1 15 15 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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 Corporate Author: 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 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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 Corporate Author: 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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 Corporate Author: 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 5246 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. Title A name given to the resource Notes: Comments on McNulty Study with TCDD in Monkeys as Reported in C & E News, August 7, 1978; dated September 13, 1978 ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/b7c8b709888b609b38980112e55b33c7.pdf feb633cc7cf7071073c9d019dab55491 PDF Text Text Item D Number °5244 Author Long, Marguerite L. D Not Scanned Corporate Author Report/Article TitlO Realist c i Evaluation of Human Exposure from Application of 2,4,5-T Sprays Journal/Book Title Year 1978 Month/Day Au ust 4 Color 9 D Number of Images ° Descrlpton Notes Friday, March 01, 2002 Page 5244 of 5263 �CRI R & D REPORT NUMBER L A B O R A T O R Y REPORT CODE DOW CHEMICAL U.S.A. RESTRICTED: for use within The Dow Chemical Company GHR 58 D A T E ISSUED only. August 4, 1978 CAB. NO. DEPARTMENT GOVERNMENT REGISTRATION REPORT J P R O B L E M NO. I I ,1 I | | 50 Realistic Evaluation of Human Exposure from Application PAGES IN FULL REPORT of 2,4,5-T Sprays A U T H O R IS) Marguerite L. Leng A U T H O R (S> S I G N A T U R E (S) REVIEWER'S SIGNATURE INTERIM NEW and mainly: X D E S C R I P T I V E SUMMARY WITH CONCLUSIONS: ( Include reports, in this patents FINAL s p a c e r e f e r e n c e s to and publications.) data books, and to n REVIEW earlier The Environmental Protection Agency's Rebuttable Presumption Against Registration (RPAR) for products containing 2,4 ,5-trichlorophenoxyacetic acid (2,4,5-T) was triggered in part by their conclusion that exposure to this herbicide could be hazardous to women of child bearing age. EPA's evaluation is based on "worst case" estimates for contamination of applicators using various types of equipment, and on a margin of safety much higher than for every-day exposure to known teratogens such as table salt, vitamin A and caffeine. Data from studies with 2,4,5-T itself in humans demonstrate that EPA's estimates are orders of magnitude too high. In actual practice, the hazard is extremely slight from exposure to this useful herbicide, even for pregnant women who might be employed "as pesticide applicators, operators of highway construction and maintenance equipment, foresters, and chemical formulators." DISTRIBUTION: FORM C-4300 DEPARTMENT FILES R & D ADMINISTRATION C E N T R A L REPORT INDEX ( 5 6 6 Bldg. - M i d l a n d ) PRINTED R-l-73 - 5 COPIES D istri bution l i s t is c o n t i n u e d on attached page. related �REALISTIC EVALUATION OF HUMAN EXPOSURE FROM APPLICATION OF 2,4,5-T SPRAYS by Marguerite L. Leng Health § Environmental Sciences The Dow Chemical Company Midland, Michigan Submitted to U.S. Environmental Protection Agency in Response to the Rebuttable Presumption Against Registration of Pesticide Products Containing 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) August 4, 1978 �REALISTIC EVALUATION OF HUMAN EXPOSURE FROM APPLICATION OF 2,4,5-T SPRAYS TABLE OF CONTENTS SUMMARY EPA ESTIMATES FOR EXPOSURE TO 2,4,5-T DIRECT AND INDIRECT MEASUREMENT OF EXPOSURE TO PESTICIDES I. Estimates by EPA Based on Direct Measurements A. B. Use Pattern for 2,4,5-T C. Evaluation of Studies Selected by EPA D. II. Review of EPA Assumptions Conclusions About EPA's Estimates Based on Direct Measurements Realistic Estimates of Exposure Based on Indirect Measurements with 2,4,5-T A. Ingestion Studies with 2,4,5-T in Humans 1. 2. 3. B. Exposure in Workers Manufacturing 2,4,5-T 1. 2. C. Dow Japan India Japan Dow Exposure During Actual Application of 2,4,5-T 1. 2. Dow study EPA study MARGIN OF SAFETY BASED ON DATA FOR 2,4,5-T IN APPLICATORS REFERENCES �SUMMARY EPA's Rebuttable Presumption Against Registration (RPAR) for products containing 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) was triggered in part by their conclusion that exposure to this herbicide could be hazardous to women of child bearing age (Position Document, April 21, 1978). (3) Exposure Analysis, in order to determine whether a rebuttable presumption should be Issued based on reproductive and fetotoxlc effects. pursuant to } l«3.1KaX3XilXB), the Working Group must determine whether or not an ample margin of safety exists between the levels of 2,4,5-T and/or TCDD which produce reproductive and fetotoxic effects, and the leveUs) to which humans can reasonably be anticipated to be exposed. The cancellation of uses of 2,4,5-T on food crops Intended for human consumption and for use around the home, recreation sites, aquatic areas, and ditch banks in 1970 was thought to have eliminated the potential exposure to that portion of the population at risk (women of child bearing age). Social changes over the last few years, however, have given women the opportunity for employment In areas that once were considered open only to men. Since women of child-bearing age are now employed In occupations such as pesticide applicators, operators of highway construction and maintenance equipment, foresters, and chemical formulators. they have become part of the population at risk with potential exposure to 2.44-T and/or TCDD. In order to determine whether an ample margin of safety exists, the Working Group must first determine how much 2,4,5-T a woman could be exposed to through oral, dermal, or Inhalation exposure. For each of these analysis, the Working Group assumes a woman to weigh 60 kg. The following calculations are based on an exposure analyses for 3,4£>T and TCDD performed by EPA's Criteria and Evaluation Division CCED1 EPA's evaluation is based on "worst case" estimates for contamination of applicators using various types of equipment, and on a margin of safety much higher than for everyday exposure to known teratogens such as table salt, vitamin A and caffeine. Data from studies with 2,4,5-T itself in humans demonstrate that EPA's estimates are orders of magnitude too high. In actual practice, the hazard is extremely slight from exposure to this useful herbicide, even for pregnant women who might be employed "as pesticide applicators, operators of highway construction and maintenance equipmentf foresters^ and chemical formulators." �-2- EPA ESTIMATES FOR EXPOSURE TO 2,4,5-T EPA estimated effective doses for women applying 2,4,5-T by extrapolating data from direct measurements of contamination in workers applying chemically dissimilar pesticides under different application conditions. EPA also assumed that the woman would spend 8 hours each day actually applying the herbicide with a hand-pressured backpack sprayer, or operating a "tractor-mounted low-boom sprayer", or standing in an open area directly under the spray path of an aircraft applying the herbicide. Table . lists EPA's estimates for daily exposure in a 1 60-kilogram woman under these conditions as calculated by their Criteria and Evaluation Division (EPA #164). In each case they assumed that the woman was using a commercial product containing 4 pounds of 2,4,5-T acid equivalent (a.e.) per gallon diluted 10-fold with water (a spray containing about 4% 2,4,5-T a.e.). The 2,4,5-T was assumed to contain 0.1 ppm of the trace contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), resulting in effective doses of TCDD 10 million times less than those estimated for 2,4,5-T. The complete text of this portion on Exposure Analysis in the RPAR Position Document is attached for ease of reference. �Table 1. SUMMARY OF EPA ESTIMATES OF EXPOSURE TO 2,4,5-T AND TCDD IN A 60 KG WOMAN TCDD ug/kg/day Equipment; Location. Treatment Conditions Contamination per 8 Hours Backpack sprayer; for rights-of-way, spots in pasture or rangeland 4 Ib a.e./gal diluted 10-fold with water; applied to wet 0.18 pint (1/3 cup or 86 ml) on bare skin 6.8 (dermal) 0.2 (inhalation) () 3* 000 .07 (dermal) negligible (inhalation) (0* 4) Tractor mounted low boom sprayer; for rights-of-way, rangeland. 4 Ib a.e./gal diluted 10-fold with water; applied to wet 0.048 pint (3/4 fl. oz or 23 ml) on bare skin 1.8 (dermal) 0.05 (inhalation) ( D I * 0008 .01 (dermal) negligible (inhalation) (7) 10* 4 Ib a.e. in Aerial application 10 gal water on person directly beneath spray path, per acre as medium to in the open with very light clothing, coarse spray. and who remains there all day. 3.1 mg on bare skin 0.34 mg by inhalation in 2 hr. 2,4,5-T mg/kg/day (Margin of Safety) vs 20 mg/kg 001 .5 (dermal) 0.023 per 8 hr (Margin of Safety) vs 0 0 yg/kg .3 (0) 40* 5 x 1" 06 (dermal) (00 60) (7) 80* 2 x 10~6 (50) 100 (inhalation) (inhalation) 0.074 (cumulative) (7) 20* 7 x 10"6 (cumulative) (30 40) *According to EPA, these estimated exposures do not offer an adequate margin of safety when compared to dosage levels which caused no effect when administered daily during the critical stage of pregnancy in mice for 2,4,5-T, or in rats for TCDD. �-4- EPA also assumed that she was wearing very light clothing with no protective equipment and that 10% of all active ingredient in spray falling on bare skin was absorbed before any was washed off. They also assumed that 2% of an aerial spray was in droplets small enough to be inhaled (less than 60 microns in diameter), and that exposure by inhalation would amount to 3% of that by dermal contamination when using ground equipment. In either case, 100% of the active ingredient in the inhaled material was absorbed. Margins of safety for each situation have been calculated by comparison of these estimated exposure rates with levels which caused no adverse effect in pregnant animals or their offspring, even when administered daily for as long as half the gestation period. Based on data from many studies, EPA concluded that no-effect-levels had been established for 2,4,5-T at 20 milligrams per kilogram of body weight per day (mg/kg/day) and for TCDD at 0.03 micrograms per kilogram of body weight per day (ug/kg/day). It should be noted that higher doses caused embryotoxic or fetotoxic effects in several species of animals, but teratogenic effects were observed only in mice, a specie which is known to be very sensitive to any kind of stress during pregnancy (Golberg 1971, Dow #46) . �-5- Although the Position Document (see excerpt above) states that "the Working Group must determine whether or not an ample margin of safety exists between the levels of 2j4f5-T and/or TCDD whiah produce reproduative and fetotoxio effeats and the levels to which humans aan reasonably be anticipated to be exposed" (emphasis added), EPA has not indicated what levels would produce such effects, nor what margin of safety would be considered ample. Using these "worst case" estimates for potential exposure, EPA concluded that the margins of safety were not adequate for 2,4,5-T and/or its TCDD contaminant when applied by ground equipment. In the case of aerial application, the margin of safety was deemed adequate for exposure to TCDD (calculated as 6000-fold for skin absorption, 15000-fold for inhalation, and 4300-fold for cumulative dermal and inhalation exposure compared to the no-effect level of 0.03 ug/kg per day). However, the margin of safety was deemed to be inadequate for 2,4,5-T itself (calculated as 400-fold for dermal, 870-fold for inhalation and 270-fold for cumulative exposure, compared to the no-effect level of 20 mg/kg/day in mice). It should be noted that many products used daily by pregnant women (such as aspirin, vitamin A, or caffeine), have very low margins of safety for effects of much greater consequence �-6- than those produced in laboratory animals by considerably higher doses of 2,4,5-T containing traces of TCDD. (See Dow Rebuttal Document, Section III, C.I. Teratogenic/fetotoxic effects). DIRECT AND INDIRECT MEASUREMENT OF EXPOSURE TO PESTICIDES As discussed by Durham et al. (1962, EPA '#163) both direct and indirect methods can be used to measure exposure to pesticides in applicators. Direct measurement of a pesticide in samples collected during spraying is frequently easier than measurement of the same compound or its derivatives in tissues or other biological materials. It provides an estimate of the total potential exposure but does not give information on the portion of contacted material that is actually absorbed. EPA's estimates for 2,4,5-T are all based on direct measurements for potential exposure in applicators using other pesticides under dissimilar conditions, and are greatly exaggerated due to a series of erroneous assumptions as discussed in Part I below. On the other hand, EPA has not considered available data from indirect measurements on 2,4,5-T and related compounds in humans including studies conducted in their own �-7- laboratory (shafik- et al. 1971, EPA 133). Such data provide a more realistic estimate of exposure to humans under actual use conditions for this herbicide, as discussed in Part II herein. I. ESTIMATES BY EPA BASED ON DIRECT MEASUREMENTS Most of the studies on exposure to applicators have been conducted by a government research group located in Wenatchee, WA, who were formerly associated with the Communicable Disease Center of the Public Health Service, Department of Health, Education and Welfare (HEW), and later incorporated into the Office of Research and Monitoring of EPA. A number of these studies were cited in EPA's 2,4,5-T RPAR Position Document (Wolfe et al. 1959, EPA 1145; Task Group on Occupational Exposure to Pesticides 1974, EPA #146; Staiff et al. 1975, EPA #147; Durham et al. 1962, EPA #163; Wolfe et al. 1974, EPA #166; and Wolfe 1972, EPA #179). Other studies by this group also furnish additional pertinent information as discussed herein (Wolfe et al. 1963, Dow #128; 1966, Dow #129; 1967, Dow #130;and 1972, Dow #131). A. Review of EPA Assumptions EPA's Criteria and Evaluation Division (EPA #164) utilized data from these studies but made a series of erroneous �-8- 11 worst case" assumptions which led to greatly exaggerated estimates for exposure of applicators to 2,4,5-T: (1) They extrapolated linearly from data for contamination with totally different chemicals applied under dissimilar conditions (rate of application, concentration of spray, total volume per acre, solvent, droplet size, pressure, direction of spray, avoidance of spray drift, etc.) (2) They assumed that all applications of 2,4,5-T were at the high rate of 4 Ib/A although virtually all treatments in rice, rangeland, and forests are at 0.5 to 2 Ib/A. They also assumed that the dilution rate was 1 gallon of product made to 10 gallons with water although ground applications are generally at 1 to 3 gallons in. 100 gallons of water, and many are made in oil or oil/water rather than in water alone. (3) They assumed that applicators would be wearing very light clothing although many states require pesticide applicators to wear coveralls or similar minimal protection (e.g. California 1977, Dow #135). Calculations by Wolfe et al. (1959, EPA #145) "indicate that protective clothing such as long-sleeved �-9- shirtj long trousers3 shoes, rubberized gauntlet gloves, and a tropical helmet and veil would decrease potential exposure almost to zero (less than 2% of unprotected value)". The amount of protection required also depends on the job. For example, a training manual for aerial applicator ground crews (Haley 1973, Dow #136) recommends that a flagman wear a jacket or coveralls, whereas a loader would need overboots, an apron or coveralls, rubber gloves, respirator, and goggles. (4) They neglected to consider that the greatest potential for exposure is on the hands, particularly when handling the concentrate during loading and mixing, and can be avoided by simply wearing gloves (Wolfe et al. 1966, 1967, Dow #129, 130). They compounded this error by assuming that values for total exposure to an insecticide concentrate and its very dilute spray solution were due to only the dilute spray, and by extrapolating linearly from the dilute spray (e.g. 0.06% fenthion) to a 4% 2,4,5-T solution. Furthermore, workers tend to avoid excess exposure of hands to the dilute and concentrate liquid sprays materials (Wolfe et al. 1974, EPA #166). �-10- (5) They assumed that exposure would be continuous during 8 hours each day, even for a person using a backpack sprayer to squirt 2,4,5-T on individual trees or patches of weeds and brush, interspersed with frequent trips back to reload the sprayer. Furthermore, exposure with this equipment is mainly on the hand and forearm holding the wand and can be avoided by wearing even one glove. (6) They assumed that an applicator using a backpack sprayer would get 0.18 pint (86 ml) of spray on exposed skin daily, without considering that the carrier solvent might be diesel oil which is very irritating and soiling (Haley 1973, Dow #136). (7) They assumed that 10% of the 2,4,5-T and its trace contaminant falling on bare skin would be absorbed on the day of spraying. Although not cited in the Position Document, EPA's Criteria & Evaluation Division (EPA #164) discussed a study in which only 5.8% of the 2,4-D applied to the forearm of volunteers was absorbed over a period of 5 days after exposure, chiefly on the second or third day, if not washed off for at least 24 hours (Feldmann and Maibach 1974, Dow #132). �They assumed that the amount inhaled during applications with ground equipment would be 3% of the dermal exposure such as in applications of insecticides as aerosols in orchards. However, 2,4,5-T is applied at low pressures as a coarse to medium spray to avoid drift, so only a negligible portion of the droplets would be small enough to be inhaled (Wolfe et al. 1967, Dow #130). (9) They also assumed that aerial spraying of 2,4,5-T would continue for 8 hours each day rather than only when wind velocity, temperature, etc., are within acceptable limits. (See excerpt of label for ESTERON* 245 low-volatile herbicide which follows) . (10) They assumed that a flagger would remain standing directly beneath the spray path for 8 hours each day and that 2% of the spray would be in droplets small enough to be inhaled (less than 60 microns in diameter). However, 2,4,5-T is applied as a coarse to medium spray from a height of generally less than 10 feet above the target area. *Trademark of The Dow Chemical Company. �-12- Thus EPA appears to have neglected many factors in selecting conditions for their examples, and further compounded the error by using additive "worst case" conditions for each situation. Since 2,4,5-T is a potent broadleaf herbicide, considerable effort is made to avoid off-target drift. For example approved labeling for ESTERON 245 herbicide specifies; USE PRECAUTIONS AVOID CONTACT WITH J,4,S-T SUSCEPTIBLE CROPS AND OTHER DESIRABLE BROAOUAF PLANTS —6STERON 2*i Herbicide ii injurigutto most broadleaf plants, Therefore, da not apply directly la of otherwise permit even minute amounts to contact cotton, grapes, tobacco, frvif treet, vegetables, flowers, ornamentals