TOXICITY OF PEROXISOME PROLIFERATORS

Peroxisome proliferators are not a chemical class of compounds. They do not have a similar chemical structure but all induce characteristic effects in the liver of treated rats or mice. They produce within a few days a striking dose-dependent hepatomegaly accompanied by a characteristic proliferation of the peroxisomal and microsomal compartment as assessed morphologically and biochemically. Such effects are not observed in other species including human. In addition, life-long feeding of the susceptible laboratory animals results in the formation of liver tumor. The effects induced in subchronic studies can be reproduced and investigated in cultured hepatocytes, the target cells. The species specificity is observed with all peroxisome proliferators, and by large the effects observed in subchronic studies are reversible. The hepatocarcinogenesis by peroxisome proliferators is not fully understood, because these compounds are not directly genotoxic, but the understanding of their tumor promotor potential has some implications for the toxicological testing and risk assessment.