Disposition, pharmacokinetics, and metabolism of a dermal dose of [14C]2,5-hexanedione in hens.

A dermal dose of 50 mg/kg (7.5 microCi/kg) of [14C]2,5-hexanedione (2,5-HD) was applied on a protected area on the backs of hens. Five groups of three hens were killed after 4, 8, 24, 36, and 48 hr. 2,5-HD disappeared monoexponentially from the application site with a half-life of 6 hr. After 48 hr, 35% of the radioactivity was expired as volatile material, largely as 2,5-HD. The combined urinary fecal excreta accounted for 15% of the eliminated radioactivity, while the 14CO2 accounted for 11.9% of the radioactive dose. The highest concentration of 14C was detected in the bile. Among tissues analyzed, liver and kidney contained the highest concentrations of radioactivity, whereas the brain, spinal cord, and peripheral nerves showed smaller concentrations. The half-lives for the elimination of 14C were longest for muscle (71 hr) and shortest for adipose tissue (12 hr), while the remaining tissues showed half-lives ranging from 20 to 30 hr. Radioactivity in the plasma reached a peak at 4 hr. Most of this radioactivity was identified as 5-hydroxy-2-hexanone followed by 2,5-HD and 2,5-dimethylfuran; these chemicals then disappeared biexponentially with terminal half-lives of 7.6 hr, 12.6 hr, and 28.6 hr, respectively. 2,5-HD was the most accounted chemical found in the liver, lung, and kidney, while 5-hydroxy-2-hexanone was found to be most abundant in the combined urinary-fecal excreta.