title: Nonlinearity of dose-response functions for carcinogenicity.
abstract: Carcinogenesis data for 315 chemicals were obtained from the National Cancer Institute-National Toxicology Program (NCI-NTP) bioassay programs and were analyzed to examine the shape of carcinogenesis dose-response curves. Tumor site data were more often consistent with a quadratic response than with a linear response, suggesting that the routine use of linear dose-response models will often overestimate risk. Information from in vivo short-term mutagenicity and genotoxicity assays was also obtained for most of these rodent bioassays. It was found that there were no clear relationships between the shape of the carcinogenesis dose-response curve and the result of the short-term test. These observations argue against the concept that carcinogens that are positive in a short-term assay be regulated using a linear dose-response curve and those that are negative be regulated using a sublinear dose-response curve or a safety factor approach.
authors.affiliation: National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
authors.forename: D G
authors.initials: DG
authors.lastname: Hoel
authors.forename: C J
authors.initials: CJ
authors.lastname: Portier
mesh_terms: D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008954:Models, Biological; D015233:Models, Statistical; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens