1 15 9 https://www.nal.usda.gov/exhibits/speccoll/files/original/feedee5138378232713d4506b35a7e95.pdf 4eecc61c9623b6fbf2364968db6eb841 PDF Text Text Item ID Number °1353 Author Barnes, Donald G. Corporate Author Report/Article TltlO Memorandum: FDA Risk Assessment for Higher Chlorinated Dibenzo-p-dioxins, from Donald G. Barnes to Alvin Young and others, May 13, 1983 Journal/Book Title Year 0000 Month/Day Color D Number of limps 21 DeSCTlptOn Notes Includes as an attachment this article: "The Use of Epidemiology in the Regulation of Dioxins in Food Supply," Regulatory Toxicology and Pharmacology, 1, 379-387(1981). Thursday, May 03, 2001 Page 1353 of 1403 �UNITED STATES ENVIRONMENTAL PROTECTION AGENCY tp WASHINGTON, D.C. 20460 < 1 3 1983 OFFICE OF PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM TO: Addressees SUBJECT: FDA Risk Assessment for Higher Chlorinated Dibenzo-p-dioxins Attached is a recently prepared risk assessment by the Food and Drug Administration for hexa-, hepta- and octachlorodibenzo-p-dioxins in chicken eggs. I believe the analysis presented here is an interesting one and could provide fodder for a future first Friday feed. Donald G. Barnes, Ph.D. Senior Science Advisor to the Assistant Administrator for Pesticidees and Toxi-'C, .Sujsst-.ances Attachment Addressees : Lisa Barrera Pat Roberts Judy Bellin David Vanormer Priscilla Holtzclaw Bob McGaughy (/Al Young Carl Keller A-101 '-' A-132 WH-565 TS-769C WH-548D RD-689 f Veterans Adm. <£— T4 NIEHS �DEPARTMENT OF HEALTH & HUMAN SERVICES Public Health Service Memorandum Date April 29, 1983 Prom Acting Chief, Contaminants & Natural Toxicants Evaluation Branch (HFF-159) Subject Levels of Concern for Hexa- (HCDD), Hepta- (HpCDD) and Octachlorodibenzo-p-dioxins (XDD) in Chicken and Eggs To Mr. John Taylor Director, Division of Guidance (HFF-310) Through: Dr. Gary Flamm Acting, Associate Director for Toxicological Sciences (HFF-100) As a result of concerns for higher chlorinated dioxin contamination of chickens and eggs the Texas Department of Health has requested "that FDA provide guidance as to health or regulatory significance as well as action guidance" (W. Remle Grove, see attachment # 1). In response to this request, as submitted through DRG, we have reviewed the available information on the toxicity of several dioxin congeners. Based on this review we are suggesting the following levels of concern (LOG) for these substances in chicken and eggs. Levels of Concern^/ HCDD HpCDD OCDD 300 parts per trillion 500 parts per trillion 3 parts per million a/ Because the amounts of chicken and eggs consumed are similar, a uniform level of concern for the respective contaminants can be applied to each food item. The rationale, biological and/or toxicological end-points and factors utilized in the development of the above LX are identified in subsequent pages and attachments. It is important to recognize that the available literature from which these levels were derived is limited. We emphasize that these levels apply only to the present situation in Texas .and do not have general applicability to contamination by the dioxin congeners HCDD, HpCDD and OCDD in food. In this situation the various isomers of each congener will not be dealt with individually but rather as a group (e.g., as congeners). This is so because of a lack of- a) biological and/or toxicological studies on specific isomers, and b) knowledge of the presence of individual isomers involved in the Texas situation. It should also be noted that while the carcinogenicity of these congeners was assssed, where specific studies were available, the potential exposure to them in the Texas incident is considered to be of a relatively �-2- short duration (e.g.,-possibly several weeks up to several months). Therefore, carcinogenic potential was not used as the toxicological determinant in deriving the LXs for dioxins in chicken and eggs. It is equally important to recognize that other toxic manifestations, such as reproductive and/or teratogenic effects, may result from pulse (single) or short-term (days to weeks) exposures to dioxins such as the HCDD congener. It is the concern for these non-carcinogenic effects which serves as the basis for our evaluation, again since lifetime exposure is not an issue. Since the tetrachlorodibenzo-p-dioxin (TCDD) congener is the best studied and most toxic member of this class of toxicants, the health assessment performed on tha presence of TCDD in freshwater fish from various areas of the Great Lakes (F. Cordle, Reg. Tox. Pharm., 1;379-387, 1981; see attachment # 2) will be used as the basis for the establishment of LXs for HCDD, HpCDD and OCDD. In that assessment it was determined from a multi-generation reproduction study in rats that the no-effect level for TCDD was 1 nanogram (ng)/kg b.w./day. In keeping with these findings, a concern level of 25 ppt TCDD in fish was recommended by FDA to State officials. The value of 25 ppt TCDD and a fish consumption value of 37 g/day (99th percentile) is used in the present assessment to derive maximum daily intakes for the other dioxins (HCDD, HpCDD and OCDD) based on appropriate safety factors and their biological and/or' toxicological potency in relation to TCDD. In order to evaluate the relative biological/toxicological potency of these toxicants, several different types of studies were assessed. A number of studies have shown that there is a distinct relationship between the ability of the dioxins to elicit several of their toxic and/or biological manifestations and to bind to a cytosolic-receptor. These studies have shown that for the dioxins to produce any appreciable degree of toxicological and/or biological activity the four lateral ring positions must be occupied by chlorine atoms and at least one ring position must be unsubstituted. The comparative induction of aryl hydrocarbon hydroxylase (AHH) by a number of dioxins, including TCDD, HCDD, HpCDD and XDD has been studied in rat hepatoma cell cultures by J. Bradlaw and co-workers (Fd. Cosmet. Tox., .18:627-635, 1980). Their studies showed that the relative potency of the most active congeners of HCDD, HpCDD and XDD were 1/10, 1/200 and 1/25,000 of that of TCDD (relative potency of 1), respectively. In similar studies performed ty A. Poland and associates (Mole. Pharm., 2-736-747, 1973) on AHH induction in chicken embryonic livers, the relative biological potency Of HCDD was determined to be approximately 1/4.5 when the potency of TCDD was 1, while OCDD was shown to be inactive. Another type of study which was used to evaluate relative toxicological potency was acute oral toxicity. The following table is a compilation of acute oral LD5QS in the guinea-pig for those congeners that have been studied (from 3. Huff and co-workers, Enviro. Heal. Perspec.. 36:221-240, 1980). �-3- Single Oral LD$Q (ug/kg b.w.) Congener 2,3,7,8-TCDO 1,2,3,4,7,8-HCDD 1,2,3,6,7,8-HCDD 1,2,3,7,8,9-HCDD 1,2,3,4,6,7,8-HpCDD Guinea-pig 2 73 70-100 60-100 > 600 Acute oral toxicity of dioxin congeners has been studied in other species, however, the guinea-pig is being used in this analysis because on an acute basis it is the most sensitive species. An examination of these values reveals that the acute oral LDjns for the three HCDD isomers are very similar. To compare the acute toxicity of HCDD to that of TCDD the lowest reported value of 60 ug/kg b.w. will be used. As in the previous derivation of relative potency, if TCDD is given a value of 1, it follows that the relative potency of HCDD is 1/30 (60 ug/kg-HCDD/2 ug/kg-TCDD) of that of TCDD. Relative potencies for HpCDD and OCDD could not be calculated, because the acute LD$Q for HpCDD was not specifically identified ( > 600 ug/kg b.w.) and no value for OCDD has been reported. A number of reproductive/teratogenic studies have been performed with TCDD, HCDD and OCDD, while none have been reported for HpCDD. In these studies the lowest no observed effect level (NOEL) for TCDD was shown to be at a dosage of 0.001 ug TCDD/kg b.w./day (3-year rat reproduction study; F. Murray and co-workers, Tox. Appl. Pharm., 50:241-252, 1979). In a teratology study by B. Schwetz et al. (Enviro. Health Perspec.. 5_: 87-99, 1973) the lowest dosage shown not to effect embryonal or fetal development for HCDD was 0.1 ug/kg b.w./day. In this same study OCDD did produce embryotoxicity (subcutaneous edema), but no teratogenic effects at 500 mg/kg b.w./day, however, the next lowest dosage, 100 mg/kg b.w./day, did not cause either teratogenic or embryotoxic effects. In comparing the NOELs for these dioxins a relative potency of 1 is assigned to TCDD. It follows that the relative potency of HCDD is 1/100 and that of OCDD is 1/1 X 108 in terms of reproductive toxicity/teratogenicity. Only one of the congeners of interest, namely HCDD, has been studied in a long-term carcinogenic bioassay (NCI, Technical Report Series No. 198, NTP No. 80-12, 1980). In this study a mixture of two isomers, 1,2,3,6,7,8- and 1,2,3,7,8,9-HCDD, was shown to exhibit a lowest effect level (uEL) for neoplasia in B6C3F1 mice of 0.2 ug/kg b.w./day. This compares to the LEL of 0.01 ug/kg b.w./day which was observed by Kociba and co-workers (Tox. Appl. PhaTm., _46:279-303, 1978), in a two-year chronic study in rats. The relative ootency for neoplasia of HCDD in comparison to TCDD would, �-4- therefore, be 1/20. It must be emphasized that in this instance the toxic end-point of neoplasia was used solely to derive a relative potency factor for HCDD, not to address the issue of carcinogenicity, per se. The following table contains a summary of the relative potencies determined for HCDD, HpCDD and OCDD by the methods discussed above. Relative Biological/Toxicological Potencies* Dioxin Conqenar AHH Induction Chicken Liver Rat Embryo Hepatomas 1 1 1/4.5 1/10 HpCDD NR 1/200 OCDD NA 1/25,000 Acute Oral LDsn TCDD HCDD ' Reproductive/ Teratogenic Carcinogenic Bioassay Studies 1 1 1 1/100 1/20 NR NR NR NR 1/1 X 108 NR 1/30 * - 1 is the highest level of activity. NR - not reported; studies have not been performed. NA - not active It is apparent that of the three congeners of interest HCDD demonstrates the greatest activity with HpCDD and OCDD following in order of magnitude. This follows the structure activity relationship for this class of compounds which indicates that those congeners with chlorines in positions 2,3,7 and 8 and with at least one unoccupied ring position will demonstrate the greatest biological/toxicological activity. Derivation of LQCs HCDD The relative potencies of HCDO derived from the various studies cited above range between 1/4.5 and 1/100. Since the incident in question involves an acute or short-term exposure the risk of a pulse (single) exposure during pregnancy would be of most concern. Therefore, while not ignoring the trend suggested by the smaller relative potency factors for HCOD, more weight is given to the larger factor determined on the basis of the teratogenic study performed with HCDD. It was, therefore, decided that a more appropriate relative potency for HCDD is 50. This was then used to derive the LOG for HCDD according to the following calculation - �25 ppt* X 50 X (36.8 g/53.9 g)** = 853 ppt (rounded to 850 ppt) *-• The 25 ppt used in this calculation is the health advisory level which was issued for the TCDD contamination of fish from the Great Lakes. As it was stated previously it is the Great Lakes health advisory which is used as the basis for the derivation of the levels of concern for the higher chlorinated dioxins in the present assessment. **- ratio of food factors; 36.8 g/day - 99th percentile intake for fish; 53.9 g/day - total intake for eggs (28.5 g) and chicken (25.4 g) consumed by children 2 to 5 years of age (supplied by Dr. F. Cordle, HFF-108, 4/14/83, see attachment #3). This level of' 850 ppt, however, applies to the adult and not to children. The latter are of greater concern in this case because they are likely to consume more eggs and chicken per kg of body weight than adult. Therefore, the 850 ppt level is divided by a factor of 3 to account for this increased exposure of children to give a value of 283 ppt which is rounded off to give a LOG of 300 ppt for HCDD. HpCDD The amount of data available on HpCDD is quite meager. If the relative potency value of 1/200 is used, a LOG is derived which is unduly high, particularly in light of the information on the structure-activity relationship of the dioxins. The two hepta isomers have chlorine atoms at carbon positions 2,3,7, and 8, one unoccupied carbon position, and only differ from the most toxic hexa-isomers by the presence of one additional chlorine atom. Therefore, it is felt that a LOG of 500 ppt would be more appropriate. XDD After evaluating the available information on the toxicological and/or biological potency of XDO it was determined that the most reliable data was that from the reproductive/teratology study reported by Schwetz e_t al. (1973). In that study the NOEL for OCDD was 100 mg/kg b.w./day Using this value together with a 1000 fold safety factor and accounting for the lower body weight of 2 to 5 year old child, a tentative LOG of concern equivalent to 30 ppm was determined, as shown below: ' LOG = a « a 100 mg/kg b.w./day (NOEL) $ 1000 (S.F.) 0.1 mg/kg b.w./day x 16 kg b.w. (child) 1.6 mg/day f 53.9 g/day (total consumption of chicken and eggs by child) 29.68 ppm or 30 ppm Wh:!le the value is based on "in vivo" experimentation, it appears to be unrealistically high for a congener which belongs to a class of toxicants, e.g., dioxins, for which so much concern has been expressed. Furthermore, it should be stressed that this value is derived from a single study using �-6- only one animal species, e.g., the rat. If we consider the-"in vitro" data on AHH enzyme induction, it is seen that OCDD has only a minute fraction of the activity reported for TCDD. Nevertheless, there is some concern over the possibility that exposure to OCDD at the level suggested by the tentative LOG of 30 pprn may result in some degree of enzyme induction activity in humans. Therefore, the application of a further safety factor of at least 10 is considered appropriate. Thus, a LOG of 3 ppm is recommended for OCDD in chicken and eggs. Since the amounts of chicken and eggs consumed are similar, a uniform LOG for the respective congeners can be applied to each food item. Again it must be emphasized that these levels apply only to the present situation in Texas and have rio application to other incidents. It should also be reiterated that while the induction of neoplasia was used to derive one of the comparative relative potency factors for HCDD the issue of carcinogenicity was not utilized directly in this evaluation because of the limited, short-term exposure of this situation. Finally, although structure-activity information was considered in deriving the LQCs for the higher chlorinated dioxins it is recognized that additional data on such relationships is required to refine the significance of such parameters in the toxicoldgical assessments of these toxicants. ichael Bolgef, Ph.D. Garfield N. Biddle, Ph.D. Attachments cc: HFF-100 HFF-150 (Blumenthal) HFF-152 (Jackson/Edwards) HFF-159 (Shibko) HFF-159:GNBiddle:MBolger:clw:4/29/83:472-5706:2095A �15. 83--261-360 m PROCESS 12 SUBS - SCRAPINGS FROM EQUIPMENT lb. 33-292-061 1 SUB - SHEEP WOOL FROM SHEEP HEAL SCREEN RECEIVED FROM H.T.C. RENDERING, SAN ANGELO, TEXAS j?. 83-261-062 1 SUB - «EAJ S BONE HEAL SHEEP HEAL 18, 83-292-063 1 SJ!J - POULTRY MEAL !•>. S3- 292- 064 1 SUB - POULTRY HEAL 20. 83-232-065 1 SUB - MEAT 1 BONE MEAL *Ji. 33-292-066 1 SUB - POULTRY HEAL i2. 82-292-067 1 SUB - HEA1 1 BONE HEAL L'li. 83-292-068 J SUB - MEAT I BONE HEAL :'. 33-2^2-069 ;. 1 SUB - UlftTf DEBRI5» ffcOH IKS7PE HEARTH OF OLD 1NCENERATOR •:.Mirriii 10 ciNCiMMAii LABORATORY: 23 SUBS - LUBRICANTS, DEORORANTS, INSECTICIDES. BOILER COMPOUNDS, VARIOUS LIQUIDS ANO POUtERS. UPON RECEIPT OF C/R'S, I WILL DESCRIBE SUBS THAT RELATE TO EACH SAMPLE. i.M RICAKDS TO 83-261-350, SUB 41 HEAT t bONE MEAL* SUB 42 ANIHAL FAT, COLLECTED 5ROH LOAPS RECEIVED FROM TEXAS 6Y PRODUCTS COMPANY, SAN ANTONlD. IT miEVElr TKAt B0TK COMPANIES #RF UNUER THE SftKE 0«NE«T, 1K1S: «2tt & 4/11/83. AS TO COMMON SUPPLIERS, PROCESSING, ETC. �<'«JTL THAI 83-261-350. COLLECTED ON 4/4/83 WAS RECEIVED FROM TEXAS BY-PRODUCTS mnt-ANY, SAN ANTONIO, TEXAS. SUB *1 HF.AT 1 BONE HEAL WAS COLLECTED FROM THE TRANSPORT TRUCK, AND ANALYSIS REVEALED 25.!> PPK. OUR SAMPLE 83-260-356. MEAT i BONE MEAL. COLLECTED 0« 3/H/B3 REVEALED 16.0 ?pH TCP'S. THIS SAMPLE WAS COLLECTED FROM A STORAGE BIN, AND IS NOW BELIEVED TO BE A PORTION RECEIVE* n»DH TEXAS BIT-PRODUCTS. TEXAS WNUER1N6 IS OWNED BY HUBEW L. L1NENBERQER, AND ALSO FUNCTIONS AS THE PRESIDENT. LINENBER6ER ALSO OWNS 75* OF THE STOCK OF TEXAS BY-PRODUCTS, SAN '.rtlOMlO, AS WELL AS OWNING A hAJOR INTEREST 1M TEX -HENS, INC., MIXON, TEXAS. TE/.AS kENliERlNG RECEIVED APPROX. 3-4 LOADS OF HEAT I BONE iiEAL PEft WEEK FROM TrxAS BY-PRODUCTS, ESTIMATED AT APPROX. 150,000 LBS. OK MORE. IT WAS REPORTED THnT THIS HEAT 1 BONE HEAL IS VERY HIGH IN FAt CONTENT AND IS RUN THROUGH THE EQUIPMENT AT TEXAS RENDERING TO EXTRACT ADDITIONAL FAT, IT IS ALSO REPORTED THAT PRODUCT SAMPLED UNDER 03-261-350, SUB 12, ANIMAL FAT FROM TEXAS ST-PRODUC7S IS ACTUALLY STREET GREASE. Ml IS NOT ANIMAL FAT PROCESSED BY ANTONIO. REPORTEDLY DOES TO JACOB-SIERNS, HOUSTON, TEXAS. WHILE TEXAS PJNDER2WJ RECEI'/ES KEAT I PONE HEAL AND STREET GREASE- FROK TEXAS BY-PRODUCTS, SAN ANTONIO, TEXAS RENDERIMf, JOES NOT SHIJ1 PRODUCTS TO THEM. ALSO IT WAS REPORTED, THESE FIRMS DO NOT HAVE COMMON SUPPLIERS. ALSO NO PRODUCTS ARE SHIPPED PROM TEXAS RENDERING TO TEX-HENS, INC., NIXON, TEXAS. (. GENERAL PROCESSING FLOW AT TEXAS RENDERING IS AS FOLLOWS: AS PRODUCT IS RECEIVED, HEAT X BONE MEAL, DEAD ANIMALS, SCRAPS, ETC., IT IS ^JftPED JKTO A P3T WHERE 37 IS AUGCRED TO 70 AH 3NI>US?kiAL 6K3MER, AUGERS OVER rAGMETIC PLATE (REMOVE HE? AD TO MEAT STORAGE VAT, 10 QHE OF 5 HEAT COOKERS. THE COOKERS ARE CHARGED WITH APPROX. 6,000 L*S. OF PRODUCT AND APPKOX. 2,000 LK-. OF ANIMAL FAT- JS ADBE& (USUALLY PROCESSED THE rtiGHT BE?OR£>. AFTER COOKING AT APPROX, 313 DEGREES t. THE PRODUCT EXITS AND SCREENED WITH THE FAT V.CIM13 TO ONE OF 3/20,000 LB. WORKING VATS. THE FAT IN THESE VAIS IS USED TO INTO THE COOKING VATS AS STATED ABOVE. IS NKXBCD FROM THESE WORKING VATS. IT MAINS TO A FLAT DRYING VAT TO »>r off WATER. FROM HERE, XT. is PUMPED TO EITHER OF 3/30,000 LF\ STORAGE VATS. ^r. THE MEAT EXITS THE COOKER, IT GOES TO THE PRESSES «HESE BORE FAT IS UTKACTED (PAT GOES TO THE WORKING VATS). THE MEAT THEN PASSES THE SCfcEENEJc, .MJBCIXI kA»a« ftiaeso A* »««4S, MAIM, »*o.t >H».» M«MOV»». *M» HBis* *t*0*4 ««aa *o T'riE HAMMER t»U. THEM THE MEAt T& EITHER OF 8/60,000 t&3. STORAGE BINS AS iTMISHED MEAL. THE BONES, ETC., REMOVED BY THE SCREENER, GOES BACK TO THE L'KJSINAL AUGER AT THE STARTING POINT OF THE PROCESS. L'JSCUSSIONS WERE HELD OK MONDAY. 