A Comprehensive, Integrated Review and Evaluation of the Scientific Evidence Relating to the Safety of the Herbicide 2,4-D

In 1977 a number of patients with soft-tissue sarcomas and previous exposure to phenoxyacetic acids were described. Following from these observations a matched case-control study was made. Exposure to chlorophenols was also included in this study. The results showed that exposure to phenoxyacetic acids or chlorophenols gave an approximately 6-fold increase in the risk for this type of tumour. It was not possible to determine, however, whether the carcinogenic effect was exerted by these compounds or by impurities such as chlorinated dibenzodioxins and dibenzofurans that in almost all cases were part of the commercial preparations.

In this critical review, I would like to provide a brief outline of the morphology, biochemical composition, distribution, and functions of peroxisomes. The induction of peroxisome proliferation and peroxisome-associated enzymes in the rodent liver by two classes of chemicals (hypolipidemic drugs and the industrial plasticizers) will be considered. The role of peroxisomes in lipid metabolism will be discussed. Carcinogenicity studies in rats and mice with these peroxisome proliferators will be evaluated critically. Careful consideration will be given to the hypothesis that "potent hepatic peroxisome proliferators as a class are carcinogenic." The possible mechanism(s) by which peroxisome proliferators induce liver tumors will be outlined. Particular attention will be paid to the possible role of peroxisome proliferation-mediated radical toxicity and generation of endogenous initiators of carcinogenesis.