Journal of Law and Policy Volume 13 Issue 2 SCIENCE FOR JUDGES IV: Article 3 Revisited and Human Behavior Research

2005 Connections: The aE rly History of Scientific nda Medical Research on "Agent Orange" David A. Butler

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Recommended Citation David A. Butler, Connections: The Early History of Scientific na d Medical Research on "Agent Orange", 13 J. L. & Pol'y (2005). Available at: https://brooklynworks.brooklaw.edu/jlp/vol13/iss2/3

This Article is brought to you for free and open access by the Law Journals at BrooklynWorks. It has been accepted for inclusion in Journal of Law and Policy by an authorized editor of BrooklynWorks. 20313_blp_13-2 Sheet No. 18 Side A 06/23/2005 10:19:08 1  when referencing the particular particular the referencing when 527 Washington, D.C., Washington, and has directed a number es of veterans’ health. health. veterans’ Vietnam of es David A. Butler, Ph.D. David A. Butler, “AGENT ORANGE” ORANGE” “AGENT 5/23/2005 10:24 PM DOC 051705. ACROED This paper uses the term “Agent Orange” as a catch-all to refer to all of as a catch-all to refer “Agent Orange” the term uses This paper M The author is Senior Program Officer at the National Academy of National Academy The Officer at the author is Senior Program 1  Scientists, accustomed to working with and advancing the state to working with and advancing Scientists, accustomed important for understanding Historical perspective is especially CONNECTIONS: THE EARLY HISTORY OF OF HISTORY THE EARLY CONNECTIONS: SCIENTIFIC AND MEDICAL RESEARCH ON RESEARCH MEDICAL AND SCIENTIFIC UTLER NTRODUCTION M K the herbicides employed in Vietnam and the controversy that resulted from that that resulted from the controversy and Vietnam in employed the herbicides removed are quotation marks The action. name. that given was formulation that chemical Sciences, Institute of Medicine in Sciences, Institute of the National Academies’ studi National Academies’ of the litigation issues, for example, are the subject of many present-day the subject of many litigation issues, for example, are these preceded events that challenges and fascinations. The Unfortunately, they remain challenges are no less interesting. I did not times in earlier those to forget that apt of the art, are in the take for granted. Individuals they possess the information for this reality tend to have a better appreciation legal profession in the evolutionary process that since their work is grounded of “who knew what and defines precedent; indeed, questions too and judges lawyers cases. However, when” are central to some of the facts and mindsets a better understanding can benefit from past. in the decisions made that have informed advanced health questions because the field has environmental exposed attitudes of and the decades, in the past several quickly scientific, and and medical, populations, industry, government, “Agent Orange” changed accordingly. legal professionals have B C Y 20313_blp_13-2 Sheet No. 18 Side A 06/23/2005 10:19:08 A 06/23/2005 18 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 18 Side B 06/23/2005 10:19:08 M K C Y HE HE not :T U.S. 3 On the [ available available AND EUTSCHEN SSESSMENT H D A ANCH ODERN R M MPACT I ll/findaids/agentorange/ ll/findaids/agentorange/ /fulltext/operation_ranch_ /fulltext/operation_ranch_ ERICHTE DER PERATION , 1961-1971 (1982), ESTICIDE NDUSTRIES ,O I SIA The researchers included a The researchers included .P A 4 The Alvin L. Young Collection on TAGE FOR THE ORCE ., ], 5 B F GRIC S The History of 2,4-D and Its Impact on Its Impact 2,4-D and of The History -dioxin (OCDD). This is the -dioxin (OCDD). This is the p A IBR IR L legal community, in part because because part in community, legal ERBICIDE ’ .L OUTHEAST H Zur Kenntnis des Perchlorphenols des Perchlorphenols Kenntnis Zur AT S GRIC ., U.S. A www.nal.usda.gov/specco A 458 (1872). 458 R J nam aerial spray program). aerial spray program). nam L ETTING THE ’ AT :S S 5/23/2005 10:24 PM N Orvin C. Burnside, Orvin C. Burnside, DOC ERBICIDES IN JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL H HEMICAL AND available at ESELLSCHAFT -1900 C , UCKINGHAM S ., No. 1-PA-96, N G 051705. (NAPIAP) 5 (1996) (explaining the history of 2,4-D development); 2,4-D the history of (1996) (explaining 5 (NAPIAP) A. B GRIC 1870 ACROED A and because they tend to appear in journals or venues to appear in journals they tend and because See generally See generally Weith, W. V. Merz & See generally See generally ORCE AND M 2 T F 3 4 2 The modern chemical industry evolved in the late 1800s as evolved in the late industry chemical The modern https://www.airforcehistory.hq.af.mil/Publications HE ’ ILLIAM IR EP HEMISCHEN ROGRAM UTLER NDUSTRIAL Development of the Discipline of Weed Science in the United States, in States, United Science in the of Weed of the Discipline Development D W Agent Orange Agent (providing numerous references used in this paper). paper). this in used references numerous (providing description of a byproduct of potassium pentachlorophenol of potassium description of a byproduct production: octachlorodibenzo- A C P I production processes. These mass researchers invented and refined of existing manufacture advances led not only to the more-efficient of the variety and to a significant expansion but also chemicals, papers relating the myriad Among properties of new compounds. produced by the formidable results, many of them experimental account of 1872 is an industry complex, chemical German on wood preservatives. experiments 528 the to inaccessible largely be issues tend to and health science accounts of salient historical at the larger phenomena rather than on discrete subissues focused hand this goal is to address This paper’s by legal scholars. frequented and events of the primary a lay summary gap by providing that up to the time the “Agent Orange” issue advances that defined herbicide spray operations decided to suspend the U.S. government a context for so doing, this paper provides in Vietnam. In the parties to this long- of of the past actions understanding some running controversy. I. T B Characteristics of Pentachlorophenol Characteristics at Viet (detailing the hand.pdf 20313_blp_13-2 Sheet No. 18 Side B 06/23/2005 10:19:08 B 06/23/2005 18 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 19 Side A 06/23/2005 10:19:08 IOXIN 529 529 ], 46 CIENCES 9 S , D EALTH EALTH H .H NST I (citing Theophil Ciesielski, L 6 It appears in hindsight It appears in hindsight ’ 7 oc/factsheets/dioxin.htm (last oc/factsheets/dioxin.htm Regarding Chloracne Regarding [ AT Multiple Discovery of the First Multiple Discovery of the or, in English, chloracne. or, in English, 278(1899). in the scientific literature. In In literature. scientific in the NVIRONMENTAL NVIRONMENTAL ., N E CI S related nonmetallic related nonmetallic elements—fluorine, primer on dioxins). on primer chlorakne associated with exposure to halogens associated with exposure . 290, 291 (2001) CI EALTH S OCHENSCHRIFT is responsible for the original account of original account for the is responsible NSTITUTE OF I 8 Über Chlorakne Über Chlorakne W .H EED In the Beginning: The In the Beginning: e, or astatine—that readily form negative ions and are ions negative e, or astatine—that readily form http://www.niehs.nih.gov/ NVTL 6/6/2005 12:56 PM , 49 W , 49 ATIONAL .E DOC N are a class of chemical compounds that are a that compounds class of chemical are a 5 EDIZINISCHE NST App. B (presenting a primer on chloracne). on chloracne). primer a B (presenting App. App. A (presenting a I Research conducted in the early twentieth century Research conducted in the early M 051705. 10 L ’ available at available AT ACROED James R. Troyer, R. Troyer, James The halogens are any of five any halogens are The Karl Herxheimer, See infra See infra N M 7 8 9 10 5 6 A separate, and at this point distinct, line of scientific inquiry A separate, and at this point distinct, An important innovation of this time was the implementation was the implementation of this time innovation An important ÜNCHENER ESEARCH AT THE UTLER M K modified Nov. 18, 2002). 18, 2002). Nov. modified , bromine, iodin chlorine, bromine, reactive. highly thus Hormone Herbicides Hormone R (NIEHS), brief, dioxins later contribute to the “Agent also produced knowledge that would late nineteenth that three Troyer notes Orange” story. James Charlescentury botanists (Theophil Ciesielski, Darwin, and to that a stimulus Vöchting) independently established Hermann response in a different part of result in a one part of a plant might the plant. RESEARCH OF HISTORY THE ORANGE” ON “AGENT “dioxin” to reference known earliest in fat, they accumulate because public health concern modern-day and have been animals, experimental toxicity in some exhibit high in humans. health problems with associated These chemicals. to make production methods of electrolytic catalyze reactions, were far which use electric current to methods, a result, led to a earlier techniques and, as more efficient than of chlorine- of the commercial production significant expansion halogenated compounds. based and other by the to refer to the condition this disease or was at least the first known— that it is now name exposure to tars that were from The condition he described resulted process producing chlorine. generated during an electrolytic B had an unintendedthat this expansion consequence: for the first an and case reports of literature, descriptions in the medical time illness acne-like occupational appear. Karl Herxheimer M C Y 20313_blp_13-2 Sheet No. 19 Side A 06/23/2005 10:19:08 A 06/23/2005 19 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 19 Side B 06/23/2005 10:19:08 M K , 1 ., C Y CI .S ECUEIL CAD at II-1. at FLANZEN ONINKLIJKE A P available at 592 (1880); 592 (1880); K L 501 (1888)). 