Metabolism of 2-ethylhexanol administered orally and dermally to the female Fischer 344 rat

Abstract

1. Excretion balance studies were conducted with 2-ethylhexanol (2-EH) in female Fischer 344 rats following single high (500 mg/kg) and low (50 mg/kg) oral doses of [¹⁴C]2-EH, following repeated oral dosing with unlabelled 2-EH at the low level, following dermal exposure for 6 h with a 1 g/kg applied dose of [¹⁴C]2-EH, and following a 1 mg/kg i.v. dose of [¹⁴C]2-EH.

2. The high, low and repeated low oral dose studies with 2-EH showed similar excretion balance profiles of [¹⁴C], with some evidence of metabolic saturation at the high dose.

3. No evidence of metabolic induction was seen following the repeated low oral dosing.

4. All of the oral doses were eliminated rapidly, predominantly in the urine during the first 24 h following dosing.

5. The dermal dosing resulted in only about 5% absorption of the 1 g/kg dose, with the major portion of the dose recovered unabsorbed from the dermal exposure cell at 6h.

6. Urinary metabolites eliminated following the oral and dermal doses were predominately glucuronides of oxidized metabolites of 2-EH, including glucuronides of 2-ethyladipic acid, 2-ethylhexanoic acid, 5-hydroxy-2-ethylhexanoic acid and 6-hydroxy-2-ethylhexanoic acid.