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 fiver and testicular damage are probably due to a direct effect of NB or its metabolites.

Toxicity of Tetryl (N-Methyl-N,2,4,6–Tetranitroaniline) in F344 Rats

“…Observed toxic effects of tetryl in subacute and subchronic toxicity studies have includedchangeshematological,renal, splenic, and hepatic organs. These effects are similar to the target organ toxicity of other nitroaromatic compounds such as nitrobenzenes (Bond et al 1991;Cody et al 1981;Blackburn et al 1988;Chandra et al 1995Chandra et al , 1997aReddy et al 1996Reddy et al , 1998 and nitrotoluenes (Levine et al 1983(Levine et al , 1984Furedi et al 1984;Rickert 1985).…”

Fourteen-day Toxicity Study of 1,3,5-Trinitrobenzene in Fischer 344 Rats

“…16 The cerebellar lesions evident in two out of five females in the 1200 mg TNB dose group were remarkably analogous to changes previously described for DNB" and nitrobenzene. 18 The affected areas had prominent vacuoles in association with hemorrhage and malacia with numerous infiltrating glial cells (Fig. 6).…”

Wildlife Toxicity Assessment for 1,3,5-Trinitrobenzene (TNB)

“…Based on their data the authors considered the most sensitive endpoint to be the kidney lesions evident in male F344 rats and assigned the 3.91 mg/kg/day dose as the subchronic LOAEL for TNB [26]. These effects were evident in males at all doses.…”

“…However, the mechanisms by which such responses are brought about are poorly understood, although the induction of an imbalance in neurotransmitters and their metabolites may play at least a partial role in bringing about these effects [26]. However, the mechanisms by which such responses are brought about are poorly understood, although the induction of an imbalance in neurotransmitters and their metabolites may play at least a partial role in bringing about these effects [26].…”