4/U/83, BY HOUSTON STATION WITH OFFICIALS Of TrlC TEXAS KEPT. OF AGRICULTURE AND TEXAS DEPT. OF HEALTH AND OUR SAMPLE ilTSULIS KNOWN AT THE PRESENT TIME WERE PISUCSSED. THE INTRASTATE SHELL EG^S «t*£ DISCUSSED WITH TEXAS DEPT. OF HEALTH, HOWEVER, THEY DO MOT HAVE THE :«*AmniES OF ANALYSING FOR POP'S 10- DETESHINEiTHS CU»*EM STAJUS- or EGGSC t A "P:0n SMITH FARMS AMD POSSIBLY OTHERS. !PJ^ **<WHifc- CU5RENT ASSAYS. THEY \Ki «ILL1HG TO ACT., HOWEVER ^REQUESTED THAT FDA PRO'/lIiE GUIDANCE AS TO HEALTH '•¥" REGULATORY SICNifANCE AS WELL AS ACTION GUIDANCE. �nr xcxft* DEFT. OF AGRICULTURE IS QUITE CONCERNED AND 15 CURRENTLY lVG SAMPLES SUBMITTED BY 1KB F1RH OF FINISHED PROBUCT, HO«BVBR> THEY •ilSO R£QU£S7£H TKun THE HIGH LEVELS Of ?C?'& FOU*fB IW «EAI I BOME HEAL FUtOM TEXAS Pr-PRQPUClS, SAN ANTOfilO, IT A?f-EARS THAT THIS COULD BE A CONTINUOUS SOURCE OF LOfJTAMiNATEB PRODUCTS. AN INVESTIGATION OF THIS FIKH IS CURRENTLY BEING. UISUUSSED. �/'*• REGULATORY TOXICOLOGY AND PHARMACOLOGY 1, 379-387 (1981) The Use of Epidemiology in the Regulation of Dioxins in the Food Supply1 FRANK CORDLE Epidemiology and Clinical Toxicology, Bureau of Foods, food and Drug Administration, Washington, D. C. 20204 Received November 1981 Residues of teirachlorodibenzo-p-dioxins (TCDD) were detected recently in several species of freshwater fish from various areas of the Great Lakes. Concern for the potential human health risk associated with the consumption of these fish prompted the Food and Drug Administration to assess epidemiological and toxicologies! TCDD data in order to determine the need for regulatory action. In the assessment, pertinent animal and human data and daia for the TCDD residues in the freshwater fish, for the amounts of the different fish species consumed and for the number of individuals who consumed the fish, were evaluated. The various methods of evaluation used to reach a regulatory decision are described. * INTRODUCTION Although epidemiology may have first been used by Hippocrates, the definition or meaning has undergone some significant changes since then. First described as the study of epidemics and, later, as the study of the determinants of differences in disease distributions in human populations, epidemiology today, especially in regulatory agencies, refers essentially to the activities of the epidemiologist. In a regulatory agency such as the Food and Drug Administration (FDA) the role of the epidemiologist is to assimilate, digest, and synthesize the best available data from survey, clinical, and laboratory experiences, either firsthand or from the scientific literature: these human and animal data are then combined and interpreted in order to address a basic question: Does the evidence of adverse human health effects from exposure to the various chemical substances that fall under FDA regulatory authority present a risk to public health safety that is sufficient for FDA to initiate or make a change in regulatory action? The importance of the contri• Presented at the international symposium Human Health Aspects io Accidental Chemical Exposure of Dicxir.s—S::aisgy for Environmental Reclamation snc Corr.mur.itv Protection, organized by the International Academy of Environmental Safety (1AES) and the International Society of Ecotoxicolojy and Er.viro.-.rncnta! Safety (SECOTOX) joiniiy with the Institute Superiore di Sanita. Rome, and the Geseilschafrfur Strahien- und Umweh Forshung MbH, Munich. 379 o::?-::-oo;si/o:>o379-o9so:.oo/o Cc??Ti9i: 5 19M tv Academic Presi. Int .Mi nf hu of rep.'odumor. in >nv form reserved �380 FRANK CORDLE bution of epidemiology in the regulatory public health arena seems obvious. Without adequate assessment of factors that appear"to increase the risk of disease in humans from chemical substances in the food supply, food may be destroyed, the public may be unnecessarily inconvenienced or inadequately protected, and the costs may be enormous. In short, epidemiological efforts are directed toward the prediction of such risk at the community, state, or national level. It is quite likely that the majority of humans are exposed to a large number of chemical substances in small amounts over an extended period of time rather than to large doses such as those described in the mercury episode in Minamata or in the PCB exposure in Japan. The importance of the possible cumulative effects from these small doses versus the importance of the effects from a single large dose or .from relatively large doses over a short period of time is the subject of considerable scientific debate. Much of the information concerning the toxicity of various chemical substances has been obtained from experiments in animals. In general, safety testing depends upon the fact that as the exposure dose is decreased, toxic effects also decrease, and a dose is finally established at which "no observed effects" are seen. Such dose-response relations are central to toxicity studies in animals and should be ef equal concern in the evaluation of human exposure to a variety of environmental and other insults. However, dose-response relations in humans must be established or identified with a great deal of care and caution. Outcome may vary greatly in significance: At one extreme is death and at the other are changes in physiological or psychological function. The weight that should be given to each relation in formulating regulatory policy may vary greatly. The lack of good examples of dose-response 'relation, even in the area of occupational exposure, is remarkable. Where dramatic incidents of exposure to environmental contamination have occurred through ingestion of contaminated food, efforts to establish an acceptable dose-response relation in humans have met with little success. However, epidemiologies! study should not be limited to outbreaks of disease that are obviously caused by high exposures to toxic chemicals: it should be squally concerned with the effects of lower, more prolonged, and sometimes insidious exposures. EPIDEMIOLOGICAL METHODS In the traditional manner, epidemiologists deal wi;h epidemics by interpreting patterns of disease, testing hypotheses, and assessing the risks and benefits of various options. Their methods involve the use of two categories of epidemiology often referred to. as analytical and descriptive epidemiology. The analytical epidemiclogical methods generally involve either a case-control, retrospective approach or a cohort, prospective approach. In analytical epidemiology, the goal of epicsmioiogica! activity is to identify and. if possible, to quantify the association between a cuusii exposure or characteristic and a disease under circumstances that permit the best possible discrimination between cause and aiternative hypotheses. Chance will always affect the alternatives: thus the feasibility of such a study is limited by factors such as sample size. �EPIDEMIOLOGY AND REGULATION'OF D1OXINS -" 381 Since a precise hypothesis permits the use of a well-thought-out and properly planned study design, it is better to use the cohort approach to measure relative and attributable risk, for example, than to try to detect trends from descriptive data. Nevertheless, sample size considerations, cost, and time constraints often restrict the kind of epidemiological study undertaken, even though the cohort approach might be preferred for a given problem. Case-control studies of disease, i.e., studies looking at the past history of exposure, are often more feasible than cohort studies because they can be conducted in a relatively short time and are easily repeatable, and because a large number of cases can be studied economically. They do have some special liabilities, however, in terms of validity, since such studies depend entirely on the comparability of cases and controls and on the specific methods used to measure the exposure. Although frequently used, the methods for estimating relative risk or risk ratio from casecontrol studies also present some special problems of inference. Cohort studies, i.e..-studies looking forward in time, are especially costly because of the time involved in the prospective follow-up. They do, however, provide an opportunity to compute a more reasonable relati%re and attributable risk, and specious relationships resulting from bias in data collection are less likely to occur. Descriptive epidemioiogical methods can be used by a regulatory agency such as FDA to determine trends in disease and magnitudes of exposed populations largely from data that are readily available, e.g., mortality dau. data from National Cancer Institute (NCI) surveys, census data, and food consumption data. The goal of these studies is io identify any unexpected changes in incidents or.mortality through surveillance of the available data for time trends and through probes of specific data collected during research activities or gathered in support of regulatory decisions. Epidemiological studies also provide information that is used to identify and quantify differences in species responsiveness to environmental agents in a variety of other ways. One use. for example, pertains to the difficulty associated with cornparir.c data derived from studies of highly inbred animal strains to data of a genetically heterogeneous human population. In this case, epidemiological methodologies provide the means for stratification of study data according to sex, age, race, and other variables that characterize human populations. Certain problems rr.ay also be minimized when epiderniological considerations are employed in risk assessments that are based on comparisons involving data of humans and data of animal models. These include problems associated with limited sample sizes, znigra'.ior. in and out of the exposure area, and toxicity due to causes other than that as-sociated Vjth exposure to the etioiogic agent under study. EPIDEMIOLOGICAL AND TOXICOLOGICAL ASSESSMENT OF TCDD EXPOSURE Recent concern for the potential human health risk associated with exposure to residues of the tetrachiorocibenzo-p-dioxins (TCDD) in several species of freshwater fish from various areas of the Greai Lakes has resulted in an epidemioiogical arc toxicological assessment of the problem that utilizes currently available data from a variety of data sets. For a regulatory decision to be made, several elements �3S2 FRANK CORDLE were needed. These included data for the TCDD residues in the freshwater fish, for the amounts of the various fish species consumed and for the number of individuals who consumed the fish, and assessments of pertinent animal data and previous human exposure to TCDD. Animal Data A number of lexicological studies with TCDD have been conducted to assess the potential for acute toxicity and teratogenesis. Kociba et al. (1976) reported the results of a subchronic study using rats that were given 1.0, 0.1, 0.01, 0.001, or 0 /jg TCDD/kg body wt/day for 5 days/week for 13 weeks. Doses of 1.0 Mg TCDD/ kg/day caused some mortality, inactivity, decreased body weights and food consumption, pathornorphologic changes in the liver, lymphoid depletion of the thymus, increased urinary excretion of porphyrins, and minimal alterations of some hematopoietic components. Doses of 0.1 ^g TCDD/kg/day caused decreased body weights and food consumption and slight degrees of liver degeneration and lymphoid depletion. These data indicate that no discernible ill effects occurred in rats given 0.01 or 0.001 jig TCDD/kg/day for 5 days/week for 13 weeks. In a 2-year chronic study in rats Kociba et al. (1978) reported that the ingestion of 0.1 ,ug TCDD/kg/day caused an increased incidence of hepatocellular carcinomas and squamous cell carcinomas of the lung, hard palate/nasal turbinates, or tongue, whereas a reduced incidence of tumors of the pituitary, uterus, mammary glands, pancreas, and adrenal glands was noted. Other indications of toxicity at this dose level included increased mortality, decreased weight gain, slight depression of erythroid parameters, and increased urinary excretion of porphyrins. Gross and histopathologic charges were noted in the hepatic lymphoid. respiratory, and vascular '.issues. The primary hepatic ultrastructural change at this high dose level was proliferation of the rough endopiasmic reticulum. Terminal liver and fat samples from rats given this high dose level contained 24.000 and S100 parts per trillion (ppt) TCDD, respectively. Rats giver. 0.01 ng TCDD/kg/day for 2 years showed less severe toxicological effects than those given the highest dose level. These included liver lesions (including hepstocellular nodules) and lung lesions (including focal alveolar hyperplasia). Terminal liver and fat samples from rats given this dose level contained 5100 and 1700 ppt TCDD, respectively. Ingestion of 0.001 yg TCDD/kg/day (22 ppt in the die;) caused no effects of any toxicological significance. Terminal liver and fat samples from rats given this low dose level each confined 5-^0 ppt TCDD. ]- a 3-year reproduction study in rais given doss levels of 0. O.OOL 0.01, or 0.1 ug TCDD/'kg/day, Murray ei al. 'J979) reported no significant toxic effects in the/c-ceneration rats of cither se.x curing the 90 days of TCDD ingestion prior to ': mating. However; significant decreases in fertility and neonatal survival were observed in the/o-generation rats receiving 0.1 ps TCDD/kg/day. At 0.01 Mg TCDD/ kg/day, fertility was significantly decreased in the/i and/ : generations, but not in the/; generation, and decre55.es in litter size at birth, gestations! survival, and neonatal survival and growth were also noted. Among the rats receiving 0.001 ^g TCDD/kg/day, no effect on fertility. !i;:er <ize at birth, or postnatal body weight was observed in any generation. No consistent effect on neonatal survival was observed at a dose level of 0.001 pg TCDD/kg/day. • �EPIDEMIOLOGY AND REGULATION OF DIOXINS 383 Allen et al. (1977) reported results of a subchronic study in which female rhesus monkeys consumed a diet containing 500 ppt TCDD for periods as long as 9 months. It was calculated that these monkeys ingested a total of 2-3 Mg TCDD/kg body wt over the course of the 9-month study. Clinically, these monkeys showed changes similar to those described by McConnell et al. (1978) as well as some hematoiogic depression and hemorrhages in various tissues. Hypertrophy, hyperplasia, and/or metaplasia were noted in the epithelium of the bile ducts, salivary glands, bronchi, pancreatic ducts, sebaceous glands, skin, gastric linings, and urinary tracts of these monkeys given diets containing 500 ppt TCDD. Human Experience Alihough 22 incidents of human exposure to TCDD in connection with the manufacture of chlorinated phenols have been reported worldwide since 1949 (Holmstedt, 1980). there remains a scarcity of reliable information concerning the results of these exposures. In a recent report of the mortality experience of a cohort of workers exposed to TCDD in Nitro, West Virginia, in 1949. Zack and Suskind (1980) described some of the signs and symptoms observed in the exposed population shortly, after the accident occurred. Employees who-worked in the area of 2,4.5-trichlorophinol (TCP) production or were involved in the cleanup began to develop symptoms immediately following exposure to the material, which was discharged froir. the autoclave. Symptoms included eye and respiratory tract irritation, headache, dizziness and nausea, and a severe irritant reaction of the exposed skin. After these initial symptoms subsided, chioracne and other symptoms became evident. A total of 12 more severely affected workers were examined or. three occasions during the period 1949-1953. Another 26 persons with chioracne :hat was apparently unrelated to the accident were also examined in 1953. The ciinical symptoms included acneform lesions: severe pains in muscles of upper and lower extremities, shoulders, and thorax on exertion: fatigue: nervousness and irritability: decrease in libido: dyspnea: vertigo: and intolerance to cole. All of the cases showed evidence of chioracne. For the six workers examined curing 1949 and 1950. another examination was carried out in 1953. and at that time six additional workers involved in the accident were also examined! The findings in ihis later examination indicated a general regression of both the cutaneous and ne.-cuiijriccus symptoms w h i c h had been present earlier. No specific leveis o; exposure could be determined. In other reports of industrial exposure 10 TCDD frc.T. Great Britain, the Netherlands. \\fisi Germany, and Czechoslovakia, chioracne was the most common and prominent sign observed following exposure. In some -sports liver function tests indicated liver damage, whereas in other reports they die not. Two major problems er.cour,:e:tc in all of these studies were the lack of 2. tltitr identification of •.hose e.v-<>=d. other than their subsequent development of chioracne. and the absence of any measures for the levels of exposure ihar might have taken place. Pszdsrova-Vejlupkova et a!. ( 1 9 8 1 ) reported results of a 10-year follow-up study of workers exposed ;o TCDD between 1965 snd 196s curing the production of 2.4.5-trichloropheno.xyacetic acid (2/,5-T). In this s t u d y group of 55 individuals �384 FRANK CORDLE (originally 80 of the 400 persons engaged in., the production became ill), the first indications of illness were feelings of sickness, fatigue, weakness in the lower extremities, and the formation of chloracne. Subsequent examinations indicated that about 20% had mild hepatic lesions. During the 10-year follow-up study of these exposed individuals, most of the patients did not experience all of the symptoms and signs of intoxication, and some patients showed the same symptoms and signs as others, but in different combinations. It is assumed that in this type of intoxication all the systems and organs mentioned in the study were simultaneously affected, although some were affected only slightly. This assumption is supported by several facts. Fluorescence of liver tissues in ultraviolet light, which is a sign of pathological porphyrin metabolism, was present in all cases of necropsy and biopsy, i.e., in persons for whom long-term monitoring of porphyrin excretion in urine was carried out and in whom 5-aminolevulinic acid values were constantly within normal limits'. Probably a slight subclinical lesion was present in each of these patients. Further evidence was furnished in repeated neurological examinations. Polyneuropathy of the lower extremities was manifest in some patients only in the third or fourth year of illness. There is definite clinical and electromyographic evidence that the results of the first examinations conducted when the illness commenced showed that the patients were entirely normal. Additional study results have been reported recently by Zack and Suskind 0980), Ott et al. (1980), and Cook et al. (1980), describing ;hs mortality of employees engaged in the manufacture of 2.4.5,-T. In two of these studies cohorts of employees were assembled on the basis of their exposure to T.CDD. which was indicated,by the presence of chloracne; the ihird cohort consisted of individuals employed over the same time period. Unfortunately, each of these three cohorts comprised a limited number of individuals: e.g., the chloracne groups contained 121 and 49 individuals and the employee group contained 204. In each of these studies there does not appear to be an apparent