501 (1888)). Id. ], 24 R 24 ], ’ s/agentorange/ Regarding the the Regarding stances in the stances Weeds and Their and Their Weeds [ AT He and other LANTS 12 ,N was the first to was the P Investigations of the EITUNG 11 [ Z IOLOGIE DER B IETNAM 10 (1926); Frits Warmolt Warmolt Frits 10 (1926); V chemicals later came to be to be later came chemicals der Laubblätter ov/speccoll/findaid OVEMENT IN OTANISCHE A. Robert Mazur, Mazur, A. Robert n that some chemicals had chemicals n that some , Sept. 1969, at 1, , Sept. Part A - Summary and Conclusions - Part A M : 1 (1928). 1 ROCEEDINGSTHE OF and other inorganic compounds compounds and other inorganic ], 46 B 13 ECORD EITRAEGE ZUR EITRAEGE ERBICIDES IN R see also see also ETENSCHAPPEN H Growth-substance and Growth and Growth-substance OWER OF OF OWER W [ P On Growth-Accelerating Sub ], 1 B ÉERLANDAIS HE N ECTION ,T S 60s/1969/690901.pdf. 60s/1969/690901.pdf. FFECTS OF http://www.nal.usda.g note 2, note 2, at 5; E 5/23/2005 10:24 PM Über die Lichtstellung ARWIN REEN DOC JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL D KADEMIE VAN supra OTANIQUES A B Avena30 Sativa, P ON THE . 051705. available at available herbicidal properties, and the work stimulated HARLES OMM , USGA G This was the first indicatio This was the ACROED C mixture. in Bordeaux ingredient is an active Copper sulfate Burnside, Frits Warmolt Went, Frits Warmolt Wuchsstoff und Wachstum Wuchsstoff M RAVAUX 14 12 13 14 11 T EDERLANDSE UTLER text/00181.pdf. The Effects of Herbicides in in of Herbicides The Effects (1974), II-1 Position of Leaves in Response to Light Leaves Position of Hermann Vöchting, Vöchting, Hermann (1872); C researchers in Germany and the United States pursued this finding States pursued this finding and the United researchers in Germany salts that copper and established selective that could be used in agricultural of herbicides investigations applications. N 530 chemical by governed was phenomenon that this established that were the effects growth was among and that plant signaling Went Frits Warmolt in this manner. controlled acid substance—3-indoleacetic a growth-controlling isolate This class of plant tissues. (IAA)—from because they function in an analogous called plant “hormones” an effect on the hormones, that is, they produce to animal manner point their from remote of cells activity of origin. Meanwhile, a bordelaise observed in 1896 that bouillie French viticulturist used in vineyards to control fungicide (“Bordeaux mixture”)—a eradicated certain weeds. powdery mildew—also in the same weeds, but not cereals growing would kill broadleaf area. B DES Went, http://turf.lib.msu.edu/19 Control Untersuchungen über die Abwärtskrümmung der Wurzel die Abwärtskrümmung über Untersuchungen Downward Curvature of Roots Curvature Downward Coleoptile of 20313_blp_13-2 Sheet No. 19 Side B 06/23/2005 10:19:08 B 06/23/2005 19 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 20 Side A 06/23/2005 10:19:08 15 Id. that 531 531 LINISCHE at 9-12. at Id. available at available at available Report to the to Report es; however, in ], 6 K EALTH , Keynote Address at Address , Keynote 305, 305-06 (Colin F. HEMICALS diphenyls that were not as C U.S. H Chloracne OOD PCB-1268—is highly (68%) PCB-1268—is highly F (July 30, 1994), (July 30, [ in the distillation of chlorinated of chlorinated in the distillation LIKE - Polychlorinated Biphenyls, Dioxins Biphenyls, Polychlorinated as Environmental Contaminants in Contaminants as Environmental s) consist of two benzene rings and rings benzene of two s) consist Cecil K. Drinker, Cecil K. Drinker, The first comprehensive study The first comprehensive experienced severe chloracne and other other and chloracne severe experienced 17 IOXIN EPORTS OF EPORTS een 1 and 8 chlorin 8 een 1 and tml (noting, but not providing a citation providing (noting, but not tml D R an three years after the initial exposure. years after the an three compare Archives of Dermatology and Syphilology Dermatology of Archives ated diphenyl #1268”), ated diphenyl aw in Teleky’s earlier presumption. presumption. earlier aw in Teleky’s IRST ONTAMINANTS IN (Sept. 15, 1938) (evaluating, among other topics, topics, other among 15, 1938) (evaluating, (Sept. F C was stimulated by health problems in by health problems was stimulated that it was less toxic than that it was less toxic than Die Pernakrankheit called Aroclor 1268 or 1268 called Aroclor 18 The Political History of Dioxin The Political History of HE nference on Dioxin nference on :T XPOSURE TO 6/6/2005 12:57 PM S E DOC s.org/s-r/078/07-03.h 845 (1927); (1927); 845 051705. NVIRONMENTAL 16 E 1900-1940 ACROED Barry Commoner, Barry Commoner, David E. Wells & Jacob de Boer, Boer, de Wells & Jacob E. David Teleky, Ludwig Polychlorinated naphthalenes (PCN naphthalenes Polychlorinated in M , HE 18 16 17 In 1927, Ludwig Teleky published (in German) an German) Teleky published (in In 1927, Ludwig 15 Many of the early reports of chloracne and other diseases now now other diseases of chloracne and the early reports Many of OCHENSCHRIFT ROBLEMS FROM UTLER M K chlorinated. Drinker found chlorinated. Drinker http://www.chemicalindustryarchives.org/search/pdfs/anniston/19380915_545.p df. This compound—now fl a exposing highly chlorinated, Chemical Company Monsanto Chemical the toxicity of “chlorin symptoms that were present more th symptoms describes a Monsanto worker who “began work who “began worker a Monsanto describes employee The 1930”). diphenyl in April for, a 1936 case history in the history in the for, a 1936 case Food Co the Second Citizens http://www.green and Other Polyhalogenated Hydrocarbons Polyhalogenated and Other naphthalenes, the rings are directly joined at two adjacent carbons. Their Their carbons. adjacent at two joined directly are the rings naphthalenes, polychlorinated to those of similar properties are largely physical and chemical toxicity. dioxin-like exhibit some and (PCBs), biphenyls Moffat & Kevin J. Whittle eds., 1999). Whittle eds., J. Kevin Moffat & W investigation of occupational chloracne, which reported that the reported that which occupational chloracne, investigation of the less naphthalene, present in the chlorinated fewer the chlorines exposed subject. the acne in the published in English RESEARCH OF HISTORY THE ORANGE” ON “AGENT II. T P settings in occupational intoxication with acute dioxin associated chlorinated naphthalenes. the use of with were associated documentation is lacking,Although contemporaneous David E. exposure to de Boer noted that occupational Wells and Jacob of gas masks used in the production chlorinated naphthalenes incidents of the with numerous I was associated War during World disease. B comprise 75 congeners with betw with 75 congeners comprise C Y 20313_blp_13-2 Sheet No. 20 Side A 06/23/2005 10:19:08 A 06/23/2005 20 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 20 Side B 06/23/2005 10:19:08 M K . C Y & ED 283 283 , 21 J. , 21 &M YGIENE In their 19 .H 21 OXICOLOGY IOLOGY NDUS B &T , 20 J. I Skin Conditions Resulting Skin Conditions YGIENE Halowax Acne (Queries and (Queries Acne Halowax Further Observations on the on the Observations Further .H XPERIMENTAL E a rat model) into the effect of the effect into a rat model) toxicity of chlorinated naphthalenes. toxicity of chlorinated NDUS ctric and Monsanto Chemical ctric and Monsanto Chemical Lewis Schwartz & Samuel M. Peck, & Samuel Lewis Schwartz Y FOR ’ , 19 J. I 155 (1939); (1939); 155 OC S The Problem of Possible Systemic Effects from Possible of The Problem oncentrations in the Air of Workrooms Air oncentrations in the Certain of the Chlorinated Hydrocarbons with Hydrocarbons Certain of the Chlorinated The Drinker et al. paper includes what is al. paper includes what The Drinker et hysician researcher at Harvard University, University, researcher at Harvard hysician Action of Certain Chlorinated Napthalenes on the 20 OXICOLOGY note 19, at 299. 5/23/2005 10:24 PM Of particular interest is Leonard Greenburg and DOC &T JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL 22 , supra , 12 JAMA 471 (1943); , 12 JAMA 051705. Cecil 244 (1938); K. Drinker, ROCEEDINGS OF THE May R. Mayers & Mabel G. Silverberg, & Mabel G. May R. Mayers at 300-11. at YGIENE ACROED Drinker Id. See Cecil K. Drinker et al., Cecil K. Drinker .H M , 35 P 21 22 A number of English-language papers on chloracne and the of English-language papers A number 19 20 OXICOLOGY UTLER NDUS 118, 119 (1936). (1936). 118, 119 From Exposure to Certain Chlorinated Hydrocarbons Chlorinated to Certain From Exposure Minor Notes) Minor health impacts of chlorinated naphthalenes followed Drinker’s naphthalenes of chlorinated health impacts effort. seminal was asked by Halowax in the spring of 1936 to investigate these 1936 to investigate in the spring of by Halowax was asked jaundice. included three fatal cases of which problems, 532 used chlorinated which Corporation, Halowax of the employees to chlorinated diphenyls) (then called and PCBs naphthalenes and fireproofing waterproofing, coatings for insulating, produce Drinker, a p wires. Cecil conveneddiscuss the to of a colloquium presented as a transcript of the U.S. participants included the chief findings. Colloquium of Industrial Hygiene; state health Public Health Service’s Division and Ohio; Connecticut, Massachusetts, officials from Ele representatives of the General Corporation. and the president of Halowax companies; B concluded that hydrocarbons on the liver. They these chlorinated that high-level exposure was effects were possible, but systemic that Accordingly, they concluded result. this required to trigger these compounds, other . and many . . to benzene “[c]ompared them can little toxic and operations employing substances are very easily be safeguarded.” 