‘V‘ Veterans \a‘. Administration Review of Literature on Herbicides, Including Phenoxy Herbicides and. Associated Dioxins Volume Vl ' Annotated Bibliography of Recent Literature on. Health Effects VA Contract Number: V10(93)P—953 REVIEW OF LITERATURE OF HERBICIDES, INCLUDING PHENOXY HERBICIDES AND ASSOCIATED DIOXINS Annotated Bibliography of Literature on Health Effects Published in 1984 Volume VI Prepared for Contracting Officers Technical Representative: Barclay M. Shepard, M.D. Director, Agent Orange Projects Office Department of Medicine and Surgery Veterans Administration 810 Vermont Avenue, N.W. Washington, D.C. 20420 Submitted by: Clement Associates, Inc. 1515 Wilson Boulevard Arlington, VA 22209 May 2, 1985 71¢%%297 For sale by the Superintendent of Documents. U.S. Government Printing Office Washington. DC. 20402 uét47 AIZW? BIBLIOGRAPHY I 7 g ( v.19 pudL Winn This volume is a bibliography of published and unpublisned literature relevant to the human health effects of 2,4—D, 2,4,5—T, PCDD, cacodylic acid, and picloram that became available during 1984. The citations are arranged alphabetically by author. Each citation is followed by a series of keywords. These keywords describe the information contained in the paper including the health etfects(s) or type of study, the route of administration/expo- sure, the chemical, the species, and the type of report. Following the key words is a line that indicates those pages of the critical review (Volume V) in which that document is discussed. Because many resources, e.g., review articles, news reports, and commentaries, are not cited in the critical review, short narrative statements deseribing the contents of those documents are included in the bibliography. REFERENCES Anonymous. 1983a. Final report on the congenital defects and other unfavorable outcomes of pregnancy found in the population of the Seveso area affected by TCDD pollution on 10/7/76. Report to the Special Office for Seveso, Seveso, Italy. 57 pages KEYWORDS: Chlorinated dibenzo—p—dioxins, Environmental exposure, Genotoxicity, Human, Reproductive effects, Teratogenic effects See Pages 7, 8, 13, 77, and 93. Anonymous. 1983b. Wbrker's suits over dioxin pick up speed. Chem. Week. 133:86-88 KEYWORDS: Chloracne, Neurobehavioral effects, Occupational exposure, Chlorinated dibenzo—p—dioxins, Human This news article describes a number of suits filed by workers who were employed in the manufacture of phenoxy herbicides and are seeking compensation for a series of adverse health effects which they attribute to dioxin. Anonymous. 1984a. valuiazione dei rischi associati all esposizione alla TCDD della popolazione in zona b. Report to the Special Office for Seveso, Seveso, Italy. 4 pages (Italian) KEYWORDS: Cancer, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human, Review This risk assessment was performed by the Instituto Superiore di Sanita e della Regione Lombardia. The dose of TCDD corresponding to a cancer risk of 1 in 1,000,000 was estimated to be 0.028 pg/kg/day. The authors then estimated cancer risks associated with the ingestion of soil, vegetables, meat, and eggs from the dioxin-contaminated areas of Seveso. Anonymous. 1984b. Relazione generale: Sarcomi dei tessuti molli ed esposizioni a fenossiacidi e clorofenoli: Studio epidemiologico. Report to the Special Office for Seveso, Seveso, Italy. 9 pages (Italian) KEYWORDS: Cancer, Epidemiologic investigation, Environmental exposure, Phenoxy herbicide formulations, Chlorinated dibenzo-p—dioxins, Human See Pages 7, 8, and 14. This document, produced for discussion at the Milan meeting, reviews the evidence for an association between soft—tissue sarcomas and exposure to phenoxy acid herbicides or chlorinated phenols, both of which may be contaminated with chlorinated dibenzo—p—dioxins. It also contains a detailed protocol for a proposed case—control study of soft-tissue sarcoma in provinces where phenoxy herbicides were used in agriculture and where chlorophenols were used as wood preservatives. Anonymous. 1984c. Ultrastructural findings on placental tissue from pregnant women living in the TCDD—polluted zone (Seveso) subjected to voluntary termination of pregnancy between 1/3/80 and 30/6/82. Report to the Special Office for Seveso, Seveso, Italy. 8 pages KEYWORDS: Other toxic effect, Chlorinated dibenzo—p—dioxins, Environmental exposure, Human, Reproductive effects See Page 78. Abernethy, D.J., Huband, J.C., Greenlee, W.F., and Boreilco, C.J. 1983. The effect of TCDD upon the transformation, initiation, and promotion of C3H/10T 1/2 cells. Presented at the 15th Annual Meeting of the Environmental Mutagen Society. 1 page (abstract) KEYWORDS: Abstract, Cancer, Cultured mammalian cells, Mouse, Chlorinated dibenzo-p—dioxins, In vitro study See Page 63. Andersen, M.E., George, M.E., Rogers, A.M., and Back, K.C. 1983. Toxicity of Perfluoro—N-decanoic Acid and 2,3,7,8—Tetrachloro- dibenzo-p—dioxin in L5178Y Mouse Lymphoma Cells. Air Force Aerospace Medical Research Laboratory, Wright-Patterson Air Force Base, Ohio. NTIS/AFAMRL—TR—82-50. 14 pages KEYWORDS: Cultured mammalian cells, Cytotoxicity, Chlorinated dibenzo-p—dioxins, In vitro study, Mechanism of toxic action The authors studied the effect of TCDD on the growth of L5178Y mouse lymphoma cells in suspension. Doses of TCDD below those that caused cell lysis had no effect on growth but did cause reversible alterations in cell morphology. The authors suggest that TCDD may exert its effect by altering the normal structure and/or function of cell membranes. Angela, P., Valerio, G., Riccardo, P., Maria, R.A., and Angelo, B. 1984. Study of cancer incidence at Seveso: 1975-80. Report to the Special Office for Seveso, Seveso, Italy. 4 pages KEYWORDS: Cancer, Epidemiologic investigation, Environmental exposure, Chlorinated dibenzo-p—dioxins, Human See Pages 6, 8, 13, and 52. Apricena, M., Falliva, L., Ghioldi, R., Puntoni, R., Stagnaro, E., and Vercelli, M. 1984. Survey of mortality in the Seveso area: 1915-1981. Report to the Special Office for Seveso, Seveso, Italy. 9 pages KEYWORDS: Epidemiologic investigation, Environmental exposure, Chlorinated dibenzo—p-dioxins, Human See Pages 6, 8, 13, and 53. Axelrod, D. 1984. Lessons learned from the transformer fire at the Binghamton, New York State Office Building. Presented at 4th International Symposium on Chlorinated Dioxins and Related compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Environmental exposure, Chlorinated dibenzo-p—dioxins, Herbicide impurities other than PCDDs, Human, Abstract See Page 134. This abstract of a talk given at a symposium describes the effects of a transformer fire in the New York State Office Building in Binghamton, N.Y., and the administrative and scientific response to that problem. Azatian, R.A., Avakian, V.A., and Mirzoyan, G.I. 1984. [Cytogenic activity of 2,4—D and treflane herbicides on the chromosomes of 9:32.15 samllaria LJ. Biol. Zh. Arm- 37:460—463 (Russian, summary in English) KEYWORDS: 2,4-D and its esters, Genotoxicity See Pages 61 and 64. The brief English summary of this study reports that 2,4-D produced chromosome aberrations throughout the cell cycle by a mechanism of delayed action. These findings cannot be evaluated. Balk, J.,.and Piper, W. 1984. Altered blood levels of cortico- steroids in the rat after exposure to 2,3,7,8—tetrachloro— dibenzo-p—dioxin. Biochem. Pharmacol. 33:2531-2535 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p-dioxins, Rat The authors administered a single oral dose of 25 ug/kg TCDD to male Sprague—Dawley rats. Plasma corticosterone levels were significantly lower in treated rats 14 and 21 days after administration than in vehicle controls, and TCDD also caused an accumulation of 11—beta—hydroxyprogesterone. The authors speculated that TCDD may interfere with adrenal steroidogenesis. Bandiera, S.M. 1983. Binding of polychlorinated biphenyls and related compounds to the cytosolic 2,3,7,8—tetrachlorodi— benzo-p—dioxin receptor. Diss. Abstr. Int. B 1984. 44:2137-8 KEYWORDS: Mechanism of toxic action, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells, Abstract This is an abstract of the author's Ph.D. dissertation. The author characterized the properties of the cytosolic "TCDD receptor" and developed an in vitro bioassay to assess the relative potencies of complex mixtures of halogenated aromatic compounds. Banxowsxa, J. 1982. [Hepatotoxicity of certain polychlorinated aromatic hydrocarbons]. Rocz. Panstw. Zakl. Hig. 33:303—305 (Polish) KEYWORDS: Acute toxic effects, Hepatic effects, Porphyria cutanea tarda, Enzyme induction or inhibition, Unspecified route of exposure, Chlorinated dibenzo-p-dioxins, Rat, Abstract This is an abstract of a monograph on the acute toxicity of hexachlorobenzene, pentachlorophenol, and TCDD with special emphasis on hepatotoxicity, and porphyriogenic effects. Barr, M. 1983. Post concussion syndrome, hypoglycemia and Agent Orange. Aust. Fam. Physician. 12:224 (letter) KEYWORDS: Neurobehavioral effects, Environmental exposure, Phenoxy herbicide formulations, Human, Commentary In this letter to the editor, the author Speculates that Agent Orange causes axonapathy and demyelination of the subcortical long fiber axons, particularly in the optic tract, and comments on the similarity to symptoms of hypoglycemia. Bianco, V., Meazza, L., and Remotti, G. 1984. Obstetric monitoring in Brianza di Seveso from 1975 to 1981. Report to the Special Office for Seveso, Seveso, Italy. 15 pages. KEYWORDS: Chlorinated dibenzo—p—dioxins, Environmental exposure, Epidemiologic investigation, Human, Reproductive effects See Pages 7, 8, 13, 77, and 93. Bombick, D.W., Brewster, D.W., and Matsumura, F. 1984a. Reduced hepatic low density lipoprotein binding and adipose lipase activity in rabbits treated with 2,3,7,8—tetrachlorodi— benzo-p—dioxin (TCDD). Pesticide Research Center, East Lansing, Michigan. (Abstract of paper to be presented at the 1985 Annual Meeting of the Society of Toxicology, San Diego, California) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo-p-dioxins, Rabbit, Abstract This abstract describes a study of the mechanism of acute toxicity of TCDD in rabbits. A single intraperitoneal dose of 50 ug/kg caused a 50% reduction in hepatocyte low densit lip0protein binding and almost complete inhibition of adipose tissue lipoprotein lipase activity, resulting in increased serum lip0protein levels. Bombick, D.W., Madhukar, B.V., and Matsumura, F. 1984b. Reduced binding of low density lipoprotein to its hepatic plasma membrane receptor of guinea pigs treated with 2,3,7,8~tetra— chlorodibenzo—p—dioxin. Toxicologist. 4:111 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Exposure by injection, Chlorinated dibenzo—p—dioxins, Guinea pig, Abstract This abstract describes a study that is discussed in detail in Bombick et al. (1984c). Bombick, D.W., Matsumura, F., and Madhukar, B.V. 1984c. TCDD (2,3,7,8-tetrachlorodibenzo—p—dioxin) causes reduction in the low-density lipoprotein (LDL) receptor activities in the hepatic plasma membrane of the guinea pig and rat. Biochem. Biophys. Res. Commun. 118:548—554 KEYWORDS: Acute tOxic effects, Mechanism of toxic action, Other toxic effect, Exposure by injection, Chlorinated dibenzo—p-dioxins, Guinea pig Administration or a single intraperitoneal injection of 1 ug/kg TCDD to male guinea pigs caused a reduction in the binding of low—density lipoprotein (LDL) to its receptor on the plasma membrane of liver cells and cultured hepatocytes from TCDD—treated animals demonstrated reduced uptake of LDL. These alterations may explain the hyperlipidemia resulting from TCDD exposure. ‘ \ Bonaccorsi, A., Di Domenico, A., Fanelli, R., Merli, F., Motta, R., Vanzati, R., and Zapponi, G. 1984. Study of the bioavail- ability in the rabbit of the TCDD present in powdered soil from Seveso Zone A (Milan). Report to the Special Office for Seveso, Seveso, Italy. 29 pages KEYWORDS: Metabolism, Oral exposure, Chlorinated dibenzo—p—diOxins, Rabbit The authors studied the bioavailability of TCDD in contaminated soil from Seveso. Rabbits were given single oral doses of TCDD in corn oilzacetone, of TCDD added to clean soil, and three different samples of TCDD—contaminated soil from Seveso. The TCDD in the contaminated soil was on average 68% less available than TCDD in solution and was also significantly less available than TCDD added to the soil in the laboratory. Bond, G.G., Ott, M.G., Brenner, F.E., and Cook, R.R. 1983. Medical and morbidity surveillance findings among employees potentially exposed to TCDD. Br. J. Ind. Med. 40:318-324. KEYWORDS: Epidemiologic investigation, Other toxic effect, Occupational exposure, 2,4,5-T and its esters, Chlorinated dibenzo—p—dioxins, Human See Pages 6, 8, 11, 30, and 132. Bretag, A.H. 1983. Action of 2,4-D on anion and cation channels in rat soleus muscle. In Bretag, A.H., ed. Membrane Permeability: Experiment and Models. Techsearch, Inc., Adelaide. Pp. 125-131. Brewster, D.W., and Matsumura, F. 1984a. TCDD (2,3,7,8—tetrachloro— dibenzo—p-dioxin) reduces lipoprotein lipase activity in the adipose tissue of the guinea pig. Biochem. Biophys. Res. Commun. 122:810—817 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Exposure by injection, Chlorinated dibenzo-p—dioxins, Guinea pig Administration of a single intraperitoneal injection of TCDD to male guinea pigs caused a marked decrease in lipoprotein lipase activity in the adipose tissue. This inhibition correlated with increased serum triglyceride levels and appeared to be irreversible. Brewster, D.W., and Matsumura, F. 1984b. Effect of 2,3,7,8-tetra— chlorodibenzo—p—dioxin on adipose tissue lipoprotein lipase. Pesticide Research Center, East Lansing, Michigan. (Abstract of paper to be presented at the 1985 Annual Meeting of the Society of Toxicology, San Diego, California) ‘ . KEYWORDS: Acute toxic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo-p—dioxins, Guinea pig, Abstract This abstract describes a study investigating the mechanism of acute toxicity of TCDD. Intraperitoneal injection of 1 ug/kg TCDD caused a 44% decrease in adipose tissue lipoprotein lipase (LPL) activity and a twofold increase in serum triglycerides in guinea pigs compared to pair—fed controls. Decreased body weight in treated guinea pigs correlated with discussed LPL activity. Brewster, D.W., Madhukar, B.V., and Matsumura, F. 1982. Influence of 2,3,7,8-TCDD on the protein composition of the plasma membrane of hepatic cells from the rat. Biochem. Biophys. Res. Comm. 107:68—74 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Hepatic effects, Exposure by injection, Chlorinated dibenzo~p~dioxins, Rat SDS-polyacrylamide gel electrophoresis was used to examine the protein composition of the plasma membrane of liver cells from rats given a single intraperitoneal injection of TCDD. TCDD reduced the levels of a number ofproteins in the membrane. Binding of conconavalin A to hepatic plasma membrane was also reduced by TCDD treatment. Brewster, D.W., Madhukar, B.V., and Matsumura, F. 1984. In vivo administration of 2,3,7,8-tetrachlorodibenzo—p-dioxin results in an alteration of the surface characteristics of hepatic membranes. Toxicologist. 4:77 (abstract) KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo—p—dioxins, Rat, Abstract This abstract describes studies that are discussed in detail in Matsumura et al. (1984b). Buchet, J.P., and Lauwerys, R. 1983. [The risks of dioxin]. Louvain Med. 102:419-422 (French) KEYWORDS: Chlorinated dibenzo-p—dioxins, Human, Review This is a very brief review of the experimental and clinical data on the toxicity of TCDD, with an emphasis on long—term chronic effects (i;e., cancer) in humans. (10 references) Budiansky, S. 1984. U.S. Air Force reassures veterans. Nature. 308:102 KEYWORDS: Epidemiologic investigation, Occupational exposure, Phenoxy herbicide formulations, Human, Review This news report describes the U.S. Air Force Ranch Hand study (see Lathrop et a1. 1984) and discusses its implications in terms of the health concerns of Vietnam veterans. Calesnick, B. 1984. Dioxin and Agent Orange. Am. Fam. Physician. 29:303-305 KEYWORDS: Phenoxy herbicide formulations, Review The author briefly reviews the available information from animal experiments and epidemiologic studies and summarizes the health effects of Agent Orange and its constituents, with an emphasis on what physicians should look for in treating veterans who believe they were exposed. (3 references) Cantoni, L., Dal Fiume, D., Ferraroli, A., Salmona, M., and Ruggieri, R. 1984a. Different susceptibility of mouse tissues to porphyrogenic effect of 2,3,7,8—tetrachlorodibenzo—p—dioxin. Toxicol. Lett. 20:201-210. KEYWORDS: Enzyme induction or inhibition, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells, Abstract See Page 117. Cantoni, L., Dal Fiume, D., Rizzardini, M., and Ruggieri, R. 1984b. In vitro inhibitory effect on porphyrinogen carboxylase of liver extracts from TCDD—treated mice. Toxicol. Lett. 20:211-217. KEYWORDS: Enzyme induction or inhibition, Hepatic effects, Mechanism of toxic action, Porphyria cutanea tarda, Subchronic toxic erfects, Exposure by injection, Chlorinated dibenzo—p—dioxins, Rat See Pages 117 and 118. Cantoni, L., Dal Fiume, D., and Ruggieri, R. 1984c. Decarboxylation of uroporphyrinogen I and III in 2,3,7,8-tetrachlorodibenzo— phdioxin induced porphyria in mice. Int. J. Biochem. 