Toxicokinetics of [14C]hexafluoroacetone in the rat

The disposition and metabolism of [14C]hexafluoroacetone (HFA) were studied in the rat as part of an investigation of the mechanism of HFA-induced testicular atrophy. After sc injection of 13 mg/kg [14C]HFA, radioactivity was eliminated in a biphasic manner from the blood; the half-life of the initial phase was 22.6 hr and that of the elimination phase 75.1 hr. Following injection of 130 mg/kg [14C]HFA, the elimination of radioactivity was initially zero order, but with time it became first order and biphasic with half-lives of the initial and terminal elimination phases being 23.0 and 59.9 hr, respectively. The primary route of elimination was via the urine and all of the [14C]HFA was excreted unmetabolized. [14C]HFA was uniformly distributed throughout the major organs of the body with the exception of the liver which contained disproportionately higher levels of [14C]HFA. The hepatic binding of [14C]HFA was noncovalent and capacity limited. Notably, the testes, the target organ of HFA-induced toxicity, did not exhibit any unusual accumulation or retention of [14C]HFA.