excess in total mortality rate or in deaths from malignant neoplasms. It must be pointed out, however, that each of these studies does have limitations both in the size of the population studied and in other methodological areas, such as exposure levels. For a more detailed description of these studies as well as the Seveso incident, the reader is referred to the original papers and to Hoimstect (1980), Reggiani (19SO), and Pocchiari et al. (1979). Hitman Exposure to TCDD Residues in Fish Although there are no epidemiological studies which have firmly established an association between cancer in humans and TCDD exposure, 2nd although comparisons of human exposure data and animal studies appear to indicate that humans may be less sensitive than animals to TCDD exposure, prudence dictates that human exposure to TCDD be kept to 3 minimum. With :h:s public health objective ir. m;rd. FDA recently compieted an assessment of the problem of TCDD residues in some species of freshwater fish in the Great Lakes for ;he purpose of determining whether consumption of such fish provided a potential public health problem. Results of the analyses of fish samples collected by Canada and the United States �EPIDEMIOLOGY AND REGULATION OF D10XINS - 385 TABLE i HUMAN CONSUMPTION OF DIOXIN BASED ON FISH CONSUMPTION DATA Total daily intake (ng*) Total daily intake/body wt (pg'/kg) From all selected species From all selected species Hypothetical dioxin residue level in fish consumed (ppf) 90th percentile 99th percentile From pike, 99th percentile 90th percentile 99th percentile From pike, 99th percentile 100 SO 25 1.57 0.77 0.38 3.683 1.84 0.92 8.4 4.2 2.1 22 11 5.5 50 26 13 120 60 30 ' ppt • pans per trillion. " 1 microgram (»g) "..1000 nanograms (ng). ' 1 ng - 1000 picograms (pg). indicated that TCDD levels as high as 30 ppt with an average value of 25 ppt were present in the edible portion of salmonoid fish (salmon, trout) from. Lake Ontario. Lower levels of TCDD were reported to be present in the edible portions of commercial species (bullhead, perch, catfish, sucker, etc.) from Lake Ontario^ although up to 40 ppt TCDD were found in'eel and smelt from the lake. Less than 10 ppt TCDD was seen in samples from Lake Erie, and limited data for_fish from the other Great Lakes were similar to those obtained from Lake Erie fish, except that higher levels of TCDD were present .in fish from Sagir.aw Bay, Michigan. Data on fish consumption from the National Marine Fisheries Service (NMFS) were extracted for the eight Great Lakes states, Illinois. Indiana. Michigan, Minnesota. New York, Ohio, Pennsylvania, and Wisconsin. These data were collected in a national sample of households, consisting of approximately 25,000 individuals. From the data presented, individuals who consumed the species of interest, i.e., the species currently being analyzed for dioxin residues were identified in the total sample, and the mean fish consumption, in grams per cay. was computed. The 90th and 99th percentiles were also computed. On the basis of the proportion of individuals in the sample population consuming the species of interest, 17,057,791 individuals in the eight Great Lakes states would be expected to consume these same species. It must be pointed out that the number of consumers in the total population can be considered only ar. estimate because of the lack of information on potential sampling error as well as other factors. These data indicated that the 99th percentile for daily consumption for all consumers of the selected species was 36.8 g; the 90th percentile for daily consumption was 15.7 g. For a single species of fish such as pike, which appeared to be consumed in larger amounts than all the species combined, the 99th percentile of consumption was 83.95 g. Table 1, which is based on these fish consumption data, shows :he daily human consumption for a range of hypothetical dioxin residue levels. Thus, the four elements of the model for a scisn::f.c regulatory assessment, i.e., animal data, human data, consumption data, and residue data, were available. In this instance the h u m a n data concerning TCDD exposure contributed little to the regulatory decision because of the uncertainty of the exposure data as well as the �386 FRANK CORDLE uncertainty of the outcome of the exposure. It was necessary, therefore, to rely on extrapolation from animal to human. In this case the rodent data from the 2-year chronic feeding study (Kociba ei a/., 1978) were used for the extrapolation. Results of that study showed that (a) at 0.001 Mg/kg body wt/day, no adverse effects were noted in rats exposed for their lifetimes to the dioxin; (b) at 0.01 ng/kg body wt/day, hyperplasia of the liver and lung was observed to occur, thus indicating an observable effect related to enzyme induction and liver cell response to the compound; (c) at 0.1 Mg/kg body wt/day, an increase in liver carcinomas was observed. The animal-to-human extrapolation of the no-effect level for TCDD exposure from the rodent data indicated an intake of 1 ng/'kg body wt/dav or a total daily intake of 70 ng as the no-effect level. If fish containing average TCDD residue levels of 25 ppt were consumed in the amount of the 99th percentile. i.e., 36.8 g/' day. the total daily intake of TCDD would be 0.92 ng or 13 pg/kg body wt/day or less than l/70th of the no-effect level, less than 1/700th of the lowest-effect level, and less than 1 /7000th of the carcinogenic level. The safety margin at the 90th percentile of consumption is even greater. As a result of this assessment, a public health advisory was sent to the health v officers in each of the Great Lakes states, encouraging a continued mor.itoring of TCDD residues in fish, especially in certain local areas where TCDD levels mightbe higher than the average, and where Local fish consumption might also be higher than that for the Great Lakes area as a whole. This exa.r.ple in regulatory decision making illustrates FDA's role in protecting public health by ensuring a safe and nutritious food'supply. This responsibility is exercised by individuals who call upon science, law, and the regulatory process to accommodate the demands of safety, contamination, food requirements, Congress, consumers, and the courts. Although the regulatory process has often been criticized, on the whole it has provided effective public health protection for the millions who consume food in the United States. REFERENCES ALLEN. J. R.. BARSOTT;. D. A.. VAN MILLER, J. P., ABRAHAMSOS. L. L. AND LAUGH. J. J. 09"). Mcrp'-oiogica! changes in monkeys consuming a diet co.-.;aining low isvsis of ;.3.~.S-tei:ichlorodiber.io-p-c'ioxin. Food Cosmct. Toxicol. IS, 401-410. COOK. R. R.. TOWNSEND. J. C. OTT. M. G.. AND SILVERSTEIN. L. B. (!9SO). Mor.a!h> experience . cf srspic.yeej exposed to :.j.T.S-ieirachioro<Jib«.-i20-..--cio.\ir.. JO.'.f J. 0^-ap. .'•'<::. 21. <3C-<21 HOLMSTSCT. B. 119SO). Prolegomena to Scveso. Arch. Toxicoi. 44. :i l-:;-0. KOC:SA. R. J.. KsELER. P. A.. PARK. C. N.. AND GEMMING. P. J. H976). 13.7.&-7j',ri:hic-:ociber.:op-cio.\in (TCDD;: Results of a 13-week orii loxiciiy s;udy in rats. Toxicol. Appl. Phsrn-.acol. 35, 553-574. KOCISA. R. 1. KEYSS, D. G.. SEVER.-J. E.. CARRSON, R. M.. \VADE. C. £.. DITTENJIER, D. A.. KALMNS. R. ?.. FRACSON. L. E., PARK. C. N.. BARNARD. S. D.. HUMMEL, R. A.. AND HCMISTOS. C. G. ('197*1. Results of a two-year chronic :oxic::y and oncng«riici:y jiucy o.f ;.3.7.S-;e::s>ch!oro•iiber.io-p-dicxir. i.-..ra:s. Tbxifol. .*.,-,"!. Pksrmecol. 46. "9-?03, McCosvaiJ.. £. E.. .'MOORE. J. A., AND DALOARO. D. W. (197S). Toxicity of :,3.7.S-ie:;achlorocibcr.^o-/i-cioxin (TCDD) ir. rhesus rnonl.eys (Macaco mvlci;a'i follow, jr.; 2 sir.gie orai dose. Toxieol. Af-p!. Pns.'rr.cto!. 43, 175-187. MUKP.AV. F.. J.. SMITH. F. A., SITSCHKE. K. D., HAMESTON. C. G., KocibA. R. J., AVD SC.HWETZ. �EPIDEMIOLOGY AND REGULATION OF D10XINS 387 B. A. (.1979). Three-generation reproduction study of rats given 2.3,7.8-ietrachlorodibenzo-p-dioxin (TOO! ir. '.he diet. Toxicol. Appl. Pharmacol. 50, 24J-252. Orr. M. G.. HOLDER, B. B., AND OLSON. R. D- (1980). A mortality analysis of employees engaged ir. the manufacture of 2.4,5-trichlorophenoxy acetic acid. JOM J. Occup. Mtd. 22. 47-50. PA2DsROVA-V£JLUTKOv.v J.. NgWCOVA. M., PlCKOVA. J.. JlRASEK. L, AND LUKAS. E. (1981). The oeveiopmem and prognosis of chronic intoxication by t«rachlorodibenzo-/>-dioxin in men. Arch. En\-iror.. Heolih 36, 5-11. PoccHiARi. F., SILANO. V., AND ZAMPIERI. A. (1979). Human health effects from accidental release of tetrachlorodibenzo-p-dioxins (TCDD) a; Seveso. Italy. Ann. N. Y. Acad. Sci. 320, 311-320. RECC:AM, G. U9SO). Acute human exposure to TCDD in Seveso, Italy. / Toxicol. Environ. Health 6, 2?-43. ZACK. J. A.. AND SUSKIND. R. R. (1980). The mortality experience of workers exposed to tetrachiorodibenzodioxin in a trichlorophenol process accident. JOM J. Occup. Med. 22, 11-14. �f. CooiU Ajril H, t ^ S PCOD INTAKE FOR DIOXIN, PCP LEVELS OF OONCESN 18-45yrs 2-5yrs bw.71.2 bw.16.3 total red neat and poultry Ibtal red meat 212g 108g 109.6g Beef 134g 65.6g Veal Beef + veal 20g 136g Lairb + mutton Beef liver 17g 20g Pork Pork (45-64 years) 67g 75g 36^3g 8g 6.7 Pork liver Poultry (total) Poultry (total; 45-64 years) Chicken Chicken (45-64 years) -.• Chicken liver Turkey Duck ' 53g 56g 44g 47g 13g 33g 17g 25.4g 4.4g' Eggs Ecgs( 45-64 years) 47g 58g 28.5g Milk fat Milk fat( 13-17 years) Non-fat railk Ken-fat milk (13-17 years) 24g 31g 48g 74g 23.4g �Samples collected fron Smith Farms (26 operating farms) en 1/17/83 Eggs Eggs Eggs Eggs - Farm £34 - K&M Farm - Farm #40 - Benders Farm 0.20ppm (PCP) O.lSpcm (PC?) O.~13ppm (PCP) Feed Feed Feed 0.26ppn (PC?) Feed O.OSppm (PC? 0.07ppra (PC?) Trace (PCP) . Trace (PCP) Food consumotion bv days and meals: Beef Perk Chicken Eggs Milk fat Other 18-45 years 134g X 5 ireals=670g 75g X 5 neals=375g 44g X 4 meals=176g 47g X 7 msals=329g 24g X 7 iTBals=168g 30g X 7 neals»210g 1928g 1928g/7=275.4g/day 2-5 years 55.6g X 5 meals=328c 36.3g X 5 neals=182g 25.4g X 4 m=alssl02g .28.5g X 7 meals=200g .23.4g X 7 nfials=174g 10.Og X 7 maals-TO^ 1056c 1056g/7=151g/day � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 051 Folder The folder containing the original item. 1353 Series The series number of the original item. Series III 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 Barnes, Donald G. Title A name given to the resource Memorandum: FDA Risk Assessment for Higher Chlorinated Dibenzo-p-dioxins, from Donald G. Barnes to Alvin Young and others, May 13, 1983 Subject The topic of the resource dioxin dietary exposure 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 <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 052 Folder The folder containing the original item. 1395 Series The series number of the original item. Series III 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 Barnes, Donald G. Title A name given to the resource Letter: from Donald G. Barnes to Alvin Young, 24 October 1984 Subject The topic of the resource Superfund ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/e31369a2d54e1c0008881d1beef72143.pdf 9a149721cbf2e2ab0244aa2c12625dda PDF Text Text Item ID Number °1719 Author Barnes, Donald G. Corporate Author Report/Article TltlO Memorandum: Suggested Procedures for Review of CDC Protocol, from Donald G. Barnes to Members of the Science Panel, July 1,1983 Journal/Book Title Year 000 ° Month/Day Color H Number of Images 7 Descripton Notes Monday, June 11, 2001 Page 1720 of 1793 �A , j % lmm \ ~" UNITED STATES ENVIRONMENTAL PROTECTION AGENCY .$ WASHINGTON, D.C. Z0460 % na& JUL OFFICE OF PESTICIDES AND TOXIC SUBSTANCES MEMORANDUM TO: Members of the Science Panel SUBJECT: Suggested Procedures for Review of CDC Protocol The Science Panel has requested the assistance of the Ranch Hand Oversight Committee in the review of CDC's protocols of epidemiologic studies of the health of Vietnam veterans. Based on conversations with Dr. John Moore, it was agreed that the Science Panel would supply the Ranch Hand Oversight Committee with a list of concerns that would focus the Committee's attention on those issues which the Science Panel feels are most urgent, with the assumption that the individual committee members would be free to make any additional recommendations that they feel are appropriate. The attached "Outline of Concerns" were drafted with the cooperation of Major Bob Capell (USAF), Dr. Phil Kearney (USDA), Jason Toth (EPA), and myself (EPA) after a telephone conference last Thursday, June 23. In addition, Dr. Carl Keller and Jason Toth, attended the Office of Technology Assessment ' s review of the CDC protocols on Friday, June 24, and felt it desirable to include a discussion of some of the more generic aspects of the protocol. At the same time, we do not want to discourage reviewers from missing this opportunity to comment on more specific aspects of the protocol. We believe that our objective today should be to reach a consensus among ourselves as to which general concerns are most appropriately addressed by the Oversight Committee and what the format for such a review should be. We recommend that individual Science Panel members use this same outline in structuring their review of the protocols. Donald G. Barnes, Ph.D. EPA Representative to Agent Orange Work Group Chairman, Subcommittee on Protocol Review �Outline of General Concerns I. Background and Review of the Literature Although the CDC literature review is relatively current and appropriately takes advantage of previous published comprehensive literature reviews, there is relatively little discussion of the clinical experience of the presently on-going Veterans studies. Recent Congressional testimony by Dr. Custis of the V.A. stated that there have been over 350,000 Agent Orange related outpatient visits, over 100,000 physical examinations, approximately 20,000 veterans who have received more than one exam and about 9000 Agent Orange related hospital admissions (May 1983). Although the physical examinations of veterans conducted by the V.A. represent a self-selected group, they nevertheless may provide a valuable data base from which to refine and modify physical examination protocols as well as providing reviewers with a basis for evaluating the relative merits of individual studies. 1. II. Do reviewers feel that it would be desirable to include a more thorough discussion of all relevant on-going epidemiologic studies of veterans in the final protocol, especially the V.A. Agent Orange Registry examinations and any preliminary findings of the Ranch Hand study? Exposure Index Accurately classifying Vietnam veterans with respect to herbicide exposure is the single most important aspect of this investigation, and CDC appropriately described several reasons as to why these obstacles have been a "formidable impediment to the accurate assessment of health effects related to herbicide exposure" thus far. Nevertheless, CDC feels that the "Herbs" tape and other-available records are sufficient to make a reasonable determination of a veteran's potential exposure to Agent Orange. It is not clear however, how the CDC intends to validate this exposure index. �-2- 1. Do the reviewers have any specific recommendations for validating the exposure index proposed by CDC (such as crosschecking the pilot study sample against yet another source of data or using a sensitive biological marker of exposure)? The second major concern with respect to classifying veterans by potential exposure status is to investigate the influence of all confounding exposures, particularly combat experiences and insecticide exposure. 2. Do reviewers have any recommendations for minimizing the influence of confounding exposures? 3. Do reviewers have any concerns or suggestions relating to the sampling procedures and potential selection bias posed by the proposed scheme for selecting study participants? For instance, what are the potential consequences of randomly choosing one day of the week and then selecting study participants from company records? Would it be desirable to estimate quantitatively the influence of misclassification bias in several hypothetical scenarios and then recalculate power estimates? III. General Study Design With respect to the rationale and general study design, the case-control study of soft tissue sarcoma, the retrospective cohort mortality study, and the Vietnam experience study all represent needed additions to the current Investigations of Vietnam veterans and appear to be relatively straight forward. However, the assessment of morbidity outcomes among Agent Orange exposed veterans is not as straight-forward as the above studies. The utilization of a one-time physical examination and health questionnaire as the major instrument for assessing health status has certain limitations, such as: (1) missing those individuals whose overt manifestations related to Agent Orange exposure 15 years ago may not have persisted until the time of examination; (2) secondly, missing those individuals who currently have no apparent physical manifestations of disease but may nevertheless have subclinical metabolic changes of medical significance which may not be adequately investigated during the exam; (3) and thirdly, some veterans may not yet have had sufficient time to develop signs and symptoms associated with Agent Orange exposure. �1. 2. A consistent recommendation made by the National Research Council, the University of Texas and the Department of Defense Armed Forces Epidemiological Board in review of the Ranch Hand study was that the physical and neuropsychological examinations should be more refined by "evaluating a limited number of morbidity endpoints, each in greater details." Do reviewers feel that the clinical examination should be expanded further to include more sophisticated tests such as nerve conduction velocity or should the clinical examination remain broad scoped unless physical findings indicate more refined tests? Do reviewers have any other suggestions for Improving the clinical examination protocol? 3. Do reviewers feel that it would be desirable for a more thorough discussion of the rationale for those tests whose purpose is not obvious, as well as a discussion of the criteria that will be used to evaluate the results of its pretests? Should the results of of the pretests be a major check point before proceeding with the rest of the investigation? 4. Do reviewers feel that the proposed timetable is overly optimistic? 5. What are the consequences on the power of study to detect potential adverse health outcomes if substantive modifications of the protocol are made during the course of the actual investigation? 6. IV. What is the cumulative influence of these considerations on the liklihood of detecting a true adverse health effect attributable to Agent Orange exposure? Would it be desirable to follow a subset of individuals for a longer period of time, with periodic examinations and updated questionnaires such as in the Ranch Hand study? Do reviewers feel that there needs to be a clearer delineation between the pilot study phase and the principal investigation? Specific Concerns A. 1. Sarcoma-Lymphoma Study What is the effect of non-uniform histologic classification of soft tissue sarcoma, especially if non-SEER cancer registries are utilized? �-4- 2. Do reviewers have any suggestions for miniimizing hypothesis testing problems posed by the simultaneous investigation of multiple cancer sites? 