Oncogenic Evaluation of Tetrachlorvinphos in the B6C3F1 Mouse

Abstract

Oncogenic Evaluation of Tetrachlorvinphos in the B6C3F1 Mouse. PARKER, C. M., VAN GELDER, G. A., CHAI, E. Y., GELLATLY, J. B. M., SEROTA, D. G., VOELKER, R. W., AND VESSELINOVITCH, S. D. (1985). Fundam. Appl. Toxicol.. 5,840-854. Groups of 80 male and 80 female B6C3F1 mice were fed diets containing 17.5, 64, 320, 1600, 8000, and 16000 ppm tetrachlorvinphos (TCVP) for up to 103 weeks. Another group of 80 male and 80 female mice were fed TCVP (16000 ppm) that was used in a previous bioassay. One hundred-sixty male and 160 female mice served as the control group. Ten treated and 20 control mice/sex/group were killed at 6, 12, and 18 months. It was estimated that the study maximum-tolerated dose was exceeded by three- and sixfold in the 8000- and 16000-ppm dose groups, respectively. Consequently, these exposures produced excessive cytotoxicity and regenerative changes in the liver and kidneys which were associated with sex-hormonal imbalance and metabolic overload in liver. A significant decrease (15–40%) in body weight was observed in mice fed 8000 and 16000 ppm TCVP. These treated mice did not gain weight during the study. Reduced food consumption and caloric intake throughout the study were probably responsible for the increased survival and the decreased incidence of spontaneous neoplasia in mice fed 8000 and 16000 ppm TCVP. Classification of pathologic lesions observed in these high-dose groups differed among study and consulting pathologists. The consultant and Shell pathologists concluded that the liver and kidney changes were causally related to excessive toxicity which was manifest primarily by hepatocellular hyperplasia and renal tubular adenoma. Study pathologist in accordance with his classification found statistically significant increases in hepatocellular carcinoma, hepatocellular adenoma or carcinoma, and renal tubular carcinoma in male mice fed 16000 ppm TCVP. The incidence of hepatic neoplasms as evaluated by the study pathologist in female mice fed 8000 and 16000 ppm TCVP although statistically significant was of questionable biologic significance when compared with historical female controls. The only statistically significant finding observed by the consulting pathologist was an increased incidence of renal tubular adenoma and renal tubular adenoma or carcinoma in male mice fed 16000 ppm TCVP. Use of results from these high-dose groups is contraindicated due to the many compromising factors affecting mice fed 8000 and 16000 ppm TCVP. TCVP was found not to be oncogenic in B6C3F1 mice at dose levels not exceeding the maximum tolerated dose.