1937 paper, Drinker and his colleagues discussed the findings of discussed the findings and his colleagues 1937 paper, Drinker (using investigations their laboratory T (1937). These cases were previously described and by Flinn who were Jarvik, described previously cases (1937). were These to investigate the using laboratory animals Jarvik, N.E. F.B. Flinn & Liver Certain Chlorinated Hydrocarbons Certain Chlorinated Possible Systemic Toxicity of Possible Suggestions for Permissible C Suggestions for Permissible I 20313_blp_13-2 Sheet No. 20 Side B 06/23/2005 10:19:08 B 06/23/2005 20 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 21 Side A 06/23/2005 10:19:08 . ED 24 , 20 M 533 533 HEMIE C AVY OXICOLOGY ORMONE Regarding the from Exposure &T H [ and Folke Skoog , 42 U.S., 42 N LANT 25 illnesses occurring occurring illnesses YGIENE HYSIOLOGISCHE P P all .H . P. 1711 (1943); Thomas Further Experiments on the Experiments Further ED NDUS M the Chemical Nature of the Auxins Auxins of the Nature the Chemical OF OF J. , 21 J. I These investigators recommended recommended These investigators EITSCHRIFT FÜR 23 DVANCEMENT OF The Systemic Effects Resulting Auxins der Graskoleoptilen TATE Chloracne (Cable Rash) (Cable Chloracne A are credited with first observing that IAA are credited with first observing ], 228 Z ], 228 HE 26 :T Über den Einfluss der auxine auf das Wurzelwachstum auf das Wurzelwachstum auxine der den Einfluss Über S 6/6/2005 12:58 PM , 43N.Y. S DOC -1940 S ize Coleoptiles ize 051705. 403 (1944). 403 at 38 at original). in (emphasis 1930 ACROED Id. Fritz Kögl et al., V. Folke Skoog & Thimann, Kenneth Leonard Greenburg et al., Greenburg Leonard HE M 24 25 26 The burgeoning research on plant hormones in the 1930s is hormones The burgeoning research on plant 23 It is important to note that while these early research efforts to note that while these It is important ESEARCH ULLETIN UTLER M K B Influence of Auxins on Root Growth and Growth on Root of Auxins Influence Found in Ma Inhibition of the Development of Lateral Buds by Growth Hormone the Development of Lateral Buds Inhibition of to Certain Chlorinated Hydrocarbons to Certain Chlorinated des und die chemische Natur Connelly & WilliamConnelly & C. Marsh, and Kenneth Thimann 29, 36 (1939). (1934). 104, 121 now recognized as having laid the foundation for the modern now recognized as having laid Kögl and colleagues herbicides industry. Fritz associated various health problems with exposure to specific to with exposure problems health associated various of the full evaluation incomplete reflect an they might chemicals, that it is unlikely exposures. Furthermore, range of the subjects’ some were conducted. While contaminants any tests for to—notably Halowaxes— that workers were exposed compounds may others in impurities chloracnegens themselves, are strong reported health problems. have caused or contributed to the III. T R RESEARCH OF HISTORY THE ORANGE” ON “AGENT and one males (two adults young of three account colleagues’ chlorinated working with to have been “known female) with died after presenting who and diphenyls” naphthalenes and other symptoms. jaundice of by physicians reporting “conscientious naphthalenes and workers exposed to chlorinated among up, so that the cases that have been worked diphenyls, particularly such exposures can be from resulting entities disease clinical in the future.” and thus more readily recognized further clarified B Occupational Acne C Y 20313_blp_13-2 Sheet No. 21 Side A 06/23/2005 10:19:08 A 06/23/2005 21 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 21 Side B 06/23/2005 10:19:08 M K C Y 28 7 .76 GRIC A http://dictionary. However, these However, these See 31 Growth-Substances on Growth-Substances The term “auxin” The term XPERIMENTAL 27 Several Chemical Growth Growth Several Chemical E note 10, at 291. 480, 482-83 (1934). (1934). 482-83 480, OF J. . 209, 225-26 (1935). . 209, 225-26 supra NST acids as potential plant growth plant growth potential as acids I CIENCES MPIRE Roots and Other Responses in Plants, in Responses and Other Roots S OF . , 7 E , meaning “to grow.” “to , meaning The Effect of Some Plant HOMPSON CAD T A L auxein ’ OYCE AT note 2, note 2, at 5-6. note 2, at 5-6; Troyer, 2, at 5-6; Troyer, note B 6/6/2005 12:59 PM N DOC JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL supra supra that certain phenylacetic acids and naphthylacetic acids and naphthylacetic phenylacetic that certain 051705. 30 29 ACROED From the Greek From Percy W. Zimmerman & Frank Wilcoxon, Burnside, William G. Templeman, Burnside, M 29 30 31 27 28 The aryloxyacetic acids that were to become the primary primary the that were to become acids The aryloxyacetic ONTRIBUTIONS FROM ROCEEDINGS OF THEROCEEDINGS OF UTLER C (1939). reference.com/search?q=auxin. reference.com/search?q=auxin. Substances Which Cause Initiation of Cause Initiation Which Substances Dry-Matter Production in Plants Dry-Matter

constituents of Agent Orange were first synthesized in the late Agent Orange were first synthesized constituents of 1930s. 1937, work in 1936 and Templeman’s Gladstone William paper, established that both IAA in a 1939 which he documented and NAA could have toxic effects in plants. 534 the on depending growth, or inhibit promote either could natural identified soon researchers used. Several concentration chemically others that were and synthesized in urine compounds properties. the same to IAA and had similar with synthetic substances natural and to signify both was coined and Frank The discovery by Percy Zimmerman these properties. Wilcoxon important, as this as auxins was particularly acids (NAA) acted aryloxyacetic in generated interest regulators. expensive to isolate and not stable in the were compounds for widespread use. unsuitable them making environment, Industries Chemical Imperial who was affiliated with Templeman, of to synthesize a number expertise (ICI), tapped that company’s 2,4- was these Among compounds. similar chemically for which a patent application acid (2,4-D), dichlorophenoxyacetic an Americanwas filed in April 1941. Robert Pokorny, for working C.B. Dolge, is responsible for the company the specialty chemical 2,4-D and the other Agent that mentions publication first scientific acid (2,4,5-T). 2,4,5-trichlorophenoxyacetic Orange component: one-paragraph descriptions of their synthesis, one He disseminated to a section of the submission after the other, in a March 27, 1941 B P 20313_blp_13-2 Sheet No. 21 Side B 06/23/2005 10:19:08 B 06/23/2005 21 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 22 Side A 06/23/2005 10:19:08 . ., ., , 63 NST GRIC I SE OF SE OF 535 535 U , 41A the ecological ESEARCH EPEATED R R called “New “New called . (1942). 321 http://pubs.acs.org/cgi- Substituted Phenoxy and relates that the chair NST I 34 IDWEST note 10. Troyer details the details 10. Troyer note M ILITARY supra XTENSIVE OR See E lation of Structure to Physiological to Physiological of Structure lation M available at Institute’s study of HOMPSON Order No. 1086) [hereinafter MRI], MRI], 1086) [hereinafter No. Order the important properties of phenoxy of properties the important T pdf/f_ ja01851a601.pdf. pdf/f_ ja01851a601.pdf. OYCE B FFECTS OF E n’s history is summarized and in some cases some and in is summarized n’s history note 2; Troyer note 2; Troyer 1768(1941), Y ’ The Discovery and of 2,4-D Development 33 New Compounds: Some Chlorophenoxyacetic Acids supra OC 5/23/2005 10:24 PM .S ERBICIDES AND THE COLOGICAL DOC E :H HEM 32 S .C Burnside, http://www.nal.usda.gov/speccoll/findaids/agentorange/text/03632. http://www.nal.usda.gov/speccoll/findaids/agentorange/text/03632. ONTRIBUTIONS FROM 051705. M (1967) (project monitored by the Department of the Army under under Army the of Department the by monitored (1967) (project A 1940 243 (1967). Peterso , 12 C ACROED Robert Pokorny, W.Hitchcock, Percy & Alfred E. Zimmerman Gale E. Peterson, HE M see also see also 32 33 34 In addition to this publicly available work, other research was publicly available In addition to this Other researchers were apparently monitoring these monitoring apparently researchers were Other SSESSMENT OF ERBICIDES ISTORY OF THE UTLER M K effects of repeated use of herbicides. herbicides. use of effects of repeated H contract No. DAHC15-68-C-0119; ARPA ARPA No. DAHC15-68-C-0119; contract pdf; of of many discovery simultaneous near researchers. of by a number herbicides available at A J. and the Re Substances Acid Growth Benzoic Activity supplemented by the Midwest Research by the Midwest Research supplemented H of the University of Chicago’s botany department, Ezra Kraus, was Ezra Kraus, department, of the University of Chicago’s botany first to note with being the work. Kraus is credited central to this at sufficiently if applied be useful as herbicides that auxins might by Kraus to two