3. Are the power calculations of the ability to detect a statistically significant elevation of cancer risk based on appropriate data? For Instance, does the protocol take into consideration the anticipated fraction of Vietnam veterans who were likely to have been exposed to herbicides between the years 1963-1969 and are now living within the boundaries of participating SEER registries? 4. Does the Committee have any recommendations concerning the selection of controls or minimizing recall bias among cases? 5. Could this study be conducted more efficiently and rapidly by closer collaboration with NCI and their investigations of soft tissue sarcoma? Alternatively, should all presently on-going casecontrol studies of soft tissue sarcoma utilize CDC's questionnaire for investigating Vietnam Agent Orange exposure? 6. What are the relative advantages and disadvantages of utilizing next-of-kin interviews of deceased cases, thereby offering the possibility of completing the study earlier than planned? B. Vietnam Experience Study 1. Should this study be given more emphasis in view of its potential to investigate "many factors in addition to herbicide exposure which could have adversely affected those who served in Vietnam" as well as satisfying veterans' demands for an investigation of compensatable disabilities? 2. Do reviewers have any recommendations which could improve the ability of this study to investigate the morbidity of veterans who had combat experience but were not exposed to herbicides? 3. Do reviewers feel that there should be a discussion of how CDC's proposed Vietnam experience study relates to the "Vietnam Veterans Mortality Study" and the V.A. "Survey of Patient Treatment File for Vietnam Veteran In-Patient Care?" For instance, could the power of detecting conditions of low prevalence be improved by combining all three efforts? �-5- Co Agent Orange Study 1 <> Do members of the Committee feel that the present ongoing CDC investigation of birth defects, which is focused primarily on structural abnormalities, is sufficient to investigate all possible reproductive hazards? If not, would a more detailed questionnaire or spouse interview be sufficient to improve the investigation of reproductive hazards in the present study or would it be necessary to measure sperm count, morphology or sister chromatid exchanges to investigate adequately these endpoints? 2» Should there be a much more detailed discussion of the selection of tests for the neuro-psychologic examination? Would it be possible to describe a psychological syndrome or set of symptoms which have been reported most frequently by the V.A. examiners (and in the literature) and then investigate this "pattern" of symptoms more systematically? 3. Do the reviewers have any further recommendations that would improve the scientific validity of this study? For instance, does the Committee have any recommendations concerning the relative merits of CDC's efforts to balance misclassification bias against comparability of study participants? 4. Do the reviewers feel that the CDC is being realistic in their estimates of the number of physicals and specialist examinations that could be conducted by individual physicians? Is it absolutely necessary to examine all study participants at one or two centers, or could blood samples and test results be sent to a single laboratory for analysis, while at the same time examining many more veterans at multiple facilities? In order to minimize the inter-observer variation that multiple examining centers would present, would it be possible to develop strict clinical classification criteria or to document suspected cases of chloracne with photographs that could later be read by a panel of specialists? 5. Is there any way to include veterans who served multiple tours without compromising the comparability of the study participants or introducing too much selection bias? �-6- V. Overall Objectives and Purpose of Investigation It is clear that the major impetus for the current mandate by Congress (Public Law 96-151) to require the Veterans Administration to conduct an epidemiological investigation of U.S. veterans derives from the persistent and legitimate demands of veterans' organizations that the U.S. government investigate their claims for war related disability compensation. Although statements of purpose such as "to assess the possible health effects of exposure to herbicides and dioxin during the Vietnam experience" can certainly be understood to encompass the development of a data base from which such claims may be evaluated, the stated objectives of the CDC protocol do not reflect full cognizance of the potential problems of interpretation and litigation that are likely to follow a study of such complexity and controversy as this one. For instance, Representative Thomas A. Daschle has sponsored a special service-connected disability compensation bill which contains a sunset provision to retract the presumption of association for chloracne, porphyria cutanea tarda, and soft tissue sarcoma if data from the ground troops study does not confirm these associations. It would appear then that there are expectations, which although legitimate may be unreasonable, and it may be necessary to evaluate the objectives of the proposed studies within this context. 1. Do reviewers feel that the proposed studies, either individually or collectively, are sufficient to adequately resolve compensation issues? Are there potential modifications which could improve the ability of this study to resolve such issues? 2. With respect to the stated objectives, will the proposed studies contribute substantively to our understanding of the adverse health effects of 2,4,5-T and dioxin exposure among veterans? � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 064 Folder The folder containing the original item. 1719 Series The series number of the original item. Series III Subseries III 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 Barnes, Donald G. Title A name given to the resource Memorandum: Suggested Procedures for Review of CDC Protocol, from Donald G. Barnes to Members of the Science Panel, July 1, 1983 Subject The topic of the resource Agent Orange Exposure Study study protocol study criticism Vietnam Experience Study ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/303056d230e58afc50f49f117e65dcf4.pdf 74d93fdd921ad400779edc1c34632f44 PDF Text Text Item ID Number 01733 Author Barnes, Donald G. Corporate Author Roport/Artido TitlO Typescript: Comments on "Proportionate Mortally Study of Army and Marine Corps Veterans of the Vietnam War," Septembers, 1987 Journal/Book Titlo Year oooo Month/Day Color n Number of Images 1 Doscrlpton Notes Monday, June 11, 2001 Page 1784 of 1793 �9/8/87 COMMENTS ON "PROPORTIONATE MORTALITY STUDY OF ARMY AND MARINE CORPS VETERANS OF THE VIETNAM WAR" Donald G. Barnes U.S. Environmental Protection Agency 1. Proportionate mortality studies have inherent limitations which restrict their interpretation and conclusions; e.g., reduced PMR in one area necessitates increased PMR in another area. This particular study is a generally welldesigned example of this type of investigation. The report clearly discusses the procedures, methods of analysis, and the conclusions, including caveats. The results should not be cited without an thorough appreciation of these caveats. 2. The study is a descriptive study which essentially suggests hypotheses for further investigation. As such, the study does not test any particular association, let alone prove any cause-effect relationship. 3. It should be noted that of all the PMRs the two identified as being of concern, while statistically significant, are modest (roughly 2) — a tribute to the scale of the study. 4. Among the areas of concern is the question of whether there is an inherent difference between Marines in Vietnam, compared to non-Vietnam Marines and all Army troops. It has been suggested that the Marines in Vietnam had attitudes and behaviors (e.g., risk takers) which were distinguishable from other troops. 5. The diagnosis of Non-Hogkins lymphoma is not easy. There might be a bias in the recording of this diagnosis in cases in which it was known that the patient had served in Vietnam. 6. If one is concerned about the etiology of cancer vis a vis Vietnam, it would be preferable to exclude any cancers that' appear prior to some minimal latency period; e.g., 10 years. 7. It would be enlightening to look at the proportionate cancer mortality ratios (PMCRs), which would examine the relative cancer experience in greater detail. 8. Possible followups include: a. An I Corps study of the Army veterans — planned b. A periodic updating of the current study to take into account latency, etc. — planned? c. A cohort study of the Marines d. A case-control study of the NHL and lung cancers in the Marines. The question of exposure still remains. Given the recent results of the CDC exposure validation study, it is not clear that options c and d are tenable. � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 066 Folder The folder containing the original item. 1783 Series The series number of the original item. Series III Subseries III 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 Barnes, Donald G. Title A name given to the resource Typescript: Comments on "Proportionate Mortality Study of Army and Marine Corps Veterans of the Vietnam War," September 8, 1987 Subject The topic of the resource VA Mortality Study lymphomas study criticism ao_seriesIII https://www.nal.usda.gov/exhibits/speccoll/files/original/12629149767c55695acc21d9b6acc892.pdf 3e98d969481c7c54bbfabc8f9c3e6e79 PDF Text Text Item D Number °2409 Author Barnes, Donald G. Corporate Author Report/Article TltlB Description of Times Beach, Missouri and the Times Beach Dioxin Research Facility Journal/Book Title Year 000 ° Month/Day Color n Number of Images 8 DeSCrbtOn NOtBa Included in the description are maps of the area. Item also includes an announcement of the paper "United States Environmental Protection Agency's Approach to Dealing with 2,4,7,8-TCDD in the Environment." Friday, October 05, 2001 Page 2409 of 2422 �UNITED STATES ENVIRONMENTAL PROTECTION AGENCY'S APPROACH TO DEALING WITH 2,3,7,8-TCDD IN THE ENVIRONMENT Donald G. Barnes, Ph.D. Science Advisor to the Assistant Administrator for Pesticides and Toxic Substances Chairman, Chlorinated Dioxins Work Group US Environmental Protection Agency Washington, D.C. 20460 In 1976, an explosion in Seveso, Italy focused the world's attention on the environmental risks associated with 2,3,7,8TCDD. Earlier, the United States had confronted related condi-tjbns on a smaller scale in horse arenas in the state of Missouri. Since that time, the issue has grown in intensity and complexity. There are currently more than forty confirmed sites of 2,3,7,8-TCDD contamination in Missouri, and several states with reported contamination within their boundries. In December, 1983, the United States Environmental Protection Agency announced its "Dioxin Strategy", which addresses the discovery and clean-up of contaminated sites, research projects, and the significance of "dioxins" other than 2,3,7,8-TCDD. In August, 1984, a major step in the implementation of this strategy was taken with the announcement of the National Dioxin Study. This paper will review the Dioxin Strategy and the National Dixoin Study, relating these to the past and continuing experiences at Seveso. �TIMES BEACH DIOXIN RESEARCH FACILITY One of the conclusions of the Missouri Dioxin Task Force was that further research needs to be conducted to determine dioxin destruction methods. The Missouri Department of CO 55 Natural Resources (MDNR) recently assisted in establishing a e>2 C£ O CO UJ c: dioxin research group. This group consists of governmental agencies (MDNR, EPA, Missouri Division of Health), industry and the University of Missouri. This group also has concluded that in-situ research at Tiroes Beach, Missouri, would be of great help in determining destruction methods for dioxin contaminated soils. Based on the group's conclusions, the MDNR is soliciting proposals for conducting in-situ research on dioxin contaminated soil at Times Beach, Missouri, beginning during the summer of 1984. Li- £ Of The objectives of this project are twofold. The first is to isolate those technologies that have potential to detoxify dioxin contaminated material. The second objective is to compare different successful technologies for application to solve the crisis. Once potential technologies have been identified, long-term funding mechanisms can be looked at for those processes by the regulatory agencies. Laurel Road in Times Beach, Missouri, has been selected as the area for conducting in-situ dioxin destruction investigations. The street is bounded on the west and east sides by Orchid Drive and Beach Drive, respectively (see map). The concentration of dioxin in soils is in the range of 100-300 ppb. Christopher S. Bond Governor Fred A. Lofser Director Division of Environmental Quality Robert J. Schrelber Jr. P£. Director �The MDNR ectine on the suggestions of the research group has set up the program by excavating a two block portion of Laurel Road. The soil and gravel were homogenized by mixing them thoroughly. The soil was then screened to remove the larger gravel end rocks. The screened material was then laid back into stainless steel bins six feet by eight feet by two feet deep and compacted back to the original density. A bottom liner was installed to drain liquids seeping through the soil. plot. Water and power outlets are being provided at each An on-site soils laboratory is also available. *- S e c u r i t y arrangements such as lockers and a d e c o n t a m i n a t i o n f a c i l i t y are also a v a i l a b l e . A f u l l - t i m e MDNR on-site coordinator is a v a i l a b l e to oversee operations and ensure that s e c u r i t y is m a i n t a i n e d . Emergency services are also available. A comprehensive sampling and analysis program was * conducted to determine initial reference levels prior to implementing research proposals. The plots are currently available for in-situ investigations. The group has decided that at least three units be made available per research group. This, would give the researcher an opportunity to create a standard reference unit and vary parameters as necessary in the other two units. Standardized soil could be made available for in-house research, if the researcher demonstrates that he has the resources for in-house management of dioxin. �During the investigation, close monitoring will be maintained by the research group to assess the progress. At the end of the investigation, the group will review the project's accomplishments and will take the appropriate actions such as disbursing the information or recommending that the process be applied at a given site. Funding mechanisms for the program are being evaluated. It is anticipated that the majority of the proposers would be self-funded industrial entities. The cost for leasing a plot (set of three units) is $16,500 to be paid initially. This *one time fee is essentially the cost of preparation of the plot along with sampling and analysis costs before and after a research project is complete. This sampling and analysis will provide MDNR verification of a project's success. For further information, contact either Robert Schreiber or Vivek Goswamy at (31*4) 751-32*41. �TIMES BEACH Location Legal Description: Floodplain of the Meramec River, principally W 1/2, Sec. 32, and E 1/2, E 1/2, Sec. 31, T.44 N.t N., R. 4 E., 5th P.M. Manchester Quadrangle St. Louis County Latitude: 38° 30' 33" Longitude: 90° 36' 08" Population 2,061 (None at Present) Accessibility Times Beach can be entered by any of three routes. Interstate 44 exits onto a northern outer road which goes into the City. Lewis Road from the north also connects with the 1-44 outer road. The third access route is from the City of Eureka south of 1-44 onto Times Beach Service Road. History Summary , In June 1972, a city ordinance was passed to contract with a waste oil hauler to spray the roads for dust control. Apparently all of the gravel streets were oiled that summer twice and a third time where needed, as recalled by residents. In 1973, the roads were again sprayed by contract. The agreement was to have approximately ten miles of road oiled. Five additional streets had been paved so less oiling was done that year. EPA sampled the roads and right-of-ways in November and December 1982, and found 2,3,7,8-TCDD levels up to 127 ppb. In December 1982, the Meramec River flooded the town. EPA sampling in January 1983 following the flood showed that the contaminated soil remained quite immobile throughout the flooding. On February 22, 1983, the EPA Administrator announced a $33 million pledge from superfund to purchase the Times Beach property under a relocation plan to be developed and implemented by the Federal Emergency Management Agency (FEMA). EPA is planning to have a feasibility study conducted to determine the scope and costs of cleanup alternatives. The city 1s on the National Priorities List. Site Description (see maps) Times Beach is principally bounded by the Meramec River, Interstate 44, and the Burlington Northern Railroad tracks. Being in the 100-year floodplain, the area is relatively flat. The majority of the city's 28 miles of paved and gravel road, shoulders, and ditches are contaminated. Maximum levels of 2,3,7,8-TCDD are shown on the city map. Contamination has been found down to at least two feet below the surface. The City of Eureka, population 3,862 lies Immediately to the south and west of Times Beach. None of Eureka's streets were oiled and no contamination has been found within the city. Results of all groundwater sampling in the area have been negative. �Geologic and Soils Description Times Beach 1s on an alluvial setting, underlain by alluvial silt to a depth of more than 5 feet. Below the alluvial silts; sand, gravel, and a mixture of silt, sand, and clay would be expected to a depth of from 40 to 50 feet where bedrock 1s encountered. The water table would be expect:> ed to be about at the Meramec River level, between 10 and 20 feet from the surface in most of the area. The alluvial silt has a relatively low permeability and would be expected to be wet natured in that it does not readily or rapidly drain water. Due to this and the screening effect of the silt, it 1s not likely that soil particles contaminated with dioxin would move down Into the water table. It can be assumed that the contaminated material consists of road bed material plus native soil where the contamination has eroded into the ditches. �ft^-7^^ LJrV-ts-xvtrSs.. MANCHESTER, MO. > - ka l « Times Beach- Mapped by the Army Map Service Published for civil use by the Geological Survey Control by US6S. USCiGS. and USCE Topography from aerial photographs by photogrammetric methods Atria! photographs taken 1952. Field check 1954 f*o»yconic projection. 