Two-week oral toxicity study of 1,4-Dichloro-2-nitrobenzene in rats and mice

Subacute toxicity of 1,4-dichloro-2-nitrobenzene (DCNB) was examined by feeding F344 rats and BDF1 mice of both sexes a diet containing DCNB at 625, 1250, 2500, 5000 or 10,000 ppm (w/w) for 2 weeks. All DCNB-fed rats survived to the end of the 2-week administration period, but 2 male and 6 female mice fed 10,000 ppm died during this period. The subacute toxicity was characterized by lesions affecting the liver, kidney, testis and hematopoietic system. The liver was the most responsive to DCNB, as evidenced by a dose-related increase in relative liver weight in rats and mice and centrilobular hypertrophy of hepatocytes in mice. An alteration in liver-associated lipid metabolism was suggested from the concomitant increases in serum concentrations of total cholesterol and phospholipid. A lower confidence limit of the benchmark dose yielding the response with 10% extra risk (BMDL10) for the relative liver weight indicated that rats were more responsive to DCNB than mice. The kidney lesion was characterized by alpha2upsilon-globulin-accumulated hyaline droplets in the renal tubular epithelial cells only in male rats, as indicated by positive anti-alpha2upsilon-globulin immunohistochemical staining. Testicular and hematopoietic lesions appeared at higher dose levels than did the liver and kidney lesions.