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44 PUHVEL. ERTL. AND LYNBERG 1982). Essentially, epidermal hyperplasia ac companied by involution of sebaceous glands, hyperkeratinization of the epidermis, and keratinization of dermal cysts are the hallmarks of hairless mouse "chloracne." These gross morphologic changes were ac companied by significant elevations in epi dermal transglutaminase activity. By the end of the second week of treatment, the epidermal transglutaminase (ETG) levels were more than sixfold the baseline levels, or the levels in the skin of acetone-treated mice (Fig. I). By the end of the third week of treatment, ETG levels had decreased from the initial peak but still remained at more than twice the baseline levels at the termination of the experiment at 4 weeks. To test for the possibility that TCDD pres ent in the treated mouse skins was carried into WEEKS OF TREATMENT Fig. 1. Epidermal tran sjlu u m iiu se activity in skin of hairless mice treated with TCDD ( ------ ) and in con trols ( O ------ O k expressed as cpm incorporated during 30 min of incubation/mg of epidermal cytosol protein. See Methods for details. the ETG assay and exerted a direct activating effect on the enzyme in the epidermal cytosol preparation, 0.2 ng of TCDD was added di rectly to the ETG assay mixture and the effect monitored. No changes in radioactivity of the resulting precipitates was observed. In Vitro Studies O The ionic concentration of calcium in t h ^ medium has been well established as a re g u -^ lator of mouse epidermal cell terminal d iffe r-_ entiation in in vitro tissues cultures (Henningsgo et al,, 1980) and our results were in line w ith e s this finding. In low calcium medium, mouse r>4 keratinocytes did not undergo terminal differentiation but continued to proliferate as-CO ' basal cells in monolayers (Fig. 2A). Addition of 10"* M TCDD did not change this pattern of growth at least in so far as could be deter mined by light microscopy (Fig. 2B). Nor did addition of TCDD have any elfect on the rate of cell proliferation as measured by compar ison of total cell counts of cultures, 24, 48, 72, and 96 hr after the addition of TCDD or DMSO to the low calcium medium. Total protein content (measured to the twelfth day) was similar in cultures grown with or without TCDD. Cells grown in high calcium medium started to stratify and differentiate 72 hr after plating (Fig. 2Q . ETG activity in the TCDD-treated cells in low calcium medium gradually increased over the 12-day period of growth, so that on the twelfth day ETG levels in the TCDD-treated, undifferentiated cells were almost identical to levels in the fully differentiating cells grown in high calcium medium (Fig. 3). ETG levels in the undifferentiating cells grown in low cal cium medium without the addition of TCDD also increased slightly over the 12-day incu bation period, but remained at about half the level of activity in the previously described cultures. That this was a genuine increase of ETG production by the cells, rather than an acti vation of ETG activity already present in the cells, was shown by the fact that 10"* m TCDD added directly to the transglutaminase assay did not have any effect on the results. C P H / HS OF PROTEIN 18384 INCREASED e p id e r m a l t r a n s g l u t a m in a s e a c t iv it y f o l l o w in g t c d d 45 treated cells (0.7%) than in the control cells (0.3%), but it remained much lower than the counts of comified envelopes in cells grown in high CaJ* medium from the beginning (12 to 14%). Morphologically, terminal differen tiation and cell death were delayed in the TCDD-treated cultures, in a manner similar to what has been reported for retinoic acidtreated cultures by Yuspa et ai (1981) (Fig. 4). DISCUSSION Tlie changes induced in human skin by TCDD exposure are among the more observ able and well-defined biological effects of this potent man-made toxin. In the hairless mouse model, topical application of minute amounts ofTCDD induces a distinct hyperproliferative, hyperkeratinizing response (Puhvei et ai. 1982; Knutson and Poland, 1982). Epidermal trans glutaminase is considered a marker enzyme for terminal epidennal differentiation (Gold smith and Martin, 197S; Buxman and Wuepper, 1976). This soluble, calcium-dependent enzyme which catalyses the formation of co- DOH2I60ZM t Fig. 2. Neonatal m ouse epidermal cell cultures (A) in 0.07 m u CaJ* medium; (B) in 0.07 mM Ca1* and 10'* M TCD D ; and ( Q in 1.2 mM CaJ* medium at 7 days after plating. Note that TCD D did not affect cell culture morphology in the low calcium medium. Changing keratinocyte cultures from low calcium to high calcium medium on Day 7, at a time when it had been established that ETG activity was high in the TCDD-treated, undifferentiated cells, indicated that terminal differentiation was not the same in TCDDtreated cells as in control cells grown in low calcium medium without the presence of TCDD. The comified envelope count was consistently slightly higher in the TCDD- PO**M TCOO Addid Fig. 3. Epidermal transglutaminase activity in cultures grown in 1.2 mM CaJ' ( ------ ) , in cultures grown in 0.07 mM Ci?" plus 10'* M T C D D ( O ------ O), and in 0.07 mM CaJ* without TCD D ( A ------ A). 18385 l U 0 8 IZHOQ 46 PUHVEL. ERTL. AND LYNBERG Fig. 4. (Quotation o fth cd d ay in terminai diffrentiation of mouse epidermal cell cultures following treatm ent with 10"* m TCDD. Parallel cultures were lin t grown in 0.07 ntM C l1' for 7 days in the presence (A) and without the presence of I0-* MTCDD (BX Cultures were then switched to 1-2 mM CaJ* (without TCDD). Terminal differentiation and cell death were delayed in the TCDD-treated cultures (A) compared to controls (BX The photograph was taken 5 days after transfer to 1.2 mM Ca1* medium. valent crosslinks, involving t {7-gluytamyl-lysine) dipeptide bonds, is thought to be involved in the conversion of soluble st.uctural protein beneath the plasma membranes of epidermal cells, to insoluble, high-molecular-weight pro teins which form the comified cell envelopes of differentiated kratinocytes. Levels of transglutaminase activity in vivo in mouse ear epidermis are affected by agents which alter epidermal differentiation, such as anthralin, retinoic acid, and fluocinolone acetonide (DeYoung and Ballaron, 1982). In the present in vivo studies, a significant increase of this enzyme activity was demonstrated fol lowing changes in cutaneous differentiation after TCDD application. One possible com plication in interpreting results of in vivo ex periments which involve analyses of crude epidermal extracts is that during the dermalepidermal separation procedure, dermal transglutaminases may theoretically contam inate the epidermal preparations. Substances applied topically to the skin, particularly those which induce an inflammatory cutaneous re sponse, may affect the dermal as well as epi dermal transglutam inase levels. Previous studiesby DeYoungand Ballaron ( 1982)which investigated this problem suggested that their results were not affected by inflammatory changes. In the present paper, in vitro tissue culture studies were used to confirm the in vivo observations in a system which was free of dermal components. The observation that mouse epidermal kr atinocytes in low Ca2* medium have lower levels of transglutaminase activity than dif ferentiating kratinocytes in high CaJ* me dium has been established previously by Hen nings et al. (1981). Our finding that TCDD increases unexpressed transglutaminase activ ity in the nondifferentiating cells in low Ca2* medium confirms our in vivo observations about the increase of this enzyme by TCDD in epidermal cells. Very similar effects on transglutaminase in duction by epidermal basal ceils in vitro have been demonstrated by the addition of retinoic acid (Yuspa et ai. 1981) or 12-O-tetradecanoylphorbol-13-acetate and other tumor pro motors (Yuspa et al.. 1980) to low calcium mouse epidermal tissue cultures. In those studies as in the present experiments, it ap peared that the effect was one of induction rather than activation of enzyme activity, since addition of the chemical (in this case 10'' M TCDD) directly to the enzyme assay had no effect on the results. In the studies by Yuspa et al. ( 1980, 1981) retinoic acid had a different effect on terminal differentiation of the cell cultures after transfer to high calcium (1 .2 m M ) medium. Normally, when epidermal basal cells are transferred to high calcium medium after being cultured in low calcium medium for 5 to 7 days, terminal differentiation ac companied by cell death occurs within 2 to 5 days after transfer. In cells grown in the pres ence of retinoic add (at 10"* Mconcentration). 18386 et,Z09UHOa INCREASED EPIDERMAL TRANSGLUTAMINASE ACTIVITY FOLLOWING TCDD 47 this pattern of terminal differentiation was significantly delayed. Phorboi esters did not affect the rate of terminal differentiation. In the present study, TCDD also delayed ter minal differentiation of the cultures, despite the fact that insoluble cell envelope counts appeared to be higher in the TCDD-treated transferred cultures than in the untreated con trols. Knutson and Poland (1982) have suggested that cutaneous sensitivity to TCDD in mice is associated with the gene for hairlessness, and that hr/hr (hairless) animals have &more acute cutaneous response to TCDD than do the hr/+ (haired) counterparts. In the present studies, epidermal cell cultures were estab lished with BALB/c hr/+ (haired) neonatal mice as tissue donors. Interestingly, such cells in culture responded to TCDD exposure. It could be that the effects of TCDD on epider mal cell cultures would be even more striking in epidermal cultures from hr/hr (hairless) skin donors. ACKNOWLEDGMENTS T his research was supported in p a n by G rants AM 17423 and OH 1108 from the National Institute o f Health, by Veterans Administration Medical Research funds, and funds from the Dermatologic Research Foundation of California. Inc. REFERENCES Bradford, M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein uti lizing the principle of protein dying binding. Anal. Biochem. 72, 248-254. Bu x m an, M. M.. and Wuepper. K_ D. ( 1976). Isolation, purification and characterization o f epidermal trans glutaminase. Biochim. Biophys. Acta 452,1 5 6 -3 6 9 . DeYoung, L , AND Bauaron, S. (1982). The effect of topical d ro p on mouse ear transglutaminase activity. J Invest. Dermatoi. 79, 189-193. Goldsmith. L. A., and Martin. C. M. (1975). Human epidermal transamidase. J. Invest. Dermatol. 64, 3 lb 321. Hennings, H.. Michael. D., Cheng, C.. Steinert, P.. Holbrook, K., and Yuspa, S. H. (1980). Calcium regulation o f growth and differentiation of mouse epi dermal cells in culture. Celt 19. 245-254. Hennings, H.. Steinert, P.. and Buxman, ,M. M. (1981). Calcium induction of transglutaminase and the formation of <(t glutamyl) lysine cross-links in cultured mouse epidermal cells. Biochem. Biophys. Res. Com mit. <02, 739-745. Knutson, J. C.. and Poland, A. (1982). Response of m urine epidermis to 2.3.7.8-tcirachlorodibcnzo-pdioxin. Interaction o f the Ah and hr loci. Celt 30, 225234. Marcelo, C . Kjm, Y. G - Kleine. J. L . and Vorhees. J. J. (1978). Stratification, specialization and prolifer ation o f primary keratinocytc cultures. J. Ceil Biol. 79, 356-370. MOORE, J. A. (1978). Toxicity o f 2,3,7,8-tetrachlorodibenzo-p-dioxin. Ecol. Bull (Stockholm ) 27, 134-144. Ogawa. H., ano Goldsmith, L. A. (1976). H um an epi dermal transglutaminase. J. Biot. Chem. 251, 72817288. Puhvel, S. M.. Sakamoto. M.. Ertu D. C . ano Reisnex, R. M. (1982). Hairless mice as models for chloracne: a study of cutaneous changes induced by topical application o f established chloracnegens. Toxicol. Appl. Pharmacol. 64, 492-503. Yuspa, S. H., Ben, T.. Hennings, H., ano Lichti. cl. (1980) . Phorboi ester tum or promo-ers induce epidermal transglutam inase activity. Biochem . Biophys. Res. Commun. 97, 700-708. Yuspa. S. H., L tc im , U.. Ben, T ,, and Hennings. H. (1981) . Modulation o f terminal differentiation and re sponses to tum or promoters by retinoids in mouse epi dermal cell cultures.-Ann. N.Y. Acad. Sci. 359. 260- 273. Yuspa, S.. Ben, T,, and Steinert, P. (1982). Retinoic acid induces transglutaminase activity but inhibits cornification of cultured epidermal cells. / Biol. Chem. 257, 9906-9708. "1 18387 NATIONAL LIBRARY o f MEDICINE 237K r h?W I - U O L I &* No. 83-19 LITERATURE SEARCH DON 2160178 DIOXIN TOXICOLOGY (INCLUDING AGENT ORANGE) January 1981 through September 1983 128 Citations Prepared by S ila s Jackson Updates Literature Search No. 80-30 Agent Orange, 1972-1980 This bibliography pertains to a ll adverse or toxic effects of or of any exposure or potential exposure to 2,3,7,8,-tetrachlorodibenzo-p= dioxin. Agent orange particles are included. See also: Dioxin report. Chemical & Engineering News 1983 June 6; 61(23): 20-64 passim. Accidental exposure to dioxins: human health aspects. Edited by Frederick Coulston, Francesco Pocchiari. New York: Academic Press, 1983. 294p. The TOXLINE database may also be consulted for additional citatio n s. This bibliography contains references to recent articles selected from some 3.000 English and foreign language journals and a limited number of monographs. Articles from these journals and mono graphs are indexed for inclusion in Index Medicus and other bibliographies produced by the National Library of Medicine. The references in this Literature Search were retrieved from NLM's MEDLINE data base; the dates above show the period during which the references were added to MEDLINE. Each citation is listed with the descriptors selected from NLM's list of Medical Subject Headings (McSH) under which the article was indexed. MeSH descriptors of most significance in an article are identified with an asterisk. The article cited will be found in Index Medicus only under these starred descriptors. A bracketed title indicates the article is in a foreign language. For foreign language articles the designation ENG.ABSTR. follows the publication date if the article includes an English abstract; language abbreviation in parenthesis follows. A full explanation of the elements included in each citation, as well as a complete list of current NI.M Literature Searches are included in Index Medicus and Abridged Index Medicus. To obtain a current list of Literature Search titles, write; Literature Search Program. Reference Section. National Library of Medicine. 8600 Rockville Pike. Hcthcsda. Maryland 20209. Please include your name and address typed on a gummed label (no return postage necessary). U.S. DEPARTMENT O f HEALTH AND HUMAN SERVICES Public H ealth Service N ational Institute of Health I* 1QqpO A .* - 8 / 1 0 9 1 ZM0Q A Ahaleee PH: Chlorinated djoiins [editorial] Scirncr I9S3 Jun 24;220(4d04):l337 ANIMAL/ DERMATITIS. CONTACT, ctiolofy/ 'DIOXINS, advene efTccu/ DIOXINS, tosicity/ HUMAN/ TETRACHLORODIBENZODtOXIN. advene effects/ TETRACHLORODIBENZODIOXIN. loaidiy Alberanf V, Slalacalrhl P, Dl M an* L, at a t Dgradaslone delTambtcnie. III. Igicnc del suolo e proweditnenti cooceraenti le tone colpite da contaminazionc da TCDD. Ann 1st Super Sanita 19ll;17(2):323-33 (lu) DIOXINS/ ENVIRONMENTAL POLLUTION/ ITALY/ LEGISLATION/ SOIL POLLUTANTS/ TETRACHLORODIBENZODIOXIN B Bgk W, Faff J, KlaletiishI T: Wartofci niektdrych ikiadnikow Itrwt swiack monkich w ostrym zatruciu 2.3.7,S-czterodwubcnxo-p-dioksyng (TCDD). Med Pr 19I2;33(5-d):269-7S (Eng. Absir.) (Pol) ACUTE DISEASE/ ANIMAL/ DIOXINS. t)zoning/ ENGLISH ABSTRACT/ RYTHROCYTE COUNT/ ERYTHROCYTES. meuboUsm/ ERYTHROCYTES, pathology/ GUINEA PIGS/ HEMOGLOBINS, analysis/ LEUKOCYTE COUNT/ LEUKOCYTES, metabolism/ LEUKOCYTES, pathology/ MALE/ REFERENCE VALUES/ TETRACHLORODIBENZODIOXIN, poisoning Ball LM, Chhakra RS: Intestinal absorption of nutrients in rats treated with 2.3,7.t-ietrachlorodibcnzo-p-dioxia (TCDD). J Toxicol Environ Health 1911 Oct;4):629-3l ANIMAL/ ' DIOXINS, toxicity/ EATING, drag effects/ GLUCOSE, metabolism/ 'INTESTINAL ABSORPTION, drag effects/ LEUCINE, metabolism/ MALE/ RATS/ RATS, INBRED STRAINS/ TETRACHLORODIBENZODIOXIN. toxicity n a ils w hs J: Hepatoloiuycxnoid wybnnych poiichlorowanych wegkrwodordw aromatycznych. Rocz Panstw ZaU Hi* I912;33(4):303-J (Eng. Abatr.) (Pal) ANIMAL/ CHLOROBENZENES, toxicity/ CHLOROPHENOLS. toxicity/ `DIOXINS, toxicity/ ENGLISH ABSTRACT/ HEXACHLOROBENZENE. toxicity/ LIVER DISEASES, chemically induced/ LIVER, drag effects/ PENTACHLOROPHENOL. toxicity/ PORPHYRIA, chemically induced/ RATS/ TETRACHLORODIBENZODIOXIN, toxicity Barr M: Neuropaychiatric effects of herbicides (letter) Aust NZ J Psychiatry 1912 Jun;16<2):ll-9 DIOXINS, advene effects/ HUMAN/ MALE/ NERVOUS SYSTEM DISEASES, chemically induced/ ^ORGANIC MENTAL DISORDERS. SUBSTANCE-INDUCED, etiology/ T E T R A CHLORODIBENZODIOXIN. advene effects/ VETERANS, psychology/ 2,4-DICHLOROPHENOXYACe TIC ACID, advene effects/ 2.4.J-TRICHLOROPHENOXYACET1C ACID, advans effect* Bicfcal MH: Polychlorinated persistent compounds. Experience 1912 Aug 13;3Kl):179-t2 ADIPOSE TISSUE, metabolism/ ANIMAL/ CHEMISTRY/ DOGS/ DDT. metabolism/ ENVIRONMENTAL POLLUTION/ GUINEA PIG S/ HUMAN/ `HYDROCARBONS. CHLORINATED, metabolism/ HYDROCARBONS. CHLORINATED, toxicity/ KINETICS/ POLYCHLOROBIPHENYL COMPOUNDS, metabolism/ RATS/ TETRACHLORODIBENZODIOXIN. n c u b o lin Bidtd MH, Mae*Ishark S: Pharmacokinetics and ecodrspoaipon of polybalogcnatcd hydrocarbons: aspects and concepts. Drag Metab Rev 1910:1 l(2):M9-90 (237 ref.) ANIMAL/ BIODEGRADATION/ BIOTRANSFORMATION/ DDT. analyst/ ENVIRONMENTAL POLLUTANTS, analysis/ HYDROCARBONS. HALOGENATED. metabolism/ KINETICS/ POLYCHLOROBIPHENYL COMPOUNDS, analysts/ REVIEW/ TETRACHLORODIBENZODIOXIN. analysis Blaaad L, Bonettl F, rsn m sartl P, cl al: Experiences from the accident of Seveso. A cu Morphoi Acad Sd Hung I9SO:28(I-2):I39-37 ABNORMALITIES. DRUG-INDUCED, occurrence/ ABORTION, chemically induced/ ABORTION, occurrence/ ACCIDENTS. OCCUPATIONAL/ ACNE chemically induced/ ACNE occurrence/ ADOLESCENCE/ ADULT/ AGE FACTORS/ BIRTH RATE/ CHILD/ CHILD. PRESCHOOL/ DIOXINS, toxicity/ ENVIRONMENTAL POLLUTION/ FEMALE/ HUMAN/ INFANT/ ITALY/ MORTALITY/ PREGNANCY/ SOIL, analysis/ TETRACHLORODIBENZODIOXIN. analysis/ TETRACHLORODIBENZODIOXIN. toxicity Bishop CM, Jaaaa AH: Non-Hodgkin's lymphoma of the scalp in workers exposed to dioxins (letter) Lancet 1911 Aug 13;2(I242):369 A GED/ CASE REPORT/ DIOXINS, advene effects/ HUMAN/ ` LYMPHOMA, chemically induced/ MALE/ MIDDLE AGE/ OCCUPATIONAL DISEASES, chemically induced/ SCALP/ 'SKIN NEOPLASMS, chemically induced/ TETRACHLORODIBENZODIOXIN. analop A derivatives/ TETRACHLORODIBENZODIOXIN. advene effects Blackbars AB: Review of the effects of Agent Orange: a psychiatric perspective on the controversy. Mtlit Med 1913 Aprl4(4):333-40 ANIMAL/ DIOXINS, toxicity/ HUMAN/ PSYCHOSES. SUBSTANCE-INDUCED, psychology/ SKIN DISEASES, chemically induced/ TETRACHLORODIBENZODIOXIN. toxicity/ UNITED STATES/ VIETNAM/ 2.2-DICHLOROPHENOXYACETIC ACID, toxicity/ 2,4,5-TRlCHLOROPHENOXYACETIC ACID, toxicity Boorman GA, Lamar ML Doan JH, at al: Assessment of myelotoxicity caused by environmental chemicals. Environ Health Perspcct 1912 Feb;43:129-35 ANIMAL/ BENZOPYRENES, toxicity/ ` BONE MARROW, drag effects/ DIETHYLSTILBESTROL. toxicity/ ENVIRONMENTAL POLLUTANTS, toxicity/ ERYTHROPOIESIS. drag effects/ FEMALE/ GRANULOCYTES, drug effects/ HEMATOPOIETIC STEM CELLS, drag effects/ MACROPHAGES, drag effects/ MICE/ POLYBROMOBIPHENYL COMPOUNDS, toxicity/ TETRACHLORODIBENZODIOXIN, toxicity Bradlan JA. Garthoff LH, Hurley NE, at ah Comparative induction of aryl hydrocarbon hydroxylase activity in vitro by analogues of dibenxo-p-dioxin. Food Coamet Toxicol 1910 Deel6):427-33 ANIMAL/ ARYL HYDROCARBON HYDROXYLASES, biosynthesis/ CELLS. CULTURED/ COMPARATIVE STUDY/ DIOXANES. toxicity/ DIOXINS, toxicity/ ENZYME INDUCTION, drug effects/ HALOGENS, toxicity/ HEPATOMA. EXPERIMENTAL, enxymology/ RATS/ TETRACHLORODIBENZODIOXIN. toxicity Baah RR. C ra a a ttt WB, Cade SS. at ab Truce chemistries of fire: a source of chlorinated dioxins. Science 1910 Oct: 210(4461)J 1 J - 9 0 AIR POLLUTANTS, analysis/ AUTOMOBILE EXHAUST, analysis/ CHEMISTRY/ CHROMATOGRAPHY. HIGH PRESSURE LIQUID/ DIOXINS/ DIOXINS, analysis/ CTO C C / P n U /P B P I .A M T S / S U H IC R u u l v i i i / 1 18389 SOIL POLLUTANTS, analysis/ TETRACHLORODIBENZODIOXIN. snalysis/ WATER POLLUTANTS CHEMICAL, analysis c f n M L, Salmons M, nirrardlal M; Porphyrogceic effect of chronic treatment with 2.3.7,1-lelrachiorodibcflzo-p--dtoiin in female rau. Dene--effect relatioMhip following urinary excretion of porphyrins. Toxicol AppJ Pharmacol 1911 Feb; 57(2): 136-43 ANIMAL/ DIOXINS toxicity/ DOSE-RESPONSE RELATIONSHIP. DRUG/ FEM ALE/ KIDNEY, metabolism/ LIVER, metabolism/ KJRPHYR1NS. biosynthesis/ PORPHYRINS urine/ RATS/ SPLEEN, metabolism/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN. toxicity Caramurbl F, i d Caron G. FararetU C, et ah Chloracne following environmental contamination by TCDD in Sizeso. Italy. Ini J Epidemiol 19(1 Jun:10(2):I3S-43 ACCIDENTS. OCCUPATIONAL/ ACNE, chemically induced/ ACNE, diagnosis/ ACNE occurrence/ ADOLESCENCE/ CHILD/ CHILD. PRESCHOOL/ DIOXINS toxicity/ ENVIRONMENTAL POLLUTANTS toxicity/ FEMALE/ HUMAN/ ITALY/ MALE/ RESIDENCE CHARACTERISTICS/ SYNDROME/ TETRACHLORODIBENZODIOXIN, toxicity rtttsnsu M, Rtxinttl G, CnrleUa D, et ah Repent istologici placeman in soggetti provenienti da area inquinau da TCDD. Ann Ostet Ginecol Med Perinat 1911 May-Jun; 102<3);I55--6k (Eng. Abur.) (Ital ABORTION, chemically induced/ ADULT/ AIR POLLUTANTS adverse effects/ DIOXINS adverse effects/ ENGLISH ABSTRACT/ ENVIRONMENTAL POLLUTANTS adverse effects/ FEMALE/ HUMAN/ ' PLACENTA DISEASES chemically induced/ PREGNANCY/ SOIL POLLUTANTS adverse effects/ TETRACHLORODIBENZODIOXIN. adverse effects Chaeng MO, Gilbert EF, P ittin g RE: Cardiovascular teratogenicity of 2. 3. 7, l-tetnchlorodibcnzo-p-dioxin in the chick embryo. Toxicol Appl Pharmacol 1911 Nov; 41(2): 197-204 ABNORMALITIES DRUG-INDUCED/ ANIMAL/ BLOOD VESSELS abnormalities/ CHICK EMBRYO/ DIOXINS. toxicity/ DOSE-RESPONSE RELATIONSHIP. DRUG/ HEART DEFECTS CONGENITAL, chemically induced/ SUPPORT. NON-U.S. G O V T / SUPPORT. U.S GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN. toxicity Comma D, Achcaan ED: Do phenoay herbicides cause cancer in man? Lancet 19(2 May (; l((2(0):I0S7-9 CHLOROPHENOLS advene effects/ DIOXINS adverse effects/ HUMAN/ LYMPHOMA, chemically induced/ OCCUPATIONAL DISEASES chemically induced/ SARCOMA, chemically induced/ SOFT TISSUE NEOPLASMS chemically induced/ TETRACHLORODIBENZODIOXIN. advene effects/ 2.4.5-TRICHLOROFHENOXYACETIC ACID, advene effects Cask RJL Dioxin. chloracne, and soft tissue sarcoma (letter! Lancet 19(1 Mar l4;l(t2H> Pi 1)61(-9 ACNE, chemically induced/ COCARCINOGENESIS/ DIOXINS poisoning/ HUMAN/ MIDDLE AG E/ OCCUPATIONAL DISEASES chemically induced/ SARCOMA, chemically induced/ SMOKING/ SOFT TISSUE NEOPLASMS chemically induced/ TETRACHLORODIBENZODIOXIN, pnooning Csagsr CL, Oaaktay S Taftn^l M, et ah Anencephaly: agent orange implications? 1 Nall Med Axaoc 19(3 Jan; 75(l)*3-4 ABNORMALITIES DRUG-INDUCED. 2 etiology/ ADULT/ ANENCEPHALY. chemically induced/ CASE REPORT/ ___ DIOXINS, adverse effects/ FEMALE/ FETAL DEATH, chemically induced/ HUMAN/ PREGNANCY D DieIdas M. Secfeld MD, Peterson RE: Enhanced liver DNA synthesis in partially bepatectomized rau ?retreated with 2.3.7,-tctrachiorodibento-p-diotm. 'oxicol Appl Pharmacol 19(1 May-,5((3):3(9-9( ANIMAL/ COMPARATIVE STUDY/ DIOXINS, toxicity/ DNA, biosynthesis/ HEPATECTOMY/ LIVER REGENERATION, drug effects/ LIVER, drug effects/ LIVER, physroiogy/ MALE/ RATS/ SUPPORT. U.S. GOVT. P.H.S/ TETRACHLORODIBENZODIOXIN. toxicity/ THYMIDINE metabolism/ TIME FACTORS Dickson D: The embarrassing odyssey of Seven's dioxin (news) Science 19(3 Jue 24020(4404):1342-3 DIOXINS, advene effects/ FRANCE/ INDUSTRIAL WASTE, adverse effects/ ITALY/ TETRACHLORODIBENZODIOXIN. advene effects dl Domssdca A, SUane V, VMano G, et ah Accidental release of 2,J.7.S-tetrachiorodibcuo-p-dioiia (TCDD) at Seveso. Italy. V. Environmental persistence of TCDD in soil. Ecotoxicol Environ Safety 19(0 Scp-,4(3):339-43 ACCIDENTS. OCCUPATIONAL/ DIOXINS, analysis/ ITALY/ SOIL POLLUTANTS, analysis/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN. snalysis dl Damenlro A, SUane V. Vhrtans G. tt ah Accidental release of 2J,7,(-tctrachlorodibeaxo-p-dioxia (TCDD) at Severe, Italy. IV. Vertical distribution of TCDD in solL Ecotoxicol Environ Safety 19(0 Scp;4(3)-327-3( ACCIDENTS, OCCUPATIONAL/ DIOXINS, analysis/ ITALY/ SOIL POLLUTANTS, analysis/ SUPPORT, NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN. analysis/ TIME FACTORS dl Dnsnalrn A, SUane V, Vhrtroa G, st ah Accidental release of 2J,7,(-ietnchlorodibeiut>-p-dioxin (TCDD) at Skveso, Italy. III. Monitoring of residual TCDD levels in reclaimed buildings. Ecotoxicol Environ Safety 19(0 Sep?K3):32!-4 ACCIDENTS, OCCUPATIONAL/ DIOXINS, analysis/ ENVIRONMENTAL POLLUTANTS, analysis/ ITALY/ SOIL POLLUTANTS, analysis/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN. analysis dl Damsalm A. Silane V, VMasm G, ah Accidental release of 2,3,7,(-tctrachlorodibeaxo-p-dioxin (TCDD) at Skvcao, Italy. II. TCDD distribution in the toil surface layer. Ecotoxicol Environ Safety 19(0 Sep;4(3):29(-320 ACCIDENTS. OCCUPATIONAL/ DIOXINS, analysis/ ITALY/ SOIL POLLUTANTS, analysis/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN, analysis dl Domesirs A, Silane V, Vivians G, st ah Accidental release of 2J.7,S-tctrachlorodibenio-p-dioxia (TCDD) at Skveso, Italy. Ecotoxicol Environ Safety 19(0 Sep; 4(3)3(3-97 ACCIDENTS. OCCUPATIONAL/ DIOXINS, analysis/ ENVIRONMENTAL POLLUTANTS, analysis/ ITALY/ MASS FRAGMENTOGRAPHY/ PLANTS, analysis/ SOIL POLLUTANTS, analysis/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN. analysis Deaatdll L, Lampa E, Craaa E: Coosidcrationa on the epidemiology of the Seveso accident. Toxicol Eur Res 19(1 Jan;3(l):9-I4 ACCIDENTS. OCCUPATIONAL/ AGED/ ANIMAL/ DIOXINS, poisoning/ DRUO INTERACTIONS/ FEMALE/ HUMAN/ INFANT. NEWBORN/ ITALY/ LETHAL DOSE 30/ MALE/ SPECIES SPECIFICITY/ TETRACHLORODIBENZODIOXIN. poisoning/ D0W2I 60 I 8 Q TETRACHLORODIBENZODIOXIN. losiciiy Daaagla WG: Dioxin effect on humxn health. Mo Med 1913 Mar;(0(3):l27-JI (29 rtf.) ACCIDENTS. OCCUPATIONAL/ ACNE, chemically induced/ ` DIOXINS, advene effect/ ENVIRONMENTAL EXPOSURE/ GERMANY. WEST/ HUMAN/ ITALY/ MILITARY MEDICINE/ OCCUPATIONAL DISEASES, chemically induced/ REVIEW/ `TETRACHLORODIBENZODIOXIN. advene effect/ UNITED STATES/ VIETNAM F Faaeill R. CMahraado C, Boaaceoni A: TCDD contamination in ihe Seveao incident. Drug Metab Rev 1982:13(33:407-22 ANIMAL/ CATTLE/ ` DIOXINE analyii/ ENVIRONMENTAL POLLUTANTS, analytic/ ENVIRONMENTAL POLLUTANTS, poisoning/ ITALY/ MILK, analyii/ RABBITS/ SOIL POLLUTANTS, analyii/ SUPPORT. NON-U.a. G O V T / `TETRACHLORODIBENZODIOXIN. analyti/ TETRACHLORODIBENZODIOXIN. poisoning/ TISSUE DISTRIBUTION Fanelll R Beeteal MP. CaatelU MG. ct ah 2.3.7.(-Tctrachlorodibenzo-p-dioxin toxic effect and tiuue level in animal from the contaminated area of Seveao, Italy. Arch Environ Conlam Toxicol 1980. 9(J):369-77 ACCIDENTS. OCCUPATIONAL/ ANIMAL/ BIRDS/ CATS/ CATTLE/ CHICKENS/ DIOXINS, toxicity/ ENVIRONMENTAL POLLUTANTS/ GOATS/ GUINEA PIGS/ HORSES/ ITALY/ RABBITS/ SHEEP/ SUPPORT. NON-U.S. G O V T / SWINE/ TETRACHLORODIBENZODIOXIN. analyii/ `TETRACHLORODIBENZODIOXIN, toxicity FcMe G: Get the facta oo Agent Orange. Imprint 19(2 Sep; 29(3): 17. 61 CHEMICAL WARFARE/ `DIOXINS, pononing/ HUMAN/ MILITARY MEDICINE/ `TETRACHLORODIBENZODIOXIN. pononing/ UNITED STATES/ VIETNAM/ 2,4-DICHLOROPHENOXYACETIC ACID, pononing/ 2,4.3-TRICHLOROPHENOXYACETIC a c id , pononing Fllipplai G, Bordo B, Ocean P, ct ah Relationship between clinical and electrophysiological ftndinp and indicaton of heavy exposure to 2.3.7,(-tetrachlorodibcnxo-dioxin. Scand i Work Environ Health 19(1 Dcc7(4):237-62 ACNE, chemically induced/ ADOLESCENCE/ ADULT/ CHILD/ CHILD. PRESCHOOL/ ` DIOXINS, poisoning/ ELECTROPHYSIOLOGY/ ENVIRONMENTAL POLLUTANTS, poisoning/ HUMAN/ ITALY/ LIVER, enzymology/ MIDDLE A G E / `PERIPHERAL NERVE DISEASES, chemically induced/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN, Flak DJ: Exposure to agent orange (letter) JAMA 19(0 Sep 5;244(10): 1094-3 ENVIRONMENTAL EXPOSURE/ HUMAN/ TETRACHLORODIBENZODIOXIN. toxicity/ V IETN A M / W A R/ 2,4-DICHLOROPHENOXYACETIC ACID, toxicity/ 2,4.3-TRICHLOROPHENOXYACETIC ACID, toxicity Flowed FF, Feeeka NA, Whtsaaan PA: Agent Orange: what't it all about7 J Fla Med Assoc 19(1 Dec; 6((12)99l-2 DIOXINS, advene effects/ `HERBICIDES, advene effect/ HUMAN/ MILITARY MEDICINE/ `TETRACHLORODIBENZODIOXIN, sdvene effect/ UNITED STATES/ VIETNAM/ `2,4-DICHLOROPHENOXYACETIC ACID, advene effects G GaraMai S: TCDD toxicology with particular reference to Seveao: introductory remark. Drug Metab Rev 19(2; 13(3):343-53 (36 ref.) ANIMAL/ ` DIOXINS, toxicity/ ENVIRONMENTAL POLLUTANTS, loaidty/ HUMAN/ ITALY/ KIDNEY, pathology/ LIVER, pathology/ REVIEW / `TETRACHLORODIBENZODIOXIN. toxicity/ TETRACHLORODIBENZODIOXIN. utiue Geiger LE, Neal RA: Mutagenicity toting of 2.3,7,1-tetrachlordibciuo-p-dioxin in htttidiac auaotrophi of Salmooclla lyphimurium. Toaicoi Appl Pharmacol 1981 Jun 13;J9(l):125-9 ANIMAL/ ` DIOXINS, loaidty/ HAMSTERS/ HISTIDINE, metaboliim/ MALE/ MESOCR1CETUS/ MUTAGENICITY TESTS/ MUTAGENS/ RATS/ `SALMONELLA TYPHIMUR1UM. drug effect!/ SALMONELLA TYPHIMURIUM. metaboliui/ SUPPORT. U.S. GO V T, P.H.SV TETRACHLORODIBENZODIOXIN. metabolism/ `TETRACHLORODIBENZODIOXIN. toxicity Glarial E, Prat! M. Vlimara C Effect of 2,J,7,g-ictrchlorodibcnxo-p-dioain adminitterad to pregnant ran during the preimplanUlioa period. Environ R o 1912 Ocl:29(l):lJ-9 `ABNORMALITIES. DRUG-INDUCED, etiology/ ANIMAL/ ` DIOXINS, advene effect/ FEMALE/ NIDATION/ PREGNANCY/ ` PREGNANCY. ANIMAL, drug effect/ RATS/ RATS, INBRED STRAINS/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN. adminttlration A dotage/ `TETRACHLORODIBENZODIOXIN. advene effect Gieriml E, Prat! M, Vtamara C Rabbit teratology ttudy with 2,3.7,(-ietrachlorodibenzo-p-dioain. Envrmi Rea 19(2 Feb*.27(l):74-( ABNORMALITIES. DRUG-INDUCED, etiology/ ABORTION, chemically induced/ ANIMAL/ ` DIOXINS, advene effect/ FEM ALE/ KIDNEY, abnormalilica/ PREGNANCY/ RABBITS/ RIBS, abaormalhiea/ SUPPORT. NON-U.S. G O V T / `TETRACHLORODIBENZODIOXIN. advene effect Glarial E, Pied M, Vismara CS Embryotoaic effects of 2.1.7.8 tctrachiorodibcnzo-f>-dioain administered to female rata before mating. Environ Res 19(3 Jun; 31(0:103-10 ABNORMALITIES. DRUO-1NDUCED/ ANIMAL/ BODY WEIGHT, drug effect/ DIOXINS, toaicity/ ` EMBRYO, drug effects/ FEMALE/ `MATERNAL-FETAL EXCHANGE/ OVULATION, drug effects/ PREGNANCY/ ` PREGNANCY. ANIMAL. drug effects/ RATS/ SUPPORT. NON-US. G O V T/ `TERATOGENS/ TETRACHLORODIBENZODIOXIN. loaidty Geldeteln JA. Unite P, D ir ^ e e H: Induction of porphyria in the tat by chronic versus acute exposure to 2.3,7.S-tctrachlorodibeuo-p-dioain. Biochcm Pharmacol 19(2 Apr 13:31(0:1607-13 AMINOLEVULINIC ACID SYNTHETASE metabolism/ ANIMAL/ ARYL HYDROCARBON HYDROXYLASES, metabolism/ ` DIOXINS, toaidty/ FEM ALE/ LIVER, enzymology/ MIXED FUNCTION OXIDASES, metabolism/ ` PORPHYRIA, chemically induced/ RA TS/ RATS, INBRED STRAINS/ `TETRACHLORODIBENZODIOXIN. toaicity/ TIME FACTORS Irons M U Application of mam spectromtrie methods to analysis of aenobiotics in biological systems. 1ARC Sd Publ l9(2;(39)r443-62 ANIMAL/ `DIOXINE analysis/ FOURIER ANALYSIS/ HUMAN/ MACACA M ULATTA/ MASS FRAGMENTOORAPHY. methods/ MILK. HUMAN, analysis/ 3 DOW2 I 6 0 I 8 I 'SPECTRUM ANALYSIS. MASS, method/ SUPPORT. U.S GOVT. NON-P.H.S./ TETRACHLORODIBENZODIOXIN, analysis/ TETRACHLORODIBENZODIOXIN. metabolism/ VETERANS Genby P: Light at end of tunnel in Orange eontroveny [newt] JAMA 1912 Mar I2:247(I0):IJI2 'DIOXINS, poisoning/ HUMAN/ LEGISLATION, DRUG/ MILITARY MEDICINE/ TETRACHLORODIBENZODIOXIN. poisoning/ UNITED STATES/ VIETNAM/ WAR/ '2,4-DICHLOROPHENOXYACETIC ACID, poisoning/ 2.4.5-TR1CHLOROPHENOXYACETIC ACID, poisoning Gaaby P-. More questions, not answers, emerge from Agent Orange studies (news) JAMA 1983 May 27; 249(20):2743-4 ABNORMALITIES. DRUG-INDUCED, etiology/ ` DIOXINS, poisoning/ FATHERS/ FEMALE/ HUMAN/ INFANT NEWBORN/ MALE/ MATERNAL-FETAL EXCHANGE/ PREGNANCY/ TETRACHLORODIBENZODIOXIN. Siisoning/ UNITED STATES/ VETERANS ISABlLlTY CLAIMS, legislation A jurisprudence/ 2,4-DICHLOROPHENOXYACETIC ACID, poisoning/ 2.4.5-TRICHLOROPHENOXYACETIC ACID, poisoning H Hall P. Salinger B, Field B, cl al: Antipodean 2.4,5-T [letter] Nature 1931 Mar 3:290(5801 ):B ABNORMALITIES. DRUG-INDUCED, etiology/ ANIMAL/ AUSTRALIA/ COMMERCE/ HUMAN/ 2,4-DICHLOROPHENOXYACETIC ACID/ 2.4- DICHLOROPHENOXYACETIC ACID, advene elTects/ 2,4.3-TRJCHLOROPHENOXYACETTC ACID / 2.4.3-TRICHLOROPHENOXYACET1C ACID, adverse elTects Hall RF: Herbicides: liberaton or poisoners of humankind? Vet Hum Toxicol 1983 Apr:25(2):92-3 ANIMAL/ ENVIRONMENTAL POLLUTANTS, analysis/ ' HERBICIDES, toxicity/ HUMAN/ SOIL, analysis/ TETRACHLORODIBENZODIOXIN. metabolism/ TETRACHLORODIBENZODIOXIN. toxicity/ 2.4- DICHLOROPHENOXYACETIC ACID, toxicity/ 2.4.3-TRICHLOROPHENOXYACETIC ACID, toxicity Hirdcll L, Erikasoa M: Soft-tissue sarcomas, phenoxy herbicides, and chlorinated phenols (letter) Lancet 1981 Aug 1;2(8240):250 CHLOROPHENOLS. poisoning/ HERBICIDES, poisoning/ HUMAN/ OCCUPATIONAL DISEASES, chemically induced/ ' SARCOMA, chemically induced/ SOFT TISSUE NEOPLASMS, chemically induced/ TETRACHLORODIBENZODIOXIN. poisoning/ 2,4.5-TRICHLOROPHENOXYACETIC ACID, poisoning Harvey WK, LiadnM R: Activity of varioua aldehyde-metabolizing enzymes in chemically-induced rat hepatomas. Biochem Pharmacol 1982 Mar IS; 31(6):1153--3 ALCOHOL OXIDOREDUCTASES. analysis/ ALDEHYDE OXIDOREDUCTASES. ailalysia/ ALDEHYDES, metabolism/ ANIMAL/ HEPATOMA. EXPERIMENTAL, chemically induced/ `HEPATOMA. EXPERIMENTAL, enzymoiogy/ MALE/ RATS/ RATS, INBRED STRAINS/ SUPPORT, NON-U.S. G O V T / SUPPORT. U.S. GO V T. P.H.S./ TETRACHLORODIBENZODIOXIN. toxicity/ 2-ACETYLAMINOFLUORENE, toxicity 4 Haaaeae EM, Dcnclur L TCDD embryotoxicity in the mouse may be enhanced by beu-naphthoftavone. another ligand of the Ah-rccepior. Toxicol Lett 1982 Jul; 12(2-3): 191-8 ANIMAL/ ` BENZOFLAVONES. pharmacodynamic/ *D!OXINS, toxicity/ FEMALE/ FETAL DEATH, chemically induced/ ' FLAVONES, pharmacodynamics/ LIGANDS/ MICE/ MICE. INBRED C37BL/ PREGNANCY/ ' RECEPTORS. DRUG, metabolism/ SUPPORT. NON-U.S. G O V T / TERATOGENS/ TETRACHLORODIBENZODIOXIN, toxicity Hay A: Phenoxy herbicides, trichlorophenols, snd toft-tissue sarcomas (letter) Lancet 1982 May 29; 1(8233): 1240 DIOXINS, poisoning/ HERBICIDES, poisoning/ HUMAN/ "SARCOMA, chemically induced/ 'SOFT TISSUE NEOPLASMS, chemically induced/ TETRACHLORODIBENZODIOXIN. poisoning Hay A: Chlorinated dioxins and the environment [news] Nature 1981 Jan 29J89(379i):J5l-2 ANIMAL/ BIOTRANSFORMATION/ DIOXINS, toxicity/ ' ENVIRONMENTAL POLLUTANTS, toxicity/ HUMAN/ 'SOIL MICROBIOLOGY/ TERATOGENS/ TETRACHLORODIBENZODIOXIN. metabolism/ TETRACHLORODIBENZODIOXIN, toxicity Heider T: ElTects of 2.3,7,8-tctrachlorodibenzo-dioxin (TCDD) on early life stages of rainbow trout (Salmo gairdneri. Richardson). Toiicology 1981; 19(2): 101-12 ANIMAL/ CELLULAR INCLUSIONS/ DIOXINS, toxicity/ LIVER, pathology/ OVUM, drug effect/ PANCREAS, pathology/ SALMONIDAE, growth A development/ SUPPORT, NON-U.S G O V T/ TETRACHLORODIBENZODIOXIN, toxicity/ TROUT, growth A development Heacfc JM. New MA, Kedha R l. st alt 2,3.7,8-tetnchlorodibcnzo-p-dioxin: acute oral toxicity in hamsters. Toxicol Appl Pharmacol 1981 Jun 30; J9(2):403-7 ANIMAL/ BODY WEIGHT, drug elTects/ DIOXINS, toxicity/ HAMSTERS/ LETHAL DOSE 30/ MALE/ MESOCRICETUS/ TETRACHLORODIBENZODIOXIN. toxicity Haas P, Aaahauer J, Hollaader H: The possible formation of letrachlorodibenzo-p-dioxines in the production of chloranil. Ecotoxicol Environ Safety 1982 Aug; 6(4):336-4d ANIMAL/ CHLORANIL analysis/ CHLORANIL chemical synthesis/ CHLORANIL toxicity/ CHLOROPHENOLS analysis/ CHLOROPHENOLS chemical synthesis/ CHLOROPHENOLS toxicity/ DIOXINS, chemical synthesis/ FEMALE/ LETHAL DOSE 30/ MASS FRAGMENTOGRAPHY/ QUINONES chemical synthesis/ RATS/ RATS. INBRED STRAINS/ TETRACHLORODIBENZODIOXIN. analogs A derivatives/ TETRACHLORODIBENZODIOXIN. analysis/ TETRACHLORODIBENZODIOXIN. chemical synthesis Hlwffll RD, Conch D L Spain RS: Immunosuppression in mice induced by dioxin (TCDD) in feed. J Environ Pathol Toxicol 1980 Sep;4(2-3):401-23 ANIMAL/ ANTIBODIES, analysis/ BLOOD PROTEINS, analysis/ 'DIOXINS, toxicity/ FEM ALE/ HEMAGGLUTINATION, drug effects/ ' IMMUNOSUPPRESSIVE AGENTS/ MICE/ SALMONELLA TYPHIMUR1UM. immunology/ SUPPORT. NON-U.S. G O V T / SUPPORT. U.S. GOVT. P.H.S./ TETANUS TOXOID, immunology/ TETRACHLORODIBENZODIOXIN. toxicity Haides O Reviewers pan Agent Orange study plan (news) Science 1981 Dec 4;2I4(4323):1I07 DIOXINS, adverse elTects/ HUMAN/ MILITARY MEDICINE/ OCCUPATIONAL DOM2160182 I 183S2 DISEASES, chemically minced/ TETRACHLORODIBENZODIOXIN. advene effects/ UNITED STATES/ VIETNAM/ 2.4-DICHLOROPHENOXYACETIC ACID, advene effects/ 2.4J-TRICHLOROPHENOXYACETIC ACID, advene effects I h n a t EP J r The Acent Orange controversy--physician' dilemma. Wit Med J 1911 Mar M(J):16-I ABORTION, etiology/ ANIMAL/ DIAGNOSIS/ DIOXINS, advene effects/ FEMALE/ HUMAN/ LIVER DISEASES, diagnosis/ LIVER DISEASES, etiology/ LIVER NEOPLASMS, diagnosis/ LIVER NEOPLASMS, etiology/ MALE/ MICE/ PHYSICIANS. FAMILY/ PHYSICIANS. FAMILY, psychology/ RATS/ SARCOMA, diagnosis/ SARCOMA, etiology Haff J R Metes JA, Samed R, et ah Long-term haiatdt of polychlorinated dihrnrodioxins and polychlorinated dibenzofurans. Environ Health Pen pee l 1910 Jan; 36:221-40 (135 ref.) ABNORMALITIES. DRUG-INDUCED, etiology/ ACCIDENTS. OCCUPATIONAL/ ACNE, chemically induced/ ANIMAL/ ANTHROPOIDEA/ `BENZOFURANS, poisoning/ CHICKENS/ `DIOXINS, poisoning/ FEMALE/ GUINEA PIGS/ HUMAN/ LIVER DISEASES, chemically induced/ MALE/ MICE/ OCCUPATIONAL DISEASES, chemically induced/ RATS/ REVIEW/ STRUCTURE-ACTIVITY RELATIONSHIP/ SUPPORT, NON-U.S. G O V T / SUPPORT. U.S. GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN, poisoning I Idas G. Beflsd G, Bsllahnonn A, at alt Increased urinary D-tlucaric acid excretion by children living in an area polluted with tetrachlorodibenzoparadioxin (TCDD). Clia Chins Acta 1912 Apr 23:I20(3):273-I3 CHILD/ ` DIOXINS, toxicity/ ENVIRONMENTAL EXPOSURE/ FEMALE/ OLUCARIC ACID, urine/ HUMAN/ ITALY/ MALE/ MICROSOMES. U VER. drug effects/ MICROSOMES, LIVER, enzymology/ PROSPECTIVE STUDIES/ RETROSPECTIVE STUDIES/ SKIN DISEASES, chemically induced/ `SUGAR ACIDS, mine/ SUPPORT. NON-U.S. G OVT/. TETRACHLORODIBENZODIOXIN. toxicity J Jauaeu DJ, Hummel RA: Secretion of TCDD in milk end cream following the feeding of TCDD to Isolating dairy cows. Bull Environ f t w Toxicol 1912 Oct; 29(4):440-6 ANIMAL FEED / ANIMAL/ CATTLE/ DAIRY PRODUCTS/ D IET/ `DIOXINS, metabolism/ FEM ALE/ LACTATION/ MILK. TETRACHLORODIBENZODIOXIN. analysa/ TETRACHLORODIBENZODIOXIN. 2,4,3-T1UCHLOROPHENOXYACETIC ACID. tat&abtiam Janmn DJ, Getaendnaar ME, Hamatel RA, as ah Residue studies for (2,4,5-trichlorophenoxy)acetic add and 2,3,7,t-istrachiorodibcnxo-p-dioain in grata and rice. J Agric Food Chem 1913 Jan-FeW 1(1): IU-22 DIOXINS, analysts/ GRASSES, analysis/ PESTICID E RESIDUES, analysis/ ` RICE, analysis/ TETRACHLORODIBENZODIOXIN. analysts/ 2.4,5-TRICHLOROPHENOXYACETIC ACID, analysa Janas KG, Cala FM, Ssraanay CD: The rale of iron in the toxicity of L3.7.t-ietrachlorodibenxo-<p)-dioiin (TCDD). Toxicol Appi Pharmacol 1911 Oct,-il(l)-.74-M ANIMAL/ COMPARATIVE STUDY/ DIOXINS, toxicity/ IRON, deficiency/ ` IRON, pharmacodynamics/ ` LIVER, drug effecu/ LIVER, pathology/ M ALE/ MICE/ MICE INBRED C37BL/M ICE NUDE/ PORPHYRIA, chemically induced/ ` PORPHYRIA, prevention A control/ SKIN, drug effect!/ SUPPORT. NON-U.S. O O V T / `TETRACHLORODIBENZODIOXIN. toxicity/ THYMUS GLAND, drug effecu/ TIME FACTORS K Kellogg ST, Cksfterjst DK. Chakrnherty AM: Plumtd-iuixted molecular breeding: new technique for enhanced biodegradation of penistent toxic chemicals. Science 1911 Dec 4;214<4323):1 133-3 BACTERIA, genedca/ BACTERIA, metabolism/ BIOTRANSFORMATION/ CELL DIVISION/ KINETICS/ NUCLEIC ACID HYBRIDIZATION/ ` PLASMIDS/ SUPPORT. NON-U.S. G O V T / SUPPORT. U.S. GOVT, NON-P.H.S/ 2,4.3-TRICHLOROPHENOXYACETIC ACID, metabolism Kocfha RJ, Scka sts BA: Tosidty of 2. 3. 7, S-ietrachlorodibcaao-p-dioxin (TCDD). Drug Metab Rev 1912; 13<3):387--406 (69 ref.) ACNE chemically induced/ ACUTE DISEASE/ ANIMAL/ CARCINOGENS/ CHRONIC DISEASE/ `DIOXINS, losictly/ DISEASE MODELS. ANIMAL/ ENZYME INDUCTION, drug effects/ HUMAN/ IMMUNITY, drug effects/ MICE/ MUTAGENS/ REVIEW/ TETRACHLORODIBENZODIOXIN. toxicity Knlsaodla-Hadmaa B, E m K: Extimadoo of occupsuonal exposure to pheeoxy acids (2,4-D and 2,4,i- T ) Arch Toxicol (Suppll 19SO-.4.3U-21 AIR POLLUTANTS, tnniysis/ *AIR POLLUTANTS, OCCUPATIONAL, sealyds/ HUMAN/ 2,4-DICHLOROPHENOXYACETIC ACID, analysis/ 2,4-DICHLOROPHENOXYACETIC ACID, meuboitsm/ 2.4,5-TRICHLOROPHENOXYACETIC ACID. ljulym / 2,4.3-TRICHX-OROPHENOXYACETIC ACID, rnciiholran L Lacey P, Lacey VA: Agent orange: government responsibility for the military use o f phenosy herbicides. J Leg Med (Chicago) 1912 M arjfl): 137-71 CHEMICAL WARFARE AGENTS/ DIOXINS, adverse effects/ ` ETHICS/ HUMAN/ ` LEGISLATION/ MILITARY SCIENC E/ TETRACHLORODIBENZODIOXIN. advene effects/ UNITED STATES/ VIETNAM/ 2,4-DICHLOROPHENOXYACETIC ACID, advene effects/ 2,4.3-TRICHLOROPHENOXYACETIC ACID, advene effecu Lamb JC 4th. M oan JA, Marks TA, et ah Development and viability of offspring of male mice treated with chlorinated phenosy acids sad 2.3,7, g-tctrachlorodibenso-p-diosiii. 1 Toxicol Environ Health 1911 Nov-Dec:W5-6):>35-*4 ABNORMALITIES. DRUG-INDUCED/ ANIMAL/ `DIOXINS, toxicity/ FEMALE/ FETUS, drug effecu/ MALE/ MICE/ MICE INBRED CJ7BL/ PREGNANCY/ SPERMATOZOA, drug effects/ SUPPORT. U S. GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN. toxicity/ 2,4-DICHLOROPHENOXYACETIC ACID, toxicity/ 2.4,5-TRICHLOROPHENOXYACETIC ACID, toxicity LasU JC 4th. Marks TA, Oadan BC, et ah Male fertility, uster chromatid exchange, and gsnn cell toxicity following exposure to mixtures of chlorinated phenosy acids containing 2,3,7,1-tetiuchlorodibenxo-p-dioxin. 5 DO H2160183 J Toxicol Environ Health I9S1 Nov-Dcc:S(3~6):S2$-34 ANIMAL/ CROSSING OVER (GENETICS), drug effects/ DIOXINS, loxicity/ DOSE-RESPONSE RELATIONSHIP. DRUG/ FERTILITY, drag e/Tccu/ MALE/ MICE/ MICE. INBRED C37BL/ SISTER CHROMATID EXCHANGE, drag effect*/ SPERMATOZOA, drag effects/ SUPPORT. U S. GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN, tcxiciiy/ 2.4-DICHLOROPHENOXYACETIC ACID, loxicity/ 2.4.5-TRICHLOROPHSNOXYACET1C ACID, loxicity L iab JC 4th, Marks TA, McC w r i l EE, ct all Toxicity of chlorinated phenoxy acids in combination with 2.3.7.8*!eirachtornriibenzo-p-dio*)n in C57BL/6 malt mice. J Toxicol Environ Health 1981 Nov-Dec; 8(5-6):8IS-24 ANIMAL/ BODY WEIGHT, drug efTecls/ DIOXINS, toxicity/ EATING, drag effect*/ LIVER, drug effects/ MALE/ MICE/ M ICE INBRED C37BL/ ORGAN WEIGHT, drug effects/ SUPPORT. U.S. GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN. loxicity/ THYMUS GLAND, drag effect*/ 2.4-DICHLOROPHENOXYACETIC ACID, toxicity/ 2.4,3-TRICHLOROPHENOXYACETIC ACID, toxicity LaVeccfclo FA, Paahayaa HM, Singer W: Agent Orange and birth defects flctterj N Engl J Med 1983 Mar 24; 308(12):719-20 ABNORMALITIES, DRUG-INDUCED, etiology/ DIOXINS, advene effect!/ FATHERS/ HUMAN/ INFANT. NEWBORN/ MALE/ TETRACHLORODIBENZODIOXIN. advene effects/ VETERANS/ VIETNAM/ 2.4-DICHLOROPHENOXYACETIC ACID, advene effect!/ 2.4.5-TRICHLOROPHENOXYACETIC ACID, advene effects Lae IP, K: Induction of aryl hydrocarbon hydroxylase activity in the rat prostate glands by 2.J.7.8-teirach!orodibenzo-p-doxin. J Pharmacol Exp Ther 1980 Dcc:21S<3):60!-3 ANIM AL/ARYL HYDROCARBON HYDROXYLASES, biosynthesis/ CYCLOHEXIMIDE. pharmacodynamics/ CYTOCHROME P-450, analysis/ DACT1NOMYCIN. pharmacodynamics/ "DIOXINS, toxicity/ ENZYME INDUCTION/ MALE/ PROSTATE, drug effects/ PROSTATE, enzymology/ RATS/ TETRACHLORODIBENZODIOXIN. toxicity/ TIME FACTORS M McDaniel HG: The agent orange controversy [letter) Ala i Med Sci 1980 Jul-Ocl;l7(3-4)J5b-7 ABNORMALITIES. DRUG-INDUCED, etiology/ DEFOLIANTS. CHEMICAL, adverse effects/ DIOXINS, advene effects/ HERBICIDES, advene effects/ HUMAN/ NEOPLASMS, chemically induced/ 2.4-DICHLOROPHENOXYACETIC ACID, advene effects/ 2.4.5-TR1CHLOROPHENOXYACET1C ACID, adverse effects McNulty WP, Pamaraats L FsareU T: Chronic tosicity of 2.3.7.8-tctrachlorodibenzofuran for rhesus macaques. Food Cosmet Toxicol 1981 Fcb;19(l);57-b5 ANIMAL/ ' BENZOFURANS. loxicity/ ENVIRONMENTAL POLLUTANTS, tosicity/ GASTRIC MUCOSA, drag effects/ MACACA MULATTA/ MALE/ POLYCHLOROBIPHENYL COMPOUNDS, toxicity/ SEBACEOUS GLANDS, drag effects/ SUPPORT. U.S. GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN, tosicity/ THYMUS GLAND, drag effects Menace L, Coceie P, Creel T: Persistent tissue levels of TCDD in the mouse and their reduction is related to 6 prevention of toxicity. Drug Mctab Rev 1912; 13(31:423-4 ANIMAL/ CHARCOAL/ CHOLIC ACIDS, administration A dosage/ `DIOXINS, metabolism/ DISEASE MODELS. ANIMAL/ MICE/ MICE. INBRED C3H/ MICE. INDRED C57BL/ SUPPORT. NON-U.S. G O V T / `TETRACHLORODIBENZODIOXIN. metabolism/ TETRACHLORODIBENZODIOXIN. loikity/ TISSUE DISTRIBUTION M alum era F: Biochemical aspects of action mechanisms of 2.3.7.8-tctrachiorodibcnzo-p-dioain (TCDD) and related chemicals in animals. Pharmacol Ther 1982; 19(2): 195-209 (84 ref.) ANIMAL/ ARYL HYDROCARBON HYDROXYLASES, metaboliam/ CELL MEMBRANE, drug effects/ CELL MEMBRANE, metabolism/ ` DIOXINS, pharmacodynamics/ ENZYME INDUCTION, drug effects/ REVIEW/ SUPPORT. NON-U.S. G O V T / SUPPORT. U.S. GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN. pi--,'macodynamici/ TETRACHLORODIBENZODIOXIN, poisoning Matttaon DR. SUrondn L Ntgktiagala MS: Oocyte destruction by polycyclic aromatic hydrocarbons. Prog Qin Biol Res 1983;117:191-202 (46 ref) ANIMAL/ ARYL HYDROCARBON HYDROXYLASES, metabolism/ BENZOPYRENES, toxicity/ BIOTRANSFORMATION/ CHROMATOGRAPHY. HIOH PRESSURE LIQUID/ FEMALE/ HUMAN/ MICE/ OOCYTES, drag effects/ OVARIAN DISEASES. cbmnicaJly induced/ OVARY, metabolism/ `OVUM, drag effects/ POLYCYCLIC HYDROCARBONS, toxicity/ RATS/ REVIEW/ SPECIES SPECIFICITY/ TETRACHLORODIBENZODIOXIN. toxicity May G: Tetrachlorodibenzodiosin: a survey of subjects ten yean after exposure. Br 3 lad Med 1982 May; 39(2): 1ZS--35 ABORTION, chemically induced/ ACCIDENTS. OCCUPATIONAL/ ACNE, chemically induced/ ADULT/ ALKALINE PHOSPHATASE, inelyma/ BILIRUBIN, blood/ CHEMICAL INDUSTRY/ CHLOROPHENOLS, chemical syuthesia/ CHOLESTEROL, analysia/ ' DIOXINS, poisoning/ ENGLAND/ FEMALE/ GLUCARIC ACID, urine/ GLUTAMYL TRANSPEPTIDASE, snalysts/ HUMAN/ INFANT. NEWBORN/ MALE/ OCCUPATIONAL DISEASES, chemically induced/ PREGNANCY/ TETRACHLORODIBENZODIOXIN. poiioning/ TIME FACTORS/ TRIGLYCERIDES, analyaia Musas M, SaUksff U : Soft tissue sarcomas, phenoay herbicides, and chlorinated phenols [letter) Lancet 1981 Jun 20;](S234):1370 CASE REPORT/ DIOXINS, poisoning/ HUMAN/ MALE/ MIDDLE AOE/ NEURILEMMOMA, chemically induced/ OCCUPATIONAL DISEASES, chemically induced/ RETROPERITONEAL NEOPLASMS, chemically induced/ TETRACHLORODIBENZODIOXIN. poisoning/ 2.4.5-TRICHLOROPHENOXYACET1C ACID, poisoning Mnicaky MT: Chromosome aberrations and `agent orange' [letter) Med J Ausl 1980 Nov 13;2(IO):573-4 CHROMOSOME ABERRATIONS/ MILITARY MEDICINE/ TETRACHLORODIBENZODIOXIN. adverse effects/ VIETNAM/ 2.4-DICHLOROPHENOXYACETIC ACID, advene effects/ 2,4,5-TRICHLOROPHENOXYACETIC ACID, adverse effects N I 09 IZMOQ I ! 18394 DOH2 I 60 I 85 N Nm II. Bm R: Transfer of 2.3.7.H-icirachlorodibcnxo~p-dioxin (TCDO) lo the mums embryo sod fetus. Toiicology I91I;20(4):299-JOI ANIMAL/ CLEFT PALATE, chemically induced/ ' DIOXINS, metabolism/ ' EMBRYO, metabolism/ FEMALE/ ' FETUS, metabolism/ MATERNAL-FETAL EXCHANGE/ MICE/ PREGNANCY/ SUPPORT. NON-U.S. G O V T / 'TETRACIILORODIBENZODIOX1N, metabolism/ TETRACHLORODIOENZODIOXIN. tosicity Neal RA, Otsoa JR, Gasienlci TA. et ah The toxicokinetics of 2. 2. 7, S-lctrachlorodibcnzo-p-diosin in mammalian systems. Drug Melab Rev 19S2i 13f3>:333-S3 (37 ref.) ABSORPTION/ ADMINISTRATION. ORAL/ AIR POLLUTANTS. ENVIRONMENTAL, tosicity/ ANIMAL/ CHEMISTRY/ CYTOCHROME P-430, metabolism/ ` DIOXINS, tosicity/ DOSE-RESPONSE RELATIONSHIP. DRUG/ FEM ALE/ HUMAN/ INJECTIONS. 1NTRAPERITONEAL/ INTESTINAL ABSORPTION/ KINETICS/ MALE/ M1CROSOMES. LIVER, metabolism/ PREGNANCY/ REVIEW/ SKIN ABSORPTION/ SUPPORT. US. GOVT. NON-P.II.S./ TETRACHLORODIBENZODIOX1N. metabolism/ TETRACHLORODIBENZODIOXIN, tosicity/ TISSUE DISTRIBUTION O Olson JR. Hotscker MA, Neal RA: Tosicity of 2J.7.8-ititrachlorodibcnzo-p-<lioua in the golden Syrian hanuier. Toxicol App! Pharmacol 1980 Aug;55(l):67-78 ANIMAL/ BLOOD CHEMICAL ANALYSIS/ BODY WEIGHT/ DIOXINS. toxicity/ FEMALE/ HAMSTERS/ INTESTINES, pathology/ LETHAL DOSE 50/ LIVER* ulirastructure/ MALE/ MESOCRJCETUS/ ORGAN WEIGHT/ SUPPORT. U.S. GOVT, P.H.SV *TETRACHLORODIBENZODIOXIN. toxicity Orris P: Unjustified conclusion? (letter] JOM 1981 Jan; 23(I):7-8 DIOXINS, poisoning/ HUMAN/ NEOPLASMS, chemically induced/ OCCUPATIONAL DISEASES, chemically induced/ TETRACHLORODIBENZODIOXIN. poisoning p Psssl S, Nsxsaro-Porrn M, Bsnlfsrti L, et al: Analysis of lipids and dioxin in chloracne due to tcirachloro-2,J,7,l-p-dibenzodiosin. Br J Dermatol 1911 Aug: 103(2): 137-43 'ACNE, chemically induced/ ACNE, metabolism/ CHILD. PRESCHOOL/ CHROMATOGRAPHY. OAS/ ' DIOXINS, analysis/ FEM ALE/ HUMAN/ ' LIPIDS, analysis/ MALE/ TETRACHLORODIBENZODIOXIN. advene effects Pasderara-Ve^upkeal J, LaUs E, NJaacera M. et al: The development and prognosis of chronic intoxication by tetrachlordibeaio-p-diosin in men. Arch Environ Health 1911 Jsn-Feb:36(l):5-I1 ADULT/ CHRONIC DISEASE/ ' DIOXINS, poisoning/ HUMAN/ LIPIDS, metabolism/ LIVER DISEASES, chemicslly induced/ MALE/ MIDDLE A C E / NERVOUS SYSTEM DISEASES, chemically induced/ OCCUPATIONAL DISEASES, chemically induced/ PORPHYRINS, metabolism/ PROGNOSIS/ SKIN DISEASES, chemically induced/ TETRACHLORODIBENZODIOXIN. poisoning Poland A, Kantian J C 2.3.7,!