Toxicity of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD). 1982

R J Kociba, and B A Schwetz

In summary, the toxicity of TCDD has been comprehensively examined in multiple acute, subchronic, and chronic studies. Acute toxicity studies have shown marked species differences, with up to a 10,000-fold difference between the single oral LD50 dose for the guinea pig and hamster. TCDD is capable of causing an acnegenic response in man and a similar skin response in certain animals. It is also a potent inducer of microsomal enzymes in some but not all species. A dose-related suppression of cell-mediated immunity has been observed at higher dose levels in laboratory animals but not in humans manifesting TCDD-induced acnegenic response. TCDD causes a dose-related teratogenic response in mice, with the no-adverse-effect level of 0.1 micrograms TCDD/kg/day. In rats, TCDD causes embryo- and fetotoxicity above the no-adverse-effect level of 0.03-0.125 micrograms/kg/day. Dose-related reproductive effects have also been noted in monkeys at doses that elicit maternal toxicity, and additional long-term studies are presently underway. A multigeneration reproduction study as well as a lifetime chronic toxicity study have been completed with TCDD in rats; in both studies, the no-adverse-effect level was found to be 0.001 microgram TCDD/kg/day. Numerous mutagenic studies have been performed using in vitro plant and microbial test systems as well as in vivo tests in mammals and man. A mutagenic response was noted in a few of the vitro test systems, but there are no definitive in vivo correlates of TCDD mutagenicity in higher mammals or man. TCDD has been studied for carcinogenic potential in rats and mice. There is good correlation of the results, with a carcinogenic response noted in both species only after long-term ingestion of higher dose levels that induce toxicity. No carcinogenic response occurred at continuous dose levels of 0.001-0.0014 micrograms/kg/day in rats and 0.001-0.03 micrograms/kg/day in mice. Data presently available are more supportive of a nongenetic (?promotor) rather than a genetic mechanism of carcinogenesis. The most recent research, some of which is still underway, indicates that the biologic uptake and toxicity of TCDD may be significantly decreased if the TCDD is adsorbed onto carbon or soil particles. This information is helpful in hazard assessment of exposure to TCDD.

UI MeSH Term Description Entries
D007109 Immunity Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances. Immune Process,Immune Response,Immune Processes,Immune Responses,Process, Immune,Response, Immune
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002908 Chronic Disease Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care (Dictionary of Health Services Management, 2d ed). For epidemiological studies chronic disease often includes HEART DISEASES; STROKE; CANCER; and diabetes (DIABETES MELLITUS, TYPE 2). Chronic Condition,Chronic Illness,Chronically Ill,Chronic Conditions,Chronic Diseases,Chronic Illnesses,Condition, Chronic,Disease, Chronic,Illness, Chronic
D004147 Dioxins A family of compounds that contain the 1,4-dioxin structure. Many specific dioxin derivatives are listed as CARCINOGENS; TERATOGENS; or MUTAGENS. Dioxin
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000072317 Polychlorinated Dibenzodioxins Dibenzodioxin derivatives that contain multiple chloride atoms bound to the benzene ring structures. TCDD,Tetrachlorodibenzodioxin,2,3,7,8-Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo-p-dioxins,Dibenzo(b,e)(1,4)dioxin, 2,3,7,8-tetrachloro-,PCDD,Polychlorinated Dibenzo-p-dioxins,Polychlorinated Dibenzodioxin,Polychlorodibenzo-4-dioxin,Polychlorodibenzo-p-dioxin,Tetrachlorodibenzo-p-dioxin,Chlorinated Dibenzo p dioxins,Dibenzo-p-dioxins, Chlorinated,Dibenzo-p-dioxins, Polychlorinated,Dibenzodioxin, Polychlorinated,Dibenzodioxins, Polychlorinated,Polychlorinated Dibenzo p dioxins,Polychlorodibenzo 4 dioxin,Polychlorodibenzo p dioxin,Tetrachlorodibenzo p dioxin
D000152 Acne Vulgaris A chronic disorder of the pilosebaceous apparatus associated with an increase in sebum secretion. It is characterized by open comedones (blackheads), closed comedones (whiteheads), and pustular nodules. The cause is unknown, but heredity and age are predisposing factors. Acne

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