Histopathology of neoplastic and nonneoplastic hepatic lesions in mice fed diets containing tetrachlorvinphos

Tetrachlorvinphos was fed at 8, 000 or 16, 000 ppm in diets to male and female (C57BL/6N × C3H/HeN)F₁, mice for 80 weeks. Surviving mice were killed at 92 weeks, and all mice were completely necropsied. A high incidence of unusual nonneoplastic hepatic lesions in treated mice was present and characterized by pericellular fibrosis, hepatocyte nuclear pleomorphism, and intrasinusoidal foci of macrophages with intracytoplasmic crystalline structures. From 84 to 94% of the treated male mice and from 21 to 23% of the treated females had hepatocellular neoplasms. Only 17% of the control males and 7% of the control females had liver tumors. The induced tumors were frequently multiple In the liver, whereas the tumors In the controls were usually singular. The morphology of 241 liver tumors in 110 treated mice was different from that of tumors in controls. Liver tumors in control mice were generally composed of small basophilic hepatocytes. In treated mice, tumors were hepatocellular carcinomas composed of solid sheets of large basophilic or eosinophilic hepatocytes. Foci of prominent trabecular formation were seen in 51 tumors. Fifteen tumors were composed of small basophilic hepatocytes with oval cells Interposed among them. Foci of capillary formation were noted in 3 of these tumors. In addition, 7 more typical hemangiosarcomas forming sinusoids and with thrombosis were observed.—JNCI 63: 111–118, 1979.