Chemical Key in vivo findings MeIQx Dose-dependent increase of MeIQx-DNA adducts, elevation of 8-OHdG, lacI and H-ras mutation levels, and induction of GST-P+ foci and liver tumors (100 to 400 ppm) in rats. Existence of a no-effect level (1 ppm) for the carcinogenicity of MeIQx in the rat liver (4, 16, 32-week assays in F344, BN and BigBlue rats, 2-step carcinogenicity test, 2-year carcinogenicity test, medium-term rat liver bioassay). Existence of no-effect levels of combinations of MeIQx and DEN treatments in the rat liver (16 weeks assays of concurrent treatment with DEN and MeIQx). Metabolic activation by CYP1A2 and NAT. Induction of CYP1A1, CYP1A2, UGT1A1, p53, p21WAF1/Cip1, GADD45a and BAX. IQ Existence of no-effect level (0.001 ppm) for the carcinogenicity in the rat liver (16 weeks assay). Induction of CYP1A1, CYP1A2, APE-1, GADD45, p21WAF1/Cip1 (10 ppm and below) PhIP Existence of no-effect level (10 ppm) for the carcinogenicity in the rat colon (16 weeks assay). Induction of oxidative stress, Stat1, VEGF, c-fos, c-jun, inactivation of p16 and BCRP. DEN Existence of no-effect level (0.01 ppm) for the carcinogenicity in the rat liver (16 weeks assay) DMN Existence of no-effect level (0.1 ppm) for the carcinogenicity in the rat liver (16 weeks assay).

Table 1: Key in vivo findings observed with several genotoxic carcinogens.