Enhancement of toxicity and enzyme-repressing activity of p-dioxane by chlorination: stereoselective effects.
The acute toxicity of p-dioxane may be enhanced up to 1000-fold by chlorination of the compound. The effect was stereoselective. Of the stereoisomers tested, tetrachloro-p-dioxane, isomer I (2r, 3t, 5t, 6c) was over 80 times more toxic than isomer II (2r, 3c, 5t, 6t). The latter compound was also a potent repressor of hepatic dimethylnitrosamine-demethylase I (DMN-d) and aryl hydrocarbon hydroxylase (AHH).
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors*; D002274:Carcinogens, Environmental / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D002713:Chlorine / Q000633:toxicity; D004128:Dimethylnitrosamine / Q000378:metabolism; D004146:Dioxanes / Q000633:toxicity*; D004147:Dioxins / Q000633:toxicity*; D004790:Enzyme Induction; D008297:Male; D010089:Oxidoreductases, N-Demethylating / Q000037:antagonists & inhibitors*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D002274:Carcinogens, Environmental; D004146:Dioxanes; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D002713:Chlorine; D001189:Aryl Hydrocarbon Hydroxylases; D010089:Oxidoreductases, N-Demethylating; D004128:Dimethylnitrosamine