THIRTEEN-WEEK ORAL TOXICITY OF PARA- AND ORTHO- CHLORONITROBENZENE IN RATS AND MICE

Abstract

Para- and ortho-chloronitrobenzene (p- and o-CNB) were compared for subchronic toxicity by feeding F344 rats and BDF(1) mice of both sexes p-CNB-or o-CNB-containing diets at 5 different concentrations for 13 weeks. The two isomers induced hematotoxicity and hepatotoxicity of different toxic potencies. p-CNB produced an anemic sign of external appearance in rats and mice, while o-CNB did not. Significant increases in the incidences of increased erythropoiesis in the bone marrow and increased extramedullary hematopoiesis in the spleen and liver, and in serum total bilirubin in rats and mice appeared at lower dose levels of p-CNB than o-CNB. A significant increase in serum ALT activity appeared at lower dose levels of o-CNB than p-CNB, together with appearance of both necrosis and hydropic degeneration of hepatocytes only in the o-CNB-fed rats and nuclear enlargement with atypia of hepatocytes only in the o-CNB-fed mice. BMDL(10)s of p- and o-CNB for the hematotoxic endpoint, substitutes for NOAELs, were 0.177 mg/kg/day and 1.03 mg/kg/day for the rats, respectively. For the mice, the NOAELs of p-and o-CNB for the hematotoxic endpoint were 10.5 mg/kg/day and 10.4 mg/kg/day, respectively. A NOEL of o-CNB for the hepatotoxic endpoint resulted in 13.8 mg/kg/day for the rats and 12.2 mg/kg/day for the mice. These results suggest that p-CNB is a more potent hematotoxicant than o-CNB, whereas o-CNB is a more potent hepatotoxicant than p-CNB, and that the rat hematopoietic system is more susceptible to p-CNB than the mouse hematopoietic system.