of his former sent letter high doses. An early 1941 and Charles Hamner— graduate students—John Mitchell to their initiating research on the suggestion and led documented IV. T after wartime known that would only become being conducted Peterson secrecy concerns had passed. Gale RESEARCH OF HISTORY THE ORANGE” ON “AGENT Society Chemical the American of Journal Compounds.” several lines because similar working along or developments next few place over the and 2,4,5-T took regarding 2,4-D advances were Percy the publications years. Notable among and Zimmerman an auxin that 2,4-D was 1942 findings Alfred Hitchcock’s more of action) 300 times and that it was mode (establishing its widely used growth the most acid, powerful than indolebutyric at the time. promoter B bin/abstract.cgi/jacsat/1941/63/i06/f- C Y 20313_blp_13-2 Sheet No. 22 Side A 06/23/2005 10:19:08 A 06/23/2005 22 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 22 Side B 06/23/2005 10:19:08 M K C Y 36 Of the more 38 and 2,4,5-T were and 2,4,5-T were 224 (1944) (noting the the (noting (1944) 224 39 AZETTE 2,4-Dichlorophenoxyacetic Acid G Growth-Regulating Substances as Substances Growth-Regulating the most popular of the commercial commercial popular of the the most Field trials, including aerial 40 like cereals and grains)). This meant it This grains)). like cereals and ithout laying waste to desirable growth. growth. ithout laying waste to desirable ile sparing monocotyledons (monocots, (monocots, monocotyledons ile sparing 301, 302 (1947). OTANICAL Meanwhile, in October 1941, Secretary Secretary 1941, in October Meanwhile, AZETTE 35 G , 106 , 106 B note 34, at 245 & n.12. note 34, at 248. 5/23/2005 10:24 PM note 34. DOC JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL OTANICAL In response to these comments and to these comments In response supra supra 37 051705. supra supra , 108 B ; Paul C. Marth & John W. Mitchell, W. & John ; Paul C. Marth at 246. The committee may have instead been the “ABC committee,” at 246. The committee been the “ABC may have instead ACROED Id. MRI, Peterson, Id. Mitchell, W. Ezra J. Kraus & John Peterson, M 40 35 36 37 38 39 UTLER herbicides—it selectively killed dicotyledon plants (dichots, which include include which plants (dichots, selectively killed herbicides—it dicotyledon like weeds) wh most plants broadleaf one property that would make 2,4-D among 2,4-D make would property that one food plants grasses and many including w be applied on fields and lawns could property. this also has 2,4,5-T Herbicides spraying, were conducted in the Florida Everglades, and an conducted in the spraying, were was developed for possible formulation thiocyanate ammonium that war ended without use in the Pacific Theater. However, application. It was not until the a military used in herbicides being to that attempted insurgency so-called “”—an Malaysia—that administration of overthrow the British colonial used aerial as a weapon. British troops herbicides were employed of herbicides for defoliation and crop destruction dissemination 536 year. later that the topic Sciences of Academy National asked the Stimson Henry of War a committee in the of knowledge to assess the state form (NAS) to 1943 1942 or early In a late biological warfare. field of Consultants” committee, Bureau of to the “War presentation growth-regulating that “the toxic properties of Kraus suggested of crop limitation destruction of crops or the substances for the application and should be have military production” might investigated. committee, research was greatly the NAS from recommendations Fort Detrick), named (later Detrick, Maryland Camp accelerated. for weapons been established as a center which had recently poured Army work on herbicides and the U.S. research, began and other investigators’ studies. funding into Kraus’s agents screened, 2,4-D than 1,000 potential promising. found to be the most B a successor working group given a nonsense name to hide the nature of its work. of its nature the to hide name nonsense given a group working a successor as a Differential Herbicide 20313_blp_13-2 Sheet No. 22 Side B 06/23/2005 10:19:08 B 06/23/2005 22 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 23 Side A 06/23/2005 10:19:08 74 537 537 CALE CALE -S ISARMAMENT ARGE & Apr. 1950) & D L exceeded limits, a n process for 2,4,5-T and ONTINUATION OF ONTINUATION 42 C HEMICAL HEMICAL College of Medicine,Univ. of ,C EGINNING OF EGINNING vessel’s contents into the air into the air vessel’s contents as trichlorophenol or TCP) is a B ARFARE HE W :T Nitro, WV (Oct. 1949 S , 1950 41 diate step of the productio diate step of the HEMICAL RODUCTION AND THE RODUCTION P -dioxin (2,3,7,8-TCDD or TCDD). The -dioxin (2,3,7,8-TCDD ,C ESEARCH p S AND 5/23/2005 10:24 PM R DOC DAMS A orts for Dep’t of Envtl. Health, 1940 but were not addressed in a peer-reviewed journal journal peer-reviewed but were not addressed in a ERBICIDE ERBICIDE 051705. ECTOR 43 H S ATE ALERIE L ACROED V (abbreviated 2,4,5-trichlorophenol Cases, on Chloracne Reports R. Suskind, & Raymond F. Ashe William M HE 41 42 43 The commercialization and widespread use of 2,4-D and 2,4,5- and widespread use of 2,4-D The commercialization IVILIAN HENOXY UTLER M K (1990). some other biocides. other some (unpublished rep chemical made in an interme chemical Monsanto Chemical Company Chemical Monsanto

RESEARCH OF HISTORY THE ORANGE” ON “AGENT and 1953. 1951 between V. T P C the end of World began in the years following T-based herbicides research efforts. results of wartime by the in part War II, spurred industry geared were established and the As production processes to the first time of workers were exposed for the up, large numbers This precursors, and unintentional contaminants. herbicides, their health first mass what is now regarded as the led in 1949 to dioxin 2,3,7,8- attributable to the incident specifically tetrachlorodibenzo- vented the safety valve released and with the cleanup (there wasoutside the building. Workers tasked were in those who and and repair of the unit no decontamination) of a number incident reported after the in the days the vicinity including irritation, headache, tract eye and respiratory symptoms, weeks, Within skin irritation. dizziness, nausea, and severe muscle liver impairment, function chloracne, hyperpigmentation, disturbances were system pain, and a variety of central nervous in were documented observed. These health problems for unpublished reports by physicians working contemporaneous Monsanto, B at a Nitro, West Virginia, plant incident began on March 8, 1949 the Corporation. When operated by Monsanto Chemical an autoclave) vessel (called and pressure in a reactor temperature 2,4,5-trichlorophenol that was used to make C Y 20313_blp_13-2 Sheet No. 23 Side A 06/23/2005 10:19:08 A 06/23/2005 23 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 23 Side B 06/23/2005 10:19:08 M K C Y 149 OUNG OUNG ISK OF R L. Y AUTARZT V. (July 1953) V. (July LVIN H The BASF The BASF UMAN at two C.H. 49 H 46 ER osed to Dioxin in a Dioxin in a osed to rkers in Chemical Plant rkers in Chemical ] 24 D EWERBEPATHOLOGIE UND UND EWERBEPATHOLOGIE G ings in the Production of ings in the Production of rkers with Past Exposure to The Mortality Experience of Experience The Mortality ATE AND V-7 (1978). F 286 (1951); A (1951); 286 Industrial Intoxication Due to Company, Nitro, W. Nitro, Company, urred in the BASF/AG on November on November in the BASF/AG urred IOXIN n of Findings With and Without With and Without n of Findings Severe Acute Chloracne, A Mass Mass A Chloracne, Severe Acute D URGERY [ 959 (1991). 959 RCHIV FÜR d as Atkins, Davis, and Suskind in some in some Suskind and Davis, Atkins, d as . 11 (1980). .&S ED ANCET ED . 161, 164 tbl.1 (1984). 164 tbl.1 (1984). . 161, and at a Hamburg-Moorfleet plant plant and at a Hamburg-Moorfleet NVIRONMENTAL M SSOCIATED . 179, 179-80 (1953). . 179, 48 .M ED -dioxin in the Manufacture of 2,4,5- the Manufacture in -dioxin Occupational Poison A Mortality Study of Persons Exp , Health Status of Wo , Health Status ,E p ED ], 18 A ], Berufliche Vergiftungen bei der Herstellung von von Herstellung bei der Vergiftungen Berufliche [ .M 7-Tetrachlorodibenzodioxin , 338 L TS I Schwerste akute Chloracne, eine Massenintoxikation Massenintoxikation eine Chloracne, akute Schwerste Cancer Mortality Among Wo Mortality Among Cancer .M NDUS 5/23/2005 10:24 PM NDUS NDUS , 20 I DOC 538 (1961). JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL .J.I CCUPATIONAL OXICOLOGY M .J.I T Interestingly, Marion Moses et al. indicated that while that while indicated et al. Moses Marion Interestingly, M 051705. RANGE AND 44 45 O HE , 5 A at a BASF (Badische Anilin- & Soda-Fabrik) factory in & Soda-Fabrik) factory Anilin- at a BASF (Badische , 22 J. O , 3 A ACROED P. J. Goldman, Goldman, P. J. et al., A. Manz Marion Moses et al. Marion Moses E.W. Baader & H. J. Bauer, al., et H. Bauer Judith A. Zack & Raymond R. Suskind, R. Suskind, Raymond & Zack A. Judith 47 ., T M 48 49 45 46 47 44 There were at least four other exposure incidents associated associated incidents exposure other at least four There were EWERBEHYGIENE ERBICIDE UTLER Intoxication Due to 2,3,6, Intoxication Chloracne 2,3,7,8-Tetrachlorodibenzo- Acid: Compariso Trichlorophenoxyacetic Contaminated with Dioxin Contaminated Pentachlorophenol Chlorophenol Compounds 2,3,6,7-Tetrachlorodibenzodioxin durch Workers Exposed to Tetrachlorodibenzodioxin in a Trichlorophenol Process Process in a Trichlorophenol to Tetrachlorodibenzodioxin Workers Exposed Accident ET AL G H

