Mutagens that are not carcinogens: faulty theory or faulty tests?
In the National Toxicology Program database of 172 chemicals that were judged non-carcinogenic or equivocal in 2 year rodent studies in both sexes of rats and mice, there are 38 chemicals that were mutagenic in Salmonella. All but two of the chemicals had structural alerts for mutagenicity. The largest proportion of the mutagenic non-carcinogens were benzeneamines and substituted benzeneamines. In all, 12 of the mutagenic non-carcinogens had mutagenic carcinogen analogues, and for two chemicals, the carcinogenic analogues were not mutagenic. Non-carcinogens that were mutagenic in Salmonella also tended to be mutagenic and clastogenic in mammalian in vitro tests. The mutagenic responses are discussed and explanations offered for the mutagenicity and lack of carcinogenic activity of these chemicals.
Zeiger
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Environmental Toxicology Program, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA. zeiger@nc.rr.com
D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000145:classification* / Q000633:toxicity; D016208:Databases, Factual; D005189:False Positive Reactions; D005260:Female; D008297:Male; D051379:Mice; D009152:Mutagenicity Tests; D009153:Mutagens / Q000145:classification* / Q000633:toxicity; D051381:Rats; D015203:Reproducibility of Results; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D015262:Xenobiotics / Q000145:classification* / Q000633:toxicity
D002273:Carcinogens; D009153:Mutagens; D015262:Xenobiotics