Is 1,4-dioxane a genotoxic carcinogen?
Female Sprague-Dawley rats were given 0, 168, 840, 2550 or 4200 mg/kg of 1,4-dioxane 21 and 4 h before sacrifice. Hepatic DNA damage (by the alkaline elution technique), ornithine decarboxylase activity (ODC), reduced glutathione content, cytochrome P-450 content and serum alanine aminotransferase activity (ALT) were determined. Treatment with 1,4-dioxane increased hepatic DNA damage and cytochrome P-450 content at doses of 2550 and 4200 mg/kg. Large increases in the activity of hepatic ODC were observed at 840, 2550 and 4200 mg/kg of 1,4-dioxane. Thus the data suggest that 1,4-dioxane is a weak genotoxic carcinogen in addition to being a strong promoter of carcinogenesis (a non-genotoxic carcinogen).
Kitchin
K T
KT
Environmental Toxicology Division, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711.
Brown
J L
JL
D000818:Animals; D002273:Carcinogens / Q000633:toxicity; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004146:Dioxanes / Q000633:toxicity*; D004147:Dioxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005796:Genes / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004146:Dioxanes; D004147:Dioxins; D004247:DNA; C025223:1,4-dioxane