N-nitrosodiethylamine mechanistic data and risk assessment: bioactivation, DNA-adduct formation, mutagenicity, and tumor initiation

Abstract

N-Nitrosodiethylamine (NDEA) is DNA reactive after bioactivation and produces tumors in every animal species tested. Bioactivation is effected by several P450 isozymes including CYP2E1, which is ethanol inducible. Tumor formation in rat liver was proportional to O4-ethyldeoxythymidine formation in DNA, which was generally proportional to NDEA dose. At low doses in the 0.033-1.1 ppm range, the dose-response for esophageal tumor formation was sublinear, possibly due to DNA repair. Although no epidemiological studies have specifically evaluated NDEA, sufficient exposure levels would be expected to cause cancer in humans.