Disposition of radioactivity in Fischer 344 rats after single and multipleinhalation exposure to [C-14]octamethylcyclotetrasiloxane ([C-14]D-4)

The retention, distribution, metabolism, and excretion of [C-14]octamethylc yclotetrasiloxane (D-4) were studied in Fischer 344 rats after single and m ultiple exposures to 7, 70, or 700 ppm [C-14]D-4. Subset groups were establ ished for body burden, distribution, and elimination. Retention of inhaled D-4 was relatively low (5-6% of inhaled D-4). Radioactivity derived from [C -14]D-4 inhalation was widely distributed to tissues of the rat. Maximum co ncentrations of radioactivity in plasma and tissues (except fat) occurred a t the end of exposure and up to 3 h postexposure. Maximum concentrations of radioactivity in fat occurred as late as 24 h postexposure. Fat was a depo t, elimination of radioactivity from this tissue was much slower than from plasma and other tissues. With minor exceptions, there were no consistent g ender effects on the distribution of radioactivity and the concentrations o f radioactivity were nearly proportional to exposure concentration over the exposure range. Excretion of radioactivity was via exhaled breath and urin e, and, to a much lesser extent, feces. Urinary metabolites included dimeth ylsilanediol and methylsilanetriol plus five minor metabolites. Relative ab undance of these metabolites was the same from every test group. Eliminatio n was rapid during the first 24 h after exposure and was slower thereafter (measured up to 168 h postexposure). In singly-exposed female (but not male ) rats, small dose-dependent shifts in elimination pathways were seen. Afte r multiple exposures, the elimination pathways were dose- and gender-indepe ndent. These data define possible pathways for metabolism of D-4 and allow estimation of the persistence of D-4 and/or its metabolites in rats.