Risks and Benefits of Agents Which Induce Hepatic Peroxisome Proliferation

Abstract

Subchronic treatment of rodents with a variety of structurally diverse compounds leads to hepatic peroxisome proliferation, whilst life-time feeding with such compounds is associated with an elevated incidence of hepatocellular carcinomas. These findings led to the proposition that peroxisome proliferation was causally related to the subsequent tumour development. Such a relationship would have very important consequences when assessing the risk to man of exposure to peroxisome proliferators, particularly in view of the marked species differences in the susceptibility to these compounds. Much information indicates that peroxisome proliferators cause tumour development by indirect mechanisms. However, at present the evidence for a causal relationship between peroxisome proliferation and tumour induction is insufficient. Consequently risk must be assessed on a case by case basis taking all the available information into consideration.