16:561—565. KEYWORDS: Mechanism of toxic action, Porphyria cutanea tarda, Exposure by injection, Chlorinated dibenzo-p—dioxins, Mouse Casey, P.H., and Collie, W.R. 1984. Severe mental retardation and multiple congenital anomalies of uncertain cause after extreme parental exposure to 2,4-D. J. Pediatr. 104:313-315 KEYWORDS: Reproductive effects, Occupational exposure, 2,4—D and its esters, Human, Teratogenic effects The authors report the case of a severely mentally retarded female Child with multiple physical abnormalities whose parents had considerable exposure to 2,4—D and 2,4-D amine before and after her conception. This isolated case of parental exposure and congenital defects can at most suggest that 2,4—D was causally involved. Cassimatis, N. 1983. Agent Orange. Aust. NZ J. Psychiatry. 17:95 Centers Centers (letter) KEYWORDS: Neurobehavioral effects, Environmental exposure, Phenoxy herbicide formulations, Human, Commentary The author of this letter points out the similarities among the multiple anxiety symptoms characteristic of Vietnam veterans and those that he observed among a group of migrants who believed that they had been denied compensation unjustly. He suggests that the syndrome is common among people who perceive themselves to be victims. for Disease Control (CDC) 1983. Protocol for Epidemiologic Studies of the Health of Vietnam Veterans. Atlanta, Georgia. November 1983. 101 pages KEYWORDS: Epidemiologic investigation, Occupational exposure, Phenoxy herbicide formulations, Human, Review This is the protocol for an epidemiologic investigation that is being conducted under the sponsorship of the Centers for Disease Control. The investigation consists of 3 studies: a cohort study of the health effects of exposure to Agent Orange in Vietnam, a cohort study of the health effects of military service in Vietnam, and a case-control study of specific cancer types among Vietnam veterans. for Disease Control (CDC) 1984. Health-risk estimates for 2,3,7,8-tetrachlorodibenzo-p—dioxin in soil. MMWR. 33:25-27 KEYWORDS: Cancer, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human, Review This brief report summarizes the approach to, and the results of, a risk assessment performed by CDC to establish a level of concern for TCDD in soil in residential areas. Chapman, D.E., and Schiller, C.M. 1984. Comparative toxicity of 2,3,7,8-tetrachlorodibenzo—p—dioxin (TCDD). Tbxicologist. 4:187 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo-p—dioxins, Mouse, Abstract C57Bl/6J mice were more sensitive to the acute lethal tOxicity of TCDD than were DBA/ZJ mice with BGDZFl/J mice being intermediate suggesting mediation by the cytosolic TCDD receptor. TCDD treatment also caused dose—related decreases in serum total and esterified cholesterol, glucose, and triglyceride suggesting alterations in lipid and carbohydrate metabolism. Christian, B.J., and Peterson, R.E. 1983a. Effects of 2,3,7,8—tetrach1orodibenzo—p-dioxin on [3H]thymidine incorporation into rat liver deoxyribonucleic acid. Toxicology. 8:133-146 KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo-p—dioxins, Rat TCDD treatment did not stimulate thymidine incorporation in the liver of normal rats compared to controls. However, thymidine incorporation was increased in the livers of rats subjected to partial hepatectomy or laparotomy as a result of TCDD pretreatment. This differential effect was not effected by adrenal hormones. Christian, B.J., and Peterson, R.E. 1983b. The role of reduced food consumption in the lethality of TCDD-treated rats. Pharmacologist. 25:169 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Unspecified route of exposure, Chlorinated dibenzo-p-dioxins, Rat, Abstract Rats treated with lethal doses of TCDD lost weight at the same rate and died at the same time as pair—fed controls, and carcass composition was similar at death. Christian, B.J., Menahan, L.A., and Peterson, R.E. 1984. A longitudinal metabolic profile following 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) treatment in the Sprague-Dawley rat. Tbxicologist. 4:186 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Unspec1fied route of exposure, Chlorinated dibenzo-p-dioxins, Rat, Abstract Measurement of plasma and urine concentrations of various indicators of carbohydrate, lipid, and protein metabolism in rats treated with Single toxic doses of TCDD indicated no differences from pair—fed controls indicating that TCDD probably does not alter metabolic pathways. 10 Clement Associates, Inc. (Clement). 1984. Review of Literature on Herbicides Including Phenoxy Herbicides and Associated Dioxins. Vol. III: Analysis of Recent Literature on Health Effects and Vol. IV: Annotated Bibliography. veterans Administration, washington, D.C. 342 pages and 86 pages KEYWORDS: Phenoxy herbicide formulations, Chlorinated dibenzo—p—dioxins, Cacodylic acid, Picloram, Review This critical review and annotated bibliography covered scientific literature published from 1981-1983 revelant to the health effects of herbicides used in Vietnam. (over 450 references) Coox, R.R., and Cartmill, J.B. 1984a. Dioxin: Comparing apples and oranges. Chemtech. (September):534-S37 KEYWORDS: Cancer, Epidemiologic investigation, Occupational exposure, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human, Commentary, Review This commentary critically reviews the evidence that exposure to TCDD is associated with an increased incidence of soft-tissue sarcoma. Special attention is given to the case-contrOI study conducted by the Michigan Department of Public Health, which showed an excess of soft-tissue cancer among women in Midland County. The authors emphasize the importance of correct tumor classification to the outcome of such studies. (24 references) Cook, R.R., and Cartmill, J.B. 1984b. Soft tissue sarcoma and dioxins: Putting the data into perspective. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 205-216 KEYWORDS: Cancer, Epidemiologic investigation, Chlorinated dibenzo-p—dioxins, Human, Review In this paper presented at a symposium, the authors critically review the evidence for an association between soft-tissue sarcoma and exposure to TCDD and conclude that no such assoc1ation has been established. (23 references) Crow, K.D. 1983. Chloracne (halogen acne). In Marzulli, G.N., and Maibach, H.I., eds. Dermatotoxicology. 2nd ed. McGraw—Hill International Book Co., New York. Pp. 461-482 KEYWORDS: Chloracne, Other dermal effects, Environmental exposure, Occupational exposure, Chlorinated dibenzo—p—dioxins, Human, Review This book chapter is a generic discussion of Chloracne and related skin lesions seen in individuals exposed to 11 chlorinated aromatic hydrocarbons; TCDD is the chemical studied most thoroughly. (59 references) D'Argy, R., Hassoun, E., and Dencker, L. 1984. Teratogenicity of TCDD and the congener 3,3',4,4'-tetrachloroazoxybenzene in sensitive and non—sensitive mouse strains after reciprocal blastocyst transfer. Toxicol. Lett. 21:197-202. KEYWORDS: Chlorinated dibenzo—p—dioxins, Exposure by injection, Mouse, Reproductive effects, Teratogenic effects See Pages 97 and 98. Dan, B. 1984. Vietnam and birth defects. JAMA. 252:936—937 KEYWORDS: Environmental exposure, Commentary, Epidemiologic investigation, Genotoxicity, Human, Phenoxy herbicide formulations, Teratogenic effects This editorial discusses the CDC study by Erickson et al. (1984a,b) on the relationship between service in Vietnam and fathering a child with congenital malformations. Brief summaries of chemical spraying in Vietnam and of the accidents at Nitro, west Virginia, and Seveso, Italy, are presented. The author concludes that "it is unlikely that serious congenital anomalies in children of men serving in Vietnam were results of that experience." David, P. 1983. Dioxin lawsuits: Agent Orange in the courts. Nature. 304:6 KEYWORDS: Environmental exposure, Phenoxy herbicide formulations, Human, Commentary This news article describes the veterans' suit against Agent Orange manufacturers and the role of the federal government in ongoing research into the health effects of Agent Orange. David, P. 1984. Agent Orange: Veterans' case comes to court. Nature. 309:5 KEYWORDS: Epidemiologic investigation, Phenoxy herbicide formulations, Human, Commentary This news article reviews the status of a class action suit by Vietnam veterans against seven manufacturers of Agent Orange and describes ongoing epidemiologic studies. Dean, J.H., and Lauer, L.D. 1984. Immunological effects following exposure to 2,3,7,8—tetrachlorodibenzo—p—dioxin: A review. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 275-294 12 KEYWORDS: Immunological effects, Mechanism of toxic action, Chlorinated dibenzo—p-dioxins, Review The authors review studies of the effects of TCDD on immune function in experimental animals and in humans. In animals, TCDD causes thymic atrophy, bone marrow suppression, decreased cell—mediated and humoral immunity, and decreased host resistance to infectious agents or tumor cells. The effects are more severe if TCDD is administered when maturation of T—lymphocytes is maximal. In humans, significant immune impairment has not been observed. (36 references) De Carli, L., Mottura, A., Nuzzo, F., Zei, G., Tenchini, M.L., Fraccaro, M., Nicoletti, B., Simoni, G., and Mocarelli, P. 1982. Cytogenetic investigations of the Seveso population exposed to TCDD. In Plans for Clinical and Epidemiological Follow—up After Area-Wide Chemical Contamination: Proceedings of an International Workshop, March 17—19, 1980. National Academy Press, Wasnington, D.C. Pp. 292—319 KEYWORDS: Cultured mammalian cells, Human, Chlorinated dibenzo—p—dioxins, Environmental exposure, Epidemiologic investigation, Genotoxicity, Review This article reviews previously evaluated cytogenetic studies on subjects exposed at Seveso: cell cultures of tissues obtained from therapeutic abortions (Tenchini et a1. 1979, 1983) and lymphocytes from acutely exposed, chronically exposed, and control subjects (Reggiani 1979, Mottura et a1. 1981). The results are suggestive of an increase in chromosome aberrations. DiBartolomeis, M.J., Jefcoate, C.R., Christian, B.J., Moore, R.W., and Peterson, R.E. 1984. The effect of 2,3,7,8—tetrachlorodi- benzo-p-dioxin (TCDD) on adrenal steroidogenesis, in 1i 9. Toxicologist. 4:187 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p-dioxins, Rat, Abstract This is an abstract of a study in which plasma corticosterone levels were measured in rats 13 days after oral administration of a single dose of 50 ug/kg TCDD. Levels were reduced to 50% of pair-fed contr01 levels. The authors suggest that TCDD inhibits adrenal steroidogenesis. These findings are consistent with those of Balk and Piper (1984). DiGiovanni, J. 1984. Modification of chemical carcinogenesis by halogenated hydrocarbons and other enzyme inducers. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 161—172. 13 KEYWORDS: Cancer, Enzyme induction or inhibition, Mechanism of toxic action, Chlorinated dibenzo—p-dioxins, Review See Page 72. Donna, A., Betta, P.G., Robutti, P., Crosignani, P., Berrino, P., and Bellingeri, D. 1984. Ovarian mesothelial tumors and herbicides: A case-control study. Carcinogenesis. 5:941—942. KEYWORDS: Cancer, Epidemiologic investigation, Occupational exposure, Phenoxy herbicide formulations, Human See Pages 6, 8, 13, 50, and 54. Doss, M., Sauer, H., Von Tiepermann, R., and Colombi, A.M. 1984. Development of chronic hepatic porphyria (porphyria cutanea tarda) with inherited uroporphyrinogen decarbOxylase deficiency under exposure to dioxin. Int. J. Biochem. 16:369-373. KEYWORDS: Porphyria cutanea tarda, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human See Pages 7, 8, 14, 114, and 119. Dougherty, J.A., Schulze, G.E., Taylor, R.T., and Blake, J. 1984. Behavioral Toxicity of an Agent Orange Component: 2,4-D. Oral presentation to the veterans Administration Advisory Committee on Health-Related Effects of Herbicides. December 11, 1984, washington, D.C. 2 pages. KEYWORDS: Neurobehavioral effects, Subchronic toxic effects, Exposure by injection, 2,4-D and its esters, Rat See Page 126. Dunagin, W.G. 1984. Cutaneous signs of systemic tOxicity due to dioxin and related chemicals. J. Am. Acad. Dermatol. 10:688-700 KEYWORDS: Chloracne, Porphyria cutanea tarda, Other dermal effects, Neurobehavioral effects, Other toxic effect, Occupational exposure, Environmental exposure, Chlorinated dibenzo—p-dioxins, Human, Review This is a fairly detailed review of the health effects information on dioxin and other chloracnegens. Written by a dermatologist, it concentrated on skin lesions but surveys all the known health effects. (82 references) Erickson, J.D., Mulinare, J., McClain, P.W., Fitch, T.G., James, L.M., McClearn, A.B., and Adams, M.J. 1984a. Vietnam veterans' l4 risks for fathering babies with birth defects. JAMA. 252:903—912 KEYWORDS: Environmental exposure, Epidemiologic investigation, Genotoxicity, Teratogenic effects, Human, Phenoxy herbicide formulations See Pages 7, 8, 14, 88, 93, and 94. This is a journal article summarizing the full report (Erickson et al. 1984b) of the CDC study of birth defects and the Vietnam-service status of the fathers of case-control pairs of children in Atlanta. Erickson, J.D., Mulinare, J., McClain, P.W., Fitch, T.G., James, L.M., McClearn, A.B., and Adams, M.J. 1984b. Vietnam Veterans' Risks for Fathering Babies with Birth Defects. Centers for Disease Control, Atlanta, Georgia. 370 pages. KEYWORDS: Environmental exposure, Epidemiologic investigation, Human, Phenoxy herbicide formulations, Genotoxicity, Teratogenic effects See Pages 7, 8, 14, 88, 93, and 94. Erti, D.C., and Puhvel, S.M. 1983. Induction of epidermal transglutaminase (ETG) activity by 2,3,7,8—tetrachloro— dibenzo—p—dioxin (TCDD) in mouse keratinocytes. Clin. Res. 31:564A (abstract) KEYWORDS: Chloracne, Enzyme induction or inhibition, Mechanism of toxic action, In vitro study, Chlorinated dibenzo—p—dioxins, Mouse, Abstract This abstract describes studies that have been published in a full-length paper (see Puhvel et al. 1984). Fanelli, R., Chiabrando, C., and Bonaccorsi, A. 1982. 2,3,7,8-Tetra- chlorodibenzo-p—dioxin contamination in the Seveso, Italy incident. Drug Metab. Rev. 13:407-422 KEYWORDS: Environmental exposure, Chlorinated dibenzo—p— dioxins, Human, Review This is a review of the Seveso accident focusing on the time course of TCDD contamination and aspects of assessing human exposure. (20 references) Feeiey, M.M., and Dufresne, M.J. 1983. Competitive interaction for the Ah receptor by polycyclic aromatic hydrocarbons which do not induce aryl hydrocarbon hydroxylase in C3H/10T 1/2 mouse embryo fibroblasts. Prog. Clin. Biol. Res. 135:373—377 15 KEYWORDS: Cancer, Enzyme induction or inhibition, Mechanism of tOxic action, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells Studies of TCDD binding to a specific receptor in cultured C3H/10T 1/2 cell lines indicates that some aromatic hydrocarbons competively inhibit TCDD binding in these cells but do not induce aryl hydrocarbon hydroxylase activity. Fenton, B.K. 1984. A fatal case of 2,4—D toxicity? Vet. Rec. 114:599 (letter) KEYWORDS: Acute toxic effects, Lethality, Unspecified route of exposure, 2,4—D and its esters, Dog This brief letter describes a case of fatal poisoning of a male English pointing dog presumed to have resulted from using 2,4-D to treat a residential lawn. Analysis of the stomach and intestinal tract showed a concentration of 4 mg/kg 2,4-D. Fett, M.J., Dunn, M., Adena, M.A., O'Toole, B.I., and Forcier, L. 1984. Australian Veterans Health Studies: The Mortality Report, Part I: A Retrospective Cohort Study of Mortality among Australian National Serviceman of the Vietnam Conflict Era, and an Executive Summary of the Mortality Report. Australian Government Publishing Service, Canberra, Australia. 217 pages. KEYWORDS: Cancer, Cardiovascular effects, Epidemiologic investigation, Other toxic effect, Environmental exposure, Phenoxy herbicide formulations, Human See Pages 6, 8, ll, 28, 39, and 134. Fingerhut, M.A., Halperin, W.E., Honchar, P.A., Smith, A.B., Groth, D.H., and Russell, W.O. 1984. Review of exposure and pathology data for seven cases reported as soft—tissue sarcoma among persons occupationally exposed to dioxin-contaminated herbicides. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. l8/-203 KEYWORDS: Cancer, Epidemiologic investigation, Occupational exposure, Chlorinated dibenzo—p—dioxins, Human, Review See Page 44. This paper, presented at a symposium held in October 1983 at the Rockefeller University, describes the results of a review of seven cases of soft-tissue sarcoma reported in several occupational cohorts exposed to TCDD through employment in plants where 2,4,5-T or chlorophenols were manufactured. TWO 16 of the cases were misdiagnosed, and two others probably were not exposed. The results of this analysis were discussed in an earlier review of the literature (Clement 1984). Foreier, L., Hudson, H.M., and Fett, M.J. 1984. Australian Veterans Health Studies: The Mortality Report, Part III: The Relationship between Aspects of Vietnam Service and Subsequent Mortality among Australian National Servicemen of the Vietnam Conflict Era. Australian Government Publishing Service, Canberra, Australia. 