Do structure‐activity relationships for the acute toxicity of pcbs and pbbs also apply for induction of hepatocellular carcinoma?

Studies of the carcinogenic activity of commercial polychlorinated biphenyl (PCB) and polybrominated biphenyl (PBB) formulations in rodents have shown that (a) when given at appropriate doses and for extended periods of time, PCB and PBB mixtures cause preneoplastic lesions and carcinomas; (b) cancerous lesions are confined principally to the liver; (c) there is a marked trend from enzyme‐altered foci to neoplastic nodules to hepatocellular carcinoma with time; and (d) PCB mixtures with high chlorine content are more potent in causing hepatocellular carcinoma than mixtures with low chlorine content. Practically no data are available on the activity of individual PCBs or PBBs as carcinogens; however, considerable data exist on the activity of congeneric PCBs and PBBs as promoters/initiators of two‐stage hepatocarcinogenesis in the rat. The compounds studied were either acutely toxic (coplanar) biphenyl congeners, nonacutely toxic congeners or halogenated biphenyls with intermediate acute toxicity. Acutely toxic PCBs/PBBs as well as those without acute toxicity and those with intermediate toxicity may all promote hepatocarcinogenesis in the rat, but probably by different mechanisms. The ability of congeneric PCBs and PBBs to stimulate cellular growth and division (mitogenic effects) on the one hand and/or hepatotoxic effects on the other most likely contributes to the carcinogenic effects seen. We assert that the assessment of risk for PCB/PBB exposure must take into account the potential long‐term toxic effects of exposure to all three groups of polyhalogenated biphenyls.