • There are, generally, no data on exposure concentrations and exposure times. Lacking a reliable estimate of exposure, the interpretation of the results would be highly unreliable, and • Identifying an appropriate control group would be virtually impossible. For any group to serve as appropriate control, it would be necessary to show that these people were not exposed to herbicide orange, and that they have, essentially, the same shared influences on their health as those of the exposed group. The DoD believes, however, that an epidemiological study of an appropriate group would be valuable to determine the long-term human health effects of TCDD (dtoxin). Ideally such a study would require a population with known exposure conditions and a similar unexposed cohort for controls. We are, therefore, supporting the current effort of the National Academy of Science's Committee of Toxicology to develop a study team, comprised of knowledgeable technical personnel from all areas, to perform a cooperative study with the Italian government and universities to assess the health effects of the release of large amounts of TCDD into the environment from an industrial accident in Seveso, Italy. This will provide a comprehensive, real-time epidemiological study where known concentrations of TCDD were measured, known exposures are documented and prompt medical follow-up has been performed. It will provide a far better analysis of the effects of TCDD on humans (and animals) than the sort of retrospective study proposed in the GAO report. Sincerely, ~^x Richard DanzJ" ^ * Acting Principal Dep\fEy /ssistant Secretary of Defense (MRA&L) Enclosure GAO note; The enclosure to this letter was considered in the preparation of our final report but has not been included. 33 �APPENDIX IV APPENDIX IV VETERANS ADMINISTRATION OFFICE OF THE ADMINISTRATOR OF VETERANS AFFAIRS WASHINGTON, D.C. 20420 JANUARY 2 5 1979 Mr. Gregory J. Ahart Director, Human Resources Division U. S. General Accounting Office 441 G Street, NW Washington, DC 20548 Dear Mr. Ahart: We have reviewed the November 24, 1978 draft report, "Need to Determine Long-Term Health Effects of Exposure to the Herbicide Agent Orange in South Vietnam," which discusses the military herbicide operations in South Vietnam and Agent Orange, the most widely used herbicide. A component of Agent Orange contains a highly toxic contaminant, TCDD (Dioxin). Its use has caused great public concern. The report states the VA actions have been hampered by lack of information on the long-term health effects of herbicides, and VA is having difficulties identifying veterans who were exposed to herbicides in Vietnam. We offer our comments on the report and the recommendations /JSee GAO note 1, p. 36^7 (2) that veterans submitting claims to VA Regional Offices are encouraged to contact VA health care facilities, and (3) that regional offices obtain all military record information pertaining to a veteran's possible exposure to herbicides in Vietnam. The VA concurs in the recommendation that regional offices obtain all military record information pertaining to a veteran's possible exposure to herbicides in Vietnam. /See GAO note 1, p. 36_./ 34 �APPENDIX IV APPENDIX IV Mr. Gregory J. Ahart Director, Human Resources Division This Agency is attempting to obtain valid information on the long-term health effects of herbicides by examining all Vietnam veterans who claim exposure to herbicides and, with the aid of a central herbicide registry', follow them over a prolonged period of time. This effort should clarify many of the current uncertainties regarding the adverse health effect of herbicides. We concur in the recommendation that veterans submitting claims of possible herbicidal exposure be encouraged to contact VA health care facilities. Instructions to VA facilities are being revised to clarify the VA's policy of examining all veterans for toxicity if possible herbicidal exposure is indicated. This policy applies to all veterans whether or not they claim to have signs and symptoms resulting from such exposure. The study mentioned on page 11 of the report is a pilot study which will attempt to detect dioxin in human body fat. Ten veterans who were actual handlers of herbicides in Vietnam and therefore extensively exposed', will be studied to determine whether or not any unusual concentration of dioxin is found in the fat tissues of those exposed to herbicides as compared to 10 controls. If no differences are found between the two groups, the determination of dioxin levels in body fat will not be used as a diagnostic test. £See GAO note 1, p. 36/7 35 �APPENDIX IV APPENDIX IV Mr. Gregory J. Ahart Director, Human Resources Division /See GAO note 1 below_._/ Thank you for the opportunity to review this draft report. Sincerely. MAX CLELAND Administrator GAO notes: 1. Deleted material pertained to a matter contained in the draft report which has been changed or is not included in this report. 2. Page references in this appendix refer to our draft report and do not necessarily agree with this final report. 