Correlations between bioassay dose-level, mutagenicity to Salmonella, chemical structure and sites of carcinogenesis among 226 chemicals evaluated for carcinogenicity by the U.S. NTP.
Bioassay dose-level data for 226 chemicals unequivocally defined as carcinogens or non-carcinogens in mice and/or rats by the U.S. NTP have been standardized to gavage equivalent dose-levels according to a modification of the methods of Gold et al. Correlations by bioassay dose-level with chemical structure, mutagenicity to Salmonella, sites of carcinogenesis and extent of trans-species activity have been studied. The data obtained add further weight to the proposition that two classes of rodent carcinogen are present in the NTP database--genotoxic carcinogens that occur predominantly in the dose range 20-800 mg/kg and putative non-genotoxic carcinogens that are equally distributed over the dose range less than 20- greater than 3000 mg/kg. The latter carcinogens are characterized by the lack of structural alerts to DNA reactivity, the absence of mutagenicity to Salmonella, an inability to induce tumours in 8 reference tissues and a strong tendency to be tissue and species-specific in their activity. Where comparisons can be made, the present findings for the NTP carcinogens and non-carcinogens are consistent with the recent observations by Gold et al. for a larger group of carcinogens.
Brown
L P
LP
ICI Central Toxicology Laboratory and Epidemiology Unit, Macclesfield, Cheshire, Great Britain.
Ashby
J
J
D000818:Animals; D002273:Carcinogens; D055598:Chemical Phenomena; D002621:Chemistry; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D051379:Mice; D009153:Mutagens; D009369:Neoplasms / Q000139:chemically induced*; D051381:Rats; D012475:Salmonella / Q000187:drug effects*
D002273:Carcinogens; D009153:Mutagens