The testicular toxicity and
methemoglobinemia induced by
1,3-dinitrobenzene (1,3-DNB) was compared in two species, the Sprague-Dawley rat and the golden Syrian hamster. A marked difference in susceptibility to both endpoints of toxicity was observed. The hamster showed no testicular lesions at dose levels up to 50 mg/kg whereas, as previously reported by others, damage to rat testicular tubules in later stages of spermatogenesis was readily apparent at a 25 mg/kg dose level. Similarly, administration of 1,3-DNB induced substantially less
methemoglobinemia in the hamster than in the rat. For example, at the 25 mg/kg dose level peak levels of
methemoglobin in the hamster were 15% compared with 80% in the rat. Mortality in the rat also occurred at lower doses than in the hamster (50 vs 100 mg/kg, respectively). In in vitro studies, the capacity of 1,3-DNB and 1,3-DNB metabolites (
nitroaniline, nitroacetanilide, aminoacetanilide, diacetamidobenzene) to induce
methemoglobinemia was examined in
suspensions of red blood cells obtained from both species. Only 1,3-DNB caused the formation of
methemoglobin and rat red blood cells were twice as sensitive as hamster red blood cells. The species difference in susceptibility to both
methemoglobinemia and testicular toxicity could indicate differences in 1,3-DNB clearance and/or formation of toxic metabolites. Additional metabolic work is under way. This study demonstrates that the hamster is more resistant than the rat to the testicular lesion and
methemoglobinemia induced by 1,3-DNB.