Toxicity and fetotoxicity of TCDD, TCDF and PCB isomers in rhesus macaques (Macaca mulatta).
In rhesus macaques (Macaca mulatta), consumption of food containing commercial polychlorinated biphenyl (PCB) mixtures, some pure polychlorobiphenyl congeners, 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), and 2,3,7,8-tetrachlorodibenzofuran (TCDF) caused the same clinical toxic manifestations and histopathologic lesions, although the potencies of the toxicants covered a range of five orders of magnitude. Recovery from poisoning by 3,4,3',4'-tetrachlorobiphenyl (34TCB) or TCDF was rapid, whereas recovery from poisoning by Aroclor 1242, 3,4,5,3', 4', 5'-hexachlorobiphenyl (345HCB) or TCDD was protracted, if it occurred at all. 34TCB did not appreciably accumulate in body fat, but the level of 345HCB in fat rose steadily during ingestion. In one monkey, 25% of TCDD stored in fat after a single dose was still present after 2 years. Among the symmetrical tetra-and hexachlorobiphenyl isomers tested, subacute oral toxicity could be demonstrated only for those without ortho chlorine substitutions. 34TCB and 345HCB were toxic at dietary levels of less than 1 ppm, but ingestion of food containing 2,5,2',5'- tetrachlorobiphenyl at 5 ppm, or 2,4,5,2',4',5'-, 2,4,6,2',4',6'-, or 2,3,6,2',3',6'-hexachlorobiphenyl at 15 or 65 ppm, caused no discernible deleterious effects. The principal demonstrable histopathological lesions, bone marrow excepted, were metaplasias in some specialized epithelial structures, such as sebaceous glands, nail beds, gastric mucosa, ameloblast, and thymic corpuscles. These changes were interpreted as toxicant-induced, reversible redirection of differentiation. This aberration was wholly reversible. TCDD and 34TCB caused abortions when given in one or a few oral doses early in pregnancy. At the total doses used (1 or 5 micrograms/kg of body weight for TCDD, 3 or 0.6 mg/kg of body weight for 34TCB), maternal toxicity was frequently apparent subsequent to the abortion.
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D000022:Abortion, Spontaneous / Q000139:chemically induced; D000152:Acne Vulgaris / Q000139:chemically induced; D000818:Animals; D001572:Benzofurans / Q000633:toxicity*; D002454:Cell Differentiation / Q000187:drug effects; D004147:Dioxins / Q000633:toxicity*; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D005333:Fetus / Q000187:drug effects*; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology; D007536:Isomerism; D008253:Macaca mulatta; D008297:Male; D009262:Nails / Q000187:drug effects / Q000473:pathology; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D011247:Pregnancy; D013329:Structure-Activity Relationship
D001572:Benzofurans; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D011078:Polychlorinated Biphenyls; C014211:2,3,7,8-tetrachlorodibenzofuran