Species Differences in the Disposition and Metabolism of 2,4,6-Trinitrotoluene as a Function of Route of Administration

The disposition and metabolism of 2,4,6-trinitrotoluene (TNT) was studied in rats, mice, rabbits, and dogs following oral, dermal or intratracheal administration of single doses of 14C-ring labeled compound. The objective was to determine possible species and sex differences as a function of route of administration as a rationale for the design of chronic studies. TNT was absorbed in all species by all routes of administration with the most extensive absorption occurring after intratracheal instillation. Dermal absorption was the highest in rabbits followed by mice, rats, and dogs. Species differences in the rate of oral absorption could not be accurately assessed. Excretion was primarily in urine and to a lesser extent in feces. Extensive biliary excretion was also noted. Blood and tissue levels in females were generally higher than in males. TNT was extensively metabolized in all species; radioactivity excreted in urine primarily as the glucuronide conjugates. Most metabolites were reduction products inclding the 2- and 4-hydroxylamine and 2- and 4-monoaminodinitro and 2,6- and 4,6-diaminomononitro derivatives. Trace quantities of TNT, trinitrobenzyl alcohol and trinitrobenzoic acid were detected occasionally.