METABOLISM AND TESTICULAR TOXICITY OF 1,3-DINITROBENZENE IN THE RAT -EFFECT OF ROUTE OF ADMINISTRATION

Studies investigating the testicular toxicity of 1,3-dinitrobenzene (1 ,3-DNB) have utilized both the oral (po) and intraperitoneal (ip) rout es of administration. These two administration routes could be expecte d to produce different pharmacokinetic profiles and, potentially, diff erent degrees of toxicity. In the present work, the effect of route of administration upon 1,3-DNB disposition and susceptibility to testicu lar damage has been investigated. Male Sprague-Dawley rats were given 25 mg/kg 1,3-DNB either ip or po. Metabolites were quantitated in bloo d, urine, and feces, and methemoglobin levels were determined. Peak bl ood levels of 1,3-DNB and its major metabolite were three times higher in ip-dosed rats than in po-dosed rats. While the lower blood levels seen after po administration were maintained for greater than 6 hr, bl ood levels fell rapidly after ip dosing, reaching po levels at 6 hr po stadministration. Peak methemoglobin levels in ip-dosed animals were t wice that of po-dosed animals. Route of administration had a minor eff ect on the levels of urinary metabolites, while there was a significan tly higher excretion of metabolites in the feces of po-dosed animals. Despite the markedly higher 1,3-DNB blood levels after ip administrati on, there were only subtle differences in testicular damage. The data raise the possibility that above a threshold level of 1,3-DNB in the b lood, only the duration of testicular exposure to the toxicant may gov ern susceptibility to testicular toxicity. (C) 1995 Society of Toxicol ogy