or other desirable plants susceptible to 2,4,5-T. Oo not UM in or near a greenhouse. OO NOT APPIY IN THE VICINITY OF COTTON, GRAPES, TOBACCO, TOMATOES OR OTHER DESIRABLE 3,4,S-T SUSCEPTIBLE CROPS OR ORNA/nENTAt PUNTS. OO NOT SPRAY WHEN WIND IS BLOWING TOWARDS SUSCEPTIBLE CROPS OR ORNAMEN. TAt PUNTS AVOID SPRAY DRIFT—Application! should b* mad* only whin there it no haiard from spray drift >inc» very unall quantities of the spray, which may not be »i>ibl*. may severely injure susceptible crops during both growing and dormant periods. Us* coarse sarays to minimize drift tine*, under adverse weather conditions, fin* ipray droplets may drift a mil* or more. Th* ipray thickening ag*nt, N ALCO-TROL1, may b* us*d with this product to aid in reducing spray drift. If us*d follow all us* recommendations and precautions on the product label. ' NAICO-THOI—trodemork of NALCO Ch.rt.kol Company GROUND EQUIPMENT —With ground equipment, ipray drift can be lessened by keeping the spray boom as low as passible; by applying 20 gallons or more af ipray per acre; by using n« mare than 20 pounds (praying pressure with large droplet producing nozzle tipsj'by spraying when wind velocity i» 3 miles per hour or lest. Do not apply with hollow cone-type insecticide at other nozzles that produce a fine-droplet spray. AERIAL APPLICATION — With aircraft, drift can be lessened by applying a coarse tpray; by using no mare than 20 pounds spray pressure at the nozzles; by using straight stream nozzles directed straight back; by using a spray boom no longer rhon V* the wing span of the aircraft; and by spraying only when wind velocity is less than 6 mph. DO NOT APPIY BY AIRCRAFT WHEN AN AIR TEMPERATURE INVERSION EXISTS. Such a condition is characterized by little or no wind and with air temperature lower near the ground them at higher levels. The use of a continuous smoke column at or near lite of application is suggested to indicate direction and velocity of air movement, and to indicate a temperature inversion by layering of the smoke. At high temperaturts (above 9i'f) vapors from this product may injure susceptible plants growing nearby. Do not use in or near a greenhouse. Excessive amounts of this herbicide in the sail may temporarily inhibit seed germination or plant growth. Such limitations also have a moderating effect on the potential for exposure in applicators. For example, Wolfe et al. (1959, EPA #145) reported that dermal exposure to DDT increased two to three-fold for each 10 psi increase in pressure. At 50 psi, the exposure was about 11 times greater than at 20 psi. �-13- Although dermal exposure may not be greatly affected by the size of droplets landing on the skin, smaller droplets are more likely to drift and contaminate the applicator. Respiratory exposure is greater with smaller droplets, such as when using an air blast machine to penetrate the foliage canopy for insect control in orchards. Wolfe et al. (1966, Dow #129) reported droplet sizes of 20 to >150 microns in diameter for parathion and malathion applied at 0.063 to 1000 gallons of spray per acre. Such sprays would- require 10 seconds or more to fall 10 feet and could move 50 to 1000 feet downwind in a 3 mph wind (Warren 1976, Dow #133). On the other hand, 2,4,5-T is applied as a medium to coarse spray, with droplets 240 to 400 microns or more in diameter. These would fall 10 feet in about 2 seconds, and would drift only a short distance (Warren 1976, Dow #133). Thus it is unlikely that a flagger would be inhaling the spray for 8 hours each day. In a recent study by DOW (Miller 1978, Dow #134) the spray was confined nearly completely to the target area using equipment typically used in rice and rangeland. When ESTERON 245 was applied by air at 0.5 pound 2,4,5-T acid equivalent in 1 to 4 gallons of spray per acre, recovery of active material ranged from 73 to 91% on the target area, and 96 to 99% within the target area plus 165 feet �-14- downwind. Average droplet size ranged from 197 to 397 microns in diameter, and the percent of spray mass under 100 microns ranged from 1.4 to 9.4% depending on the nozzle system used. Equipment used for treatment of rights-of-way is even more restrictive than in this study. B. Use Pattern for 2,4,5-T The herbicide 2,4,5-T is an organic acid which is formulated as water soluble amine salts for weed control in rice/ and as oil-soluble long-chain amine salts or emulsifiable low-volatile esters for control of weeds and brush in pastures and rangeland, in right-of-way areas and in forests. It is selective in its activity against broadleaf weeds ys grasses, and against deciduous trees vs_ conifers. 2,4,5-T is a systemic auxin-type herbicide which is taken up from applications to foliage and, to a lesser extent, via the roots from soil. Recommended use patterns depend on the species of weeds or brush to be controlled, and on the site of application. Rice is treated midseason, generally after flooding, by air from a height of no more than 10 feet above the crop to minimize spray drift. Foliar treatments for brush control are more effective in the spring and early summer when the leaves are well developed and the plants are actively growing. Stem and �-15- stump treatments are more effective in late fall or during the dormant period so the 2,4,5-T is available for uptake when growth resumes in the spring. Conifer forests are treated before"bud break in early spring or after hardening in late spring or early summer. The solvent chosen and rate of treatment depend on the species of weeds or trees to be controlled and their stage of growth. For aerial applications, 2,4,5-T is generally applied at a rate of 0.5 to 2 pounds (occasionally 4 pounds) acid equivalent per acre, as a medium to coarse spray from a minimum height above the target area, often with the addition of a drift control agent or with a drift control system to avoid damage in susceptible plants off the target area. As shown in the attached label for ESTERON 245 herbicide, ground applications are made with either high volume sprays (1 gallon of a 4 pound per gallon ester formulation in 100 gallons of water), or low volume sprays (1 gallon in 10 gallons of water, oil/water, or oil alone), carefully directed on the target areas. The type of equipment used depends on how much of the total area needs treating and on its accessibility. A hand- pressured backpack sprayer could be used by an applicator on foot or on horseback for spot-treating weeds and brush �-16- in pastures and rangeland, and in accessible rights-of-way such as along utility lines or pipelines. Tractor mounted low-boom sprayers could be used along roadsides or railroads, and in relatively level pastures and right-of-way areas, or for forest site preparation. Small fixed-wing aircraft or helicopters equipped with special booms are used for overall treatment of rice paddies and large brushy areas of rangeland and forests. Aerial applications are especially well suited for maintaining cleared strips such > as rights-of-way along utility lines and pipelines, or for fire breaks in hardwood forests. No flaggers are needed in such sites because the areas to be sprayed are clearly demarcated . Flaggers are used only occasionally in forests because of the rough terrain and height of the vegetation. C. Evaluation of Studies Selected by EPA The three studies selected by EPA do not represent the above conditions for 2,4,5-T. The pesticides used in these studies have different chemical properties, and were applied at different concentrations and volumes, as follows : Fenthion - 0,0-dimethyl-O- [4- (methylthio) -m-tolyl] phosphorothioate. An undefined formulation was applied with a hand pressured backpack sprayer as a fine �-17- spray at 0.06% in water for mosquito control (Wolfe et al. 1974, EPA #166) . Paraquat - 1,1 '-dimethy 1-4, 4 '-bipyridium formulated as its dichloride. A concentrate containing 2 pounds per gallon was made up at 2 quarts per 100 gallons of water (a 0.12% solution) and was applied with a "tractor mounted low-boom sprayer" at 100 gallons per acre to burn down weeds and grass in an orchard (Staiff et al. 1975, EPA #147). Malathion - s- [1,2 -bis (ethoxycarbonyl) ethyl] 0,0dimethyl phosphorodithioate. An undefined formulation was applied by air from a height of 70 feet above the target area as a fine spray containing 7.5% technical active ingredient, mainly in medium grade diesel oil, at the rate of 0.46 pound malathion per acre (about 1 gallon total spray per acre) to control mosquitoes in a populated area (Caplan et al. 1956, EPA #167) . In each example cited by EPA, the applicators wore very light clothing and took no precautionary measures when loading and mixing the pesticides, nor during actual application. The malathion study was conducted more than 20 years ago when less was known of the potential hazards from exposure to toxic pesticides . �-18- According to EPA's estimates (C&E Division, EPA #164), the hazard from exposure using ground equipment was much greater than during flagging for aerial application, even when the flagger remained directly under the spray path for 8 hours each day. For example, application of fenthion with a hand pressured backpack sprayer caused dermal contamination ranging from 0.1 to 6.3 mg/hour (mean 3,6 mg/hr) with about 80% of the total on the hand and forearm holding the spray wand.. (Wolfe et al. 1974, EPA #166). Application of paraquat caused dermal contamination ranging from 0.01 to 3.4 mg/hour (mean of only 0.4 mg/hour) with practically all on the hands of the operator (Staiff et al. 1975, EPA #147). Nevertheless, EPA used linear extrapolation o£ these maximum values (6.3 and 3.4 mg/hour) to estimate potential exposure to 2,4,5-T. In both cases, practically all contamination could be avoided by wearing light coveralls and at least one impervious glove. Cotton gloves should not be worn since occlusion could increase the potential for absorption of concentrate or spray splashed on the gloves (Task Group on Occupational Exposure to Pesticides, EPA #146). Exposure during application with a tractor-mounted lowboom sprayer would be minimized by staying upwind to the spray, and by being in the cab of the vehicles above the �-19- spray directed at the weeds and brush. Similarly, aerial applications are made upwind to avoid contamination of the aircraft, particularly the windshield. Furthermore, 2,4,5-T is not applied when there is a potential for spray drift, to avoid damaging off-target vegetation, as discussed previously. Wolfe et al. (1967, Dow #130) reported that potential exposure was 12 times greater during application of parathion with an air blast machine in an orchard than when the same chemical was applied on row crops with a boom-type sprayer that directed the spray downward. Thus, exposure depends in great part on whether the spray is applied overhead, underfoot, or alongside and downwind. Further evidence for this can be found in a summary paper by Wolfe et al. (1967, Dow #130) which tabulates data from over 80 exposure studies involving more than 5000 measurements of exposures to 23 pesticide chemicals in a variety of formulations and under a variety of methods of application. Many of these studies were done with insecticides applied with air blast equipment in fruit orchards, a practice which causes heavier exposure than when spraying row crops (Wolfe 1966, Dow 1129). Table 2 lists eight studies representing conditions resembling �Table 2. SUMMARY OF PUBLISHED STUDIES ON POTENTIAL EXPOSURE OF WORKERS TO PESTICIDES USING DIRECT METHODS Pesticide Used Application Equipment Activity, Location Spray % ai Rate Ib ai/A Av. Exposure/Hour Dermal Inhal. mg (ml)* mg Inhalation Reference vs Dermal Cited %** Endrin High pressure power hand gun directed downward Spraying orchard cover crops for mouse control 0.05% 1.2 3.1 () 6 0.01 0.3 Wolfe 1967 Dow #130 Endrin Power air blast on boom sprayer directed downward Treating orchard cover crops for mouse control 0.05% 1.2 2.5 () 5 0.01 0.4 Wolfe 1967 Dow #130 Demeton High pressure power hand gun Driving tractor in nursery 0.05% 1.2 1.9 () 4 0.01 0.5 Wolfe 1967 Dow #130 Parathion Gasoline powered knapsacker mister Directed spraying on tomato bushes 0.4% 0.5 9.1 () 2 0.29 3.2 Simpson '65 Dow #135 Parathion Tractor mounted boom ground sprayer Operating tractor in row crops 0.9% 4.7 () 5 <0.01 Parathion Air application for insect control Flagging in fruit orchard 9% () 1 Malathion Air application for mosquito control Standing outdoors in populated area 7.5% 0.46 0.89 (.1 00) Malathion Air application for mosquito control Standing indoors in populated area 7.5% 0.46 0.25 « . 1 0.012 0 0 ) (est.) 0.5 1.5 84 <0.2 Wolfe 1967 Dow #130 0.02 0.02 Wolfe 1967 Dow #130 0.055 6.2 Cap Ian '56 EPA #167 4.8 Caplan ' 6 5 EPA #167 (est.) * ml on exposed skin, calculated from total dermal contamination due to handling concentrate plus dilute spray, as all due to dilute spray. ** Exposure by inhalation was less than 0.5% of dermal exposure except when applied as a mist (parathion), or as a fog for mosquito control (malathion). Exposure to malathion was during a 2-hr spray period and 2 hours afterwards. o i �-21- those which might be encountered during application of 2,4,5-T. Exposure during use of ground equipment amounted to about 4 to' 6 ml per hour actually spent spraying, which is much less than the 86 ml per day estimated by EPA, even for this type of application. EPA's estimates for exposure of applicators also included "worst case" calculations of the amount contributed by inhalation. They erroneously interpreted the footnote j under Table 34 of the Position Document to mean that 17142 | FIOIRAL RIGKTM, VOL 43, NO. 7«-«IOAY, APRIl 21, W» . T a b l e 3ftf C u m u l a t i v e Exn.oa.ui"> to 2. fr. 5*.^ a n d T C D D S i t u a t i o n *1j , 2 v f r S-T | S i t u a t i o n i) ! TCDD (Oral(Dermalllnhal.iCuffl. a I 0.0007 mg/kg 6.8 ng/kg 0.2 mg/Icg*7 7.0 ng/kg lOral[DermalIInhal.I Cum. a 0.0007 mg/kg 1.8 ng/kg 0.05A/ 1.85 mg/kg I Slfrua.tion «2; 2. 4.5-T, I | I Oral— . I Dermal- 0.0007 ug/kg I Inhal;- negligible*' I Gun. a 0.0007 ug/kg I | Situation «2; TCPD iOralI Dermal- 0.00018 ug/kg llnhal.- negligible*' I Cum, » 0.00018 ug/kg ! SituatlQt) »\; , _ . 2. H.?-T 1 | f j I I I j . I t i ! I Sjl-tuatipn t^t.,. TCDD i lOral0.0007 mg/kg I OralI iDermal- 0.051 ng/kg iDermal- 5 X 10~6 ug/kg • i llnhal.- 0.026 mg/kg llnhal.- 2 X 10~6 ug/kg I JCun. a 0.0777 mg/lcg J C u m . a 7 X 10" ug/ltg I r A/ Calculations were made on a worst-case basis as 3$ of dermal exposure baaed on Wolfe (179) who atatea, "over 97> of the pesticide to which the body is subjected dTTring moat exposure situations, and 'especially to applioators of liquid sprays, is deposited on the akin." TCDD inhalation exposure values were negligible: Situation #1, 21 X 10~ ug/kg; Situation #2, 54 X 10~7 ug/kg. exposure by inhalation would be 3% of the dermal exposure during application with a backpack sprayer or a tractormounted sprayer (situation #1 and #2, respectively). On �-22- the contrary, available data indicate that only trace amounts of pesticides are likely to be inhaled during application of dilute, sprays (Table 2). The respiratory exposure depends in large part on the type of formulation being applied. According to Wolfe et al. (1967, Dow #130), the relative respiratory exposure expressed as the mean percentage of total (dermal plus respiratory exposure) was 0.23% for a dilutespray, 2.87% for an aerosol (fine spray), and 0.94% for a dust. In the study on fenthion (Wolfe 1974, EPA 1166), inhalation exposure ranged from <0.001 to 0.067 mg/hr during application using a hand pressure sprayer and <0.001 to 0.092 mg/hr using a power sprayer. Mean values were less than 0.6% of the dermal exposure under the same conditions. EPA's estimates for inhalation during aerial applications of 2,4,5-T is also erroneous, since it is based on data for malathion applied as a fine spray for mosquito control (Caplan et al. 1956, EPA #167). EPA assumed that 2% of the 2,4,5-T spray droplets would be less than 60 microns in diameter, and that the applicator would be inhaling these fine droplets for 8 hours each day. Data in Table 2 indicate that inhalation exposure would be negligible for applications resembling how 2,4,5-T �-23- is used. Values approaching 3% were obtained only for aerosol type sprays such as with jnalathion for mosquito control (study 7) or parathion as a mist in tomatoes (study 4). Furthermore, a person would not be exposed to 2,4,5-T by inhalation for 8 hours per day since coarse droplets fall rapidly (Warren 1976, Dow #133). D. Conclusions About BPA's Estimates Based on Direct Measurements > EPA appears to have made a number of erroneous assumptions and to have selected poor models for predicting exposure of applicators to 2,4,5-T. Consideration of mediating factors such as clothing worn and care taken during application would seem to be essential for EPA to make reliable estimates of the potential for contamination of applicators by 2,4,5-T. It should also be noted that many of the "worst case" assumptions are contrary to label practice and thus provide a built-in margin of safety which is not accounted for in EPA's numerical derivations. CAUTION MAY BE HARMFUL IF SWALLOWED • MAY CAUSE IRRITATION Avoid Contact with Eyes, Skin and Clothing Do Not Cut or Weld Container �- 24 - II. REALISTIC ESTIMATES OF EXPOSURE BASED 'ON INDIRECT MEASUREMENTS WITH 2 , 4 , 5 - T According to Durham et al. (1962, EPA #163) "any measure of absorption or its necessary sequelae constitutes an indirect measure of exposure. It is not often convenient to measure absorption itself, but measurement of a compound or its biotransformation, products in the blood, tissues or excreta gives information on minimal absorption. Such indirect measurements may be used in evaluating the relative hazard of different routes of exposure, different operational procedures and different protective devices (as described previously for direct measurements) . In addition, they are more useful in relating exposure under observed use conditions to clinical effects". In 1962 when the above observation was made, there was not a single pesticide for which the inter-relationships between occupational exposure to different formulations by different routes, the fate of the compound in the body, and its clinical effects were all adequately known. However, more studies have been conducted in recent years on 2 , 4 , 5 - T and its TCDD contaminant than for most if not all other chemicals. Among these are several controlled studies in humans which have provided much needed information to refute claims of effect from exposure to this useful herbicide. ill Studies have also been conducted on excretion of 2,4,5-T by manufacturing plant workers and by pesticide applicators which show conclusively that EPA's estimates for exposure are grossly exaggerated, as discussed previously herein. �- 25 - A. Ingestion Studies in Humans (Dow, Japan, India) Numerous studies on the metabolism of 2,4-dichlorophenoxyacetic acid (2,4-D) and related herbicides have shown that these chemicals are absorbed and distributed rapidly in the body, and are excreted, unchanged, relatively quantitatively in the urine within a week after administration (Leng 1977, EPA #79). Pharmacokinetic studies with 2,4,5-T in rats and dogs (Piper et al. 1973, EPA #67) and in humans (Gehring et al. 1973, EPA #74) corroborated these findings and demonstrated that rates of clearance from plasma and elimination in urine depend on dosage level, animal species, and chemical structure of the phenoxy acid in question (Table 3). Phenol metabolites were detected only in ruminants (Leng 1977, EPA #79) or in trace amounts in urine of rats fed excessively high doses (Shafik et al. 1971, EPA #33). TABLE 3 Effect M. L Leng fill (£/»/» #7?) of species on fate of 2,4,5-T in animals. Species Studied Single Oral Dose, mg/kg Rat' Number of Animals/Tests Duration of Study, Days 6 4-6 4 9 Peak Plasma Cone., ug/ml Interval Post-Administration, Hour 15 12 20 <4 57 7 Volume of Distribution, ml/kg Number of Body Compartments 144 1 221 1 80 1 Average Rate of Clearance, T^ , Hour from Plasma from Body via Urine 4.7 13.6 77 87 23.1 23.1 Excretion as Percent of Dose in Urine, Total Ether Soluble (as Altered 2,4,5-T) in Feccs 83 (none) (little) 42 (4) 20 89 (little) 83 62 90 Total in Excreta as Percent of Dose Piper et ,il.. 1973. (6 I* A 2 Gehring el al., 1973. | 5 Dog' 5 5/7 4 �- 26 - In the study by Dow with 2,4,5-T in humans (Gehring et al. 1973, EPA #74), five male volunteers weighing 73 to 94 kilograms ingested a single dose of 5 mg/kg. Plasma levels attained a peak.,of about 60 ug/ml within about 2 hours and. decreased rapidly with a half-life of about 23 hours. As shown in Table 4, urinary excretion was rapid with a diurnal fluctuation, and a total of about 90% of the dose was recovered largely as free 2,4,5-T within 4 days after administration. It is interesting to note that the fraction Table 4. Excretion of 2,4,5-T in Urine After Single Oral Dose at 5 mg/kg in Five Male Volunteers Interval After Ingestion (hr) (day) Incremental % of Dose Excreted 0-12 12-24 1 26.8 .14.1 24-36 36-48 2 48-60 60-72 72-84 84-96 Cumulative % of Dose Excreted Fraction in Daytime Collection3 38.12 0.70 20.7 8.7 67.5 0. 