2,3,7,8-Tetrachlorodibenzo-p-dioxin

CAS RN: 1746-01-6

Toxicity Summary

INDENTIFICATION AND USE: 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a colorless to white crystalline solid. It has no known commercial applications, but it is used as a research chemical. It was tested, but never used commercially, as a flame proofing agent and as a pesticide against insects and wood-destroying fungi. TCDD occurred as a contaminant in chlorophenoxy herbicides, including 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), that were widely used in the 1960s and 1970s to control weeds (including controlling weeds on pastureland and food crops) and as a defoliant during the Vietnam War. HUMAN EXPOSURE AND TOXICITY: The most commonly reported symptom related to TCDD exposure in man has been chloracne. The acneform lesions of the skin may develop a few weeks after the exposure and may persist for over a year following the cessation of exposure. Other skin problems include hyperpigmentation, hirsutism, increased skin fragility, and vesicular eruptions on exposed areas of the skin. Cancer incidence and cause specific mortality were examined in a group of 243 industrial workers who were exposed to TCDD. Increased cancer risk ratios were found with higher doses of TCDD and longer interval since first exposure, digestive and respiratory cancers in particular. Within the high dose group, total cancer mortality was increased 20 yr after first exposure as was respiratory cancer. This study provided further evidence of a relation between cumulative dose of TCDD and occurrence of both overall and digestive cancer. No evidence of an effect of TCDD on overall mortality or deaths due to circulatory disease was found and no cases of non-Hodgkin's lymphoma or soft tissue sarcoma have been found to date. ANIMAL STUDIES: The potency of TCDD to produce chloracne in the rabbit ear was tested. Threshold levels for the induction of lesions were between 1 ug for the pure compound and 160 ug when the compound was adsorbed onto charcoal. Chemical thyroidectomy effectively protected athyroid rats from mortality during 45 days after dosing with 100 ug TCDD/kg, whereas 70-80% of nonthyroidectomized-euthyroid and thyroidectomized-T4 (thyroxine)-maintained-euthyroid rats died within same period of time. These data indicate that thyroid hormones play an important role in mediating toxicity of TCDD. In order to test the potential of TCDD as a promoter of hepatocarcinogenesis, rats which had received a single 10 mg/kg dose of diethylnitrosamine following partial hepatectomy were given TCDD (0.14 and 1.4 ug/kg sc once every 2 weeks) for 7 months. Animals which received (a) only a single initiating dose of diethylnitrosamine after partial hepatectomy and no further treatment or (b) TCDD alone with no initiating dose of diethylnitrosamine exhibited relatively few enzyme altered foci and no hepatocellular carcinomas. However, animals initiated with diethylnitrosamine and then given TCDD had a marked increase in enzyme altered foci. At the higher dose of TCDD, hepatocellular carcinomas were present in five of seven rats. The total volume of the liver occupied by the enzyme altered foci, but not their number, increased with the dose of TCDD administered following diethylnitrosamine plus partial hepatectomy. TCDD was not mutagenic in any of several in vitro and in vivo short-term tests. No induction of gene mutations was seen in S. typhimurium strains TA98, TA100, TA1535, or TA1537 exposed to TCDD with or without S9 activation enzymes. No induction of trifluorothymidine resistance (gene mutations) was observed in L5178Y tk+/-mouse lymphoma cells tested with or without S9 activation. ECOTOXICITY STUDIES: TCDD is toxic to aquatic life. Medaka (Oryzias latipes) immersed in TCDD-treated water for 28 day, followed by immersion in clean water for up to 8 months, led to an increase in tumors at multiple sites, including gills, thyroid, and swimbladder. Guppies that survived exposure to TCDD for 10 days, showed necrosis of maxillary cartilage and fins.
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