538 1980. until an result of the incident, chloracne as a developed 117 workers prior to this signs of chloracne (111) showed number equal almost exposure. the next five years: at a during Germany facilities in with TCP in in 1949; plant in Nordrhein-Westfalen chemical Rhine in 1952 and facilities located in the middle Boehringer Sohn 1953; 1953; Ludwigshafen in and explosion, result of an autoclave also was the incident the performing plant workers and persons involved not only B contract to Boehringer in 1954. working under (1973); A. M. Thiess et al., (1973); A. M. That Occ Accident Trichlorophenol-Process 17, 1953 Cincinnati); Raymond R. Suskind & William F. Ashe, A Clinical and F. & William Ashe, R. Suskind Raymond Cincinnati); Chemical Survey, Monsanto Environmental (the of Cincinnati) Univ. Kettering Laboratory, the of report (unpublished cite also are report of this authors sources). Chlorphend-Verbindungen 20313_blp_13-2 Sheet No. 23 Side B 06/23/2005 10:19:08 B 06/23/2005 23 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 24 Side A 06/23/2005 10:19:08 . . , 2 OF . ROT P NDUS EP 539 539 I CIENCE S DVISORY DVISORY , R EPORT ON 85, 94-95 94-95 85, S A ’ ,R NVTL NVTL XPERIMENTAL E E GENCY RCHIVES .A and the first Toxicity of 2,4- Toxicity RESIDENT 55 OXICOLOGY P RESIDENT Y FOR ROT P . 68 (November 26-28, 26-28, . 68 (November ’ OF THE OF . &T .P OC ONF S EPORT OF THE C The authors, who tested DMIN , 7 A.M.A. A 7 A.M.A. , 56 NVTL A YGIENE lorophenoxyacetic Acid: A Report the first 2,4,5-T toxicology paper the first 2,4,5-T toxicology . 226, 232 (1946). 232 (1946). . 226, 50 .H FFICE OFTHE CI ONTROL Toxicity of 2,4-Dichlorophenoxyacetic Toxicity of 2,4-Dichlorophenoxyacetic S O C ERBICIDES OF THE NDUS H TO THE EED NIMAL who examined acute and subacute acute who examined . 61 (1953). E 54 In 1946, John Mitchell and colleagues In 1946, John Mitchell Effects of 2,4-Dichlorophenoxyacetic Acid on Acid 2,4-Dichlorophenoxyacetic of Effects .W ED XECUTIVE , 29 J. I 51 2,4,5-T ROCEEDINGS OFTHE M Other early studies include that of Nancy Other early studies 1963) [hereinafter R 1963) [hereinafter ANEL ON 5 J. A , E ENT Tolerance of Farm Animals to Food Containing 2,4- Containing to Food Animals of Farm Tolerance P 52 ON EOD . 39 (1971). note 48. Panel Discussion on New Chemicals for Weed Control Weed on New Chemicals for Panel Discussion N. C , 63 P L 5/23/2005 10:24 PM AC DOC OMM supra C . (1946). 205 204, CCUPATIONAL ED M. M 051705. OMMITTEE EPORT OF THE who found that repeated injections of 2,4-D did not 2,4-D repeated injections of who found that C &O &M 53 OLIN , (1971) (incorrectly asserting that asserting that , (1971) (incorrectly ACROED Victor A. Drill & Tomiharu Hiratzka, Drill & Tomiharu A. Victor L. W. Kephart, L. W. Kephart, J.W. Mitchell et al., L. R. Bucher, Nancy Carlisle, Hill & Harold V. Edwin C Goldman, Goldman, DVISORY M A 56 51 52 53 54 55 50 Preliminary toxicologic research on the herbicides was also the herbicides on research toxicologic Preliminary 2,4,5-T were conducted in theThe first toxicity studies of DVISORY YGIENE GENCY IOLOGY ROCEEDINGS OF THEROCEEDINGS OF UTLER M K H A (1947). Acid for Experimental Animals Acid for Experimental Dichlorophenoxyacetic Acid and 2,4,5-Trich P Animals Experimental Toxicity in Dogs and Chronic Acute on Their 1945). 2,4,5-T: A R A publication of results was made in 1953. publication of results was made B influence the growth rate of sarcomas in mice, and that of Edwin and that rate of sarcomas in mice, influence the growth Carlisle, Hill and Harold RESEARCH OF HISTORY THE ORANGE” ON “AGENT child The employees. of the of one child also a but cleanup, into contact of coming as a result developed chloracne apparently scarf. towel and with a contaminated on Kraus experimented reports that LW Kephart being conducted. of 2,4-D 0.5 grams no ill effect from ingesting and found himself weeks. per day for three and stating that cows of 2,4-D, animal studies published the first did not pastures treated with the compound sheep grazing on toxic effects. manifest toxic determined and in a variety of mammals effects of ingestion doses. Company (Dow) 1950s by Dow Chemical B Bucher, THE was not published until Dichlorophenoxyacetic Acid C Y 20313_blp_13-2 Sheet No. 24 Side A 06/23/2005 10:19:08 A 06/23/2005 24 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 24 Side B 06/23/2005 10:19:08 M K , C Y RCHIVES ERVICES S 11 (1998) UBSTANCES S , 44 A OXIC UMAN /toxprofiles/ tp104. /toxprofiles/ T DIOXINS - P - &H IBENZO GENCY FOR D EALTH ed to kill a hamster than a guinea guinea than a hamster kill a ed to ere are unusually large variations variations are unusually large ere to translate animal tests of dioxin to translate animal H T ’ ADE EP M http://www.atsdr.cdc.gov S HLORINATED I C http://www.nal.usda.gov/speccoll/findaids/agent by body weight. A , U.S. D Prolegomena to Seveso Ecclesiastes I 18 to Seveso Prolegomena available at 5/23/2005 10:24 PM ONNECTION ROFILE FOR DOC JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL P C EGISTRY 211, 216 (1980). 211, 216 available at available R The case stimulated Schulz to begin studying The case stimulated HE 051705. 58 ], 57 ACROED Bo Holmstedt, Bo Holmstedt, Later research would show that th would Later research ISEASE M OXICOLOGY 58 57 Thus, by the mid-1950s, there had been a series of incidents in there had been a series Thus, by the mid-1950s, T OMMITTEE OXICOLOGICAL UTLER pdf. This characteristic makes it difficult [hereinafter ATSDR], [hereinafter T between and among species in susceptibility to TCDD’s effects. For example, example, effects. For to TCDD’s species in susceptibility and among between need TCDD is more times several thousand are doses equalized pig, when &D chloracne problems at the facility. In cooperation with a chemist at the facility. In cooperation with a chemist chloracne problems of 2,4,5-T that Schulz obtained samples Georg Sorge, there named of purity. Tests performed at various levels had been manufactured purity samples (formulated on rabbit ears showed that the highest did not elicit a skin reaction, while the for use in experimentation) which workers exposed to 2,4,5-trichlorophenolwhich workers exposed had experienced a in industries that had previously been seen set of health problems polychlorinated naphthalenes (PCDDs) and using polychlorinated workers had The physicians treating these biphenyls (PCBs). health of the the source to explain theories advanced various The set of events yet to identify a mechanism. but had problems began in 1956. Karl H. Schulz, a that would clarify this connection at the Eppendorfer of Dermatology physician in the Department the was referred a patient from Krankenhaus in Hamburg, factory who was suffering from Boehringer Hamburg-Moorfleet chloracne. 540 level dose highest that their found on dogs, ingestion of the effects survived that but that animals in death, resulted mg/kg/day) (20 in the liver or lesions develop significant levels did not lower dose in these 2,4,5-T used the to which The extent other organs. dioxins is not with contaminated have been may experiments known. VI. 1957: T B OF orange/text/01152.pdf. toxicity to humans. humans. toxicity to C 20313_blp_13-2 Sheet No. 24 Side B 06/23/2005 10:19:08 B 06/23/2005 24 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 25 Side A 06/23/2005 10:19:08 63 541 541 This ERICHTE 59 B ERMATOLOGIE ERMATOLOGIA lorakne) Durch lorakne) D r Ätiologie der tic Cyclic Ethers 31 (1986). 337 (1957); K. H. K. (1957); 337 HEMISCHE ACTS ) 690 (1957). (1957). ) 690 ], 115 D F HE ] 90 C ations into the Etiology of into the Etiology ations :T XPERIMENTELLE Occupational Acne (So-Called Occupational Acne (So-Called tersuchungen zu E [ Chlorinated Aroma RANGE ESELLSCHAFT chloracne cases and contacted chloracne cases [ O G Chlorierte Aromatische Cyclische Äther Cyclische Aromatische Chlorierte Berufliche Akne (sog. Ch ATURWISSENSCHAFTEN GENT Michael Gough reports that although Michael Gough reports that although Über die Pyrolyse des Pentachlorphenols die Pyrolyse Über Aromatic Cyclic Ether ,A 64 LINISCHE UND note 45, at 161-62. K ], 44 N 44 ], IOXIN ,D supra lorinated lorinated 6/6/2005 1:01 PM OUGH DOC He was referred to Schulz, who recognized the to Schulz, who recognized He was referred RCHIV FÜR EUTSCHEN CHEMISCHEN G 60 D 62 051705. Clinical and Experimental Investig and Experimental Clinical [ ] 206 A at 217. There was no economic incentive to eliminate trace to eliminate incentive no economic was There at 217. 33; Moses, at Klinische und Experimentelle Un The chemist isolated TCDD from technical grade TCP technical grade TCDD from isolated The chemist ICHAEL 61 ACROED W. Sandermann et al., Sandermann W. Id. M Id. Id. H. Schulz, & K. J. Kimmig M 64 59 60 61 62 63 In 1957, Schulz and a colleague published three papers (in In 1957, Schulz and a colleague ERICHTE DER UTLER Regarding the Pyrolysis of Pentacholorphenols the Pyrolysis Regarding M K Schultz, Chloracne Chlorakne Chlorakne [ Chlorierte Aromatische Zyklische Äther Zyklische Chlorierte Aromatische Chloracne) Due to Ch Chloracne) as the Cause of Chloracne of as the Cause (1957). 