70 3 9.9 4.4 81.8 0. 69 4 4.8 1.8 88.5 (K 73 av. 0. 71 1 Gehring et al. 1973 (EPA #74) 2 One subject pooled the 0-12 and 12-24 specimens so the mean excretion for day 1 is not the sum of the mean excretions for 0-12 and 12-24 hours. Calculated from 26.8/38.1 = 0.70; 20.7/29.4 = 0.70; 9.9/14.3 - 0.69; 4.8/6.6 = 0.73. IWBHB �- 2.7 - excreted during the daytime was constant at 0.71 of the total per day. Similar studies in humans were conducted by Dow with 2,4-D in five males (Sauerhoff et al. 1977a, Dow #140) and with silvex in seven males and one female (Sauerhoff et al. 1977b, Dow #141) . The results are compared in Table 5 (Leng 1977, EPA #79) . 64 M.LLeng TABLE 5 fate of three phenoxy herbicides in humans. Phenoxy Herbicide Administered 2,4,5-T1 2,4-Dz Single Oral Dose, mg/kg 5 5 1 Number of Subjects/Tests 5/7 5 8 Duration of Study, Days 4-6 4 6 Peak Plasma Concentration, ug/ml Interval Post Administration, Hour 57 7 25 4 Volume of Distribution, ml/kg Number of Body Compartments 80 1 Average Rate of Clearance, TH , Hour from Plasma from Body via Urine Excretion as Percent of Dose in Urine as Free Acid as Conjugate(s) in Feces (First 2 Days) Total Excreted as Percent of Dose >200, 83 1 or 2 6 2-4 115,107 2 23.1 23.1 11.7 17.7 3.7, 19 5, 26 88.5*5.1 (little) < 1 70-88 0-27 - 30-80 15-54 0-3 88-106 67 - 95 *90 iQehring et al., 1973 2Sauerhoff et al.. Wfltr 1111 «• 3Dow,fefripublijhedM77& In an independent study with 2,4,5-T in Japanese volunteers (Matsumura 1970, EPA #73), a peak plasma level of 21.1 yg/ml was reached at 4 hours after ingestion of a single dose of 150 mg 2,4,5-T by a male weighing 68 kg (i.e. 2.2 mg/kg) . �- 28 - As in the Dow study with 2,4,5-T (Gehring at al. 1973/ EPA 174), more than 80% of the administered dose was recovered in the urine within 3 days after a dose of 100 mg in two volunteers weighing 68 and 53 kg (Figures 1 and 2). About 45% of the dose was recovered in the first 24-hour urine collection after doses of <2 mg/kg, compared to the average 38% recovered in the Dow study at 5 mg/kg. 'Excretion of 2,4,5-T in the Urine "(Matsumura 1970, EPA #73) 100 (0 0 •s 0 0) 5* CD > -M 0) O M 0) o 0 a; CU 7» Time (hours) Figure 1. Male, 28 years old, body weight 68 kg, 100 mg 2,4,5-T ingested for dose of 1.5 mg/kg Time (hours) Figure 2. Male, 27 years old, body weight 53 kg, 100 mg 2,4,5-T ingested for dose of 1.9 mg/kg The fate of phenoxy herbicides in humans has also been studied in India. In their study with 2,4-D (Kohli et al. 1974, Dow #140), a single oral dose of 5 mg/kg was given to six male volunteers. As in the Dow study with 2,4-D (Sauerhoff et al. 1977a, Dow #138), 75% of the administered dose �- 29 - was excreted unchanged in the urine within 96 hours after administration, but no metabolites were detected. In their study with 2,4,5-T (Kohli et al. 1974b, EPA #75), a total of eight male volunteers received single oral doses of 2, 3 or 5 mg/kg of body weight. Again as in the Dow study (Gehring et al. 1973, EPA #74}, the chemical was absorbed readily from the gastrointestinal tract and was excreted rapidly via the kidneys without undergoing any metabolic alteration. The half-life for clearance of 2,4,5-T from the plasma was about 19 hours in the Indian study, compared to 23 hours in the Dow study. Of the total amount excreted in 96 hours, nearly 80% was excreted within the first 48 hours (Table 6). Table 6. Excretion of 2,4,5-T by Eight Male Volunteers in India (Kohli et al. 1974, EPA #75). Interval After Ingestion (day) Cumulative % of Dose Excreted in Urine 2 mg/kg 3 mg/kg 5 mg/kg (6)1 (1) (1) 1 57 27 2 48 73 50 3 66 76 60 4 1 26 73 79 63 Average for six subjects given oral dose of 5 mg 2,4,5-T per kg of body weight. �- 30 - Although considerable variation was noted among individuals in each study, particularly those conducted in India/ the overall agreement is remarkable. As summarized in Table 7, about one-third of the dose was excreted, on the average, in the urine collected the first day after administration of a single dose. If the dose was 5 mg/kg in a 60 kg person, the total amount administered was 300 mg of which about onethird (100 mg) would be in the first 24-hour urine specimen. Similarly, about one-fourth (75 mg) would be in the second daily sample, and one-tenth (30 mg) in the third daily sample. These data can be used to estimate the effective dosage rate for 2,4,5-T in exposed individuals for whom urinary levels are known. Table 7. Study by Summary of Excretion Studies with 2,4,5-T in Humans (EPA #73, 74, 75) Mean % of Dose in Urine Day 1 Day 2 Day 3 Day 4 Dosage mg/kg Number of Subjects 5 5 38 29 14 Japan 1.5 1.9 1 1 45 45 30 30 5 5 India 2 3 5 1 1 26 57 27 22 16 23 18 35: 25 11 Dow Total 6 15 3 10 7 7 3 4 Approximation obtained by taking average of total for all 15 subjects [i.e. (5 x 38)+ 45. . . + (6 x 27) -s- 15]. �- 31 - For example, a concentration of 15 ppm 2,4,5-T in 1500 ml of urine (the normal average 24-hr output for an adult human) amounts to excretion of 15 x 10~ x 1500 ml x 1000 mg/ml = 22.5 mg 2,4,5-T. Since the average amount of 2,4,5-T ex- creted in urine in the first 24-hr following a single dose is about one-third of the dose (day 1, Table 7), the 22.5 mg represents one-third of a single 67.5 mg dose. In a person weighing 60 kg, this represents a dose of 1.1 mg/kg. On the other hand, daily dosage results in a steady-state condition wherein the total daily input is equal to the total daily output. Thus, in a daily exposure situation, 22.5 mg 2,4,5- T in a 24-hr urine would result from daily dosage of 22.5 mg/60 kg = 0.4 mg/kg of body weight. A more sophisticated estimate of the dosage by dermal exposure can be made using a pharmacokinetic model developed for computer analysis of the data generated in the Dow study with 2,4,5-T (Gearing et al. 1973, EPA #74). Estimates of exposure using this model corroborates the above approx* imation that similar urinary levels would be attained from daily exposure at one-third the single dose rate as from the single dose. B. Exposure in Workers Manufacturing 2,4,5-T The Japanese study (Matsumura 1970, EPA #73) also reported finding 0.5 to 3.6 mg 2,4,5-T in urine specimens from eleven workers in a "chemical manure factory" (Table 8). Based on the data for excretion following a single oral dose in the �- 32 - same study (Table 7), it is estimated that those factory workers had received a single dose of 2,4,5-T ranging from about 0.02 to 0.15 mg/kg1 during the previous day or two, or about 0.007 to 0.05 mg/kg if they were exposed daily. Their exposure to 2,4,5-T was from working in a room which contained 0.62 to 15.4 mg/m3 at different locations, and from 0.21 to 0.67 mg/m3 in their breathing zones in this fertilizer factory (Tables 9 and 10). Table 8 Date Name Age Sex No. Apr. 9 / A. M. a S. S. 3 Y. I . f T. Ki. S. H. * & T. T. Apr. IS / A. M. A S. S. 3 Y. I . S S. H. t T. N. ? S. K. Apr. 16 T. Ki. 3 Y. I . 2 S. s. * to Table $ Concentrations of 2, 4, 5-T in thesurroundings of a chemical manure factory. 2,-1,5-T in the urine o( workers of a chemical manure factory. S. N. T. Ko. Apr. 22 // Y. O. A S. S. ¥ T. Ki. 3 Y. I . 28 50 60 •10 26 20 28 50 60 26 38 21 •10 60 50 •11 53 38 50 •40 60 Male Male Male Female Female Male Male Male Male Female Female Male Female Male Male Male Female Female Male Female Male Urine , 4 e.r volume (/*!g_'i,,' i (ml/day) m / d a >> 2. 060 1. 400 1, 570 1, 020 1. 020 870 2, 000 2. 220 2. 400 1, 260 1, 760 1, 400 750 1, 670 3. 020 1, 470 450 250 850 180 1, 150 Calc. ppm 1. S 0 .73 1. 3 1. 2 0. 5 3. 6 1.27 1.18 0 .57 ,1 .80 S a m p l i n g points \Veighins box I n l e t of mixer Outlet of mixer Center of work-room 1.53 2 .57 15.4 1.37 0.82 0.62 milligrams per cubic meter. Tahlc/0. Concentrations of 2, 4, 5-T at the breathing location of workers. Workmen 2. 7 3. 6 1. 0* Concentrations* Concentrations 4 A n C U 0.21 0.31 0.67 0.38 m i l l i g r a m s per cubic meter. 2. 2 3. 5' 1.50 Matsumura 1970 (EPA #73) 1. 9* milligrams per liter. 0.5 rag in urine rag 45% of TOIJ mg in urine x 1.9 mg/kg b.w. =0.02 mg/kg b.w. 100 3.6 mg in urine 45% of 10 mg in urine x 1.9 mg/kg b.w. = 0.15 mg/kg b.w. 100 �- 33 - In a survey of 204 Dow factory workers (Ott et al. 1978, Dow #28), no adverse effect was noted for exposures ranging from one to ten years at levels estimated to be 0.2 to 0.8 mg/m3 for 2,4,5-T as the sodium salt. It should be noted that this study covered a period of more than 20 years (from 1950 to 1971) when the exposure to 2,4,5-T was greater than in the current process for making esters, and the TCDD level in the 2,4,5-T was higher than the current limit of <0.1 ppm. Nevertheless, the incidence of cancer in this group of factory workers is less than the national average. A surveillance study was recently initiated for Dow factory workers currently employed in the manufacture of esters of 2,4-D, 2,4,5-T, and silvex. Preliminary analyses of urine specimens taken during routine physical examinations of three workers indicated the presence of 1.3 to 2.6- ppm 2,4-D, 0.2 to 1.6 ppm 2,4,5-T, and 0.01 to 0.03 ppm silvex. Four months later, urine samples collected from four manufacturing workers contained only 0.27 to 0.52 ppm 2,4-D, 0.17 to 0.54 ppm 2,4,5-T, and 0.004 to 0.023 ppm silvex. Levels in blood samples taken at the same time ranged from 2 to 9 parts per billion for both 2,4-D and 2,4,5-T, while silvex was not detected at a minimum sensitivity of 1 ppb. These values indicate that the workers were receiving a low daily exposure of <0.007 mg/kg for each of 2,4-D and 2,4,5-T and considerably less for silvex. �- 34 - C. Exposure During Actual Application of 2,4,5-T Several studies have already been conducted on urinary levels of 2,4,5-T in applicators, and others are currently • underway. The most complete data available is from a study by Dow in eight field applicators and two controls conducted on a confidential basis for a customer. Air samples and samples simulating skin contact were taken for direct measurement of exposure, while blood samples and 24-hour urine collections provided data for indirect measure of actual exposure in the individuals. The 2,4,5-T product used was a 59.1% butoxyethanol ester formulation containing 4 pounds of 2,4,5-T acid equivalent per gallon (Amchem WEEDONE T). It was diluted at 3 gal/100 gal with fuel oil (2% 2,4,5-T a.e.) and was applied selectively to the lower 3 to 4 feet of trees and brush in a utility right-of-way using a hand pressured backpack sprayer (2 1/2 gal capacity). The applicators wore short-sleeved shirts open at the neck, long pants, no gloves and no hat. One of the backpacks leaked as evidenced by soaking of the applicator's clothing at the lower back. This latter par- ticular circumstance is considered to be gross misuse and directly contrary to the label precautionary direction: CAUTION' Avoid contact with eyes, skin and clothing. �- 35 - The results of this' study are -summarized in Table 11. As expected, urinary levels were higher in the applicators than in the foremen, and were barely detectable in the Dow personnel conducting the study. The highest estimated dose was 0.2 mg/kg/day in applicator L.A. who was wearing the leaking backpack sprayer. This confirms that E P A ' s estimate of 7 . 0 mg/kg for cumulative exposure using a backpack sprayer is grossly exaggerated, even for a "worst-case" situation (Position Document, Table 34, situation # 1 ) . It is likely that exposure would be very low ( < 0 . 0 1 mg/kg) if these applicators had worn long-sleeved shirts or coveralls and gloves. Proper maintenance of equipment and better personal hygiene would also have prevented the high exposure experienced by applicator L.A. in this study. Table 11. 2,4,5-T in Urine of Spray Applicators 2,4,5-T in Urine ppm mg/24 hr Dose mg/kg1 Subject Occupation kg B.W. B.F. J.L. D.M.. L.A. Applicator Applicator Applicator Applicator 73 73 59 68 0.85 4.30 3.00 17.00 1.45 7.06 3.58 13.18 0.02 0.10- R.L. B.B. T.H. J.M. Foreman Foreman Foreman General Foreman 77 87 70 78 0.75 3.80 0.07 0.03 1.25 4.79 0.09 0.08 0.02 0.06 0.001 0.001 R.O. E.G. Ind. Hygienist Clin. Chemist 75 73 0.02 <0.01 0.03 <0.03 0.0004 <0.0004 0.06 0.202 Calculated from the urinary levels using the pharmacokinetic model for 2,4,5-T excretion in humans (Gehring et al., 1973, EPA #74). 2 This situation with a leaking backpack which soaked the applicator's clothing is considered gross misuse contrary to label precautionary handling directions. "CAUTION1. May be harmful if swallowed. May cause irritation. Avoid contact with eyes, skin and clothing." �- 36 - Data are also available from an indirect study conducted in 1970 by EPA or its predecessors at the Perrine Laboratory in Florida. Urine samples were collected from people occupa- tionally exposed to 2,4-D and 2,4,5-T, and were analyzed .for both the phenoxy acids and their expected phenol metabolites (Shafik et al. 1971, EPA #33). As shown in Table 12, only low ppm levels of the parent compounds were found in the urine of spray operators, and little or none in those whose occupation afforded less direct contact. These samples were collected in 1970 as part of the Community Studies Network in South Dakota, Arkansas and Kentucky (personal communication to M. L. Leng from H. F. Enos, EPA, Athens GA, June 1978) . The samples from Arkansas were collected from four spraymen employed by the Arkansas Electric Cooperative Inc., working out of Fayetteville (personal communication to M. L. Leng from M, L. Anderson, now Chief of Pesticides Technical Assistance Section, EPA, Dallas TX, July 1978). They were applying ESTERON* 245 herbicide (label attached) at 2 gallons in 40 gallons of diesel oil (about 3% 2,4,5-T a.e.) using knapsack equipment to spray around the base of individual trees and up to 2 feet on the trunks. They were wearing jeans and gloves but little care was taken to avoid skin contact. A total of eight urine samples were collected, four in the early morning on July 22 following exposure the * Trademark of The Dow Chemical Company �-3732 ' (EPA #33) M. T. SHAFIK, H. C. SULLIVAN, AND H. F. ENOS Intern. J. Environ. Anal. Chem. !_, 23-33, 1971 33 A METHOD FOR DETERMINATION OF LOW LEVELS OF EXPOSURE TO 2,4-D AND 2,4,5-T To demonstrate the applicability of the method for monitoring occupational exposure, urine from people directly and indirectly involved in the application of 2,4-D and 2,4,5-T derivatives was analyzed. The results, as shown in Table V, indicate a higher degree of exposure for spray operators than those whose occupations afforded less direct contact. It can be generally concluded that the method suggested for the determination of 2,4-D and 2,4,5-T in urine may be used to determine low levels of exposure to these herbicides. Levels of exposure of 3.75 meg/kg for 2,4-D and 5.00 meg/kg for 2,4,5-T in rats can be determined in urine within 24 hr from exposure. TABLE Results of analysis of urine from people occupationally exposed to 2,4-D and 2,4,5-T1 Results (ppm) Sample Exposure compound 2,4-D 2,4,5-T Spray operator 1 2 3 N.D.' N.D. . N.D. N.D. N.D. N.D. 1.1 1 .