1927 North American datum 10.000-foot gric based on Missouri coordinate system, east zona 1000-meter Universal Transverse Mercator grid ticks, zone 15. shown in blue Dashed land lines indicate approximate locations Unchecked elevations u* shown in brown To place on the predicted North American Datum 1963 move the projection lines 2 meters_toutii and 10 meters east as shown by tesnee comer ticks MM «N 1000 nr I if MIL! VTM CHID AND tta: MAGNFTIC NOKTN BCCUNATIDN AT CCNTEft OF SMCET There may be private inholdings within the boundaries of the National or State reservations shown on this map THIS FOR SALE BY U. S. GEOL5 AN MSSOtmt DF A FOLDER OE$ �TIMES BEACH, MISSOURI U.S. ENVIRONMENTAL PKOTECTlOM REGION 7 - KANSAS CITY 183 «f3«9 Stmptec JUathtle •* of 2/4*1 vaKtr atturantc ^t^ LEGEND Kit than I - 10 UlllllK 20 - loo 100 - 300 •t f art» P*r Y © * .. -.! � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 095 Folder The folder containing the original item. 2409 Series The series number of the original item. Series IV Subseries IV 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 Barnes, Donald G. Title A name given to the resource Description of Times Beach, Missouri and the Times Beach Dioxin Research Facility Subject The topic of the resource Missouri EPA Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 118 Folder The folder containing the original item. 3167 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 Barnes, Donald G. Source A related resource from which the described resource is derived Chemosphere Date A point or period of time associated with an event in the lifecycle of the resource 1983 Title A name given to the resource Assessing TCDD Emissions from Municipal Waste Combustors Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 118 Folder The folder containing the original item. 3168 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 Barnes, Donald G. Source A related resource from which the described resource is derived Accidental Exposure to Dioxins: Human Health Aspects Date A point or period of time associated with an event in the lifecycle of the resource 1983 Title A name given to the resource Chapter 17: Possible Consequences of Sharing an Environment with Dioxins https://www.nal.usda.gov/exhibits/speccoll/files/original/c20db01fb4daaa355ded5f50fb080c0e.pdf a6c630bc7652374e83f6c4b4c076c858 PDF Text Text item D Number °5108 Author Barnes, Donald G. D Not Scanned Corporate Author Report/Article Title Tr 'P ReP°rt Highlights and Analytical Chemistry and Source Notes for the World Health Organization Meetings in Naples, Italy and Copenhagen, Denmark, March 15-27, 1986 Journal/Book Title Year 000 ° Month/Day Color Number of Images D ° Descripton Notos Friday, February 22, 2002 Page 5108 of 5115 �T R I P R E P O R T H I G H L I G H T S WHO MEETINGS ON "DIOXINS" Municipal Waste/Sewage Sludge Incineration -- Naples, Italy Human Milk -- Copenhagen, Denmark March 15-27, 1986 Donald G.Barnes This report contains the highlights of the meetings. In the coming days, I plan to prepare more extensive "discussion papers" on the variety of topics list in item 8 below. 1. My presence at these meetings proved to be more important than I first envisioned. As events unfolded, I was able to contribute materially (perhaps "disproportionately" would be a better descriptor) to the process, the substance, and the outcomes of the meetings -- for better or worse! 2. Municipal Waste Combustion (MWC) and Municipal Sewage Sludge Combustion (MSSC) Meeting WHO-Geneva and WHO-EURO had/have an on-going tussle over "who's in charge" of the CDD/CDF risk assessment issue. At Geneva's strong encouragement, the Naples meeting steered clear of a direct assessment of risk. Rather, we developed what I would call a "relative exposure assessment". This entailed accepting certain calculations which have been done to estimate the daily intake of 2,3,7,8-TCDD equivalents necessary to maintain the apparent background body burden; i.e., 1-5 pg/kg-d. Then we looked at how much of this is likely to be coning from municipal waste combustors (MWCs) and municipal sewage sludge combustors (MSSCs). The analytical chemists gave us estimates of the emissions from such units under best conditions, most likely achievable conditions and anomalous conditions. We concluded the following: a. Direct inhalation of emissions from MWCs and MSSCs which are operating at most likely or most likely achievable conditions does not constitute a large contribution to the daily background dose. Note: This is the only exposure EPa generally considers. b. Indirect contributions; e.g., via the food chain, are unknown, but for a variety of reasons, are arguably moderate-to-low. c. Recent data indicate that the best case emissions can be substantially improved by additional control technology. d. The increasing number of sources of CDDs and CDFs which are being proposed and/or identified in the environment tends to lessen the actual contribution of MWCs and MSSCs to the total impact. There was a healthy discussion about the likelihood of any effects in humans, given the epidemiological evidence to date. The group deferred to the alleged recent judgment of IARC that the evidence of human carcinogenicity for -1 - �2,3,7,8-TCDD has been elevated from "inadequate" to "limited". However, there remained strong feeling that the threat to humans is likely to be much less than many currently believe based on animal evidence. 3. CDDs/CDFs/PCBs in Human Milk Meeting The purpose of the meeting was to determine whether there were any additional data/studies which should be .-••• • .•. ••• ••; gathered/collected'prior to -conducting a risk assessment on the CDDs/CDFs/PCBs in human milk issue late this year. '•••' , "'We' concluded that we probably have now all that we will have then. Therefore, we drew up an outline of what the '•••'• report should look like:. ' • • '•''• ''•• : " ' ; There will be three reports, individually drafted, that will _-:. -•:. --feed into; one''maih paper: • : - ; '•' •'•' '••• •'•' : a. Chemistry: Sources, residues data, and analytical problems '-- b. Estimated'intake'of CDDs/CDFs/PCBs : c. Epidemiology studies to be conducted in the long term ••"-!•. Hazard" Identification (Why'should anyone be concerned?) A. Human data '••' - 1 B.''Animal'data '''" : '! 1J"^ C. Toxicity equivalents : D. Uncertainties : ••'•' ' ' '' ' •'"•' 1. Link between sensitive effects in animals and anything •'••' ''in' humans ' ' ' •'''• ' :' ' • '•• ' ' ;"'''' ' •' '"" ' 2. Toxicity equivalents •••'••" '•'• 3. Different mixtures 4. Etc. II. Exposure Assessment A. Sources B. Estimated intake's and relative contribution of human milk C. Historical trends III. Benefits of Breast 'Feeding IV. Preventive Strategies A. What to do in the near term B. Epidemiological study in the long term V. Conclusions and Recommendations 4. WHO is interested in EPA's continuing to cooperate in the area of CDDs/CDFs. Specifically, they would like to see EPA contribute to the funding of a preparation of the report on human milk. Given the import and impact of the issue, I believe that the Agency should stay actively involved with this project. 5. WHO-Geneva is producing criteria documents on both PCBs and CDDs/CDFs. Several of us are reviewing the latter. We should be assured that our overall participation is appropriate, focused and sustained. 6. In the minds of some, the emissions of any combustion source are qualitatively similar to those of MWCs. Therefore, folks are speculating that MWCs many not be the main source of CDDs/CDFs in the environment that some have -2- �envisioned. Other candidates include forest fires and auto exhaust. Multiple, small combustors may constitute a serious problem; e..g., hospital incinerators, crematoria, and supermarket incinerators. 7. Dr. Chris Rappe will try to arrange a visit/seminar here at HQ on April 17. 8. Subjects for future discussion papers (cf. #1): a. Details on the MWC/MSSC decisions b. Details on the human milk decisions c. Notes on analytical chemistry d. Current and pending governmental positions/regulations on CDDs/CDFs e. Human study in Sweden f. Aspects of TEFs g. Notes for the future h. Risk assessment issues i. WHO activities in this area j. PCBs as an emerging old issue k. PCP as an emerging old issue 1. Issues which remain unaddressed: metals emissions and flyash disposal -3- �3/29/86 ' Don Barnes ANALYTICAL CHEMISTRY AND SOURCE NOTES Gathered During Meetings ,of WORLD HEALTH ORGANIZATION Held in Naples and Copenhagen March 17-16, 1986 INTRODUCTION The European Regional Office of the World Health Organization (WHO-EURO) held meetings on the above dates to consider two aspects of a three-year effort on "dioxins" and PCBs (see separate report for more extensive information this larger effort): A. The health implications of the emissions of CDDs/CDFs from municipal waste combustors (MWCs) and municipal sewage sludge combustors (MSSCs). B. Additional information which should be gathered prior to conducting an assessment of the risk of breast feeding newborns with milk contaminated with CDDs/CDFs and PCBs. The major points of these meetings were contained in a trip report submitted on March 28, 1986. The summary below, dealing with analytical chemistry and sources, is one of several summaries promised in the trip report which amplify on certain aspects of and information gleaned from the WHO meetings. Technique Sampling spikes: a. Following Rappe, Sweden has dictated that CDD/CDF analysis should include addition of a labelled spike to the sampling equipment (e.g., XAD-2 resin or urethane foam plug). Final analytical results will be corrected for the percent recovery of this spike, in a fashion analogous to the correction made for the recovery of spikes during the extraction and clean-up phase. Rappe generally finds that the recovery is in the 30-60% range, but see below. Therefore, there are three spikes in the life history of every sample: the one in the sampling device (4 congeners), the one added prior to extraction and clean-up (3 congeners), and the one added as a concurrent internal standard. There was some discussion of the effectiveness of this procedure, but, in summary, it did highlight the question of the adequacy of the sampling phase of the analysis -- which we often assume to be 100%. b. Some investigators report that ambient air monitoring for CDDs/CDFs has been effective only during the winter months. Apparently, during the warmer periods of the year, the sorbant material (e.g., urethane foam) does not retain the analyte of the sampling spike which has been added to check for efficiency of sampling. -1 - �Feeding studies One lab took a large volume of flyash and homogenized it. Repeated sampling from the large mass showed variations in CDD/CDF content in excess of 100X. Analysis of PCBs a. Analysis of the PCBs is even more difficult than that analysis of the CDDs/CDFs. The lack of standards for the congeners, the difficulty in identifying the toxic congeners, and the variable methods of analysis have made it difficult to develop a standardized an approach. However, within recent years there is an emerging consensus about how many and which congeners to quantitate and to use as a basis for quantitating the amount of PCBs; e.g., 1 1 - 1 2 peaks, as opposed to 2-3 peacks. Therefore, the reported results of some labs have decreased by a factor of about 2, simply due to a different approach to analysis. Consequently, one needs to closely examine reports of reductions in PCB levels to be assured that these are not simply a reflection of altered analytical approaches. b. A WHO meeting in February recommended quantitating PCBs based on about 7 peaks. However, only three of these peaks have been found to any significant exent in human milk; therefore, includng the othe other four in the procedure may be irrelevant, if not expensive and damaging. Laboratory capabilities a. It is estimated that there are roughly 10 labs in Europe which have the ability to measure CDDs/CDFs at very low levels. These labs are found in Sweden, the Netherlands, Denmark, Germany, Norway, Italy (3-4), and Finland. Media a. Rappe reports successful analysis of CDDs/CDFs in blood in the low ppt range, starting with 150 ml of blood. b. Rappe is conducting an inter-lab validation study for the analysis of CDDs/CDFs in human milk. They have collected a homogeneous sample of 10 liters of milk. Given the complexity of uniformly spiking this much material, each investigator will prepare his/her own samples, using prepared aliquots of spiking solution provided by the referee lab. c. Cows grazing in the plume of MWCs are reported to have higher levels of CDDs/CDFs than those grazing outside the plume. However, there is some question about the significance of this difference since the number of cows is small and the difference between the two groups of cows is not as great as one might think. d. Rappe finds that the HxCDD/F fingerprinting found in human samples matches the isomer pattern found in cows -2- �milk. Sources Air sampled in a Hamburg auto tunnel is purported to display CDD/CDF emissions similar to those from MWCs -in fact, from any combustion source. This includes the 1,2,3,7,8-PeCDD, which had been thought to be a marker for MWC emissions. At best, it is now a marker for emissions from combustion sources, in general. The three main contenders for the " Major CDD/CDF Contributor" in the environment seem to be: a) MWCs, b) automobiles, and c) PCP. Several of the analysts believe that PVC will serve as a legitimate source of CDD/CDF emissions in a MWC. This is in contrast to the position set forth by FDA in a recent EIS, in which they cite primarily one study in which increased amounts of PVC in the waste stream did not seem to materially elevate the CDD/CDF emissions. I have conveyed this information to Paul Kaldjian of the Federal Activities Office, who is coordinating the EPA response to the FDA EIS. Note that an increased possibility of CDD/CDF emissions is not equivalent to a conclusion of a significant increase in health risk. The pulp and paper industry in some parts of the world are using an N02 based bleaching process, which apparently is associated with CDDs/CDFs as well. In addition, there is indication that some parts of the industry use bromine-based slimicides; again, potential sources of halogenated dioxins and furans. I read the Kites article in the recent Environmental Science and Technology and found it wanting. Alledgedly, the article provides further evidence for the combustion of chloro-organics as the source of the CDDs/CDFs in the sediments of the Great Lakes. I did not find the evidence of the explanation convincing. First, the data displayed in the articles seemed, to me, to argue strongly for a significant admixture of higher CDDs/CDFs from pentachlorolphenol to any contribution from combustion sources. Second, I found some of the argument lack the clear compelling logic one looks for in a scientific exposition. Instead, it seemed that possibility and speculation in early parts of the paper transmuted into "fact" later in the paper. Further, I understand that there is some question about the investigator's clean up procedures. Hagenmaier (German analyst) still feels that the data say "PCP" to him. The Stiglitz experiment descrbed in Bayreuth has been investigated by Hagenmaier. He has found a lot of strangeness going on as he heats flyash at elevated temperatures for a matter of hours. For example, spikes disappear and there is a decrease in some CDDs/CDFs and an increase in others. There is evidence of the flyash's acting as a catalyst to facilitate -3- �g. h. i. j. k. 1. m. n. o. transformation of the higher CDDs/CDFs to the lower ones. Rappe has found that the homologue profiles may differ from one combustion source to the next. However, he has found that the isomer pattern (e.g., the distribution of the TCDDs) is the same from one combustion source to the next. Note: This has implications for the application of the estimation of 2,3,7,8-TCDD equivalents in risk assessment. Ballschmiter says that "Everyone knows" the percent of 2378-isomers within each homologous group that are sampled from a combustion source. He will sent me what "everyone knows". Note: This may raise questions about the Townsend explanation (cf., Bayreuth) for the origin of the CDDs/CDFs in Midland soil samples. Some folks feel that day-to-day variations at the same plant could be 10X, making an assessment of the effect of conditions and controls very difficult. Others did not agree. The general consensus is that, with current sampling methods, it is futile to discuss the percent partitioning between gaseous and particulate phases. Rappe has not seen an increase in the CDD/CDF contamination of the Baltic Sea organisms that matches the increase of in the number of MWCs. This could argue against MWC as the significant source, or it could reflect more recent improvements in combustion efficiency. Other potential sources include a) autos, b) wire reclamation plants, and metal mills burning off "cutting oils"; i.e., chlorinated paraffins. I understand that Hagenmaier reported finding 2,3,7,8-TCDD in NaPCP produced by Dynamit-Noble at a plant where trichlorophenol was produced. Further, he has found 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD in a sample of Dowicide G. Finally, he found 2,3,7,8-TCDD in a sample of 2,4-D. I have a preprint of the report which has been submitted to Chemosphere. Emissions from all kinds of incineration processes are considered to be likely sources; e.g., hospital incinerators, crematoria, and supermarket incincerators. These are likely to be small in volume, but their levels could be high. OCDD has been found in essentially all samples of house dust at a combined level of 70 ppb. A likely source is PGP which is rather pervasive; e.g., these Hx-, Hp- and OCDD have been found in toilet paper. New automobile engine oil is reported has containing Hx-, Hp- and OCDD. Again, this is suspected as having a PCP origin. An estimate of Hx-, Hp- and OCDD contributions to the German environment: 800 kg/yr from MWC 250 Kg/yr from PCP use -4- �More than 1000 kg/yr from PCP waste Controls "Metals emissions from MWCs and MSSCs could be troublesome. Swedish work seems to confirm our understanding that most metals emissions will be significatnly reduced by the controls designed to reduce acid gases, particulate, and CDD/CDF emissions. Sweden is developing a method to control mercury emission, which seem to be among the most difficult to control. It would seem that metals control at the front end could be more effective than currently practiced. Even though some authorities have implemented input conrols (primarily on batteries coming into the water stream), these attempts have not met with resounding success. Where are we in moving ahead oan this issue via RCRA, TSCA, and CPSC? Nomenclature Rappe calls the "fingerprint" based on homologue-specific data the "CDD/CDF profile" of the sample. The "fingerprint" of the isomer-specific data, he calls the "pattern" of the sample. Tidbits There is some indication of covalent reactions between PCP and fat in vivo. On a fat basis there is little, if any difference, in the CDDs/CDFs or the PCB levels in fat, organ, milk, or blood. Folks are investigating the transformation between homologues. IPCS has apparently published a report on "Principles of Risk Assessment in Infants". Canada is doing flyash leachate studies. Levels Average PCB in background human milk fat: .5-1.5 ppm " workers' " " " : 3-15 ppm The most prominent congener in milk fat is the 2,2',2,4,4',5-HxPCB See attached list for the major and minor components of PCDDs and PCDFs in human milk. Reggiani, J. of Appl Tox 1_, 323 (1981) cites three analyses of human milk by McKinney. We need to find the original report. Netherlands data on human milk will be released in April and should add to the current picture. PCP workers show an 85% decrease in their blood level of OCDD within one year. -5- � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 172 Folder The folder containing the original item. 5108 Series The series number of the original item. Series VII 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 Barnes, Donald G. Title A name given to the resource Trip Report Highlights and Analytical Chemistry and Source Notes for the World Health Organization Meetings in Naples, Italy and Copenhagen, Denmark, March 15-27, 1986 https://www.nal.usda.gov/exhibits/speccoll/files/original/53305e04de4370835d5ad2a7783c8ce1.pdf ba94c470326c0083415544ffb09c232b PDF Text Text Item D Number 05720 Author G Barnes, Donald G. Corporate Author Report/Article Title Memorandum: From Don Barnes, US EPA, to Fellow Members of the Agent Orange Working Group (AOWG) Science Panel Distribution List, regarding Trip Report on the Las Vegas "Dioxin" Meeting, dated November 13, 1987 with attachments Journal/Book Title Year 1987 Month/Day Color D Number of Images 28 DOSCrlptOll NOtBS Attachments include Trip Report, 7th International Symposium on Chlorinated Dioxins and Related Compounds, Las Vegas, Nevada, October 4-9,1987; and Program from Dioxin '87: Seventh International Symposium on Chlorinated Dioxins and Related Compounds, University of Nevada, Las Vegas, Nevada, October 4-9,1987 Tuesday, March 26, 2002 Page 5720 of 5743 �11/13/87 RE: Report on the Las Vegas "Dioxin" Meeting TO: Fellow Members of the AOWG Science Panel Distribution List FROM: Don Barnes, US EPA As you may recall, I was appointed, commissioned, and otherwise ordained to be the representative of the AOWG Science Panel at the Seventh International Symposium on Chlorinated Dioxins and Related Compounds held in Las Vegas last month. As such, I recieved and duly exercised all rights and priveleges thereunto apertaining. In order to steal -- and thereby limit -- my own thunder when I file my report at the meeting of the Science Panel on Nov. 24, I am sending you a copy of my trip report. Those of you who were at the meeting might want to examine this report as to its completeness and accuracy. Those of your who were not at the meeting might want to examine it as to its "originality, neatness and aptness of thought." In either case, I promise to limit the formal report on the 24th to less than one page. Seriously, if there are topics/areas that any of you feel merit further atteniton, I would appreciate your input. Famous last words overheard at the conference: "I never gamble when I come to Las Vegas. I keep all my assests in good sound stocks...and I am doing very well, thank you." �IQ/ 13/97 TRIP R E P O R T 7th International Symposium on Chlorinated Dioxins and Related Compounds Las Vegas, NV October 4-9, 1987 Donald G. Barnes Highlights A. Hazard Identification _ B. Dose-Response Assessment C. Exposure Assessment «_ D. Risk Characterization E. Control Technologies ___ F. Risk Management „_ . _ II. Technical Presentations A. Plenary B. Hazard Identification ^ 1 . Human Data 2. Animal Data 3. Ancillary Data C. Dose-Response Assessment 1 . Direct Potency 2. TEF-related Data D. Exposure Assessment „ 1 . Analytical 2. Sources (MWCs) 3. Sources (Other Than MWCs) 4. Transport and Fate 5. Environmental Levels 6. Human Tissue Levels E. Risk Characterization F. Control Technology G. Risk Management III. Scuttlebutt, etc. IV. Personal Activities -1- P<xg£ _ _ _ _ _ �I. HIGHLIGHTS A. Hazard Identification 1. Human Data a. No new human data were presented that would increase our concern. ' b. On the other side of the ledger, the 1986 CDC Missouri "immunotoxicity anomaly" did not hold up under closer scrutiny. c. The NIOSH study remains the "last, best hope" of getting something semi-definitive. It should be reported on at the meeting next year. 2. Animal Data a. Low level administration of OCDD for 13 weeks elicits effects that begin to look like initial stages of "dioxin" toxicity. Longer term studies need to be conducted to verify the true "dioxin" toxicity; e.g., weight loss, thymic atrophy, etc. b. High levels of some "non-toxic" CDD/CDF-like compounds appear to act as antagonists for "dioxin" toxicity. This may be a blessing for public health (God is good) and a curse for risk assessment (How can this be taken into account?). c. The Univ. of Wise, monkey data was presented with something of a flurry, including press reports. Some effects (behavioral effects and learning deficits) were reported. However, I think there was less there than met the eye. On the other hand, the analysis of the reproductive effects in these animals suggests a NOEL of .05 ng/kg-d; cf. the Murray NOEL of 1 ng/kg-d. d. 2,3,7,8-TBrDD and 2,3,7,8-TBrDF are 100x less toxic than their chlorinated counterparts as measured in rabbit ear and LD50 studies. There are implications of these data for our mandated limit of detection for the TSCA Section 4 D/F test rule. 3. Ancillary Data a. No TCDD-induced DNA adducts were observed at a detection of about 1 in 10**11. b. More information was generated on metabolism of CDDs/CDFs. c. The receptor-mediated model of toxicity remains generally accepted. B. Dose-Response Assessment » t 1. The 3 order of magnitude spred in "the window" describing international views of the potency of 2,3,7,8-TCDD remains. 2. Relatively little research is being directed at examining this issue. Each jurisdiction is basically maintaining its position. 3. Some additional subchronic, whole animal data have been -2- �generated. The TEFs generally agree with these results, with some exceptions which should probably be addressed. A previous detractor of the TEF approach has generated data that supports the approach. However, vitamin A reduction does not seem to follow the TEF predictions. 4. The NATO CCMS group is proposing a common set of TEFs for everyone. C. Exposure Assessment The majority of papers at the conference were devoted to analytical chemistry, sources, fate and transport, and levels. 1. Analytical chemistry a. Biological analyses (Safe, Gierthy, and Poland) are viewed as competing favorably with GC/MS in detection limits. In addition, these approaches seem to integrate the total biological response; i.e., these approaches might even be better for analysis of mixtures. Gierthy's analysis has been effective in assessing fish, following a cleanup which is less extensive than that needed for GC/MS. The Agency should move smartly to complete the mission of developing these approaches to replace the TEF method. b. The waxy cuticles of some leaves contain CDDs/CDFs which may reflect airborne levels of these compounds. This could be important both for monitoring purposes and for risk assessment — if those leaves happen to be cabbage leaves, etc. c. The detection limit of .1 ppb for the HDD/F TSCA rule is unattainable (according to some folks) due to the overlap of the BrDDs with the brominated diphenylethers in the clean up. d. Infrared techniques can now detect and determine structure of CDDs/CDFs in the ng range. > 2. Sources a. Sources receiving more than usual attention this year included Pulp Paper (1986 German work found 2,3,7,8-TCDD in tissue, coffee filter, and newsprint) Automobiles -- CDDs/Fs, BrDDs/Fs, and mixed C/BrDDs/Fs. (In all, there are more than 5000 chemicals in this family -- which is enough to make even the best analytical chemist blanch...and then get a gleam in his eye!) Burning of straw — which has .1% natural Cl Home heating b. We are likely to find other sources. However, we probably has found most of the "biggies". There is a need to put these sources into relative perspective. c. De novo synthesis of CDDs/Fs from C, Cl and "clean" -3- �flyash has apparently been shown. 3. Transport and Fate a. Evidence is being gathered that supports the notion of long range transport of CDDs/CDFs by air. b. Hutzinger believes that aerial deposition/collection in leafy plants is a more important exposure route to humans by direct ingestion or via grazing animals than is soil uptake by plants or sediment/water uptake by fish. c. Consensus is emerging on the half life of 2,3,7,8-TCDD at 5-8 years. (Yes, Dr. Poiger was there again looking fit and, theoretically, with only 750 pg of his original 1000 pg of labelled 2,3,7,8-TCDD. He says he has not acquired a taste for more.) d. 2,3,7,8-TCDD may be a major sink for the photodegradation of OCDD. e. Freeman and Schroy now agree with Yanders on the volatilization of 2,3,7,8-TCDD from soil; about 100X less than they had previously said. f. Vapor phase 2,3,7,8-TCDD photodegrades in solar wavelength UV. g. There is a lack of correlation between modeled dispersion and environmental samples of CDD/F emissions from a "dirty" MWC. This raises questions about the model or the sampling. h. Chloranil is apparently a source of CDDs and CDFs. Therefore, are we addressing chloranil? 4.. Levels a. There is growing consensus that there is a background level of CDDs/CDFs in humans, which in Western societies is roughly 10 ppt on a lipid weight basis. b. This body burden is probably being maintained via a dietary intake of 1 pg TEQs/kg-d. Ingestion of beef is viewed by many as being the principal component in the diet c. High body burdens of CDDs/CDFs are markers for high exposures; in some cases, for exposure which occurred long ago. d. A limited review of pooled samples of human milk in Sweden suggests that levels of TEQs have dropped by 60% over the last decade. (Note that Sweden has eliminated use of chlorophenols during this time.) D. Risk Characterization 1. Only a few true risk characterizations were presented: human milk, pulp and paper sludge use in land reclamation, and occupational exposure limit. 2. It is clear that more needs to be done in dealing with uncertainties. The human milk effort was notable in that > it used three approaches: extrapolation from animals, comparison to human data (Yusho/Yucheng patients), and -4- �background levels. 3. There is a real need to link up the analytical chemists and the exposure modellers in order to validate some of the remarkable predicitons which can now be made. 4. Kay Jones's analysis suggests that the difference between "worst case" homologue-specific assumption (all congeners are 2378-substitute'd) and the isomer-specific data is more than 10X. E. Control Technology I did not attend these sessions; however, it is my impression that USEPA is in the lead in these matters. F. Risk Management Success has been met in some instances; e.g., portions of the Missouri problem. Good risk management does not happen without good risk communication. G. Other Some folks are using "congener" where we use "homologue". goodness! -5- Oh, �II. TECHNICAL PRESENTATIONS See attached list of papers and posters. Full abstracts are available. Papers will be published in Chemosphere next year. A. Plenary 1. Hazard Identification — Steve Safe (Texas A and M) The 5000X spread seen in LD50 in different species is larger than that seen for other toxic endpoints. The AHH induction assay correlates well with subchronic responses. (Isn't it time that we began to move away from TEFs and toward this approach?) Good antagonists are those which have high binding affinity to the receptor/ but do not turn on the responses; e.g., AHH. These include Aroclor 1254, PCBs and 1,3,6,8-TCDF. Antagonism also seen in immunotoxicity endpoint; i.e., sheep red blood cell (SRBC) plaque-forming assay. 2. Dose-Response -- Bob Scheuplein (FDA) Listed all the difficulties with modeling. Sielken makes some good points; cf., Food Cosmet. Tox. article. Wee need to address this substantively. The Moolgavkar model makes testable predictions. The LMS does not. 3. Exposure (Analytical and environmental levels) — Christopher Rappe (Sweden) There are 5020 chlorinated and brominated Ds/Fs and they are being found in the environment. We need to look at "homologue profiles" (e.g., histograms of TCDDs vs. PeCDDs vs. HxCDDs, etc.) and "isomer patterns" (e.g., histograms of 2,3,7,8-TCDD vs. 1,3,6,8-TCDD vs. 1,2,3,4-TCDD, etc.) The patterns may be more indicative of source than are the profiles. The emission patterns from a number of combustion sources are essentially the same; e.g., MWC, automobiles, and PVC pyrolysis. Tissue levels Essentially the same in US, Sweden, Germany, Japan and South Vietnam Relatively lower in Chian and North Vietnam In general for CDDs: T Pe Hx Hp 0 In general for CDFs: T Pe = Hx Hp 0 Special cases Spanish family who ingested contaminated olive oil Level in the blood for OCDD is about 1 ppm'! A girl who died at 6 days old had levels just a bit below background. Routes/sources of exposure Dermal: Low Inhalation: .1 pg TEQs/kg-d Ingestion: 1 pg TEQs/kg-d Nursing: 70 pg TEQs/kg-d -6- �4. Exposure (Sources, fate and transport) -- Otto Hutzinger (FRG) Home heating and automobiles have been underestimated as sources of CDDs/CDFs. He suggested that home heating emission would be about equal to the MWC fly ash. 84 chlorinated chemicals have been analyzed for Ds/Fs in Germany. Their analytical criteria were "under 2 ppb for 2,3,7,8-TCDD and under 5 ppb for all of the other toxic CDDs/Fs". OCDD was found in many places, including aliphatic compounds. He suggested a "Trace Chemistry of Cl" theory for predicting the presence of OCDD; i.e., wherever you have Cl, you are likely to find OCDD. Possible sources include a. Chloroaromatic precursors b. Chloroaliphatic precursors c. Pyrolysis of natural precursors; cf. lignon and Cl d. Formation from ethylene units; cf. organics and Cl Combustion air could be source of feed materials leading to CDD/F emissions. See ES and T article. The amount of CDDs/Fs (mostly OCDD) in the needles of a Christmas tree is about 1 ug, or 3 kg in all of the trees in Germany. This compares to 3-4 gm TEQs/yr from automobiles. 5. Risk Characterization -- Barnes Hard copy of slides available. (Golly, they're swell!) 6. Control Options -- Tom Hauser Has a good one page summary of approaches. See des Rosiers. 7.'Risk Management — Boddington Ontario has a different SF for assessing 2,3,7,8-TCDD in air compared to fish. [Note: I would express this as saying that the risk managers had decided to accept different margins of exposure (MOEs) in the two cases in reaching their "regulatory dose (RgD)".] We do more crisis management than we do risk management. In fact, we should be doing more issue management, since we really don't know what the risk is. [This is a good thought which should be more fully developed and discussed.] We all know that funding does not support low profiles projects. B. Hazard Identification (Papers in Epidemiology, Mechanism-of-Action, Animal Toxicology, and selected posters) 1. Human data a. EP01 — "Use of Phenoxy Acid Herbicides in Sweden" A attempt to correlate production and use figures. Only a small portion was contaminated with 2,3,7,8-TCDD. b. EP02 — "Risk of STS, Hodgkin's Disease and NHL Among Swedish Licensed Pesticide Applicators" -7- �c. d. e. f. g. h. i. j. Small study of about 300 out of a cohort of 20,000. Mean follow-up time was 12 yrs. Relative risk: For STS, 6 (obs)/6.4 (exptd) = .94 For HD, 11 (obs)/9.1 (exptd) = 1.20 For NHL, 21(obs)/20.8(exptd) = 1.01 For the latter two, there was a non-significant increase with time since license. EP03 — "NHL Among Phenoxy Acetic Acid Herbicide-Exposed Farm Workers in WA State" Some "blips", particularly for other chemical exposures; e.g., chlordane, DDT, organic solvents and arsenic compounds. Nothing sticks out for 2,4-D and 2,4,5-T. There was adequate power to detect 1.3-fold excess risk. (Shiela Hoare commented that her study had detected 1.4-fold excess risk to those who had been exposed for more than 10 yrs.) "These results...do not implicate phenoxy acetic acid herbicides or their contaminants alone as sufficient causes for NHL..." The author noted that there could be a promoter or a co-carcinogen active here. EP04 — "NHL, STS and Exposure to Phenoxy Herbicides in New Zealand: Relationship to Frequency and Duration of Exposure" : Withdrawn EPOS -- "Follow-up of Chloracne Cases Following TCDD Exposure at Seveso" The abstract states: "...shows the absence of effects other than chloracne and its whole reversibility in the Seveso population." EP06 — "... Seveso...and Ten Year Mortality Experience" The abstract states: "...suggestions of an increased risk of cardiovascular diseases shortly after the accident and of a later possibly increased mortality from liver cancer in selected subgroups were obtained." EP07 — "Spontaneous Abortion and Exposure to Emissions from Waste Electrical Products Combustion" I didn't hear this paper from Taiwan, but the abstract states that "...former study shoes that pregnant women in polluted area have higher prevalence rate of spontaneous abortion." The abstract promises more info in the presentation. EP08 — "Medical Follow-up of the Health Effects of Long-Term Exposure to 2,3,7,8-TCDD" Failure to confirm the original (flawed?) study which reported immuntox effects in exposed folks in Missouri. Includes a somewhat generous discussion of what might have gone wrong and suggests additional study. (Heaven help us!) PS12 — "Case-Control Study of Women Giving Birth to Deformed Babies and on Patients Having Hydatiform Mole in the Obstetrical and Gynecologic Hospital of Ho Chi Minh city in South of Vietnam" PS 13 — "Retrospective Study on the Incidence of Birth -8- �k. 1. m. n. Defects and Other Reproductive Anomalies in the Obstetrical and Gynecological Hospital of Ho Chi Minh City" PS23 — "Surveys on Incidence of Reproductive Anomalies in Herbicide-Sprayed and Non-Herbicide-Sprayed Villages in the South of Vietnam" PS28 -- "Lab Assessment of Immune System in Individuals Occupationally Exposed to 2,3,7,8-TCDD: Test Selection, Assay Methods, and QC in a Cross-Sectional Epi Study" Preliminary work to determine the variation in the endpoints. It is going to be hard to interpret, given the intra-individual variations in these endpoints. MA06 -- "Humans Exposed to PCBs and PCDFs Exhibit Increase SCE Frequencies in Lymphocytes When Incubated with a-Naphthoflavone (ANF)" The presence of ANF increases the frequency of observed SCE in a blood cultures. True for smokers vs non-smokers. True for Yucheng patients in which the blood concentrations were 15 ppb for PCBs and 14 ppt for PCDFs. It is thought that the pollutants result in greater metabolism of ANF to genotoxic metabolites. Note TCDD receptor concentrations: rat lymphocyte -- 2 fmol/mg; human lymphocyte -- .3 fmol/mg. ANF assay also active with Chinese hamster ovary cells and TCDD induced liver microsomes. ANF-DNA adduct detected (but see lack of adducts noted by Safe). Phenobarbitol is not effective, even with ANF. P-450c is implicated. MA15 -- "Placental Markers of Human Exposure to PCBs and PCDFs" Placentas obtained 4 years after exposure in Taiwan. Marked AHH activity (10-1 OCX). Significantly lower EGF stimulated receptor autophosphorylation, correlating with decreased birthweight. However, no alteration in EGF receptor binding kinetics. Only very low concentration of specific binding sites. This suggests "...that the potent AHH induction can occur in humans in the absence of high concentrations of the Ah receptor" (cf., similar receptor concentrations in species of differing susceptibility). Marked elevation of some PCBs and PCDFs in the placental tissue; e.g., 2,3,4,7,8-PeCDF (120 ppt) 1,2,3,4,7,8-HxCDF (380 ppt), and some PCB isomers at a ppb. "Total PCB values might be better predictors of response than PCDF values following human exposure..." 