589 (B H. Schulz, Kimmig & K. (1957); J. 540 Chlorakne der Sogenannten als Ursachen and independently synthesized the dioxin; both yielded positive positive both yielded the dioxin; synthesized and independently connection was ear tests conducted by Schulz. The results in rabbit solution of TCDD to his 0.01% a when Schulz applied confirmed within the next lesion and developed a chloracneform forearm several days. agent in the chloracne as the causative implicating TCDD German) observed in persons exposed to chlorinated hydrocarbons. description of TCDD their et al. also released Sandermann synthesis, again in German. RESEARCH OF HISTORY THE ORANGE” ON “AGENT in for use (formulated samples grade” “technical so-called did. production) such as 2,4,5-T processes chemical was TCP in lower-grade impurity that some suggested led of researchers a team time, the same At about chloracnegenic. of Hamburg the University of Sandermann by Wilhelm for use while investigating new chlorophenols synthesized TCDD developed team An assistant on the as wood preservatives. blew accidentally of the dried compound some chloracne when face. into his with his other possible connection Sorge. B contaminants that did not affect the performance of the final product. final of the the performance affect not that did contaminants C Y 20313_blp_13-2 Sheet No. 25 Side A 06/23/2005 10:19:08 A 06/23/2005 25 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 25 Side B 06/23/2005 10:19:08 M K , C Y OUTH S UDDLE (1978), ATE AND EPORT TO F ,R IOXIN D ATTER ROGRAM IN . (1st Sess. 1969), . (1st Sess. ERBICIDES P M H EVELOPMENTTHE OF Alvin Young and Alvin Young and ONG D C 66 NVIRONMENTAL NVIRONMENTAL 472 (1946); F.(1946); 472 P. H SSOCIATED ST ,E A ERBICIDE SES OF EFOLIANT AND H , U D ,91 TS I CIENCE Use of 2,4-Dichlorophenoxyacetic Acid Use IETNAM ESEARCH OXICOLOGY , 103 S T ILITARY V ,R HE EVIEW OF THE STRONAUTICS :M RANGE AND http://www.nal.usda.gov/speccoll/findaids/agent http://www.nal.usda.gov/speccoll/findaids/agent S A O ., T , A R CIENCE ORE S F -1960 S ARREN 5/23/2005 10:24 PM note 60, at 33. ERBICIDE DOC available at OUNG ET AL OUNG H CIENCE AND AND CIENCE JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL SSESSMENT OF THE 1950 F. W S A supra L. Y http://www.nal.usda.gov/speccoll/findaids/agentorange/text/01165. http://www.nal.usda.gov/speccoll/findaids/agentorange/text/01165. http://www.nal.usda.gov/speccoll/findaids/agentorange/text/05167. http://www.nal.usda.gov/speccoll/findaids/agentorange/text/05167. 051705. ATE Research also included some refinement Research also included some of aerial L ISK OF OME TO THE OME TO THE ILLIAM 65 (1968), 67 LVIN R C ACROED J. van Overbeek & Ismael Vélez, & Ismael Overbeek J. van Gough, W A HE UBCOMMITTEE ON 68 M S 68 65 66 67 All herbicide research funding at Fort Detrick ended in fiscal All herbicide research funding U.S. military interest in herbicides did not end with the WWII not end with the WWII did herbicides in interest U.S. military ECHNOLOGY GAIN IETNAM UMAN OMMITTEE ON UTLER AT as a Selective Herbicide in the Tropics in the Selective Herbicide a as available at pdf. C V H dissemination hardware and the testing of formulations in Puerto in Puerto hardware and the testing of formulations dissemination Rico. stock was turned over to the year 1958 and the facility’s remaining months However, only of Agriculture (USDA). U.S. Department an help clear vegetation from to facility was asked later, the 542 by was applied his research papers, out any turn did not Sorge in the production TCDD contamination to reduce Boehringer process. VII. T A the pace of work diminishedresearch effort, although after the end and candidate development herbicide Wartime of the conflict. lower in 1950, and a much terminated were screening programs 1957 under the carried on between 1950 and level effort was anticrop warfare research. general rubric of Detrick by Fort that one of the findings made colleagues indicate of 2,4- of the butyl esters 1951) was that mixtures investigators (in of choice for vegetation D and 2,4,5-T were the chemicals control. B THE pdf. pdf. available at orange/text/03121.pdf. 20313_blp_13-2 Sheet No. 25 Side B 06/23/2005 10:19:08 B 06/23/2005 25 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 26 Side A 06/23/2005 10:19:08 . 71 EV (U) at 19 543 543 &D Id. ANUAL FOR 75 available at available M over a four over a UPPLEMENT 70 ,S ESEARCH R Some of the of stock Some 69 IETNAM ORPS V NFORMATION .C (Dec. 1969), , I OUTH SIA S HEM A RMY C crops, where 2,4-D and 2,4,5-T were were where 2,4-D and 2,4,5-T crops, A T ’ RMY ESTS IN EP T OUTHEAST ., D S PRAY S , U.S. A /speccoll/findaids/agentorange/text/00073.pdf. http://www.nal.usda.gov/speccoll/findaids/agentorange/ http://www.nal.usda.gov/speccoll/findaids/agentorange/ 5/23/2005 10:24 PM ROWN DOC RISH ET AL 72 ONTROL IN W. B C Of the eighteen formulations tested, the Agent Purple tested, Of the eighteen formulations R. I EGETATIONAL 051705. 73 This determination was based not only on efficacy, but was based This determination available at available ,V at 9. at 10. at 4, 9. 74 at 18-20. The other was , which was composed of the acid was composed Agent Blue, which was other at 18-20. The 9. at ENT AMES ACROED Id. Id. Id. Id. Id. K J M 71 72 73 74 75 In the first aerial herbicide spray mission, which was conducted mission, In the first aerial herbicide spray 69 70 The operation was deemed a success, and in May 1961, the a success, deemed The operation was EGETATION OMMAND UTLER M K http://www.nal.usda.gov C 26 (1962), 26 (1962), on January 10, 1962, Agent Purple was applied to an area adjacent on January 10, 1962, Agent Purple V Department of Defense’sDepartment Research Projects (DOD’s) Advanced andAgency tasked Brown researchers to travel other Fort Detrick of various herbicides, and evaluate the effect to Vietnam on indigenous trees and and application methods formulations, foodstuffs. were deemed other formulation of 2,4-D and 2,4,5-T and one mix the best. quantities, and “known or proven also on cost, availability of large and animals.” to their toxicity to humans safety in regard RESEARCH OF HISTORY THE ORANGE” ON “AGENT New York. in Fort Drum range at test artillery 1959. An out in June was carried and the operation was retrieved (this and 2,4,5-T esters of 2,4-D butyl of 1:1 mixture undiluted Purple”) then “Agent and “Purple,” was later called formulation a helicopter attached to from booms was sprayed 6 lbs/acre. of approximately at a concentration area square mile a researcher in the Crops Brown, James W. Operation director the leaves of the hardwood Detrick, reported that Division at Fort color turned area in the testing sugar maples) trees (primarily and dead after brown and appeared after the application shortly about a month. B text/00337.pdf. tbl.1. Agent Blue was used against rice against used was Blue Agent tbl.1. and sodium salt of cacodylic acid (also called dimethylarsinic acid). dimethylarsinic called salt of cacodylic acid (also and sodium ineffective. C Y 20313_blp_13-2 Sheet No. 26 Side A 06/23/2005 10:19:08 A 06/23/2005 26 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 26 Side B 06/23/2005 10:19:08 M K , C Y See See at 19 SED IN EDICINE U Id. MPACTS Among M I 78 Production Act Production during a test a test during 77 76 79 (1986) (addressing EALTH ERBICIDES In re Agent Orange H H report series, including including report series, NSTITUTE OF se Production Act of 1950 Jeanne Mager Stellman et Stellman Mager Jeanne the n-butyl and isobutyl esters RANGE and the Defense FFECTS OF O . 495, 512-14 . 495, E See also nt Orange and Other Herbicides in in Herbicides and Other nt Orange EV note 2; I note ONCERNS OVER GENT only sparingly during the war. the during only sparingly A EALTH .L.R :C XPOSURE supra S E :H , ROOK -1960 RANGE 52 B O note 55, at 17. 55, at note ATE , and 2004 Updates. 2004 Updates. , and ETERANS AND L 681 (2003). lications of invoking the Defen the lications of invoking 5/23/2005 10:24 PM ERBICIDES UCKINGHAM H supra DOC GENT The Government Contract Defense: Is Sovereign Immunity A Defense: Is Contract The Government JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL TO , A - , B ATURE ID EOD 051705. L M (1994) subsequent numerous are There IOM]. [hereinafter ARTIME ARTIME at 87. Agent Pink was a 60:40 mix of mix was a 60:40 Pink at 87. Agent AC HE , 422 N ACROED The need for Agent Orange and its chemical precursors exceeded the exceeded precursors and its chemical Orange Agent for need The M Id. See, e.g. W M 79 76 77 78 The mid-1960s was also a time of burgeoning interest in of burgeoning interest was also a time The mid-1960s Domestic manufacturers struggled to meet the great demand the great demand manufacturers struggled to meet Domestic The Extent and Patterns of Usage of Age of Usage and Patterns Extent The ETERANS AND IETNAM UTLER 1996, 1998, 2000, 2002 Vietnam al., total domestic production capacity in late 1966 total domestic of 1950 was invoked in March 1967 to accelerate delivery of supplies. delivery of supplies. accelerate 1967 to in March was invoked 1950 of Glasser, Jonathan Necessary Prerequisite?, publications in the V the publications in V studies of the mutagenic, carcinogenic, and reproductive effects of carcinogenic, and reproductive effects of studies of the mutagenic, an investigation launched The National Cancer Institute chemicals. 