« 2.8) 2.6 \ A o 4 5 6 2,4,5-T 2,4,5-T 2,4,5-T 2,4,5-T 2,4,5-T 2,4,5-T 7 8 2,4-D and 2,4,5-T 2,4-D and 2,4,5-T 0.20 0.19 N.D. N.D. 2,4,5-T 2,4,5-T N.D. N.D. 1-21 /j o 0.5) 2,4-D 2,4-D N.D. N.D. N.D, N.D. 2,4-D 2,4-D 2,4-D 2,4-D N.D. N.D. N.D. N.D. N.D, N.D. N.D. N.D. 2,4-D 2,4-D N.D. N.D. N.D. N.D. 2,4-D 2,4-D 1.0 0.2 N.D. N.D. 2,4-D and 2,4,5-T 2,4-D and 2,4,5-T 0.4 1.0 0.05 0.05 3.61 3.01 A f l 1.3f ** Farmer Foreman, spray crew 9 10 Herdsman 11 12 • Farm laborer 13 14 15 16 Pesticide project officer 17 IS Spray operator 19 20 Aircraft spray operator 21 22 •The derivative is unknown. *>N.D.. not delected. �- 38 - previous day, and four in the afternoon after exposure since 7 a.m. that day. The corresponding samples in Table 12 are 1-2, 3-4, 5-6, and 9-10 for the four members of this crew. Although 24-hour urine collections were not made, data from Tables 4 and 11 (Dow studies) can be used to estimate the effective dose of 2,4,5-T received by dermal exposure in these applicators. Based on an average 2.0 ppm 2,4,5-T in the eight daytime urine samples (range 0.5 to 3.6 ppm in Table 12), and assuming a daily volume of 1500 ml urine divided equally between 0-12 and 12-24 hours with 0.71 of the total 2,4,5-T in the daytime sample (Table 4), the estimated daily excretion in these applicators was 0.21 mg. This corresponds to an effective dose of about 0.03 mg/kg compared to the average 0.06 mg/kg found in applicators in the Dow study, excluding the one wearing a leaking backpack sprayer (Table 11). In either case, the exposure is at least two orders of magnitude less than the cumulative dose of 7.0 mg/kg estimated by EPA for use of this type of equipment (.Position Document, Table 34, Situation #1) . Information has also been obtained recently about the samples collected in Kentucky. According to Edsel Moore of the Kentucky Health Department (personal communication to M. L. Leng, July 1978), their situation also represented a "worst-case". Two groups of people were involved, one inexperienced group of students employed by Western Kentucky �- 39 - University and one made up of employees of the Kentucky ' State Department of Agriculture. They were applying 2,4-D or 2,4-0/2,4,5-T with a tractor drawn boom sprayer, or with a tractor drawn "gun nozzle" aimed over a ridge at vegetation growing along a right-of-way. They wore light summer clothing and no protective equipment. Examination of Table 12 reveals that few remaining samples of urine contained detectable levels of either 2,4-D or' 2,4,5-T. Thus, the cumulative dose by both dermal exposure and inhalation must be considerably less than 0.01 rag/kg in applicators using this type of ground equipment, even when no special precautions are taken to avoid contact with the spray. Again, the exposure is at least two orders of magnitude less than EPA's estimate of 1.85 mg/kg for application of 2,4,5-T with a "tractor-mounted low boom sprayer". (Position Document, Table 34, Situation #2). Additional data will be obtained in a comprehensive study being conducted by the National Forest Products Association. According to the proposed protocol presented to EPA in late July 1978, both direct and indirect measurements of 2,4,5-T exposure will be made during application of the herbicide with backpack sprayers and mist blowers, or by air. �- 40 - MARGIN OF SAFETY BASED ON DATA FOR 2,4,5-T IN APPLICATORS Analyses of urine from applicators exposed to 2,4/5-T in various real world situations and comparison with data from known exposures in humans, provide convincing evidence that EPA's estimates are grossly exaggerated. The margin of safety is actually many times greater than calculated by EPA, even for pregnant women, compared to the no-effect level in mice treated daily during organogenesis. For example, EPA calculated a cumulative exposure of 7-.0 mg/kg for a woman using a backpack sprayer to apply 2,4,5-T for 8 hours. Data from the Dow study and the EPA study (Shafik et al. 1971, EPA #33) indicate .that the effective dose would be <0.01 mg/kg if the applicator takes even the reasonable precautions as directed by labeling. This would provide a margin of safety at least 2000-fold over the noeffect level in mice and several times that for levels which caused only minor fetotoxic effects in rats. Exposures using other types of equipment would be even less than with backpack sprayers. Furthermore, increasing aware- ness of potential problems from exposure to other pesticides has resulted in more specific label precautions and better enforcement of regulations pertaining to wearing of protective equipment and avoiding contact with sprays. �- 41 - In conclusion, there is little likelihood that a woman of child-bearing age, whether pregnant or not, will suffer any harm from proper use of 2,4,5-T during employment as a pesticide applicator, operator of highway construction and maintenance equipment, forester, or chemical formulator. REFERENCES Position Document, 1978. Environmental Protection Agency, Pesticide Programs, Rebuttable Presumption Against Registration and Continued Registration of Products Containing 2,4,5-T. Federal Register 4_3_ (78), 17116-17157, April 21, 1978. (Exposure Analysis, p. 17137-17142, attached). Criteria and Evaluation Division, 1978. Environmental Protection Agency, Pesticide'Programs, Memo: Exposure analysis, 2,4,5-T, dated February 1978; from Chief, Chemistry Branch, Criteria and Evaluation Division, to Project Manager, Office of Special Pesticide Reviews. (EPA #164 in RPAR Position Document 1, supra). Golberg, L. 1971. Trace Chemical Contaminants in Food: Potential for Harm. Fd. Cosmetic Toxicol. 9, 65-80. (Dow #46). Durham, W.F. and Wolfe, H.R. 26_, 75-91. (EPA #163) . 1962. Bull. World Health Org. Wolfe, H.R., Armstrong, J.E., and Durham, W.F. 1974. Exposure of Mosquito Control Workers to Fenthion. Mosquito News'3_4_(.3) , 263-267. (EPA #166) . Staiff, D.C., Comer, S.W., Armstrong, J.F. and Wolfe, H.R. 1975. Exposure to the Herbicide Paraquat. Bull. Environ. Contam. Toxicol. 14_(3) , . 334-340. (EPA #147). Caplan, P.E., Culver, D., and Thielen, W.C. 1956. Human Exposure in Populated Areas During Airplane Application of Malathion. AMA Arch. Indust. Health 14, 326-332. (EPA #167) . Wolfe, H.R., Durham, W.F., and Armstrong, J.F. 1963. Health. Hazards and the Pesticides Endrin and Dieldrin. Arch. Environ. Health 6_, 458-464. (Dow #128). Wolfe, H.R., Atmstrong, J.F., AND Durham, W.F. 1966. Pesticide Exposure from Concentrate Spraying. Arch. Environ. Health 13, 340-344. (Dow #129).. �- 42 - Wolfe, H.R., Durham, W.F., and Armstrong, J.F. 1967. Exposure of Workers to Pesticides. Arch. Environ. Health 14, 622-633. CDow #130).. Wolfe, H.R., Armstrong, J.F., Staiff, D.C., and Comer, S.W. 1972. Exposure of Spraymen to Pesticides. Arch. Environ. Health Z5, 29-31. (.Dow #131) . Task Group on Occupational Exposure to Pesticides, 1974. Report to the Federal Working Group on Pest Management, Washington, DC, Jan. 1974. (EPA #146). Feldmann, R.J. and Maibach, H.I. 1974. Percutaneous Penetration of Some Pesticides and Herbicides in Man. Toxicol. Appl. Pharmacol. 28, 126-132. (Dow #132). Wolfe, H.R., Walker, K.C., Elliott, J.W., and Durham, W.F. 1959. Evaluation of Health Hazards Involved in House Spraying with DDT. Bull. World Health Org. 20, 1-14. (EPA #145). ESTERON 245 Herbicide, approved label for product registered by Dow under EPA Reg. No. 464-205, printed in April 1978. (attached). Warren, L.E. Controlling Drift of Herbicides, Part I. World Agr. Aviation, March 1976. (Dow #133). Miller, C.D.M. 1978. Aerial Deposition of Pesticides from Aircraft: Results of 2,4,5-T Deposition Experiments. Unpublished report of The Dow Chemical Company. (Dow #134). California Administrative Code, Article 23, Sections 2477, 2479, effective March 3, 1977. (Dow #135). Haley, J. 1973. Expert Flagging - a Training Manual for Aerial Applicator Ground Crews. Department of Aviation, University of North Dakota Press, Grand Forks, ND. (Dow #136) . Simpson, G.R., and Beck, A. 1965. Exposure to Parathion. Arch. Environ. Health 11, 784-876. (Dow #137). Leng, M.L. 1977. Comparative Metabolism of Phenoxy Herbicides in Animals. IN Fate of Pesticides in Large Animals, ed. by Ivie, G.W. and Dorough, H.W., Academic Press, New York (p. 53-76). (EPA #79). Piper, W.N., Rose, J.Q., Leng, M.L., and Gehring, P.J. 1973. The Fate of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) Following Oral Administration to Rats and Dogs. Toxicol. Appl. Pharmacol. 26, 339-351. (EPA #67). �- 43 - Gehring, P.J., Kramer, C.G., Schwetz, B.A., Rose/ J.Q., and Rowe, V.K. 1973. The Fate of 2,4,5-Trichlorophenoxyacetic Acid (2,4,5-T) Following Oral Administration to Man. Toxicol. Appl. Pharmacol. 26_, 352-361. (EPA #74) . Shafik, M.T., Sullivan, H.C., and Enos, H.F. 1971. A Method for. Determination of Low Levels of Exposure to 2,4-D and 2,4,5-T, Intern. J. Environ. Anal. Chem. 1, 23-33. (EPA #33) . Sauerhoff, M.W., Braun, W.H., Blau, G.E., and Gehring, P.J. 1977a. The Fate of 2,4-Dichlorophenoxyacetic Acid (2,4-D) Following Oral Administration to Man. Toxicology 8, 3-11. (Dow #138) . Sauerhoff, M.W., Chenoweth, M.B., Karbowski, R. J. , Braun, W.H., Ramsey, J.C., Gehring, P.J., and Blau, G.E. 1977b. Fate of Silvex Following Oral Administration to Man. J. Toxicol. Environ. Health 3_, 941-952-. (Dow #139) . Matsumura, A. 1970. The Fate of 2,4,5-Trichlorophenoxyacetic Acid in'Man. Japanese J. Occupational Medicine 12.(9) , 20-25. (In Translation) . (EPA #73) . Kohli, J.D., Khanna, R.N., Gupta, R.N., Dhar, M.M., Tandon, J.S., and Sircar, K.P. 1974a. Absorption and Excretion of 2,4-Dichlorophenoxyacetic Acid in Man. Xenobiotica 4(2), 97-100. (Dow #140). Kohli, J.D., Khanna, R.N., Gupta, B.N., Dhar, M.M., Tandon, J.S., and Sircar, K.P. 1974b. Absorption and Excretion of 2,4,5-Trichlorophenoxyacetic Acid in Man. Arch. Int. Pharmacodyn. Ther. 2jLO>(2) , 250-255. (EPA #75). Ott, M.G., Holder, B.B., Olson, R.D. 1978. A Longevity Survey of Employees Exposed to 2,4,5-Trichlorophenoxyacetic Acid. Unpublished Report of The Dow Chemical Company. (Dow #28) . �FRIDAY, APRIL 21, 1978 PART II 17137 ENVIRONMENTAL PROTECTION AGENCY PESTICIDE PROGRAMS > Rebuttable Presumption Against Registration and Continued Registration of Pesticide Products Containing 2, 4, 5-T (3) Expotun Analysis. In order to determine whether a rebuttable presumption should be Issued based on reproductive and fetotoxic effects. pursuant to 5182.n(aX3)UiXB). the Working Group must determine whether or not an ample margin of safety exists between the levels of 2.4,5-T and/or TCDD which produce reproductive and fetotoxlc effects, and the level(s) to which humans can reasonably be anticipated to be exposed. The cancellation of uses of 2,4,5-T on food crops Intended for human consumption and for use around the home, recreation sites, aquatic areas, and ditch banks in 1970 was thought to have eliminated the potential exposure to that portion of the population at risk (women of child bearing age). Social changes over the last few years, however, have given women the opportunity for employment In areas that once were considered open only to men. Since women of child-bearing age are now employed In occupations such as pesticide applicators, operators of highway construction and maintenance equipment, foresters, and chemical fonnulators, they have become part of the FfDCRAl HECHSTtt, VOL 43, NO. 7*-«lDAY, AflUl 21, 197* �17138 NOTICES ity of oral exposure to 2,4,5-T and/or TCDD effects has not been met or exceeded, a reexisted. Treatment of range and pasture buttable presumption docs not arise. land could result In oral exposure through (b) Dermal Exposure. In order to conduct Ingestion of meat and milk from anirpo.!* these analyses, the Working Group must degrazing on the treated area. Since actual termine the amount of 2,4,5-T and/or data on residues of 2.4.5-T In animals graz- TCDD which would come In contact with ing on treated rangeland Is unavailable, for the akin and the amount that would be abpurposes of the 2,4,5-T oral exposure analy- sorbed. sis, the Working Group used residue Infor(I) Sony Applicator: Back-pack Sprayer. mation obtained In a feeding study (3D In • For purposes of this analysis, the Working which cattle were fed considerably higher Group assumes the applicator to be a 60-kg amounts of 2,4,5-T than they would normalsite of ly be exposed to in grazing on treated land. woman of child-bearing age, and theor spot either a For purposes of thJ5 The following calculations are based on the application of pasture right-of-way treatment or rangeland. - analysis, the Working Group considered average quantities of food eaten per day (1.5 equipment Is a back-pack sprayer (1561. The The • currently registered uaes where the possibil- kg), aa reported by Lehman U 44,155). following calculations of exposure are based , on dilution for spraying of three pints of Table 3S- g.U.S-T Oral Exposure Analysis ' formulated product per 32 pints of water. Whole Mi Ik Heat (Beefy! Typical 2.4,5-T formulations, based on in(No-adverse-effact 20 mg/kg ! 20 . spectlon of a large number of registered (level for teratolabels (1641, range from 4 to 8 pounds active Ingredient (acid equivalent) per gallon. The Igenioity in mice product used in this exposure analysis has (Average level of 0.10-3 ppm* 0.2 p pm an assumed concentration of 4 pounds 2,4,5• , ' « |2,4,5-T identified T per gallon. Label recommendations vary j from a recommended dilution of 0.094 to 4 i pounds acid equivalent per 32 pints of 1* of food item in 4.6$ 19.6* water. A dilution rate of 1.6 pounds per 32 (total human diet pints has been selected as representative of i •1 a typically-used spray mixture. 1 (Average amount of Wolfe et aL (155) studied dermal exposure 1.5 leg *5 kg.; to fenthion during hand back-pack spraying (food eaten per day ' • •'.." , i '• for mosquitoes for ten situations. Exposure i i ranged from 0.1 to 3.3 mg/hr. with a mean (Exposure to 2,4,5-T 0.0005 0.0002 ' ' value of 3.3 mg/hr (3 ml/hr). Method of ap1 o« e d a v plication was a hand pressure sprayer, using a 0.03 Workers wore short* &./ Animals were fed at 300 ppm 2,4,5-T in the diet for 2 to sleeved,percent spray. shirts with no gloves open-necked •"3 weeks. This is a worst oase assumption for cows grazing or hat. Based on Wolfe's data, CKD (ISM f on freshly-treated pasture without a withdrawal period; all calculated a dermal exposure of approximately 0.177 pints per day, CKD (164) also .4'milk and meat was obtained from such cows. Maat (beef) 'determined that approximately 10 percent ';. includes muscle, fat, and liver tissues which constitute the .: of the 2,4,5-T and TCDD coming In contact vmajor portion of edible meat. • with the skin of the applicators would be absorbed even after washing, based on abTo find the average dally Intake of a constitute an ample margin of safety. Since sorption studies with other pesticides (US, 'duals food item, multiply the average daily this risk criterion for other chronic adverse 146, 163). food intake by the percent of that Item In Table 36. Baek-oaek Soraver Dermal Exnosiurg Data the total diet: For milk, 1.5 kgxl9.8%-0.294 kg: and for meat (beef). 1.S kgx4.8%-0.089 2,4,5-T IS.2,2. i kg. ItJse Dilution rate 3 pints 3 pints The quantity of 2.4,5-T in the average (1.6 pounds (0.00000016 1 dally diet equals the average daily intake of pounds TCDD) ' 2,4,5-T) per each food item multiplied by the level of 2,4,5-T in the food Item: For milk, 0.294 I>«r 32 pints 1 " 32 pints kgx0.103 ppm-0.03 mg; and for meat water water 1 <beef). 0.069 kgx0.2 ppm-0.014 mg. t . The theoretical exposure of an average 1 0.18 pint 0.18 pint woman equals the amount-of 2.4,5-T In the (Amount of diluted dally diet divided by the weight of the aver- (material gotten age woman: For milk, 0.03 mg/80 kg-0.0005 Ion skin daily mg/kg; and for meat (beef). 0.014 mg/60 kg»0.0002 mg/kg; total exposure from milk 10* , 10* - • and beef products could be 0.0007 mg/kg It Diluted material per day. (absorbed ••v Existing data on TCDD residues In ani- 1i .•.._•' mala grazing on treated rangeland are too (Exposure level 0.0409 ug 409 mg ',:•••: meager to use for aa analysis of TCDD ex- 1 i ;-?;-•• posure to humans through Ingestion of : iDose level 6,3 mg/kg -V_. meat or milk from animals so exposed. 0.0007 ug/kg v".£i The Working Group considers that the I . -A difference between the no-adverse-effect (Ho- Adverse-Effect 20 mg/kg 0.03 ug/kg ;,.-. level of 2,4,5-T for teratogenlc effects (20 .' . ' mg/kg) and the calculated oral exposure (level for terato• level for 2,4.5-T (0.0007 mg/kg per day) does 1 a ania ef_f »qt a population at risk with potential exposure fr^l to 2.4,8-T and/or TCDD. "jvTJj In order to determine whether an ample S»v. margin of safety exists, the Working Group V>JK must first determine how much 2,4,5-T a •?>"''-. woman could be exposed to through oral, each of •J4? dermal, or Inhalation exposure. For assumes Working Group y.^ these analysis, the 30 kg. The following cala woman to weigh culations are based on an exposure analyses for 2,4.5-T and TCDD performed by EPA'a Criteria and Evaluation Division CCED1 1 . "*i ' ' RDflAl. UOISTEK, VOL. 43, NO. 7»—rtlDAY, AMll 21, 197S �NOTICES The following calculations (see Table 27 for mathematics) will give the dally dermal exposure for both 2,4.5-T and TCDD: (1) Convert the dilution rate to grams: (2) multiply this figure by 1.000 (for 2.4.5-T) to convert to milligrams and by 1,000,000 (for TCDD) to convert to micrograms: (3) multiply this figure by the dally dermal dose of diluted material; (4) multiply this figure by the percent absorbed; and (5) divide this figure by the weight of the applicator for the daily exposure to 2.4.S-T or TCDD per 8-hour working day, ' The Working Group considers that the difference between the no-adverse-effect level of 2,4.5-T for teratogenic effects (20 tag/kg) and this calculated dermal exposure level for 2,4.5-T (6.8 mg/kg), as well as the difference between the no-adverse-effect level of TCDD for teratogenic effects (0.03 fig/kg) and this calculated exposure level for TCDD (0.0007 MeAg), do not constitute an ample margin of safety. The Working Group therefore recommends issuance of a rebuttable presumption against pesticide products containing 2.4,5-T and/or TCDD pursuant to 40 CFR Section 182.11(aX 3X11X3). (UJ Spray Applicator: Tractor-mounted, Low-boom Spray Equipment. For the purpose of this analysts, the Working Group assumes the applicator to be a 60-kg female of cbildbeartng age clearing brush on either rmngeland "br rlghta-of-way. The same product cited above < 2,4.5-T at 4 pounds/gal) is being used, and the dilution rate '& 1.8 pounds of formulation to 32 pints of water (equal to 4 pounds of 2,4.5-T per 10 gallons of water). Based on exposure studies using similar equipment but a different herbicide U47), the Working Group determined that. during an eight-hour working day, the applicator would get 0.048 pints of diluted material on her skin. The Working Group determined that 10 percent of the pesticide on the skin would be absorbed 1145,14S, 163). • The following calculations (see Table 29 for mathematics) will give the dally dermal exposure for both 2.4,5-T and TCDD: (1) Convert the dilution rate to grams; (2) multiply this figure by 1,000 (for 2.4,5-T) to convert to milligrams and by 1,000,000 (for TCDD) to convert to micrograms; (3) multiply this figure by the daily dermal dose of diluted material: (4) multiply this figure by the percent absorbed; and (5) divide this figure by the weight of the applicator for the daily exposure to 2,4.5-T or TCDD per 8-hour working day. 17139 Table 27 2. 4 f q-T TCDD 1) 1.6 pounds/32 pt X 454 g/pound a 22.70 g/pt; 2) 22.70 g/pt X 1,000 mg/g s 22,700 mg/pt; . 3) 22,700 mg/pt X 0,18 pt s 4,086 mg; 4) .4,036 mg X 10$ a 408.6 mg 5) 408.6 mg / 60 kg s fi.fl.Bg/1fg nar Table 28. rlav 1) 0.00000016 pounds/32 pt X 454 g/pound a 0.00000227 g/pt; 2) 0,00000227 g/pt X 1,000,000 ug/g * 2.27 ug/pt; 3) 2.27 ug/pt X 0.18 pt a 0.41 ug; 4) 0.41 ug X 10J = 0.041 ug; 5) 0.041 ug / 60 kg s Q.OOdT us/kjf n_er day Daraal Exposure Data (Tractor Mounted Equipment 2 f 4PS.T 3 pints (1.6 pounds 2,4,5-T) per 32 pints water TCDD 3 pints (0.00000016 pounds TCDD) per 32 pints water Amount of diluted material gotten on akin daily 0,048 pint- 0.048 pint % Diluted material absorbed 10J 10* Exposure level 109 mg 0.0109 ug Dose level 1.8 mg/kg. 0.00013 ug/kg No-Adverse.Effect level for teratogenie effects 20 mg/kg 0.03 ug/kg lUso Dilution rate Tabls 2<i _ 1) 1.6.pounds/32 pt X 454 g/ • pound a 22.70 g/pt; 1) 0.00000016 pounds/32 pt X 454 g/pound a 0.00000227 g/pt; 2) 22.70 g/pt X 1,000 mg/g a • 22,700 mg/pt; 2) 0.00000227 g/pt X 1,000,000 ug/g * 2.27 ug/pt; 2.27 ug/pt X 0.048 pt 3) 22,700 mg/pt X 0.048 pt » 1,089.6 mg; 4) 1,089.6 mg X 10* a 108.96 mg; 5) 108.96 mg / 60 kg a 1.8 mg/kg oar day FEDERAL REGISTER, VOL. 43, NO. 7«—«1DAY, APRIL 21, 197S 0.109 ug; 0.109 ug X 10J a 0.011 ug; 0.011 ug / 60 kg s 0.0001.8 ug/kg. per day �17140 NOTICES . The Working Group considers that the stltute an ample margin of safety. The malathlon In oil sprays applied at 0.43 difference between the no-adverse-effect Working Group therefore recommends Issu- pounds per 0.76 gallons water/acre, deterlevel of 2.4.5-T for teratogenlc effects (20 ance of a rebuttable presumption against mined a dermal exposure to persons directly mg/kg) and this calculated dermal exposure pesticide products containing 2,4,5-T and/or beneath the spray plane for bare skin (head, pursuant to 40 CFB neck, shoulders, forearms, hands, and • level for 2.4.5-T (1.8 mg/kg). as well as the TCDD thighs) of 3.558 mg/day. With these data, difference between the no-adverse-effect 182.11<aX3)(iiXB). for 2,4.5-T (ill) Aerial Application: Exposed Popula- an equivalent dermal exposure pounds acid ' level of TCDD for teratogenlc effects and TCDD, aerially applied at 4 (0.03pg/kg) and this calculated exposure tion Directly Beneath Spray Plane. Caplan equivalent 2.4,5-T per 10 gallons water/acre, level for TCDD (0.00018 Mg/kg). do not con- et al. (1ST), working with aerially applied can be determined. Table 30, Dermal.Exposure Data (Aqrial Application) 1 Dermal exposure to 3.556 ng/0.46 p ounds malathion • .. ." • • " (aerially applied ; per aore 1 malathion , : . " ' '' 1 '."