-ietrachlorodibcnzo-p-dioain and related halogcnaicd atomatic hydrocarbons: examination of the mechanism of toxicity. Annu Rev Pharmacol Toxicol 1912;22:317-34 (221 ref.) ANIMAL/ ARYL HYDROCARBON HYDROXYLASES, bmaynlhciia/ ARYL HYDROCARBON HYDROXYLASES, genetics/ CARCINOGENS/ COMPARATIVE STUDY/ DIOXINS, tosicity/ FEM ALE/ HYDROCARBONS. HALOGENATED, tosicity/ MALE/ MICE/ MODELS. BIOLOOICAL/ NEOPLASMS. EXPERIMENTAL, chemicslly induced/ PREONANCY/ RATS/ RECEPTORS. DRUG, drug cflccu/ REVIEW/ SUPPORT. U.S. OOVT, P.H.S./ TETRACHLORODIBENZODIOXIN. analogs A derivatives/ TETRACHLORODIBENZODIOXIN. metabolism/ TETRACHLORODIBENZODIOXIN. loamiy Potter CL, Slpca IG, RanatO DH: Hypothyroxinemia and hypothermia in rats in response lo 2.3,7.1-tetrachlarodibenzo-p-diosin administration. Toxicol Appi Pharmacol 1913 Jun l3:69(l):l9-93 ANIMAL/ SLOOD GLUCOSE, metabolism/ DIOXINS, tosicity/ OLUCAOON. blood/ 'HYPOTHERMIA, chemically induced/ INSULIN, metabolism/ MALE/ RATS/ RATS. INBRED STRAINS/ SOMATOTROPIN RELEASE INHIBITING HORMONE, metabolism/ SUPPORT. U.S. GOVT, P.H S./ TETRACHLORODIBENZODIOXIN. tosioty/ THYROXINE, blood Puked SM, Sai l at . M, Ertl DC ft ah Hairless mice as models for chloracne: a study of cutaneous changes induced by topical application of established chloracacgeas. Toxicol Appi Pharmacol 1912 Jul; &4(3H92-303 ACNE, chemically induced/ ANIMAL/ ARYL HYDROCARBON HYDROXYLASES, metabolism/ DISEASE MODELS, ANIMAL/ ENZYME INDUCTION, drug effects/ HYDROCARBONS. CHLORINATED, tosicity/ MICE/ MICE, INBRED HRS/ NAPHTHALENES, tosicity/ POLYCHLOROBIPHENYL COMPOUNDS, tosicity/ SUPPORT. U.S. GO V T. NON-P.H S./ SUPPORT. U.S. GOVT. P.H.SV TETRACHLORODIBENZODIOXIN. tosicity R Rcaotti G. SHarris M, Blanen V, et el: Primi riauluti suU'ibonivna spontanea a d periodo Lug! 1976 - Giugno 1971 ncll'area di Seveso inquinau da TCOO. Ann Ostet Ginecol Med Pcrioat 1912 Jul-Aug; l03(4):249-33 (Ena. Abstr.) (Ital ABORTION; chemically induced/ `ABORTION, occurrence/ 'AIR POLLUTANTS, tosicity/ AIR POLLUTANTS, ENVIRONMENTAL. tosicity/ ' DIOXINS, toxicity/ ENGLISH ABSTRACT/ FEMALE/ HUMAN/ ITALY/ PREGNANCY/ TETRACHLORODIBENZODIOXIN. loaiciiy Bsmottl G, De VlrgUlla G, W arn V, et ah The morphology of early trophobiaai after dioxin poisoning in the Seveso area. Placenta 1911 Jan-Mar-JO):33-62 ABORTION, THERAPEUTIC/ CELLULAR INCLUSIONS. ultraunKture/ COMPARATIVE STUDY/ ' DIOXINS, poisoning/ ELECTRON PROBE MICROANALYSIS/ ENVIRONMENTAL POLLUTION/ FEM ALE/ HUMAN/ ITALY/ MICROSCOPY. ELECTRON/ PLACENTA, ulirastructure/ PREONANCY TRIMESTER. FIRST/ PREGNANCY/ TETRACHLORODIBENZODIOXIN. poisoning/ TROPHOBLAST. drug effects/ TROPHOBLAST, uitrastructure H IM -in V, Asp S, Herubarg S: Mortality of 2.4-dichloropluaosyacctic acid and 2,4.3-trichlorophenosyacetic acid herbicide applicaion in Finland: first repon of an ongoing prospective cohort study. Scind J Work Environ Hedtn 1912 Mar; l(l):37-42 ADULT/ FINLAND/ HUMAN/ MALE/ 7 18395 MIDDLE AGE/ MORTALITY/ NEOPLASMS, chemically induced/ 'NEOPLASMS, mortality/ OCCUPATIONAL DISEASES, chemically induced/ OCCUPATIONAL DISEASES, mortality/ OCCUPATIONS/ PROSPECTIVE STUDIES/ 2.4-DICHLOROPHENOXYACETIC ACID, advene effects/ 2,4.3-TRICHLOROPHENOXYACETIC ACID, advene effccu Hinder DF, Flecker JR: A radioimmunoassay to icreen for 2,4,-dichlorophenoayacctic acid and 2.4.3-tnchlOFophcnoxyicclic acid in lurface water. Bull Environ Contam Toxicol 1981 Mar:26(3):373-80 ANIMAL/ FRESH WATER, aaaiyxii/ RABBITS, immunology/ RADIOIMMUNOASSAY, methoda/ STAPHYLOCOCCAL PROTEIN A. immunology/ SUPPORT. NON-U.S. G O V T / WATER POLLUTANTS, analytic/ 'WATER POLLUTANTS. CHEMICAL, analytic/ 2.4-DICHLOROPHENOXYACETIC ACID, analytic/ 2.4.3-TRICHLOROPHENOXYACETIC ACID, analytic Rogen AM. Aadcnen M E Bach KG Mutagenicity of 2.3.7.8-tetrachlorodibcnzo-p-dioxin and pcrfluoro-n-decxnoic acid in L317SY mouae-lymphoma cells. Muut Res 1982 Dec; !03<6):445-9 ANIMAL/ CELL SURVIVAL, drug effects/ DECANOIC ACIDS, pharmacodynamics/ DECANOIC ACIDS, toxicity/ ` DIOXINS, pharmacodynamics/ ` LEUKEMIA L3178. physiopathology/ ` LEUKEMIA, EXPERIMENTAL, physiopathology/ MICE/ MUTAGENICITY TESTS/ `MUTAGENS/ MUTATION/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN, pharmacodynamics/ TETRACHLORODIBENZODIOXIN. toxicity s Safe S, Robertson LW, Safe L. el ah Halogenatcd biphenyls: molecular toxicology. Can J Physiol Pharmacol 1982 Jul; 60(7): 1037-64 ANIMAL/ ARYL HYDROCARBON HYDROXYLASES, biosynthesis/ ENZYME INDUCTION/ HUMAN/ MICE/ POLYCHLOROBIPHENYL COMPOUNDS, adverse effects/ POLYCHLOROBIPHENYL COMPOUNDS, tneubolism/ RATS/ RECEPTORS. DRUG, metabolism/ STRUCTURE-ACTIVITY RELATIONSHIP/ SUPPORT. NON-U S. G O V T / SUPPORT. U.S. GOVT. P.H.S./ TETRACHLORODIBENZODIOXIN. analogs A derivatives/ TETRACHLORODIBENZODIOXIN. adverse effects/ TETRACHLORODIBENZODIOXIN, meubolism Sand L, Bocri R, Remotti G, el ah Five years after Seveso [letter) Lancet 1982 Feb 6;l(8267):343-4 ABNORMALITIES. DRUG-INDUCED, etiology/ ACCIDENTS. OCCUPATIONAL/ CHILD/ ` DIOXINS, penciling/ FEM ALE/ HUMAN/ INFANT. NEWBORN/ ITALY/ MALE/ PREGNANCY/ TETRACHLORODIBENZODIOXIN. . poisoning Sanaa PR, Jacobs J: Thoracic soft-tissue sarcoma in Vietnam veterans exposed to Agent Orange Pctter| N Engl J Med 1982 May 6;30i<IS)-.ll09 ADULT/ CASE REPORT/ `DEFOLIANTS. CHEMICAL, poisoning/ ` DIOXINS, poisoning/ ` HERBICIDES, poisoning/ HUMAN/ MALE/ MIDDLE A G E / ` MILITARY MEDICINE/ ` SARCOMA, chemically induced/ ` SOFT TISSUE NEOPLASMS, chemically induced/ TETRACHLORODIBENZODIOXIN. poisoning/ `THORACIC NEOPLASMS, chemically induced/ UNITED STATES/ VIETNAM/ 2.4-DICHLOROPHENOXYACETIC ACID, poisoning/ 8 2,4,3-TRICHLOROPHENOXYACETIC ACID. poisoning Sckczak W, Pogoneiska H: Budowa chemiczna a toksykodynamicxne wlalciwoict pochodnych kwasdw Icnokiykarbokxylowych. Ci. IIL Przchicg wchlaniania do krwi orax pomiary wydalania z modem pochodnych kwasdw lenoksyoctowego i fenoktypropionowego. Roci Panstw Zakl Hig 198l-.3Z(S-6):419-26 (Eng. Abstr.) (Poll ABSORPTION/ ANIMAL/ CHEMISTRY/ ENGLISH ABSTRACT/ `GLYCOLATES. metabolism/ MALE/ MCPA. analogs A derivatives/ MCPA. mctaboliiin/ MCPA, toxicity/ PHENOXYACETATES. metabolism/ PHENOXYACETATES, toxicity/ PROPIONATES, metabolisin/ PROPIONATES, toxicity/ RATS/ STRUCTURE-ACTIVITY RELATIONSHIP/ TIME FACTORS/ 2.4- DICHLOROPHENOXYACETIC ACID. metabolism/ 2.4- DICHLOROPHENOXYACETIC ACID, toxicity/ 2.4.3- TRICHLOROPHENOXYACETIC ACID, meubolism/ 2.4.3- TRICHLOROPHENOXYACEFIC ACID, toxicity Siager R, Motea M. Valdnkas J, ct ah Nerve conduction velocity studies of workers employed in the manufacture of phenoxy herbicides. Environ Ret 1982 Dec; 29(21:297-311 ADULT/ AGE FACTORS/ ALCOHOL DRINKING/ ENVIRONMENTAL EXPOSURE/ HUMAN/ MEDIAN NERVE, physiology/ ` NEURAL CONDUCTION, drug effects/ `OCCUPATIONAL MEDICINE/ SUPPORT. U.S. GOVT. P.H.SV SURAL NERVE phytiology/ 2,4-DICHLOROPrIENOXYACETIC ACID, adverse effects/ 2.4,3-TRICHLOROPHENOXYACETIC ACID, adverse effects Smith AG. Frauds JE, Kay SJ, et ah Hepatic toxicity and uroporphyrinogen decarboxylase activity following a single dose of 2.3.7.8-ietrachlorodibenxo-p-dioxin to mice. Biochem Pharmacol 1981 Oct;30(2Q):2l23-30 ANIMAL/ `CARBOXY-LYASES. antagonists A inhibitors/ ` DIOXINS, toxicity/ DOSE-RESPONSE RELATIONSHIP, DRUG/ FEMALE/ KINETICS/ ` LIVER. drug effects/ LIVER, eruymology/ MALE/ MICE/ MICE. INBRED C37BL/ MICE. INBRED DBA/ PORPHYRINS, meubolism/ SEX FACTORS/ TETRACHLORODIBENZODIOXIN. toxicity/ UROPORPHYRINOGEN DECARBOXYLASE, aaugoaisu A inhibitors Stanley T: Vietnam veterans [letter) Aust NZ i Psychiatry 1982 Sep; 16(3): 196-7 DIOXINS, advene effects/ HUMAN/ MALE/ ORGANIC MENTAL DISORDERS. SUBSTANCE-INDUCED, psychology/ TETRACHLORODIBENZODIOXIN. adverse effects/ 'VETERANS, psychology/ VIETNAM/ 2.4-DICHLOROPHENOXYACETIC ACID, advene effects/ 2.4.3-TRICHL0R0PHEN03CYACET1C ACID, adverse effecu Surens KM: Agent Orange toxicity: a quantitative perspective. Hum Toxicol 1981:1 (1):31--9 ABNORMALITIES. DRUG-INDUCED, etiology/ ANIMAL/ BENZOFURANS, toxicity/ DIOXINS, toxicity/ ` ENVIRONMENTAL POLLUTANTS, toxicity/ FEMALE/ FOOD CONTAMINATION/ `HERBICIDES, toxicity/ HUMAN/ M ALE/ PREGNANCY/ SOIL POLLUTANTS, toxicity/ TETRACHLORODIBENZODIOXIN. toxicity/ VIETNAM/ 2.4-DICHLOROPHENOXYACETIC ACID, toxicity/ 2.4.3-TRICHLOROPHENOXYACETIC ACID, toxicity Stohs SJ. H asau MQ. Marray WJ; Lipid peroxidation as a possible cause of TCDD toxicity. Biochem Biophys Res Oirnmun 1983 Mar 29; lll(3):834-9 OOW2I60I86 28I09IZMOQ ANIMAL/ ` DIOXINS, toxicity/ FEMALE/ ` LIPID PEROXIDES, metabolism/ ` MICROSOMES. LIVER. d n i| effects/ MICROSOMES. LIVER, metabolism/ OXIDATION-REDUCTION/ RATS/ RATS. INBRED STRAINS/ `TETRACHLORODIBENZODIOXIN. toxicity Strik JJ: Detection of chemical-induced porphyria in man. Possibilities in biomoniioring of exposure to chemicals. Dev Toxicol Environ Sci 1980:8:337-43 AIR POLLUTANTS, toxicity/ ` AIR POLLUTANTS. ENVIRONMENTAL, toxicity/ CHILD/ CHILD. PRESCHOOL/ COMPARATIVE STUDY/ ENVIRONMENTAL EXPOSURE/ FEMALE/ HUMAN/ ` LIVER DISEASES, chemically induced/ MALE/ ` PORPHYRIA, chemically induced/ PORPHYRINS, urine/ TETRACHLORODIBENZODIOXIN. toxicity Strik JJ. de Wh JM: Health aspects of rabbits in a low-TCDD contaminated area. Int J Biochcm 1980; 12(3-41:999-1001 ANIMAL/ BODY WEIGHT, drug effects/ CREATININE, meubolism/ CYTOCHROMES, metabolism/ ` DIOXINS, adverse effects/ FEM ALE/ GLUCARIC ACID, metabolism/ KIDNEY, drug effects/ 'KIDNEY, pathology/ LIVER GLYCOGEN, metabolism/ LIVER, drug effects/ LIVER, meubolism/ `LIVER, pathology/ MALE/ ORGAN WEIGHT, drug effects/ PORPHYRINS, metabolism/ RABBITS/ SOIL POLLUTANTS, sdverse effects/ 7 ETRACHLORODIBENZODIOXIN, adverse effccu Strik JJ, Jaaasen MM, Coiomb! AM: The incidence of chronic hepatic porphyria in an Italian family. Int J Biochcm l980;l2(3-4):879-g| CHRONIC DISEASE/ FEMALE/ HUMAN/ ITALY/ LIVER DISEASES, chemically induced/ ` LIVER DISEASES, familial A genetic/ MALE/ PEDIGREE/ PORPHYRIA, chemically induced/ ` PORPHYRIA, familial A genetic/ SKIN DISEASES, chemically induced/ ` SKIN DISEASES, familial A genetic/ TETRACHLORODIBENZODIOXIN. adverse effects Sniff LL, Gaaicwicx TA, Dnaa GD, at a t Characterization of ihe hyperlipidemia in guinea p ip induced by 2.3.7.8-tetrachiorodibenzo-p-dioxm. Toxicol Appl Pharmacol 1981 JuL39(3):489-99 ADIPOSE TISSUE metabolism/ ANIMAL/ DIOXINS, toxicity/ FATTY ACIDS, meubolism/ GUINEA PIG5/ ` HYPERLIPIDEMIA, chemically induced/ LIPIDS, blood/ LIPOPROTEINS, blood/ M ALE/ SUPPORT. U.S. GOVT. P H.S./ TETRACHLORODIBENZODIOXIN. toxicity T Tcdcscfci LG: Dioxin. A case in point. Am I Forensic Med Pathol 1980 Jun;l(2):|43-8 ABNORMALITIES, DRUG-INDUCED/ ABORTION, chemically induced/ ANIMAL/ CATS/ ` DEFOLIANTS. CHEMICAL, sdverse effccu/ ` DIOXINS, adverse effects/ DOGS/ FEM ALE/ `HERBICIDES, adverse effccu/ HORSE DISEASES, chemically induced/ HORSES/ HUMAN/ INFANT. NEWBORN/ LIVER DISEASES, chemically induced/ M A LE/ MENTAL DISORDERS, chemically induced/ M ICE/ MISSOURI/ PREGNANCY/ RATS/ ` SKIN DISEASES, chemically induced/ UNITED STATES/ VIETNAM T em dai B: Considerslions on the epidemiology of the Severn accident (letter) Toxicol Eur Res 1981 Sep; 3(51:262-3 ACCIDENTS/ c h e m ic a l in d u s t r y / ` DIOXINS, poisoning/ HUMAN/ ITALY/ `TETRACHLORODIBENZODIOXIN. poisoning Thlaaa AM, Freatxel-Bcyme R, Link R: Mortality study of persons exposed to dioxin in a Inchlorophenol-process accident that occurred in the BASF AG on November 17. 1933. Am J lnd Med 1982;3(2):l79-89 ACCIDENTS. OCCUPATIONAL/ ADOLESCENCE/ ADULT/ AGED/ COLONIC NEOPLASMS, chemically induced/ `DIOXINS, advene effccu/ FOLLOW-UP STUDIES/ HUMAN/ LUNO NEOPLASMS, chemically induced/ MALE/ MIDDLE AO E/ ` NEOPLASMS, chemically induced/ NEOPLASMS, m orulity/ OCCUPATIONAL DERMATITIS. chemically induced/ STOMACH NEOPLASMS, chemically induced/ TETRACHLORODIBENZODIOXIN. advene effccu Thomas JA: Target organ toxicity: endocrine system. Introductory remarks: the testis. Environ Health Penned 1981 Apr,38:3-4 ANDROGENS, metabolism/ ANIMAL/ BIOTRANSFORMATION/ DDT. metabolism/ DDT, pharmacodynamics/ ` GENITALIA. MALE, metabolism/ HUMAN/ MICE/ OROAN SPECIFICITY/ PROSTATE, drug effccu/ SEVIN, metabolism/ `TESTIS, metabolism/ TETRACHLORODIBENZODIOXIN. meubolism/ 2.4-DICHLOROPHENOXYACETIC ACID, meubolism/ 2.4.3-TRICHLOROPHENOXYACETIC ACID, metabolism H e ib e rg T, Ablbsrg UGt Effecu of dietary vitamin A (retinol) on the reduction of hepatic retinol Stonge caused by 2. 3. 7, 8-tcirachlorodibenzo-p-dioiin. Dev Toxicol Environ Sci 1980;8:321-1 ANIMAL/ ` DIOXINS, toxicity/ ` LIVER, drug effecu/ LIVER, meubolism/ MALE/ RATS/ RATS. INBRED STRAINS/ SUPPORT. NON-U S. G O V T / TETRACHLORODIBENZODIOXIN, anugoniste k inhibitors/ TETRACHLORODIBENZODIOXIN. tosidty/ UDP GLUCURONOSYLTRANSFERASE meubolism/ VITAMIN A, metabolism/ `VITAMIN A. pharmacodynamics Temmal G, Bsaarrnrd A: Epidemiological problems with TCDD (a critical view). Drug Mctab Rev 1982: l3(3):447-49 ACCIDENTS. OCCUPATIONAL/ 'DIOXINS, poisoning/ ` ENVIRONMENTAL POLLUTANTS, poisoning/ EPIDEMIOLOGY/ HUMAN/ ITALY/ PUBLIC HEALTH/ SUPPORT. NON-U.S. G O V T / `TETRACHLORODIBENZODIOXIN. poisoning Townsend OI: The use of dioxin isomer group ratios to identify sources sad define background levels of dioxins in the environment. J Environ Sci Health [B] 1980: I5(3):37l-609 ` DIOXINS, analysis/ ` ENVIRONMENTAL POLLUTANTS, analysis/ ISOMERISM/ k i n e t i c s / Ma t h e m a t i c s / m o d e l s , THEORETICAL/ OXIDATION-REDUCTION/ STRUCTURE-ACTIVITY RELATIONSHIP/ TETRACHLORODIBENZODIOXIN, analysis Townsend JC, Bsffair KM, Van Peseta PP, at ah Survey of reproductive evenu of wives of employees exposed to chlorinated dioxins. Am J Epidemiol 1982 May: 113(3):693-713 ABNORMALITIES. DRUG-INDUCED/ ABORTION, chemically induced/ ADOLESCENCE/ ADULT/ COMPARATIVE STUDY/ ` DIOXINS, poisonm|/ ENVIRONMENTAL EXPOSURE/ FATHERS/ FEM ALE/ FETAL DEATH, chemically induced/ HUMAN/ MALE/ MICHIGAN/ PREGNANCY/ QUESTIONNAIRES/ REPRODUCTION, drug effecu/ TETRACHLORODIBENZODIOXIN, poisoning Tachmnne-DnpleBde H: The experimental approach to teratogenicity. Ecotonccl Environ Safety 1980 Dec; 4(4):422-33 ANIMAL/ EMBRYO, drug effccu/ ENVIRONMENTAL POLLUTANTS, toxicity/ FEM ALE/ FETUS, drag effects/ PREGNANCY/ RESEARCH DESIGN/ 9 18337 88 I 09 IZKOQ SPECIES SPECIFICITY/ TERATOOENS, toxicity/ TETRACHLOROOIBENZODIOX1N, loiiciiy/ THALIDOMIDE, toxidty/ TOXICOLOGY Ter--e JN, Colli-- DNi Liver morphology in guinea pigs administered eiiher pyrolysis products of polychlorinated biphenyl transformer fluid or 2.3.7.(-ieirachlorodibcnzo-p-dioxia. Toxicol Appl Pharmacol 1913 M ir 13:67(3)417-39 ANIhiAL/ DIOXINS, toxicity/ FEM ALE/ GUINEA PIGS/ HEAT/ LIVER, drag effect1/ LIVER, pathology/ LIVER, ultraatnocture/ MALE/ MICROSCOPY. ELECTRON/ POLYCHLOROBIPHENYL COMPOUNDS, toxicity/ TETRACHLORODIBENZODIOXIN. toxicity V r-- Logics MJ. Gupta BN. MC--ntfl EE, it ah The influence of malnutrition on the toxicity of 1.3.7,S-ietrachlorodibeiuo-p-dioiin (TCDD) in rata. Toxicology I9SUI(1):77-U ANIMAL/ BODY W EIGHT/ CALORIC INTAKE/ D IET/ DIETARY PROTEINS, pharmacodynamics/ DIOXINS, toxicity/ EATING/ FEMALE/ NUTRITION DISORDERS, phyiiopatholofy/ ORGAN WEIGHT/ PROTEIN DEFICIENCY, physiopaihoiogy/ RATS/ RATS. INBRED F344/ 'TETRACHLORODIBENZODIOXIN, toxicity VeerM A. Slroni M. Caacgroti MA, ct ok Immunoxuppretiive effects of 2.3.7,(-tetnch)oradibenxo-p-dioxm in uraina of mice with different tuaceptibility to induction of aryl hydrocatboo hydroxylase. Toxicol Appl Pharmacol 19(3 May;68(J):434--41 ANIMAL/ ANTIBODY FORMATION, drag eflecta/ ARYL HYDROCARBON HYDROXYLASES, bioaynthexo/ CROSSES. GENETIC/ DIOXINS, toxicity/ ENZYME INDUCTION, drag eflecta/ IMMUNOSUPPRESSION/ MALE/ ' MICE/ MICE. INBRED STRAINS/ SPECIES SPECIFICITY/ SUPPORT. NON-U.S- OOVT7 TETRACHLORODIBENZODIOXIN. toxicity V-- JG, V-- Leenven FX, 6c Jong P: Acaegenic activity of 3-meihyicholanthrcne and bcnxo(a]pyrene, and a comparative xtudy with 2.3.7,8-tctncblorodibenzo-p-dioxin in the rabbit and hairteu mouse Toxicology 19S2;23(2-3):187-96 ACNE, chemically induced/ ANIMAL/ BENZOPYRENES. loxicUy/ COMPARATIVE STUDY/ DIOXINS, toxicity/ METHYLCHOLANTHRENE. toxicity/ MICE/ MICE INBRED HRS/ RABBITS/ SKIN, pathology/ TETRACHLORODIBENZODIOXIN. toxidty w Weber H, Pniger H, Scbdrier G Fate of 2.3.7.(-ieirachlorodibeiixo-p-dioxiiii metabolilea from dogs in rata. Xcnobioticu 19(2 Jtm;l2(6)d33-7 ANIMAL/ BILE tnetabolixm/ DIOXINS, urine/ DOGS/ FECES. a a a lW FEMALE/ RATS/ SPECIES SPECIFICITY/ TETRACHLORODIBENZODIOXIN. toxicity/ TETRACHLORODIBENZODIOXIN. urine Weber H, Pdgw H, flrhluWar G Acuta oral toxidty of TCDD-metabolites m anile guinea pigs. Toxicol Lett 19(2 Nov;I4(I-2):117-22 ANIMAL/ BILE metabolism/ BODY WEIGHT. dra( eflecta/ DIOXINS, toxidty/ GUINEA PIG S/ L IV E R metabolism/ MALE/ METABOLIC DETOXICATION. DRUG/ TETRACHLORODIBENZODIOXIN. metabolism/ TETRACHLORODIBENZODIOXIN. toxidty Y Yaag KH, Y-- BS, Choc SY: Eflecta of haiogenated to dibenao-p-dioxinx on plasma disappearance and biliary excretion of ouabain in rata. Toxrcol Lett 1913 Feb: 13<2-3):239-64 ANIMAL/ BILE tnetabolixm/ BODY WEIGHT, drag eflecta/ DIOXINS, toxicity/ LIVER, drag eflecta/ MALE/ OUABAIN, metaholiam/ RATS/ RATS. INBRED STRAINS/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN, analogi A derivatives/ TETRACHLORODIBENZODIOXIN. toxicity Yang KH, CVst EJ, Ch-- SY: Cytotoxicity of 2.3.7.1-tctruchlocodibcnxo-p-dioxia on primary cultures of adult rat hepatocytea. Arch Environ Contain Toxicol 19(3 Mar; 12(2): 183-8 ANIMAL/ CELLS. CULTURED/ DIOXINS, toxicity/ ENZYME INDUCTION, drag eflecta/ LIVER, drag eflecta/ LIVER metabolism/ MALE/ RATS/ RATS. INBRED STRAINS/ SUPPORT. NON-U.S. G O V T / TETRACHLORODIBENZODIOXIN. toxidty ANONYMOUS Aar Fam Physician Agent orange [editorial] Am Fam Physician 19(2 Apr; 23(4)91-2 DIOXINS, toxicity/ HUMAN/ TETRACHLORODIBENZODIOXIN. toxidty/ 2.4-DICHLOROPHENOXYACETIC ACID, toxicity/ 2.4.J-TRICHLOROPHENOXYACET1C ACID, toxicity Am J Form ic Med Pathol Agent Orange [letter] Am 3 Forensic Med Pathol 19(3 Jun;4(2): 190-2 ABORTION, etiology/ DIOXINS, poisoning/ FEM ALE/ HUMAN/ MALE/ MILITARY MEDICINE/ PREGNANCY/ TETRACHLORODIBENZODIOXIN, poisoning/ VIETNAM/ WAR/ 2.4-DICHLOROPHENOXYACETIC ACID. Ld^rftlCHLOROPHENOXYACETIC ACID, poMOoiag JAMA Health eflecta of Agent Orange and dioxin contaminant!. Council 00 scientific aflatra. JAMA 19(2 Oct 13; 24(05>.l(9S-7 ACCIDENTS. OCCUPATIONAL/ ACNE chemically induced.' AGRICULTURAL WORKERS' DISEASES, chemically induced/ AMERICAN MEDICAL ASSOCIATION/ ANIMAL/ DEFOLIANTS. CHEMICAL. advene eflecta/ DEFOLIANTS. CHEMICAL, classification/ DIOXINS, advenu eflecta/ FEM ALE/ HERBICIDES, advene eflecta/ HUMAN/ MALE/ PREGNANCY/ 'TETRACHLORODIBENZODIOXIN, advene eflecta/ TETRACHLORODIBENZODIOXIN. classification/ UNITED STATES/ VIETNAM/ WAR/ 2.4-DICHLOROPHENOXYACETIC ACID, advene eflecta/ 2.4-DICHLOROPHENOXYACETIC ACID, clmification/ *2,4.5-TRICHLOROPHENOXYACETlC ACID, advene effects/ 2,4,5-TRICHLOROPHENOXYACETIC ACID, cUuificstk Scvcao aAct five yean {editorial] Lancet 1981 Oct J; 9 18398 BOW 2160181 2<U49):73l-2 ACCIDENTS, OCCUPATIONAL/ ACNE, chemically induced/ ACNE hniory/ 'DIOXINS, poiaonin*/ HISTORICAL ARTICLE/ HISTORY OF MEDICINE lOTH C E N T / HUMAN/ ITALY/ TETRACHLORODIBENZODIOXIN. potaooing I D . f . SOVSnSfEHT n tn R IM e OTTICI I 1 M 3 - 4 ] I - I ) 2 : ] 3 \ II 18389 MN71891M 240 74 III I AN* y f, 2 , 1V7: IIIUMINGII.VM .UXIDH.N f IIOSP1 M l. Sia, V n h regard to sm ir rr|*irt the threat io ih r h u m mgham A co Jrn t |(Hpilai vM aish IV, p. 64-4' may I .* iJu i ih r Hirmingham AcCiJctU Hospital i ' m*i a~vcutie ol v ^ d IriKY, U n i c rrilir ol adequate u r c seen jg a i'ivi . I*j. kgr* umJ *i| tpjsdiiiig i>.,i,kni ihnngh*ui the icsi ! me country. I he AcetJem Hospital iUwl]*cU von,-|n* %vvh .v imihuliHi|4inry iraiiiwurk. mtcgraicd rrhal'ihjai.on, and connnuuy til care m io a working w iiem in the I'Min. Ihirty years later many ot us arc Mill struggling with such concepts, though ic p iim and inquiries u ir daily that the'* jrc Im\ k rc* i(iiu-meiiu ol any mts-icc in any disci|4m e ami that the lack id them is m p u w N r lor (fagrdicl Sj'iM h-jllv the AbfcHtrui H ospinl liKklnl the j'r**Mrnis id <jm *-1w departm ents, the tm p n te n p an em , separatum *4 die v i c r d v ill I ttm the wiwthlol, multiple vuigcims neat mg multiple m iuncv the m iurrd drunk, and real training u * . u e J u a l tall in a prag m a!* , largely l u t t r n l u l m anner As lor dispersal, the AcCitknt'4fc*cf'itiil has Jsoqi ilnpnii i / j ns Jo c io n hie year; all have learned that iliese vum rpts ami problem can be laced, Hu! *J<pcf*ald the aw e **4*tin t A s k ing rampie *>f team work will he J'fesigady* m >ij4t"*i.*c Hirmingham, nor miiy hr acodcm surger* W f >4 us who are trying lu in.ike the uuegraiMm <il eare uwue th u a a concept m whatever discipline. v(k I l* drti. v.wv a.m.i it rc i, i i us :tu \ j i i: k L O N G -TH K M K FK K C TS O F O IO X IN K M 'O S l'K P . hi*. In July, l **(. a reacute n a hctnwal plant oiustde Milan o p tn J e J rvlrav.ng a c h ild ui tostcA uocs u h u h cuU-J *cr die Unrn ol Sc y c x i. 1 fa( ! d i .u vNii.i:nrd 2, S, *, 1 u`t(akhltfis.Uh*tv4t'4f4Jioiin J u t u n ', *itc 4 the compsHinds known. W ithin Ju)fc *4 die .icihU'M h*j.ulrr.h >( small am m ah h a j died and many nt the iiM n'i m nabiiant* had developed chlofJcne. v*ne vd the lo s serums ir:anilcs(utio:;> 4 du*\*n e ip n u r c IhuKin I* rarth refatugenic and letotosic in a n u n jli.1 I he chemical also has a wide range ol toucitv in m an, including hepatic, renal, and neurological damage and even death.4 1he mg-icrm effect* ti d to u n r ip H u r r arc virtually unknown In 1^"1 we treated a vaung p .ite n t with dioam pmsumng and ner isicr and m other whs were also eapsned in dioam hut io a lo se r tite n t. ^ licr the beveso caiatirnphc wc were akcd lollow'up uur p3t;cnt. arvd we report our ltnd:ng\ in the h*jK that thev til i n t t m i the physicians and health j i i i h m n n re tfsinsthle luf the vare ot !he jmpulaimn ol Scvcio. A ft-year-uld g:rl pescmed in August. r O . <*uh a brie; his tory ul nuacblcedi headaches, diarrtura. Uk'd in her ur:nv, anJ pam iul nuciurilnNi. Her past medical record a a unre markable. hhe Used m a hone*breeding farm m eastern Mis toon. In May, 19?K an indoor arena on the tarm had hern ipravesJ i(h waste ml as a duu-connvJ measure. .Shiirilv altcrw ania hundreds ut turds and several d\*gs and cats having access to the arena died. Fourteen horses manifested a vaneis i*r symptoms including weight Urn, daggering gau, polvdipsia. oral uiccraiMnt, alopecia, conjunctivitis, diarrhoea, and hxm u tu n a . Several horses died, and w*vre louiui at necropsy io base avoirs, o rrh o siv JRI submucosal N m el hxm orrhage. 1he paitent had ptaved on the arena dailv (rum the das ot the srraving unit! he onset ol her svtnpi.*m\. Iter sister .age I 111 years* and m otner jlso Ircquenud the aiena bui ih o r ssitiptoms were Umued u* a`>Jommal pat:., diarrhoea, and m icrmutem headaches On aiimissisn ih r palieni had 'm sjerair supra(>ulus i^p.irr ; V . | | . 1 IV U.,*M M (l la. ti ! . II. -s , VI.,.Aril. | . : >1 JfcS. 1.1 Cxi A.,!.-. K I I I ** Sr . :* I..'.** ness uftii^lsMs ii'sraK 'J I 'rmeui and m m u'ious rrd ii^ While M**sl \vlts m miouNon*!.. n i-iuiuim n. A urm e cullurr was negative. V riu n rlrviriiKtev, H*J urea nitrogen, o t a u :ime. and User l||^l^**n n*s!s were all ro irn al A suultng C)su> /,am dutl a mvh sn*ra,ird tedcuuioiis MaJdcr Pul n. vvl*Mi4*ut *d*Mi;ii lion i >n iiiirj.nitM . |*vvl*grain ihe ki.lneu ind ii||er ir.uis ap|v.*rvij ;n>Mii.d. es,cpt |.ir a calyseal discr. Mvidmii m die nyht u a j kidney Ihe .nly .her ahnurinantv w:s a sssiulu inunm ir ihniiglii in he tun o u in al. I lie U'ltip'fal reU;iMtship K'twecn the p aiicm 't svmptutm ;md the um*spl.i;n** t Uss |.rm anuitalv raised ihe pivsibditv < a tiNiniN.n imi-. .n:i*ii. I*i |li.wmg ituh ^.aito n io ihe ( `enter l**r Ihv<as^(%iqir*t, AtUo*a. (ic o rc u . , u vwl..gy search w* us.hyflel)jgi eds^h irseiitrd >n ilse uU'(i:ii,,a*iun ul diusm as 4 4<ii iim id liar sfkCuynl ihJ r v u lue.' flfrm m Vssqiffrwn s re v d s c i m H days and did noi rsitxiiwiwrMi and pnw innuru were ahscni afier 1 week " ` " f p c g f a i ) months laier appeared nurrr.al, py ak tbts time deim -nsirated num erout hm? areas m (he Madder, cspcually in the tng;m e. 5 ) years alter the iJouio n p * iu r e , *ar rc uiv-sitgjicd iIk p.tiietu wuh (he m iurmed s-uscm <1 herself and her nwwhcr In ih r ' ear intrrsal i*r patieni had grown I.unulls, ami Kt(i li<i hcighi -n d acighi were above ihe 75ih v ru 'n iiiei Hivvital cs.utimaiiMii. m.lu i.ng a detailed n ru ru (civil esaitmvaium, wav iiu n iu i lU*r u n n r was prinetn Irre and ihe u n n r sediment was inrinal A i'.ci^ r< < n was norm! I he iriravctii-us p\*d*itr.m J*;**.i rsu.*uil norm al mterval gf. wth *4 the kidney the mly ahn*?ma:i:y heu.g the 4iv<r- cuioin m ihe . a l..c a l ivvicir. ol she right kulnev. HIo*d u ro - /mr*<ren. seiurvt sn a n m n e . -ar,d ;nuhn clearance 'U l m lm ia 'I 7^ in4 surface area were all norm al. I nr lurciior.al heart ;i:urmur was vidl present bn: ihe ciei.:rocarJiograin >x, ni*emal and ihe cardiac r**vpuse u e\crs:s< under ili* dar-.li-vd u<tc)tJ:iinv w.*v im rmat 1 u*m ih.s u*v| u wav til.'a- jicd ihal (Ik* p^iicn* s %*'* capaorv *,<i i c A m 4 .141 alsve as<*.*gr. I tver I4.*.1m*o ir-.ts. including iransarm na-~., Arc >u*rmal. as was th.- urinary TSsrcu*n ol urnporphyuns and v; r.*p,r|*nvrins. ) l.yr ad lur.tn-n a a* normal. 1 he vanw* viu.lirv were d**ne the paiienr s ivier. a n j ihe rvwills were normal, as wav an evaluation ol the patient's ItlxlllCf. I here are a num ber vr Jih u n in es *0 com paring ihe situation > in Neseso us the corvlitmns on the M;">ourt tur:n. People living , t in the two areas were espoved to Julcrem concentration* ot u diosin l-ir variable peruiJt ul time. In ihe paneni presented * here the ttm cir. nt the ctonpuund appeared relatively carlv and was scIH im iifj. However, our raperienee dcmonsiratci it.i people cifsivrJ io di**s*n can recover comp<t<lv wuh na apparent eqsieix trims the tu sia U rem ains in be dcicrmineJ w briber the rs|* * u rc * diosin m these children will result >BW.. jln*iruial prrgiuncies *r adccl iheir uflspr.ng. Ihv *rjJv 4 o.pr*tird by gr^ntKHMNi.iA ir.*m \ao o eal lion-'-r- uur Mraiti,. N *.i Vi. Imi>|i>.Ii I-) HiKritl a I ,... Cfk a >4 VU.*i,i|. I SS it rM sas it. Ill si. i.*ir, \\ 11 1 1 s v* T. .Shi ami i,^f; M; nvi 1 At. K u i |{; At s> M. Ruwstts j; *76 IN C O N T IN E N T WOMEN ,r' ' nse*. As a gsnj-cM opil doing urudsnam ics, I hcarid,/. ^ a::.t wuh voiir eiiiiorul ul M arch J p. i 21 rn is. We are now beginning u* understand m conim ence ol u rio ^ (t hut 111 1 netand and Wa*ev alequaic la o tu iei tor in v c m |a u ( ;hi% comimm and Jistrrtsm g condiiiun are -.Carer, hes* ccn:n ,a n d* proper w tubfonoiis pressure, ll:w vtuJics at hlling *t , loidinp vvsiourcti.rograpnv recorded vijco*pe. lh c eq a, , . . 