Threshold for carcinogenicity of N-nitrosodiethylamine for esophageal tumors in rats.
In a study on 4080 rats by Peto et al. [Cancer Res. 51 (1991) 6415], esophageal neoplasms induced by N-nitrosodiethylamine (NDEA) were the tumors most clearly demonstrated to have a dose response from administration of the compound to male rats. However, they were unable to predict the shape of the dose-response curve at low doses. These data were reanalyzed in the present study for dose response on a logarithmic scale for dose. In contrast to the conclusion of Peto et al., the reanalysis shows a convincingly sharp threshold at 10(17.1) molecules/kg/day. This unequivocal threshold has substantial implications for risk assessment of chemical carcinogens.
Waddell
W J
WJ
Department of Pharmacology and Toxicology, School of Medicine, University of Louisville, KY, USA. bwaddell@louisville.edu
D000477:Alkylating Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002273:Carcinogens / Q000008:administration & dosage / Q000009:adverse effects*; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004938:Esophageal Neoplasms / Q000139:chemically induced*; D051381:Rats; D012016:Reference Values; D015203:Reproducibility of Results; D018570:Risk Assessment
D000477:Alkylating Agents; D002273:Carcinogens; D004052:Diethylnitrosamine