92 pages. KEYWORDS: Cancer, Cardiovascular effects, Epidemiologic investigation, Other toxic effect, Environmental exposure, Phenoxy herbicide formulations, Human See Pages 6, 11, and 28. Fortunati, G.U. 1984. The Seveso accident: Background emergency and the lessons learned. Presented at the 4th International Symposium on Chlorinated DiOXins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Epidemiologic investigation, Environmental exposure, Chlorinated dibenzo-p-dioxins, Human, Abstract, Review This abstract of a talk given at a symposium reviews the history of the Seveso accident and describes the response to that accident. Fox, J.L. 1984a. Agent Orange study is like a chameleon. Science. 223:1156-1158 KEYWORDS: Cancer, Epidemiologic investigation, Neurobehavioral effects, Porphyria cutanea tarda, Reproductive effects, Occupational exposure, Phenoxy herbicide formulations, Human, Review This is a news article describing the Air Force Ranch Hand study (see Lathrop et a1. l984a,b) and the various interpretations of the results voiced by scientists and interest groups. Fox, J.L. l984b. Agent Orange: Guarded reassurance. Science. 205:909 KEYWORDS: Epidemiologic investigation, Reproductive effects, Occupational exposure, Phenoxy herbicide formulations, Human, Review This news report describes the results of the CDC birth defects study (see Erickson et al. 1984a,b) and reports some reaccions to it. 17 Friedman, J.M. 1984. Does Agent Orange cause birth defects? Teratology. 29:193—221 KEYWORDS: 2,4-D and its esters, 2,4,5-T and its esters, Chlorinated dibenzo—p-dioxins, Phenoxy herbicide formulations, Reproductive effects, Teratogenic effects, Genotoxicity, Review This is an extensive review of the animal and epidemiologic studies examining the possibility that Agent Orange may have caused birth defects in the children of men exposed to this substance. Gatfey, W.R. 1983. Agent Orange and birth defects. N. Engl. J. Med. 309:492 (letter) KEYWORDS: Commentary, Epidemiologic investigation, Genotoxicity, Human, Occupational exposure, Phenoxy herbicide formulations, Reproductive effects, Teratogenic effects In response to the letter of LaVecchio et al. (N. Engl. J. Med. 308:719-720), the correspondent notes the negative findings for an association between birth defects and exposure to TCDD (Townsend et a1. 1983, Australian Veterans Health Studies 1983) and the ongoing studies by CDC (Erickson et al. 1984a,b; Lathrop et al. 1984a,b). Garattini, S. 1982. 2,3,7,8-Tetrachlorodibenzo-p—dioxin toxicology with particular reference to Seveso, Italy: Introductory remarks. Drug Metab. Rev. 13:345-354 KEYWORDS: Enzyme induction or inhibition, Immunological effects, Porphyria cutanea tarda, Environmental exposure, Chlorinated dibenzo-p—dioxins, Review This brief review was the introductory talk at a symposium on Metabolism and Pharmacokinetics of Environmental Chemicals in Man held in 1981. It summarizes the health effects information on TCDD. (36 references) Gasiewicz, T.A. 1984. Receptors for 2,3,7,8-tetrachlorodibenzo—p- dioxin: Their inter- and intra—species distribution and relationship to the toxicity of this compound. National Technical Information Service, NTIS/AD-P001978/6. 20 pages KEYWORDS: Hepatic effects, Mechanism of toxic action, Other toxic effect, Chlorinated dibenzo-p-dioxins, Review The author reviews the evidence supporting the presence of a cytosolic receptor for TCDD. He discusses interorgan and interspecies differences in receptor properties. (37 references) 18 Gasiewicz, T.A., and Neal, R.A. 1982. The examination and quantitation of tissue cytosolic receptors for 2,3,7,8-tetrachlorodibenzo-p—dioxin using hydroxylapatite. Anal. Biochem. 124:1-11 KEYWORDS: Hepatic effects, Enzyme induction or inhibition, Mechanism of toxic action, In vitro study, Chlorinated dibenzo-p—dioxins, Cultured mammalian cells The quantity and TCDD-binding affinity of cytosolic Ah receptor in the livers of Sprague-Dawley rats were determined and compared with similar parameters for C57Bl/6J, DBA/ZJ, and BGDZFl/J mice. The specific binding affinity in rat liver was comparable to that in C57Bl/6J (sensitive) mice and mucn greater than in DBA/ZJ (insensitive) mice. Gasiewicz, T.A., and Rucci, G. 1984a. Examination and rapid analysis of hepatic cytosolic receptors for 2,3,7,8—tetrachlorodi— benzo-p-dioxin using gel-permeation high performance liquid chromatography. Biochim. Biophys. Acta. 798:37—45 KEYWORDS: Mechanism of toxic action, Exposure by injection, In vitro study, Chlorinated dibenzo—p—dioxins, Mouse, Rat The authors used gel-permeation high performance liquid chromatography to isolate a specific receptor for TCDD from the cytosol and nuclei of rat hepatocytes. They determined the speCific binding of this receptor in both receptive and nonreceptive strains of mice. Ga51ewicz, T.A., and Rucci, G. 1984b. Uptake and properties of receptors for 2,3,7,8—tetrachlorodibenzo-p—dioxin in hepatic nuclei from various mammalian species. Fed. Proc. 43:692 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo—p—dioxins, Guinea pig, Hamster, Rat, Abstract This abstract describes studies that are described in full in Gasiewicz and Rucci 1984a. GaSiewicz, T.A., and Rucci, G. 1984c. Cytosolic receptor for 2,3,7,8—tetrachlorodibenzo—p—dioxin: Evidence for a homologous nature among various mammalian species. Mol. Pharmacol. 26:90-98 KEYWORDS: Nonhuman primate The properties of the cytosolic Ah receptor were determined and compared in various species and strains of animals. All species were quite similar. 19 Gasiewicz, T.A., Ness, W.C., and Rucci, G. 1984. Ontogeny of the cytosolic receptor for 2,3,7,8—tetrachlorodibenzo—p—dioxin in rat liver, lung, and thymus. Biochem. Biophys. Res. Commun. 118:185—190 KEYWORDS: Mechanism of toxic action, In vitro study, Chlorinated dibenzo—p-dioxins, Rat The authors measured changes in the concentration of the cytosolic Ah receptor in liver, lung, and thymus of Sprague—Dawley rats as a function of time after birth. Liver and lung concentrations increased until day 21 and then slowly decreased whereas thymus levels remained constant for at least 42 days. Georgian, L., and Tarnavschi, R. 1983. [Chromosomal modifications induced in vivo and in vitro by a pest-control agent (2,4-D)]. Rev. Ig. Bacteriol. Virusol. Parazitol. Epidemiol. Pneumoftiziol. 32:265-269 (Rumanian, summary in English). KEYWORDS: Cultured mammalian cells, 2,4—D and its esters, Genotoxicity, Human, In vitro study, Exposure by injection, Rat See Pages 60, 61, and 64. Gershbein, L.L. 1984. Effect of phenoxy acids on rat liver Ghezzi, regeneration. Res. Commun. Chem. Pathol. Pharmacol. 43:325-334 KEYWORDS: Acute toxic effects, Hepatic effects, Oral exposure, 2,4-D and its esters, 2,4,5—T and its esters, Rat The authors studied the effect of a large number of structural analogs including 2,4-D and 2,4,5-T on liver regeneration when fed to partially hepatectomized male rats. Whereas several compounds structurally related to the hypolipidemic drug, clofibrate, stimulated liver regeneration, feeding of 2,4-D or 2,4,5-T at 0.1% of the diet for 10 days had a slight inhibitory effect on liver regeneration. 1., Aseennato, G., Brambilla, P., Cannatelli, P., Meazza, L., Merlo, P., Mocarelli, P., and Sicurello, F. 1984. Prospective longitudinal epidemiological survey of clean-up workers at work from 1980 in high-contaminated A zone. Report to the Special Office for Seveso, Seveso, Italy. 13 pages KEYWORDS: Epidemiologic investigation, Occupational exposure, Chlorinated dibenzo—p—dioxins, Human 20 This report describes a prospective cohort epidemiologic study of 36 workers involved in the cleanup at Seveso and a control group of 36. There were no differences in clinical chemistries or in the findings of physical examinations of the two groups. This is not surprising in view of the fact that elaborate safety precautions were taken to mininize TCDD exposure among the cleanup workers. No monitoring data are included. Gierthy, J.F., and Crane, D. 1984. Reversible inhibition of in vitro epithelial cell proliferation by 2,3,7,8-tetrachlorodibenzo— p—dioxin. Toxicol. Appl. Pharmacol. 74:91-98 KEYWORDS: Chloracne, Other dermal effects, In vitro study, Chlorinated dibenzo-p-dioxins, Cultured mammalian cells Treatment of subconfluent cultures of a mouse epithelial cell line WIth low concentrations of TCDD caused a decline in cell proliferation and increased sensitivity to density—dependent inhibition of replication. This was accompanied by a change in morphology. All of these effects were reversible upon resuspension in TCDD—free media. These results are very similar to those of Anderson et al.(1983). Gilbert, P., Saint-Ruf, G., Poncelet, F., and Mercier, M. 1980. Genetic effects of chlorinated anilines and azobenzenes on fialmgnella W. Arch. Environ. Contam. Toxicol. 9:533-541. KEYWORDS: Chlorinated dibenzo—p—dioxins, Genotoxicity, In vitro study, Microbial test system See Pages 62 and 64. Goldstein, J.A., and Linko, P. 1984. Differential induction of two 2,3,7,8-tetrachlorodibenzo—p-dioxin—inducible forms of cytochrome P—450 in extrahepatic versus hepatic tissues. Mol. Pharmacol. 25:185-191 KEYWORDS: Mechanism of toxic action, Oral exposure, Chlorinated dibenzo-p—dioxins, Rat The authors studied the inducing effect of oral administration of TCDD on two isozymes of cytochrome P-450 in a number of different tissues in male Sprague-Dawley rats. In the liver TCDD induced both isozymes but in the kidney, lung, spleen, and testes it induced only the 3-MC inducible isozyme. Greenlee, W.F., Dold, K.M., and Irons, R.D. 1984. 2,3,7,8-Tetra- chlorodibenzo—p—dioxin (TCDD) inhibits the induction by thymic epithelial (TE) cells of T—lymphocyte mitogen responsiveness. Toxicologist. 4:188 (abstract) 21 KEYWORDS: Immunological effects, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells, Abstract This abstract describes a study of the effect of TCDD on cultured thymic epithelium. TCDD at levels that did not cause cytotoxicity decreased the ability of thymocytes to respond to Con A or PHA. Greenwald, P., Kovasznay, 8., Collins, D.N., and Therriault, G. 1984. Sarcomas of soft tissues after Vietnam service. JNCI. 73:1107-1109. KEYWORDS: Cancer, Epidemiologic investigation, Occupational exposure, Phenoxy herbicide formulations, Human See Pages 6, 8, 13, and 40. Grieg, J.B., and Osborne, G. 1981. Biochemical and morphological changes induced by 2,3,7,8-tetrachlorodibenzo—p—dioxin in the rat liver cell plasma membrane. J. Appl. Toxicol. 1:334-338 KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo—p-dioxins, Rat The authors investigated the effect of single oral doses of TCDD on characteristics of the plasma membrane of liver cells in female Lac:P rats. TCDD caused a decrease in plasma membrane ATPase activity and also decreased the density of the plama membrane suggesting possible distrubances in lipid metabolism. Greig, J.B., Francis, J.B., Kay, S.J.E., Lovell, D.P., and Smith, A.G. 1984. Incomplete correlation of 2,3,7,8-tetrachlorodibenzo— p-dioxin hepatotoxicity with Ah phenotype in mice. Toxicol. Appl. Pharmacol. 74:17-25 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Hepatic effects, Porphyria cutanea tarda, Oral exposure, Chlorinated dibenzo—p—dioxins, Mouse A study of porphyin levels and serum levels of enzymes indicative of liver damage (ALT and SDH) in a number of mouse strains indicated that sensitivity to porphyria and liver damage did not correlate precisely to aryl hydrocarbon hydroxylase induction. The authors conclude that genes other than the Ah gene influence sensitivity to TCDD—induced hepatotoxicity. Gross, M.L., Lay, J.O., Lyon, P.A., Lippstreu, D., Kangas, N., Harless, R.L., Taylor, S.E., and Dupuy, A.E. 1984. 2,3,7,8-Tetrachlorodibenzo—p~dioxin levels in adipose tissue of Vietnam veterans. Environ. Res. 33:261-268 22 KEYWORDS: Metabolism, Unspecified route of exposure, Chlorinated dibenzo-p—dioxins, Human This study was described in Volume IV of this review (See Holson et a1. 1983 in Clement 1984). The results of this study are preliminary and provide limited insight into the question of whether adipose tissue levels of TCDD are reliable measures of past exposure. Grutman, G., Schoofs, L., Lontie, J.-F., and Van Larebeke, N. 1984. The mutagenicity in prokaryotes of herbicides. Residue Rev. 91:1—46 KEYWORDS: 2,4—D and its esters, Genotoxicity, Review After reviewing the available data, Grutman et a1. concluded that 2,4-D is not mutagenic in prokaryotes but may induce other DNA damage. Gunny, P. 1984. Military looks toward 1985 in ongoing defoliant study. JAMA. 251:2067—2068 KEYWORDS: Cancer, Reproductive effects, Other dermal effects, Occupational exposure, Phenoxy herbicide formulations, Human, Review, Commentary This news article describes the results of the Air Force's Ranch Hand study (see Lathrop et al. 1984a,b) and comments on the implications of the study. Gustafsson, J.A., Wrange, 0., Poellinger, L., Lund, J., Payvar, F., and Yamamoto, K. 1983. Soluble receptor proteins in contr01 of gene expression. In Rydstroem, J., Montelius, J., and Bengtsson, M., eds. Extrahepatic Drug Metabolism and Chemical Carcinogenesis: Proceedings of an International Meeting. Elsevier Science Publishers, Amsterdam. Pp. 401—408 KEYWORDS: Cancer, Enzyme induction or inhibition, Mechanism of toxic action, Other toxic effect, Chlorinated dibenzo—p-dioxins, Review The authors cite their own published research as well as that of other workers to support the hypothesis that the "TCDD receptor" in rat and receptive mouse strain livers is physiochemically similar to the hepatic glucocorticoid receptor complex, a gene regulatory protein. (36 references) Haaparanta, T., Glaumann, H., and Gustafsson, J.A. 1983. Induction of cytochrome P450 dependent reactions in the rat ventral prostate by beta—naphthoflavone and 2,3,7,8—tetrachlorodi- benzo—p—dioxin. Toxicology. 29:61—75 KEYWORDS: Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo-p—dioxins, Rat 23 Intraperitoneal injection of a single dose of TCDD in male Sprague-Dawley rats resulted in a SOD—fold increase in the activities of aryl hydrocarbon hydroxylase and 7—ethoxyresorufin O—deethylase in the prostate. A macromolecule which bound TCDD with great affinity was isolated. Hairapetian, R.B., Avakian, V.A., and Azatian, R.A. 1984. [Cytogenetic activity of 2,4-D, dalapon and semeron herbicides on the Chromosomes of Alligm ggpa LL]. Biol. Zh. Arm. 37:404—408 (Russian, summary in English) KEYWORDS: 2,4-D and its esters, In vitro study, Genotoxicity, Plant species See Pages 61 and 64. A terse English summary of this article reports that 2,4-D produced cytogenetic effects in plant cells. Hall, P., Field, B., and Kerr, C. 1981. Mouse data on dioxin effects. Search. 12:388 (letter) KEYWORDS: Commentary, 2,4-D and its esters, 2,4,5-T and its esters, Chlorinated dibenzo—p—dioxins, Phenoxy herbicide formulations, Reproductive effects, Mouse This letter is concerned with the NTP studies (Lamb et a1. 1980) on the reproductive effects of phenoxy herbicides and TCDD on male mice. The correspondents wrote that although statistically significant effects were not found, the results are consistent with a dose-related effect from TCDD and should not be used as evidence of no effect. Hardell, L. 1983. Exposure to polychlorinated dibenzo-p—dioxins and dibenzofurans in the environment. Prog. Clin. Biol. Res. 132E:357—369 KEYWORDS: Cancer, Environmental exposure, Occupational exposure, Chlorinated dibenzo-p—dioxins, Phenoxy herbicide formulations , Human , Review The author reviews potential sources of human exposure to PCDD and PCDF and briefly reviews the information on adverse human health effects. (57 references) Hardell, L., and Bengtsson, N.O. 1983. Epidemiological study of socioeconomic factors and clinical findings in Hodgkin's disease, and reanalysis of previous data regarding chemical exposure. Br. J. Cancer. 48:217—225 KEYWORDS: Cancer, Epidemiologic investigation, Occupational exposure, Phenoxy herbicide formulations, Human 24 The earlier findings of an association between malignant lymphoma and exposure to phenoxy herbicides and chlorophenols by the first author and his colleagues had been criticized because socioeconomic status and other clinical findings were not included in the analysis. This reanalysis of the data of Hodgkin's Disease cases and their controls taking socioeconomic factors and previous diseases into account still found an association with exposure to phenoxy herbicides and chlorophenols. Hassan, M.Q., Stohs, S.J., and Murray, W.J. 1983. Comparative ability of TCDD to induce lipid peroxidation in rats, guinea pigs, and Syrian golden hamsters. Bull. Environ. Contam. Toxicol. 31:649—657 KEYWORDS: Acute toxic effects, Hepatic effects, Unspecified route of exposure, Chlorinated dibenzo—p—dioxins, Guinea pig, Hamster, Rat In rats 60 ug/kg/day of TCDD caused sevenfold increases in lipid peroxidation and AHH activity and decreases in reduced glutathione peroxidase activity. In the hamster 200 ug/kg had no effect on these parameters. In the guinea pig 1 ug/kg caused small increases in lipid peroxidation and AHH activity but had little effect on glutathione metabolism. Hatch, M. 1984. Reproductive effects of the dioxins. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 255-274 KEYWORDS: Chlorinated dibenzo—p—dioxins, Occupational exposure, Environmental exposure, Reproductive effects, Teratogenic effects, Genotoxicity, Epidemiologic investigation, Human, Review This article reviews epidemiologic studies in which adverse reproductive outcomes have been investigated with respect to possible TCDD exposure. Some findings, especially from the Vietnamese studies, were suggestive, but the body of evidence was found to be inadequate for drawing a definitive conclusion about TCDD's potential as a reproductive toxin. Hay, A. 1983. Defoliants in Vietnam: The long—term effects. Nature. 302:208-209 KEYWORDS: Cancer, Reproductive effects, Genotoxicity, Environmental exposure, Phenoxy herbicide formulations, Human, Review The author discusses the international symposium on herbicides and defoliants in war held in Ho Chi Minh City in January 1983. He also reviews the effects of herbicides, 25 especially Agent Orange, on vegetation, wildlife, and human health. (6 references) Hoffman, D.J., and Albers, P.H. 1984. Evaluation of potential embryotoxicity and teratogenicity of 42 herbicides, insecuicides, and petroleum contaminants to mallard eggs. Arch. Environ. Contam. Toxicol. 13:15-27 KEYWORDS: 2,4-D and its esters, 2,4,5-T and its esters, Teratogenic effects, Avian species, Other route of exposure See Page 96. The findings for 2,4,5-T were presented in Hoffman and Eastin (1982) and have already been reviewed. The new data on 2,4-D are evaluated in this document. Holden, C. 1984a. VA to study twins. Science. 223:1157 KEYWORDS: Epidemiologic investigation, Neurobehavioral effects, Occupational exposure, Phenoxy herbicide . formulations, Human, commentary This news article describes the planned study of twin veterans to be conducted by the Veterans Administration to characterize the psychological, psychosocial, and health effects of service in Vietnam. One aspect of this study is designed to ascertain the effects of exposure to Agent Orange. Holden, C. 1984b. VA study of twins may be canceled. Science. 226:521 KEYWORDS: Epidemiologic investigation, Neurobehavioral effects, Environmental exposure, Phenoxy herbicide formulations, Human, Commentary This news article reports that a Veterans Administration— sponsored epidemiologic study of twins may be canceled on the grounds that the study would not be sensitive enough to detect the effects it was designed to reveal. Hook, J.B., and Serbia, V.C. 1982. Effects of pesticides on the kidney. In Chambers, J.B., and Yarbrough, J.D., eds. Effects of Chronic Exposures to Pesticides on Animal Systems. Raven Press, New York. Pp. 61—84 KEYWORDS: Renal effects, Chlorinated dibenzo-prdioxins, 2,4,5-T and its esters, Review 2,4,5-T and TCDD are two of the chemicals discussed in this review. The authors conclude that the kidney is not a primary site of toxic action for either of these compounds, although both compounds interfere with active transport in 26 the renal tubules and TCDD is a potent inducer of microsomal mixed function oxidase in the kidneys. (67 references) Hope, W., Lischwe, D., Russell, W., and Weiss, S. 1984. Porphyria Idco, G. cutanea tarda and sarcoma in a worker exposed to 2,3,7,8-tetrachlorodibenzo—p—dioxin: Missouri. JAMA. 251:1534. KEYWORDS: Cancer, Porphyria cutanea tarda, Occupational exposure, Chlorinated dibenzo-p—dioxins, Human See Pages 6, 8, 13, 50, and 117. 1984. Final report on the results of D-gluaric acid determinations done at Seveso in adults and children in the period 1978-1982. Report to the Special Office for Seveso, Seveso, Italy. 29 pages. KEYWORDS: Enzyme induction or inhibition, Epidemiologic investigation, Environmental exposure, Chlorinated dibenzo—p-dioxins, Human See Pages 7, 8, 13, and 70. Instituto Superiore di Sanita 1984. Approaches to the risk Israel 7 assessment of health effects related to areas contaminated with 2,3,7,8-tetrachlorodibenzo—p—dioxin(TCDD). Report to the Special Office for Seveso, Seveso, Italy. 22 pages KEYWORDS: Cancer, Reproductive effects, Chloracne, Neurobehavioral effects, Immunological effects, Environmental exposure, Chlorinated dibenzo—p-dioxins, Human, Review This a summary report of discussions held by an international group of scientists on how to approach the assessment of human health risks from exposure to dioxins via contaminated soil. The ba51s for the discussion was a draft report entitled "Health Implications of TCDD Contamination of ReSidential Soil." D.I., and Whitlock, J;P. 1984. Regulation of cytochrome P1—450 gene transcription by 2,3,7,8-tetrachlorodibenzo- p—dioxin in wild type and variant mouse hepatoma cells. J. Biol. Chem. 259:5400-5402 KEYWORDS: Hepatic effects, Enzyme induction or inhibition, Mechanism of toxic action, In vitro study, Chlorinated dibenzo-p-dioxins, Cultured mammalian cells The authors investigated the molecular mechanism of TCDD induction of aryl hydrocarbon hydroxylase activity in cultured mouse hepatoma cells. The results suggest that nuclear localization of the TCDD—receptor complex is critical. 27 Jackson, J.D., and Sharp, J.G. 1982. Functional and quantitative effects of 2,3,7,8-tetrachlorodibenzo—p—dioxin exposure on the cell mediated immune system in mice. Int. J. Immunopharmacol. 4:323a (abstract) KEYWORDS: Immunological effects, Oral exposure, Chlorinated dibenzo—p—dioxins, Mouse, Abstract This abstract describes a study of the effect on the immune system of two oral doses of 5 ug/kg TCDD given one week apart to female C57B1/6J mice. There were decreases in spleen cell numbers and in thymus weight and a suppression of spleen cell-mediated immune function as measured by mitogen, hemolytic—plaque, and DTH assays. Johansen, M.G., McGowan, J.P., Tu, S.H., and Shirachi, D., Y. 1984. Tumorigenic effect of dimethylarsinic acid in the rat. Proc. West. Pharmacol. Soc. 27:289—292. KEYWORDS: Cancer, Oral exposure, Cacodylic acid, Rat See Pages 147 and 148. Jones, P.B.C., Miller, A.G., Israel, D.I., Galeazzi, D.R., and Whitlock, J.P. 1984. Biochemical and genetic analysis of variant mouse hepatoma cells which overtranscribe the cytochrome P1-450 gene in response to 2,3,7,8—tetrachloro— dibenzo—p—dioxin. J. Biol. Chem. 259:12357-12363 KEYWORDS: Hepatic effects, Enzyme induction or inhibition, Mecnanism of toxic action, In vitro study, Chlorinated dibenzo-p—dioxins, Cultured mammalian cells The authors isolated a variant mouse hepatoma cell type that exhibits increased aryl hydrocarbon hydroxylase induction in response to TCDD as a result of increased rate of transcription of cytychrome P1-450 gene. The properties of the gene are investigated. JRB Associates, Inc. (JRB). 1981. Review of Literature on Herbicides, Including Phenoxy Herbicides and Associated Dioxins. Vol. I: Analysis of Literature and Vol. II: Annotated Bibliography. veterans Administration, washington, D.C. 325 pages and 397 pages KEYWORDS: Phenoxy herbicide formulations, Chlorinated dibenzo-p—dioxins, Cacodylic acid, Picloram, Review This critical review and annotated bibliography covers scientific literature published prior to the middle of 1981 on the composition, environmental fate and health effects of herbicides used in Vietnam. 28 Kamata, K. 1983. [Effect of 1,3,6,8-tetrachlorodibenzo—p—dioxin on rat fetus]. Oyo Kakuri. 25:713—718 (Japanese, summary and tables in English). KEYWORDS: Chlorinated dibenzo—p—dioxins, Oral exposure, Rat, Subchronic toxic effects, Teratogenic effects See Page 98. Kaminsky, L.S., DeCaprio, A.P., Gierthy, J.F., and Silkworth, J.B. 1984. The role of environmental matrices in chlorinated dioxin and dibenzofuran toxicity. Presented at 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Acute toxic effects, Metabolism, Oral exposure, Chlorinated dibenzo—p—dioxins, Guinea pig, Abstract Soot contaminated with TCDD and TCDF, taken from the Binghamton State office building, was given to guinea pigs. The absorption of the TCDD and TCDF was quantitated by comparing the lethality of the soot to a benzene extract of the soot. The extract was about 30 percent more toxic than the soot. Kao, J., Hall, J., Shugart, L.R., and Holland, J;M. 1984. An in vitro approach to studying cutaneous metabolism and disposition of topically applied xenobiotics. Tbxicol. Appl. Pharmacol. 75:289—298 KEYWORDS: Enzyme induction or inhibition, Dermal, Injection In vitro study, Dioxins, Mouse The penetration of benzo(a)pyrene (BP) through structurally intact mouse skin in culture was studies.Pretreatment of mice with TCDD increased the penetration of BP through the skin. Measurement of metabolism in cultured skin indicated that TCDD enhanced the metabolism of BP to water soluble metabolites. Karenlampi, S.O., Eisen, H.J., Hankinson, 0., and Nebert, D.W. 1983. Effects of cytochrome P1-450 inducers on the cell—surface receptors for epidermal growth factor, phorbol 12, 13-dibutyrate, or insulin of cultured mouse hepatoma cells. J. Biol. Chem. 258:10378-10383 KEYWORDS: Cancer, Mechanism of toxic action, Other toxic effect, Other dermal effects, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells The effect of cytochrome P1—450 inducers, including TCDD, on the cell—surface receptors was studied in cultured mouse 29 hepatoma cells. The ability to induce P1-450 did not corre- late with inhibition of epidermal growth factor binding. Katz, L.B., Theobald, H.M., and Peterson, R.E. 1983. Effect of antiinflammatory drugs on the enhanced edema response to carrageenan and dextran in rats treated with 2,3,7,8-tetra— chlorodibenzo-p-dioxin (TCDD). Pharmacologist. 25:103 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Unspecified route of exposure, Chlorinated dibenzo—p—dioxins, Rat, Abstract This abstract describes a study in rats of the ability of a single dose of TCDD to enhance paw edema caused by the injection of carrageenan or dextran. These results have been publisned by Theobald et a1. (1983) as a full-length paper. Katz, L.B., Theobald, H.M., Bookstaff, R;C., and Peterson, R.E. 1984. Characterization of the enhanced paw edema response to carrageenan and dextran in 2,3,7,8-tetrachlorodibenzo—para— dioxin treated rats. J. Pharmacol. Exp. Ther. 230:670-678 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Exposure by injection, Chlorinated dibenzo—p-dioxins, Mouse, Rat The mechanism by which TCDD pretreatment enhances the paw edema induced by carrageenan and dextran in rats and mice was investigated using various mediators of edema. The authors concluded that TCDD potentiates the stimulation of phosphOlipase activity in vascular endothelial cells. Kawamura, K., Sato, R., and Kashima, M. 1983. [Acute and chronic toxicity of l,3,6,8-tetrachlorodibenzo—p—dioxin (1,3,6,8- TCDD)]. Oyo Yakuri. 25:703-711 (Japanese, summary in English) KEYWORDS: Acute toxic effects, Subchronic toxic effects, Hepatic effects, Hematological effects, Other toxic effect, Oral exposure, Exposure by injection, Herbicide impurities other than PCDDs, Mouse, Rat, Guinea pig The English abstract of this Japanese article indicates that the authors studied the acute and subchronic toxicity of l,3,6,8-TCDD in rats, mice, and guinea pigs. In contrast to 2,3,7,8—TCDD, rats tolerated oral doses of 1,3,6,8-TCDD as high as 5,000 mg/kg for 6 months without significant toxic effects. Kawashima, Y., Hanioka, N., and Kozuka, H. 1984a. Induction of microsomal stearoyl-CoA desaturase by the administration of 30 various phenoxyacetic acid derivatives. J. Pharmacobio— Dynamics. 7:286-293 KEYWORDS: Enzyme induction or inhibition, Oral exposure, 2,4—D and its esters, 2,4,5-T and its esters, Rat The authors examined the induction of hepatic microsomal stearoyl-CoA desaturation activity. 2,4,5-T had a weak inducing effect compared to 2-(4-chlorophenoxy)-2—methy1- propianic acid (clofibric acid). There was no effect on (NADH)-cytochrome b5 reductase activity. 2,4-D had little effect on stearoyl-CoA desaturase. Kawashima, Y., Katoh, H., Nakajima, S., Kozuka, H., and Uchiyama, M. 1984b. Effects of 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid on peroxisomal enzymes in rat liver. Biochem. Pharmacol. 33:241-246 KEYWORDS: Acute toxic effects, Enzyme induction or inhibition, Hepatic effects, Oral exposure, 2,4-D and its esters, 2,4,5-T and its esters, Rat On the basis of structural similarity to chlofibric acid, the authors assessed the ability of 2,4—D and 2,4,5-T to cause peroxisomal proliferation in rat liver. Rats fed a diet containing 0.25% 2,4-D or 2,4,5—T for 7 days had decreased serum triglyceride and chlolesterol levels, increased catalase activity, and increased carnitine acetyltransfuase activity. 2,4—D was less active than 2,4,5-T. Many compounds that stimulate peroxisomal prolification also cause liver tumors in rodents. Keith, L.H., Rappe, C., and Choudhary, G., Eds. 1983. Chlorinated Dioxins and Dibenzofurans in the Total Environment. Vol.2. Butterworth Publishers, Stoneham, Massachusetts. 540 pages This collection of papers is the proceedings of a symposium of the same title held at the 1982 National Meeting of the American Chemical Society. Individual papers from this volume are entered separately in this and earlier volumes of the literature update. Kelling, C.K., Christian, B.J., and Peterson, R.E. 1984. Effect of 2,3,7,8—tetrachlorodibenzo-p-dioxin (TCDD) on food intake, body weight and lethality in guinea pigs, rats and mice: A pair-feeding study. Toxicologist. 4:186 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Unspecified route of exposure, Chlorinated dibenzo-p-dioxins, Guinea pig, Mouse, Rat, Abstract The nature of the wasting syndrome following a single acutely toxic dose of TCDD was examined in mice, rats, and guinea 31 pigs. The authors conclude that weight loss in these species is due to hypophagia. Kester, J.E., and Gasiewicz, T.A. 1984. The Ah receptor: Physical and chemical affectors of stability. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16—18, 1984. 1 page (abstract) KEYWORDS: Mechanism of toxic action, In vitro study, Chlorinated dibenzo—p-dioxins, Abstract This abstract summarizes the results of a number of studies of the properties of the "TCDD receptor." The authors conclude that the structure, behavior, and/or enzymatic regulation of the Ab receptor may be different from those of the steroid receptors. Kimbrough, R.D., Falk, H., Stehr, P., Portier, C;, and Fries, G. 1983. Risk assessment document on 2,3,7,8—tetrachlorodi- benzodioxin (TCDD) levels in soil. Centers for Disease Control (CDC). 85 pages KEYWORDS: Cancer, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human, Review This risk assessment, prepared by U.S. government health officials, critically reviews health effects, bioavailability, and metabolic information in order to arrive at a concentration of 2,3,7,8—TCDD in soil that constitutes a level of concern in residential areas. The authors conclude that levels greater than 1 ppb are of concern based on the carcinogenic activity of TCDD in female rats. (99 references) Kimbrough, R.D., Falk, H., Stehr, P., and Fries, G. 1984. Health implications of 2,3,7,8-tetrachlorodibenzodioxin (TCDD) contamination of residential soil. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 121-150 KEYWORDS: Cancer, Reproductive effects, Environmental exposure, Chlorinated dibenzo-p—dioxins, Review This description of the CDC risk assessment for TCDD in soil was presented at a symposium and is essentially the same as the full report by Kimbrough et a1. (1983). (27 references) Knutsen, A.P. 1984i Immunologic effects of TCDD exposure in humans. Bull. Environ. Contam. Toxicol. 33:673-681. 32 KEYWORDS: Immunological effects, Environmental exposure, Chlorinated dibenzo-p-dioxins, Human See Pages 7, 8, l4, and 107. Knutson, J.C., and Poland, A. 1984a. 2,3,7,8—Tetrachlorodibenzo— p—dioxin: Examination of biochemical effects involved in the proliferation and differentiation of XB cells. J. Cell. Physiol. 121:143-151 KEYWORDS: Enzyme induction or inhibition, Mechanism of toxic action, Other dermal effects, Chlorinated dibenzo—p—dioxins, Review In this review, the authors use the results of whole animal and in vitro studies to support a conclusion that induction of aryl hydrocarbon hydroxylase activity and induction of epithelial hyperproliferation and hyperkeratinization by TCDD are independent responses even though both are mediated by the cytosolic TCDD receptor. (24 references) Knutson, J.C., and Poland, A. 1984b. The Cytosol receptor for Kociba, 2,3,7,8-tetrachlorodibenzo—p-dioxin: Mediator of two distinctive pleiotropic responses. National Technical Information Service, NTIS/AD—P001976/0. 12 pages KEYWORDS: Cancer, Mechanism of toxic action, Other dermal effects, In vitro study, Chlorinated dibenzo—p-dioxins, Cultured mammalian cells The authors studied the mechanism by which TCDD causes cultured mouse teratoma cells to differentiate into stratified squamous epithelium by comparing the effects of TCDD to those of epidermal growth factor, cholera toxin, and l2-O—tetradecanoylphorbol—l3—acetate (TPA). Measurement of thymidine incorporation, arachidonic acid release, cAMP accumulation, and phospholipid turnover indicated that TCDD does not cause hyperkeratinization by mechanisms similar to any of the other agents. R.J. 1984. Summary and critique of rodent carcinogenicity studies of chlorinated dibenzo-p—dioxins. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 77-98 KEYWORDS: Cancer, Genotoxicity, Chlorinated dibenzo-p-dioxins, Rat, Mouse, Review The author summarizes and reviews the results of carcinogenesis bioassays, promotion studies, and genetic toxicity studies of chlorinated dioxin congeners in rodents and concludes that TCDD provokes a carcinogenic response by a mechanism other than gene mutation. (38 references) 33 Kociba, R.J., and Cabey, O. 1984. Comparative toxicity and biologic activity of chlorinated dibenzo-p—dioxins and furans relative to 2,3,7,8-tetrach1orodibenzo-p—dioxin. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Acute toxic effects, Chloracne, Teratogenic effects, Cancer, Unspecified route of exposure, Chlorinated dibenzo—p—dioxins, Abstract, Review This is an abstract of a talk given at a symposium. The authors reviewed the evidence for interspecies variability in sensitivity to the toxic effects of chlorinated dibenzo-p—dioxins and furans, as well as the available information on the relative toxicity of various congeners of this series of compounds. Korgeski, G.P., and Leon, G.R. 1983. Correlates of self-reported and objectively determined exposure to Agent Orange. Am. J. Psychiatry. 140:1443—1449 KEYWORDS: Epidemiologic investigation, Neurobehavioral effects, Environmental exposure, Phenoxy herbicide formulations, Human This is a publication based on Dr. Korgeski's doctoral dissertation, which was reviewed in the previous volume. Koshakji, R.P., Harbison, R12., and Bush, M.T. 1984. Studies on the metabolic fate of [ C]2,3,7,8-tetrach1orodibenzo—p—dioxin (TCDD) in the mouse. Toxicol. Appl. Pharmacol. 73:69-77 KEYWORDS: Metabolism, Oral exposure, Chlorinated dibenzo—p—dioxins, Mouse Radiolabelled TCDD was used to determine the metabolic fate of orally administered TCDD in the mouse. At least 2/3 of the administered dose was eliminated in the feces within 24 hours and was probably not absorbed. The remainder was eliminated as both unchanged TCDD and metabolite. The half—life of radioactivity in the body was approximately 20 days. Laksnman, R. 1984. Mechanism of absorption, distribution and metabolism of TCDD. Oral presentation to the Veterans Administration Advisory Committee on Health-Related Effects of Herbicides. December 11, 1984, washington, D.C. 1 page KEYWORDS: Metabolism, Unspecified route of exposure, In vitro study, Chlorinated dibenzo-p-dioxins, Abstract This abstract of an oral presentation to the Veterans Administration Advisory Committee summarizes the preliminary results of metabolism and pharmacodynamic studies in an 34 unspecified animal species. After intravenous administration, TCDD accumulates preferentially in adipose tissue and the liver. The half-life of 17 hours in the liver is considerably shorter than in adipose tissue. Lamb, J.C., and Moore, J.A. 1982. Effects of phenoxy acid herbicides on male reproductive function. Contracept. Delivery Syst. 3:171 KEYWORDS: Abstract, Reproductive effects, Teratogenic effects, Phenoxy herbicide formulations, Chlorinated dibenzo-p—dioxins, Rat, Human This abstract concerning the reproductive effects of the phenoxy herbicides and their contaminant TCDD contains no new information. Lathrop, G.D., Wolfe, W.H., Albanese, R.A., and Moynahan, P.M. 1984a. An Epidemiologic Investigation of Health Effects in Air Force Personnel Following Exposure to Herbicides: Baseline Morbidity Study Results. USAF School of Aerospace Medicine, Brooks Air Force Base, Texas. 19 chapters. KEYWORDS: Chloracne, Cancer, Cardiovascular effects, Epidemiologic investigation, Hematological effects, Hepatic effects, Immunological effects, Neurobehavioral effects, Renal effeccs, Reproductive effects, Respiratory effects, Occupational exposure, Phenoxy herbicide formulations, Human See Pages 6, 8, 11, 23, 37, 54, 68, 70, 84, 88, 93, 94, 106, 110, 115, 133, 138, 139, and 141. Lathrop, G.D., Wblfe, W.H., Albanese, R.A., and Moynahan, P.M. 1984b. An epidemiologic investigation of health effects in Air Force personnel following exposure to herbicides and associated dioxins. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Chloracne, Cancer, Cardiovascular effects, Epidemiologic investigation, Hematological effects, Hepatic effects, Immunological effects, Neurobehavioral effects, Reproductive effects, Other dermal effects, Occupational exposure, Phenoxy herbicide formulations, Human, Abstract See Pages 6, 8, 11, 23, 37, 54, 68, 70, 84, 88, 93, 94, 106, 110, 115, 122, 133, 138, 139, and 141. This abstract of a talk given at a symposium summarizes the study that is reported in full in Lathrop et al. (1984a). LaVecchio, F., Pashayan, H., and Singer, W. 1983. Agent Orange and birth detects. N. Engl. J. Med. 309:492 (letter) 35 KEYWORDS: Commentary, Epidemiologic investigation, Genotoxicity, Human, Occupational exposure, Phenoxy herbicide formulations, Reproductive effects, Teratogenic effects This is a response to two letters appearing in the same issue (Lipson 1983, Gaffey 1983). The correspondents stated their awareness of the ongoing CDC (Erickson et al. 1984a,b) and Air Force (Lathrop et al. 1984a,b) studies and that their purpose is to promote more comprehensive study of dioxin as an inducer of chromosome alterations and birth defects in humans. Lawrence, C.E. 1984. New York State proportional mortality study. Lesca , Oral presentation to the veterans Administration Advisory Committee on Health—Related Effects of Herbicides. December 11, 1984, washington, D.C. KEYWORDS: Cancer, Epidemiologic investigation, Environmental exposure, Phenoxy herbicide formulations, Human See Pages 6, 8, 13, and 42. P. 1983. Modulating effects of 2,3,7,8-tetrachlorodibenzo—p— dioxin on skin carcinogenesis initiated by 7,12-dimethyl— benz[a]anthracene in CF—l Swiss mice. In Rydstroem, J., Montelius, J., and Bengtsson, M., eds. Extrahepatic Drug Metabolism and Chemical Carcinogenesis: Proceedings of an International Meeting. Elsevier Science Publishers, Amsterdam. Pp. 589—590. KEYWORDS: Cancer, Enzyme induction or inhibition, Dermal exposure, Chlorinated dibenzo—p—dioxins, Mouse See Page 73. Linnainmaa, K. 1984. Induction of sister chromatid exchanges by Lipson, peroxisome proliferators 2,4—D, MCPA, and clofibrate in vivo and in vitro. Carcinogenesis. 5:703-707 KEYWORDS: 2,4-D and its esters, Genotoxicity, Cultured mammalian cells, Rat, Hamster, Oral exposure, In vitro study This is the third of five articles derived from the author's Ph.D. dissertation (1983), which was reviewed previously. A. 1983. Agent Orange and birth defects. N. Engl. J. Med. 309:491 (letter) KEYWORDS: Commentary, Epidemiologic investigation, Genotoxicity, Human, Occupational exposure, Phenoxy herbicide formulations, Reproductive effects, Teratogenic effects In response to the letter of LaVecchio et al. (N. Engl. J. Med. 308:712—720), the correspondent calls attention to the 36 negative results in the Australian Vietnam Veterans study of birth defects (Australian Veterans Health Studies 1983). Lock, J.H., Barone, M., and Eyster, J. 1984. Birth defect data and the production of chlorophenolic compounds. Office on Vital and Health Statistics, Michigan Department of Public Health. 18 pages. KEYWORDS: Chlorinated dibenzo—p—dioxins, Environmental exposure, Epidemiologic investigation, Human, Reproductive effects, Teratogenic effects, Genotoxicity See Pages 7, 8, 14, and 81. Lovati, M.R., Galbussera, M., Franceschini, G., weber, G., Resi, L., Tanganelli, P., and Sirtori, C.R. 1984. Increased plasma and aortic triglycerides in rabbits after acute administration of 2,3,7,8-tetrachlorodibenzo—p—dioxin. Toxicol. Appl. Pharmacol. 75:91—97 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p—dioxins, Rabbit Administration of a single oral dose of TCDD to rabbits caused an increase in the concentration of triglycerides in the plasma and in the aorta. The increase was primarily in the very low-density lipoprotein fraction. TCDD probably inhibited triglyceride breakdown. Lyons, R. 1984. U.S. embarks on $100 million study of Agent Orange. New York Times. September 25, 1984 KEYWORDS: Occupational exposure, Phenoxy herbicide formulations, Human, Review This newspaper article describes ongoing and anticipated research funded by the U.S. government for the purpose of characterizing the human health effects of exposure to Agent Orange. Madhukar, B.V., Brewster, D.W., Bombick, D.W., and Matsumura, F. 1984a. In vivo administered 2,3,7,8-tetrachlorodibenzo—p— dioxin (TCDD) reduces epidermal growth factor (EGF) binding to rat hepatic plasma membrane. Toxicologist. 4:78 (abstract) KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Unspecified route of exposure, Chlorinated dibenzo—p-dioxins, Rat, Abstract This abstract describes studies that are discussed in detail in Madhekar et al. 1984b. 37 Madhukar, B.V., Brewster, D.W., and Matsumura, F. 1984b. Effects of Martin, in vivo administered 2,3,7,8-tetrachlorodibenzo-p—dioxin (TCDD) on the receptor binding of epidermal growth factor in the hepatic plasma membrane of the rat, the guinea pig, the mouse and the hamster. Proc. Natl. Acad. Sci. U.S.A. 18 pages (accepted for publication) KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Other toxic effect, Exposure by injection, Chlorinated dibenzo—p—dioxins, Rat, Hamster, Mouse, Guinea pig Administration of single intraperitoneal injections of TCDD to rats, guinea pigs, hamsters, and mice cause a decrease in the binding of epidermal growth factor to hepatic plasma membranes. Receptive mice strains (C57B1/6) were more responsive to this effect than were non-receptive strains (DBA/2). In vitro studies suggest a biochemical role for this effect. J.V. 1984. Lipid abnormalities in workers exposed to dioxin. KEYWORDS: Cardiovascular effects, Enzyme induction or inhibition, Epidemiologic investigation, Other toxic effect, Occupational exposure, Chlorinated dibenzo—p—dioxins, Human See Pages 7, 8, 69, 70, 137, and 139. Matsumura, F. 1983. Biocnemical aspects of action mechanisms of 2,3,7,8—tetrachlorodibenzo—p-dioxin and related chemicals in animals. Pharmacol. Ther. 19:195-210 KEYWORDS: Mechanism of toxic action, Hepatic effects, Other toxic erfect, Chlorinated dibenzo—p—dioxins, Review The author reviews published information on the mechanism of toxic action of TCDD and suggests that many of the effects are explained by alterations to the plasma membrane of cells. These alterations, which may be secondary to binding to the Ah receptor, could explain the carcinogenic response and thymic atrophy caused by TCDD. (75 references) Matsumura, F., Brewster, D.W., Madhukar, B.V., and Bombick, D.W. 1984a. Alteration of rat hepatic plasma membrane functions by TCDD (2,3,7,8—tetrach1orodibenzo—p—dioxin). In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 295—314 KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo—p~dioxins, Rat 38 The studies and results presented in this symposium presentation are essentially the same as those described in Matsumura et al. 1984b. Matsumura, F., Brewster, D.W., Madhukar, B.V., and Bombick, D.W. 1984b. Alteration of rat hepatic plasma membrane functions by 2,3,7,8-tetrachlorodibenzo—p—dioxin (TCDD). Arch. Environ. Contam. Toxicol. 13:509-515 KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo-p—dioxins, Rat Male rats were treated with a single i.p. injection of TCDD and various enzyme and receptor activities were studied in plasma membrane fractions prepared from liver cells. Significant reductions in protein kinase activities and in insulin, conconavalin A, glucagon, and epidermal growth factor binding were seen. Matsumura, F., Madhukar, B.V., Bombick, D.W., and Brewster, D.W. 1984c. Toxicological significance of pleiotropic changes of plasma membrane function particularly that of EGF receptor caused by 2,3,7,8-tetrachlorodibenzo—p—dioxin. Presented at Symposium on Biological Mechanisms of Dioxin Action, Cold Spring Harbor, New York. 23 pages KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo-p~dioxins, Rat This conference presentation describes studies and results that are published in Matsumura et al. 1984b and Madhukai et al. 1984b. Mattison, D.R., Nightingale, M.S., and Silbergeld, E.K. 1984. Reproductive toxicity of tetrachlorodibenzo-p-dioxin. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 217-243 KEYWORDS: Chlorinated dibenzo-p—dioxins, Reproductive effects, Teratogenic effects, Genotoxicity, Review This review summarizes the various types of reproductive toxicity produced by TCDD in experimental animals at doses lower than 1 ug/kg/day and emphasizes the metabolism of reproductive hormones. The generally negative results of epidemiologic studies of reproductive function are presented, but it is noted that more systematic approaches may be neccessary to detect the reproductive effects that TCDD is likely to have in humans. 39 McConnell, E.E., Harris, M.W., Harvan, D.J., Albro, P.W., and Bass, J.R. 1984a. Studies on the bioavailability in guinea pigs of dioxin in soil. Toxicologist KEYWORDS: Metabolism, Acute toxic effects, Oral exposure, Chlorinated dibenzo—p-dioxins, Guinea pig, Abstract This is an abstract of the study described in full in McConnell et al. 1984b. McConnell, E.E., LuCier, G.W., Rumbaugh, R.C., Albro, P.W., Harvan, D.J., Hass, J.R., and Harris, M.W. 1984b. Dioxin in soil: Bioavailability after ingestion by rats and guinea pigs. Science. 223:1077-1078 KEYWORDS: Metabolism, Oral exposure, Chlorinated dibenzo—p—dioxins, Guinea pig, Rat The bioavailability of TCDD in contaminated soil to guinea pigs and rats was assessed. In both guinea pigs and rats, the bioavailability of the TCDD in the contaminated soil was at least 50 percent of that observed when TCDD was administered in corn oil. McNulty, hLP. 1984a. Fetotoxicity of 2,3,7,B—tetrachlorodibenzo-p- dioxin (TCDD) for rhesus macaques (Maggga mulatgg). Am. KEYWORDS: Chlorinated dibenzo-p—dioxins, Lethality, Nonhuman primate, Oral exposure, Reproductive effects, Teratogenic effects McNulty, W.P. 1984b. Fetocidal and teratogenic actions of TCDD. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 245—253 KEYWORDS: Chlorinated dibenzo-p—dioxins, Nonhuman primate, Reproductive effects, Teratogenic effects, Review This article presents previously published results of studies of the reproductive toxicity of TCDD in animals, particularly rhesus macaques, and discusses the suitability of using studies of these monkeys to predict reproductive toxicity in humans. Michigan Department of Public Health (MDPH) 1983. Evaluation of Congenital Malformation Rates for Midland and Other Selected Michigan Counties Compared Nationally and Statewide: 1970-1981. Lansing, Michigan. 33 pages. KEYWORDS: Chlorinated dibenzo-p—dioxins, Environmental 40 exposure, Epidemiologic investigation, Human, Reproductive effects, Teratogenic effects, Genotoxicity See Pages 7, 8, 14, 79, and 93. Milstone, L.M., and LaVigne, J.F. 1984. 2,3,7,8—Tetrachlorodi— benzo-p—dioxin induces hyperplasia in confluent cultures of human keratinocytes. J. Invest. Dermatol. 82:532-534 KEYWORDS: Chloracne, Other dermal effects, In vitro study, Chlorinated dibenzo—p—dioxins, Human Addition of TCDD to confluent cultures of neonatal human foreskin keratinocytes caused increased proliferation as indicated by increased thymidine uptake and altered gross and microscopic morphology. This system may be useful for studying mechanisms of hyperplasia and tumor promotion. MOCarelli, P. 1984. 1976-1980: Study of laboratory tests of pregnant women from TCDD polluted areas. Report to the Special Office for Seveso, Seveso, Italy. 13 pages. KEYWORDS: Chlorinated dibenzo-p—dioxins, Environmental exposure, Epidemiologic investigation, Human, Enzyme induction or inhibition, Hematological effects, Reproductive effects See Pages 7, 9, and 13. McCarelli, P., Marocchi, A., Brambilla, P., and Gerthoux, P.M. 1984a. 1976-1980: Laboratory data of chloracneic children 2-12 years old from A zone: Evidence for TCDD receptor? Report to the Special Office for Seveso, Seveso, Italy. 19 pages. KEYWORDS: Chloracne, Epidemiologic investigation, Hepatic effects, Other toxic effect, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human See Pages 7, 8, 13, 66, and 138. Mocarelli, P., Marocchi, A., Brambilla, P., Gerthoux, P.M., and Young, ILS. 1984b. Clinical laboratory manifestations of exposure to dioxin in children:A five—year study of the effects of an environmental disaster in Seveso, Italy. Report to the Special Office for Seveso, Seveso, Italy. 19 pages. KEYWORDS: Epidemiologic investigation, Hepatic effects, Other toxic effect, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human See Pages 7, 8, 13, 66, and 138. Moody, L., Halperin, W.E., Fingerhut, M.A., and Landrigan, P.J. The chronic health effects of occupational exposure to dioxin: Unanswered questions. Am. J. Ind. Med. 41 1984. 5:157-160 KEYWORDS: Epidemiologic investigation, Occupational exposure, Chlorinated dibenzo—p-dioxins, Phenoxy herbicide formulations, Human, Commentary, Review This editorial presents a brief, critical evaluation of epidemiologic studies of workers occupationally exposed to TCDD and evaluates the current state of knowledge. (19 references) Moore, R.W., Potter, C.L., Robinson, J.A., and Peterson, R.E. 1984. Effects of 2,3,7,8—tetrach1orodibenzo-p-dioxin on the pituitary-testis axis in rats. ToxiCOIOgist. 4:187 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat, Abstract This abstract describes a study of the effect of single oral doses of TCDD on plasma testosterone, dihydrotestosterone, and luteinizing hormone in male rat 5. TCDD caused 10-fold and 4—fold reductions in testosterone and dihydrotestosterone respectively but did not affect luteinizing hormone levels. No information was available regarding the mechanism or human health significance of these effects. Mortelmans, K., Haworth, 8., Speck, W., and Zeiger, E. 1984. Mutagenicity testing of Agent Orange components and related chemicals. Toxicol. Appl. Pharmacol. 75:137—146. KEYWORDS: 2,4—D and its esters, Chlorinated dibenzo—p-dioxins, Genotoxicity, In vitro study, Microbial test system, 2,4,5-T and its esters See Pages 59, 61, 63, and 64. Moses, M., Lilis, R., Crow, K.D., Thornton, J., Fischbein, A., Anderson, H.A., and Selikoff, I.J. 1984. Health status of workers with past exposure to 2,3,7,8—tetrachlorodibenzo- p—dioxin in the manufacture of 2,4,5—trichlorophenoxyacetic acid: Comparison of findings with and without chloracne. Am. J. Ind. Med. 5:161-182. KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo-p—dioxins, Rat See Pages 6, 8, 12, 31, 33, 34, 44, 45, 45, 54, 68, 69, 70, 110, 116, 125, 136, and 139. Nagarkatti, P.S., Sweeney, G.D., Gauldie, J., and Clark, D.A. 1984. Sensitivity to suppression of cytotoxic T cell-generation by 42 Nagayama 2,3,7,8-tetrachlorodibenzo—p-dioxin (TCDD) is dependent on the Ah genotype of the murine host. Toxicol. Appl. Pharmacol. 72:169-176 KEYWORDS: Acute toxic effects, Immunological effects, Mechanism of toxic action, Exposure by injection, In vitro study, Chlorinated dibenzo-p—dioxins, Mouse The authors investigated the ability of TCDD to suppress the generation of allospecific cytotoxic T cells by lymphocytes from "susceptible" and "nonspecific" strains of mice. Bone marrOw chimeras of these strains were also tested. The results indicated that susceptibility to the immunosuppressive effects of TCDD segregated with the Ah genotype of the host and that TCDD promotes development of suppressor T cells. , J., Kiyahara, C., Yamaguchi, S., Nishizumi, M., Horie, A., Handa, S., and Masuda, Y. 1984. Comparative toxicologic study with 2,3,7,8—tetrachlorodibenzo—p—dioxin in inbred strains of mice. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Enzyme induction or inhibition, Hepatic effects, Metabolism, Other toxic effect, Subchronic toxic effects, Exposure by injection, Chlorinated dibenzo—p—dioxins, Mouse, Abstract This abstract describes a study in which male mice of the C—57 (responsive) and DDD (nonresponsive) strains were given weekly doses of 30 ug/kg TCDD intraperitoneally for 6 or 12 weeks. Both strains showed similar toxic signs, but they were more severe in the C—57 strain mice. Effects included hypertrophy of the liver, thymic atrophy, body weight loss, increased SGOT and SGPT, and increased AHH activity. National Institute for Occupational Safety and Health (NIOSH) 1984. Neal, R. 2,3,7,8-Tetrachlorodibenzo—p—dioxin (TCDD, “dioxin"): Current Intelligence Bulletin 40. January 23, 1984. Cincinnati, Ohio. 21 pages KEYWORDS: Occupational exposure, Chlorinated dibenzo—p—dioxins, Human, Review This review summarizes the animal and human health effects information on 2,3,7,8-tetrach1orodibenzo-p~dioxin, emphasiz1ng information particularly relevant to occupational exposure. The document also discusses worker protection and decontamination procedures. (88 references). A. 1984. Biological effects of 2,3,7,8-tetrachlorodibenzo— p—dioxin in experimental animals. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 15—29 43 KEYWORDS: Acute toxic effects, Enzyme induction or inhibition, Metabolism, Other toxic effect, Chlorinated dibenzo—p-dioxins, Review The author summarizes data on the acute toxic effects of TCDD in various species, and the relationship between interspecies differences in susceptibility and metabolism is examined. The author concludes that the acute toxic effects are not directly related to the rate of metabolism. (27 references) Nolan, R.J., Freshour, N.L., Kastl, P.E., and Saunders, J.H. 1984. Pharmacokinetics of picloram in male volunteers. Toxicol. Appl. Pharmacol. 76:264—269. KEYWORDS: Metabolism, Dermal exposure, Oral exposure, Picloram, Human See Page 144. O'Toole, B.I., Adena, M.A., and Fett, M.J. 1984. Australian Veterans Health Studies: The Mortality Report, Part II: Factors Influencing Mortality Rates of Australian National Servicemen of the Vietnam Conflict Era. Australian Government Publishing Service, Canberra, Australia. 89 pages. KEYWORDS: Cancer, Cardiovascular effects, Epidemiologic investigation, Other toxic effect, Environmental exposure, Phenoxy herbicide formulations, Human See Pages 6, 11, and 28. Okey, A.B., and Vella, L.M. 1984. Elevated binding of 2,3,7,8—tetrachlorodibenzo—p—dioxin and 3—methylcholanthrene to the Ah receptor in hepatic cytosols from phenobarbital-treated rats and mice. Biochem. Pharmacol. 33:531-538 KEYWORDS: Enzyme induction or inhibition, Mechanism of texic action, In vitro study, Chlorinated dibenzo—p-dioxins, Rat, Mouse Administration of phenobarbital increased the concentration of cytosolic Ah receptor in the livers of Spraque-Dawley rats and C57Bl/6J (responsive) mice but not in DBH/ZJ (nonresponsive) mice. Okey, A.B., Mason, M.E., and Vella, L.M. 1983. The Ah receptor: Species and tissue variation in binding of 2,3,7,8-tetra- chlorodibenzo-p—dioxin and carcinogenic aromatic hydrocarbons. In Rydstroem, J., Montelius, J., and Bengtsson, M., eds. Extrahepatic Drug Metabolism and Chemical CarcinOgenesis: Proceedings of an International Meeting. Elsevier Science Publishers, Amsterdam. Pp. 389-399 44 KEYWORDS: Cancer, Mechanism of toxic action, Other toxic effeCt, Chlorinated dibenzo—p—dioxins, Review The authors review the properties of the cytosolic Ah receptor, describing its binding properties with different PAH ligands and TCDD and discussing the possible role of this receptor in carcinogenesis. They conclude that the receptor is not directly involved in AHH induction and chemical carcinogenesis. (18 references) Okey, A.B., Vella, L.M., and Iverson, F. 1984. Ah receptor in primate liver: Binding of 2,3,7,8-tetrachlorodibenzo-p—dioxin and carcinogenic aromatic hydrocarbons. Can. J. Physiol. Pharmacol. 62:1292-1295 KEYWORDS: Enzyme induction or inhibition, Mechanism of toxic action, In vitro study, Chlorinated dibenzo—p-dioxins, Nonhuman primate A cytosolic receptor which binds TCDD with high affinity was isolated from the livers of cynomolgus monkeys. It's properties were Similar to the Ah receptor in rodents but it was present at about one—fourth of the concentration seen in rodent livers. Olson, J., and Wroolewski, V.J. 1984. Metabolism of 2,3,7,8—tetra— chlorodibenzo—p~dioxin (TCDD) in isolated hepatocytes from guinea pigs and rats. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Metabolism, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells, Abstract, Cancer This abstract describes a study of the comparative metabolism of TCDD by cultured hepatocytes from rats and guinea pigs. TCDD pretreatment induced its own metabolism in hepatocytes from rats but not in those from guinea pigs. Osborne, R., and Greenlee, W.F. 1984. Altered regulation of human epidermal cell proliferation and differentiation by 2,3,7,8-tetrachlorodibenzo—pndioxin (TCDD). Toxicologist. 4:188 (abstract) KEYWORDS: Chloracne, Mechanism of toxic action, Other dermal effects, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells, Abstract This abstract presents the results of studies of the effects of TCDD on human squamous cell carcinoma cells and normal human foreskin epithelial cells in culture. TCDD treatment inhibited growth and DNA synthesis and stimulated 45 keratinization suggesting enhanced committment to terminal differentiation. Pazdernik, T., and Rozman, K. 1984. Role of thyroid hormones in 2,3,7,8-tetrachlorodibenzo—p—dioxin induced immunotoxicity. Fed. Proc. 43:369 (abstract) KEYWORDS: Immunological effects, Acute toxic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo—p—dioxins, Rat, Abstract According to this abstract, chemical thyroidectomy of male rats was partially protective against the immunotoxic effects of TCDD as determined by thymus weight and splenic sheep red blood cell plaque forming cells. The authors conclude that thyroid hormone plays a role in mediating these responses. Peterson, R.E., Potter, C;L., and Moore, R.W. 1984. The wasting syndrome and hormonal alterations in 2,3,7,8-tetrachlorodi— benzo—p—dioxin toxicity. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kauffman, Los Altos, California. Pp. 315-349 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Chlorinated dibenzo-p—dioxins, Review This symposium presentation examines the mechanism by which TCDD elicits a wasting syndrome in several species. It is adapted, in part, from articles by Seefield and Peterson (1984) and Seefield et al. (1984b). (85 references) Poeilinger, L., Lund, J., and Gustafsson, J. 1984. The rat liver Poland, receptor for 2,3,7,8-tetrachlorodibenzo-p~dioxin: Similarities and dissimilarities with steroid hormone receptors. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16—18, 1984. 1 page (abstract) KEYWORDS: Mechanism of toxic action, Unspecified route of exposure, Chlorinated dibenzo—p—dioxins, Abstract This abstract compares the hepatic "TCDD receptor" to the steroid hormone receptor. Similarities include sedimentation constant, Stakes radius, molecular weight, and affinity to certain adsorbents. However, steroid hormones do not bind to the TCDD receptor, and column chromatography on variously modified Sepharose gels indicates that the TCDD receptor is more hydrophobic than the steroid hormone receptor. A., and Glover, E. 1979. An estimate of the maximum in vivo covalent binding of 2,3,7,8-tetrachlorodibenzo—p—dioxin to rat liver protein, ribosomal RNA, and DNA. Cancer Res. 39:3341-3344. 46 Poland, Poland, POtter, Puhvel, KEYWORDS: Acute toxic effects, Mechanism of toxic action, Cancer, Exposure by injection, Chlorinated dibenzo-p—dioxins, Rat A., and Knutson, J. 1982. Tumor promotion by TCDD in the skin of HRS/J mice. Naunyn Schmiedebergs Arch. Pharmacol. 321(suppl.):R4 KEYWORDS: Cancer, Mechanism of toxic action, Dermal exposure, Chlorinated dibenzo-p—dioxins, Mouse, Abstract See Page 73. This abstract describes studies that are described in the full-length paper by Poland et a1. (1983). A., Knutson, J., Glover, E., and Kende, A. 1983. Tumor promotion in the skin of hairless mice by halogenated aromatic hydrocarbons. In Weinstein, I.B., and Vogel, H.J., eds. P & S Biomedical Sciences Symposia: Genes and Proteins in Oncogenesis. June 4—6, 1982. Academic Press, New York. Pp. 143—161. KEYWORDS: Cancer, Mechanism of toxic action, Chlorinated dibenzo-p-dioxins, Review C.L., Lopachin, R.M., Seefeld, M.D., and Peterson, R.E. 1984. Effect of oral and intrahypothalamic administration of 2,3,7,8-tetrachlorodibenzo-p—dioxin (TCDD) on food intake and oxygen consumption in rats. ToxiCOIOgist. 4:185 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Exposure by injection, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat, Abstract This abstract describes a study in which the effect of intrahypothalamic injection of TCDD on food intake and body weight was compared with that of oral administration. Intrahypothalamic injection caused only a transient effect,unlike oral administration, indicating that the lateralhypothalamus is not the primary site of action for the hypophagiceffect of TCDD. S.M., and Ertl, D.C. 1984. Decreased induction of aryl hydrocarbon hydroxylase activity in hyperproliferative hairless mouse epidermis. Br. J. Dermatol. 110:29-35 KEYWORDS: Chloracne, Mechanism of toxic action, Dermal exposure, Chlorinated dibenzo-p—dioxins, Mouse Hairless HRS/J mice treated with repeated dermal applications of TCDD developed hyperproliferative and hyperkeratotic skin changes similar to chloracne. These changes were accompanied 47 by a decrease in AHH activity in the skin. Similar decreases in AHH activity were elicited by repeated tape stripping of stratum and by repeated application of 50% oleic acid. The authors suggest that AHH levels vary with the state of epidermal differentiation. Puhvel, S.M., Ertl, D.C., and Lynberg, C.A. 1984a. Increased epidermal transglutaminase activity following 2,3,7,8-tetra- chlorodibenzo—p—dioxin: In vivo and in vitro studies with mouse skin. Toxicol. Appl. Pharmacol. 73:42-47 KEYWORDS: Chloracne, Enzyme induction or inhibition, Mechanism of toxic action, Dermal exposure,.In vitro study, Chlorinated dibenzo—p-dioxins, Mouse Repeated application of TCDD to the skin of HRS/J hairless mice caused an increase in epidermal transglutaminase (ETG) activity paralleling the hyperprolification and hyperkeratinization of epidermis. Increased ETG activity was also seen in cultured basal keratinocytes from neonatal BALB/c mice that were incubated with TCDD. ETG activity is associated with terminal epidermal differentiation. Puhvel, S.M., Reinser, R.M., and Ertl, D.C. 1984b. The effect of TCDD on murine keratinocytes in tissue culture. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16—18, 1984. 1 page (abstract) KEYWORDS: Other dermal effects, In vitro study, Chlorinated dibenzo—p—dioxins, Mouse, Abstract The authors of this abstract describe the effect of TCDD on cultured epidermal cells from neonatal mice. These effects include stimulation of transglutaminase activity, an increased number of cells with cornified envelopes, and stimulation of differentiation. These effects indicate that hairless mice might be useful models for the study of the effects of TCDD in humans. Raisanen,.S;, and Salkinoja-Salonen, M. 1983. [Chlorinated dioxins and furans]. Kem.-Kemi. 10:903-908 (Finnish) KEYWORDS: Review, Human, Chlorinated dibenzo-p—dioxins This review describes the chemistry and toxicology of chlorinated dibenzo—diOxins and -furans with particular emphasis on structure—activity relationships and on the similarity between these chemicals and PCBs. (59 references) Rappe, C. 1984. Chemical analyses of adipose tissue. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 57-61 48 Rashid, Rasnid, Raunio, KEYWORDS: Metabolism, Environmental exposure, Chlorinated dibenzo-p-dioxins, Human, Abstract In this symposium presentation, the author presented very preliminary data on levels of various PCDD and PCDF isomers in human adipose tissue samples. No attempt was made to correlate levels with exposure. The author tentatively concluded that there may be "background" tissue levels of PCDD and PCDF from unidentified environmental sources. K.A., and Mumma, R;O. 1983. Mutagenicity assays with (2,4-dichlorophenoxy)acetic acid-amino acid conjugates. J. Agric. Food Chem. 31:1371-1372. KEYWORDS: 2,4-D and its esters, Microbial test system, In vitro study, Genotoxicity See Pages 61 and 64. K.A., Babish, J.G., and Mumma, R.O. 1984. Testing of 2,4,5-T—amino acid conjugates for mutagenic activity in fialmgnglla typhimgrigm strains. Mutat. Res. 136:217—221. KEYWORDS: Genotoxicity, In vitro study, Microbial test system, 2,4,5—T and its esters See Pages 59 and 63. H., and Pelkonen, O. 1982. Independent induction and inhibition of ornithine decarboxylase and aryl hydrocarbon hydroxylase activities in rat epidermis. J. Invest. Dermatol. 79:246-249 KEYWORDS: Enzyme induction or inhibition, Dermal exposure, Chlorinated dibenzo—p—dioxins, Rat The authors examined the induction of ornithine decarboxylase (ODC) and aryl hydrocarbon hydroxylase (AHH) in epidermis by wounding and compound application. Wbunding increased ODC activity. TCDD increased AHH activity in wounded skin without affecting ODC activity. The authors believe that induction of the 2 enzyme activities are independent. Reggiani, G. 1983. Anatomy of a TCDD spill: The Seveso accident. In Saxena, J., ed. Hazard Assessment of Chemicals: Current Developments. Academic Press, New York. Vol. 2, pp. 269-342 KEYWORDS: Chloracne, Hepatic effects, Neurobehavioral effects, Reproductive effects, Genotoxicity, Immunological effects, Other toxic effect, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human, Review 49 See Page 77. This 73 page article gives a detailed account of the Seveso accident, the health effects and exposure studies conducted afterward, and the ongoing cleanup efforts. (191 references) Remotti, G., De Virgiliis, G., Bianco, V., and Battista Candiani, G. 1981. The morphology of early trophoblast after diOXin poisoning in the Seveso area. Placenta. 2:53—62. KEYWORDS: Environmental exposure, Epidemiologic investigation, Human, Reproductive effects See Pages 7, 8, 14, and 78. Rice, R;H., and Cline, P.R. 1984. Opposing effects of 2,3,7,8—tetrachlorodibenzo—p—dioxin and hydrocortisone on growth and differentiation of cultured malignant human keratinocytes. CarcinOgenesis. 5:367—371 KEYWORDS: Cancer, Mechanism of toxic action, Other dermal effects, In vitro study, Chlorinated dibenzo—p—dioxins, Cultured mammalian cells Addition of TCDD to cultures of human squamous cell carninoma cells inhibited growth. Addition of hydrocortisone to the medium protected against this inhibition. TCDD inhibited hydrocortisone—stimulated differentiation. The effects of TCDD on skin may be mediated through hormones. Roberts, E.A., Shear, N.H., and Okey, A.B. 1984. Ah receptor and dioxin toxicity: From rodent to human tissues. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Mechanism of tOxic action, Chlorinated dibenzo-p—dioxins, Abstract, Review This abstract of a talk given at a symposium reviews information about the Ah receptor, its distribution among various tissues, its occurrence in various species, and evidence that it is present in human tissues. Roberts, E.A., Shear, N.H., and Okey, A.B. 1985. The Ah receptor and dioxin toxicity: From rodent to human tissues. Chemosphere. (in press) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Chlorinated dibenzo—p—dioxins, Review The authors summarize and review evidence for the presence of the Ah receptor and assess the evidence that this receptor mediates the toxicity of TCDD. A major portion of the review 50 addresses the question of whether the receptor is present in human tissue. The limited evidence available suggests that levels of Ah receptor in human tissues are relatively low and there is great individual variation. (31 references) Rodwell, D.E., Wilson, R.D., Nemec, M.D., and Mercieca, M.D. 1984a. A teratology study in Fischer 344 rats with 2,4—dichloro— phenol. Toxicologist. 4:167 (abstract) KEYWORDS: Abstract, Oral exposure, Rat, Teratogenic effects This abstract reports the results of a teratology study in which Fischer 344 rats were treated by gavage on days 6 to 15 of gestation with 200, 375, or 750 mg/kg/day of 2,4—dichlorophenol. The high dose group showed a slight increase in fetal loss and a decrease in fetal weight, but in conjunction with maternal toxicity. Rodwell, D.E., Wilson, R.D., Nemec, M.D., and Tasker, E.J. 1984b. A Rogers, Rozman ' teratology study in Fischer 344 rats with 2,4-dichlorophenoxy— acetic acid. Toxicologist. 4:166 (abstract) KEYWORDS: Abstract, 2,4-D and its esters, Oral exposure, Rat, Teratogenic effects This abstract reports negative results for fetotoxicity and teratogenicity in the offspring of Fischer 344 females treated by gavage with 8, 25, or 75 mg/kg/day of 2,4-D on days 6 to 15 of gestation. L. 1983. Herbicides and the development of brain and behaviour: A study in behavioural toxicology. In Kidman, A.D., Tomkins, J;K., Morris, C.A., and Cooper, N.A., eds. Molecular Pathology of Nerve and Muscle: Noxious Agents and Genetic Le51ons. Humana Press, Clifton, New Jersey. Pp. 267—281 KEYWORDS: Neurobehavioral effects, Reproductive effects, Oral exposure, 2,4-D and its esters, 2,4,5-T and its esters, Rat See Pages 94 and 95. In this symposium presentation, the author describes the importance of behavorial tests in assessing the toxicity and reproductive effects of chemicals. He summarizes results of studies in his and other laboratories on the behavioral toxicity of 2,4—D and 2,4,5—T in chickens and rats concluding that behavioral effects are very sensitive indicators of toxicity for these compounds. (25 references) K. 1984a. Hexadecane enhances the toxicity of TCDD. Toxicologist. 4:189 (abstract) 51 Rozman, Rozman, Rozman, Rozman, KEYWORDS: Acute toxic effects, Mechanism of toxic action, Metabolism, Exposure by injection, Chlorinated dibenzo—p- dioxins, Rat, Abstract This abstract describes studies which are discussed in full in Rozman 1984. K. 1984b. Separation of wasting syndrome and lethality caused by 2,3,7,8-tetrachlorodibenzo—p—dioxin. Toxicol. Lett. 22:279—285 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo-p—dioxins, Rat Treatment of male rats with hexadecane 48 hours after administration of a single oral dose of TCDD at the LDSO increased lethality to 100% without altering food intake, weight loss, and time course of weight loss and recovery. Hexadecane increases the rate of clearance of TCDD from fat. The author concludes that the lethal effect of TCDD is independent of its abiltiy to cause weight loss. K., Hazelton, G., and Klassen, C. 1984a. Induction of UDP glucuronosyl transferase by 2,3,7,8-tetrachlorodibenzo-p— dioxin in thyroidectomized and in thyroxine treated rats. Fed. Proc. 43:740 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Unspecified route of exposure, Rat, Abstract Chemical thyroidectomy did not alter the induction of UDP-glucuronosyl—transferase by TCDD in rats. K., Rozman, T., and Greim, H. 1984b. Effect of thyroidectomy and thyroxine on 2,3,7,8-tetrachlorodibenzo-p—dioxin (TCDD) induced toxicity. Toxicol. Appl. Pharmacol. 72:372-376 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Exposure by injection, Chlorinated dibenzo-p—dioxins, Rat Chemical thyroidectomy of male rats protected against the lethal effects of a single dose of 100 ug/kg TCDD. Thyroidectomized rats consumed the same amount of feed as control rats and lost weight at a slower rate than did euthyroid rats. The authors conclude that thyroid hormone plays an important role in mediating the toxicity of TCDD. K., Scheufler, E., Pazdernik, T., and Greim, H. 1984c. Effect of thyroxine (T4) and triiodotyrosine (T3) on TCDD toxicity in thyroidectomized rats. Toxicologist. 4:189 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, 52 Rozman, Other toxic effect, Exposure by injection, Chlorinated dibenzo-p—dioxins, Rat, Abstract This abstact describes experimental results from studies described in detail in Rozman et al. 1984a. T., Rozman, R., and Greim, H. 1984d. Role of thyroid function in TCDD induced toxicity. Toxicologist. 4:189 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Exposure by injection, Chlorinated dibenzo-p—dioxins, Rat, Abstract This is an abstract of a study that is described in more detail in an article by Rozman et a1. (1984) entitled "Effect of thyroidectomy and thyroxine on 2,3,7,8—tetrachlorodibenzo- p—dioxin (TCDD) induced toxicity." Rubinstein, C., Jone, C., Trosko, J.E., and Chang, C.-C. 1984. Inhibition of intercellular communication in cultures of Chinese hamster V79 cells by 2,4—dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid. Fundam. Appl. Toxicol. 4:731-739 KEYWORDS: Cultured mammalian cells, Hamster, In vitro study, Teratogenic effects, 2,4-D and its esters, 2,4,5-T and its esters, Mechanism of toxic action Both 2,4-D and 2,4,5—T gave positive results for inhibition of intercellular communication in the V79 assay of resistance to 6—thioguanine by HEPRT— cells cocultivated with HGPRT+ CEllS at concentrations above 100 and 75 ug/ml, respectively. This assay is gaining increasing acceptance as being predective for tumor promoting and teratogenic activity. Rumbaugh, R.C., McCoy, Z., and Lucier, G.W. 1984. Induction of hepatic microsomal aryl hydrocarbon hydroxylase in rats by administration of soil contaminated with 2,3,7,8-tetrachloro— dibenzo—p—dioxin (TCDD). Tbxicologist. 4:113 (abstracn) KEYWORDS: Metabolism, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo-p-dioxins, Rat, Abstract This is an abstract of a study that is described in full in McConnell et al. (1984b). Ryan, J.J., Lizotte, R., and Lau, B.P.Y. 1984. Chlorinated dibenzo-p—dioxins and furans in Canadian human adipose tissue. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16—18, 1984. 1 page (abstract) 53 KEYWORDS: Metabolism, Environmental exposure, Chlorinated dibenzo—p~dioxins, Human, Abstract Analysis of human adipose tissue taken at autopsies throughout Canada revealed similarity in the quantities and patterns of PCDD and PCDF and these, in turn, were similar to results obtained by Rappe in Sweden. The patterns were different from those found in animal tissues. This suggests a common environmental source. Safe, S., Sawyer, T., Bandiera, S., Mason, G., Keys, B., Ramkes, M., Sate, L., and Zmudzka, B. 1984. Polychlorinated dibenzo- furans: Chemistry, biochemistry, and toxicology. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Mechanism of toxic action, Chlorinated dibenzo—p-dioxins, Abstract, Review This abstract of a talk given at a symposium reviews information relating the relative toxicity of various chlorinated dibenzo—p—dioxin and furan congeners to theirstructure. The authors conclude that correlations among such parameters as AHH induction, Ah receptor binding, and acute toxicity were good in both families of compounds. Scnantz, S.L., and Bowman, R.E. 1984. Learning performance of offspring of rhesus monkeys exposed to low levels of 2,3,7,8-tetrachlorodibenzo—p—dioxin (TCDD). Tbxicologist. 4:84 (abstract). KEYWORDS: Neurobehavioral effects, Reproductive effects, Teratogenic effects, Oral exposure, Chlorinated dibenzo—p—dioxins, Nonhuman primate, Abstract See Page 101. Scheccer, A., Ga51ewicz, T., Schaffer, F., and Eisen, H. 1984. Ultrastructural alterations in liver cells of humans, rats and mouse heptoma cells in response to 2,3,7,8—TCDD and related compounds. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract). KEYWORDS: Hepatic effects, Mechanism of toxic action, Environmental exposure, Oral exposure, In vitro study, Chlorinated dibenzo—p-dioxins, Cultured mammalian cells, Human, Rat, Abstract Schiller, C.M., Shoaf, C.R., Chapnan, D.E., and Walden, R. 1983. Alterations in lipid assimilation induced by 2,3,7,8—tetra— chlorodibenzo—p-dioxin in male Fischer rats. Fed. Proc. 42:355 (abstract) 54 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat, Abstract A single oral dose of TCDD causes increases in serum triglycerides and lipoprotein lipose in rats. These changes appear to be the result of alterations in intestinal absorptoin of lipids and and hepatic lipid metabolism. Schiller, C.M., walden, R., Shoaf, C.R., and King, M.W. 1984. Composition of serum lipoproteins obtained from control and 2,3,7,8—tetrachlorodibenzo—p—dioxin exposed adult male Fischer rats after fasting or corn oil feeding. Fed. Proc. 43:365 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat, Abstract This abstract describes results essentially similar to those in Schiller et a1. (1983). Schultz, T.W., and Dumont, J.N. 1984. Teratogenicity and embryotoxicity of monosodium methanearsonate herbicide. Trans. Am. Microsc. Soc. 103:263-273. KEYWORDS: Reproductive effects, Teratogenic effects, Other route of exposure, Cacodylic acid, Other species Seefeld, M.D., and Peterson, R.E. 1984. Digestible energy and efficiency of feed utilization in rats treated with 2,3,7,8-tetrachlorodibenzo—prdioxin. Tbxicol. Appl. Pharmacol. 74:214—222 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat The authors investigated the weight loss exhibited by rats in response to single lethal and sub-lethal oral doses of TCDD. TCDD-treated and pair fed contr01 rats lost weight at similar rates, and absorbed the same amount of feed energy from the intestinal tract. The authors conclude that hypophagia rather than malabsorption is the mechanism of toxic action. Seefeld, M.D., Albrecht, R.M., Gilchrist, K.W., and Peterson, R.E. 1980. Blood clearance tests for detecting 2,3,7,8—tetra— chlorodibenzo—p—dioxin hepatotoxicity in rats and rabbits. Arch. Environ. Contam. Toxicol. 9:317-327. KEYWORDS: Acute toxic effects, Hepatic effects, Oral exposure, Exposure by injection, Chlorinated dibenzo-p—dioxins, Rat, Rabbit, Guinea pig 55 Seefeld, M.D., Christian, B.J., and Peterson, R;E. 1984a. Effect of 2,3,7,8-tetrachlorodibenzo—p—dioxin (TCDD) on caloric balance in the rat. Toxicologist. 4:186 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Unspecified route of exposure, Chlorinated dibenzo—p—dioxins, Rat, Abstract This abstract presents the results of studies that are described in detail in Seefield and Peterson (1984). Seefeld, M.D., Corbett, S.W., Keesey, R.E., and Peterson, R.E. 1984b Characterization of the wasting syndrome in rats treated with 2,3,7,8—tetrachlorodibenzo-p-dioxin. Toxicol. Appl. Pharmacol. 73:311—322 KEYWORDS: Acute toxic effects, Lethality, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo-p—dioxins, Rat Male rats were subjected to food restriction prior to treatment with a single sub—lethal oral dose of TCDD. Both TCDD—treated and control rats exhibited hyperphagia immediatey after treatment suggesting that TCDD affects a system that regulates body weight rather than one that determines feed intake. Sell, C.R., and Maitlen,.J.C. 1983. Procedure for the determination of residues of (2,4-dichlorophenoxy) acetic acid in dermal exposure pads, hand rinses, urine and perspiration from agricultural workers exposed to the herbicide. J. Agric. Food Chem. 31:572-575 KEYWORDS: Metabolism, Dermal exposure, 2,4—D and its esters, Human This paper describes methodology for analyzing for 2,4-D exposure in workers applying 2,4-D. 2,4—D was detected in the urine and perspiration of these workers. A forthcoming paper will present the results of an actual exposure analysis. Shiverick, K.T., and Muther, T.F. 1983a. 2,3,7,8-Tetrachloro— dibenzo—p—dioxin effects on hepatic microsomal steroid metabolism and serum estradiol of pregnant rats. Biochem. Pharmacol. 32:991-996 KEYWORDS: Enzyme induction or inhibition, Teratogenic effects, Oral exposure, Chlorinated dibenzo—p-dioxins, Rat See Page 99. 56 The authors investigated the effect of single oral doses of TCDD on steriod metabolism in pregnant rats. Whereas, TCDD altered cytochrome P—450 activity and steriod metabolism in liver microsomes in vitro, there was no change in serum estradiol levels in vivo. Shiverick, K.T., and Muther, T.F. 1983b. Effects of 2,3,7,8-tetra— chlorodbenzo—p—dioxin administered to pregnant rats on steroid metabolism in liver microsomes and on serum estradiol concentrations. Fed. Proc. 42:644 (abstract) KEYWORDS: Enzyme induction or inhibition, Teratogenic effects, Oral exposure, Chlorinated dibenzo-p—dioxins, Rat, Abstract This is an abstract of a study described in detail in Shiverick and Muther (1983a). Shoaf, C.R., Mehta, A.H., and Schiller, C.M. 1983. Apo proteins obtained from lymph lipoproteins produced by the intestinal epithelium after treatment of rats with 2,3,7,8-tetrachlorodi— benzo—p—dioxin. Fed. Proc. 42:1820 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat This abstract describes studies very similar to that described in Shoaf et a1. 1984. Shoaf, C.R., walden, R., Chapman, D.E., and Schiller, C.M. 1984. Altered apoprotein (apo) composition of chylomicra and very low density lipoproteins (VLDL) from mesenteric lymph after exposure of adult male Fischer rats with 2,3,7,8—tetrachloro— dibenzo—p-dioxin (TCDD). Toxicologist. 4:188 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat, Abstract The authors studied the effect of a single dose of TCDD on the composition of serum lipoproteins and lipids in rats. TCDD altered the protein composition of chylomicia and VLDL and this may explain altered intestinal absorption and serum clearance of lipids. Siegel, J.M. 1984. Effects of Agent Orange on sleep. Oral presentation to the Veterans Administration Advisory Committee on Health-Related Effects of Herbicides. December 11, 1984, Washington, D.C. 2 pages KEYWORDS: Acute toxic effects, Neurobehavioral effects, Oral exposure, Phenoxy herbicide formulations, Cat, Abstract 57 This abstract of an oral presentation to the Veterans Administration Advisory Committee describes a study of the effect of a single oral dose of 385 mg/kg of dioxin-free Agent Orange on sleep in cats. Forty—eight hour electrophysiological recordings were made before and for a year after administration. Agent Orange significantly decreased REM sleep time for the first 21 days following administration, and this effect was not duplicated by food deprivation. Smith, A.H., Pearce, N.E., Fisher, D.0., Giles, H.J., Teague, C.A., and Howard, J.K. 1984. Soft tissue sarcoma and exposure to phenoxyherbicides and chlorophenols in New Zealand. JNCI. 73:1111-1117. KEYWORDS: Cancer, Epidemiologic investigation, Occupational exposure, Phenoxy herbicide formulations, Chlorinated dibenzo—p—dioxins , Human See Pages 6, 8, l3, and 46. Spitsbergen, J.M., Kleeman, J.M., and Peterson, R.E. 1984. Toxicity of 2,3,7,8-tetrachlorodibenzo-p—dioxin (TCDD) in freshwater fisn. Tbxicologist. 4:190 (abstract). KEYWORDS: Acute toxic effects, Exposure by injection, Chlorinated dibenzo-p—dioxins, Fish, Abstract Sterling, T.D. 1984. Technical comment: Health effects of dioxin. Science. 223:1202 (letter) KEYWORDS: Cancer, Reproductive effects, Teratogenic effects, Chlorinated dibenzo-p—dioxins, Phenoxy herbicide formulations, Human, Commentary This letter to the editor takes exception to an editorial by Philip Abelson in Science 220:1337 (1983). The writer contends that environmental exposure to TCDD and TCDD-contaminated herbicides causes soft-tissue sarcoma and birth defects and interferes with reproduction. Stohs, S.J., Hassan, M.Q., and Murray, W.J. 1983. Lipid peroxidation as a possible cause of 2,3,7,8—tetrachlorodibenzo-p—dioxin toxicity. Biochem. Biophys. Res. Commun. 111:854-859 KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat Female Sprague-Dawley rats were treated with one or three daily oral doses of TCDD and lipid peroxidation in the liver was measured by the thiobarbituric acid and conjugated diene methods. Lipid peroxidation was significantly increased after a single dose of 80 ug/kg. The effect persisted for 11 58 days after treatment. The authors postulate that cell membrane alterations leading to cell death may be the mechanism of acute lethality of TCDD. Stohs, S.J., Hassan, M.Q., and Murray, W.J. 1984. Effects of BHA, d-alpha—tocopherol and retinol acetate on TCDD-mediated changes in lipid peroxidation, glutathione peroxidase activity and survival. Xenobiotica. 