1 , II,of < 1*1 1 wp u w y n :r i w.: w ^ v ^ ^ ^ . r *,t* .k. i OM2 1GO 33 ENb II I I H I I C ^l \ \ ti o co vH i i i i Reprinted from British Journal o f Industriai Medicine 1983;40:314-324 Copyright 1983 British Journal o f Industriai Medicine AU rights o f reproduction o f this reprint are reserved in ail countries o f the world 249 <t\I Q0 0 0 9 l 3K00 Medical and morbidity surveillance findings among employees potentially exposed to TCDD G G BOND, M G OTT, F E BRENNER, AND R R COOK British Medical Association, Tavistock Square, London WC1H 9JR 18402 0 1 0 0 9 1 ZM0Q British Journal o f Industrial Medicine 1983;40:318-324 Medical and morbidity surveillance findings among employees potentially exposed to TCDD G G BOND,' M G O TT,1F E BRENNER,1 AND R R COOK' From US Area Medical' and Michigan Division Medical,* Dow Chemical USA, Midland, Michigan 48640, USA a b str a c t Available medical and morbidity surveillance findings from 1976 to 1978 for two employee cohorts potentially exposed to 2,3,7,8>tetrachlorodibenzo*p-dioxin (TCDD) were compared with those of matched unexposed employees. The medical surveillance findings were derived from a screening programme offered to all active employees and included an analysis of various medical history questions and blood chemistry results. Group medical insurance claims served as the source of morbidity surveillance data and the period prevalence of selected-diseases was analysed. Few significant differences between the exposed and unexposed were detected. Among the cohort of employees potentially exposed during the manufacture of 2,4,5trichlorophenoxyacetic add (2,4,5 ,-T), a significantly greater frequency ofx-ray proved ulcer was reported and significantly more members of this group had diseases of the digestive system diagnosed. Such findings were absent in the more highly TCDD-exposed cohort engaged in 2,4,5-mchlorophenol production, making it unlikely that dioxin was a cause. The trace impurity 23,7,8-tetrachIorodibenzo-pdioxin (TCDD) is formed as a byproduct during the manufacture o f 2,4,5-trichlorophenol (TCP) under alkaline conditions at raised temperatures and high pressures. Since TCP is a precursor for the produc tion of the herbicide 2,4,5-trichlorophenoxy acetic add (2,4,5-T), low level contamination of the herbitide by TCDD is expected. Thus the potential for occupational exposure to TCDD may arise among employees making either TCP or 2,4,5-T. Recent evidence suggests that TCDD may also be formed during the routine combustion of car bonaceous fuels.1 Chlorinated dioxins have been found in trace amounts in samples gathered from incinerator stacks as well as from chemical tar bur ners and a fossil fuelled power plant, vehide silencers, fireplaces, chimneys, dgarette smoke, and portions of charcoal broiled steaks. Mortality studies and case summaries of occupa tional cohorts presumably exposed to high levels of TCDD during the production of TCP, or exposed to lower levels during the synthesis of 2,4,5-T, have been published1-* (J A Tack, unpublished observa tions). Reports have appeared of soft tissue sarcoma among employees with exposure severe enough to M o v e d 11 AufOO 1982 Accepted 30 September 1982 cause chloracne<-,; however, no consistent unique mortality patterns have been noted among those with lower level exposure' (J A Zack). A survey of reproductive outcomes among wives of employees exposed to dioxins was also recently completed and indicated no biologically important associations.l Available evidence suggests that occupational cohorts exposed to lower levels of TCDD in the manufacture of 2,4,5-T experience no important long term health risks. Investigations, induding the evaluation of health examination findings and morbidity data for TCDD-exposed individuals with long latency, have only recently been started." Clinical follow up 10 yean later of 41 out of 79 individuals who developed chloracne in a 1968 TCP production aeddent, showed that other than minor persistent chloracne, there was no evidence of adverse health effects.11 While relatively little data are available from sound epidemiological follow up of other exposed cohorts, reported systemic health effects after exposure to large amounts of TCDD indude impaired liver function, nephropathy, gastrointesti nal irritation, myopathy, and neuropathy, induding depression and irritation of the central nervous sys tem. These symptoms have not been progressive and have been reported to disappear with time. Vietnam war veterans, presumably exposed to lower levels of 318 18403 ,1 1609 I ZMOfl Medical and morbidity surveillance findings among employees potentially exposed to TCDD 319 TCDD and for shorter periods than industrial been considered separately in the analysis to allow cohorts, have alleged a number of medical for differences in their potential for TCDD expos complaints--for instance, weight loss, liver damage, ure, and for differences in their exposures to other recurrent rashes, deformed offspring, stillbirths, agents. cancer, sterility, personality changes, and " other" Data of interest were derived from two separate illnesses--which they attribute to their exposure to sources: health examination findings from the Agent Orange.11 To date, there have been no well routinely administered medical surveillance pro controlled epidemiological studies to substantiate gramme and morbidity surveillance as reflected in the allegations that these complaints are attributable diagnoses from external medical service providers to exposure to the trace amounts of TCDD in Agent reported for payment of fee to the group insurance Orange. department. Medical follow up of inhabitants of Seveso The medical surveillance examination has been exposed to TCDD as a result of an explosion of a offered to all employees since 1967. The time trichlorophenol reactor has continued to document required for the programme to cyde through the a lack of severe lasting health effects. While the entire manufacturing complex is about two years. findings are still regarded as preliminary, no organs Only cohort members who had partidpated in a or body functions, except the skin, have been found medical surveillance examination between 1976 and to be impaired; no excessive derangement of gesta 1978 were eligible for consideration for this portion tion, fetal lethality and loss, gross malformations, of the study. growth retardation at term or cytogenetic abnor Controls for the medical surveillance analyses malities have yet occurred.11 were selected from among other white men em The present study reports the cross sectional ployed at this location who had also partidpated in medical and morbidity surveillance findings from such an examination between 1976 and 1978. Em 1976 to 1978 among employees at Dow Chemical, ployees considered at high risk because of a history Michigan, who were considered potentially exposed of a job assignment ss a pipe coverer, in the produc to TCDD and for whom mortality surveys have been tion or parkaging of arsenical pestiddes, considered reported.1* The objective of the present investiga as potentially exposed to high levels of vinyl tion was to determine whether patterns of selected chloride, or potentially exposed to dioxins were health examination findinp from the routinely exduded from consideration as potential controls. administered medical surveillance examination, and Four controls were then matched from those eligible indices of morbidity as reflected in medical insur to each exposed on year of birth - five years, ance claims for employees potentially exposed to whether hourly or salaried, smoking habit (never TCDD, differed from those of employees not smoker, ex-smoker, current smoker) and. when exposed. possible, month and year of the most recent medical Methods and nsatetteb surveillance examination taken. When more than four controls were eligible for matching, the four The study population was assembled from two pre with the date of lure nearest that of the exposed viously identified cohorts: (1) a group of employees were selected. who had been engaged in the manufacture of Based on a review of relevant reports on animal 2.4.5- T for at least one month between 19S0 and and human exposure to TCDD, selected medical 1971 and (2) a cohort of employees involved in a history questions and blood chemistry results were 1964 chloracne incident in the area of TCP produc considered for analyses. The matching was retained tion. throughout. For the dichotomous questionnaire The methods for the selection of these cohorts responses (yes or no), the analysis was that which have been described previously.1* Briefly, the 204 has been proposed for a fixed R : 1 matching ratio white men comprising the 2,4,5-T cohort were with R " 4.14 Exact confidence limits were calcu identified from annual department census lists and lated with a (HO using a packaged set of pro work history records as having worked one month or grammes for a programmable calculator.11 Blood longer between 1950 and 1971 on one of four job chemistry values for each exposed subject were con assignments (reactor operator, salt wheel operator, trasted with the mean for the four matched controls, add wheel operator, or dryer operator) in the and a paired r-test was used to test the hypothesis 2.4.5- T process. The TCP cohort of 61 white male that the mean difference between the exposed and employees was identified from monthly department matched controls was zero. Linear regression was census lists and lists of maintenance personnel who done to test the correlation between log,, (days of were known to have worked in the process area dur employment in 2,4,5-T production) and the differ ing a 1964 chloracne inddent. The two cohorts have ence in blood chemistry values. 'O 3404 320 Bond, Oa, Brenner, and Cook i1 009 IZMOO Group medical insurance claims filed by em ployees for medical expenses incurred between 1 January 1976 and 31 December 1978 served as the source of morbidity data. Members of the original study cohorts who were eligible for benefits on 31 December 1978 from the Medical Care Programme administered by the group insurance department were incheVsd for study. This time restriction ensured that morbid events reported were indepen dent of mortality as reported in earlier studies of these cohorts.1* Controls for morbidity comparisons were selected from among ail white male employees eligible for Medical Care Programme benefits as of 31 December 1978. Employees with a history of certain job assignments were excluded from con sideration as controls, as has been described above. From among the pool of eligible controls, four were matched to each exposed on the basis of year of birth five years, and whether hourly or salaried. When more than four controls were eligible, the four with the date of hire nearest that of the exposed were selected. Diagnoses and expense dates were abstracted from Medical Care Programme claims by a regis tered nurse, who was unaware of the exposure status of the subjects. Only diagnoses for claims for hospi tal inpatient care, hospital outpatient cate, surgery, diagnostic expenses, or emergency first aid were considered. This excluded diagnoses from physician office visits, unless diagnostic expenses were incur red or surgery was done, and information from drug prescriptions. No validation of diagnoses with any external source was attempted. Coding of diagnoses to the international classification of diseases--ninth revision--clinical modification (ICD-9-CM) waa done by trained cod ers without knowledge of the exposure status of sub jects. Diagnostic categories of interest were derived based on the relevant animal and human toxicology data. An individual could contribute, at most, only one observation to each diagnostic category. Period pre valence of all cancer, various a te specific malignan cies, diseases of porphyrin metabolism, digestive system diseases, hepatic disorders, renal disorders, and diseases of skin and subcutaneous tissue was compared, using an analysis that maintained the matching.1* DEMOGRAPHIC CHARACTERISTICS Table 1 presents the vital and employment status distributions for the two cohorts, together with eligibility for the medical surveillance and morbidity surveillance portions of the study. Two years of Table 1 Vital and employment tu n a o f exposed cohorts as o f31 December 978. (Percentage o foriginal cohorts in parentheses) Sh u TCP cohort O hftul 61 ssr OiBHaad 40 11 4 Lebabrn (Ms ftrougfa w n m C 6 D n niii 0 K aom slh 6y Uakaoua 0 P m tdpm a in a a d o l am rihoi fttBI 27(44) EUpbto tor wadkai o n pragnoBM ind aurtidity m nnitliim 4S<79) 1.4.1-Tcohon 204 116 21 11 56 2 2 12 S7(43) 135(64) additional follow up with company records of the 2,4,5-T cohort identified two deaths not previously reported--one ham cerebrovascular disease and the other from cardiovascular disease. Some 44% of the original 61 members of the TCP cohort and 43% of the 204 members of the 2,4,5-T cohort participated in m edial surveillance examination between 1976 and 1978. Of those who were actively employed and thus eligible to participate, 68% of the TCP cohort and 72% of the 2,4,5-T cohort did so. These partici pation r a ta are signifleudy lower than the partici pation rate of 80% among all other white men em ployed at this location (p - 0-04 and p ~ 0-02, respectively). Of the 49 individuals in the original TCP cohort who had evidence of acne like lesions in 1964, 22 participated in a medical surveillance examination. Nearly ail members of both cohorts (94% of TCP and 97% of 2,4,5-T), who were active or retired, were eligible for medical care programme benefits and thus could be surveyed for morbidity in this study. Table 2 presents a comparison of demographic data for the sublets of each original cohort eligible for the medical surveillance examination and for morbidity surveillance and their matched controls. The exposed cohorts and their matched controls compared well with respect to all variables consi dered. In the analyaa, potential confounding by dgarette smoking, age, year of hire, and socioeconomic status was controlled by matching and sratifiatic n on these variables or correlates. MEDICAL SURVEILLANCE FINDINOS Table 3 presents a comparison of the frequency of positive screens with selected questions from the medical surveillance examination for the two exposed cohorts and their matched controls. The frequency of posidve screens was low for nearly all the questions, and the exposed and controls responded comparably. -The only statistically 1 1009 I ZHOCJ Medical and morbidity surveillance findings among employees potentially exposed to TCDD ' TaNe 2 Comparison o fexposed cohorts and their matched controls on selected demographic variables D m ogrephk verieblt Marhal ardllaiica: Mo ebgiMe to t study Mean um x SO Year oc&tf* Seiened Paid by tte hour O m an tauter E iiu n o ter MvaN-o-rae-ano-ns---ymfo-ute--irrs mrma---o-c- -r No ehgibk tar study M e a a i x SD Yew 0( 00 Salaried Paid by dw bow TCP cohort 27 43-4 s 7-6 1933-6 * 7-9 5 22 6 10 11 48 49-2 a 9-3 1931-4 8*0 3 43 CoruroU 108 43-4 7-8 1933-3 9-2 20 >8 24 40 44 192 49-2 9-6 1931-7 103 20 172 2t4,5-T cohort 87 42-: 8-2 1937-1 8-5 14 73 23 37 23 133 43-3 102 1936-7 7-9 17 118 CororoU 348 42-8 8-3 19566 to o 36 292 100 148 inn 540 45-3 102 1935-0 106 68 472 321 Table 3 Frequency o fpositive teretnt to selected medical surveillance examination questions among TCP and 2,4,i-T cohorts and matched controls, moatrecent exam 1976-9 Qiiasute Since yooz law Do physical e n o or health inventory, haw you had u y oi the foAoviog? SUa troubia Ycflo jauadlee ProbUuM with anncooe A lb u m or sugar in urine Blood m trite Frequent inrtitiuym or teanbura latauanal trouble Loaa<riuk|ht up oi blood niaiwe ue bourn! tebisa Blood n smote Tarty nook Do you have or have you had any o< tte following? High Mood pressure U m troubk (hepatitis) Kidney or Madder troubk Cancer or mabanom growsti x-rey proved ufctr 'Rml M l: Xmh - 1-78. 9 0 a - 1-06-C20. Ng - M usteraicxpoM dresponding " Yes." Nc - M uster at coaaok icspoading " Yes.1' TCP cohort Ne (n - 27) 2 0 0 0 0 0 0 0 0 0 0 0 1 1 2 0 2 Nc in - 108) 2.4.S-T cohort S e (n - 87) S c (n - 348) 56 00 0l 00 10 34 01 43 00 00 l0 10 76 42 7. 5 00 7 9* 14 0 3 3 19 2 6 1 0 2 1 24 12 19 3 18 significant difference was the greater frequency of positive screens for x-ray proved ulcer among memben of the 2.4,5-T cohort ( R ^ 2-11, 90% Cl 1-06-4-20), based on nine of those exposed having reported such a history. As asked, the question of x-ray proved ulcer does not discriminate between incidence or prevalence, so the temporal relation between exposure and disease is not known. Table 4 presents a comparison of results for nine selected blood chemistry tests performed as a pan of the medical surveillance examination. Mean total bilirubin was slightly lower in both exposed cohorts and mean serum aspartate transaminase was lower in the 2,4,3-T cohort than in their respective con trols; and while these differences were stansdcally significant at a (HO, two tailed, they were not regarded as clinically significant. Given the number of comparisons done and the level of accepting a type 1 error, some statistically significant differences were to be expected. When the mean difference between blood chemis try values for the exposed and their matched con trols was regressed against log,, (days of employ ment in 2,4,5-T), there was a lack of significant association for all laboratory tests except for a significant positive slope for blood urea nitrogen (p 0-922); however, the independent variable explained only 6% of the variability in the depen dent variable, suggesting that duration of employ ment in 2,4,5-T was not an important determinant. Analyses of medical surveillance findings among only those members of the TCP cohort who had 18406 BOM 2 1 8001V 322 Bond, Ott, Brenner, and Cook Table 4 Com panion o f exposed cohorts with matched controls fo r nine selected laboratory tests, moss recent medical surveillance exandnadons 1976-3 T m procedirt Trichlorophtnoi cohort M xSD Total bilmbin (merlOO ml) Total prem a (R10O ml) Protam atem aa (R100 ml) Blood a n a s tr o p * L kqc dahyrtrnfiii-- (murimi) Scram m panua iranmimnaiM (trial) Sanaa lanina amm irarm (ubai) AJkatias AJbonan-stobulio ratio 0-31 - 0-17 (a - 26) 7-17 x 0-43 (a - 26) 4-16 X 0-43 (a - 26) 16-0 s 3-79 (a - 26) 114-7 x 30-4 (a - 26) 27-69 x 64 (a - 26) 32-26 x 13-34 (n - 23) 70-8 x 21-32 (a - 26) 1-3 x 0-23 (o - 23) (a - Number a l matched qatm pka) Trichlomphenol cohort let* connais d X 90% a - o o e x 0-07 0-04 x 0-16 0002 X 012 0-37 X 1-34 4-4M X 6-73 3-32 x 6-39 1-21 X 5-20 - 0 3 6 x 6-1 -OOM x 008 2.4.J-T cahon M xSD 030 X 021 (a - 4) 7-10 x 033 (a - 4) 4-11 x 035 (a - *4) 16-07 x 3-64 ( a - *4) 10S-3 X 23-9 (a - 2) 2099 X 7-72 ( a - 3) - 33-24 x 14-66 (a - 79) 71-05 X 24-13 ( a -4) 1-40 x 032 (a - 7) 2.0-7* cohort has controls d - 90% a -0-06 x 004 - o o t x 007 -005 x 006 0-61 X 065 -3-67 x 4-49 -2-53 x 1-83 059 x 2 95 021 X 4-54 -0003 x 006 Table S Comparison o fnumber o fprevalent cases o fejected disease conditions by exposure group: diagnoses from Medical Care Programme, 1976-3 iVo T C f cohort 2.4,S-T cohort Ng In - 4S) Nc (n - 192) Ng In - 133) ,VC In - 340) Maliernnr mania on. (140-209) l 449 Ma of Ivar (155) 0 001 Ma a t n ad u a . broadum. and litui (162) r 0i1 Ma of m o u B h . tad otter tod attua (17;) Ma of ikia (172-173) 0 0 1 1 0 0 0 2 Malignai* lympoma (200-202) r 0 G0 Dtaaaaa a i perpyna metabolism (277-1) 0 000 DfcaaaM otf t e digarv syaua sduding liver teaaaa (330-5337353-55. 54-1) 3 10 17T 27 Diaorte oi t e ttvar (570-573) o~ 3 2 5 Qlomaruiopaend (360-583) c 000 R a l tehua (5*4-586) 0 001 Infarnoat of kidasy (590) 0 000 ObiaMi e Wr rm * g h o iu iM 3 u t -- (680-686, 692, 693) 0 2 2 11 'R etef to f esa li individual. tRfcO. - 2 51 x h - 2-937, 9 0 * a - 1-30-4-1. Ne Number atprevmknt cues a c a i cxpoeed oobon. N c -N u m b e r of prevaie enee a o o o | ooouoia. exhibited acne like lesion in 1964 produced similar results to the analysis of the total eligible cohort. MORBIDITY SURVEILLANCE FINDINGS Of the 913 members of the exposed cohorts and the matched control groups eligible for Medical Care Programme benefits, 636 (71-7%) filed at least one daim for medical services during the study period 1976-8. A total of 6339 separate diagnostic entries were abstracted and coded and constituted the total morbidity dam base from which the analyses of con ditions of interest were carried out. The diagnostic entries were distributed fairly evenly across the study years with 2126 entries in 1976, 2243 in 1977, and 2168 in 1978. Most of the diagnoses were on claims for physician's services (38-4%) and daims for hospital services (33*3%), with few diagnoses provided solely from laboratories (4*7%) or other sources (1-3%). About one quarter of all diagnoses provided were preceded to some disease categorisa tion scheme by the service provider. Table 3 presents a comparison of the number of prevalent cases of diieasr, conditions of interest for each of the exposed cohorts and their matched con- 184G7 B 0 H 2 I 600 11 Medical and morbidity airveillance findings among employees potentially exposed to TCDD 323 Table 6 Detailed breakdown o f diseases o f digestive system among 2,4,3-T cohort and matched controls. Diagnoses from M edical Cart Programme, 1976-8 Disease cm tfory No o fpreveiam cates Ne NC Diseases at oesaefa (330) S a n k u k v (331) D uodnai vikct (332) P a n e aJar, n a j r y nfMri (333) O taaom fouti e k 7 l3 4 ) O ttaw a tad C jsdtam t (333) **ip ~ iil n u iin i (333) O tter aoanatacboas ftem ea term t lad cot (33t) Im aM c coioa (564>1) 2 2 3 2 0 3 0 i 4 1 3 3 7 0 4 1 10 3 Noes: An individaal a n have more dun oat caadinoa. Ne - Number ot y n tn le tt cm et im oaf 2.4J - T codoct. N j * Number ol pieeelem c a n im oaf minbert coatrob. trol groups. The period prevalence of most condi tions was low and was comparable between the exposed and their controls. An exception was the significantly greater prevalence of diseases of the digestive system excluding liver disease among the 2 ,4 > T cohort (Rml - 2-51, 9096 a - 1-50-4-18) based on 17 prevalent cases among the exposed. Table 6 gives a detailed breakdown of the distribu tion of prevalent cases among the 2,4,3-T cohort and their controls by disease within this category. The difference in prevalence cannot be explained on the basis of a preponderance of any one specific dis ease entity; instead, the 2,4,5-T cohort had rela tively more cases of each condition. Diacntrinn Results from this cross sectional examination of medical and morbidity surveillance findings among two cohorts who were potentially exposed to TCDD at some point in the past and their matched unex posed controls showed few differences. Those em ployees who were engaged in 2,4,3-T production at some point, between 1930 and 1971, reported the prevalence of x-ray proved ulcer significantly more often than their matched controls, and recorded significantly more diagnoses of diseases of the diges tive system. The lack of a similar finding among the more highly TCDD-exposed in the TCP cohort makes it unlikely that the dioxin is associated with this finding. The departmental unit under which the 2,4,5-T process was first organised was also respons ible for manufacturing various other products. Thus many of the individuals in the 2,4,3-T cohort were potentially exposed to numerous other substances during their employment with this unit. The 2,4,3-T dust concentrations found in the plant were often high enough to be noticeably irritating, and were believed to have resulted primarily from finishing operations where the end product was dried and fed through a hammer mill. One could postulate that ingested dust could lead to a greater frequency of diseases of the digestive sys tem. The 2,4,3-T exposures, however, were incurred by subjects in this study a minimum of five years before the indication of disease prevalence, thus making latency an important issue. A limitation of cross sectional studies is the uncer tainty surrounding the temporal sequence in the exposure disease relationship. As was the case in this study, it is usually not possible to discriminate between disease incidence and prevalence, so that one is uncertain whether or not the exposure pre ceded the disease and could possibly be a cause. Data on health outcome from medical and mor bidity surveillance of the two cohorts in the present study were limited to the active or recently retired workforce. Members of the two cohorts who left the company for reasons other than retirement could not be studied. Inferences from the present study concerning the health status of former employees must be drawn carefully owing to posable retire ment of former employees on the basis of health. The study was further limited to medical and morbidity surveillance for a three year period (1976-8). Owing to tbe large amount of time required to locate and code archived medical claims, a larger sample was deemed unfeasible. With the completion of this study, these em ployees have now been surveyed for morbidity, mor tality, and reproductive outcomes. To date, tbe available data do not indicate serious long term health risks associated with exposures to TCDD at the levels encountered by these two industrial cohorts. Consideration is being given to continued medical and morbidity surveillance of these cohorts, and we recommend that other cohorts with similar exposures also be surveyed. We gratefully acknowledge the contributions of Mr Bernard Lasich. Mr Stewart Gudmundsen, Mrs Janice Cartmill, Mrs Jean Townsend, Mrs Elsie McLaren, Dr Robert Kofesar, and Mrs Angie Grzcgorczyk of Dow Chemical, USA, and of Mr Larry Silvcntein, formerly of Dow Chemical, USA, and now with the Dow Coining Corporation. Ufm soi 1Bun* RK. ClumSMQ WB, Cu m S S .it aL Tnoa dtem ntria ai On: t m ir a at itsrwitn Samoa 19S0:21S:38S-9. 1Cook RR. T o a a m d JC On MO. 3 ih m t a LC. Mortiinr experience at iii|iliijnr iipnuit to 2.3,7,8-<cmdik>fO- 18408 II009 UHQQ 324 tE b m o vd la m (TCDD). JOM 1940:23:330-2. *te c k JA, Salinari RR. The mortaliry czpcricaot ai o r tio nrpmad to atmehloredilwajodiorim ia * tnchloroplteiiol prooMi aoodaat. JOM 190002:11-. *Thiaw AM, Praattal-Baymaa R_ Moitaliiy ady oi panca* rrpmril lo danza ia a oichlorepeool-ptocee acddaal tbai occoziad ia iba BASF AG oa Novambcr 17, 1933. A m i r i f Journet o flm a m eitieM d n t 19820:179-39. Hoectur FA, Halpaha WE. 2.4.3-T, TnrtiiocoplMDoI tad toA-QMi im o o m . L m ( 1961x 266-9. * Cook RiL Diana, cannona, and sort-tun sanarne. Laneti 1961x616-9. ' Cook RIL SoA-o m i rc o n n r duce tnd <airion. la: Tiackar R, Yooaf AL. G ny A?, da. Emnronmrmmi in w r t ru aaed t and dheery. Voi 26. //im m W emnronmetmi nxir ofddohneeod diadm and ndmod compound! New York: Plenum Pubtiehtng Corporeo. 