•' 2^4. S-T' ' • TCDD .'•; 0.0000004 lUae Dilution rate • : , /. 4 pounds pounds TCDD 2,4,5-T per i •. i per 10 gal10 gallons of lons of water water/aore per aore i ' \* • i - II Diluted material ,10* (absorbed I '' ' '" i {Exposure level 3.1 mg ii IDosa level I ' 1 iNo-Adverse-Effect [level for"terato1 *enie effect s . - The following calculations (see Table 31 - for mathematics) will give the daily dermal ^ exposure for both 2.4.5-T and TCDD: (1) £ Divide the dermal exposure to malathlon by iri>*: 10$ 0.0003 ug . 5 X 10'6 • ug/kg 20 mg/kg . ! the malathion application rate and multiply by the appUcation rate of 2,4,5-T and TCDD to obtain the dermal exposure: for TCDD, multiply this figure by 1,000 to convert to . Tabl* 3L 5-T TCDD 1) 3.556 ng/0.46 pounds Z . 4 pounds « 31 ng| " 2) 31 Bg Z 10$ * 3.1 13) 3.1 mg/ 60 kg = | 0.051 mg/kg per day 0.03 ug/kg.' mlcrograms; (2) multiply this figure by the percent absorbed; and (3) divide this figure by the weight of the applicator for the daily exposure to 2,4,3-T or TCDD per 8-hour working day. I 1) 3.556 mg/0.46 pounds X 0.0000004 pounds s 0.000003 mg X 1,000 a 0.003 ug; 2) 0,003 ug X 10J a 0.0003 ug; 3) 0.0003 ug / 60 kg s S . T . 10 ug/ktt par day The Working Group considers that the stitute an ample margin of safety. The model for this 2,4,5-T exposure analysis , difference between the no-adverse-effect Working Group therefore recommends Issu- U64). Caplan et al. (1ST) determined an air level of TCDD for teratogenlc effects (0.03 ance of a rebuttable presumption against concentration, for unprotected persons difig/kg) and this calculated dermal exposure pesticide products containing 2,4,5-T pursu- rectly beneath the spray plane during applilevel for TCDD (5 x 10'« jig/kg) does consti- ant to 40 CFR 162.11(aX3XliXB>, cation and for two hours afterward, of 0,067 tute &n ample margin of safety. The Workmg maiathlon/m' from aerial application of (c) Inhalation Exposure.' Aerial Applica- 0.46 pounds Al/gallon per acre. The collecIng Group also considers, however, that the difference between the no-adverse-effect tion. There are no studies available on Inha- tion period spanned the course of the actual level of 2,4,5-T for teratogenlc effects (20 lation exposure of 2.4,5-T. There are. howev- application time plus two hours thereafter. mg/kg) and this calculated dermal exposure, er, several studies on Inhalation exposure to The authors considered the sampling tech.level for 2,4,5-T (0.051 mg/kg) does not con- .malathion (187, 168) which CED used as a nique to be equivalent to average insprira- FEDERAL REGISTER, YOU 43, NO. 78—«ID AY, APML 21, 1978 �17141 NOTICES tioa through the nostrils. This Inhalation exposure (amount available for inhalation) was 12 percent at the applied malathion. Caplan et aL further reported that the average median diameter (- volume median diameter, or vmd ") was 109 microns. Based on work by Akesson and Yates (7SS), CED (164) estimated that the size of the malathion droplets which could be Inhaled was under 80 microns. Since 2,4,5-T Is typically applied as a medium or coarse spray, while malathion is applied as a fine spray, the percent of 3,4,5-T droplets small enough to be Inhaled (under 80 microns) would be less than the percent of malathion droplets small enough to be Inhaled. According to Akesson and Yates USS), 2 percent of 2,4,5-T spray droplets would be available for Inhalation (or H the amount of malathion droplets available for Inhalation), on a "worst case" basis. "The vmd Is that droplet size which di- „ The following calculations (see Table 33 vides the total volume of drop* In half. Le., for mathematics) will give the dally inhala50 percent of the volume Is In drops above tion exposure for both 2,4,5-T and TCDD: (1) Multiply the air concentration of mathe vmd size and 60 percent below it. a 32. Tnhalation Eacnoaur* Data (Aerial Application) I Air concentration of (aerially applied Imalathion 0.067 mg/a° with application rate of 0.46 pounds malathion -per gallon per acre 2.11.«5..T Oa« Dilution rate v " 4 pounds • " -2,4,5-T per 10 gallons of water/acre ' Lung Absorption" . 100* Hate ; , - , , ' • ...- ';. _/" '*'.:. - ' •<; TCDD 0.0000004 pounds TCDD per 10 galIons of water p«r acre 100$ . ' ' '••} ' Breathing Rate 1.8 m3/hr 1.8 a3/hr. Exposure level 0.34 ag per 2 hr 0.000032 ug.per 2 hr 0.023 mg/kg per 8 hr 2 X 10~6ug/kg par 8 hr 20 ag/kg 0.03 ug/kg DOS* 1«V«1 ' •—••?•• No-Adverse-Effeot level for terato*fl«iC; effects Table 31. 2 . 4.5-T 1) 0.067 mg/ou a per 0.46 pounds X 4 pounds a 0.58 ag/ou a X 1/6 a 0*097 . ag/ou a; 2) 0.097 mg/ou a X 1.8 ou a/hr a 0.17 ag/hr; 3) 0.17 mg/hr X 8 > 1.36 ag; 4) 1,36 ag / 60 kg a 0.026 ag/kg exposure oar dav 1) 0*067 ag/ou a per 0.46 pounds X 0.0000004 pounds a 0.000000058 mg/cu a X 1/6 a 0.000000009 mg/ou a X 1,000 a 0.000009 ug/ou a; 2) 0.000009 ug/ou a X 1.8 ou a/hr « 0.000016 ug/hr; 3) 0,000016 ug/hr X 8 a 0.000128 ug; 4) 0.000128 / 60 kg a ' 2 T 10 u«/ka per day lathion by the amount of 2,4,5-T and TCDD applied, then multiply this figure by Vt tor the Inhalation exposure to 2,4,5-T and TCDD; for TCDD, multiply this figure by 1,000 to convert to micrograms; (2) multiply this figure by the breathing rate; (3) multiply this figure by eight [8] to get the 8-hour exposure total: and (4) divide this figure by the weight of the applicator for the Inhalation exposure to 3,4,5-T or TCDD per 8hours exposure. The Working. Oroup considers, that the difference between the no-adverse-effect level of TCDD for teratogenic effects (0.03 jtg/kg) and this calculated dermal exposure level for TCDD (2 x 10 •• fig/kg) does constitute an ample margin of safety. The 1 Working Oroup also considers, however, that the difference between the no-adverseeffect level of 2,4,5-T for teratogenic effects (20 mg/kg) and this calculated dermal exposure level for 2,4,5-T (0.028 mg/kg") does not constitute an ample margin of safety. The Working Oroup therefore recommends Issuance of a rebuttable presumption against pesticide products containing 2,4,5-T pursuant to 40 CFB 162.11(aX3XiiXB). (d) Cumvtative Exposure. The Working Oroup has also considered the possibility of \ a single individual being exposed through two or more of the above routes. The results (derived from Tables 27, 29, and 31) are shown In Table 34. The Working Oroup also notes that possible cumulative exposure to several dioxin-containing pesticides could Increase the total body burden and Increase total risk from dloxin exposure. The Working Oroup considers that the differences between the no-adverse-effect level of TCDD for teratogenic effects (0.03 jig/kg) and the calculated cumulative exposure levels for TCDD in Situations 2 and 3 (see Table 34) do constitute an ample margin of safety. The Working Oroup also considers, however, that the differences between the no-adverse-effect levels of 2,4,5-T and TCDD for teratogenic effects (20 mg/kg and 0.03 Mg/kg, respectively) and the calculated cumulative exposure levels for 2,4,5,-T In Situations 1, 2, and 3 and TCDD In Situation 1 (see Table 34) do not constitute an ample margin of safety. The Working Oroup therefore recommends Issuance of a rebuttable presumption against pesticide products containing 2,4,-fl-T pursuant to 40 CFB 182.11(a)(3XllXB>. "Johnson (83) (see Section I.Q.(3)). In a review article, calculated a dally Inhalation exposure to phenoxy herbicides of 0.025 pg/ kg for a TO-kg adult. The calculations were based on actual air monitoring data of air samples collected in two wheat-growing areas In the state of Washingon during spring and summer and analyzed for phenoxy herbicides. The author did not specify how soon after application the samples were taken. FEDIRAL MOISTS*, VOL, 43, NO. 7«—HIDAY, APRIL 21, 1971 �17142 1 Table ?il. Cumulative Exnosure to 2.4.5-T and TCDD Situation * 1 : TCDD SJitrWB tlon *1 ' 2.4.5-T I OralI Dermalilnhal — (Cum. a I 1 NOTICES 0.0007 mg/kg 6.8 mg/kg 0.2 eg/kg*7 7.0 ng/kg Situation #2: S^tUf lOral0.0007 mg/kg {Dermal- .1.8 mg/kg Ilnhal.- 0.05A/ I Cum. a 1.85 mg/kg I 1 Dermal- 0.0007 ug/kg Inhal;- negligible-47 Cum. s 0.0007 ug/kg Situation tti 2.fl.«5-T - TCDD Dermal- 0.00018 ug/kg Inhal— negligible47 Cuo. a 0.00018 ug/kg Si-tu,ation #3: TCDD (Oral0.0007 mg/kg ! iDarmal- 0.051 ag/kg Dermal- 5 X 10~6 ug/kg • llnhal — 0.026 ag/kg Inhal— 2 X 10'6 ug/kg I Cum. a 0,0777 mz/ki? Cum. s 7 X 10 utt/kfl: A/ Calculations ware made on a worst-case basis as 3J of dermal exposure based on Wolfe (179) who states, "over 97% of the pesticide to which the body is subjected during most exposure situations, and especially to applicators of liquid sprays, is deposited on the skin." fCDD inhalation exposure values were negligible: Situation 11, 21 X 10 u«/kg; Situation »2, 54 X 10~7 ug/kg. KDERAl RCOISTEK, VOL. 43, NO. 79—FRIDAY, AMUl 2), 1978 �DOW HERBICIDE FOR THE CONTROL OF TREES, BRUSH AND BROADLEAF WEEDS Low-Volatile Brush and Weed Herbicide for Industrial, Forestry, Rangeland and Pasture Uses KEEP OUT OF THE REACH OF CHILDREN ACTIVE INGREDIENT: id. Propylene CAUTION Glycol Butyl Ether Esters c Acid Equivalent—45.0°o 4 Pounds per Gallon 30.8°o INERT INGREDIENTS: E.P.A. Registration No. 464-205 E.P.A. Est. 464-MI-1 MAY BE HARMFUL IF SWALLOWED • MAY CAUSE IRRITATION Avoid Contact with Eyes. Skin and Clothing Do Not Cut or Weld Container PRECAUCION AL USUARIO: Si usted no lee ingles, no use este producto hasta que la etiqueta le haya sido explicada ampliamente. In case of an emergency endangering life or property involving this product call collect TRANSLATION: (TO THE USER: If you cannot read English, do not use this >el has been fully explained to you.) 517-636-4400 18.93 L / 5 GAL 8 - 0 4 PRINTED IN U.S.A. IN APRIL, 1978. 616 REPLACES SPECIMEN LABEL 86-1064 PRINTED OCTOBER, 1977. DISCARD PREVIOUS SPECIMEN LABELS. REVISIONS INCLUDE: (1)EMERGENCY RESPONSE PHONE NUMBER ADDED. (2) "DO NOT CUT OR WELD CONTAINER" ADDED. AGRICULTURAL CHEMICAL Do Not Ship or Store with Food. Feeds, Drugs or Clothing �Dow ESTERON 245 HERBICIDE Contains Propylene Glycol Butyl Ether Esters of 2,4,5-T • Acid Equivalent: 4 Pounds per Gallon DIRECTIONS ESTERON 245 herbicide is recommended for industrial vegetation control in forest areas; on right-of-ways, such as communicotian lines, electrical powerlines, pipelines/ highways, and railroads; fence raws; and on rangelands and pastures. This herbicide controls herbaceous and woody plants including such 2,4-D resistant species as — ash, black gum, brambles, groundcherry, hawthorn, horsenettle, maple, mesquite, oak, osageorange, palmetto, poison ivy, pricklypear cactus, redbay, salmonberry, sweetgum, wild blackberry, wild rose, and certain species of Ribes. Do not apply ESTERON 245 where spray drift may contact nearby 2,4,5-T susceptible crops or other desirable plants or may contaminate water intended for irrigation or domestic purposes. Read and follow ail Use Precautions given an this label. PREPARING THE SPRAY Use only diesel oil. No. 1 or No, 2 fuel oil or kerosene where oil is recommended in the spray mixture. Oil Sprays: Add ESTERON 2-45 to the required amount of oil in the spray tank or mixing tank and mix thoroughly. This mixture can be made at any time before actual use and no separation will occur. Do not let any water, or oil-water mixture sprays get into the ESTERON 245 or into the finished mixture, as it may form a gel. Water Sprays: Fill the spray tank about half full with clean water, add the required amount of ESTERON 245 and complete filling the tank. Mix thoroughly and continue agitation while spraying. Caution; See NOTE in paragraph on Oil-Water Mixture Sprays. Oil-Water Mixture Sprays: When vigorous agitation is used, 1 gallon of ESTERON 245 will emulsify up to 10 gallons of oil in 100 gallons of spray mixture. First, premix the ESTERON 245 and oil in a separate container. Do not allow any water or mixtures containing water to get into the ESTERON 245 or the premix. Fill the spray tank about half full with water, then slowly add the premix with continuous agitation and complete filling the tank with water. If the premix is put in the tank without any water, the first water added may form a thick "invert" (water in oil) emulsion which will be hard to break. As an alternate procedure, the oil may be added after the ESTERON. 245 is mixed in the water; but highly vigorous mechanical agitation is required and a poor emulsion may be formed. The premix method is preferred. NOTE: ESTERON 245 in water or oil-water sprays forms an emulsion, not a solution, and separation may take place unless sprays are agitated continuously. Mechanical agitation Is recommended. INDUSTRIAL BRUSH AND WEED CONTROL INCLUDING FORESTRY USES in 4 gallons) of oil, mixed thoroughly. For more resistant species, use 4 gallons of ESTERON 245 in 100 get (Ions (1 pint in 3 gallons) of oil. Wet thoroughly all exposed bark, as well as cut surfaces. This means spraying until run-down or run-off to the ground line is noticeable. Old or rough bark requires more spray volume than young or smooth bark. Apply at any time, including the winter months, except when ice, snow or water prevent spraying to the ground line. Best results are obtained on freshly cut stumps two inches across or larger. Adequate coverage normally requires from 10 to 100 gallons per acre depending on density of stumps and stubs. "Frill" Treatment: For large trees, make a singlehack girdle or "frill" of overlapping axe cuts completely around the tree as close to the ground as feasible. Spray the frill thoroughly using a mixture of 2 gallons of ESTERON 245 in 100 gallons (V2 pint in 3 gallons) of oil. Spot Foliage Treatment: Use VA pint of ESTERON 245 in 3 gallons of water and spray to wet all foliage, shoots, stems and bark without runoff, LOW VOLUME SPRAYS Apply low volume sprays containing ESTERON 245 when foliage is well developed and plants are actively growing. For best results an woody species, soil moisture should be sufficient to promote foliar growth. Spraying during prolonged hot, dry weather or after leaves have lost their normal green color and vigor may not give satisfactory control. Apply low volume sprays by air or ground equipment only when spray drift will not be a problem — note use precau ions. Right-of-Ways and Forest Site Preparation Foliage Treatment: Use 1 to 3 gallons of ESTERON 245 in enough water to make 10 to 30 gallons of total spray per acre. If desired, oil can be added to the spray in accordance with directions for "Oil-Water Mixture Sprays" given under PREPARING THE SPRAY. Use With TORDON 101 Mixture: ESTERON 245 may be used with TORDON* 101 Mixture herbicide in a tank mix combination spray applied by aircraft for improved control of roof sucker ing species and other species often not adequately controlled with 2,4,5-T. Use 1 to 2Va gallons of ESTERON 245 Herbicide plusl'Ato 2J/2 gallons of TORDON 107 Mixture peracre by diluting with water to a total spray volume of 10 to 30 gallons per acre. Use the higher rates where resistant species such as red maple, sourwood, ash, oaks, hawthorn and cedar are prevalent and especially during unfavorable conditions for plant growth such as drought. Do not add oil or NORBAK* particulating agent to the spray. Aerial applications of the tank mixture should be made only with a helicopter mounted Microfoil applicator or art equipment system providing equivalent drift control. Read the directions and all the Use Precautions on both labels before using this tank mix. HIGH VOLUME SPRAYS Foliage Treatment: For control of woody vegetation up to 8 feet tall, apply when foliage is well developed and plants are actively growing. Spraying during prolonged hot, dry weather or after leaves have tost their normal green color and vigor may not give satisfactory control. Use 3 to 4 quarts of ESTERON 245 in 100 gallons of water and apply as a full coverage spray. Usually 100 to 200 gallons per acre will be required, although dense stands of brush may require up to -400 gallons per acre. Completely wet all plant parts including leaves, stems and bark. Poison ivy, some brambles and many broadleaf weeds may be controlled using 2 quarts of ESTERON 245 in 100 gallons of water. To control grasses as well as broadleaf weeds and woody plants on conifer forest planting sites, ESTERON 245 may be used in a tank mixture with DOVVPON* grass herbicide. Consult label directions and precautions for DOWPQN to determine recommended use of this product. Basal Bark Treatment: Brush and small trees can be controlled by spraying the basal parts of brush stems and tree trunks to a height of 12 to 15 inches from the ground line. Use a solution of 3 gallons of ESTERON 245 in TOO gallons (T pint in 4 gallons) of oil. With certain resistant species, 4 gallons of ESTERON 245 in TOO gallons (1 pint in 3 gallons) of oil, is effective. As only the basal portions of the brush are treated on a spot basis, the total amount sprayed per acre would not be expected to exceed 100 gallons. Knapsack or power equipment may be used, but complete wetting of the indicated area is necessary, particularly at the ground line. This means spraying until run-down or run-off to the ground line ts noticeable. Old or rough bark requires more spray than young or smooth bark. Low pressures are desirable. Apply at any time, including the winter months, except when snow, ice or water prevent spraying to the ground line. Often delayed response and killing can be expected. Dormant Brush: Treat any time after brush is dormant and most of the foliage has dropped. Spray should be concentrated at the base of stems and in addition, the upper parts of the stems should be broadcast sprayed enough to wet them. Under rootsockering species such as sumac, persimmon, sassafras and locust, also spray the ground area to control small root suckers that may not be readily visible. Mix 1 Vz gallons of ESTERON 245 in 100 gallons of oil. Brush of average density and 4 to 6 feet high may take up to 150 gallons of spray mixture per acre. Stump Treatment: Where growth is more than 6 to JHeet tall, cut it close to the ground and spray the freshly cut stumps and stubs with 3 gallons of ESTERON 245 in 100 gallons (1 pint Note: Do not plant conifer seedlings on treated areas for at least 6 months