14:533-538 KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo-p-dioxins, Rat Administration of BHA and Vitamin A to rats protected them against the acute lethality of TCDD. This protection was assocrated with decreased lipid peroxidation activity and increased glutathione peroxidase activity. Vitamin E was protecrive. Strigini, P., Bisanti, L., Basso, P., Borgna Pignatti, C., Bruzzi, P., Formigaro, P., and Marni, E. 1982. Preliminary observations on reproductive toxicity following an industrial accident at Seveso, Italy. Teratology. 26:12A (abstract) KEYWORDS: Abstract, Chlorinated dibenzo—p—dioxins, Environmental exposure, Epidemiologic investigation, Human, Reproductive effects, Teratogenic effects, Genotoxicity See Page 77. This abstract contains no new information on attempts to correlate reported TCDD exposure after the Seveso accident with adverse reproductive outcomes. Suskind, R.R., and Hertzberg, V.S. 1984. Human health effects of 2,4,5-T and its toxic contaminants. JAMA. 251:2372—2380. KEYWORDS: Chloracne, Cancer, Cardiovascular effects, Epidemiologic investigation, Hepatic effects, Neurobehavioral effects, Other toxic effect, Renal effects, Reproductive effects, Respiratory effects, Other dermal effects, Occupational exposure, 2,4,5—T and its esters, Chlorinated dibenzo-p—dioxins, Human See Pages 12, 33, 45, 69, 70, 111, 125, 126, 133, 139, 141, and 142. Sweatlock, J.A., and Gasiewicz, T.A. 1984. The effect of TCDD exposure on the concentration of blood ketone bodies in the rat. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) 59 KEYWORDS: Acute toxic effects, Mechanism of toxic action, Exposure by injection, Chlorinated dibenzo—p—dioxins, Rat, Abstract This abstract indicates that in rats treated with a single intraperitoneal dose of 100 ug/kg TCDD there was a significant decrease in whole blood levels of beta-hydroxybutyrate and acetoacetate 3, 7, and 10 days post—treatment as compared to both pair—fed and ad libitum fed controls. This finding suggests an alteration in lipid metabolism. Tedeschi, L.G. 1983. Agent Orange: Update. Am. J. Forensic Med. Pathol. 4:319-321 KEYWORDS: Cancer, Epidemiologic investigation, Reproductive effects, Occupational exposure, Environmental exposure, Chlorinated dibenzo-p—dioxins, Human, Review, Commentary The author reviews and comments upon several recently published epidemiologic studies and case reports concerning the health effects of phenoxy herbicides and their dioxin impurities. He finds the studies to be inconclusive and believes that the scientific issues are clouded by emotionalism and sensationalism (13 references) Theobald, H.M., Bookstaff, R;C., and Peterson, R.E. 1984. Enhance- ment of bradykinin and histamine—induced paw edema by 2,3,7,8- tetrachlorodibenzo—p—dioxin. Toxicologist. 4:186 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Unspecified route of exposure, Chlorinated dibenzo-p—dioxins, Rat, Abstract This abstract describes the same study described in Katz et a1. 1983 and Theobald et a1. 1983. Thunberg, T., Ahlborg, U.G., and Wahlstrom, B. 1984. Comparison between the effects of 2,3,7,8-tetrachlorodibenzo—p—dioxin and 6 other compounds on the vitamin A storage, the UDP- glucuronosyltranferase and the aryl hydrocarbon hydroxylase activity in the rat liver. Arch. Toxicol. 55:16-19 KEYWORDS: Enzyme induction or inhibition, Oral exposure, Chlorinated dibenzo-p—dioxins, Rat The authors examined the effect of a number of compounds on Vitamin A storage and UDPGT and AHH activities in the livers of rats. TCDD reduced Vitamin A liver levels and induced enzyme activities. The reduction of Vitamin A did not correlate with enzyme induction. Tolstopiatova, G.V. 1984. [Toxicological and hygienic characteristics or polychlorodibenzofurans and polychlorodibenzo—p-dioxins 60 Turner, (a review of the literature)]. Vrach. Delo. 2:99-103 (Russian) This brief review is in Russian with no English summary. It appears to be a qualitative summary of the health effects of the polychlorinated dibenzodioxins and dibenzofurans. (34 references) J.N., and Collins, D.N. 1984. Membrane proliferation and excretion from guinea pig hepatocytes exposed to 2,3,7,8—TCDD and PCB pyrolysis products. Presented at the 4th Interna— tional symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Acute toxic effects, Hepatic effects, Mechanism of toxic action, Oral exposure, Chlorinated dibenzo—p-dioxins, Guinea pig, Abstract This abstract describes a high-voltage electron microscopic study of liver tissue from guinea pigs treated with a single oral dose of TCDD. Detailed investigation shows that proliferating smooth endoplasmic reticulum forms vacuoles that directly communicate with the sinusoids and bile canaliculi, with membrane fragments being shed into the sinusoids and canaliculi. Umbreit, T.H., Patel, D., and Gallo, M.A. 1984. Acute toxicity of Vahter, Van Den TCDD contaminated soil from an industrial site. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16—18, 1984. 1 page (abstract) KEYWORDS: Acute toxic effects, Metabolism, Oral exposure, Chlorinated dibenzo—p-dioxins, Mouse, Abstract This abstract describes a study of the bioavailability of TCDD in soil from a contaminated industrial site. Guinea pigs were fed uncontaminated soil, contaminated soil, TCDD in corn oil, TCDD added to clean soil, or corn oil. Animals receiving contaminated soil at greater than the LD50 of TCDD did not die but displayed signs of TCDD toxicity indicating less than 100% availability of the TCDD. M., Marafante, E.7 and Dencker, L. 1984. Tissue distribution and retention or 4As—dimethylarsinic acid in mice and rats. Arch. Environ. Contam. Toxicol. 13:259—264. KEYWORDS: Cacodylic acid, Metabolism, Oral exposure, Mouse, Rat See Pages 148, 149, and 150. Berg, M., Olie, K., and Hutzinger, O. 1984. Bioavailability of fly-ash: Adsorbed PCDD's and PCDF's in the rat, guinea pig 61 and Syrian golden hamster. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16—18, 1984. 1 page (abstract) KEYWORDS: Metabolism, Oral exposure, Chlorinated dibenzo—p—dioxins, Rat, Guinea pig, Hamster, Abstract Lab animals were fed fly ash from a municipal incinerator for 1, 2, and 3 months and then their livers were analyzed for PCDDs and PCDFs. Rats and hamsters retained TCDD and TCDF in considerable amounts. Guinea pigs also retained PCDDs and PCDFs, but the pattern of isomers retained was different. Van Miller, J.P. 1981. Chemical and Pathological Observations of Chlorinated Aromatic Hydrocarbons Administered to Rats and Rhesus Monkeys. University Microfilms International, Ann Arbor, Michigan. 255 pages (Ph.D. dissertation). KEYWORDS: Cancer, Rat, Nonhuman primate, Reproductive effects, Lethality, Metabolism See Page 101. Vessey, D.A., and Boyer, T.D. 1984. Differential activation and inhibition of different forms of rat liver glutathione S—transferase by the herbicides 2,4—dichlorophenoxyacetate (2,4—D) and 2,4,S-trichlorophenoxyacetate (2,4,5-T). Toxicol. Appl. Pharmacol. 73:492—499 KEYWORDS: Mechanism of toxic action, In vitro study, 2,4-D and its esters, 2,4,5—T and its esters, Rat The authors studied the effects of 2,4-D and 2,4,5-T on two different forms of glutathione S-transferase isolated from rat liver. Both compound inhibited both forms of the enzyme suggesting an ability for these compounds to interfere with the deactivation of electrophiles. Veterans Administration Advisory Committee on Health-Related Effects of Herbicides 1984a. Transcript of Proceedings: 19th Meeting. March 6, 1984. veterans Administration, wasnington, D.C. 143 pages. Veterans Administration Advisory Committee on Health—Related Effects of Herbicides 1984b. Transcript of Proceedings: 20th Meeting. June 5, 1984. veterans Administration, Wasnington, D.C. 160 pages. veterans Administration Advisory Committee on Health-Related Effects of Herbicides 1984c. Transcript of Proceedings: let Meeting. September 12, 1984. veterans Administration, waShington, D.C. 125 pages. 62 Walden, Walden, Watson, R., and Schiller, C.M. 1983. Dose-related responses to 2,3,7,8-tetrachlorodibenzo—p—dioxin (TCDD) in male, Fischer rats. Fed. Proc. 42:355 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo—p-dioxins, Rat, Abstract The administration of single oral doses of TCDD to male Fischer rats caused a dose-related increase in serum triglyceride concentrations one week after treatment. The effect was particularly pronounced after fat feeding implicating altered triglyceride utilization. R., Shoaf, C.R., Chapman, D.E., and Schiller, C.M. 1984. Changes in serum triglyceride (TG) metabolism induced by 2,3,7,8—tetrachlorodibenzo—p—dioxin (TCDD) in adult male Fischer rats. Toxicologist. 4:187 (abstract) KEYWORDS: Acute toxic effects, Mechanism of toxic action, Other toxic effect, Oral exposure, Chlorinated dibenzo-p-dioxins, Rat, Abstract A single oral dose of TCDD altered the clearance of radiOLabelled chylomicra in rats. Also chylomicra from TCDD—treated rats were cleared more slowly by normal rats. TCDD may change the composition and the removal of chylomicra. I.P. 1983. Vietnam veterans. Aust. NZ J. Psychiatry. 17:93-94 (letter) KEYWORDS: Neuro/behavorial, Environmental, Phenoxy herbicide formulation, Human, Comment This letter to the editor comments on previous publications and letters in the same journal regarding psychiatric symptoms in Vietnam veterans. The author emphasizes the precise diagnostic criteria for post—traumatic stress disorder and that not all Vietnam veterans with psychiatric symptoms meet the criteria thus allowing for a pathogenic role of Agent Orange. Webb, K.B. 1984. The pilot Missouri health effect study. Bull. Environ. Contam. Toxicol. 33:662-672. KEYWORDS: Epidemiologic investigation, Reproductive effects, Chloracne, Neurobehavioral effects, Porphyria cutanea tarda, Hepatic effects, Renal effects, Other toxic effect, Environmental exposure, Chlorinated dibenzo-p-dioxins, Human Webb, K., Ayres, S., Slavin, R., Knutsen, A., Roodman, S., Gedney, W.B., Schramm, W., Hotchkiss, R.L., Miller, R., and Donnell, H.D. 1984. Results of a pilot study of health effects due to 63 2,3,7,8-tetrachlorodibenzo—p—dioxin contamination: Missouri. JAMA. 251:1139-1140. KEYWORDS: Epidemiologic investigation, Chloracne, Porphyria cutanea tarda, Renal effects, Immunological effects, Other toxic effect, Environmental exposure, Chlorinated dibenzo—p—dioxins, Human See Pages 7, 8, 14, 112, 117, and 129. Weber, G., Luzi, P., Resi, L., Tanganelli, P., Lovati, M.R., and P011, A. 1983. Natural history of TCDD—induced liver lesions in rats as observed by transmission electron microscopy during a 32-week period after a single intraperitoneal injection. J. Toxicol. Environ. Health. 12:533-540 KEYWORDS: Acute toxic effects, Hepatic effects, Exposure by injection, Chlorinated dibenzo-p-dioxins, Rat The authors studied the time course of histopathological changes in the liver of male Sprague—Dawley rats following a single intraperitoneal dose of TCDD at the L050 level. Liver changes characterized by vacuolar alterations, lipid accumulation, proliferation of the rough and smooth endoplasmic reticulum, and diffuse necrosis reached a peak 16 weeks after treatment; the pathOlogy nearly disappeared after 32 weeks. Weinstein, 1.8. 1984. Dioxins as carcinogenic promoters. In Lowrance, W.W., ed. Public Health Risks of the Dioxins. William Kaufmann, Los Altos, California. Pp. 155-160 KEYWORDS: Cancer, Chlorinated dibenzo—p—dioxins, Review, Commentary The author reviews evidence that several compounds, including TCDD, act as promoters of carcinogenesis but cautions that, for risk assessment purposes, it is not appropriate to assume that there is a threshold for this effect. Whitlock, J;P., and Galeazzi, D.R. 1984. 2,3,7,8-Tetrachlorodibenzo— p—dioxin receptors in wild type and variant mouse hepatoma cells: Nuclear location and strength of nuclear binding. J. Biol. Chem. 259:980-985 KEYWORDS: Epidemiologic investigation, Occupational exposure, Phenoxy herbicide formulations, Human, Review In this study of the molecular mechanism of TCDD action, the authors demonstrate that localization of the "TCDD-receptor" in cultured mouse hepatoma cells is temperature dependent and that 80% of the receptor is in the nucleus. Occupied receptor binds more strongly in the nucleus than unoccupied receptor and deficient cells show less nuclear binding. 64 Whitlock, J.P., Galeazzi, D., Israel, D., and Miller, A.G. 1983. Cytocnrome P1-450 induction by TCDD: Biochemical and genetic analyses in mouse hepatoma cells. In Singer, T.P., Mansour, T.E., and Undarza, R.N., eds. Mechanism of Drug Action: Symposium on the Biochemical Basis of Drug Action.Academic Press, Orlando, Florida. Pp. 327—340 KEYWORDS: Enzyme induction or inhibition, In vitro study, Chlorinated dibenzo-p—dioxins, Cultured mammalian cells In this study, TCDD is used as a representative compound to study AHH induction in cultured mouse hepatoma cells. In wild—type cells, TCDD stimulates the synthesis of Pl-450 mRNA through the accumulation of TCDD-receptor complex in the nucleus of the cell. P1—450 mRNA synthesis is much lower in receptor-deficient cells. Willey, J.C., Saladino, A.J., Ozanne, C., Lechner, J;F., and Harris, C.C. 1984. Acute effects of l2-O—tetradecanoylphorbol-l3- acetate, teleocidin B, or 2,3,7,B—tetrachlorodibenzo—p—dioxin on cultured normal human bronchial epithelial cells. Carcin- ogenesis. 5:209-215 KEYWORDS: Cancer, Mechanism of toxic action, In vitro study, Chlorinated dibenzo—p-dioxins, Cultured mammalian cells TCDD inhibited growth and caused morphological alterations when added to cultures of normal human bronchial epithelial cells. These effects were similar but not identical to changes induced by other tumor promotors. Wolfe, W.H., and Lathrop, G.D. 1983. A medical surveillance program for scientists exposed to dioxins and furans. In Tucker, R.E., Young, A.L., and Gray, A.P., eds. Human and Environmental Risks of Chlorinated Dioxins and Related Compounds.P1enum Press, New York. Pp. 707-716 KEYWORDS: Occupational exposure, Chlorinated dibenzo-p—dioxins, Human, Review Based upon their review of the health effects information available on occupational exposure to polychlorinated dibenzodioxins and dibenzofurans, the authors recommend a medical surveillance program for scientists who work with these compounds. (9 references) WOods, J;S. 1984. Toxicological issues in an epidemiologic study of human cancer and exposure to dioxin-containing chemicals. Toxicologist. 4:7 (abstract) KEYWORDS: Cancer, Epidemiologic investigation, Occupational 65 exposure, Environmental exposure, Chlorinated dibenzo-p- dioxins, PhenOxy herbicide formulations, Human, Abstract This abstract describes the design of a case—control study of the incidence of soft-tissue sarcoma and lymphoma among men residing in a portion of washington State where phenoxy herbicides and other dioxin-containing formulations have been used extensively for over 30 years. Woods, J.S. 1984. Cancer incidence and phen0xy herbicide exposure. Oral presentation to the veterans Administration Advisory Committee on Health—Related Effects of Herbicides. December 11, 1984, washington, D.C. 2 pages KEYWORDS: Epidemiologic investigation, Cancer, Occupational exposure, Phenoxy herbicide formulations, Chlorinated dibenzo—p-dioxins, Human, Abstract The speaker described an ongoing case-control study of sort-tissue sarcoma and lymphoma in 13 counties in Washington state. Cases and controls will be compared on the basis of exposure to phenoxy herbicides. Yamauchi, H., and Yamamura, Y. 1984. Metabolism and excretion of orally administered dimethylarsinic acid in the hamster. Toxicol. Appl. Pharmacol. 74:134—140. KEYWORDS: Metabolism, Oral exposure, Cacodylic acid, Hamster See Pages 148 and 150. Young, A.L., and Kang, H.K. 1984. Status and results of federal epidemiologic studies of populations exposed to TCDD. Presented at the 4th International Symposium on Chlorinated Dioxins and Related Compounds, Ottawa. October 16-18, 1984. 1 page (abstract) KEYWORDS: Epidemiologic investigation, Occupational exposure, Phen0xy herbicide formulations, Human, Abstract, Review This abstract of a talk given at a symposium describes ongoing studies sponsored by the U.S. government that are designed to provide information on the potential health effects of phenoxy herbicides and their impurities. Young, A., Kang, H.K., and Shepard, B.M. 1983. Chlorinated dioxins as herbicide contaminants. Environ. Sci. Technol. 17:530A—537A KEYWORDS: Chloracne, Cancer, Reproductive effects, Occupational exposure, Environmental exposure, Phenoxy herbicide formulations, Chlorinated dibenzo-p-dioxins, Human, Review 66 This review summarizes the available information on the health erfects or phenoxy herbicides and their impurities and describes ongoing and planned federal government research initiatives on the health effects of Agent Orange. (44 references) Zimmering, S., Mason, J.M., valencia, R., and Woodruff, R.C. 1984. Chemical mutagenesis testing in Drosophilia. II. Results of 20 coded compounds tested for the National Toxicology Program. Environ. Mutagen. (in press). KEYWORDS: 2,4-D and its esters, 2,4,5—T and its esters, Chlorinated dibenzo-p—dioxins, Genotoxicity, Oral exposure, Exposure by injection See Pages 58, 60, 62, 63, and 64. 67 9861 AInf‘ swaua queaH uo amxemxn luesaa ;o Audmfioqug palexouuv l/\ awnIOA sunxmo Axoszazogjlzzlgsey::p03lq13H ozpoz 3c] uolfiul 3 HO 315191318 mpiggg Mefims pue aUIOIpaW ;o luaLulzidgaAa uoueusgugwpv sumalaA LRELETDDDB IIIIIIIIIIIIl BENIN '3'“ ' MWHEI'I “BIBS