Disposition and pharmacokinetics of inhaled dimethylamine in the Fischer 344 rat.

The disposition and pharmacokinetics of [14C]dimethylamine [( 14C] DMA) following 6-hr inhalation of either 10 or 175 ppm were determined in male Fischer 344 rats. Seventy-two hours after termination of exposure, the disposition of recovered radioactivity was similar for each airborne concentration, with more than 90% in the urine and feces, 7 to 8% in selected tissues and the carcass, and 1.5% exhaled as 14CO2. Over 98% of the radioactivity in the urine was unmetabolized DMA. Analysis of tissue radioactivity immediately after exposure to [14C]DMA showed that the respiratory nasal mucosa contained the highest concentration of 14C, followed by the olfactory nasal mucosa; concentrations of 14C in liver, lung, kidney, brain, and testes were approximately 2 orders of magnitude less than in the nasal mucosal tissues. Radioactivity in plasma of rats exposed by inhalation to 175 ppm of [14C]DMA decayed in a biphasic manner. The terminal half-life for plasma radioactivity was similar to the half-lives of some plasma proteins, suggesting incorporation of 14C into proteins subsequent to metabolism of [14C]DMA. The results indicate that, while most of the inhaled DMA is excreted unchanged, a small amount of oxidative metabolism of DMA occurs.