1963. ' laamarioaai Afaacy toc ffa u rc h oo C e ra r. Evabmdon o ftke cardnogenc rtt o fd u tmcel* to human*. Some funegana, du /urpeddes 2,4*0 and 2,4,5-T, chlorinmed dibertzodioein* and tmtcadsnaota indiuatMl eAancdf. Lyoo: 1ARC 1977. (Mooofrnph 13.) Bond, Ott, Brenner, and Cook *On MG, Holder BB. Oboa RD. A mortality tally* of em ployees engaged ia the manufacture ot 2.4.3-uicfciofopheaaxyrack to d . JOM 196002:47-SO. ' Towaaead J C Bodnef KM. Van Peeoco FFD, Oboa RD. Cook RR. Surrey of reproduarre events of wives of employees etpoeed to chlorinated dionm. Am J Epidemiol 1962;116:695-713. 11 oa Vienriftr Affain Advisory P lo d oo Tone Subwantm The hm dk effect* o f "Agent Orange" and pdychbri* timed Serin eonm/mnmn. Qacago: Ancricaa Medial Aaaodariuo. 1961. 11May G. Te^echlocodibano<6og a : t surrey of subjeca tea yean after exposure. J r / Ind Med 1962:39:128-33. 11Huff JC. M oon JA S anaa R. Tomade L- Loag-tena hazards of potydriariamd dibeaaodioxmi aad potychionoaud dabeaEnviron Haobk Pvspect 1960;36:221-40. 14Meoiaea OS. Esrinerioa of felarive risk from iadhriduaily m trtis l a m Slom ario 1970;26:73-46. " Rochmaa K. Baku J, E pidpm obpe anelyn* with a progrwnmable relnikunr. Washington; US Goverameu Pntmag Office. 1979:19-24. (NTH Pttbbcaooo No 79-1649.) 18409 Ktfn M Hl lw s I it t u f t I"*7'. *4*nw t-.*rrs !'* 4 ' 252 (bb b im iM 2 j |7 ) l * T d n c l i i o r o d ] b f x i a ^ d i < i i i : A I 'H in ti I n d u c r o f t-A m io o lc w lio k A d f S v a lb rta sc Abstract. .'J 7 .* -T w r* ,W /ii ir p-JiMd* i f t 1 f i r N o iW l/Nfllfr /A<* < th m'f/'N i./.- m m ;/*. m t . c- /.* ai *ti. to hr * fHtfrnt ttiJw rr 4t hrp*:t t \ u t- ni- i#Vf* HnJ m r W i em it)ro. dr ItttU ut J ' lit mid.- it; '/ (n r /Wo Urn e t* th tnifuunt im reaie in ih.- m u n te <4 the i-h.-.iii.- InJtu in ti t<i the en it te lam i to the Jo te u t 2 -( .7Jt-tetrut ,,lnru44>< n p Jn -u n un.l ' i /Am produced with other /met. It fin 'm iir > iiu:r. u h 70 p%n cm ot the mai# m u te In ttee J activity p re te rit f J i i t t u 'n r n v.V J .iie . I h it >in ilu n iiiijn i it plicated at the likely eutnutive vent m uit uuthr. ,:k u- p erp h n iu , uiuneu lurJu in h n rie rt in a fa ttu re here ?.J.S-trii />,'r.inAi'iiiii %.<. :u .u 4 >/. /v irv tv n th e tize J . 1 3.7,l-Tetr*chlorodih<n/is./-diosin tlV D D I n a n unwanted coniamuMPi lornKd during the synthesis id the het lucide 2.4j4tkM i> (o|A niiyjci'lu: k n I t2 A -T ) ( l iF if. I. This m UimiiaM , 1CDD. perhaps the roost gotiib 4 m ri m nlu.uk t.*in known; the u n l ^ P t . |W > * lethal tinsel in guinea f>). per kilogram id hods w c ig ld U X i o rook kg I I.7). The H k sftw i mat o f 1 4 J -T as a ilelidiant in V a la M f I. 2 1 ami the ilw n ttry id the teratogenic potency id TCDU t.f) hate n a n i concern shout the potential public health harard createti by comaminatioa of the environment with TCDD. The chemistry o f the s in has been eatenahmly investigated, but lin k is known about its biological actions if . d l. In 1964, B kibcrget al. U reported an outbteak o f occupationally related sena and porphyrin cutanea tarda (J*CT) among workers hr a factory H g. I. Suucw re a f U - 7 J tetrachlarodl wl.erc 1 .4 .-T was hcina (-induced. 1 h : acnc t j s tk.ivn to be dncctly atluhuij- h k to Ti~DO <Ai. P.'rpliyru rjta o e J tarda :i-i x>|iiiictl detect in hepati. porphyrin metabolism -v uroporphvrmtiria. pti .....-nsiiivity as ntanitcsieii by blisters, an t mechanical 'fragihty of the skin 1?; (hr etioloyy ol PCT in these fact-try workers is un clear. hut up-n rcinscvipati-m ol the lacl-iry in '* d iv o v e re l that the !*C1 had itisappvars'd in all iin k ili followm- it<e in an itio n -ivscdures to reduce TCDI) aaitari.nation f t 1 Hepatic poiphy:-a can he produced ' caper .nrnlallv hv a .Timber id drugs, all of which have the iriliiv in Mintu- ale the activity id the inn- il en/*. ne m heme .ytithrsn. li-ar.ii.tolevuimK acid .tiithc'asc t .Al.A svnih.-tu* t in i Stinn.lalK-ft of Hus en/yuu. - thiiicln to represent iikJu-ImO. that >. eni incs-d ptiuctn itii'ti.-is |Vi, We tcpi-rt here that TCDD a to inducer id Al A stnine'ase. and is at least three orders of magnitude more potent than any other compound kmiwn to proJuce erpermientai |km- ph> ria. The thick embryo was cIs m s a< the esperiovrnta; ar. i.-f because III it is hig'ilv seTMtise t lS- to* -- 'rdests .. . ... - - A* >l H D D I / / ) . ( n> iikIi k I-- n . A ! A Auihctatr m jk e liver is . '! tk embrvo i / 7> ar.d lined system. <^huh 'r* rttA r-f-diosm s wcie bsTt-lc thicker, eggs. I ? to i t d a y s id gs"-lat: -ii, w ere .ip-sictl with 25 pi of the chem ical solutiiHi r -.1 solvi-pi ak-ne. th ro u g h a suiaii fa-lc p u n c h ed in lo 11a- shei! -vei the air sac. A fter the appropriate t nie interval, tbc uurPiK were \iiie d . and the asltvily of hepatic Al A s>iilhciasc - 4 - assaveti i ,' <> T he 1 ( 1 ) 0 p ro duced a dose related increase :n Al.A sin th e ta se a ciicitv t i e r 2> i*seii at the lowc'M d i e tested. 4 lit l iiiole per egg t 1.5 t-gi there w as tig. mlK'atit (C .(^ ) ikaiblm-* of c n /y m e a^liciit I'.i.vwue Jcli> ui in.re.i-a J m ore than 3 i ti-ld at tlur highest J-Ss* tested. I ' ( |tl - imde per eg it) 5 "til. I h e . -n v itro a d d itio n o f 'l< D D to a reaction ni stu ic cor.ia-u.iic control livs-r slick not m cieace c n / '.n .c a e li'iiy . l:.c sliiiii.lalioii o | Al. A -om hclasc in I-. 2 T he m J.K U .ui. by T( f> n n t A l. A s.aibelavc' dosa.ies(s-- r i:.tumM iip ( hiskrn rg e s o f 17 days' p e tiatio n w o t KiKsIrd w ith 2$ i.l <d 4>icrt ( c o n tto l) . ur .n w dvenc cutM .-mng v in - s n doses of T T U O The embry-w w eir I d lrJ 4 bourn later and assayed '-* hepatic Al A synthetaw actriiry t / ' i The pernii rrpisent the m ean s u n J a r d ** ar o ' :r.*r< m lo u r .rm n p s <d r m d r d b- .~i. rp44S&r.. \ - c%'- ; w e t - ' >y4-y->-*s; -* k ' f 7 *. r A i ' 7 * ' .r-. -y C'a . - - j > <Ac .n..-- I'i^. I. Tin* voui>< of ifUiklHMl id At A ()MlKb<(. ( b k ld i c r p 4 M Ait* *' talion n r miciiiil with J al of so4etit oaiijiiHiir J f t ' IU " *iul* id Ti DO 10 i o r of A tM ** I M . Al the iNjK'uivd iwrfi-iK. the rmbtyws t t t tillr.1, jd J thoi liii'ii n r ^vifril iir A I-\ k it'll) tIJt. I k k pMI n r t r c M ' ihr im j* ; 'U fcU iJ c u n at Com growl's f p.'ulJd li' v \ ivii can he prevented hv the simulljnc- d in administration id aclionmyTm D I.Vl /.f t or cydoheximide 'I I I / .f t . al ik n o htch did not kill itc embryos, lienee, the stinniljti*n of Al.A syn thetase prinliKvd h> T(1 )1 1 -nul other dni|ri probably represents increased sxnihcsis of ihe eo/sme. rod me activa tion or decreased degradation I J4). 1 he lime oniric of cnz\ nte induction tFig. J ) hat an initial b ( phase. protv aNy representing drug abn piion and synthesis of messenger RNA. and then ever, it seems most likely that the nut- a rapid rise in enzyme activity reach* break o f PCT in workers in the factory in ; near maximum levels hv f> hour. producing 2.4.5-T is attributable to in In coniraxt to other, porphyripenic com- duction of hepatk ALA synthetase by p.Hindi that have been, tested in this TCDO While other chlorinabai com si'te m (for example, alls listpropylacct- pounds present in the factory were amide and diethyl-l.4-dth\dro-2.4.fc- found to stimulate ALA synthetase ac tnmcthx Ipyridine - . 1 . 5 - dtcarhoxylaick tivity in our system. TCDD is by far h u h have transient effects on ALA synthetase, the induction hy TCDD a s prolonged. Embryos (IS days old) given 4.M v 10 * m*4c of TCDO per egg f 150 ng) uill had 70 percent of their maximum induced enzyme ac tivity afte r 3 days. The prolonged dura* lion o f induction ii a reflection of the long h iofofk al half-life of TCDO US). Studica with other halogenateJ dihenro p A k in s suggest that ihe hakv pra alomx must occupy at least three o f Hie 2 J .7 . ami I position on the the most potent inducer, and the re versal of the porphyria occurred when TCDD contamination wax reduced. We suggest routinely monitoring the Urinary porphyrins in workers in factories pro ducing 2.4.5-T to assess their exposure *lo TCDO. At an Pm.ANn Eowaho C i o v n t Department o f fkartnaeotogy and Toxieotuer. U niversity o f K orhrU rr School a t M edicine and fh-nriury. Koekeuer. New York 14642 ring, in order to induce ALA synthe tase. The 2.3.7-trichloco- and 2.3.7*. tnhromo-isomerx are potent mduccrv while 2.3-dkhluro-. 2.7-dichtoro-, 2.*- dichlofo-. U .M -M ra d ila n i-, and 1.2. M .-tetrachtoro-oiiers aM fad to in* duce at doses up to 2.5 pg per egg. Of the limited number of halogenated di- hc/o-/a-dio\inx which have been tested fur Icthalhy and the ability to produce gene f /AI. those which arc toxic at low doses tin t induce AI.A ' nthetaxe. Induction o f ALA syr xsc hy TCDD it the fexl speciffc l emical action idcnliffcd for this ' com t. -Depart w AJ-T a i n m e t Parmi HnSmtn at On h rx tM 'i S n a A A i w i r p-- n n * m . n n n n i P riM iti ll* a . W.Jheawe. l i t '. Mink tain. 2. "'lUf<w Wa f AJnkorr l'aaMMWa n .I.JT * IS* AOuMuraM* at On rw n-- m e Pnarataw Aae i * lO o m m i M u Of. tar. WnWapm. D C. Mr k o ( a n . D. w. cw . m n iw a It t l aW. k . It. I a n . I. StMchak. W a r MB. aaa tiri; o L. Soar*ha. h L. Dtaa. V K. la ta , M Cotant. Toa m . *. (1*711. A N. P. k I U . P. H. Daw*. O. Sim. M. r . Aatm OitaUl. O. SWM-M S nort m nanOatna 0 . I7J <t*72>; K P. l u Hat, n -P. Hru. O Sam-Uat. I. Xr-i aka XiAjau . CJt. t u t Art. Parti l a . i m . 1441 (1*711. I. I. etkihar. M. WaUm. U. W A a . L Appalk m , AttM. P rw au t U. 7*1 tMMt. . pound. Thu relationship het . t en zyme induction and the delay -polk necrath presumably m p on sd * tt the lethality o f TCDO is not known. How- flnauaUaaat phratat 4 <Ar Uka Ilea A r n m . pwtiwtmia. tern. u n J. u * aaa ma K. M. Sakata. S inomMo outtO m H i l tm H ; K. M. Sakata. M Kka. Cap aaaaaal SML IBP tieSTI. I t M e f . r t t f u ! ft V i - . * ,r. / g o Ante f t /hirN'i | '.tarh ^ t^ I Ittm ilttr, II lirJri.st-et Ijs *\|a(e li..i. v% fd . r#?;- f i|*4 \ r4. II t. M. Hr?, t. f. * . V. 4A. fg.ffr. Mrmk* tl I14 ||V7|. I fMJMaCfc, J. B+oi. I e -1 |4 | I |*g ||tp a . -- si S. - . ?. i. VtigrL 14 lAiodt mi. rrtsx. v * > | ? | t . me?. 5. II. ft. II. H w nfX lW A Ifttarf It I II. I. W itrt*. J. I t s A D C ju p iy it m . * ri*i 1:. A. K iff. C i 1 . lew?. It .Cask a. I, rfMWk, fNi. .vf A*ml \.f I 4 41 * im n . Ogr rti f um^ihtr cl Al A >***rt. j. m* *v ilk INtlhxd >4 M.lixt - ff mt \ i f f m I WigH-fkatMl a \ ' .U J,'M lt tlahiUk 4kx t.. f !|. AI A m IS- .h w k . fdf l/*. w du n w tm r it m m , on i 0 r r /is i.` I <d |m .>|a.d MU 4 IS iniiffffmwiitpt 4 Ky m OpL ' j M r y W b y t . 4 t i i k j r j Pi* tt> 4<* |fp)' 14 ft S. Ses m^r ) I. r i r t r l k frt* . rtt-t 1 h.< bit pi4r4. rtcftcJ. m l i.*1 ?../* i in Itmwr Hdinr td M !r tt** Tlu* htt.v . m <nuti(tgtd M li#Pdty Utt 2'* p..it,irm4 * fCfft 4%irw>r4J it *i* T V K llr | Al A khaloa - a im j k I mi j ( s m . t.f in. .r-u- p r a M rathi. .K h . k r^u* . '.s i ! i t* C fair ut a hail a ,k n .'S n lg m : :4 I.; t :. H t I t TSa a i < r a i .k n r j> a i Cl*:., /*. J IS aU t | l | . u . 77 mW v . u a 1. aiW -v m--*. 1 mW N . ItPfl,.. 7- aikt l h l ^ ','i a . l H : i m i i r ! . - . j i r . IS m*l \ f .i * . aae J m.'/ r<s* .I f rs.. r*v.-r 1hp*r a r-r w a s a j I t a ru/:*-, i: r m J ita tm i! a ,, tek u k ifrt hr :' t .u t l . 4 at k j .a a h a .1 ; n (auakaai .a ) p r . m . tbt rra o u a m..iar . . ihca irru itaeo J < aj-trJ *>7 .. :..trr .4 1ST ksltam K n a r e r a , an a * rvi.'rnt a a i l a r h a r M a h i w a nt u r l .t n .n t TSa u ata* a t n W i J n >1 l m !' a a a n m S-n ifea ALA- ta4 A A i-'.r t. ira*. TSa p i a t tha ' u p t r . n kt 7 * . l i t IM lia u N S W lo tto iH I li ai, a a t A A n m p n .n .r . 1 , ..h ; a l at tK k lH u aah aa . t t h pt anlair iru t W a n o a k at lha AA^rrtoIr i a t b t . k u pnerat H U * Al A rv to lr A a t ikr a q ^ o a . M m > a. icca aJTcJ la m o p u l n.bMr nt aa -l.l* j I irir-m tf*l f t On i t w h a K ? nt ihr chn.<-.*ni * * - a i a . t U r IS m - a r .. at 73 a a , au h n i n a c w a . . a ' . , it nt 5a 1 n l a t n l i i i tht o a i m i a a a r t AIA |.W| U. N. MapaiM. k. YrAa. t). KjkaiM. Atto PaaArat. t o.pt ) . III. 13 <!hAl: t . Brtckrm. *7. IIP ( l k |; O. T m * e a t o . I Mar. W vA ru. PSawaarat. I t . 7 7 (|7J|. 13. W k . Pifar. J. Q. knar. P. I. IlaSrbit. p.prr n u t lha a m o r t at lha Anar, an Shrawcat Sacicn. Wa-Aoii.Ht. D C . Srptrai- har lull 1 V. K. kaa. i. M N a m . I A. S k . n l C L N p a a K P I. (Ktujia p tr*' n tw a n t at t a anailaa at Ihr Aa-r-Kan t haamal s,kwi>. W*n k .- .: l i t Sa "rmhat I . 'I 17. M. S. M ansr. n. P. T -Su-S. M. c. ParWdk. A. CntMas I . ttr t. f i n . ta t. M l (I7*i la. . O lliaian. A m . M. I t it ! te. n Maaaarat H I I. G n a s h . J kn-r CWaa U *. IX .1*3*1. . P. DaMakars. PnrAr-r. /. U*. 7*7 ||* 1 |. 21. W* punk (i. I tu a. 13m ( Sr-.'.I ( . -- I A. P lk lw I. 1*3. I a s i JOA O n AUam..-..- thas. ak-aaaaimakt* p i - > * t u a S - < I l IM aaU aakar kah raaawJ f t h w h Unau*. SappanaU hr MM Spraial f . n t s karat PaUatihlp l .: l CXtAtsp.Marat Uiaa. far Paaak* On atPtn ixa. f t NIM ( w a r Oraat taa Tmntrpc tr u s t an t Tn n a i P IM M IIItM U i. SrpwaUrr l**7: naant > W a a t n lH DQH2I 60 0 11 t 324 B ond, O n, B renner, and C ook dibraas-p-dlaria (TCDD). JOM 19*0:12:330-2. On MO. Holder BB. Oboa RD. A mortality analytic of cm- 'I n d i JA. c-- RR- Tke mortality patience of worker* ployaat capapad ia tha manulactura of 2.4j-uidiloro- cxpoead lo Mtndilocodibsiizodionni ia tnddoropbeool pkenoxyacaoc add. JOM 19*003:47-10. p ro n a madam. JOM 1930:22:1 1--4. ' Towoacsd 1C, Bodnar KM. Van Feanao FFD. Oboa RD. Cook *Thebe AM, f m a d - l a p H R. Mortality tody at peno RR. Survey od reproductive eveata of wrva ol employee* t i p n a i lo d la m io a tncbloropkenoi-proQtai accident that ctpneert to `**^1 diontu. Am J E pidtm ui occurred ia A t BASF AO on November 17,1933. Aimricae 1982.113:693-713. latitim i o f Indndoiei M ediant 19*2J : 179-39. 11Council oa Sriamilte Aflain Adviaory Fand oo Tone Suti- >H oodar FA. Heipetia WE. 2.4J-T . Triddoropnooi aad nanoaa. The koakk tff ta t o f " Agm t O rtngt" tad potychlan- H ft-aaa awcooaa. L a m 19813:2M-9. aaaad diatta m nm m itm it Qica*o: American Medicai *Cook RR. Dinaia, cotone. nod toit-uaeue ureoau. L aica Aaaxianuo, 19(1. 19*lA61*-9. 11May O. TetracklotcrtKrencntSoiin: a wrvey ot wbiacta tea yean ' Cook RJL Sodl-bna ameotaaa: duca tad nation la: Tucker R, H u t capavate. Sr 1 lad Med 19*2J*:12-JJ. Yoaac AL, Otay AF. ada. E m irom uitid tm a* m a rch aad '* Huff JE. Moore JA. Served R. Tornati L. Loop-term hazarda od i theory. v oi 26. H anoi aad tm ironm aati r itti ofchlorintmd iiatiim end ala n d componadt New Yg>R: Menus Fabiataiaf potyeblonoatad idbanandlnaini and polychlorinated dibeaxotanm. Em ana H tddt H n p ta 19*0:36:221-40. I Cotporatioo. 19(3. " M adinaa OS. <-- ! od relative rok from individually ' Intatnatiooai Apaacy for Raaawk oa Cancer. Evtbmdon o f aka matched icriaa. M o n ta ta 1970;26:75-86. I caronopenie rltk o fdiam ctit a humana. Some fitanfantt, die " Rodman K. Batov J. Epidgmininpc taatyut with a profnm m - herbiadtt 3,4-0 end 2,4,3-T, chlorinated dibtntodioant tad tbie rnlrnlaaw. Wadbnptoa: US Govenuneat Phnaop Ottce, m tta& tntoux adunati diam ctit. Lyoo; 1ARC. 1977. 1979:19-24. (NIH FaMkanoa No 79-1649.) (Monoprepb 13.) 18412 iIt Quik Print INSTANT PRINTING A PHOTO COPYING 98 Prince William Street, Saint John, N.B. E2L 2B3 (506) 63<t-88-10 We can "Custom Print" Post-It" Notes / Q j f Q Q A i l . . . ask our sales rep. for details U iJ * r ~ 0 U '-fU 1*. ) r (.'Ml . i ! :. * . . * ' oji| : ;; ; . : ! . .: I.:! d i o r-. . i . ) r e l l . i l i o n . i n M Y ' I n i - t o r . ; j' 11 ; t u i i i v i i i - <; i. v ; - i i i x V 1" . ' ) h ( :i* tin) of 10 p a rts p e r b i l l i o n . .1 I oco f a . i - m. .1s*j c iy ,1 0 < ` D ata on i;ic rc'i'.i-in ii' j in y n c c u l ! :i.:!;.:, i. v;. ic in r mpi-.tc a n d uncon: irmcd. In a tui":;..' :/ I:-. ' o f i'v. r; - vf: : one, cr: ions j / i f;m* l.)< c . In m e e tin g , it v/ q s n oted l;; L ! **i*i:x ..nnl". ' i 1 Ji - if iJ f L-:: ::ii :ii ru: *:i' ::i i. c o n te n t is s a t '. s f ^ c - tO:y "in :.*!! ':.i! , " !:: ImM .ic mil. ' *c.,: -'.-Lti nt ;resent "'o specific concius'ons " L' I'-nli i:: ;i TiiC p o iv l ;:I r:f Vitod: `V.t d ::" 1 'e :: radii v: iv/ith v/hieii \v. a rc v/oillinu) 'here i j j a r e i n t r i n s i c urieortninlier. v/dii i>. .mu I'/tie-.: I t h u d . " _ O ADMIN loTKAaON ST1I.I. PACK; 'i'< ` LAW, TUAHi AiTIUMS - yn Tiie/V n i s 'r a t i o n 1 - . !. '. Pr-tccri- n Aocnry A * i m fe re n c e >n I '.'lls (s- :; ; lenisla iron could be : - do:. su!.;r:!.i:i<; ' o e i s . a t i o n , Cnvi:o.'.mental b a : 1 tin:; v. -.1 m s p re s s c o n i> it n. .. i i w ; i a i -:::i ; 1ic; e s tim a te at v/hen Notmtj m a t <.`o n - n e s s ha -!; !::*'! : i :ho , h-.- -ai-: In' In u s e Commcrc'. Com m itte e '.voo.Im p ro b a b ly n I ` t <- : it: :i a --/..iii.iL*- bili (See D e c. 10, rail': 1) :.r*li! lVb:n n / ,,;! 1 l-\ . t i r o, th a t the b ill is r..-t yet to the lull ( 'o;.i::tc:Ci. ( isp-i. u Ai-.- b .-naf- , ho r.i i i , bvuK..dy we inivu a iong v;ay to e o . " CPA b a u d s till-: N i-.C oilistc: !:i *I in io h-.ur*-, "w ith am en imr-ni::, " 10 s a i d , rta tin q tiut tin; oj.-ncy':: :iii*i;i s l '.l :: v/.::e ica-.iy to ijo '.v C.'.ipitoi Hill once Con g r e s s cr m es b u d ; its recess. J u s t bel--i. t . ni.n.'sn Umi , ;w-n. T u n u cy f i i - f i *f .) r . ii th a t " i n e c o n c i l a b l e <-!i:for-- c n e e s on !:'.y p ::vi s io n s " ! the I ;i :: i11i*mi "i-i-a : :.:-..*ve!i!.-vi d s nivictinent int<" Ur.v." Tu.inoy oUl1 ti* i uj p* 1!V* '>1*.19L** :i in nr. a n ecessity to p :o to c t ::u: p e iil'c !:<*i!i e n v i r u c . ; ! 1.:" at 'it: :; .e esi t:i-- c o s t s o: ontiei a i c tlie !t #*.v: :*t . '* St -tir.ii ' i- so c :;ls .; l-,,v.\ ;:L a ' tiie :l ' :l<'l Stni|0 UCCOv: jobs h av e no- V`.t ijocn C'.-::i::iit' : n i : iifi / i yip:.:. nc n.,t yoi juMcn is o d , Tur.n.uy continu- i: 'itut /n : i u : e >1:: 'i- , at m is swiji* av o id s i\e i-Min, .;;i::e iy i .:ii : : ;:; , v o : i : ,, i l . i i , P i n t M e 3 .X L C , . i *- " i f . . / H -ia i '' / < r 2oO C O 'i ^ ' ,, , 5 j p Z 't V * ' ff/u / .t -y - t ~ To attem p t-tjH H B B B B H feV proceedings of a m eeting s u c ^ ^ m ^ n ^ f n any rig o r ous sense is clearly an unreasonably am biti ous task. It is made more challenging be cause of the tentative character of much of the work commented upon here. This meeting, one of a series land I hope i growing series) for the National Institute of E nvironm ental Heaith Sciences, repre sents an extraordinarily useful concept. It is designed to brin g together a variety of scientific bedfellows who have contem plated (and indeed investigated) a subject for its academic interest and for its very timely 'topical interest. These same scientists would have learned about each other eventually but, in the best tradition o f science, it would have taken a long time. By design, we are w itnessing the cutting edge of scientific research, for this aren. This m e ttte g has as its avowed and very virtuous purpose, the calling out of the walls i good da ot unm atured and not totally intarpretad^ae confirmed research. It is im portant t t t e p this tentative and uncon firmed c h a ra c te r in mind. One is struck, too, by th e character of the research which has been reported at this meeting. T here are still many gaps in our knowledge about dibenzofurans and dioxins. Yet. the thought th a t has gone into the design of the research reported here re presents a striking degree of sophistication in many cases for which the participants should be very proud. As late as 1970 o r 1971. there existed only the crudest h in t of a ranking of biological activity of members of the family of chlorinated dioxins. U . J) ; fact that the early observations (from the occupational environment) and the early approximations of rankings have been sus tained and essentially confirmed by the data reviewed at this meeting. 18415 DIALOG F I l o 1 53: MEDLINE 73-79 (lien 390 of 486) User 5165 0295607 74030607 An analytical Method for detecting TCDO (dioxin): levels of TCD0 in saaples fro Vietnaa. Baughman R : Mose Ison M Environ Health E'er spec I (United Slates) .Sep 1973. 5 p 2 7 -35. ISSN 0091-6765 Journal Code: EIO Languages: ENGLISH Subfile: INOEX MEDICUS Tags: Animal Descriptors: CATTLE; CHLORINE; CHL0R0BEN2ENES--Analysis (AN) CHROMATOGRAPHV, GAS; CRUSTACEA; CVPRINIDAE; DIOXINS--Analysis (AN); EnvIrnnenta I Exposure; fISH PRODUCTS--Ana Iysis (AN); FISHES; Food ContaminatIon--Ana Iysis (AN); Industrial Haste; ISOTOPES; Llvei-- Analysis (AN); METHODS: SPECTRUM ANALYSIS. MASS; 2.4,5-TRICHLOROPHENOXVACETIC ACID; UNITED STATES; VIETNAM \I 0295606 74030606 Susssary: conference on dibenzodioxins and dibenzofurans. National Institute of Envir-onaental Health Services, April ~) 2 - 3 . 1873. Burger EJ Jr Languages: ENGLISH Subfile: INOEX MEDICUS Tags; Anlaal; HUMAN Descriptors: ABNORMALITIES. DRUG-INDUCED--Ettology (ET); BENZOFURANS; BENZOFURANS--Ana Iysis (AN); BENZOFURANS--Poison ing (PO); CHICKENS; CHROMATOGRAPHY. GAS; CONGRESSES; DIOXINS; DIOXINS--Analysis (AN); DIOXINS--MetabolIsa (ME); DI0XINS--PO- tsonlng (PO); DIOXINS--ToxIcIty (TO); DOSE-RESPONSE RELATIONSHIP. DRUG; EOEMA--Veter Inary (VE ); ELECTRON SPIN RESONANCE; EnvIronnental Exposure; Environmental Health; Liver--Enzynology (EN); POULTRY 01SEASES--Chen lea 11y Induced (Cl); SPECTRUM ANALYSIS; STRUCTURE-ACT IVITY RELATIONSHIP; 2,4.5-TRICHLOROPHENOXVACETIC ACID--Poisoning (PO); UNITED STATES 0295605 74030605 Tetrachlorodlbenzodloxin in the environnent: sources. fate, and decontamination. Kearney PC; Woolson EA; Isensee AR; Helling CS Environ Health Perspect (United States) .Sep 1973, 5 p2 7 3 -7, ISSN 0091-6765 Journal Code: EIO Languages : ENGL ISii Subfile: INOEX MEDICUS Descriptors; fi10TRANSFORMAT IOH; CARBON 1E IRACHLOR IDE --Cheta I- cal Synthesis (CS); CHEMICAL INDUSTRY; CHEMISIRY; CHLOROBENZENES--Analysis (AN); CHLOROBENZENES--MetaboI Ism (ME) ; Decontamination; DIOXINS; 0 1OX INS --Ana IysIs (AN); DIOXINS--MetaboI Isn (ME); ENVIRONMENT; Environmental PollutIon--Prevent Ion and Control (PC); Heat; HERBICIDES; Pesticida Residues--Analysis (ANl; Soil; 2.4.5 -1RICHLORQPI IENO - N `9decB3 XVACE1IC ACID- Ana lys Is (AN) K ". 310 0795603 74030603 Enviroraacntal generation and degradation of dibenzodloxina and dlbanzofurans. Crosby DG; Mo IIlien KW; Wong AS Environ Health Perspec (United States) .Sep 1 9 7 3 . 5 P 2 5 9 - 6 6 , ISSN 0 0 9 1 - 6 7 6 5 Journal Code: EIO 1 Languages: ENGLISH , Subfile: INDEX MEDICUS Descriptors: BEN20FURANS; Biodegradation; BIOPHYSICS; CHEMISTRY; CHLOROBENZENES; CHROMATOGRAPHY. GAS; DIOXINS; DIOXINS--Cheaical Synthesis (CS); DIOX INS--Rad latI on Effects (RE); Environmental Exposure; Heat; PentachloropnenoI--Rad lat- Ion Effects (RE); PHOTOLYSIS; SPECTRUM ANALYSIS. MASS; Sun IIght 0295602 74030602 Studies on the bioaccuaulation and M i c r o b i a l degradation of 2.3.7.8-tetrachlorodlbenzo-p-dloxln. Matsumura F; Benazet IIJ Environ Health Perspect (United States) .Sep 1 9 7 3 , 5 P 2 5 3 - 8 . ISSN 0 0 9 1 - 6 7 6 5 Journal Code: EIO Languages: ENGL ISH Subfile: INOEX MEDICUS Ta g s : An Ina I Descriptors: AEDES; BACTfR IA--MetaboI Ism (ME); BENZENE HEXACHLORIDE--MetabolIs (ME); BIOTRANSFORMAT ION; CARBAMATES- --MetaboI Is (ME); CARBON RADIOISOTOPES; CHLOROBENZENES--Me la - bolls (ME); CRUSTACEA; DOT--MetaboI Ism (ME); DIOXINS--MetabolIsa (ME); ECOLOGY; FISHES: LARVA; PESTICIOES'-MetabolIs (ME); Soil; Water; XyIenes- -MotaboI Isa (ME) f0/ Summary: Conference on Dibenzodioxins and Dibenzofurans, National Institute of Environmental Health Services, April 2-3, 1973 byEdward J.Birftr, Jr.* To attem pt to sum m arize the proceedings of a m eeting such as this one in any rig o r ous sense is clearly an unreasonably am biti ous task. It is made more challenging be cause of the tentative character of much of the work commented upon here. This m eeting, one of a series (and I hope a growing series) for the National Institute of E nvironm ental H ealth Sciences, re p re sents an extraordinarily useful concept. It is designed to b rin g together a variety of scientific bedfellows who have contem plated (and indeed investigated) a subject for its academic interest and for its very timely topical interest. These same scientists would have learned about each other eventually but, in the best tradition of science, it would have taken a long time. By design, we are w itnessing the cu ttin g edge of scientific research for this area. This m eeting has, as its avowed and very virtuous purpose, the calling out of the walls a good deal of unm atured and not totally interpreted or conArmed research. It is im portant to keep this tentative and uncon firmed c h a rac te r in mind. One is struck, too, by the character of the research which has been reported at this meeting. T here are still m any gaps in our icnowledge about dibenzofurans and dioxins. 'Office of Science and Technology, Executive Office of the President, Waahington D.C. 20S04. September 1973 Yet, the thought th at has gone into the design of the research reported here re presents a striking degree of sophistication in many cases for which the participants should be very proud. As late as 1970 or 1971, there existed only the crudest hint of a ranking of biological activity of members of the fam ily of chlorinated dioxins. (1. 