Toxicity of p-chloroaniline in rats and mice

p-Chloroaniline (PCA) was administered as PCA hydrochloride in water by gavage to groups of ten Fischer 344 rats and ten B6C3F1 mice of each sex for 13 wk. The doses, calculated as PCA rather than the hydrochloride salt, were 0, 5, 10, 20, 40 or 80 mg PCA/kg body weight/day for rats and 0, 7.5, 15, 30, 60 or 120 mg/kg body weight/day for mice. The vehicle controls were given deionized water by gavage. All male rats survived to the end of the studies. One of the ten female rats that received 80 mg PCA/kg died from unknown causes. The final body weights of rats that received 80 mg/kg were 16% lower than those of vehicle controls in the case of males and 4% lower in females. In mice, there was no mortality related to PCA administration. The final body weights of treated mice were similar to those of vehicle controls. In both rats and mice, no treatment-related effects on organ weights were observed at autopsy, except for a dose-related increase in spleen weight. The proportion of haemoglobin in the form of methaemoglobin was increased in dosed groups in both species and resulted in a secondary anaemia, the severity of which was dose related. Compound-related lesions observed histologically in rats and mice, included pigmentation (haemosiderin) in the kidney, spleen and liver and increased haematopoiesis in the liver and spleen and in the bone marrow (in rats but not mice), reflecting the response to the haemolytic anaemia and methaemoglobinaemia induced by PCA. It is concluded that the haematopoietic system is a target of PCA toxicity.