THE HERBICIDE DICAMBA (2-METHOXY-3,6-DICHLOROBENZOIC ACID) IS A PEROXISOME PROLIFERATOR IN RATS

The widely used broad leaf herbicide, dicamba, or Banvel, is similar i n structure to xenobiotics which induce hepatic drug metabolism or pro liferation of hepatic peroxisomes in rodents. The ability of xenobioti cs to effect these hepatic changes often portends their positive outco mes in chronic bioassays. Dicamba's ability to induce hepatomegaly and peroxisome proliferation was studied in male and female Sprague-Dawle y rats. Rats were placed on feed containing 0, 0.001, 0.01, 0.1, or 1% dicamba or 0.01% ciprofibrate for 3 weeks. Dicamba had no effect on r elative liver weights or feed efficiency in either female or male rats at all doses tested. Dicamba, however, caused a statistically signifi cant increase in peroxisomal beta-oxidation activity in liver homogena tes from rats of both sexes fed 1% dicamba. Fatty acyl CoA-oxidase act ivity was increased in male rats fed 1% dicamba. A protein of M(r) 80 kDa was visible when liver homogenates of female or male rats fed 1% d icamba were subjected to SDS-PAGE. Lauric acid hydroxylase activity an d CYP4A-reactive protein were increased in microsomes from male rats f ed the highest level of dicamba. Moreover, dicamba was observed to tra nscriptionally upregulate the peroxisome proliferator-activated recept or (PPAR), a peroxisome proliferator sensitive receptor previously sho wn to be linked to the transcriptional regulation of a variety of pero xisome-specific enzymes. These studies show that dicamba is a peroxiso me proliferator in rats. Although dicamba was not an efficacious induc er of peroxisomal enzymes in these rats, dicamba's ability to transcri ptionally activate the PPAR and induce peroxisomal and related enzymes must be considered in the safety evaluation of this herbicide. (C) 19 95 Society of Toxicology.