2) The reports at this conference contained descriptions of dose-response information, some beginning insight into mechanisms, and the first probings toward structureactivity relationships. I am struck by the fact that the early observations (from the occupational environment) and the early approximations' of rankings have been sus tained and essentially confirmed by the data reviewed at this meeting. Chemistry, Analysis, and Chemical and Physical Properties Dr. Langer's paper on the formation of dioxins from precursors through condensa tion reactions represents a good example of w hat we should do more of. I speak here of the attem pt to predict probable and im probable behavior in the environment from knowledge of physical and chemical pro perties. Dr. Langer's nuptial analogy is apt in more than one way. He reminded us that chemical courtship leading to m arriage (in this case, condensation) was family-specific 279 WI2l599tr and adhered to some orthodox rules. Fam ily character, and how this is perceived by the other party to the arrangem ent, seems to be im portant. It seems to me that Dr. Langer has thrown down the challenge of confirm ation for dioxin formation, reported on by some as feasible in the environment. I am sure that this challenge will be taken up. One other point was raised by Dr. Langer and was echoed independently by others was the spurious formation of condensation products within the chambers of the very instrum ents used to detect them (e.g., the gas chromatograph). W hat is the evidence of "w eathering"-- the form ation in nature of dioxins or furans from chlorinated materials through the add ition of energy from somewhere? Crosby et al. and H utzinger et al. suggested that condensation reactions to form dioxins or dibenzofurans m ight be promoted by expos ure to sunlight and presented the results of a few prelim inary experiments to examine this subject. What they properly reminded us of, however, was the fact that the story does not end there. The presence of detect able condensation products depends on the dynamics of both production and ensu ing decomposition. Decomposition, they re minded us. occurs typically through reduc tion and here depends on an available hydrogen source. (They demonstrated the point in their laboratory experiments by us ing a hydrocarbon medium.) Tetrachlorodibenzo-/>-dioxin was found to be more la bile than the octochlorinated member of the family. It was speculated that there was sufficient organic m aterial in most en vironmental situations to assure hydrogen donors. In brief, environmental persistence seems unlikely. The evidence seems to sug gest that those im purities which are found are of the less toxic varieties. However, we need more samples because of the large va riety of commercial products. A. E. Pohland et al. revealed some of the potential and the limitations of two analytic methods, electron spin resonance and visible light spectroscopy. As I heard this paper, these sounded particularly useful as con- 280 firmatory techniques. The authors cited the need for pure standards to realize the po tential of their methods. Dr. C rum m ett's paper is perhaps the latest in a growing series of examples of how the power of analytic methods tends to "drive" m anufacturing procedures to be more rigo rous and produce greater degrees of purity His point is well made. We are all better off as a result. It is heartening to note the sim ilarity ir. degrees of resolution reported both b> Crummett, et al. and by Drs. Baughman and Mcselson for m easurem ent of dioxin through mass spectroscopy. Understandably these results rested, apparently, on an exten sive clean-up procedure. (I think some may still be bothered by w hat I understand is a wide intrasam ple variability among some of the measurements.) Since they are "push ing" th eir a rt to a point near its limits perhaps these results deserve as much con formation as possible. Nevertheless, the power of sensitivity and resolution are indeed im pressive. Biotogieal Effects I think th at it is extrem ely im portant tc acknowledge the fact th at the original bio logical insight into dioxins came from a series of observations made by Dr. Suskinc of accidental occupational exposures in the late 1940's. The exposure was the result of accidental release of chemical intermediates in a 2.4.5-T plant in 1949 resulting in ex posure of a num ber of w orkers to manifest chloracne. In 1957, Kimmig and Schulz re ported chloracne among workers in 2.4.5-T plant in Germany. A th ird occupational in cident occurred in a 2.4.5-T plant in the United States in 1964. In a way, it is some what disappointing th at there is not more hum an experience reported at this meeting I think th a t there is still a clouded issue, an unclear distinction between the effects of PCB. 2.4.5-T and of dioxins and furans. F or example, we should somehow ascertain w hether Yusho disease in Jap an was a re flection of exposure to polychlorinated bi phenyls or to furan im purities. Dr. Fire- E nvironm ental H ealth Perspectives t 18418 l t66SIZHOO a stone reviewed the history of the contribu -lqer^T-teeft: kluarijifeginf >hiqgfa (n ' liver >- tion of the 2 $ 2 S B M B S |E ^ o our under fu n c tio n ^ standing of dioxins. The sleuthing: done by let deptassionr aHwed-pIatelet function. le u ~ ;. the FDA pieced together the story of the "cocytosis and- hemoconcentratiorr>~ anct'tbefj1' e large-scale loss of poultry (which happened IymjiuLfcicjsyafent"f sDragrr.^thymua'a^dlyraDli-- ..it first in 1957), related it to the use of nodes>. The atrophy^of the thymus, and the o- tallow in poultry feed- and. eventually, to general lymphoid depletion reported at this y. the presence of dioxin impurities. Higgin meeting were very"strijcingjT Jr botham et al. first offered a rough approxi As for morphological' alterations, the mation of ranking of biological activity of changes in the ultrastructure under the elec n dioxins which has turned out to be strikingly tron microscope are of course most interest :)y accurate. What has emerged from this meet ing. Perhaps the most significant point is i n ing is the very wide range of toxicity for that the morphological alterations tend to in the several members of the dioxin family follow and confirm the functional changes ly, (perhaps as much as 10r). which were described independently. THeri n- - 'Thjg.;,tpeeiing.'_^yealBiv, r o n ^ in t^restin ^* ^ Sem3 to be a delay (perhaps- on- the order, ay e x p o s u r e a m t ; m a n i f e s t ' a teiff^ fe Jg iig ii ______ ___ _____ _____ __. . . . (. The magnitude or fFfe me - - 1n r ic x l ^ B r tw iV fi- S e v e r a l - p S S a ^ a i i E T ' ' r A change is"'dbse-reiated. and the changes are ;h- r a i n d e d - u & d t i ^ - J p ^ b e s u c c e s s f i i n r a W t ] reversible with time. A particularly fascinat ts, - j n e a g n r : iiw jd g tw b h a lo g g n ^ r a y '; ing finding was that of multinucleaced hep m - atic cells. Do these represent a stage of 'er attempted regeneration and repair? Alter m - natively. are they possible precursors of eoplastic change? This conference pre sented little evidence that dioxins would ITTs'ay very little about teratogenesis. It induce or promote neoplastic changes in to >ioia ind the : or ites exesc re- seems to me that a strong case can be made for clearing the air about the mechanism of teratogenesis. Is this an example of acute (embryo 1 toxicity with a steep dose-re sponse curve and a demonstrable threshold? It's not dear that everyone who reports birth iefects is talking about the same pheno menon. Dr. Moore, at this meeting, described some fascinating, postnatal effects of ma ternal exposure to TCDD through a series cross-fostering and reciprocal cross-fost tissues. Patterns of absorption into the organism and of distribution among organs once ab sorbed are beginning to emerge. Xot unex pectedly. water and lipid solubility seems to emerge as a major inriuence. althou^h clearly ff-dlbxfn "CTugit. dosea_= in--male--rats l.-th a ^friount absorhecL.via the intestine from an_ " ingested' 'dose appears to he about T majorifo- o f the absorhed_.do.se appears in VI inthe meaore ing. sue. ects ering studies of mice. These deserve further attempts at interpretation. The effects on experimental animals are difficult to summarize completely. However, there are some underlying currents showing drought ill there is a variation in susceptibility , the feces at a.rata_-a^l-2rr foy and in the _urine_at a. rate.of 0..V5 davt-^sm all amount'**** carr be detected" in. the.expirfid^r_C day!" mVim al' resident, in., the organ- > lam, fa characteristics ly tountt. 1titll-~ f ^josajissufr and. th* live# It is notaRlyTaR- sent from certain other fatty tissues such ans. among species--gmaMll8|^ re 5 lM fWi<at > a those of the central nervous system. tain difference* J By ^contrast, for re- (31 rfetayedjsffecS ar*-very prom inent_lU yer' -achieves ab so rp tio n Again, bi- change-S'`week after.. exposure-l-=.iAk^theX a large share is found in the liver (oO^t-) 'ire- 'najor'site of toxi*>actiaa. appeftEiJftkiutA^ and in the adipose tissues (12'^-). Once in tives September 1973 281 T * ^ 'i ^ t e T ^ t ^ a p f m r e n i E f e n i S L . S i very little. It seems to me chat we still rnus r e m a i i r r e s i d e n t - f a Z l o n g - P e r i o d s - i n - t h e - l i v e c . . .. .determine whether Yusno disease was . m i c r o s o m e s , - . _____ reflection of PCB exposure or a result This meeting served- to bring together a exposure todibenzor'uran or other impurity remarkable amount of work on the effect For dioxins, we now are better equipp^' of dioxins on cellular enzymes. This was all However, we must nowreconcile a numhSf the more remarkable, as none of this work of somewhat paradoxical~observatifis^< had even been conceived of two years ago. -SSp-aoramarily high' degree of biolo^jcaLT A number of hepatic enzymes were found activity, especially tor ciManrmheini^ir- to be induced and a few depressed as a forma. ' . (tetrachlorodloenzo-p-dioxTn result of dioxin exposure. (A general caveat pointed"out to be* the most potenFlttai] was voiced over what appeared to be unu jfigtgSBltoxin-knownT; (') sm&'iTiiTspiRlt sually high doses of dioxin used in some of -drifeieflces. in,activity; iaj ex 'diftererw,. the experiments.) The degree of induction .. was at times striking. The experiments re- . biological activity tans oft rapidry-wniT*' caemical structure; to) |a4gnr vealed a dose-response relationship. Again, d f e r i f t r f - h p f n r p r n v n r m a p i f p s t a t i n n .! .- f f il C f .' ' there was an unequivocal sex difference and reTaied^effects iliLIliangdastitig^&ufe''ni^" a characteristic latent period between ex r a u i e i * i w u i b i p posure and induction. Effects were often long-lasting (for example, a persistent threefold increase 38 days after exposure in one experiment). Again, lipid solubility may play a large role. The meaning of enzyme changes is as yet unclear. There are some striking dif ferences among species. ALA synthetase, whose activity is related to the disease, por phyria. can be induced by dioxin adminis tration in the chick embryo but apparently Effects on Wildlife Understandably there is less work her than one would like. The preliminary wor* reported by Bowes concerning survey of wildlife is a good model and should be continned. Preliminary results- seemed to suggest a very wide variety of chemical species found in the animals examined with an un certain role for dioxins and furans. not in mammals. One has the impression REFERENCES of being very close to some insight into mechanisms yet not close enough. The com 1. H ig g in b o t h a m . G. R.. R e ss. J.. and Firestone. 3. C h ic k e de m a fa c to r in fata and fa t ty ic:dj. bination of enzyme induction studies and Chem. Eng. N e w s 44: 53 iL906). changes in cellular ultrastructure could 2. H ig g in b o th a m . G. R.. H u o n g. A.. Firestone. D.. prove very helpful. 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S a n it. 1974. dialvaia behavior, and resorption. E. E. Ganaei (4). 33-6 (Ru m ). A reviaw with 3 ref*. 33962r Alcohol dehydroganaae lystam d u rin g chronic 33977* Supposed m echanism o f th e action of s u rfa c ta n ts d a lc o h o lism . Gurtovanko. V. M. (T io n tr. N auchno-laxJed. Inst. on a n im a ls . K um pon. N. B. (Inst. Obahch. K oram unal'n. Gig. Sud. Pxikhiatr. im. Sorbakogo. Moaccw. USSR). Z h. N europatoL its. Syaina, Moscow, USSR). G ig. S a n it. 1974. (4). 78-80 : P ttk h ia t. im . S . S . K a n o k o v a 1974, 74(2), 291-8 (Rum ). ( R u m ). A reviaw w ith 23 refa. T h a affacts of su rfactan ts on call A review w ith 80 refa. E th a n o l [8 4 -IT -5 ] m atab. in anim al m arabranaa an d lipid m atab. are discussed. j tiia u ts is discussed in relation to pathogenesis of chronic 33978 B iological modal* o f alcohol to leran ce and alcoholism. p h y sic al d apondaaca. K aiant, H. (Dep. Pharmacol.. Univ. / 33963a C h e m ic a l m e th o d s in c r im in a l te c h n o lo g y . M aohly, T oro n to , T oronto, OnL). A d van . E x p . M ed. Biot. 1973. 35. A ndreaa iS ta ta n i K rim inaltak. L ab - Solna, Swed.). K env. 3-14 (Eng). A review, w ith 38 refs- in which eth an o l [64-17-5] T id tk r. 1974. 86(1-2). 3 8-40 (Swwd). A review w ith no refs. interference with. T h a fto d back control o f physiol, functions ia T h e S w ed ish crim in al lab . o rg a n iz atio n ia d isc u sse d w ith discussed in relation to modal* of drug dependence. r emphasis on snsl method* for am phetam ine [304-83-9] and 17979b A ddiction to b arb itu rate an d ethanol. Possible m arihuana da taction. B. P ry u biochem ical m echanism s. TtbakofT, Boris; Ungar, Frieda; e ----^ 3 9 6 4 t N ew a d v a n c e in t h a to x ic o lo g y o f c a r b o n A livisato*. S. G. A. (Dap. Burnham - Chicago Mod. S e h - d is u lfid e . T eiiinger. J . (Dep. la d . Hyg. Occup. D m - In st. Hyg. Chicago, 111.). A d uan . E x p . M ed. B iol. 1973, 35, 45-55 (Eng). E pidem iol- Prague, Czech.). A m er. In d . H yg. A m - J . 1974, A review, w ith 43 r a il - in which ad diction to barb itu rates and 35(2), 55-61 (Eng). A review w ith 37 reft. ethanol [84-17-5] if discussed in relation to biogenic am m t " 33965u B io ch em istry of alcohol. B att, R. D. (Massey Univ- taatab. by tha brain. Palm areton N orth. N. Z.). N . Z . M ed . J . 1974, 79(506). 556-60 33980V E z o to x in s a n d th a e n z y m ic sy s te m s. Busila. V. T.; (Eng). D isruptions of norm al body m atab. which are d ue to Drigom ireacu. *,L (Clin. Boll In fact- Inst. Mad. T im isoara. eth an o l [8 4 -1 7 -5 ] are re vie we d w ith several refa. T im isoara, Rom.). M icrobiol- P a m rito L , E p id em io l. 1973. U 9 8 8 e E f f e c ts at a lc o h o l o n th e k id n e y a n d b lood 18(6). 481-6 (Rom). A reviaw with 20 refs, on tha affect of ele ctro ly te . Richm ond. D. E. (D tp. M ed- Auckland H oap- bacterial exotozina on tha enzyme systama involved in metabolic AuckJand. N. Z.). N . Z. M ed . J . 1978, 79(506). 561-3 (Eng). pathway. A review with 17 reft. T h a d iu retic an d oam olality efTecta of 3398Iw P ro b le m o f p o rm ic sib lo lim its o f p o to n tia lly to x ic ethanol [84-17-5], and the relationship of gout, metckolic su b sta n c e s ia th e w o rk in g an d goaorai en v iro n m en t of acidosis, and m atn ee iu m [7 4 3 9 -9 5 -4 ] deficiency to E tO H m odern s u n . T ru h au t, Ran* (Fac. Sci. Pharm . BioL. Univ. ingestion i r e discussed in re la tio n to th a kidney and blood Rene D escartes. Pari*. Fr.). E nv iron . Q u aL S a f . 1973. 2. electrolytes. 135-65 (Fr). A reviaw with 47 refs. T ha toxicity of pollutants U K 7 w E ffec ts o f som e a i r p o llu ta n ts on fa rm a n im a la. and carcinogenic compda. is discussed in relation to ev o lu tio n of Jones. L. H. P.; Cowling, D. W. (Dep. Soils P lant N u tr- G rant. perraiMible doses. Res. In st- H urley/B erks- Engl.). N a t. Soc. C lean Air, A nna. 33982* Toxicology and epidem iology of n a tu ra l h ep ato to x in C on f., P n c . 1973. 40, P t 1, V II, 7 pp. (Eng). A review with e x p o s u re . KraybilL H. F. ( N a tl C ancer In a t- N ad . Inst. 32 refa. T h e effects of air p o llution by fluorides, d uets, an d H ealth. B ethaada, M d.). Itr. J . M ed. S c i. 1974. 1(X4). 416-25 heavy m eu ls on farm animal are discussed. (Eng). A review with 48 ra ft- of hopaiotoxins including U 9 6 8 z E ffe c ts o f p e s tic id e s o n so il a n im a ls . Newm an, J. mycotoxina. p lan t toxins, bactarial en do toxins, and m etals. F. (P lan t ProL L td - Engl.). N a t. So c. C lean A ir, A n na. Conf.. 33983y H ost factor* ia bepatatexicicy. McLean. Andre E. P roc. 1973, 40. P t. 1. V III. 6 pp. (Eng). A review rich 7 refa. M. (Univ. ColL Hoop. M ad. S c h - London, Engl.). Itr . J . M ed. M ethods for investigation o f th e effects o f pesticide* on soil S c i. 1974. 10(4), 431-5 (Eng). A review, w ith 19 refa- of the anim als, and the effects of insecticides, fungicides, and herbicides relation of liver m atab. to liver damage from environm ental on soil anim als are discussed. pollutants, industrial chama. and drugs. 13369y D evelopm ental studies on some enzym es aaaceiated 33984s Senocia and (h er p lan ts as liv er poisons. McLean. w ith detozicatiw o. D utton. G. J. (M ed. Sci. In at- Univ. EUzabrth K. (Maudsiey H asp- London. F.ngU. U r. J . M ed. D undee. D undee. Scot.). E m y m e 1973, 1 5 0 -6 ). 304-17 S r i. 1974. 10(41. 4.36--11) lEng). A rrvu-w. w ith 7 refs, of <Kng). T lie a u th o r's work no th e activ atio n and induction of p y rrn liz id in r [8 4 3 -3 0 -9 ] alkaloida from .V ftri'io and o ih er r liir iir o n id a lin g . h y d ro s y la tin g , an d asooed. enzym es, esp. plants iw liver piusotw. u D l ` e lu c u r n n ? itr a n *(r r a *r [E C 2.1.1.17) [9034-4X--(]. during 33985a U iochew sicat e f fe c ts o f a f la lo x in s . W .igan. Gvre'.d Development is sum m arized an d re la te d to th e detoxication N. (Dep. N u tr. Fim d S c i- Masssu'hukwits ln>L Tvcr.n.'L. 52 Refs, are included. C am bnoge. Maas.). Ir. J . M ed. Sci. 1974. 111,--I. i-1. -o ,c.::c A review, w nh 29 re ts- of toe u itin i. efiecv, u: * ~ 18421 71 ( i r ai ,-t/i^rw cf * V4 71), ItfTTl P atfr 7,' *4intu!ii(iMi .* inbuJim. 4 nr I haplt^iobuiina Mid 3 AfiMiu.ii. Mi and Bi in the la c accounted 2Ji a.n: .... ,4 ...... . . fiTT** <*A /ivufe |7738-94-4| p n a k ic r d icdy xlichc Iiu* ik. im p. alii-r.fituvk Ihu imsichl about a slimnlalinu at ln h 4 a fn n after .l 1334-tOvr P a lks lngy a t liver a eerneie and .-.icenm tioa nn.-i -I ii| -u re . hem analysed after 3 n o alb a at ingestion at a d m ia ia tra tia a a t d im cth y laitn iaam iaa ... mn>*iv. ^ . lic.-.i> ru'i.il.4 appeared eiaentiaily identicai to contrail. K uner. fluatavo G. R.; Wnoda. John IV. Lu ".ic. .m; 1 us.-cmui.: t l u i adaptive p ro em s had hem elicited which (M um Clin, and Mayo Found.. Rncherier. Minn.i. J . .''t. enabled me animal* u> tnictate couac. expaeure to high levela at Oncol. 1973, 5(1). 9-16 (Enp). Cantrilnhulor rnci midz r.o the reap, metal* inciudin* Hg which ie usually corwidecod toxic. conceation and nacroaia occurred in tka liver- of w - :iv .r I3343-V S u b acu u oral toxicity a t trisodlum aitrilecriacstaln lathai doao of dimtthylnitraaamina |<2-73-9, (.*...'-,.<11.- .. .1 (Naj.NTA) in doce. Budny. John A.: Nirwcnhuis. R. J.; Auxilary livor tranepUni lavad tha animal ..ve :it iw.-.-- Buehier. E. V.; (>oidenthai, E. I. (Miami Val. Lab.. Prncter the hepatic daaaapa. Curboaia of tha liver die act ur .. u v and Gamble Co.. Cincinnati. Ohio). Toxicol. Appt. Pharmacol. care. 1973. JlilU. U6-53 (Eng). Tnaodium mtrUatnacetatt I33441X Pbymioiepical and u ltn a trn c tn ra i afToei of .iuo'.ide |.*0<*i-3l-3| fed to dona Car 90 day at 0.03, 0.16. and 0J% at the on tiaenna of Rubua cultivated in vitro. Pilc. Pau' K.. R; crd. uiet produced no Mtunflcant change in nneeal appearance, Jean C. (Inat. BioL Phyrioi. Vep., Univ. Launann-. uauxarr* urvival. hetnatcl.. aerum ebem .. urinalvaia. (h o i cation Swita.). Bar. Schmaa. Bat. Gat. 1972, 5213), i K'*-.*Cl :- excretion. ..n I microacopie tiaaue eatmw Ntoflotrianerir ad d At hifh Irveia (1 0 " and 10 `Af of NaF). /Tuu-ide .lSSn4-t'- was depi^i m bone (123-42 ppm a t tba`9 J% level), but thia inhibited pow th (exprvaaad in Hrmn of chanto* fca in., wt. ai:a ante wit in- . r.-lvenm viTcct. total protein) of IT OirrihOta rirttjtriiad m arini The m a - I3343<ix Carrmpwcaaa and larp a be a ai aiaaratiaa la uptake o f fluoride n a i n a i n j ^ w th e ie n b ^ p ig . pb-jc fabuut 10 m am m als. Grarwi. R.; .Sharratt. M.; C anaiaoi. F. M. Bh Ganpoili. S 0 . (Ik. Ind. Biol. Ret. Aaaoe- C anhaltao/Suney, riboaomaa and xltreed Ori M n ^ tm r- y C m E e d w -ia ria and tne Engi.l. h'""t Co-mtt. Tnxicai. 1103. 1114). 865 14 (Bag). endoeleemic r e t f c p i t . i : Administration at carrageenan |M t > U 4 | in either native or .J ff4 3 y Oaeaw i n w M d M j k i e P ^ ^ n . ^ E f f e ^ on detruded form produced acute or ehrouic uinaearinin in the largo intestine uf s u l n 't pica and rabbita. P ra tli aliv e change G.; OeLucia. Anthony J ^ ^ e e h i Ti eeeeeXc Aith Ch.-iM0p.1er, cotuiitcd primarily of accumulation at macrepbagm ia tba Croaa. Carroll E. (Sea. M ed- Unhr. Calilhraia. Davis. v.'iif.<. lamina pn.pria and were aaeoed. with the prm enri at cam g stn an J . Lab. Clin. U td . 1173, 62(3). 357-45 lEnpl. A are fip-vinr in the uoenithatia! tiaauea. Nuns of them chaapaa oceurrad ia of rata to the environmental pollutant <uonr |1lJ2S- i i-A \ i ppir. the rat. hmuntar. *quirrel mr.okev. or ferret. Limited taata for 8 hr) dacreeaad tha O eonaummuiu >4 >unp .ion _-i r.. . mid indii-alcillh.il numana were nlwrvMMant tn th e malarial. autachondria. m did in vitro oaena traatmant of tha hon npcnaia 13.1137a Intestinal eflccta <d cam gaanaw n ia Urn rhanm or mitochondrial fraction. In centra^ uiiacuta expiwun-s 'Oh m onkey i.Mat-sea m u latto ). Beuitx, K. F.; Goibarp. L ; ppm for 10 or 20 daya) incraeaad 0 ; utilixatinn. An 1;.. -1 in Couistnn. K. (loot. Ran. Pathol. TaaicoL. Albany Med. Ceil.. tha epacific activity cf mitochondrial rapif-torv ata. - :hi . Albany. N. V.). Finia Cm mat. TaaicoL 1913. 11(4), 565-73 U ttar anim aU waa not nif&dont to account for he r i . . lEnii). Male and female rhmus muniuys ghraa native carragnenaw tim uU tioo of respiration. S ubacuu oaone ir..*n-m-eu ... n [9000-13-9i (from Chondnu crixpua) at L3 f/kx/day in thair abondanco of Typa II alveolar calla, however ar.d 'hora ccl'.* drinlunp water for 7-14 weeka all p*"4 wt. and remeinad in tvwtain many mitachondria. An increaaad no. of .:.n.horuin tond condition. and miczuacopic exams, of thair infaarinai tract may therefore account for the enhancement of 0 ennaumption ravealed litt.e ( no chan*. Mookays (ivan degraded faUowinc subacute axona exposure. carrageenan iiront .chcume spinawsm) a t 2 J g/kg/day mined ITUt l i F lavitail dzcu larin p renin activUy ia r. - h ijw ir.c considerable wt. ltd, intaarenal tract Mending. cad inmnia daaae af --a--1. ~ knaw u to induro bypartauaioii. . h. Pathoiop. changes is :ha colon rx n n d hem shallow muooaal MitcbaU. Jr.; Srianpar. Sierre ret W. (Sch. Med.. Wr r jr. eroeiona to uic<rat:nn aaaoed. with -cauular infiltration, granule" Uoiv.. S t. Louie. Mo.) J. Lab. Clin. lion tiaaua in tha Umina propria, and formation of multiple crypt 309 106 (En*). Blood renin [9915-94-3] a rti\:.y w .. y .. . ;n tI aboeacteameama. P1 .hicoase rchoanpgm r1eversed aomearbat uhan tha anrinale rata id m in iaa n j cadmium acetate [543-99-Ai in a* t*. <ui!iciem _ l recovered on ta.i w aif: for 14 to induco bypericuion but not overt toxidty or rana.. ^vL13343*b fcrsig. J. Toxic effo B.; Jone. cu at U Glianya; .7 .K cttc Butlar. Wb l.a rilh H.: anm p Berma. rie J. r iM .. The animala reciewd 1-8 amoiaa of Cd i-p or 5 .n in tnair drinkinf renter. The Cd-injectad rats hea xmuluncoua 7-<1 O n 'tm c o L Unit. Mad. Rea. Canne. L ab- C anbaltoo/Suney, elevations of both Mood presene and main activity, 'he increase ' TinpL). fo o d C o m e t. T a t * I t t i , U(4). 686-66 (Ex). in tha two p aram au n bainp ripnificantly eorreiotod. ' 1r* ro 133444a D a tm m ia a lu a a t carbon mor.oxida and carbon d lasid l a m e a n t eaiako. Rati, H.; Kuhn. n . lA.ustria rXOCc Tabak nmlu A .-G - Vienna. Austria). Fachlich* 'l u t . O t a m . Tebakregie 1973. 14. 239-51 (Gar). An pp. U uesenbed .c.r tba compis u and direct dstn. of carbon monade.. 839 06-01. carbon dioxide [12448-11, oxygon ,T733-44-7. nitrogen 2.3 7 i-T c tra ch lo m d b g m o -o -d u ,iin _ tn ~ (174641-4) [7737-37-91, and methane [7442-*| in u p a n t smoke. Tha ana pencardialedam a awn-deetn-in cturkana aitar a rinda oral doao charmai app. contains, in saquanes. a wmok .ig machine, of 25-50 g(//Ikt*. T" ha.axtrem a to' xi' c.i.t.y....o...f...I...f..o..r...f.m....n..a..a....p..ip woo sm oke-collection balloon, alsctromapoatk. vmi.e. and *as confirmad. Female rata (i**n I orally a t 200 sg-kg bad depramed cbram atotnpb equipped with a i m column filiad sritn a 5 A mol- food intake and wt. look and died ia 40 aaym. Paatmottam sieve, w han n e tad oriental tobacco bumad more clearly, and exams, revealed faetric bmaunhapa end j-- i"-- ia many 1 pmducad slightly lam CO than Virginia. Burley, or cigar tobacco. Tha liver showed patbol. ebaapm a t later period, ia particular CO prodn. eras increased by " " i with puffed or sheet tha formation o f m ultiaudaata paiaachymal calia. tobacco, but unafbetad by addmixt. with synthetic tobacco. I ~133439c E xcrntiaa t a d matabaUam a t realty admlniwarnd Inrram sd papar porosity, or indusion of a venula:ion zona or afUtoxfn B. by rhaaaa manbaya. DaUeina, J . (4 Haiab. D. P. aiscrive filter in the cig am also reduced CO prod... Thus. CO H.; Wopan. G. N. (Dap. Environ. Tm deei- Urdv. California. in cicaret emoke may b e contrallad b etu r tn* airerin* cigarst Davu. Calif.). Food C o m e t. TaticaL 1973, 11(4), 803-16 p n p n . (papar, filter otc.), than tha tobacco bland. However, (En*). R h a u a monkaya p v e n '*C labeled oflotoxw 3 , (I) synthetic tobacco can be used to lower ire u r -nd nicotine content of rifarets without increasing CO pmon. s 133446b Toxicoiopiesl. radioisotopic. ,.-.d immunofogical tody durimg tba >--rJuation of tba setioo of sorto detarg an u nadar experim ental conditions. Vsldrs. In ter or*. ...attar. S.; SaUev. V. (USSR). Gie. TV. Prof. P aul. Eat. SR 1972. No. 8. 115-19 (Rum). R au riven oral doom of tha detergents tulfonol [12963-63-7] end tipoi (39456-12-H et 20% LD-.