544 Pink Agent with been sprayed had target that to a accounts of the available Several earlier. a few weeks mission of detail the conduct Ranch Hand”) as “Operation (known program agents used. range of herbicide and the the missions VIII. T conflict. the Vietnam from that stemmed for herbicides Michigan, an initiative by Dow in a Midland, their efforts was a new production through its 2,4,5-T capacity plant to expand workforce soon cases started appearing in the process. Chloracne the began, and Dow respondedafter production by shutting down TCDD to the problem. other manufacturers alerting facility and in the plant reopened When agent. as the causative was implicated TCDD production process that limited 1966, it used a revamped (ppm). million 1 part per to less than contamination B some of the legal imp some for manufacturers of Agent Orange—a major issue in the issue major Orange—a of Agent for manufacturers litigation). FROM of 2,4,5-T. The formulation was used was formulation The of 2,4,5-T. V tbl.1. 20313_blp_13-2 Sheet No. 26 Side B 06/23/2005 10:19:08 B 06/23/2005 26 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 27 Side A 06/23/2005 10:19:08 ULY J 545 545 SIA A OUTHEAST S became concerned concerned became els that fought for the 82 80 (Vietnamese communists)— (Vietnamese http://www.nal.usda.gov/speccoll/ PERATIONS IN O http://www.encyclopedia.com/html/v/ http://www.encyclopedia.com/html/v/ See Southern Vietnam, which was Vietnam, also known Southern ERBICIDE available at Viet Nam Cong San , H 81 ited States to refer to the reb States to refer ited 5/23/2005 10:24 PM OLLINS DOC V. C (last visited Apr. 10, 2005). 051705. 1967 54 (1967) 54 (1967) 1967 at 47. at HARLES ACROED “Viet Cong”—short for C Id. UNE M 81 82 Opposition to the wartime use of herbicides within the useof herbicides within to the wartime Opposition 80 Even some [Viet Cong] leaders have misconceptions of the have misconceptions [Viet Cong] leaders Even some effects of the instruct officers VC medical herbicides. as it food not to eat the contaminated of units members and liver their health and cause stomach would “damage directs . . . VC document . Another official . disorders”. . areas or in sprayed livestock to graze the units to not allow sprayed. VC officials also to be given food that has been to men the instructed or issued gas masks wear homemade or in some physical harm as “bodily contact would cause death.” cases even UTLER M K vietc1ong.asp National Front for the Liberation of for the Liberation National Front Front. as the National Liberation 1961-J academic community in the United States led to a series of position a series of position led to in the United States community academic and organizations. These individuals and petitions from statements the president of the from 13, 1967 letter in a September culminated to of Science (AAAS) Association for the Advancement American The report also stated that “[i]t must be remembered that the the that must be remembered that “[i]t The report also stated aircrews or spray is non-toxic and has had no effects on chemical any ill- regular troops, nor have there been [south Vietnamese] United in the chemicals use of these during effects reported the among contrary to the attributed claims and States,” beliefs or propaganda. to mistaken Vietnamese RESEARCH OF HISTORY THE ORANGE” ON “AGENT of a potential and teratogenic mutagenic, tumorogenic, of the gave the in 1965 and and herbicides of insecticides number spray Aerial Laboratories. Research Bionetics to contract significantly in 1966 and 1967, increased in Vietnam operations (VC) the Viet Cong is evidence that and there to herbicides. An with exposure effects associated about the health declassified in evaluation written in 1967 and Air Force tactical 1974 stated: B findaids/agentorange/text/03116.pdf. findaids/agentorange/text/03116.pdf. is term used in the Un is term C Y 20313_blp_13-2 Sheet No. 27 Side A 06/23/2005 10:19:08 A 06/23/2005 27 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 27 Side B 06/23/2005 10:19:08 M K , , ., . C Y CI S The NNUAL , 1960- 83 Results of Results of The report The report 1970 A 88 IETNAM 84 ALFORMATIONS AL ESELSON ET V M S. M DVANCEMENT OF A http://www.nal.usda.gov/ http://www.nal.usda.gov/ note 56, at 51. EPUBLIC OF ATTHEW R published 1970. in December ONGENITAL supra , N FOR THE ., C ’ These reports raised public RESENTATIONS AT THE THE AT RESENTATIONS EF 87 available at available SS P D .A the second were presented a few months the second were presented a few months T note 2. note ’ M OMMITTEE A EP C N supra ’ , TILLBIRTHS IN THE ., D http://www.nal.usda.gov/speccoll/findaids/agent http://www.nal.usda.gov/speccoll/findaids/agent S e/text/00900.pdf. ELEVANT TO OMM R C DVISORY A note 34, at 139. 5/23/2005 10:24 PM DOC AAAS 23-25 (1971), OLES AND AND OLES UCKINGHAM JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL Dioxin is not mentioned in the report’s more than than more report’s in the Dioxin is not mentioned supra ATERIAL available at M 86 , B M UTTING ET AL SSESSMENT 051705. A MRI, The authors recommended that The authors recommended additional research be at 164. at T. C EPORT OF THE 85 ACROED See, e.g. See Id. Id. R were surveys of the of one results The M Two events in the summer of 1969 changed the outlooks of of 1969 changed summer Two events in the 83 84 85 86 87 88 EETING OF THE YDATIDIFORM ERBICIDE OBERT ACKGROUND UTLER H after the spray missions had been discontinued. M been discontinued. had missions after the spray 1969 (1970), from Findings orange/text/00579.pdf. B H R M 370 pages of text. 370 pages of text. herbicide spraying. wartime safety of with regard to the many 1969, newspapers in Vietnam Between June 26 and July 5, rates of birth defects in areas in published accounts of increased which spraying had taken place. hospital records. two surveys of concern and prompted part of the Bionetics study, also 2,4,5-T testing, conducted as The study, which was the summer. started circulating in public that exposure, found to low-level related first to address an outcome cause birth defects in some could that ingested and injected 2,4,5-T 546 an that suggesting McNamara Robert Defense of Secretary and long-term short- to evaluate the be initiated study independent in Vietnam. use of herbicides of the military’s consequences Institute to Research the Midwest already commissioned DOD had December. was released that a study, which do such the of studies literature on ecologic the then-available summarized use of herbicides” and on toxicologic “extensive or repeated effects. activity the possible teratogenic and carcinogenic undertaken into but did not offer any in Agent Blue, ingredient of the active used in agent 2,4,5-T or the other herbicides suggestions regarding formulations. B speccoll/findaids/agentorang 20313_blp_13-2 Sheet No. 27 Side B 06/23/2005 10:19:08 B 06/23/2005 27 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 28 Side A 06/23/2005 10:19:08 94 547 547 T, 168 on May Science See http://www.hhs. (BBC and Time Lifeand Time (BBC ation of 2,4,5- note 56,3. at There were limited stocks There were limited supra The Secretary of Health, of Health, The Secretary , Connections 93 91 story of major scientific and technical and technical scientific story of major n Services in 1980 upon the passage of n upon the passage Services in 1980 tion Acttion § 3441 1979, 20 U.S.C. of appeared in the journal the appeared in Teratogenic Evalu Teratogenic OMMITTEE C and the Secretaries of Agriculture and Agriculture and Secretaries of and the 92 Concurrently, restrictions were placed on were placed on restrictions Concurrently, note 2, at note 2, 166. 90 These events compelled the White House to to House White the compelled events These DVISORY note 55, at 8. 55, at note 89 A . supra 5/23/2005 10:24 PM , supra DOC , EOD 051705. L at 866. at AC 864 (1970). It included a note (apparently added on 9 April of that April on 9 added a note (apparently It included 864 (1970). UCKINGHAM EPORT OF THE Id. ACROED M Welfare was renamed of Health, Education, and Department The U.S. B from This inquiry takes its inspiration A paper reporting salient results salient A paper reporting R M 92 93 94 The early history of “Agent Orange” may therefore be viewed may The early history of “Agent Orange” 89 90 91 ONCLUSION CIENCE UTLER M K gov/about/hhshist.html (2005), which created a separate Department of Education. of Education. Department created a separate which (2005), 15, 1970. K. Diane Courtney et al., et Courtney Diane 1970. K. 15, S on the hi 1978), a series of documentaries as a series of connections between what began in the late 1800s asas a series of connections between inquiry. and medical distinct lines of scientific, technological, Education, and Education, Welfare, uses of the the suspension of many announced jointly the Interior suspended the DOD temporarily 15, 1970; the herbicide on April day. same use of 2,4,5-T the military RESEARCH OF HISTORY THE ORANGE” ON “AGENT animals. laboratory Orange in Vietnam the use of Agent of curtailment order a partial 29, 1969. on October food crops. of 2,4,5-T on the use ran out. The formulations and supplies quickly of the other agent 9, 1970, was flown on May defoliation mission last fixed-wing crop destruction out were carried although limited missions 1971, aerial spray of the year. On January 7, throughout the rest and lower the longer term to an end. Research on came missions intensified soon of Agent Orange herbicides exposure level effects biological effects and dioxin’s into thereafter, and investigations in earnest. This work and its influence on began health impacts in accompanying papers in policy and other issues are addressed this volume. C B year) that stated that the 2,4,5-T used in testing was contaminated with ~30ppm with ~30ppm was contaminated in testing used 2,4,5-T year) that stated that the TCDD. the U.S. Department of Health and Huma Department the U.S. Organiza of Education the Department C Y 20313_blp_13-2 Sheet No. 28 Side A 06/23/2005 10:19:08 A 06/23/2005 28 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 28 Side B 06/23/2005 10:19:08 M K C Y and broadcaster James Burke. James broadcaster and 5/23/2005 10:24 PM DOC JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL 051705. ACROED M UTLER

