Metabolism of 2-ethylhexanoic acid administered orally or dermally to the female Fischer 344 rat.
1. Excretion balance studies were conducted with 2-ethylhexanoic acid (EHA) in the female Fischer 344 rat following single high (1 g/kg) or low (0.1 g/kg) oral doses of [2-14C-hexyl]EHA, following repeated oral dosing with unlabelled EHA and a final [14C]EHA oral dose at the low dose level, following dermal exposure with a high (1 g/kg) and low (0.1 g/kg) applied dose of [14C]EHA, and following a 1 mg/kg i.v. dose of [14C]EHA. 2. Oral, i.v. and dermal doses were eliminated rapidly, predominantly in the urine during the first 24 h following dosing. 3. After oral dosing of 0.1 g/kg, the mean peak blood level was 85.1 micrograms equivalents EHA/g. Maximum blood concentrations were detected at either 15 or 30 min in individual animals. After dermal application of 0.1 g/kg, the mean peak blood level of 7.9 micrograms equivalents EHA/g was attained at 8 h. 4. Occlusive dermal exposure caused damage to the epidermis in the first 24 h after application and resulted in dermal absorption of 70% relative to i.v. dosing, based on the ratio of percent dose in excreta. 5. Dermal application followed by prompt washing of the skin resulted in recovery of 101.9% from the skin surface and < 0.2% in the excreta. 6. The major urinary metabolites were the glucuronide of EHA, 2-ethyl-1,6-hexanedioic acid (namely 2-ethyladipic acid), 2-ethyl-5-hydroxyhexanoic acid, 2-ethyl-6-hydroxyhexanoic acid and ethylketohexanoic acid. Evidence for metabolism via beta-oxidation was also found, consistent with the incorporation of EHA into normal cellular intermediary metabolism.
English
J C
JC
Health and Environment Laboratories, Eastman Kodak Company, Rochester, NY 14652-6272, USA.
Deisinger
P J
PJ
Guest
D
D
D000042:Absorption; D000279:Administration, Cutaneous; D000284:Administration, Oral; D000818:Animals; D002208:Caproates / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics / Q000652:urine; D005260:Female; D007275:Injections, Intravenous; D051381:Rats; D011916:Rats, Inbred F344; D012867:Skin / Q000187:drug effects / Q000378:metabolism
D002208:Caproates; C040668:2-ethylhexanoic acid