-Zday for 30 data bowed no abnormal chongas in appearance ->r behaviur. Radioisotope hepatography -showed AhaI aulfonol .ichily dacreaaed the abeorptioo-aicistary fusetion os the liver. Neither illK2-(15-A| orally et 0.015 or 0.4 mp/kp excntad 40% of tha deterrent effected skio microfloral levels or the phopncvtic r.ininactintv in the urine and 42% in tha fscaa in 7 day. Tha ectiv-.iy of blood oeutraphila. Tipoi inoccsd j temporary `i'-*il and 1- p the livnr m ain ad radioactivitv for > 5 weeka. The decrease in erythrocyte no. and itsimnia in wutrophil count. Wt. ..a jn r u rin ;. > metabolite eepd. fnnn a CHClt extn. waa e/latoein m in hy tha expti. animala slightly lapped hcliind t h ..t... cnntrol*. 1fi73.>-2::-9|, which accnuatad for IH-20% of tha administered Thereto, the* d e u rp rn u are of Ime toxidty for animat. .-.niiiuiciiviiy durinx days 1-4. Knur unidentified metabolites ^ 133118c EfToct at tk a s tru c tu re sa d physicochem ical w ere ai.wi Inurul in th? CHCL fraction. Aflatoxin P i [322i543-4|j us liUrn of soma phoaals on th air htoUcirui activity. Vriiire. . 1 ine urine represented 5% of the adminiatered radioactivity. I Inaxbor* {USSR}. Gig. TV. Prof. Patoi. Let. SSR 1972. N>. 8. -mi wa* e x c re te d as the xlucuronide end the SO2* conjupate. j 146-54 (Rum). ^d i/a tM b id jd U S S i (ill 195-1-5-81. dimi*r'll. - Only 15% uf the fecal radioactivity was solvent extractable.' | C u i ^ S1 \ u1 i t i l i 11** 3 tlVX P 'C. mi rht est i:. vio MV ____ 7=^_18422 i. - Ift n d ). T9 ra id 1 -.S in M ill h Hi ria on if. :on si. . in ent on. .eir oui i** bon tna ' err. : for MU igcn on line. c*n"ol and acco. sheet acco. ne or CO xard /ever. :otia >Kicai *fsU lr. S.; No. 8. tlforxoi 0 days iavior. lightly sen her 2cyuc .porary ,i. Wi. >ntmU. remieoi Veidft, No. 8. u th y l* ? i m* : 4--fiMiCUbiC.r Vo*. T9. 197H (Uussl. i d i l r l bv Ysnnu>. . '.'.'iri... :..u c h . . Epidrmjoi.. Miknioial. Gigu T sllu.. 1 'uv.f . mo-. . us ... OM OM (a jmghurt like drink). Jarru* a t 'j .!-5|, . -r,. (110-44-11, andnyridanmt (CS-2M| dc.Tva.urd :ha : m ethemoglobin and tuifhcmoglofiin .1 ml. indu-cc - nitrate |14787^M 1, whan given along with NO, tilia protective affect whan iu lactic acid w-.s pptu. ... . 'f r salt. Sour milk made from unpastr rriyr. milk -:i.- - b .. mathemoglobin and sulfhamoglobin iirmam-- in h - n humana eating fond contg. N O,". Therrii.r: .. p am .u '... nhenal (1) [376-28-1 j. aad other nm hdphenrila found ia snal product should never bn consumad login hr v ith NO. ' v u ii n w showed Utile cumulative to n e propeniea whto tested furnia, a.g. vvrrtablaa. on p el. animals. S survey of iho Utefutara iho usd th at th a n 133433c T etrataconic aad e m b e o to u c actior. r.f ,. . wma no clear relation between the bud. entity of thaaa phanola nitritaa aa d n itn la a added ta feed products. Sub. tit. I i and their cham. atrucuira and pfays. chaai. pfnetartira Volknva. N. V. (Lcningr. Sanit.-Gig. MeO. inat.. 1--- - ' I33447d Combined afToct of atmily a d n la lstn w d a eraa.l and USSR). .S5. Dakl. Renpui. S n d a Epidrmi>t.. ' 3-oapbtfael oa a warn, hlaadad aegv siasi Valdr. local . Gig.. 2nd 1872, 308-11 (Rusal. Ettitad by Yanru (USaR). Gig. Tr. Prof. Palai. Sai. SSR I t t i , t a . 8. 156-84 Tallio. Nauch.-laalad. Inat. Enidaminl.. Mikrnhuii. Gig. ~... " (Rusa). RaU recaivtng orally f eran I (I) (181 ( M l a l 95001 USSR. Na nitrite (7037 88g j. gad to a lesser a u n t ' u t (701-88-41, warn atan n ly laaatapndc aad etnhryounu. \ check ambryoa whaa a d ia d a t 1 aafogw ia atar aoin. V,< .bve,. of tha fatal chicha A a n a l a a n f n t r i a - a a d fat -U;--tre; chin**. .u'' . rts . 133484d T o a ta tn a f p w a d a h i t i a. i r i n a ry product * $ . CCr". phaaal aaldaliaa. V U d o o f^ ftta ra U . tim L Ekap. K lin..-*.'. Tallin. USSR). S * . T e t * Ep-4r.-. .... Afikrohiai.. Infek. Qim W ^ t M , 53k-7 (R u n ). Ec.tvc Yannua. A. E.. T allio. N ouch.-laled. (oat. Fn.d. ' Mikrohiol. Gig.: Tallin. USSR. Tha toriciiv of a pvrocatu - - ma k ; day or S-naphthoHII) (133-184) a t 0.14 m g/kg/day Cor 8 -phenol m iit. |35458-1C*3| variad dimetiy w.ih tha pr..;>.r . . .. mom a showed abaanaalitiaa ia narvooa ayatom functions. aa p yn eateehal [120-44-*I and waa higher in famaia ru u <:-- ... indirr-.'td by chango in canditioaad taAan fonaation la faulty moles. Tha d in . pattern sf pyrnrstK hrt p-'-> min;* -i~ --. regulation of blood preaaure aliar adranlina [3l-43-4| bv gastric gavagt) in m u waa ujmewhat different f--:. administration. At 50% of thaaa daaaa the m ai pda had aa taaic phenol [188-*5-2| iu alf and w ar' characterised h; a ' effect. Tha 2 compda. upon ownhinad idiaiaiatratga vara period of inrmaaad motor activity lc.tr. running . d i' ir.v. additive in thair effects on tha amia ala storting 3-3 min poaudmintstmtioo. ben dom e . x-, c a : 132448a Effect of caloreprana aa a i tr y igassrali. Sal'nikova. finally death (usually within tha 1st faw hr. ' L. S.; Fomenko. V. N. (Inai. Gif. T r. Pmfiahnl , Moacov, 133488 E x p arim aatal taxiuolog^nl study it some USSR). G ii. Tr. Prof. L a*ol. 1873. (8). E M (Rural. nitroparaffias. 2. l-N ltn p ra p a a a . Deu -idt. J-: \ u--eur. P.: Female m u inhaling cnloroprtna (121 88 6) a t 3-4 m g/ar1 (La^ PoUociar. J . (Lab. Tooivol. Hyg. Atm-v... Ft.), huff. Sot tha max. parmiaaibla caacna. ia industrial ratahllahmapt) b u r b n P h a m . Lille 1872, (4), 121-6 (Fr). A'oatar scminiatc.-td i.p. daily throughout thair pregnancy abarrad Ugh emhrynaal or by inhalarn. 1-nUrpropane [as-? 2 induac lovrar ! . , i k mortality, reduced beai wt.. arid abuonaaU ti* la fatal vom itar of methodogiobin than thaaa pravioualy oo*c iAar i-iatiopropan= permeability. The aeo aau hewed deftc a r t wt. gaia and poor a tsaatmant of m u . 1-Nitrootapanc. iv-.evar. sas -o m to-, functioning of tha parenchymatous organa. Chtaropraae rim iuriy (inducing death at loarar ilotcai than i - .iropro;- . administered at 10 timar lower cooca. etili had aa advana affect rauta, and Ian tmdc than tha latter bs :hc r-u:mnt>an ... .t. oa tha offsorina of the m u , and at 100 d o r a l o u r csaca.l0.58 1334447 E xp arin eato l taxicclcgicai e'-y.. V aam v ir:np.tr< B i / m 'i had no affect on ambrycfinraia cr oa tha offarpiag. fla t. 3. .N1trea tbo a t . Daguiat. 4.: -- ,m . P.. 133448 S u b atn atlad aa af the raailranra perm issible (Lab. Toxscoi. Hyg. Attnoa.. Fr.). BuiI. j : .. Pharn ,, ,, ' oaacaalrattaa of dibutyl phab alata la t i n a ir aa lad u etiiai (4). 137-41 (Fr). W hether adminiattred to rati . ; prem iasi. Antonyuk. O. K.; Aidyrara. M. V. linee. Gig. nitnethane (7*-24-4| teas cun*, drmblv !er< t - Tokaikai. Partita.. Polim. Ptasa. Maes- Kiav. USSR). Gig. Tr. tha pravioualy studied l - and 2-nitropropinta- Even .. .. Prof. Zahai. 1873. (8). 28-30 (R un). AuaL af gnaw givao off acuta intoaication, only low levels uf mathamug. t ... induced by mtrovrhana. 133437c E xv v ru u rstal r t v -alngiril suidy at oersur..- COt o* ra ts. 1. Acuta ln tra p aritaaa ai in iaciratiaa. C.-r, .irHaguauoar. 3. M. (Lab. Taaicoi. Hyg. Aunra.. Fr... dm Pharm . Lilia 1*72, (4). 148-54 (rr). In mta sr.ih.). had uer.i COt M t given a star! i.p. injactn of acetonitrile (73-d5 y; >'8> coocna. of the latter ware similar in all organa te . ..'. - - i ' . i during heating of poiyfvioyi cfaiorida) malarial p laatio iad with m g /100 g). coocna. of h as hydrocyanic acid ,74- jU-b. were phthaiatea thowad th a t tha major c o n p o e n a t waa dioutyl niigibla, and lvala af daantUtad HCN rangi i :rt x a ;c. - i phthalatt (I) (84-74-21. Tnaiaoi. atu d io at tha affiacU of I on 359 Mg/100 y in the liver to highs of 1317. 1757. end 1046 -s mica. m u . ta d m bbiu ware carried out. aad extrapolations to in the splara. stomach, and skin, map the human organism indicated that tha air inaida induatriai 133438b O rder d e m is e aortain >pray inhusive* u> -v tau b lith m en u should not m n u ln m a n than 0.6 mg 1/ m1. b a a aad Uy----i--- tu h a ltp ra a due la finding of immir.t t ! 133450s Aatoimmuna pr ar n a r a la anpar i B n a u f b aran aa-iad " lu x ard ta the public hsalth. Anon. (Conaum. Prod, -b ' ucad ham epathy. Tilt liar hah. E. S.; Fraah. V. N. (Mad. Inal., Coram.. Washington. D. C.). Fed. Regtat 22 Aug !73. Sverdlovsk. USSR). Gig. Tr. Prof. Zabol. 1*73, (8). 30-3 38(182). 22568 (Eng). T h a n ia a causal connection hei\~,.> (Rural. Rnbbiu poitoned with benaene [71-43-31 (0 5 m l/kg/day xpoaur* to eparifiad spray adhesivas and chromosome ci. s.c. fr>r 2 waakal ibowed a mticuloplaamocytic m art on in thair landing to genetic birth dafacta. Distribution ol th n e pr...i< - bone marrow and inerwaad antibody utraa to tplaan aad bona for household, use ia banned under tha Federe! Haz -cu u marrow antigens and to leukocytn and arythrucytaa. C A also S ubatancn Act. \V Horn- .: had a no. of hamatol. effects. i.e. erythrocyte, reticulocyte. aad 13345*1 Q uaatU adve d a ta ra ln a tis n at lead in the h a ir -r. throm bocyu noa. decreased. During tha m tavar / period, T h ai children. K riuiugiana. Sompool; ornr.ayara. S ./t-.rr. normaliration of blood ceil coenpn. paralleled tha dacraaae ia Pringeuiaka. Prapa (Sinrx) Hoap., Bangkok. T h aila n d , .'r.rz gutmmmune antibodies. Ho,p. Gat. l n , 25(5). 743-50 (Thai). Lvala of i-.<i .g .. jo 133451a G aaeral losie afS nt at g arrh larir a d d . Setivanova. (743*-(2-l|/g w an deed, in hair samples from Pi r.cm 1.. N.: Knltunova. 1. G.: Vorob'evm. E. N. (Moaeow, USSR). chiidran. comparad to teveta of 138-2358 Mg P b /g in hair ...n |-. (tie. Tr. /'ro/. Zabnl. 1*73. (8). 33-5 (R un). Perzhlonc a n d from 4 -- -- of chronic Pb intoxicatian . Hair samples .m vc I'MlI-'JIl-tl. givrn .roily or a.c. tn rats. mica, and deg*, showed in tn collect fm n chiidfon than binad, or 24-hr urina sample-. autlii. us m im ing effect a specific analthyroid action, and also tha d o n . uf Ph ia hair a m p le r may ba usad ui uuiti..i:- iiiiim-cu uhnorm uiities in hepatic, vrnai, cardiovascular, and pots.rang. cap. in children. ;-.innvin'i il- i.uh uihw. Thera cffccu should ha ciinaiilararl when 133444c Acuta a n t toxicity af2 -a ik y i-a d 2 .t-d ia lk y la n ..i cvi.!ii..iiiiu the imlustriai Utaiciiy of 1UMO,. s. Carrrinliaw wish Upaphiiicily. Durden. J,tlui A., lr. 1.13:53b Kffcut at same feed aanpanaala a a th a arac-astd Float. Iliv.. Unsua Carbide C rap- South Clutrii-Mim. suir.ium oglabta-form ia netiaa af a u r a tea and o itrilra. J . Med. Ckam. 1873. 16(11). 131 iKng). Acuu- ..ml Kia.ioa, M.. Lutsoyn, Kh. I. (Tallin. N auchaw lnlad. lost. m u af a sanea of alkyU nilinn 1 l i t K' - H or aik< i> .ip; - i Kpiueminl., Mikroheol. Gig., Tallin, UShtU. 5'h. Dogf. Rtgpu6 . depend primarily on the lipophilictty at the d rm s .. S 'erda Epidimiai,, U ib o iia i^ Infok. Gif,, tn d 1872, 1 - 5 lipophilic compda. being tha lea toxic. The ,*1*: . i 18423  C o llii - 255 / f a le v e l 01' '0 -2 5 ?pm to le a s than. 1 ppm about 6 s o u th s b e fo re th e survey m s u r-d artak an , c u t i n a d d itio n an in c re a se d aw areness among w orkers o f tha n u c e ssity fo r sa fe ty precau tio n s say a lso have p lay ed a p a rt. 2230. HM5ACEL0B0JT~dl:"l7.0DlQXDr-- I3TIMATI0gS OP CA3CEI0GESICITr? 3uu-H oI, !T .? ., E le n , D. - P . , S a in t-S u f, G. & S e rv a in --S id o in e , J a c q u e lin e (*>971) . P r o p r la te s oancaram lm etlgues de l a t a t r a c h l o r o - 2 ,3 ,7 ,8 d ib e n z o - dioxina ("d io ad n e"). C .r. hebd. Seano. Acad. S c i., P a ris 272. 1447. The t e r a t o g e n i c i t y o f 2 ,3 ,7 > 8 - te tr a c h lo ro d ib e n z o - - d io x in ( d io x in ) p re s e n t a s a co n tam in an t i n soma co sanercial sam ples o f 2 , 4 , 5 - t r l c h l o r o ph an o x y acetic a c id ( 2 ,4 ,5 -T ) i s w a ll e s t a b li s h e d ( u r m i B u ll. 19 7 1, _10, x iv ) , though th a s i t u a t i o n re g a rd in g 2 ,4 ,5 -T i t s e l f i s le a s c le a r . The above a u th o r s have now d e s c rib e d c e r t a i n h e p a tic a f f e o t s o f d io x in n m r fn g i t s a c t i v i t y w ith t h a t o f known c a rc in o g e n s. D ioxin i n j e c t e d i a t r a p e r i t o n a a l l y in t o r a t s a t dose l e v e l s o f 0. 00510 n g /k g red u ced th e d u r a tio n o f p a r a l y s is in d u ced by zoxazoL aalna by 3 395ii, b a in g f a r n o re p o te n t i n t h i s r e s p e c t tb a n benzofa 1p y re n e . 3c such a c t i v i t y was shown by u n s u b s titu te d d ib n z o -g -d io T ln o r i t s 2 - n i t r o , 2 ,0- o r 2,7-dichloro o r octachloro d eriv ativ es, by 2 ,4 ,5 -trlchlorophanol o r by 2 ,4 ,5 -T . Mice in je c te d i a t r a p e r i t onaal l y w ith 20 e g d io x ia /k g a ls o shoved a sig n ific a n t shortening of phanobaxbitona-inducad sleep . In a d d itio n to th is in d u ctio n of m icroscaal hydroxyla tin g enzymes, d io x in in je c te d in to r a t s i n a dose o f 20 Acg fo llo w ed by a second dose o f 100 itg/)cg 7 la y s la te r caused a gradual decrease in the le v e l of hapatio arg ira se dmHnj the e n su in g 3 wk. A m arked re d u c tio n i n L iv e r a r g in s s a baa a l s o been re p o r te d in r a t e fe d w ith th a ca r c i nogen, -d im e th y la a tn o a z o b sn z a n s (S a to , Tohoku mad. J . 1963, Z> 597). [A lth o u g h su ch a f f e o t s may be produced by c a rc in o g e n s , th e r e l a t i o n ship i s by no naans ex clu siv e. In p a r tic u la r , th e stim u la tio n o f hydroxyla t i n g enzymes can be in d u ced by many compounds, In c lu d in g 3HC whose freedom from c a rc in o g e n ic ity has been dem onstrated in co n v en tio n al long-term feeding stu d ie s. T esta such a s those described above have l i t t l e o r no p re d ic tiv e value and cannot be used aa a s u b s titu te f o r p resen t methods of long-terns to x ic ity ta s tin g .] PROCESSING AND PACKAGING CONTAMINANTS 2231* PT.l^nT^Tgg^Bg 4?Tp PTC PICKS M arcel, Y.L. & J o e l, S .f . 0 9 7 0 ) . C ontam ination o f b lood sto re d in p la e tio p ack s. L ancet i_, 35. Ja e g e r, a . J . & Hubin, a . J . (1970). P la s tic iz e r s from p la s tic davlceai E x tr a c tio n , n e ta b o lia m , an d a c c u m o la tic n by b i o l o g i c a l sy ste m s. So l ano s , S .f. JJO, 460. D uring th e p a s t y e a r i t has became ap p aren t th a t s ig n ific a n t quant i t i e s o f d l- (2 -e th y lh e x y l) p h th a la te (2EB?) oan be d e te o ta d in b lo o d th a t i. .Number* o C D D " T n 2 r c f ` b o m m ts s Function of the Num ber o f Chlorine Substituents Number of Chlorine Atoms Number of O D D Isomers Number 0/ Isomers tv . A c u U Taiicttiei uf CMara4b<uf*J<tin^ [1) r and Positions irine Substituents ID s tai/ln)' Cuinru F io Mice -- -- S u -y-- 1 2 4' n- 29.4t't 1 lllHI 2 10 16 U 'lia * u.o : u :a4 ^ 3 14 28 H (V m jj* V I ^VA 1 4 22 38 K t'cnin- 1.123 5 14 28 /.N lie\.l /:.) 2> ` 6 10 16 7,H lc.t;- 7(1 1(81 1,,* h 7 tf 2 4 8.9 Ilesa- Ml HHI l,i m 1 1 f../ H U. j.isf Mtf. /.IM ............ .............. ---- . (.,7,8,9 (V ia- 1 X III' Table H. Physical Properties of Tw o Chlorinated D to x liu r* f<r f>rl *%! j* mm| t\ til fl;v. Empiric Formula Percent by Weight C O H Cl Molecular Weight Melting I'oint (" O 1VciHiipi.situnt Tcuificinfiiic C'i 'l S . . I i i Ii.( iI ic s ( g / I) i-l )n hUitnftcnrciic Llilmulicii/cnc Atit'.nlc Xylene llen/enc Chlurufurm n-Octanol Methanol Acetone Dioxane W ater 2,3,7,8-TCDD O C D D * C ,2H 4C140 j C l2C l,O j 44.7 9.95 1.23 44.1 322 305 >7141 31.3 7.0 61.7 459.8 130 . nm 1.4 72 0.37 0.37 0.048 0.01 0.11 l xi i./.t I.5K U.50 0.38 iniuary of Toxic K lfrrb of U .7 .X * 'in > li on S rirra l Animal Sju-rin* | ] .. j Mice (otinca Pitt's Moot, n s (l iai.de( n> Invoiuttnn t Reduction (white pulp) marrow Hypoplasia Mcgalocytosii/ Degeneration uct Hyperplasia ular Degeneration .-pelvis Hyperplasia ry-bladder Hyperplasia tai-cortical A trophy na Glomerulys) norhage estmal renal ' :s icous lesions css * ** 1 - - * - ... * ; * * * ** - ... * . N /A 1 j I \ effects; * mildly ailcctcd; * - moderately affected; scserely alfeetcd. OOH2 I S 9813 Substance flotulinunt Toxin Tetanus Toxin Diphtheria Toxin 2.3.7.S-TCDI)'' Saxitoxin Tcuortumxin t Bufntoxin' | Curare t hirychntne f Muscarici' Diisopropslfluorophosphate Sodium Cyanide 1.0 10* 7.2 * I04 322 372 319 737 696 334 210 184 49 ..... - tt) " 1.0 * 10'17 4 2 *' 10 * 3.1 * 10 4 2.4 10 ` 2.3 * 10 4 5 2 IQ 7 7.2 *10 7 t.J 10 * 5.2 * 10 * 1.6 10 5 2.0 * 10 4 Source; P b n J and Xende {4 ) These data were compiled b y M o she r et al. [5], and the salties indicate only relative toxicity It should be n o te d (hat the values deal with different .pccics. routes o f administration, survival times and. in one case, mean lethal dose rather >bauntemminimmicuem lethal dose. Except where noted, administration was by the tntrapernoneal J A A ? - T C 0 P 4 J . 2 t v . 7 . ? . & r t* ID # Lm .'-H- * J L f* '- K -io i7 -a j i t / C fftQ -a i i ) b 'k .H Z -p M 'O TM ) D R - / f f - V 7 V ^ ' O 0* ) g ^ j j r f ,, $ 2 S3. O - i on oral adm inistration in the guinea ptg. 'ravenous inaction th the cat. D Q .g l U - A t, ^ ,,, tt-S i-iU K H , K . m t 3 .(/a/ A '- J V n z - ( r - ) VI 1842?" T ib ie VI. Accident in C h rm tcil P lin ti M anufacturing TC P [7| Dale Manufacturer Country Personnel Injured Cause of Accident 1949 T52 1953 1953 1953.1971 1956 s I960 i 1963 j 1964 t 1964 1968 19/Of?) 1972, 1973 1976 Before 1976 Monsanto Bochrtnger Badiwhe Anilin und Soda Fabrik A O (B A S F ) Rhone Poulenc Hooker Diamond Shamrock Philip- D uphar Spola na Dow Chemical Coaliicand Chemical Products Baver Chemie, Linz lemesa (Givaudan) Thompson Hayward U.S. w. Germany w. Germany France U.S. U.S. Holland Czechoslovakia U.S. U. K. W. Germany Austna Italy U.S. . *TT*': 117 Overheating leading lo explosion 37 Exposure during m anulactunng process 55 Overheating leading to explosion - a t . 97* Staff emplovees Fiuure unknown 30 72 30 79 5 50 106 children Exposure during manufacturing process Overheating ] Overheating j Overheating leading to explosion / Exposure during manufacturing process Exposure during manulacturing process Overheating leading to explosion Exposure during manulacturing process Exposure during manufacturing process Overheating Overheating leading to explosion * Including 1? injured in a 1956 explosion and 21 in 1966. Source: A. Hav. "Accidents in Triehlorophonol Plants: A Need Fo r Realistic Surveys to Ascertain R isks to Health . in "H ealth t a c c i* o f Halogenated Arom atic Hydrocarbons*' \\ J. Nicholson and J. A . M oore. Edi. Ann. .V. Y. Acad. Set, J20:1-730 (1979). BON2 I 5981V Table V II. Higher Chlorodibcnzodioxins C D D and Chloradibcneorurans C D F C D D Detected^ Product Tetra- Tenta- Ilesa- Ilrptii* Ocia* I CT i Tut rac hio ophenoi P C I* * -- VT S11\ C\ Crbon Scsonc -- * * * ** ~ nu - - MJ - NU - ND - ND - O n e c ird in ;.hlorophenoiIs ami ltrl.1t,.! ........ e u F Delecte* Trtn*- * , Pcrt-7* * I lev. 1 -* .. --------- -- .. M l N I) N U M > N, N I) N I) N 1> M i \ ;) N I) N U N U N U ND N U NU N U N l) M ) ______ 4 ' > Concentration ranees: * a > 1 0 ppm: = 0.5 10 ppm; - = <U-5 ppcn; N* U not determined Recent analyses by Wright Suite University. Table V ili. Levels of T C O O in Varions Environm ental an Biological Samples Analyzed by the Brcbm L aboratory 01 Wright Stale University Sample Description Native TCDD D Hazardous waste landfill oil/sludge. New York state ~Trichlorophenol manufacturing waste. \ still bottom . Arkansas ' Blood sample from workers involved in * cleanup of orr/io-chlorophenol spill in tank car derailm ent, mtssouri filuod sample from Vietnam veteran Uovmc Municipal rdusc-fircd incinerator. 300-199.000 22.000 7-28 pp 41 10 Table X. Results of H R C C /L R M S Analysis of Wipe Sample from Area Conum inaicd by Transformer Fire for Tetri- Through O ctachloriluted D ibem o-p-dloslns and D lhenrofurans_________ CDD /CDF* TCDD I'C D D llxC U U iip cn n Apparent leom enk ND " a 4 -2.3.7.8 ND NU I.2.J.4.6.7.8I.2.3.4.6.7.9I oral Quantity of C D D /C D F Detected (n g /w ip e) ND NU NU 0.65 0.45 l.l Minimum Detectable Quantity (ng per isomer) J U 10 ! I 0.1 It 0 20 0 20 0 20 0.2U New York state Ion particulate emissions) Sout (rum wood-burning lircplucc Agent Orange 2.4-0 fscveral manufacturers) 15 mg hr 0.65 pph 0.1-60 ppir 0.2 1.3 ppt (X 1)1) TCDF i7C14 I.2.3.4.6.7.X 1.2,3.4,6.7,8.9 ,7C l,-O C D D 1.2.4.82.3.6.X2.3.7,8Other isom en (8) Total 1.0 2.0 3.1 9.6 35.8 50.4 o :o 0.10 U 10 0.10 0.10 Oil) Table IX. T C D D Levels In Wildlife in Seveso. Italy, Area Following TC P C D F 1.2.4.7,8- No. of Samples TCDD 1 Other isomers (13) Total Animal Analyzed Tissue Positive Average HxCD F I.2.4.6.7.9- Field M ounC / II.MC 14 5 Whole body Liver 14/14 .1 5 4.5 7.7 Other isomers (12) Total Toad Snake E arthw orm 8 1 1 2 Whole body Liver Adipose tissue Whole body l/l 1/ 1 12 0.2 H pC D F 2.7 16.0 12.0 OCDF 1.2.3.4,6.8.9- O ther isomers (4) Total ; I.2.3.4.6.7.8.9-____________ Source: Fanelli et ai. [9]. referenced in Esposito et ai. [i]. "Each sample represents a 5-g pool ol' earthworms. ' I'C D D = penta-C D O ; H xC D F = hexa-' CDF. "See text for discussion. 5.2 0 10 11.8 0.10 17.0 0.10 " 1.6 43.6 45.2 0.20 0.20 0.20 2.7 o .:u 4.6 0 20 7.3 o :o 7.3 o :u H pCD F V hepta CDF. O CD F = oeta 18426 BOtmseen i I'ahlc X I. H H C C / l . K M C Analytical Results for C D D / C D F in A sh Sam ple from Incineration of Pastes Containing P C P * cn n /cn p Mt DF D CD IIK 111 l* |i| l'( 1>1 ll>< IH ll|>< HI IK 'D I M( I jD DCPD lrC U D Tcnu FCDD H tC D D HpCDD OCDU Total Number of Apparent iMjniers j X h 7 *> i i 1 4 5 4 5 5 1 Total Detectd (t/S) 75 25 15 7 X 5 fl 2 l 5 2 4 32 81 117 198 Recent analy*.- by W nifhi State linivcnity. M in im u m Detectable Concentrated (nu/s) 0.1 0.2 . O.A 0> \ 1 i 1 U1 0..1 0.6 0.2 1 1 1 1 1,2,4,3 T ET R A CHLOROBENZENE a .4 ,3 I COOH CH2 Chlorinated Dibenzo-p-dioxin Chlorinated Dibenzofurans (PCP) PENTACHLOROPHENOL PCP, Na Salt Fi| 1,3 ,4 ,7 ,0 -p c n ta - C D F (proposed) Fijure 4. Reactions leading to formation of C D F from pyrolysis of 2.2\4.4\5,5'-hcxachlorohipnenyl. J VjV* -r . ' "" <: ' - * rv 'ail tro . '*.'C: ]*- v ;! 'i!ti.'i '' DHW CHEMEpPt CCL' -J: ^ -v ^ -1 . HTTfr D J JrfROBLEWSK I ' TLJXIC0LE6Y RESEARCH LRBRHTORIES BLD6. 1 8 0 3 ,jV, - ., -' MDLIWII HT 4 8 * 4 0 51? 636^S>7L :'***' * .- '> * * J : * \ F r i e 5- ' <* FE0- n984 fr V :g i I t e - . ) b t)U 5 8 9 # ; ^ C'HLQRth u '- .v * ` ."r* j. v ,,. - - *\ ^ - f IQXINS mj CHl ORQ JH BBtZIl HJftf8&> Rft a. ClVERViEW. T if R ^ % '.0 :` - . . . m e? *:-,. . . ' ^ ^ H ils d U f ^ ^ ^ D E P ; eHfemSTRYr W*ifeKT'STFFFE urtlV .V -aiY T D nN -B rtlfl 4 5 4 5 8 . V - EXeth?"-a- EJ3.>-- ^ D E ^ O X Ic m itlft OF HFhHRBUUX R ST E . XVT l ^ t e 3 P . -Ftftfi x Rm PkBj jOu Rk S; CIEWCE PUBLISHERSr- IftC . i 8 RRBCR niLH ISH *' USH b'U f TERtoKHS \ I M C . * WI QBURMr MHSS-*- U3RP BUTTEl?WURTHS * LTD. * ShVfcHlJHKS KEflT EMSLHHB. I L L U S . ;1SBM 0--2 5 0 --4 521--0 . U ^O!).' 1Y82 <.RtCB. 1V80 - P24&-TE!b. C D E H r .'1 5 8 7 8 - ,- O" rsj c* 09 i 18428 DOM2 I S 9 B9 r p td)., J t. J . ^ r i C H A P T E R 15 CHLORODIBENZODIOXINS AND CIH.ORO DIBEN ZO FU RANS: AN OVERVIEW Thomas 0 . Ik m a n Brthm L ib o u to ty and D tp irtm n l of Chemistry Wright Slate University D ayton. Ohio 45*59 Chlorodihenzodioxirs (CDD) and chlorodibenzofurans (CDF) are two series of tricyclic aromatic compounds that exhibit similar physical and chemical properties and that apparently induce similar biological effects. Generalized structures of the CDD and CDF and the numbering accord ing to the position of chlorine substituents on the rings arc shown in Figure I. The number of chlorine atoms in the molecule can range from one to eight: therefore, a large number of positional isomers are possible. 1 he total number of CDD is 75, and there are 1.15 CDF. The numbers of CDD and CD F isomers as a function of the number of chlorine atom substituents are indicated in Table I. In the past few years, widespread concern has arisen with respect to contamination of the environment by CDD and CDF. This concern has been prompted in part by observations, principally based on animal studies, that indicate that certain of the CDD and CDF exhibit potent toxicity. In addition, it has been recognized that, since the CDD and CDF are present as contaminants in numerous commercial chemicals that have been or are being produced and used in targe quantities ( I ), the potential for extensive environmental contamination by these compounds is very great. Moreover, CDD and CDF generally arc quite stabl<\ chemically and thermally, and are reasonably soluble in several common organic solvents (selected physical properties of two representative chlorinated I C73 n ri tH J DOW2 I 59811 144 nrSTRUCTION OF ntflXIN5 9 I Chlorinated Olbenzo-jg* dioxin 9i : & " i f j )2 < v 4 Cly Chlorinated Dlbenzofurans f lf w i I. O tn n iliiH sirg d w n of CDO i H CDF. Ti Mi I. Nmdm W CDD CDF loom m t* Fm HIm 4 ibt N m k tr of CMortoc So* iHm o N m W r of Qkwhw AIo m N w A tf of CDO tiw nrn Nmwbti of 1 2 4' 2 to 1 ) 14 2t 4 22 M 5 M 2t a to l i i 24 s1 dioxins are shown in Table II). There is some evidence to suggest that the CDD and CD F are accumulating in the environment, and that these compounds (ftrsist for considerable periods. The purpose of this chapter is to give a concise overview of the present status of knowledge of the CDD and CDF, as a prelude to discussions of cm.oRODiiirNr.nfHoxiNs a n i cin.onoinrN 7.oMtANs 143 Tibie tl. P h^dnl 'lAffrtffi of T Chlorinated IMnitm IJ.T.STCtm o a m * Empiric formula C,,11,0,0, c ,,' v> , Percent by Weigh! C 0 II a MoVvular Weight 44 7 3 75 1 23 44.1 >22 31 J 70 61.7 50 MrHing Point ((.') Ocompo'iiion Temperilo) (*C) m >700 (30 >7! SotobMities fg/l) o-OicMmobenrtne CMorobenrene Aniiole Xytrnr Henrene Chloroform rO lisol Methanol Acetone DioMne Water I4 0.72 37 37 0 04S oot O il 2 10 * lit f .73 3.3 0.36 0 >S 'O d K h lnrodilxflrA fdraiiil. 