Induction of hepatic and testicular lesions in fischer-344 rats by single oral doses of nitrobenzene

Abstract Since the acute toxicity of nitrobenzene (NB) in rats has not been characterized, experiments were performed to ascertain the possible deleterious effects of NB in different tissues of the male Fischer-344 rat. Rats were given single oral doses of NB (50–450 mg/kg) and at the time of sacrifice, 25 tissues were removed and examined histologically by light microscopy. Histopathological changes induced by a single oral dose of NB consistently involved only the liver and testes. One rat receiving 450 mg NB/kg had a microscopic cerebellar lesion. Hepatic centrolobular necrosis appeared inconsistently in rats given various doses of NB, while hepatocellular nucleolar enlargement was consistently detected in rats given doses of NB as low as 110 mg/kg. These data suggest that nucleolar enlargement was independent of cell death and subsequent regeneration. Testicular lesions were confined to the seminiferous tubules and consisted of necrosis of the primary and secondary spermatocytes with the appearance of multinucleated giant cells between one and four days after administration of NB 300 mg/kg. Necrotic debris and decreased numbers of spermatozoa were seen in the epididymis as early as three days after NB administration. The NB-induced methemoglobinemia does not appear to be solely responsible for the formation of early lesions in the rat liver, testes, or brain, since sodium nitrite administration, at dosages which produced methemoglobinemia equivalent to that of NB, did not produce any histopathological changes. Thus, the observed liver and testicular damage are probably due to a direct effect of NB or its metabolites.