Metabolism and Testicular Toxicity of 1,3-Dinitrobenzene in Rats of Different Ages

Susceptibility to 1,3-dinitrobenzene (l,3-DNB)-induced testiculardamage is known to increase with age. The present study investigatedthe possibility that age-dependent differences in metabolismand disposition could account for differences in toxicity. [¹⁴C]1,3-DNB(25 mg/kg, ip) was administered to Sprague-Dawley rats whichwere 31, 75, or 120 days of age. Levels of 1,3-DNB and 1,3-DNBmetabolites were determined in blood and urine. As animal ageincreased, peak blood concentrations of 1,3-DNB were lower anddeclined more slowly indicating an age-dependent decrease inrate of metabolism and a possible increase in volume of distribution.In younger animals, faster elimination rates were associatedwith higher blood levels of metabolites. Urinary metaboliteswere generally similar for all age groups with the exceptionof the diacetamidobenzene metabolite which was significantlylower in the urine of 31 day old rats. There were clear differencesin the toxicokinetic profile for 1,3-DNB between the 31 dayold rats and the other two age groups. However, differencesbetween the 75 and 120 day old animals were less marked. Testiculardamage induced by 1,3-DNB (25 mg/kg, ip) was hardly detectablein the youngest animals, while the intermediate age group showeda moderate lesion particularly in later stages of spermatogenesis.For the oldest animals, testicular damage was more severe, particularlyin the earlier stages of spermatogenesis. Overall, the rapidelimination rate could account for the lack of 1,3-DNB toxicityin very young animals. However, simple metabolic differenceswere less likely to adequately explain the increase in testiculardamage found as animal age increased from 75 to 120 days.