1 various methods of destroying these compounds or detoxifying wastes in which they are contained, which are presented in other chapters in this book. More comprehensive reviews of this subject can be consulted for additional details (1-3). , TOXICITY AND HEALTH EFFECTS OF CDD AND CDF The toxicity of chemical compounds is usually assessed on the basis of teats with animals. Frequently, in these tests, large doses of the material being tested are administered in an attempt lo compress the time scale for response. This testing may result in misleading conclusions, because such massive doses are usually unrealistic in terms of the doses that would he encountered in typical real-world exposures. Moreover, since toxic response is a function of the pharmacokinetics and the adaptive charac- DOH 2 1 5 9 8 * 1 24 nKSTROCTION OF DIOXINS (eristics of etch particular animal system, the response of different animal species lo a given chemical may. and frequently does, varyimarkedly. All of these considerations lead one to conclude that it a extremely difficult, if not impossible, lo extrapolate toxicologic data from one animal species to another, particularly lo humans. Still, animal tests are one measure of the toxicity of chemicals, and some CDD and CD F have been tested in this manner. On this basis, as shown by the comparison in 1 able 111(4,3). the acute toxkities of at least some CDD (in particular. 2,3,7,8-tetrachtorodibenzo-p-dioxin (2,J.7,8-TCDD)| are comparable to or exceed the loxicities of several well known poisons, and these rank among the most lethal chemical compounds known lo man. It has also been observed lhat the I.Dji doses for various CDD isomers, based on tests with guinea pigs and mice, differ substantially, depending on the number and location within the molecule of the chlorine atom substituents (Table IV). Of the CDD isomers tested, the 2J.7.8-TCDD is recognized to be the most toxic. The acute toxlciliei of C D F have been less extensively Investigated, but the LDM values for 2^,7.8-tctrachlorodibcnrofunin (2,3,7.8-TCDF) and 2,3,4,7,8-penUchlorodibenzofurin (2..M,7.S-PCDF) appear to be similar to those for the more toxic CDD, lhat is, I -100 pg/kg for the most sensitive animal species. TiWf III. T fikH In of Selreted Pohooi* Sobsfawre M U o m I r t M Dow Moltewlar WeftM (lM l/k|) pntvlmvm loxin A Ictanm loxin Diphtheria Toxin j.j.u-T run* Saxtioxin tetrad rHnain IM moiln' Cmare Strychnine Muscarin* DihnpropyHIitoroplMHpliaie Sodivm Cyanide *. i 1 10 10' 7 2 104 322 372 31V 737 m 334 210 IH4 4f 3 3 10 " 1.0 10 " 4 1 10 " 3.1 10 * 1.4 10 ' 13 * 10 * 3.1 10 ' J.l 10 ' 13 10 * 5.1 10 * 1* 10 ' 1.0 10 * 'S m w e f i n d n d K tndt (4). Then data ere tom fikd by M utter <t 1. (3). and tte w t e i radical My retain* toxicity. H i booId te aoted Steal tte valves deal with different species, footes el admints!ratio*, larvivel limes and, I* one case, mran trite! dose ratter (tea miaimoai lethal dose. Except otere noted, administration was by tte intraperitoneal noose ia mice. M.Dh on oral administration I* the |tiinca pif. 'iM rsw new insertion la tte cat. ( III.O RO I>tBF.N7.nninX IN S ANI <lt.O <UH HIIt N7.<)HlHANS 24 TiMt IV. Aralf TkH h of NotnWe af foatltom of ( S M w MKlMwHfi U>* Cofano r i n 2 .1 0 2.2.7 Til2.1.7. (dm . 1.2.3.7. redo1.2.4,7. renioI.2..1.4.7J Ite it 1.2.1.6.7.1 Mr*. 1.2.1.7 l . t Ho b I.2.3.4.6.7.I HcfHiI.I.M .M .M O n - >wo.onn 2S.444 06 20 11 1,123 72 3 70 100 60 100 >600: 7.100 *A i votoci are fot orai dote*; ict ptiiod il SO day* ff| Mfce >1.1*0 2*4 33 >5.onn 23 1.230 >1.440 > - IO* TfbW V. Sowmtaty of Tolte F.flnH <4 U .U -T C U O oa S o n a i Afriiml S p n f ' |l.* | Moofctyi Mice Colma Plfi ( l i m k l Thynuii fnvotaiion ... Spleen Reduciion fwhtlc puffi * Ponc-nurrow Hypoptaiio i * l i n i , Mrgalocylmn/Urfrneraiieoi Hite-duci Hypcrptasia f Tetlkular lirgcneration N/A Renai-privi Hyperpiatia Urinaiy-bladdcr lly|terp(iM Adrenal-conicai AOophy (Zona OVmciulyil ** llcmmorbape Interinai * Adrenal A v ito Cmbocowi leiiont ' * * ... *Kfjr: no effect; mifclly altrctrd: ** mndeealely Itcrled: * vvcfdy aftcclrd. A summary of (he observed biological effects of 2.J.7.8-I CD f) on mice guinea pigs and monkeys is presented in Table V \ 1,6). While the effects and their severity vary to some extent among these species, as already noted, in general the major organs effected are the thymus, liver and spleen, along with the reticuloendothelial system. Reproductive functions are also affected in some animals, and pronounced develop mental effects in offspring have been observed. In some animal species. CO CO OOK2I598M 2 D F5TRITTI0N OF DIOXINS 2,3,7,8-TCDD ti fetotoxic (or embryoloxk), lenlygenie and even car cinogenic 11]. A particularly apparent response to this compound ob served in rabbits, monkeys and man is an acnegenic eruption (termed chloracne in man). TCDD causes marked alteration of normal enryme activity in certain laboratory animals. It is a highly potent inducer of aryl hydrocarbon hydroxylase (AHII), as well as the mixed-function oxidases and the cytochrome P(-450 (P-448) enzymes of the liver, lung, placenta and kidney, in mice and rats [I). It also appears that TCDD may potentiate the adverse action of other toxic materials, or even cause another seem ingly innocuous agent to exhibit toxicity (I]. There are relatively lew data concerning the distribution of CDD and CD F within animal tissues and organs or excretion of these compounds following administration. Some studies with TCDD Indicate that in rats, excretion b i i i r i r via the feces, and that accumulation occurs principally In the fat and liver, with smaller amounts in the spleen, bone, heart, lungs, testes and kidney (I). Most TCDD is apparently not metabolized by the rat, or at least metabolism of this compound occurs very slowly, and the metabolites have not been Identified reliably. Information on the effects of human exposure to CDD has been obtained principally from epidemiological studies of persons exposed as a result of accidents in chemical plants or by exposure to contaminated foods, materials or areas. A summary of the major accidents occurring in trichlorophenol (TCP) plants in the past several years is given in Table VI (7). The most notable episode Involving CDD contamination in recent years was the explosion that occurred at the lemesa trichlorophenol plant located in Scveso, Italy, where TCP and 2,3,7.8-TCDD were dispersed over a wide area. Approximately 5000 persons were exposed in this accident (1,2). Shortly offer the accident, chloracne (a well-known symp tom of acute C D I) toxicity) was observed in some 134 persons. Other disorders reported included hepatic and coronary insufficiency, chronic bronchitis, muscular weakness, irritability and nervousness, urinary and pancreatic disorders, porphyria cutanea tarda, hyperpigmentation and Virsutism and chromosomal damage. A later followup study detected peripheral nerve damage and polyneuropathy in some of the exposed individuals |2J. TCDD is also known to he an inducer of delta-aminolevulinic acid (dALA) and AIIH in man. Probably this accounts for stimulation of production of certain porphyrins, which are ultimately excreted In the urine. The distribution of CDD and CDF within the human body and the modes of elimination have not been established, nor are the metabolic pathways or metabolites (if any) known. Reproductive effects of CDD 'i <iif.oRonifiFNrnDioxiNS and cm oRonm f N/oHiRANs jn 18432 j.|fsr?sp ll aI! ' S fi 8 a cS 11 c* > If 5? 9! 3 3 -3 ^ ?i X2=R l ! :s i Is *3* I D0M21598*1 1M DR5TRUCTION OF DIOXINS and CD F in humans also have noi Keen determined, in part because of the complicating factors caused by the many othef hazardous organic compounds to which man is exposed. The most notable reported episode involving human exposure to CDF occurred in Japan in 1968 as a consequence of the accidental contamina tion of rice oil used for cooking with polychlorinated biphenyls (PCB); subsequently. CDF were shown to be present in small quantities in the PCB (8|. This Incident, which has come to be known as the "yusho'* incident. Involved more than 1200 persons. There were several near-term symptoms. Including chloracne. Many of these symptoms were similar to those cited above for CD D (2). By the end of 1977, some 51 of the eaposed population had died; 11 of these were identified as resulting from malignant neoplasms of the stomach, lung, liver, breast or lymphatic system, or combinations of these [2]. Tissues (principally from the livers) of the victims of this accident were analysed for C D F, as were samples of the PCB contaminant in the rice oil. A comparison of the results showed that many cf the same CD F isomers were present in both the PCB contaminant and the liver tissues, and further indicated that certain CD F isomers, particularly those having all the lateral (2-, 3-, 7- and 8-) positions chlorinated, were preferentially retained in human tissues (8J. This is one of the few instances in which such compounds have been implicated unquestionably in severe human health effects. In several animal studies, PCB have been implicated as inducing toxic effects in animals, but in some of these investigations, it has not been clear to y h at extent PCB were contaminated with CDF, and the causative agent or agents are therefore uncertain. SOURCES AND ACCUMULATION OF CDD AND CDF IN THE ENVIRONMENT X t mentioned earlier, major sources of CDD and C D F detected in the environment are industrial chemicals. More recently, however, h has been recognized that these compounds are present in the effluents from various combustion processes. The principal environmental sources of CD D / CDF thus far identified include (I): 1. chemical prnducii for which ihe normal manofacttntng proccta fenerslct thew compoonda at by-prodwell, and which arc widely ward in Ihe environmem (peuicidea. wood-irenilnf prodnrta, eae.fc 2. nncon|fo*trd manufaclnrmi procciva. which reinft in rctcaaca of CDD and CDF tcaptoaiene of rcacloray. t ( llt.OROIMftKNr.ODIOXIN.S AND rill.O tt< H > IR .N *O H 'R ANS 251 J imptoper dnfNtuI of chemirtl manufacturing wanes nr product* containing CI>D and f'DF (fantffifH. waterway): 4 incineration of municipal, commercial and industrial waiter-, J ordinary combuMinn ptores*cf (wowt-burning and other); ami 6 accidents (iirev ipilh. etc I. Perhaps most important among the mass-produced chemicals which are known to be contaminated wiih COD and CDF are the orthochlorophenols, particularly 1 CP and pentachlorophcnol (PCP). TCP Has been used widely as a preservative, bactericide, fungicide and afgkidc in many industrial products, and is the starling material used in the manu facture of a series nf industrial and agricultural chemicals, notably the herbicide 2,4,5-T. and the related products, silvex, ronncl and hexachlorophcne, a bactericide. PCP is extensively utilized in wood-preserv ing processes. COL) and CD F that have been detected in various chlorophcnols and related pesticide products are listed in Table VII. The probable mechanism by which chlorodioxins are formed in the synthesis of or.'Ao-chlornphenols is a thermally induced condensation reaction of two molecules of the sodium or potassium chlorophenale, such as that exemplified in Figure 2 for the production of 2J.7.R-TCDD in the manu facture of 2,4,5-TCP. A so-called "predioxin," a phenoxyphenate or substituted diphenyl ether, may be an intermediate in this reaction. Similar condensation reactions can account for the formation of hexa(llxCDD). hepta- (lIpCDD) and octachlorodibcn/o-p-dioxins (O t'D D l in the manufacture of PCP (Figure 3). The extensive occurrence of CDO and/or CDF in such widely used commercial chemicals as chlorophenols, their derivatives and PCB provides a clear indication erf the need for adequate methods for destruc tion of chemical wastes and related materials that result from manu facture of these chemicals. Obviously, improper disposal of such chemical wastes can lead to extensive environmental contamination. Prominent examples of this that have received recent attention are the Love Canal area in Niagara Falls, New York, where several major chemical dumps arc located, and a 2,4,S-T/2,4-D manufacturing plant site located in Arkansas. Levels of TCDD typically found in environmental samples from these sites are shown in Table VIII. Applications of excessive quantities of herbicides contaminated with TCDD, as in South Vietnam during the conflict there and at various military sites in the United States during this period, or the contamination of tire environment resulting from such events as the T CP reacior explosion at Sevcso, Italy, can also result in elevated levels of TCDD in plants and animals (including humans} present at such sites (Table IX (9)). As already noted. CD F are also present as contaminants in some PCB c~ GO ei D0M215881t 292 DKTBtPfTION 1V DIOXINS QZ Q7, I X OX * X tQ Q 1 X. T. . O XT. t t OO XX . OQ XX . XOXQ , QX XQ ,O Q ,Q Q XX XX t t' X T. X X X :i l l B. -S J ta s L* 13 mm C N l O R O m U F N r n i M O X I N S AMO ( 111 O R O | ) l f t t ' N 7 n H ' H A N S 251 1 ,2 ,4 ,5 TETRACHLOROBENZENE 2 ,4 ,3 T COOH i CH* 18434 0 * reco: .XXtt.Ci ft CI 2,3,^8-T C O D R fw I. Resclmn involved in iyn*hem *4 2,4.5-tricMorophrm! and lelaled prmfui'M (2.4,5 T and dtnva(ivti) showing (tmiiinn o4 2.1,7.1 10)11 as c hy-ptodncl formulations (2 | In addition, it is known that pyrolysis of PCR at ceitain temperatures (obviously lower lhan the temperatures required for com plete destruction) yields CD F as products [3). The reaction scheme for I formation of CDF from pyrolysis of 2,2\4,4',5,5'-hexachlorobiphenyl, for | example, is as shown in Figure 4. An instance in which a FCB formulation (also containing hexachlorobenrene) was incinerated under conditions leading to formation of substantial quantities of CDD and CD F occurred in Binghamton. New York. This episode occurred as a J BtWZ15 154 O rS T d llC T IO N OF DIOXINS (PCP) PENTACHLOROPHENOL PCP, No Sol* -------- --- OCDO F1|*n J. RttdioM Mfolwd to ip i h n h of PCP attrf d o iw liw i bowing formatmi of octKhlorodilmiodloiiii by ptodnct. result of a transformer Orcein the basement of a large office building. Soot samples and wipes of surfaces in nearby areas showed rather large concentrations of CDD and CDF, as indicated by the data shown in i c m o i t o n t B F N r .o m o x i N .s a n i m H i. m > m rN 7 .o F tiR A N s 255 TiU t Vili. U u l i of TC1H> In Varino* F.avfrnomeoiat ind llotogiral SifH fln Analyred by Ih* Breton U lm rilor) of Wr|g|*t .Sii** llnlitnHf Ssmytc DtwHfrtiw Native T r i m Dclrrfrd llarardout w ant landfill vol/studgf. Nr York tate Tricftlornphenol manufacturing wiiic, still hntlom. Atlanta Mood ample from oovkers involved in cleanup of ortAo-eMotophenot spiff m tank cat derailment, mbsouri Mmd sample from Vietnam veteran Bovine Municipal refuse fired incinerator. Hew York state (on parumiate embaions) Soot from oopd-huming fireplare Agent Orange 1.4-0 (several manufacturers) XW 199.tWO ppt 22.000 ppt ( ?- 2n ppt 41 n * 10 n h IS mg/hr 0.M ppb 0.1 M ppm 0 2 I..1 ppb T-Wt IX. TCDD U veli In W M W t |m Sevev. Italy, A m FoHonln| T f'P ArcMrnI* Animat Analyred 71mne Fm tln Held Mouse Mate Toad Snake Earth * orm* 14 5 1 1 2 Wh.de body Liver Wh M body 1 iver Adipoae tissue Whofr oody I4M4 VS VI l/l 1/2 ' Source: Fintili el al. (9|. referenced in I tfw ifo ri al. 111 ` E n h iin iflt represents a S-g pool of ciilhom rm. K O I ) l,e*el (ng/g| Average Range 4 5 0 07 49 7 ; 2.70 n 02 27 16 0 120 Tabic X for a wipe sample f fOf. In still another instance, incineration of wood-treatment wastes containing PCS', and probably related COD/ CDF nr precursors of these, in an incinerator that apparently provided less-lhnn-optimum conditions for destruction, yielded ash residues con taining relatively large quantities of C D D /C O F (see Table XI). Another chapter in this hook 111| presents a more detailed discussion of the recent assessment of destruction of PCB by incineration unddr conditions where k CG> GO vH J HtM215 S ^ iM D f-s ru u rrio N o r m o * ins 1,3,4,7,9-pcnto- CDF (propoMd) Ftfr* 4. Reoctlom b d in f to formatloo of COP from pyrolyni of 2,7\4.4\5tJ'-he*rtilorobipKcwyf, high destruction efficiency was achieved and the level of C U O /C D F in (he combustion effluents were within limits which the U.S. Environ mental Protection Agency (EPA) deemed acceptable. ANALYSES O F C D D /C D F IN ENVIRONMENTAL SAMPLES The extraordinary toxicity of some CDD and CD F dictates the need for analytical capabilities that can delect and quantify picogram quanti ties of CDD and CDF. At the same time, great analytical methods specificity is required, because several other prominent contaminants that persist in environmental samples (e g., PCB and DDE) can interfere with the determination of CDD and CDF. The analytical capability described Was only been realized within the past 3-4 years, and it is now possible to reliably determine parts-per-trillion levels of CDD and CD F in many C H I.O H O D IM N f.O niO X IN S AND ClII.ORODIOFNJOFtiRAN .S 237 Tahir X. Rrwftr of IIR^C/M IM S A nalf* of Wlpr Satopk from Arm CwMaaAnlrf hj fU Mfw iw r Fhr for Trtra- TWm*|fc OrlitWorlMtrf IMWn-p4loiiM (M M w io f m m CDD/CDF* QaaertHy of cD D /rn f fhftfitf Mtahnwn Drtretaiite QMMflfj (r*g per h o w r) TCDU NO ''c v j j .m NO 0.10 rCDD ffeCDO HpCDD ND NO I.2.3.4.4.7J I.2J.4.4.7.9 lout " a , i.jj. NO NO 043 0 4$ II 0.10 i 9.20 0.20 020 0.20 OCDO 1CDF U J.W .M ' 'CI.OCDI I.2.4.I2..U.SJ.J.7.IOther homer* (1) Tout I j* w 20 J.l 94 35.8 30.4 0.20 0.10 0 to 0.10 o to 0 10 rcD F I.2.4.7.IOther Itomeri (1)1 Tout 52 It I 170 o to 0.10 fl 10 H*CDF U.4.4.7.9Other homer* (12) Total 14 414 4) 2 020 020 0.20 ItpCDF I.2J.4.6.I.9 Other k e n e n (4) Total 2.7 44 7.J 020 0 20 0 OCDF I.2.3.4.6.7.S.4 73 0.20 PCOD = peitla-COD; HeCDF * hex CDF: MpCDF * hepia CDF; OCDF = acta CDF. 'S e t IrM for ditcusvoo, ; type* of environmental and biological samples, hazardous chemical wastes, and chemical formulations. The Brehm Laboratory, Wright Slate University, has been one of the major contributors to the development of this highly sophisticated analytical methodology. In general, the ana lytical procedures now applied for definitive determinations of CDD and CDF isomers entail the following: oCj CO 00 tH * 1 i I MM2 I 5981 2SS DESTRUCTION OF DIOXINS TaUr XI. lIR n r/IJIM C Analytical RrmK for CDD/CDF 1o A d Sanyh from InrhwruihM of W iiin Containing TCP* CDO/CDF MCDF DCDF TrCDF TCOF PCDF HaCDF MpCDF OCDF MCDD DC DO TrCDD TCDD PCDD H.CDD HpCDD OCDD TUl N s n k r 1 Agpannl laamrri J 1 T 9 j 7 1 1 4 5 4 9 9 2 1 Total Drtecfd it/1) 79 29 1) 7 1 9 2 1 9 2 4 22 It 117 m M hJm m DnrHaMr Canwauatrd (t/S l 11 94 5 1 t 1 1 at t) n t i i i *Rtcnl analyte hy Wrigbr air Umvruiiy. 1. riiructicn of CDD am^COF from (hr tamper matria ming organic toIvnMi, 2. preliminary eparatio of CDD and CDF from oiher rmtliftKrHi of ikr M irii, which aho haw ^jtn eilrucicd (including other chlorinated irjMtiah) wing ttid-btK treatment and liquid chromatography with alumina, ilka gel and/or other tuitaWe column: J. further fractionation of ihr CDD and CDF tHmg normal and rm n e -p h av high'^rfoimanc liquid chromatography fllV t.O ; and 4. analyte of (hr prepared citrad containing CDD and CDF uriig capillary* columa gar chromalogrsphy/mau iprttrometry (OC/MS). Both low* and high-rtiolution im u apcctromrtry may he wed in thb analyu, depending on The application o f this complex analytical procedure is ledious and cosily, but such a procedure is necessary to obtain definitive data on the CDD and CDF feomert at the extremely low (parts-per-trillion) concen tration levels at which these must (x detected. The results of such an analysis are weft illustrated by data obtained from analysis of the ash sample resulting from incineration of PCP wood-preserving process wastes, which are shown In Table XI. Interestingly, the TCDD homers detected in this sample were I.J.6,8.- 1,3,7.9-, 1,3,7,8- and I.2.J.4-TCDD. rn i.o n o m iir.N 7.o n io xiN 5 a n d rin.oif<m iRrN 7.0FiiRA N s No 2,3,7,fl-TCDI) was found. Similar analyses have recently been accomplished hy (he Urchm laboratory on stack effluents from incinera tion of municipal refuse, and on effluents from incineration of wastes containing PCB. The latter work is discussed more fully and the detailed analytical techniques are also described in another chapter in this bonk (II). ENVIRONMENTAL TRANSPORT AND NATURAL DEGRADATION OK CDD < Contidenblc work h it been done in an effort lo atseii the eaten) of degradation and transport of CDD in the environment ( I ], although the conclusions from these studies u e not entirely clear. Although biodegration of TCDD does not s ^ ^ B b e a particularly important process, both TCDD and OCDD app^H ^M fT ccttvely photodegraded by both natural sunlight and s r lin c ia ltm n v 9 n (UV) radiation ( I). Transport of TCDD in soil, water and air has been investigated, but since the results depend on so many environmental factors (e.g., type of soil and organic content, temperatures and organic content of water, and method of dispersal In air), the conclusions are not straightforward. It appears, however, that TCDD can migrate to some extent in soils, especially porous, sandy soils. Transport of C D D /C D F can occur in the air, especially if these compounds are sorbed on airborne particulates. It is ab o clear that transport of C D D /C D F can occur by runoff of surface waters and or leaching into groundwaters, which ultimately may conlaminate takes, rivers and streams. In the (alter instance, TCDD appears to accumulate largely in sediments, although the content of other organic compounds in natural waters also affects the concentration of CD D / CD F therein. Finally. as discussed earlier, C D D /C D F can bioaccumulate In some plants, animals and fish exposed to these compounds; obviously, this may also result in transport and, ultimately, dispersion of these compounds in the environment. There are few baseline data on con centrations of C D D /C D F in the environment, however, except where high levels of C D D /C D F are anticipated because of massive contamina tion episodes such as those described earlier DESTRUCTION OR DETOXICATION OF CHEMICAL PRODUCTS AND WASTES CONTAINING CD D /C D F Among the methods applied in attempts lo destroy or detoxicate wastes containing CDD and/or CDF are conventional incineration, photolysis. : co .k ? : GO : vH DOM2 I 5981 i n destruction of dioxins radiolysts, ozonolysis, catalytic dechlorination and biological treatment. Several of these techniques and their applicafioA to such chlorinated compounds are discussed in more detail in several other chapters in this book. These chapters clearly demonstrate that considerable success has been achieved in devising environmentally acceptable methods for de stroying or detoxifying hazardous wastes containing CDD and/or CDF. REFERENCES I. Esposito, M. P., T. O. Tlernan and F, E. Dryden. "Drouin*." U.S. EPA Report EPA-400/2-69-197, Industrial Environmental Research Laboratory, Office of Research and Development, Cincinnati, Oil (I960). 1. Nicholson, W. J,, and J. A. Moore. Eds. "tfcahh Effects of ffalogcneicd Aromatic Hydrocarbons." Aim. N. T. Arm. Set. 320:1-730 (1979). 3. Joint NIEHS/IARC Working Group. "Long-Term Ifaiards of PolyeMo- rinaled Dibcntodloxlna and Polychlorinated Dibenzofuraat," World Health Orgama*ion/ international Agency lor Research on Cancer, Lyoo, France (1071). y 4. Pland, A . and A. Renee. "2,3,7,6-Tt`frachlorodibenro-p-Dioxia: Environ mental Contaminant and Molecular Probe," Fed. /Voc. 35fI2>:2404 (H*6). 5. Mosher, H. S.. F. A. For&ma, II. D. Bochwstd and H. O. Fischer. Scient* 144:1160-1110 (|9W ). 0. Moore, J. A., and R. E. Faith. "Immunologic Response and Factors Affecting Its Assetsment," Environ. Heehh Pertp. 16 123 (1974). 7. Hay, A. "Accidents In Trichlorophenol Plants: A Need fur Restiftic Surveys to Ascertain Rbki to Health." Arm. N.Y. Atmd Sd. J20:32M24 (1979). 1. Rappe, C., H. R. Ruser, II. Rurofci and V. Masvda. "Identification of :*oly- chlorinated Dibenzofurans (PC'DFs) Retained in Patients with Yusho," Chtmosphert 4:259-26 (197?). 9. Fsnclli, K. "Presence of 2,3,7,6-Dibcnro-p-f)ioxin in Wildlife Living Near Severn, Italy: A Preliminary Study," Institute de Rieerche Frrmacologiche "Mario Negri," Milan, Italy (I960). 10. "(Tetermination of Chlorinated Dihenro-p-Dioxtns and Dibenzofurnn* In Surface Wipes and Related Specimens from Broome County Facilities, Binghamton. NY, Contaminated as a Result of a Transformer Fire," Brchnt Laboratory. Wright State Uaiversky (1961). 11. Tierma. T. O . M. L Taylor, J. O. Solch, O. F. Vannes*. J. H. Garrett and M. D. Porter. "Incineration of Chemical Wastes Containing Polychlorinated Biphenyls: Assessment of Tests Conducted at Rollins Environmental Services. Deer Park. Texas, and Energy Systems Company. El Dorado. Arkansas," Chapter 9, this volume. L CHAPTER I< SELECTED LEGAL ASPECTS OF A DIOXIN DETOXICATION PROJECT Kent A. Stornier Synle* (U.S.A.), Inc. Palo Alio, California On a summer afternoon in 1974, Oodfrey Moll. Plant Manager of the Syntex Agribusiness chemical production facility in Verona, Missouri, rapped on the side of an old 20-foot-Ull steel tank, which had been sitting idle on the premises for many years. Syntex had purchased the plant, including the steel tank, in 1969. Moll assumed that the tank was empty because Syntex had never used it, but his knocking on the lank wall was inconclusive. Consequently, he carefully lowered a small flask into the lank and, to his surprise, it came up Tilled with a dark sludge material. Moll calculated from the sire df the tank that it contained approximately 4300 gallons of this material, which was the consistency of heavy motor oil. lab o rato ry analysis of the sludge increased his surprise considerably: the 4300 gallons of sludge contained approximately 343 ppm of dioxin. It soon became evident what had happened. In the late 1960s North Eastern Pharmaceutical and Chemical Company, Inc. (NEPACCO) leased a portion of the Verona plant from the company that then owned it. Under this lease, NEPACCO was entirely responsible for disposing of Its own wastes and trash, and agreed to operate at all times in conformity with applicable taws and regulations. NEPACCO s activities at the plant included the production of hexachtorophene. One step of that manu facturing procets. which involved the puriftemtton of trichlorophenol (TCP), apparently produced dioxin a t an unwanted by-product.