Disposition, pharmacokinetics, and metabolism of a dermal dose of [14C]2,5-hexanedione in hens.
Abstract
A study was made of the disposition, metabolism, distribution, and excretion of 2,5-hexanedione (110134) (2,5-HD) in the adult chicken. A dose of 50mg/kg of carbon-14 (C-14) labeled 2,5-HD was applied to a protected area of the backs of 15 laying hens (Gallus-gallus); the birds were sacrificed at 4, 8, 24, 36, or 48 hours after application. A half life of 6 hours was noted for the disappearance of 2,5-HD from the application site. After 48 hours about 35 percent of the total dose was excreted as volatile organic chemicals, primarily as 2,5-HD. Fifteen percent of the radioactivity was excreted in urine and feces and and 11.9 percent as carbon-dioxide. The bile contained the highest dose of C-14. Liver and kidney contained the highest radioactivity. Smaller concentrations were found in the brain, spinal cord, and peripheral nervous system. The muscle showed the longest half life, 71 hours, for the elimination of C-14 and the shortest half life was observed in the adipose tissue, 12 hours. Half lives of 20 to 30 hours were measured for most of the other tissues. Plasma radioactivity reached a peak at 4 hours, mostly as 5-hydroxy-2-hexanone (56745610) followed by 2,5-HD and 2,5-dimethylfuran (625865). The most abundant chemical in the liver, lung, and kidney was 2,5-HD. The most abundant chemical in the combined excreta was 5-hydroxy-2- hexanone. The study demonstrated the ready absorption of 2,5-HD from the skin and distribution to other parts of the body.
