Carcinogenic activity of dichloroacetic acid and trichloroacetic acid in the liver of female B6C3F1 mice

Abstract

The concentration-response relationships for the hepatocarcinogenic activity of dichloroacetic acid2 (DCA) and trichloroacetic acid (TCA), two contaminants of finished drinking water, were determined in female B6C3F1 mice. Dicholoracetic acid or trichloroacetic acid at 2.0, 6.67, or 20.0 mmol/liter was administered to the mice in the drinking water starting at 7 to 8 weeks of age and until sacrifice after 360 or 576 days of exposure. The relationships of the yield of foci of altered hepatocytes, hepatocellular adenomas, and hepatocellular carcinomas to the concentration of DCA and TCA in the water were best described by second-order and linear regressions, respectively. The liver-to-body weight ratio increased linearly for both DCA and TCA, as did the vacuolization of the liver induced by DCA. The foci of altered hepatocytes and tumors in the animals treated with DCA were predominantly eosinophilic and contained glutathione S-transferase-pi (GST-pi, over 80% of the lesions), while the tumors induced by TCA were predominantly basophilic and lacked GST-pi, including all 11 hepatocellular carcinomas. Therefore, the carcinogenic activity of DCA AND TCA appeared to differ both with respect to their dose- response relationship and to the characteristics of precancerous lesions and tumors.