548 than thirty- more now have we to be learned, remains much While when making research to consult intense relatively of five years on and dioxin exposure of herbicide about the effects decisions on the yield perspective addressed here The antecedents humans. and officials, government executives, made by industry decisions have been on when they may light planners by shedding military story. of the “Agent Orange” elements aware of particular B discoveries by the author the author by discoveries 20313_blp_13-2 Sheet No. 28 Side B 06/23/2005 10:19:08 B 06/23/2005 28 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 29 Side A 06/23/2005 10:19:08 549 549 -” in the p , the nomenclature for , the nomenclature 2,3,7,8-TCDD is often -dioxins (CDDs) are a (CDDs) -dioxins 95 p para shown to cause a large number of number cause a large shown to -dioxin (2,3,7,8-TCDD)—isthe p benzo) joined via two oxygen bridges oxygen bridges benzo) joined via two di note 57, at 11 (stating that 2,3,7,8-TCDD is the “most (stating that 2,3,7,8-TCDD is the “most note 57, at 11 5/23/2005 10:24 PM DOC supra 051705. ACROED ATSDR, ATSDR, M 95 A chemist would describe this structure as comprising two describe this structure as comprising would A chemist Appendix: A Dioxin Primer Appendix: to organic compounds given name is the general “Dioxin” oxin) at adjacent carbons on the benzene rings; the “- on the benzene carbons at adjacent oxin) UTLER di M K adverse health effects in animals”). adverse extensively studied CDD and it has been has it CDD and studied extensively chemical name is an abbreviation for name chemical respect to one another. The seven the position of the oxygens with at the 2, that have chlorine atoms polychlorinated dioxins (PCDDs) congeners. Among toxic than other are more 3, 7, and 8 positions positions at these atoms chlorine these, the congener with four only—2,3,7,8-tetrachlorodibenzo- ( studied. most potent and by far the most (and confusingly) shorted to “dioxin” in the popular literature. (and confusingly) shorted to “dioxin” benzene rings (hence, benzene rings RESEARCH OF HISTORY THE ORANGE” ON “AGENT to eight with one and hydrogen carbon, oxygen, containing dibenzo- Chlorinated chlorine atoms. congeners) that different compounds (called of seventy-five family by the stylized illustrated structure chemical share the parent below: diagram B C Y 20313_blp_13-2 Sheet No. 29 Side A 06/23/2005 10:19:08 A 06/23/2005 29 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 29 Side B 06/23/2005 10:19:08 M K C Y A single ERSPECTIVES P 96 EALTH .H NVTL 97 of PCDDs with this configuration with this configuration of PCDDs , 106 E , 106 Toxic Equivalency Factors (TEFs) for PCBs,Toxic Equivalency Factors (TEFs) 5/23/2005 10:24 PM DOC JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL 051705. ACROED This is different than the number This is different than the number Berg et al., den Martin Van M When evaluating the dioxin-related toxicity of a chemicalWhen evaluating the dioxin-related 96 97 CDFs differ from CDDs by having one direct carbon-carbon CDFs differ from Researchers often include two structurally-related compounds compounds structurally-related two often include Researchers UTLER PCDDs, PCDFs for Humans and Wildlife for PCDDs, PCDFs (1998). 775 dibenzofuran parent structure biphenyl parent structure structure parent biphenyl structure parent dibenzofuran oxygen bridges. There are ten bond substitute for one of the at the (PCDFs) with chlorine atoms polychlorinated dibenzofurans the 135 congeners. 2, 3, 7, and 8 positions out of 550 chlorinated dibenzofurans health effects: of consideration in their biphenyls polychlorinated “dioxin-like” and so-called (CDFs) (PCBs): up the benzene rings that make carbon-carbon bond unites the two bond allows the rings to rotate basic structure of PCBs. This do not have the that many means relative to one another, which to the toxic potential of PCDDs planar structure that contributes identifies Health Organization and PCDFs. However, the World “non-ortho substituted”) PCB two coplanar (also called (PCB-126) and congeners—3,3’,4,4’,5-pentachlorobiphenyl having (PCB-169)—as 3,3’,4,4’,5,5’ hexachlorobiphenyl and ten similar congeners as considerable dioxin-like toxicity toxic potential. dioxin-like having some B because the structure of PCDFs allows combinations of chlorine atoms that are atoms of chlorine allows combinations because the structure of PCDFs with not physically PCDDs. possible 20313_blp_13-2 Sheet No. 29 Side B 06/23/2005 10:19:08 B 06/23/2005 29 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 30 Side A 06/23/2005 10:19:08 551 551 AFETY S HLORINATED However, 98 ,C . 34, 27 (2001), OC http://www.ccohs.ca/ D EALTH AND The mechanism by The mechanism H /en/cicad34.pdf. /en/cicad34.pdf. 100 RGANIZATION O available at SSESSMENT , .A EALTH H CCUPATIONAL RIMER O HEM P C cs/publications/cicad ORLD L phthaline), chloric or chlorine acne, phthaline), chloric or chlorine ’ Over the years, several names have been have Over the years, several names NT na I ., W 99 ENTRE FOR 5/23/2005 10:24 PM HLORACNE chloro C ONCISE note 77, at 262. note 77, at DOC per OWE ET AL ,C 051705. supra supra B: A C What is Occupational Acne? http://www.who.int/ip ANADIAN P. D. H ACROED C IOM, M 98 99 100 Chloracne is an acne-like rash characterized by the formation the formation by acne-like rash characterized Chloracne is an PPENDIX APHTHALENES UTLER M K halogen acne, Halowax acne, and cable rash. Halowax acne, and cable halogen acne, used to refer to what is here termed “chloracne,” including including “chloracne,” termed used to refer to what is here it was caused by disease (because or Perna Pernakrankheit exposure to (CCOHS), N chloracne is not considered to be a good biomarker for dioxin be a good biomarker chloracne is not considered to widely in the dose required to exposure because individuals vary induce a skin reaction. of large numbers of comedones (plugs of sebaceous and dead skin (plugs of sebaceous of comedones of large numbers follicle) on the face. In more of a hair opening in the stuck material on the shoulders, chest, back, severe cases, cysts also form chloracne can result Dioxin-associated and extremities. abdomen, skin contact,inhalation exposure. ingestion, or from is not understood. Early which dioxin causes skin lesions exposure to dioxin-containing researchers thought that skin occurs in plugged the pores, but because the effect also chemicals this explanation is clearly inhalation and ingestion exposures, intoxication has other health inadequate. Acute dioxin RESEARCH OF HISTORY THE ORANGE” ON “AGENT (TEQs). equivalents use toxic often researchers health exposure, masses of toxicity-weighted the of calculating a means TEQ is toxic It employs of dioxins. mixtures consisting of exposures that factors (TEFs) equivalency of a congener the potency indicate which to 2,3,7,8-TCDD, with relation value of 1. has the reference vivo of in the results values derived from TEFs are consensus for humans and are different (cellular) studies in vitro and (animal) in their sensitivity vary greatly because species and other animals of the concentrations of is the sum TEQ of a mixture to dioxin. The by their TEFs. it multiplied the congeners in A B available at oshanswers/diseases/acne.html (last Dec. 1, updated 1997). oshanswers/diseases/acne.html C Y 20313_blp_13-2 Sheet No. 30 Side A 06/23/2005 10:19:08 A 06/23/2005 30 Side Sheet No. 20313_blp_13-2 20313_blp_13-2 Sheet No. 30 Side B 06/23/2005 10:19:08 M K - C Y P - 101 dioxin dioxin EALTH UND I (Dec. - XPOSURE -p- ] (1919). .H series of , E ART NVTL , P YGIENE RBEITS GENCY H A RAFT .A D , 109 E , 109 ETRACHLORODIBENZO RADE ROT T .P Epidemiologic studies Epidemiologic EVIEW 102 ,R dfs/dioxin/nas-review/. dfs/dioxin/nas-review/. 2,3,7,8-T NVTL ORK AND W EHRBUCH DER L U.S. E OMPOUNDS , Severe 2,3,7,8-Tetrachlorodibenzo Veterans and Agent Orange Veterans and Agent C URZES see also also see EXTBOOK OF T EASSESSMENT OF ,K ELATED R 103 R 5/23/2005 10:24 PM HORT note 77; n: Clinical and Laboratory Effects DOC http://www.epa.gov/ncea/p [S JOURNAL OF LAW AND POLICY POLICY AND LAW OF JOURNAL EHMANN EALTH AND H supra supra 865, 865-66 (2001). (2001). 865-66 865, 051705. (TCDD) Alexandra Geusau et al. et Geusau Alexandra K.B. L IOM, UMAN ACROED available at available M H 102 103 101 EWERBEHYGIENE IOXIN ERSPECTIVES UTLER (TCDD) Intoxicatio (TCDD) D P G

552 (nausea, symptoms gastrointestinal including consequences, and liver damage. and loss of appetite) epigastric pain, vomiting, appeared in symptoms known that these as 1919 it was As early naphthalenes. fed chlorinated animals A full exposure. effects from low-level long-term also indicate is beyond the topic sometimes-controversial discussion of this it, including However, several sources address scope of this paper. of Medicine’s the Institute ongoing Protection Agency’s U.S. Environmental reports and the dioxin reassessment. B AND 2003), 20313_blp_13-2 Sheet No. 30 Side B 06/23/2005 10:19:08 B 06/23/2005 30 Side Sheet No. 20313_blp_13-2