Carcinogenicity and Chronic Toxicity of 1,4-Dichloro-2-nitrobenzene in Rats and Mice by Two Years Feeding

Abstract

Carcinogenicity and chronic toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) were examined by feeding each group of 50 F344 rats and 50 BDF1 mice of both sexes a DCNB-containing diet at a concentration of 0 (control), 320, 800 or 2,000 ppm (w/w) for 2 yr. In rats, incidences of hepatocellular adenomas and carcinomas and their combined incidence were increased in the 2,000 ppm-fed males, together with increased incidence of basophilic cell foci in the 800 and 2,000 ppm-fed males. A dose-related increase in combined incidences of renal cell adenomas and carcinomas was noted. Incidence of Zymbal gland adenomas tended to increase in the 2,000 ppm-fed males. In mice, incidences of hepatocellular adenomas in the 800 and 2,000 ppm-fed females and hepatocellular carcinomas in the 2,000 ppm-fed males and in the 800 and 2,000 ppm-fed females were increased. Incidence of hepatoblastomas was increased in all DCNB-fed males and in the 2,000 ppm-fed females. Signs of chronic toxicity were characterized by centrilobular hypertrophy of hepatocytes with nuclear atypia in mice, increased relative liver weight in rats, a dose-related increase in incidences of chronic progressive nephropathy with advanced grades of severity in male rats, and decreased hemoglobin concentration and hematocrit accompanied by increased bone marrow hematopoiesis in female rats. Carcinogenic activity of DCNB was evaluated for the three different tumors, and sensitive signs of the chronic toxicity were dis-