Abstract |
The metabolic fate and disposition of 2- Ethylhexanoic acid (EHA) was determined in female Fischer-344 rats exposed by oral, dermal and intravenous routes. After oral administration of 100 mg/kg, a mean peak blood level (85.1 ug equivalents EHA/g) was detected at 15 to 30 minutes; after dermal exposure to 100 mg/kg, a mean peak blood level (8.5 ug equivalents EHA/g) was attained at 5.7 hours. Bioavailability of 14C after dermal application was 60 to 70% of that from i.v. administration. Terminal half-lives of 14C were 117, 98, and 251 hours for i.v., oral, and dermal administration, respectively. The major excretory route for all groups was via urine, with small amounts eliminated in feces. The major urinary metabolites of EHA were the glucuronic acid conjugate of EHA, 2-ethylhexanedioic acid, isomers of hydroxy- 2-ethylhexanoic acid, and 2 isomeric metabolites believed to be lactones. Parent compound found in urine was about 1.5 to 6.7% of the dose. Two female rats dermally exposed for 96 hours to 1 g/kg of undiluted EHA under occlusion had seriously damaged epidermal tissues within 24 hours. In a 2-week oral test with rats in which 5/sex were dosed with 0, 200, 800, or 1600 mg/kg/day by gavage in corn oil, decreased body weight was noted in mid-dosemales, and mortality in the high-dose group. A similar test with mice was proposed, but not yet conducted. Two-week dietary administration of 0, 0.75, 1.5, or 3.0% EHA to rats (5/sex/group) led to no deaths, dose-related decreased body weight and food consumption, and hepatocyte hypertrophy in mid- and high-dose groups. Identical tests with mice led to reduced body weight and food consumption in the mid- and high-dose groups, along with lesions of the liver, thymus, and spleen. |