after applying 2 gallons or more of TORDON 101 per acre in such a tank mix. Basal Treatment Using Powered Knapsack Sprayer-Mix V/s to 2 gallons of ESTERON 245 with fuel oil or kerosene to make 20 gallons of total spray solution. Apply with a portable knapsack mistblower to all sides of lower brush stems including the root collar. Good coverage of the root collar is essential for best results. Run mistblower at 14 to Vb throttle for best spray delivery and coverage, for maximum drift control use a basal nozzle attachment and do not raise nozzle above the horizontal position. Forest Conifer Release by Air or Ground Sprays Oil Spray—Apply 2 to 3 quarts of ESTERON 245 in about 10 gallons of oil per acre to control undesired hardwoods in dormant Douglas fir, true fir, hemlock and spruce. Rates higher than 2 quarts may cause conifer injury. Do not use this spray on pines (note section below for pine recommendation). Apply before conifer bud break during late dormancy, usually February and March in the northwest. Application of this spray after conifer bud break can injure the conifers, Water Spray—Apply 2 to 3 quarts of ESTERON 245 in 10 to 15 gallons of water per acre to control hardwood species in conifers including pines. Apply during the summer after the conifers cease spring growth and have "hardened off". Rates higher than 2 quarts may cause conifer injury. Consult your State, Regional or Extension Forester for recommendations to fit local con- PASTURE-FOR BROADLEAF WEED CONTROL Use 2 to 3 quarts of ESTERON 245 per acre by aircraft or ground equipment in the amount of water needed to obtain uniform application. Apply when weeds are in full leaf and after grass is well established. Do not apply on stoloniferous grasses such as bent and bermuda or on forage legumes because these can be injured or killed. Do not apply on newly seeded areas, and do not use from early boot to milk stage where grass seed production is desired. Note: Do not graze dairy animals on treated areas within 6 weeks after application. Do not graze meat animals on treated areas within 2 weeks of slaughter. USE PRECAUTIONS AVOID CONTACT WITH 2,4,5-T SUSCEPTIBLE CROPS AND OTHER DESIRABLE BROADLEAF PLANTS — ESTERON 245 Herbicide is injurious to most broadleaf plants. Therefore, do not apply directly to or otherwise permit even minute amounts to contact cotton, grapes, tobacco, fruit trees, vegetables, flowers, ornamentals or other desirable plants susceptible to 2,4,5-T. Do not use in or near a greenhouse. DO NOT APPLY IN THE VICINITY OF COTTON, GRAPES, TOBACCO, TOMATOES OR OTHER DESIRABLE 2,4,5-T SUSCEPTIBLE CROPS OR ORNAMENTAL PLANTS. DO NOT SPRAY WHEN WIND IS BLOWING TOWARDS SUSCEPTIBLE CROPS OR ORNAMENTAL PLANTS AVOID SPRAY DRIFT—Applications should be made only when there is no hazard from spray drift since very small quantities of the spray, which may not be visible,, may severely injure susceptible crops during both growing and dormant periods. Use coarse sprays to minimize drift since, under adverse weather conditions, fine spray droplets may drift a mile or more. The spray thickening agent, NALCO-TROL1, may be used with this product to aid in reducing spray drift. If used follow all use recommendations and precautions on the product label. 1 NAICO-TROI—Trademark of NALCO Chemkal Company GROUND EQUIPMENT—With ground equipment, spray drift can be lessened by keeping the spray boom as low as possible; by applying 20 gallons or more of spray peracre; by using no more than 20 pounds spraying pressure with large droplet producing nozzle tips; by spraying when wind velocity is 8 miles per hour or less. Do not apply with hollow cone-type insecticide or other nozzles that produce a fine-droplet spray. AERIAL APPLICATION—With aircraft, drift can be lessened by applying a coarse spray; by using no more than 20 pounds spray pressure at the nozzles; by using straight stream nozzles directed straight back; by using a spray boom no longer than %the wing span of the aircraft; and by spraying only when wind velocity is less than 6 mph. DO NOT APPLY BY AIRCRAFT WHEN AN AIR TEMPERATURE INVERSION EXISTS. Such a condition is characterized by little or no wind and with air temperature lower near the ground than at higher levels. The use of a continuous smoke column at or near site of application is suggested to indicate direction and velocity of air movement, and to indicate a temperature inversion by layering of the smoke. At high temperatures (above 95°F) vapors from this product may injure susceptible plants growing nearby. Do not use in or near a greenhouse. Excessive amounts of this herbicide in the soil may temporarily inhibit seed germination or plant growth. Do not use around the home, recreation areas or similar sites. Do not use on susceptible grasses, such as bent, except for spot spraying, nor on freshly seeded areas until grass has become well established. (Most legumes are usually damaged or killed). RANGELANO AND PASTURES RANGEIAND-AIR APPLICATION FOR BRUSH CONTROL Consult the Agricultural Experiment Station, your local Extension Service Weed or Range specialist for best time to treat and need for re-treatment in your area. Do not use from early boot to milk stage where grass seed production is desired. Mesquite: Use 1 pint of ESTERON 245 plus '/2 to 1 gallon of oil in enough water to make 4 gallons of total spray per acre. Apply 40 to 90 days after first leaves appear. Sand Shinnery Oak: Use '/2 to 1 quart of ESTERON 245 plus 1 gallon of oil in enough water to make 4 gallons of total spray per acre. Post and Blackjack Oaks: Use 2 quarts of ESTERON 245 plus 1 gallon of oil in enough water to make 4 to 6 gallons of total spray per acre. This product is toxic to fish. Keep out of lakes, streams, and ponds. Do not contaminate water by cleaning of equipment or disposal of wastes. Do not contaminate irrigation ditches or water used for irrigation or domestic purposes. This product can be stored in an unheated building but if exposed to subffeezing temperatures, should be wanned to at least 40°F and mixed thoroughly before using. Do not store near fertilizers, seeds, insecticides or fungicides. Do not reuse containers. To avoid injury to desirable plants, do not store, handle or apply other agricultural chemicals with the some containers or equipment used with ESTERON 245 except as specified on this label. Rinse equipment and containers and dispose of waste by burying in non-crop lands away from water supplies. Containers should be disposed by punching holes in them and burying with waste or follow official local recommendations for container disposal. Local conditions may affect the use of herbicides- Consult your State'Agricultural Experiment Station or Extension Service weed specialist for advice in selecting treatments from this label to best fit local conditions. Be sure that use of this product conforms to all applicable regulations. Apply this product only as specified on this label. NOTICE; Seller warrants that the product conforms to its chemical description and is reasonably ftt far the purposes stated on th« label when used in accordance with direction* under normal conditions of use, but neither this warranty nor any other warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE, express or implied, extends to the use of this product contrary to label instructions, or under abnormal conditions, or under conditions not reasonably foreseeable to seller, and buyer assumes the risk of any such use. 10586-049-7 THE DOW CHEMICAL COMPANY AND SUBSIDIARIES MIDLAND, MICHIGAN 4 8 6 4 0 , USA HORGEN, SWITZERLAND CORAL GABLES, FLORIDA 3 3 1 3 4 , USA HONG K O N G SARNIA, ONTARIO, CANADA * Trademark of THE DOW CHEMICAL COMPANY R278 � 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 5244 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. Date A point or period of time associated with an event in the lifecycle of the resource August 4 1978 Title A name given to the resource Realistic Evaluation of Human Exposure from Application of 2,4,5-T Sprays ao_seriesVIII https://www.nal.usda.gov/exhibits/speccoll/files/original/71ffbcbbad4ac1cfa431d23b00c5f26a.pdf ca7e266c8bcc9d9bd27ef2466f812d0a PDF Text Text item D Number °5241 Leng, Marguerite L. Corporate Author RBpOrt/ArtiClB Title Letter to Federal Register Section, Technical Services Division, Office of Pesticide Programs, EPA from Marguerite L. Leng, July 7, 1978 Journal/Book Title Year 000 ° Month/Day Color D Number of Images ° DBSCrlptOn NOtBS Letter has subject line 2,4,5-T Rebuttable Presumption Against Registration OPP 30000/26. Leng is responding to the RPAR and encloses two of her papers. First is "Comparative Metabolism of Phenoxy Herbicides in Animals" in Fate of Pesticides in Large Animals, 1977 (not scanned), and the second is a draft of "Government Requirements for Pesticide Residue Analyses and Monitoring Studies" Chapter 11 in Pesticide Residue Analysis, January 31, 1977. Friday, March 01, 2002 Page 5241 of 5263 �l>1*r* 1714 Sylvan Lane Midland, Michigan 48640 July 7, 1978 Federal Register Section Technical Services Division (WH-569) Office of Pesticide Programs, EPA Room 401, East Tower 401 M Street SW Washington, D. C. Subject: 20460 2,4,5-T Rebuttable Presumption.Against Registration OPP 30000/26 This response to the 2,4,5-T RPAR is prompted by my dedication as a scientist who is continually seeking knowledge about the effects of chemicals on man and his environment. I am submitting it as an individual who is an active member in the Division of Pesticide Chemistry of the American Chemical Society, rather than as a person who is currently employed by Dow Chemical, one of the principals in the continuing debate on the safety of this useful herbicide. Enclosed are pertinent excerpts of two documents dealing with studies on phenoxy herbicides in humans, and with the reliability of data on residues of 2,4,5-T and its trace contaminant TCDD in foods and environmental samples. The first paper summarizes three studies with phenoxy herbicides in humans. It includes a discussion about the fallacy of using data from studies at highly exaggerated dosage levels to predict what might happen at levels likely to be encountered from recommended uses of 2,4,5-T. (This paper was cited as reference 79 in EPA's 2,4,5-T Position Document No. 1, but only as a basis for calculating highly exaggerated residues for 2,4,5-T in meat and milk.) The second enclosure is from my draft chapter on government requirements for pesticide residue data and monitoring studies, scheduled for publication in 1978. As indicated in this excerpt, many of the allegations of hazard from use of 2,4,5-T are based on data from studies which do not meet even minimum requirements for such investigations. Sincerely, / ' Marguerite L. Leng, Ph.D. abc cc to attached list. �M. L. Leng letter dated 7/7/78 2,4,5-T Rebuttable Presumption Against Registration OPP 30000/26 Copies to: Federal Register Section Technical Services Division (WH-569) Office of Pesticide Programs, EPA Room 401, East Tower 401 M Street SW Washington, D. C. 20460 Dr. Gerald G. Still, Chairman Division of Pesticide Chemistry American Chemical Society USDA, ARS West Building 005 Beltsville, MD 20705 Mr. Edwin L. Johnson Deputy Assistant Administrator (WH-566) Office of Pesticide Programs, EPA 401 M Street, SW Waterside Mall, East Tower Washington, D. C. 20460 Dr. Philip C. Kearney Chairman, Technical Advisory Group National Agricultural Pesticide Impact Assessment Program USDA, Office of Environmental Activities Office of the Secretary 14th and Independence Ave., SW Washington, D. C. 20250 Dr. William A. Wells Acting Administrator Special Pesticide Reviews Div. (WH-566) U.S. Environmental Protection Agency Office of Toxic Substances 401 M Street, SW Waterside Mall, East Tower Washington, D. C. 20460 Representative James G. Martin (North Carolina) 115 Cannon House Office Building Washington, D. C. 20515 Mr. Douglas M. Costle Administrator (A-100) Environmental Protection Agency Room 1200 Waterside Mall, West Tower 401 M Street SW Washington, D. C. 20460 Harvey L. Warnick Office of Special Pesticide Review (WH-566) Environmental Protection Agency Waterside Mall, East Tower 401 M Street SW Washington, D. C. 20460 Dr. Anna Harrison, President American Chemical Society Carr Laboratory Mount Holyoke College South Hadley, Massachusetts 01075 �GOVERNMENT REQUIREMENTS FOR PESTICIDE RESIDUE ANALYSES AND MONITORING STUDIES by Marguerite L. Leng Government Registration Dow Chemical U.S.A. Midland, Michigan Chapter 11 in PESTICIDE RESIDUE ANALYSIS edited by H. Anson Moye No. 43 in Wiley Interscience Series of Monographs on Analytical Chemistry and Its Applications Philip Ebving and James D. Winefordner, Editors January 31/ 1977 �TABLE OF CONTENTS 1. INTRODUCTION 2. REGULATION OF PESTICIDES 2.1 Government Agencies 2.2 Laws Regulating Pesticides 2.2.1 The Federal Insecticide/ Fungicide, and Rodenticide Act 2.2.2 The Federal Food, Drug, and Cosmetic Act 2.2.3 Implementation of Laws on Pesticide Residues 2.2.4 3. History of Tolerances for 2,4-D in Food Crops RESIDUE DATA REQUIREMENTS 3.1 Analytical Methodology 3.1.1 Validation of the Method 3.1.2 Extraction Efficiency 3.1.3 3.1.4 Total Residue Including Metabolites Regulatory Method 3.2 Residue Studies in Plants 3.2.1 3.2.2 3.2.3 3.2.4 3.2.5 3.2.6 3.2.7 3.3 Field Experiments Sampling Residues in Crops Residues in Crop Byproducts Crop Groupings for Residue Data Negligible or Low Level Residues Temporary Tolerances Residue Studies in Animals 3.3.1 3.3.2 3.3.3 Residues from Treated Plants Residues from Treatment of Animals Residues from Treatment of Agricultural Premises 3.4 Miscellaneous Residue Studies 3.4.1 Aquatic Sites 3.4.2 Stored Commodities 3.4.3 3.4.4 3.4.5 3.4.6 3.4.7 Food Handling Establishments Seed Crops and Seeds Postharvest Treatments Minor Changes in Use or Formulation Imported Foods 3.4.8 Environmental Studies �3.5 Reporting of Residue Data 3.5.1 3.5.2 3.5.3 3.5.4 4. Identification of Report Residue Summary Body of Report Tables and Figures MONITORING STUDIES 4.1 National Pesticides Monitoring Program 4.1.1 Working Group and Monitoring Panel 4.1.2 Pesticides Monitoring Journal 4.1.3 Pesticides in National Monitoring Program 4.2 National Food and Feed Monitoring Program 4.2.1 Surveillance of Unprocessed Food and Feed 4.2.2 Surveillance of Meat and Poultry 4.2.3 Total Diet Studies on Market Basket Samples 4.3 Pesticide Residues in Environmental Samples 4.3.1 Monitoring Studies in Fish/ Wildlife and Estuaries 4.3.2 Monitoring for Pesticides in Soil/ Water and Air —— 4.4 Monitoring in Humans -—— 4.5 Special Monitoring Programs 5. INTERPRETATION OF RESIDUE DATA *—"— 5.1 Variability among Samples 5.2 Sensitivity vs Limit of Detection —— 5.3 Interpretation of Monitoring Data —— 5.4 Confirmation of Residue Identity — "• 5.5 Statistical Evaluation of Results 6. CONCLUSION 7. ACKNOWLEDGEMENT 8. REFERENCES �-4- 1. INTRODUCTION Requirements for analysis of pesticide residues have increased vastly since the 1950's when regulations were first implemented to require tolerances (maximum residue limits) for these useful chemicals in food crops intended for human and animal consumption. The evolution of changes in such requirements can be traced in reviews published between 1955 and 1971 by Gunther and Blinn (1), Pogelman (2), Harris (3), Vorhes (4), Frehse (5), Harris and Cummings (6), and Bevenue and Kawano (7). In 1968/ the U.S. Food and Drug Administration issued FDA Guidelines for Chemistry and Residue Data Requirements of Pesticide Petitions (8). These official guidelines described the studies needed at that time for obtaining analytical data suitable for establishment of tolerances for pesticides in food and feed crops and their byproducts, as well as in meat, milk, poultry and eggs. During the early 1970's bills were passed in the U.S. House and Senate proposing major revisions in the Federal Insecticide, Fungicide/ and Rodenticide Act (FIFRA), resulting in passage of the Federal Environmental Pesticide Control Act (FEPCA) on October 8, 1972. Detailed regulations for implementation of Section 3 on Registration of Pesticides were finalized by publication in the Federal Register on July 3, 1975 (9). �-5- At that time certain sections were "Reserved" for later issuance, Registration Procedures were published as regulations on September 9, 1975 (11). A preliminary draft of sections on Petitions for Tolerances (12) was made available by EPA in 1975 for comment by outside experts, but a revised version has not been issued as of this writing. Review of the draft indicated that requirements for residue data by the Environmental Protection Agency (EPA) under FIPRA as amended will be similar but more extensive than those outlined by FDA under the Food, Drug ( and Cosmetic Act in' 1968 (8) . Proposed guidelines for studies to meet Section 3 Regulations were published in the Federal Register on June 25, 1975 along with extensive appendices outlining how the studies should be conducted (10). Final guidelines are scheduled for publication in 1977 incorporating revisions based on comments by other government agencies, industry, and any interested parties. This chapter presents a brief outline of how certain government agencies control.pesticides, of the laws under which they operate, of regulations implemented to carry out this task, and of how tolerances were established for the herbicide 2,4dichlorophenoxyacetic acid (2,4-D) over a period of 25 years under these laws and regulations. It also provides a detailed description of current requirements for residue data based on �proposed EPA Guidelines, based in part on personal experience during more than ten years of compiling data in petitions for tolerances, including many volumes on residue studies with 2,4-D. Finally, it discusses monitoring studies for pesticide residues in raw agricultural commodities, total diet samples, and environmental samples, as well as pitfalls in interpretation of "positive" findings. �-78- 4. MONITORING STUDIES During the 1960's, concern grew about potential long-term effects of persistent pesticides in the environment. This concern was fed in part by reports of finding residues of DDT in samples such as pelicans, walruses, and even soil far removed from where the insecticide had been used. The impact of such reports has continued long after many of the results of early studies have been refuted by more specific analytical data. Positive findings originally attributed to DDT have often been shown to be due to the presence of PCB's (polychlorinated biphenyls) (48). More recently, environmental and laboratory contamination by phthalate esters has been shown to cause responses frequently mistaken for DDT residues (49). Thus, it is imperative that analytical methods used in monitoring for pesticides are specific for the chemicals being sought and that positive findings are confirmed by secondary methods based on different principles of analysis. 4.1 NATIONAL PESTICIDES MONITORING PROGRAM The National Pesticide Monitfsring Program (NPMP) was initially designed on the basis of the minimum monitoring needed to establish baseline levels of pesticideSvin substrates of food and feed, humans, soil, water, air, wildlirX, fish and estuaries, �-98- Variables such as wihdjrain, temperature, snow, and inversion are unpredictable and sfr®nl.d be recorded during the sampling period. 