36 �APPENDIX V APPENDIX V UNITED STATES ENVIRONMENTAL PROTECTION AGENCY WASHINGTON, D.C. 20460 2 2 MAR 1979 OFFICE OF PLANNING AND MANAGEMENT Honorable Henry Eschwege Director, Community and Economic Development Division United States General Accounting Office Washington, D.C. 20548 Dear Mr. Eschwege: The Environmental Protection Agency (EPA) has reviewed the General Accounting Office (GAO) proposed report entitled "Need to Determine Long-Term Health Effects of Exposure to the Herbicide Agent Orange in South Vietnam." GAO makes a number of recommendations concerning the identification of veterans with adverse health effects resulting from exposure to herbicides in South Vietnam, and the evaluation of herbicide-related compensation claims received by the Veterans Administration (VA) . GAO also recommends that the Department of Defense, with the assistance and guidance of an interagency group which would include EPA, conduct a comprehensive study of any long-term medical effects on military personnel who were likely to have been exposed to Agent Orange in South Vietnam, as compared with an appropriate control group. It is the latter recommendation, which entails EPA's participation, that I would like to address. On March 1, 1979, Deputy Administrator Barbara Blum announced the emergency suspension of and the Agency's intention to cancel 2,4,5-T (a component of Agent Orange) for use in forests and on pastures and rights-of-way. The intensive review of the risks and benefits of 2,4,5-T initiated in April 1978 continues for uses not affected by the suspension such as rice paddies and rangeland uses. 37 �APPENDIX V APPENDS V Agent Orange per se was never registered or used in the United States, though its components and other similar herbicides were. However, the use pattern of Agent Orange in Vietnam differed from the use authorized for its component herbicides in the United States. Further, the level of dioxin contamination in Agent Orange was much higher than the levels of dioxin found in domestically registered phenoxy herbicides. Therefore, we are not sure how meaningful the proposed study would be to our rebuttable presumption against registration (RPAR) review, for rice and rangeland, or to consideration of the risks and benefits of 2,4,5-T, during the cancellation proceedings. We would, of course, welcome all possible data on human health effects of Agent Orange and would attempt to draw whatever conclusions are scientifically possible from the Vietnam experience. We see the best potential for the study as being a possible source of valuable information for the treatment of veterans potentially affected by use' of Agent Orange and evaluation of VA claims possibly resulting from herbicide exposure. EPA already participates in an existing interagency advisory group to assist in evaluating the medical aspects of veterans' exposure to herbicides, and will afford the VA scientific and technical support through that group should the recommended study be undertaken. We appreciate the opportunity to comment on this report prior to its issuance to Congress. Sincerely yours, 0^--William Dray ton. Jr. n Assistant Administrator ^ for Planning and Management (08766) 38 �Single copies of GAO reports are available free of charge. Requests (except by Members of Congress) for additional quantities should be accompanied by payment of $1.00 per copy. Requests for single copies (without charge) should be sent to: U.S. General Accounting Office Distribution Section, Room 1518 441 G Street, NW. Washington, DC 20548 Requests for multiple copies should be sent with checks or money orders to: U.S. General Accounting Office Distribution Section P.O. Box 1020 Washington, DC 20013 Checks or money orders should be made payable to the U.S. General Accounting Office. NOTE: Stamps or Superintendent of Documents coupons will not be accepted. PLEASE DO NOT SEND CASH To expedite filling your order, use the report number and date in the lower right corner of the front cover. GAO reports are now available on microfiche. If such copies will meet your needs, be sure to specify that you want microfiche copies. �AN EQUAL OPPORTUNITY EMPLOYER UNITED STATES GENERAL ACCOUNTING OFFICE WASHINGTON, D.C. 20548 POSTAGE AND FEES PAID U. S. G E N E R A L A C C O U N T I N G O F F I C E OFFICIAL BUSINESS PENALTY FOR PRIVATE USE.I300 Alvin L.' Young 5226 Prince Valiant San Atonio TX 78218 THIRD CLASS � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 180 Folder The folder containing the original item. 5271 Series The series number of the original item. Series VIII Subseries I Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Description An account of the resource <strong>Corporate Author: </strong>Comptroller General of the United States Date A point or period of time associated with an event in the lifecycle of the resource April 6 1979 Title A name given to the resource Report by the Comptroller General of the United States: Health Effects of Exposure to Herbicide Orange in South Vietnam Should be Resolved ao_seriesVIII