METABOLISM AND TESTICULAR TOXICITY OF 1,3-DINITROBENZENE IN RATS OF DIFFERENT AGES

Susceptibility to 1,3-dinitrobenzene (1,3-DNB)-induced testicular dama ge is known to increase with age. The present study investigated the p ossibility that age-dependent differences in metabolism and dispositio n could account far differences in toxicity. [C-14]1,3-DNB (25 mg/kg, ip) was administered to Sprague-Dawley rats which were 31, 75, or 120 days of age. Levels of 1,3-DNB and 1,3-DNB metabolites were determined in blood and urine. As animal age increased, peak blood concentration s of 1,3-DNB were lower and declined more slowly indicating an age-dep endent decrease in rate of metabolism and a possible increase in volum e of distribution. In younger animals, faster elimination rates were a ssociated with higher brood levels of metabolites. Urinary metabolites were generally similar for all age groups with the exception of the d iacetamidobenzene metabolite which was significantly lower in the urin e of 31 day old rats. There were clear differences in the toxicokineti c profile for 1,3-DNB between the 31 day old rats and the other two ag e groups. However, differences between the 75 and 120 day old animals were less marked. Testicular damage induced by 1,3-DNB (25 mg/kg, ip) was hardly detectable in the youngest animals, while the intermediate age group showed a moderate region particularly in later stages of spe rmatogenesis. For the oldest animals, testicular damage was more sever e, particularly in the earlier stages of spermatogenesis. Overall, the rapid elimination rate could account for the lack of 1,3-DNB toxicity in very young animals. However, simple metabolic differences were les s likely to adequately explain the increase in testicular damage found as animal age increased from 75 to 120 days. (C) 1994 Society of Toxi cology.