4-4 MONITORING IN HUMANS Concern about potential long-term effects of persistent chemicals led to the National Human Monitoring Program for Pesticides. In 1967, the Division of Pesticide Community Studies initiated a program in which adipose tissue (fat) was to be collected from postmortem and surgical specimens (50). The design provided for sampling which would yield valid data concerning pesticide incidence variation with geographic distribution, and with age, sex, and race variation of the donors. The sampling population was drawn from sources in cities of 25,000 or more population (1960 figures) distributed among the four census regions (Northeast, North Central, South, and West), without regard for the donor's occupation. The total number of collection points (or pathologists) was 39 and each was to provide a minimum of 50 samples per year, for an annual total of at least 1950 random samples. For each collection point, the sample quota was further broken down by age and sex: 14 years and under, male and female; 15 through 49 years, male and female; and 50 years and over, male and female. Since the program objective was to reflect �-99- the incidences in the normal (man-on-the-street) general population, samples were excluded from cases of known or suspected acute pesticide poisoning or chronic debilitating illness, and from patients who had been institutionalized for long periods. Analyses of human adipose tissue were initially limited to the measurement of certain chlorinated hydrocarbons due to sensitivity limitations of available analytical methodology. The program originally included only DDT and its metabolites, dieldrin, heptachlor epoxide, and the isomers of BHC. As refinements of methodology progressed, additional pesticide chemicals or metabolites were added such as oxichlordane and mirex. Other pollutants such as PCB's (polychlorinated biphenyls) were added as they became identifiable. 4.5 SPECIAL MONITORING PROGRAMS Special programs are instituted as problems arise or are suspected. Many of these are a result of industrial pollution or accidental contamination rather than from direct use of pesticides. One such example was a monitoring program for mercury, or more specifically methyl mercury, in fish and bottom sediments in the Great Lakes attributed to dumping of wastes from giant electrolytic processes. A more localized �-100- problem was contamination of cattle and poultry in Michigan beginning in 1973 from ingestion of feed containing polybrominated biphenyls (PBB's). Intensified programs are also put into operation when emergency use of cancelled pesticides is authorized. During recent years, EPA has taken stepwise action against DDT, mirex, aldrin and dieldrin, heptachlor and chlordane, and other chlorinated hydrocarbons are expected to follow. However, in the absence of adequate substitutes, EPA occasionally approves limited use of DDT to prevent spread of a specific pest. Similarly, EPA issued a permit in 1976 for aerial application of mirex to control fire ants on six million acres in Georgia, Mississippi, Louisiana, and Arkansas. Scientists from APHIS will monitor water, soil, sediment, invertebrates (crabs and crayfish), and vertebrates (mostly birds) to determine the fate of residues in the non-target environment. Such monitoring programs using specific method- ology should provide more reliable information on the persistence of these useful pesticides in the environment. Expansion of special programs is anticipated as EPA continues to review data for other pesticides on their list of candidates for Rebuttable Presumption Against Registration (RPAR). Several chlorinated phenols and phenoxy herbicides are included �-101- in the list, due in part to the presence of dioxin contaminants. The most widely publicized of these is the herbicide 2,4,5trichlorophenoxyacetic acid (2,4,5-T), originally implicated as a teratogen in screening studies at high doses in susceptible strains of mice. The 2,4,5-T used in the first teratogenic studies by Bionetics (60) contained about 30 ppm of the highly toxic 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). This dioxin is formed during the manufacture of 2,4,5-trichlorophenol from tetrachlorobenzene at high temperatures under alkaline conditions. Current specifications are for less than 0.1 ppm TCDD in 2,4,5-T and other pesticides derived from 2,4,5-trichlorophenol, such as the herbicide silvex (2,4,5-trichlorophenoxypropionic acid) and the fungicide hexachlorophene (2,2'-methylene bis(3,4,6-trichlorophenol)). Cancellation proceedings against 2,4,5-T were withdrawn by EPA in June 1974 pending results of extensive monitoring studies for TCDD. Analytical methods have been developed capable of detecting residues down to 10 parts per trillion (0.00001 ppm) or less in milk, fat, .and environmental samples (61, 62). However, caution is needed in attributing positive responses at this level to the actual presence of TCDD residues due to interferences from unrelated substances in the same samples. The TCDD monitoring program initially called for sampling of many substrates including human milk, fat, and liver. �-102- Substrates most likely to contain residues were samples taken from range cattle maintained in areas with a confirmed history of repeated treatment with 2,4,5-T for many years, and slaughtered without the usual fattening period in a feed lot. Samples of fat from these animals were distributed to several cooperating laboratories including EPA and The Dow Chemical Company. Preliminary results were erroneously reported in 1975 to indicate "positive" results for about 50% of the initial 34 fat samples analyzed, but the findings were not consistent among the laboratories conducting the analyses. As reported by Dr. Ralph T. Ross, Chairman of the EPA Dioxin Project in June 1976 (63), only one of the 85 beef fat samples analyzed showed a positive TCDD level at 60 ppt, and two samples appeared to have TCDD levels at 20 ppt. He also stated that the analytical method is not valid below 10 ppt. The method used in the above analyses involves use of gas chromatographic separation to remove interfering substances, in combination with high resolution mass spectrometry for quantitation. This method has also been used to analyze other monitoring samples collected by Dow. As reported by Shadoff in 1975 (64), no residues of TCDD were detected in samples of fish, water and mud from two locations in Arkansas and Texas that have a long history of treatment with 2,4,5-T �-103- containing considerably more than the current limit of 0.1 ppm TCDD. Thus, it seems unlikely that continued use of 2,4,5-T would result in significant residues of TCDD in the environment. Addendum, July 1978 Reports of the study by Shadoff et al. (above) and of two studies on surveillance samples of milk and beef fat were published in 1977 and 1978. Summaries of these studies are quoted below. Summary -' As part of a broad study to determine whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is accumulating in the environment due to approved uses of 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) based herbicides, samples of fish, water, mud and human milk were collected from areas in Arkansas and Texas where 2,4,5-T herbicides are used and were analyzed for TCDD. No TCDD was detected by a GC-MS procedure with a detection limit which averaged less than 10 ppt. 2/ Conclusion •=* Surveillance samples of milk from the states of Oklahoma, Arkansas, and Missouri were collected from cows grazing on pasture or rangeland treated with normal applications of 2,4,5-T. These samples and control samples were analyzed for TCDD by GC/MS. A detection limit of 1 ppt was achieved. With this sensitivity the control samples were indistinguishable from those from treated areas. Hence, TCDD was not found. 3/ Summary — Specimens of fat taken from steers which had grazed on rangeland previously treated with 2,4,5-T herbicides were analyzed for the presence of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). A cleanup procedure resulting in a 500-fold concentration was followed by a gas chromatographymass spectrometry detection technique. The limit of detection of TCDD (2.5 times peak to peak noise) was found to be in the 30-60 picogram range (3-6 ppt in beef fat using 10 gram samples). None of the sixteen samples comprising two of the three studies showed any response for TCDD. In the third study, in which the animals were confined to a fenced pasture sprayed in its entirety with a 2,4,5-T herbicide, samples from three of the seven animals gave a positive response at the extremely low level of 3 to 4 ppt TCDD. which is'at the detection limit. — Shadoff, L.A., Hummel, R.A., Lamparski, L., and Davidson, J.H. A Search for 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) in an Environment Exposed Annually to 2,4,5-Trichlorophenoxyacetic Acid Ester (2,4,5-T) Herbicides. Bull. Environ. Contam. Toxicology 18_, 478-485, 1977. 2/ — Mahle, N.H., Higgins, H.S., and Getzendaner, M.E. Search for the Presence of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Bovine Milk. Bull. Environ. Contam. Toxicology 18., 123-130, 1977. -^Kocher, C.W., Mahle, N.H., Hummel, R.A., Shadoff, L.A., and Getzendaner, M.E. A Search for the Presence of 2,3,7,8-Tetrachlorodibenzo-p-dioxin in Beef Fat. Bull. Environ. Contam, Toxicology, ]J9, 229-236, 1978. �-104- 5. INTERPRETATION OF RESIDUE DATA Several basic principles should be applied in the interpretation of positive responses obtained in pesticide residue analyses. For example, a nanogram quantity of a pesticide in a solvent may cause a measurable peak in a gas chromatogram. However, the same quantity may not be distinguishable when superimposed on the "noisy" background obtained from extracts of a substrate. Similarly a small peak from a treated sample should not be compared directly to a large peak from a sample spiked at a considerably higher level. Recovery studies should include complete analyses of several control samples fortified at the claimed sensitivity of the method. Any "positive" responses below that should be reported as "less than" or "traces". A response below the limit of detection should be reported as "none-detected" since it is not possible to demonstrate a zero residue. For example, a residue of only 0.01 ppm DDT still represents 1013 molecules per gram of foodstuff (65). Above all, confirmation of residue identity is needed before instrument responses can be translated into positive values. 5.1 VARIABILITY AMONG SAMPLES The inherent biological variation among individuals of the same species can cause differences in response during analysis which might be interpreted as positive residue �-105- values unless numerous samples were analyzed. For example, in a recent study reported by Clark et al, (66), residues of several chlorinated hydrocarbon insecticides in fat of groups of feedlot cattle were compared to the residues in the feed given to them for 112 days prior to slaughter. Both feed and fat samples contained detectable levels of lindane, dieldrin, DDT, DDE, and DDD. Except for dieldrin, each insecticide was found at higher levels in fat than in feed. However, the levels were consistently low except for DDT and its degradation products in fat. Average values for lindane were 0.002 ppm in feed and ranged from 0.014 ppm to 0.032 ppm in fat of five groups of ten calves each given various levels of ammonium salts in addition to the feed. Average levels found for DDT were 0.083 ppm in feed and ranged from 0.324 ± 0.256 ppm in fat from Group II to 0.518 ± 0.104 ppm in Group IV. If only average values for DDT are compared, a significant difference appears to exist between Groups II and IV. However, overlap of values for individuals in the two groups shows that they are not different (i.e., 0.324 +0.256 = 0.580 which is higher than 0.518 - 0.104 = 0.414) .' 5.2 SENSITIVITY VS LIMIT OF DETECTION As discussed recently by the Federal Working Group on Pest Management, the terms sensitivity and limit of detection do �-106- not have the same meaning (52). Sensitivity depends on the response of an instrument such as a gas chromatograph under a specific set of conditions. However, as the instrument sensitivity is adjusted to a maximum, the baseline "noise" level generally increases too. The response due to a pesti- cide residue can be considered significant only if the peak height at the maximum usable sensitivity is twice the peakto-peak height of the noise on the chart. Operation of the instrument at less than maximum sensitivity may be preferable, particularly for comparative analyses in different laboratories, For example, FDA analysts set instruments to give 50% of full scale recorder deflection on injection of one nanogram of heptachlor epoxide or two nanograms of parathion to assure that each laboratory operates at the same sensitivity. On the other hand, the limit o_f detection of an analytical method may be defined as the concentration of pesticide above which a given sample of material can be said, with a high degree of confidence, to actually contain the chemical analyzed. This limit of detection depends upon a number of factors in addition to the instrument sensitivity, including sample size, adequacy of extraction and cleanup, size of aliquot injected, and knowledge and experience of the analyst. Deviations in peaks or baselines caused by inade- quate cleanup are more evident when the instrument is operated at maximum sensitivity. These deviations may �-107- cast doubt on the validity of the peaks of interest in assigning positive values for specific residues. Sutherland has reviewed the analytical limit of detectability for residues (67) . For all practical purposes, the response of control samples to a specified analytical method is the sole determinant of the limit of detectability. However, these control samples must be taken from plants or animals exactly comparable to the treated samples. They must be sampled at the same time, from identical varieties of the same degree of maturity, and must have been treated in all respects the same as the treated samples except that the chemical to be determined must not have been used on them. Furthermore, the samples must be independent and normally distributed according to statistical definitions. The responses given by, or apparent residues found in these control samples will usually follow a bell-shaped distribution curve. average of all samples analyzed will be the true mean. The An old rule-of-thumb was that any uncorrected residue value greater than twice the average control represented a real residue (65) . However, this is not necessarily so depending on the spread of the frequency distribution around the mean for that substrate. Hahn has recently discussed the conse- quences of incorrectly assuming that distribution is normal about the mean (68). �-108- Even greater care must be taken in interpreting data for extremely low residues of highly toxic chemicals in the environment. This was demonstrated following collaborative studies on TCDD conducted as part of the EPA Dioxin Implementation Plan in 1976. Agreement was reached among scientists from EPA, USDA, Harvard, University of Utah and Dow that it takes a response of 2.5 times background noise to indicate a positive finding. Furthermore, it takes a response of 10 times background noise before quantitative values at low parts per trillion can be assigned. 5.3 INTERPRETATION OF MONITORING DATA Unfortunately, analysts conducting monitoring studies do not have the benefit of comparisons to control samples because samples reliably free from pesticides are usually not available. In such cases, the limit of detection is based on the analytical variability for each pesticide on each substrate, generally by carrying through the entire method at least six replicate samples containing levels near the estimated limit of detection of the pesticide (52). Under these conditions, the limit of detection is considered equal to two standard deviations (approximately 95% confidence level) calculated from the replicated results. The identity of any peak larger than this should be subject to confirmation �-109- as discussed in Section 5.4, but practical limitations preclude confirmation of most "positive" values. Although variability among analyses of six replicates may be adequate for samples of certain species of plants or animal tissues, it may not be adequate to establish a reliable baseline for samples of soil or water from widely divergent geographical locations subjected to contamination by a great variety of chemicals. Unfortunately, some chemists do not recognize such limitations and interpret any positive response similar to that produced by a pesticide as proof that a residue is present. Furthermore, reports of moni- toring studies tend to emphasize the frequency of positive responses without regard to the significance of the "residues" found. One such report issued in 1973 was entitled Pesticides in Selected Western Streams — 1968-1971 (69). It gave results of analyses by the U.S. Geological Survey for nine chlorinated hydrocarbon insecticides and three phenoxy herbicides in water from twenty locations in fourteen states. The authors reported "total occurrence (of phenoxy residues) reached a peak of 106 during 1968-69 and declined sharply to 54 during 1970-71. This decrease of about 50% was due to 'reduced occurrences of 2,4-D and 2,4,5-T1." Examination of the lengthy data tables revealed that traces of phenoxy herbicides �-110- amounting to less than 0.0005 ppm (0.5 part per billion) appeared to be present in about 16% of the samples for 2,4-D and 2,4,5-T and 7% of the samples for silvex. Furthermore, four-fifths of the positive findings were at levels below 0.1 part per billion (ppb). The detected limits were listed at 0.005 yg/liter for silvex and 2,4,5-T and 0.02 yg/liter for 2,4-D (i.e., a sensitivity of 5 to 20 parts per trillion). Recoveries of 80 to 100% were claimed for validation studies but the spiking levels were not specified and may not have approached the claimed sensitivity. Furthermore, confirmatory analyses for phenoxy compounds were" not mentioned although other methods or other columns were discussed for confirmation of the insecticides found. The report also stated that 64% of the silvex occurrences were at one station in Nevada and 47% of the 2,4,5-T occurrences were in two associated sites in Arkansas and Oklahoma. In view of the localization of positive findings, it is possible that the parts per trillion residues "found" may have been due to the presence of interfering substances in samples from these locations rather than to actual residues of silvex or 2,4,5-T in the water. Unfortunately, the report has been cited as evidence of widespread contamination of water by these controversial herbicides in Western States. �-111Another example is a paper in the September 1974 issue of Bulletin of Environmental Contamination and Toxicology (70). A total of 13 authors summarize studies on the distribution of pesticides in randomly selected soil samples taken from diverse environments in five west Alabama counties. Pesti- cide residues were found in all samples examined/ even soil samples from areas where records indicated that no pesticides had been applied directly. The pesticides included eleven chlorinated hydrocarbon insecticides, six nonchlorinated insecticides, and two herbicides (atrazine and 2,4,5-T). They reported finding 2,4,5-T in 24% of the samples of top soil analyzed. Examination of the data revealed that 37 samples of top soil contained no detectable residues (sensitivity not specified) and only one sample containing more than 0.1 ppm 2,4,5-T. The samples were analyzed twice by GLC using two columns. No analytical data were provided to indicate reliability for the eight samples reported as "positive" at <0.1 ppm. Unfortunately, such data are used as evidence of persistence of pesticides in the environment. The above examples also demonstrate the pitfalls in drawing conclusions from reports which emphasize the maximum residue found or the percent "positive" samples without adequate allowance for variations in background "noise". This becomes even more important in special monitoring programs for highly �-112- toxic chemicals at extremely low levels. An example dis- cussed previously was the premature release of preliminary data from, analyses for TCDD at levels around 10 parts per trillion in beef fat which could be construed by some as sufficient evidence that 2,4,5-T and related pesticides should be banned (63). 