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PREDICTING RODENT CARCINOGENICITY OF HALOGENATED HYDROCARBON BY IN VIVO BIOCHEMICAL PARAMETERS
Citation:
Kitchin, K., J. Brown, AND A. Kulkarni. PREDICTING RODENT CARCINOGENICITY OF HALOGENATED HYDROCARBON BY IN VIVO BIOCHEMICAL PARAMETERS. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/J-95/140.
Description:
Forty halogenated hydrocarbons of known rodent carcinogenicity (24 carcinogens, 16 noncarcinogens), including many promoters of carcinogenesis, nongenotoxic carcinogens and hepatocarcinogens were selected for study. he effects of these 40 chemicals on four biochemical assays (hepatic DNA damage by alkaline elution (DD), hepatic ornithine decarboxylase activity (ODC), serum alanine aminotransferase activity (ALT), and hepatic cytochrome P-450 content (P450)) were determined. omposite predictive parameters are defined as follows: CP = [ODC and P4501, CT (ALT and ODC], and TS = [DD or CP or CT). he operational characteristics of TS for predicting rodent cancer were sensitivity 58%, specificity 81%, Positive productivity 82%, negative productivity 57%, and concordance 68%. he concordance for the Ames test (45%) and. structural alerts (SA) (46%) was much lower. S also outperformed the Ames test and SA in producing fewer false positives, (the specificity of TS was 81% versus only 63% for the Ames test and 57% for SA). or predicting the carcinogenicity of the most difficult halogenated hydrocarbons (Ames and SA negative chemicals), TS was capable of successfully predicting the carcinogenicity of 8 out of 16 of these non DNA-reactive halogenated hydrocarbon carcinogens. ll 8 of these halogenated hydrocarbons were positive in either CP or CT. his evidence shows that nongenotoxic carcinogenesis is best predicted by nongenotoxic parameters such as CP and/or CT (components of the predictor TS).