2. Animal data a. AT01 — "Interleukin 1 Responsiveness and Production in 2,3,7,8-TCDF-Treated Mice" Response of thymocytes to IL-1 used as a probe for 2,3,7,8-TCDF treated mice. Perinatally exposed -9- �animals compared to postnatally exposed. Some effects seen. AT02 — "Behavioral Effects in Monkeys Exposed to 2,3,7,8-TCDD Transmitted Maternally during Gestation and for Four Months of Nursing" This is a follow-up of the Allen work. "There were no observed physiological indications of toxicity in either the mother monkey or their offspring..." Fat data are reported: e.g., offspring of the 5 ppt moms had about 350 ppt, while those from 25 ppt moms had 370, 760 and 1350 ppt. Certain social behavioral differences are noted; e.g., "...increased maternal care of the [treated] offspring..." A series of "learning data" were present allegedly showing some sort of D-R relationship. This is strange stuff, however; e.g., for some effects the trend is up with dose, for other effects the trend is down with dose. In nearly every case, the responses of the treated animals are within the range of the controlsi During the Qs and As, the author (Bowman) characterized the learning data as "Not strong, subtle". For me, this is some interesting, preliminary data for "... a relatively new area of research in which the methodology is still at an early stage of development". It certainly doesn't seem to be the type of thing that would support a story in a San Francisco newspaper. AT03 -- "Chronic Dietary Intake of 2,3,7,8-TCDD...: Kinetics and Dose-Effect Estimate of Reproductive Toxicity" The abstract indicates that a lot of tissue (fat/milk from mom/kids) have been gathered. Mom's fat cone of 2,3,7,8-TCDD is less than that of the kid. However, the moms' levels are proportional to the kids'. There is a 20-30% transfer of mom's body burden to the kid via nursing. Begin to see toxic effects in animals having a fat level of 200 ppt. Apparent half-life is a bit over a year. An index of reproductive success was developed. (Comment, anyone?) Extrapolation suggests a NOEL of about .05 ng/kg-d. (This is 20X lower than the Murray NOEL of 1 ng/kg-d or the level used by CDC, derived from these same monkeys at an earlier date.) AT04 — "Increase in Epidermal Langerhans Cells in Mouse Skin Following Treatment with TCDD" Langerhans cells are strange little fellas, 'being immunologic cells of skin. Contrary to expectation, these cells increased 3-4X following treatment of the skin with 2,3,7,8-TCDD. In vitro, both the haired and the hairless mice responded to the chloracnegen. In vivo, however, only the hairless responded. Note that phorbol esters also stimulate Langerhans cell proliferation in hairless mice. -10- �AT05 -- "Metabolism of Some PCDFs in the Rat" Chemicals studied: 1,3,7,8-TCDF 2,3,6,8-TCDF 1,2,3,4,8-PeCDF 1,2,3,7,8-PeCDF 2,3,4,7,8-PeCDF ' 1,2,3,6,7,8-HxCDF 1,2,3,4,6,7,8-HpCDF Breaking the ether linkage is tough. Metabolism of the persistent 2,3,4,7,8-PeCDF is complex. The Hx- and Hp- are not metabolized very much. AT06 — "Subchronic Toxicity of some PCDDs/PCDFs in the Rat" Compounds studied: 2,3,7,8-TCDD TEFs: 1.0 1 ,2,3,7,8-PeCDD .4 1,2,3,4,8-PeCDF .001 1,2,3,7,8-PeCDF .01 2,3,4,7,8-PeCDF .4 1,2,3,6,7,8-HxCDF .1 13 week studies. A variety of endpoints examined. Differences were noted in the manner in which the compounds distributed in the body. Tests with mixtures showed that additivity holds. (Safe predicts that antagonism would be seen if non-toxic congeners were also used.) AT07 -- "Relay Toxicity Study with a Mixture of PCDDs and PCDFs" This was presented as a poster session, which I did not see. However, the abstract talks about feeding flyash to rabbits, excising the liver, extracting the CDDs/CDFs from the liver, analyzing by GC/MS, and feeding the extract to rats. The toxicity predicted by their TEFs were in good agreement with the results of the rat study. This marks a change in the Suter-Hoffman stance in that she now finds that the TEF approach (using factors somewhat different from EPA's) works rather well, thank you. The toxic effects of the CDDs/CDFs in mixtures appear to be additive. AT08 — "Effects of Combinations of PCDDs/PCDFs Given to Rats" Vitamin A reduction does not seem to follow the TEF predictions very well. AT09 — "Is the TCDD-Induced Embryotoxicity in Rats Due to Maternal Toxicity?" Yes, and principally. AT10 -- "2,3,7,8-TCDD Induced Alterations in Vitamin A Homeostasis and in the EROD Activity in Rats and Guinea Pigs" Lots of data, including the fact that rats can recover when guinea pigs can't. AT11 -- "Distribution of 2,3,7,8-TCDD between Parenchymal and Non-Parenchymal Rat Hepatic Cells and Its Effect on the Vitamin A Content of These Cells" -11- �"...long-lasting inhibition of the normal vitamin A accumulation occuring in the stellate cells..." 1. AT12 -- "immune Abnormalities Associated with Chronic TCDD Exposure in Rhesus" "...these immunological alterations are not global, nor are they of such severity that an immunodeficient state of major clinical significant is apparent...[Tjhere have been no clinical manifestations consistent with major loss of a host defense system...[T]he observed immunological alterations occurred quite consistently in the mother carrying the higher levels of TCDD in fat for years after the exposure." m. PS44 -- "Two-dimensional Polyacrylamide Gel Electrophoresis of Liver Microsomal Proteins from Rats Treated with 2,3,7,8-TCDD, 3-Methylcholanthrene, and Phenobarbital" Characteristic patterns developed. n. PS69 — "Response of Murine Skin to 2,3,7,8-TCDD: Comparison of Haired and Hairless Genotypes" Response of newborn mouse skin to TCDD was similar to that of adults. Also looked at some skin enzyme and added treatment with other chemicals. o. SE16 -- "Investigation of Comparative Toxicity of [Flame Retardant Treated Plastics] Using 2,3,7,8-TBrDD and 2,3,7,8-TBrCF as Positive Controls" By the LD50 test and by the rabbit ear test, the TEFs for the brominated analogs are .01 or less. There is some question about portions of the experiment, but apparently BrDDs are formed a non-detectable levels. However, the BrDFs have a pretty good yield; e.g., .1%. 3. Ancillary Data (Mechanism-of-Action and selected posters, including information on physical properties) a. MA01 — "Evidence for the Formation of Chlorinated Biphenyls, Phenoxyphenols and "Dioxins" Upon Metabolism of 2,4,5-TCP in Rat Liver S9-Fractions" Apparently, a hydoxylated HxCDD has been detected in this in vitro experiment which is not observed in the absence of the S9 fraction. Previously, this biochemistry had only been observed in a fungus. b. MA02 — "A Physiologically Based Pharmacokinetic Model for 2,3,7,8-TCDDrt The model was developed using data from the C57B6 vs the DBA vs rat. It estimates tissue distributions in terms of organs volumes, blood flow rates,' etc. It postulates two groups of liver binding proteins; cf. cytosolic receptor and the microsomal monooxygenase system. c. MA03 — "Elimination and Pharmacokinetic Interaction of some PCDFs in the Liver the Rat" Half lives: 1,2,3,7,8-PeCDF 3.3 days 2,3,4,7,8-PeCDF 108 days; longer than -12- �2,3,7,8-TCDD 1,2,3,6,7,8-HxCDF 61 days; " " " " First order kinetics. No interaction in binary mix. MA04 -- "Selective Retention of PCDDs and PCDFs in Mammals: A Multiple Cause Problem" Posits that more than differential metabolism is involved. Suggests "...primary involvement of carrier-protein(s)...". Similar thoughts as MA02. MA05 -- "Liver DNA Alterations by 2,3,7,8-TCDD and 1,2,3,7,8-PeCDD in Female Rat" This was an investigation of "l-spots", liver alterations which have been suggested as sites of spontaneous initiation. Both the TCDD and PeCDD dosing led to a decrease in the concentration of these I-spots. Hmmm. MA07 -- "Effects of 2,3,7,8-TCDD on Enzyme-Altered Foci, Hepatocellular Tumors, and Estradiol Metabolism in a Two-Stage Hepatocarcinogenesis Model" Ovarectomized rats did not yield the Pitot-like promotion of DEN-initiated rats. Studies with whole rats indicated that DEN potentiates estradiol metabolic effects of 2,3,7,8-TCDD. There is some confusion about what this means regarding the promotion behavior of the compound. MA08 — "Potentiation of the Toxic Action of 2,3,7,8-TCDD by Some PCBs, as Assessed by E.I.S-bioassy" Extension of bioassay using fish to examine TEFs. Several unanswered questions about the study remain. MA09 -- " Inhibitory Effect of Methylsulphonyl PCBs on AHH Activity" These chemicals are human metabolites of PCBs found in Yusho patients. Surprisingly, they reduced AHH activity. MA10 -- "Aroclor 1254 as a 2,3,7,8-TCDD Antagonist in Mice" Safe's report of his work. Effects noted in immuno-assay. Also development of cleft palate. MA11 — "Effect of TCDD and Comparable Inducers Upon Synthesis and Mono-oxygenase Molecular Forms P-450c and P-450d Among Mammals" The first Russian contribution at these conferences. TCDD microsomes have a low content of P-450c but have much higher benzpyrene-hydroxylase activity than the enzymes induced by other "MC-type" inducers. MA12 -- "Dynamic Comparision of Rat Liver Benzpyrene-Hydroxylase Induction by 2,3,7/8-TCDD and 3-MC" A kinetic investigation of the previous paper. MA13 -- "Kinetic Models for Association of 2,3,7,8-TCDD with the Ah Receptor" Usual determinations of dissociation constant of the receptor complex assume equilibrium. Due to the rapid dissociation of the unbound receptor, this -13- �m. n. o. p. q. r. assumption is likely to be incorrect. An alternative method of determining the dissociation constant leads to values for Kd which are two orders of magnitude less than previous values; i.e., the complex is "tighter". MA14 — "TCDD Mediated Decrease in Dexamethasone Binding to the Hepatic '"Glucocorticoid Receptor is Not Accompanied by a Decrease in Immunodetectable Glucocorticoid Receptor Concentrations: The Role of Adrenal Steroids" Adrenalectomized rats are more sensitive; therefore, "...circulating adrenal hormones may exert a protective role in modifying the animal's response to TCDD..." TCDD reduced the number of glucocorticoid receptor binding sites, but did not affect the concentration of the protein itself. The role of the Ah receptor is being investigated in "susceptible" and "unsusceptible" mice. The hypothesis is that this effect is separate from the Ah receptor mechanism. MA16 — "Comparative Effects of 2,3,7,8-TCDD and Progesterone on Estrogenic Responses in Rats" Both lead to decrease in estrogen receptor. 2,3,7,8-TCDD also reduces the level of progesterone receptor. The pathway of 2,3,7,8-TCDD activity is different from that of progesterone. PS08 -- "Prediction of Vapor Pressures, Boiling Points and Enthalpies of Fusion for 29 HDDs and 53 HDFs by Vapor Pressure Correlation Method" Data from 14 CDDs/CDFs led to predictions for a number of other C1-, Br-, I-, F- and mixed DDs and 53 CDFs. PS41 — "Solubility Studies Using a Generator Column for 2,3,7,8-TCDD" Solubility of 13 ppt determined at 4 degrees C. Solubility at 25 degrees was much higher (over 100 ppt?) These values differ from the 1986 value of Marple, which EPA is citing these days. This wide variation in the literature cautions against our using any value as a "real number". PS48 — "Molecular Geometry Approximations for CDDs by Fourier Transform IR Spectroscopy" Vapor spectra of 14 different CDDs. Calculated COG bond angles to determine geometry. Ranged from nearly planar for lateral substitution with high electron withdrawing groups to tetrahedral for low electron withdrawing groups. Attempts to correlate with toxicity; cf., polarizability (Safe's" earlier work), geometry, and steric interactions; cf. PS51. PS 51 — "Calculated Molecular Geometries and Energies of All CDDs Using MMP2" A "non-quanatum mechanical technique", involving "forcefield calculatiohs", leads to estimates of geometry. The COC bond angles are determined from IR and correlated with toxicity; cf. PS48. -14- �s. PS55 -- "Thermal Decomposition Curves of HDDs by Scanned Flow Tube Pyrolysis Method with On-line Ion Trap MS Detection" t. PS59 — "An Evaluation of the Molecular Structure of OCDF" (and HpBrDF) Planar. Low energy UV preferentially removes Cl at the 9 position. Higher energy UV is less selective. Apparently OBrDF cannot be made due to steric hindrance; you get decabromodiphenyloxide instead. Further, only one HpBrDF forms (9 position vacant), while four HpCDFs form, u. PS68 -- "Receptor Binding Characteristics of 2378-CDF Radioligands" Kds: 2,3,7,8-TCDF = 1.3 nM 1,2,3,7,8-PeCDF= 5.9 nM 1,2,3,6,7,8-HxCDF= 2.3 nm These values did not correlate with competitive displacement of tritiated 2,3,7,8-TCDD of in vitro AHH induction. Apparently the oral presentation discussed the implication of these results. -15- �C. Dose-Response Assessment (Dose-Response, some Risk Characterization, and selected posters dealing with TEFs) 1 . Direct Potency a. D R 0 1 — "Reexamination of the D-R Relationship for Induction of the Hepatic Monooxygenase System by 2,3,7,8-TCDD" Looked at enzyme induction at near lethal doses. An unanticipated "super induction" is seen. b. RC08 — "Cancer Risk Characterization of HxCDD" The GAG potency calculation. Reference to a Moolgavkar model result that is two orders of magnitude lower. c. PS42 -- "Quantitative Model for the Tumor Promoting Activity of 2,3,7,8-TCDD" The application of Moolgavkar to 2,3,7,8-TCDD gives results that are two orders of magnitude lower than the UCL of the LMS. "More than half of this difference can be attributed to the differences between the higher background female rat liver tumor and lower human liver cancer rates. The second major factor is the difference between the MLE of the M-V-K model vs the UCL used with the LMS." 2. TEF related data a. DR02 -- "Effect of Pharmacodynamic Considerations on TEFs for CDDs and CDFs" Might want to consider changing values for 2,3,4,7,8-PeCDF, 1,3,4,7,8-PeCDF, and OCDD. .b. DR03 -- "Applications of the In Vtiro AHH Induction Bioassay for Determining TEQs: Pyrolyzed Flame Retardant Mixtures" Good correlation between in vitro AHH induction and in vivo AHH and EROD induction, body weight loss and thymic atrophy. c. DR04 — "Subchronic Effect of Exposure to OCDD" Linear absorption of small doses over time. Final levels: liver, 222 ppt; adipose, 165 ppt; skin 160 ppt; and blood 70 ppt. (Cf. Rappe's Spaniard with 900,000 ppt OCDD in the blood.) Increased liver/body wt, but no change in thymus. EROD and P-450 show D-R. Analyzed both the chemical and the liver for all CDDs/CDFs. Non-OCDD contaminant levels cannot account for observations. TEF = .009. Commenters noted that "classical dioxin-like activity" (e.g., thymus and body wt decrease) have not yet been seen. Response: The response seen here is like that seen at low doses of 2,3,7,8-TCDD. More work is underway. d. PS11 — "TEFs for 2378-CDDs/CDFs by the E.L.S. Bioassay" This is a fish fry assay, which has not yet been generally accepted. However, the TEFs are as follows: 2,3,4,7,8-PeCDF = .4 1,2,3,7,8-PeCDF = .04 -16- �1,2,3,6,7,8-HxCDF = .04 PS43 -- "Validation of the AHH Induction Bioassay for the Determination of TEQs" Safe's work for CDDs, CDFs, and PCBs. Demonstrated log-log linearity between in vitro AHH induction and in vivo AHH induction, body wt loss and thymus atrophy. PS45 — "Relative Toxicity of CDDs and CDFs Measured by Thymus Weight and Liver Enzyme Induction in Perinatally Dose Rats: 2,3,7,8-TCDD, 2,3,4,7,8-PeCDF, and 1,2,3,7,8-PeCDD" TEFs 1,2,3,7,8-PeCDD = .16 2,3,4,7,8-PeCDF = .05 (Ed. note: Strange) In utero exposure is about equal to exposure via milk. -17- �D. Exposure 1 . Analytical These are found in the 32 papers of the Analytical Methods section and several of the Poster papers. There were too many to discuss here. Some were somewhat arcane', but generally lead to lower detection limits in various media. Others were related to new methods, both instrumental and biologically based. 