5.4 CONFIRMATION OF RESIDUE IDENTITY Residue analyses without confirmatory tests provide only qualitative information. It is not safe to assume that a response similar to that produced by a known pesticide means the pesticide is actually present. Many instances have been noted in which one material masquerades as another in any one test (e.g. PCB's, phthalate esters, etc.). The certainty of identification is increased when the behavior of the unknown and the standard is the same in a number of tests. Subscribers to Pesticides Monitoring Journal received a June 1975 issue entitled Guidelines on Analytical Methodology for Pesticide Residue Monitoring (52). The following specific guidelines on confirmation of residue identity were listed: Residues reported should be confirmed by tests such as TLC, element specific GCf p-value determinations, derivatization, ultraviolet photolysis, etc., in addition to EC-GC. �-113- PCB's or other suspected complex interfering substances must be separated and confirmed. Combinations of confirmatory tests that measure the same physical property parameters as tests that measure the same parameters as the initial analysis, although they may help to support the identification, are not the best means of doing so. If sufficient material is available/ excellent identifications can be made by infrared spectrometry, particularly with the use of microcell techniques or Attenuated Total Reflectance. Mass spectrometry (MS) or combined GC-MS is recommended for identifying or confirming identity of important residues not adequately identified by other techniques. The methods used for confirming residue identity should always be described in the report of residue results. Although some laboratories may not have time to confirm every residue tentatively identified by <3C, confirmatory analyses should be conducted at intervals such as one in every five samples when the same residues are apparently present throughout the group. When insufficient sample is available, con- firmatory analyses may be conducted on a pool of several cleaned up sample extracts. �-114- 5.5 STATISTICAL EVALUATION OF RESULTS The Federal Working Group on Pest Management also differentiates between accuracy and precision of pesticide residue analyses (52). Accuracy involves statistical measurements that relate to the differences between the test results and the true result when the latter is known or assumed, and may be expressed as the mean error or relative error. Preci- sion involves statistical measurements that relate to the variation among test results themselves — i.e., the scatter or dispersion of a series of test results without assumption of any prior information as to the true result. Precision may be expressed in terms of the variance, standard deviation, relative standard deviation, range, etc. Values from single or duplicate injections of extracts from duplicate samples are more meaningful than values from multiple injections from single samples. These should be differentiated in evaluating differences among groups of data. As noted in Section 3.1.1, pesticide residue methods are often subjected to collaborative studies through the Association of Official Analytical Chemists (AOAC). These studies evaluate specificity, repeatability, and reproducibility of independent analyses for various samples. Repeatabi1ity is a measure of how well an analyst can expect to agree with �-115- himself from day to day, whereas reproducib i 1i ty is how well analyses in one laboratory are likely to agree with results from other laboratories. The Statistical Manual of the AOAC presents excellent information on formulating and statistically analyzing collaborative studies (71). �-116- 6. CONCLUSION The regulation of pesticides involves .a complex maze of rules implemented by various government agencies in their everchanging interpretation of laws enacted and amended by the U.S. congress to control the use of such chemicals. Two basic elements in these laws are that all pesticide products must be registered and that tolerances must be set for safe residue limits of all pesticides used in food or feed crops. Requirements for residue data in support of these tolerances are discussed in Section 3. Monitoring studies are conducted by groups within several government agencies to assure that excessive residues are not present in foods or accumulating in the environment, as discussed in Section 4. The importance of careful interpretation of residue data is discussed in Section 5 of this chapter. Concern about the significance of monitoring data was expressed at a 1973 hearing on EPA studies of specific chemicals in estuarine and freshwater environments. At that time the agency's Hazardous Materials Advisory Committee was told that virtually all measurements of DDT in the environment were suspect due to interferences in the analyses (72) . Early data did not distinguish between DDT and residues of PCB's used extensively in transformer fluids, etc. (48, 52). �-117- Furthermore, phthalate esters used widely as plasticizers accompany DDT through virtually all clean-up procedures according to D. G. Crosby of the University of California (49), Crosby also reported that interferences have been a major factor in chemical analyses for arsenic residues, and for mercury and phenoxy herbicides such as 2,4-D and 2,4,5-T. Responsibilities in the use and misuse of scientific data were discussed during a symposium of the American Association for the Advancement of Science (AAAS) at their national meeting in New York in 1975. It was concluded that responsi- bility for proper reporting of data lies with individual scientists/ scientific societies, and publishers. One of the speakers, Dr. Richard W. Roberts, director of the National Bureau of Standards, estimated that at least half of the data reported in scientific literature are unusable, often because too little information has been provided for inde. pendent evaluations (73) . Dr. Mary L. Good, a director of the American Chemical Society, cited four areas in need of responsible attention: determination of permissible levels of potentially dangerous materials in the biosphere, lack of information on error limits and credibility of published data, overmassage or excessive manipulation of raw data by computer techniques, and evaluation and use of computerized data banks. Also, care must be taken to �-118- delineate between those parts of reports that are factual and can be repeated by other workers and those reflecting interpretation of the data (74). Dr. Bernard L. Oser entitled his presentation Exaggerated Conclusions Based on Inadequate Data (75). He defined scientific data as observations and findings generally expressed in numerical or descriptive terms and stated that, even when correctly reported/ "data" are not necessarily equatable with "facts". Implicit in the term "facts" are the accuracy and reproducibility of findings and the competence and integrity of those responsible for the design, execution, and interpretation of the studies. Data are often statistically manipulated or "staticulated", such as by use of average values without expressing the range or distribution around the mean. Scientists may also draw false or misleading conclusions from their own data or from that of others. This may take the form of overestimating the importance of uncorroborated findings, or as one writer expressed it, extrapolation of unproven speculations. Thus, problems arise from misuse of scientific data as well as from use of unscientific data. Emphasis in this chapter has been on the care needed in conducting analyses for pesticide residues at sub-part-per-million �•119- levels in a variety of substrates, of the need for adequate reporting of such residue data, and of pitfalls in interpretation of data at levels below the validated sensitivity of the method. More specificity is needed rather than "picogram" measurements as often pushed by the scientific community. Premature or unwise interpretation of data can lead to precipitous action by regulatory agencies who have to respond to public pressures from individuals or groups of persons. Unfortunately, most pressure comes from lawyers and politicians who do not comprehend the limitations of pesticide residue analyses, particularly when the identity of the residues "found" has not been adequately confirmed. �-121- 8. 1. REFERENCES F. A. Gunther and R. C. Blinn, Analysis of Insecticides * and Acaricides-. Vol. VI in'Chemical Analysis Series, Interscience, New York-London, 1955. 2. R. W. Fogelman, J. Agr. Food Chem. £, 410 (1956). 3. T. H. Harris, J. Agr. Food Chem. 4,, 413 (1956). 4. F. A. Vorhes, Jr., J. Agr. Food Chem. £, 415 (1956). 5. H. Frehse, Residue Reviews J5, 1 (1964) . 6. T. H. Harris and J. G. Cummings, Residue Reviews j>, 104 (1964). 7. A. Bevenue and Y. Kawano, Residue Reviews 35, 103 (1971) . 8. FDA Guidelines for Chemistry and Residue Data Requirements of Pesticide Petitions, Bureau of Science, Food and Drug Administration, Dept. of Health, Education, and Welfare, Washington, D.C. 20204, March 1968. �-128- 47. Handbook for Authors of Papers in the Journals of the American chemical Society, American Chemical Society Publications, Washington, D.C. (1967). 48. J. H. Ruzicka, "Methods and Problems in Analyzing for Pesticide Residues in the Environment" in Environmental Pollution by Pesticides, ed. by C. A. Edwards, Plenum Press, New York, 1973. 49. D. G. Crosby - Statement before EPA's Hazardous Materials Advisory committee, Pesticide Chemical News 1 (45), 6 (October 17, 1973). 50. National Pesticides Monitoring Program (Revised), Pest. Monit. J. 5, 35 (1971). 51. Federal Working Group on Pest Management, Guidelines on Sampling and Statistical Methodologies for Ambient Pesticide Monitoring, Washington, B.C., October 1974. (U.S. Government Printing Office 1975-626-592/216 3-1). 52. Federal Working Group on Pest Management, Guidelines on Analytical Methodology for Pesticide Monitoring, Washington, D.C., June 1975. �-129- 53. S. D. Fine - Statement before Subcommitee on Agricultural Research and General Legislation, Committee on Agriculture and Forestry, U.S. Senate, January 27, 1976. 54. Bureau of Veterinary Medicine Memo 19: Monitoring for Residues in Food - Animal Tissues, DREW Pub. No. (FDA) 76-6001, July 1975. 55. R. D. Johnson and D. D. Manske, Pest. Monit. J. J9/ (1976) . 56. F. C. Lu - Toxico logical evaluation of food additives and pesticide residues and their "acceptable daily intakes" for man; the role of WHO, in conjunction with FAQ. Residue Reviews 4J5, 81 (1973) . 57. DHEW comments on draft GAO report to Congress entitled "Federal Pesticide Registration Program: Is It Adequately Protecting the Public and the Environment from Pesticide Hazards?" (December 1975). 58. National Academy of Sciences, Principles for Evaluating Chemicals in the Environment, a report of the Committee for the Working Conferences on Principles of Protocols for Evaluating Chemicals in the Environment, Environmental Studies Board, National Academy of Sciences - National �-130- Academy of Engineering and Committee on Toxicology, National Research Council, Washington, D.C., 1975. 59. L. P. vanDyk and K. Visweswariah, Residue Reviews 55, 91 (1975) . 60. K. D. Courtney, et al., Science 168, 864 (1970). 61. R. Baughman and M. Meselson, Environmental Health Perspectives, Experimental Issue No. 5, September 27, 1973. 62. (DHEW Publication No. (NIH) 74-218). W. B. Crummett and R. H. Stehl, Environmental Health Perspectives, Experimental Issue No. 5, September 15, 1973 (DHEW Publication No. (NIH) 74-218). 63. R. T. Ross, Statement on U.S. Environmental Protection Agency's Dioxin Implementation Plan (2,4,5-T/2,3,7,8Tetrachlorodibenzo-p-dioxin), June 21, 1976. 64. L. A. Shadoff and R. A. Hummel, Paper No. 80, Division of Analytical Chemistry, 170th ACS National Meeting, Chicago IL, August 27, 1975. 65. F. A. Gunther, Adv. Pest. Control Research 5, 222 (1962). �-131- 66. D. E. Clark, H. E. Smalley, H. R. Crookshank, and F. M. Farr, Pest. Monit. J. 8, 180 (1974). 67. G. L. Sutherland, Residue Reviews 10, 85 (1965). 68. G. J. Hahn, Chemtech, August 1976 (p. 530). 69. J. A. Schulze, D. B. Manigold, and F. L. Andrews, Pest. Monit. J. 7_, 73 (1973) . 70. R. Albright, et al., gull Environ. Contain. Toxicology 1,2, 378 (1974) . 71. W. J. Youden, E. H. Steiner, Statistical Manual of the AQAC, Assoc. Offic. Anal. Chemists, 1975. 72. Pesticide Chemical News !_ (45) , 6, October 17, 1973. 73. Chemical & Engineering News, February 10, 1975 (p. 17). 74. Chemical & Engineering News, March 3, 1975 (p. 4) . 75. B. L. Oser, International Flavours and Food Additives j5, 163 (1975) . *(No.) CRF is Title (No.) of the Code of Federal Regulations, (No.) FR is Volume (No.) of the Federal Register. � 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 178 Folder The folder containing the original item. 5241 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. Title A name given to the resource Letter to Federal Register Section, Technical Services Division, Office of Pesticide Programs, EPA from Marguerite L. Leng, July 7, 1978 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 122 Folder The folder containing the original item. 3376 Series The series number of the original item. Series VI Subseries II 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. Source A related resource from which the described resource is derived Analysis of Pesticide Residues Date A point or period of time associated with an event in the lifecycle of the resource 1980 Title A name given to the resource Government Requirements for Pesticide Residue Analysis and Monitoring Studies 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 101 Folder The folder containing the original item. 2688 Series The series number of the original item. Series V 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. Source A related resource from which the described resource is derived Fate of Pesticides in the Large Animal Date A point or period of time associated with an event in the lifecycle of the resource 1977 Title A name given to the resource Comparative Metabolsim of Phenoxy Herbicides is Animals 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 101 Folder The folder containing the original item. 2687 Series The series number of the original item. Series V 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. 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 12 1982 Title A name given to the resource Letter to the Editor: Jumping Chickens: Relevance to Hazard in Humans 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 101 Folder The folder containing the original item. 2686 Series The series number of the original item. Series V 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. Source A related resource from which the described resource is derived Chemical Enigineering News Date A point or period of time associated with an event in the lifecycle of the resource October 23 1978 Title A name given to the resource Letter to the Editor: Dose Levels Misinterpreted 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 101 Folder The folder containing the original item. 2685 Series The series number of the original item. Series V 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. 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 Typescript: Comparative Toxicology of Various Chlorinated Dioxins as Related to Chemical Structure 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 101 Folder The folder containing the original item. 2684 Series The series number of the original item. Series V 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. Source A related resource from which the described resource is derived Down to Earth Date A point or period of time associated with an event in the lifecycle of the resource 1972 Title A name given to the resource Residues in Milk and Meat and Safety to Livestock from the Use of Phenoxy Herbicides in Pasture and Rangeland 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 039 Folder The folder containing the original item. 0868 Series The series number of the original item. Series III 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. 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 Typescript: Summary of Dow's Response to EPA's Risk Analysis on the Use of 2, 4, 5 -T Herbicide Subject The topic of the resource dioxin health effects animal testing ao_seriesIII 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 038 Folder The folder containing the original item. 0861 Series The series number of the original item. Series III 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. Date A point or period of time associated with an event in the lifecycle of the resource 1979-01-01 Title A name given to the resource Typescript: 2,4,5, - T/TCDD Controversy: Current Status Subject The topic of the resource EPA herbicide toxicology herbicide regulation health effects ao_seriesIII 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 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. For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a> 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. 038 Folder The folder containing the original item. 0860 Series The series number of the original item. Series III 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. Date A point or period of time associated with an event in the lifecycle of the resource 1977-09-01 Title A name given to the resource Typescript: Are Lawn Weed Killers Really Hazardous? Subject The topic of the resource congenital birth defects dioxin animal testing health effects ao_seriesIII