2. Sources (MWCs) (Source Emissions, Levels/Trends, and selected Posters) a. SE09 -- "On the De Novo Synthesis of PCDD/PCDF on Fly Ash of MWCs" Baking "clean" fly ash, carbon and inorganic Cl at 300 degrees C for two hours apparently can give rise to CDDs/CDFs in the ppb range; hence, "de novo" synthesis. The presence of a little copper as a catalyst is helpful. b. SE10 -- "Joint German/Swedish Program on Testing Sampling Equipment for MWC Incinerators" c. SE11 — "Chemistry for Formation and Fate of PCDD/PCDF ,in MWC Process" Only minor amounts of CDDs/CDFs in the fire box (650 700 degrees C). CDDs/CDFs formed on the way to the heat exchanger (250 - 350 degrees), as well as Cl-phenols formed. CDDs formed on fly ash. Amount of CDDs/CDFs varies 10x depending on operating conditions. d. SE12 -- "Air Emission Characterization of a Two Stage MWC" Results of testing at one NY facility. e. LT05 -- "CDDs/CDFs in Fly Ash from MWC" Tests the hypothesis that (effectively) total TEQs can be estimated from values for TCDD. Finds that "...fly ash does not have a very useful characteristic profile (fingerprint)." f. LT06 -- "Complete Analysis of Organic Compounds in MWC Flyash using HPLC and GC/MS" Levels of CDDs/Fs from Machida incinerator (Japan) are significantly lower than most other MWCs. Insert a barrier in order to generate more turbulence. g. PS50 — "Determination of PBrDDs and PBrDFs and Mixed Br/Cl Ds/Fs in Environmental Samples" Data have been obtained from MWCs and automobiles, h. PS54 — "Theoretical and Experimental Analysis of the Post-combustion Region of an Incinerator" i. PS61 — "Evidence for Post-Furnace Formation of PCDDs and PCDFs: Implications for Control" Review of studies in the literature ' 3. Sources (Other Than MWCs) a. S E 0 1 — "Emissions of PCDDs and PCDFs from the Swedish -18- �Pulp and Paper Industry" Found it in the emissions from combustion of "black liquor". (EPA's Tier 4 did not find any here.) Found it in wastewater in low ppqd. The suspended solids had it in the ppt range. SE02 — "Occurrence and Fate of CDDs and CDFs in Bleached Draft 'Papermaking Processes" EPA's tale. SE03 — "CDDs and CDFs in Effluents and Sludges from Pulp and Paper Mills" Comparable to EPA data. SE04 — "Emissions of CDDs and CDFs in Gasoline and Diesel Fueled Cars" Actually looked for and found Cl, Br and mixed Cl/Br dioxins and furans. Estimated total in Sweden is 3-7 g/yr, which is about 10% of the amount generated by MWCs in that country. Most the TEQs are from TCDF. SE05 — "Levels of Bioactive CDFs in Used and Unused PCB Dielectric Fluids" Concludes that "...normal usage of capacitors and transformers does not result in the conversation (sic!) of PCBs to PCDFs." SE06 — "Environmental Behavior of Monomehtyl-Substituted Polychlorinated Diphenylmethanes (Me-PCDMs) in Comparison with PCBs" These Me-PCDMs are PCBs substitutes in the electrical and hydraulic situations. It appears that they have similar problems, however. For example, pyrolysis yields up to ppthousand levels of CDFs, and fish bioaccumulation is likely to be similar to PCBs. SE07 — "Search for Industrial Sources PCDDs/PCDFs: IV. Phthalocyanine Dyes" CDDs/CDFs in the ppt/ppb range. In general, "...chlorobenzene with catalytic amounts of CuC12 or the chlorophenols which are present in most commercial chlorobenzenes cause the PCDD/PCDF formation. Some experiments were made for prevention of PCDD/PCDF formation." SE08 — "Pyrolysis of Dibenzodioxin, Dibenzofuran and 1,2,3,4-TBrDD with Different Chlorine-donors and Catalyts" SE13 — "Ash Data from Combustion Sources" EPA's Tier 4 results. Flyash levels of CDDs/CDFs are a qualitative, not quantitative, indicator of CDD/CDF stack emissions. SE14 — "Production of CDDs and CDFs During the Thermal Treatment of Soils Contaminated with Hexachlorohexane" CDDs are ND around 750 degrees C; CDFs ND about 1100. SE15 -- "PBrDD and PBrCDF from Brominated Flame Retardants" The German study. Higher Br compounds photodegrade. A .1 ppb detection limit is not realistic since the brominated diphenyl ethers cannot be separated from -19- �the BrDDs, due to the lower solubility of BrDDs 1. m. n. o. p. q. compared to CDDs. This makes EPA's detection limit of .1 ppb seem unrealistic. SE16 — The American Study of the BrDDs/Fs from retardants. PS09 — "Tetrachlorobenzoquinones as Source of PCDD/PCDF" 0-Chloranil and p-chloranil have levels of CDDs/CDFs in the ppb range, up to ppm for OCDD/F. PS27 -- "CDD/CDF and Chlorinated Phenols in Wood Preservation Formulations for Household Use" Levels are reported in PGP paints produced in the 1965-85 timeframe in Germany. In addition, levels in dust from homes are also reported, PS56 -- "CDDs and CDFs in the Environment as a Result of Outdoor Chemical Waste Burning" Uncontrolled burning of wastes, including 2,4,5-T still bottoms. PS57 -- "Emissions of PCDDs and PCDFs from the PVC Fire in Holmsund, Sweden. A Case Report" A January, 1987 plastic carpet company fire was investigated. "Surprisingly low levels of dioxins were detected" inside the building. Levels were found in the snow downwind, PS58 — "Monitoring New Source of PCDD and PCDF: Automotive and Straw Firing" Automotive data are compared with MWC. Straw is regularly burned in Denmark to clear fields and for residential and community heating. Straw contains .1% Cl. Home firing exceeds Swedish MWC standard of .1 ng TEQ/m3. Community firing is at .1 ng/m3 level. 4. Transport and Fate (Transport and Fate, Levels and Trends, and selected posters) a. TF01 — "Geometrical Description of the TCDD Contamination in Times Beach" Used the Univ of Pavia method for depicting the spatial distribution of the surface contamination. b. TF02 -- "Bioavailability of Grain and Soil Borne Tritiated 2,3,7,8-TCDD Administered to Lactating Holstein Cows" Bioavailable equally from crushed grain and "aged" soil. 50% is excreted in the feces, 40% stays in the fat. 15% comes out in the milk, mostly within 4 days. No receptor found in cows. No adverse effects are seen in 14 days. c. TF03 — "PCDD and PCDF Bioaccumulation by Lake Ontario Fish: Sediment to Fish Residue Relationships" For slimy sculpins, the ratio ranged from 1:1 to 1:.1. More data were presented and compared with predictions. d. TF04 — "Bioavailability of CDDs from Contaminated Soils" TCDD HpCDD OCDD -20- �e. f. g. h. i. j. k. 1. m. Newark: 1.6% 6.4% 2.6% Times Beach: 30% 8.7% 3.6% TF05 -- "Sorption of Dioxins to Soils" Log Koc, normalized on fraction of organic content in the soil, for some 2378-CDDs. There were more hydrophobia than predicted. ' Log Koc 2,3,7,8-TCDD 6.6 1 ,2,3,4,7,8-PeCDD 5.1 1 ,2,3,4,7,8-HxCDD 7.5 1 ,2,3,4,6,7,8-HpCDD 6.9 OCDD 7.9 TF06 — "Photolysis of OCDD on Soils: Production of 2,3,7,8-TCDDr' In solution, the lateral Cls seem most likely to be removed. On soil, the reverse is true and 2,3,7,8-TCDD is a sink. [This is similar to what the Wizards observed some time ago.] TF07 — "Measurement of the Photoinduced Loss of Vapor Phase TCDD by MS" Lab study suggests a half life of 11 min for 355 nm high pressure light. Quantum yield of .02. [Use this with the characteristics of the solar spectrum to predict environmental half life.] TF08 — "Long-Range Transport of PCDD, PCDF, Cl-PAH and PCP on Airborne Particles" Slight variation in congener (sic -- we would say "homologues") profiles. Isomeric patterns within a homologue are similar and are characteristic of auto and MWC emissions. TF09 — "Studies of Physico-Chemical Parameters Affecting Translocation of PCDDs in Soil" Mobility highest in the presence of organic solvents, but not directly related to solubility. Examines effects of surface area, pore size distribution, organic matter content, type of soil organics and the potential for micelle formation. TF10 -- "Field and Lab Studies on the Movement and Fate of TCDDs in Soil" Simulates the conditions at Times Beach. "The results obtained indicate that both the migration and loss of TCDD from soil through such processes as volatilization and subsequent photolytic degradations or through direct surface photolysis of soil-bound TCDD are substantially lower than the values previously reported in the literature." TF11 — "Comparison of the Rate of TCDD Transport at Times Beach and at Eglin AFB" Freeman and Schroy revise approach to fit Yanders1 data. TF12 and PS02-- "Estimating Exposure to 2,3,7,8-TCDD" EPA's "Fat Document" LT15 -- "Human Exposure to 2,3,7,8-TCDD" ORNL global modelling of 2,3,7,8-TCDD, leading to an -21- �estimated intake of about 1 pg/kg-d, 98% of which comes from food, especially meat and dairy products, not contaminated fish and shellfish. 5. Environmental Levels (Levels and Trends and selected posters) a. LT01 -- "PCDD/PCDF' in Dutch Inland Waters" Investigation of waste water discharges, sediments and fish. Sediments had differing profiles. "..[i]n only a few cases could (the profiles) be related to the sources." b. LT02 — "CDDs/CDFs in Selected Estuarine Sediments" Samples from New Bedford Harbor, Bridgeport and upper Narragansett Bay. PCDFs decreased with distance less rapidly in NBH than did the PCBs. [Additional sources? Differential decomposition?] c. LT03 -- Plant Surfaces: A Sampling System for Atmospheric PCDDs and PCDFs "Since uptake PCDDs and PCDFs via roots can be excluded..." [Basis?] Hutzinger's work on pine needles: ppt levels of all CDDs/Fs. Profiles typical of combustion sources. [How does this correlate with Crosby's finding of short half life on leaves?] d. LT04 — "Surface Contamination of PCDD and PCDFs in PCS Disposal Facility" Three facilities examined for air and surface levels of PCBs, employee blood levels for PCBs, and surface levels of CDDs/CDFs. e. LT07 -- "PCDDs and PCDFs in the Dust of the Working Atmosphere of a MWC" The dust is "quite different from the flyash samples usually collected in incinerators." All of the CDDs/CDFs are present. 2,3,7,8-TCDD was found a about .9 ppb and 6 pg/m3. f. LT08 — "Ambient Air and Incinerator Testing for CDDs/CDFs by LR-MS" Kites showed 1 pg/m3 per congener group or lower in ambient air around Bloomington, IN. This study also shows about 1-2 pg/m3 for the most abundant congener groups. "TCDFs predominate in some samples, while OCDD predominates in others." g. LT09 — "CDDs/CDFs in the Ambient Atmosphere: A Baseline Study" Bloomington, IN data of Kites Vapor Particle Vapor Part. TCDDS 20 fg/m3 ND TCDFs 350 20 PeCDDs 50 25 fg/m3 PeCDFs 65 35 HxCDDs 20 120 HxCDFs 20 75 HpCDDs 25 280 HpCDFs 6 100 OCDD 150 750 OCDF 9 40 h. LT10 — "Background Concentrations of CDDs and CDFs in Commercial Office Buildings" Two "clean" buildings in Boston and three in Santa Fe. 2,3,7,8-TCDF found in 36/41 of wipe samples; only in -22- �i. j. k. 1. m. n. o. p. q. r. s. 4/28 air samples. 2,3,7,8-TCDD was ND (100 pg/m2 and 1 pg/m3). Predominant presence of OCDD and OCDF. Compared to levels in PCB-fire buildings, LT11 -- "Pattern Analysis of PCDDs and PCDFs in Environmental Samples as an Approach to a Source/Occurrence Correlation" Looks at homologu'e profiles, D/F homologue ratios, isomer patterns, 2378-patterns. [This might be helpful.] LT12 — "PCDD and PCDF in Indoor Air of Kindergartens in N. FRG" Examines indoor and outdoor air of facilities treated with PCP or Lindane. Levels in wood also presented. TEQs generated. See RM02. LT13 -- "CDD/CDF Levels in Food Samples Collected in 1984-87 in N and S Vietnam" Data from pork, duck, beef, chicken, turtles, fish and snakes. LT16 — "Environmental Levels of CDDs and CDFs" General survey by Rappe. Sediments reflect long range airborne transport and local sources. Baltic Sea fish are about the same as 15-20 years ago. Levels of TCDF are found in deep (150 cm) sediment. This may be due to formation 300 years ago, or it may be due to some sort of "leaching" into the sediment. ' PS04 -- "PCDD and PCDF in Mice and Insects from Various Environments" Levels in insects are similar to the soil. Levels in mice (including skin), excised of the liver, are similar to soil. Liver is not like the soil. "...[H]erbivoran mice showed PCDD/PCDF levels much lower than carnivoran mice." PS05 -- "Survey of Background Levels of PCDDs and PCDFs in UK Soil" 100 points of a 50 km grid. No data in the abstract, PS06 -- "CDD and CDF Levels from Soil Collected in 1984-86 in N and S Vietnam" An advertisement, not an abstract, PS07 -- "Monitoring Ds/Fs in Precipitation Samples" Samples obtained from a remote area. TCDD and TCDF are ND at 4-30 ppqd. OCDD was found 120-620 ppqd. Lower levels of HpCDD and HpCDF. PS24 -- "Analysis of Fog Samples for PCDD and PCDF" OCDD predominates, although HpCDD is the only other CDD present. T- thru OCDF found at lower levels, PS25 -- "Concentrations of PCDD and PCDF in Soil from Vicinity of a Large Refuse Incinerator in'Hamilton, Ontario" Lack of correlation between predicted locations of high CDD/F levels and analytical results. And this at one of the highest "dirtiest" emitters. Hmmm. PS26 — "Mathematical Approach to the Data Analysis in Environmental Science. The Lecture Learnt from Seveso" -23- �A critique of past reports, t. PS49 — "Recoveries of the Early Analytical Procedures to Detect 2,3,7,8-TCDD in Soil Samples in Seveso" Makes the point that maps drawn before 1979 "...were characterized by underestimation, sometimes remarkable, of TCDD levels -- especially where contamination was higher." u. PS56 — "PCDD and PCDFs in the Environment as a Result of Outdoor Chemical Waste Burning" Top soil concentrations of 2,3,7,8-TCDD up to 50 ppb. Total of 159 ppt TEQs. Sediments at nearby shoreline showed Pe- thru 0- CDD/CDFs; no detectable 2,3,7,8-TCDD. Eel had only 82 ppb HpCDD; no other CDDs/CDFs. Rabbit livers had up to 500 ppt TEQs; 2,3,4,7,8-PeCDF accounting for 90% of the TEQs. v. PS64 — "Planar and Coplanar Polychloroaromatic Compounds in Baltic Salmon and White-Tailed Eagle" PCBs, DDTs, and Chlordane present in the ppm range. Some PCDDs/PCDFs seen near 1000 ppt. w. PS65 — "Survey of 2,3,7,8-TCDD in Selected Plants and Animals from Times Beach" Advertisement, not an abstract. [Should be interesting, though.] 6. Human Tissue Levels There were 24 papers and 6 posters (PS-31, -46, -47, -53, -62, and -63) addressing this subject. Basically, they re-enforced previous information; e.g., background levels in fat and blood, half life values, industrial vs. non-industrial nations, 1 pg/kg-d intake, and higher levels in occupationally exposed folks. Consult abstracts for details and some more interesting information (which is not to imply that this information is "uninteresting"!). -24- �E. Risk Characterization (Risk Characterization section) Risk characterizations were presented for Human milk (RC02 - WHO) Occupational setting (RC04 - Paustenbach) Land application of paper mill sludge (RC07 - Envirologic Data). Other papers raised questions about and pointed to the need for improvements in the exposure assessment of any RC: RC01 - need for greater attention to dealing with uncertainty RC05 - need to reassess exposure due to application to agricultural soils RC06 - need for validation of air dispersion modeling. Commenters noted that consumption of fish should yield 40 ppt in fat of people. Generally this is not seen. However, see paper by CA DOH: HT11. F. Control Options (Control Technology section and selected posters) MWCs, landfills, photochem, etc. treated. G. Risk Management (Risk Management section) Abstracts are self-explanatory. Particularly noteworthy is RM02 — "indoor Air Pollution by Dioxins in Day-Nurseriesr; RA and RM". Cf. LT16. -25- �III. Scuttlebutt A. SOme researchers are examining coffee (thru paper filter) and tea (thru paper bag) for the presence of 2,3,7,8-TCDD and 2,3,7,8-TCDF. B. The materials associated with the briefing of the Ad Hoc "Dioxin" Group to the Administrator on the "window" of 2,3,7,8-TCDD toxici'ty was released to EOF as a part of the discovery action related to the EDF-EPA law suit. C. In Sweden, these sources are approximately equal contributors of CDDs/Fs into the environment: MWCs, automobiles, steel plants, and pulp and paper plants D. The CDC 1 ppb risk assessment assumed that a cow would ingest up to 2 kg of soil while grazing. This is an outer limit. A more realistic number would be .3 kg. (There is a question, however, as to whether the grass itself would have CDDs/Fs in/on the blades.) E. I understand that concerns originally raised by the Battelle report on the collection efficiency of the EPA air sampler has been resolved; cf. Haggenmeir. Therefore, the Tier 4 data are probably firm. (We had thought that they might be as much as 10x too low.) F. At the Univ of NV at Las Vegas 90% of the students are from in-state. (All but the basketball team?!) The University will give a 4-year "free ride" to the valedictorian of any NV high school. G. There were more than 500 participants from 18 countries. Next year the conference will be in Sweden. The bidding has already begun for the following year. More people are questioning the need for an annual conclave. H.-A1 Young didn't make it this year. I. The Wizards may be able to help unravel the Battelle report. J. 2,3,7,8-TCDD volatilizes off glass at 40 degrees C. K. Harless is getting a new instrument, which will put him back into the hunt. L. Not everyone agrees with Greenpeace's assessment of Barnes! M. NTP is testing phorbol esters for carcinogenicity. The result could shed light on the question of TCDD's promoter/initiator status. N. NTP is conducting skin promotion studies with PeCDFs. 0. The proposed TEFs for the NATO CCMS are as follows: 2,3,7,8-TCDD 1 2,3,7,8-TCDF .1 2378-PeCDF .5 2,3,4,7,8PeCDF .5 Other 2378-PeCDFs .01 2378-HxCDD .1 2378-HxCDFs .1 2378-HpCDD .01 2378-HpCDF .01 OCDD 001 or .0001 OCDF .001 Ot .0001 All non-2378-TCDDs are ignored since they do not show up in biological tissue and their collective impact is small in the current scheme. The guiding principal of this proposal is simplicity. -26- �IV. Personal Activities 1. Presented plenary lecture on Risk Characterization. Paper is to be published. 2. Participated in a press conference with Eric Bretthauer, Gary Amendola, Alec McBride, Chris Rappe, and Ray Clement. 3. Participated in a conference call on levels in residue from incineration of 2,4,5-T and Silvex. I am on the point for discussing the model, which I strongly suspect as^not being applicable in this case. Consider total 2,3,7,8-TCDD and the impact of local dispersion in the environment. 4. Chaired the session on Dose-Response Assessment. 5. With Judy Bellin, co-authored a paper on TEFs with Jim Olson of SONY. Jim is the lead author and will prepare it for publication. 6. Chaired the session on Risk Characterization. 7. Presented final plenary lecture on Risk Characterization. Summary to be published. 8. Chaired a rump session of the NATO CCMS group addressing TEFs which led to a proposed "common set of TEFs" for consideration by member countries. I have to prepare this for more formal circulation to all participants and eventual publication. 9. I introduced myself to two young women from Greenpeace. We had a pleasant discussion about regulatory actions and— inactions regarding ./dioxin". I asked them to send me their views on the/biggest dioxin problems facing us and their recommendations for action. 10. I met a woman from Ohio who is concerned about land application o^r 2,3,7,8-containing sludge to old stripmined Lands. We have chatted on the phone a few times in t)*e past. She had become aware of my recent notoriety/ I put her in touch with folks from EOF and Greenpeace, as well as discussing some of her concerns with h« /p,- / ^ fv, r\&fitf.l-t- -27- � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Alvin L. Young Collection on Agent Orange Description An account of the resource <p style="margin-top: -1em; line-height: 1.2em;">The Alvin L. Young Collection on Agent Orange comprises 120 linear feet and spans the late 1800s to 2005; however, the bulk of the coverage is from the 1960s to the 1980s and there are many undated items. The collection was donated to Special Collections of the National Agricultural Library in 1985 by Dr. Alvin L. Young (1942- ). Dr. Young developed the collection as he conducted extensive research on the military defoliant Agent Orange. The collection is in good condition and includes letters, memoranda, books, reports, press releases, journal and newspaper clippings, field logs and notebooks, newsletters, maps, booklets and pamphlets, photographs, memorabilia, and audiotapes of an interview with Dr. Young.</p> <p>For more about this collection, <a href="/exhibits/speccoll/exhibits/show/alvin-l--young-collection-on-a">view the Agent Orange Exhibit.</a></p> Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Box The box containing the original item. 202 Folder The folder containing the original item. 5720 Series The series number of the original item. Series VIII 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 Barnes, Donald G. Date A point or period of time associated with an event in the lifecycle of the resource 1987 Title A name given to the resource Memorandum: From Don Barnes, US EPA, to Fellow Members of the Agent Orange Working Group (AOWG) Science Panel Distribution List, regarding Trip Report on the Las Vegas "Dioxin" Meeting, dated November 13, 1987 with attachments ao_seriesVIII