The Metabolism of 2-Ethylhexanol in Rats

Abstract

1. 2-Ethylhexanol was efficiently absorbed following oral administration to rats. ¹⁴C associated with 2-ethyl[1-¹⁴C]hexanol was rapidly excreted in respiratory CO₂ (6-7%), faeces (8-9%) and urine (80-82%), with essentially complete elimination by 28 h after administration.

2. The amount of label recovered in ¹⁴CO₂ matched the amount of unlabelled 2-heptanone plus 4-heptanone recovered from urine, suggesting that both types of metabolite may have been derived form the major urinary metabolite, 2-ethyl-hexanoic acid, by decarboxylation following partial β-oxidation. The ¹⁴CO₂ appeared not to be derived from acetate (urinary acetic acid and liver and brain cholesterol were not labelled) or by reductive decarboxylation (heptane was not present.)

3. Other identified metabolites were 2-ethyl-5-hydroxyhexanoic acid, 2-ethyl-5-ketohexanoic acid, and 2-ethyl-1,6-hexanedioic acid. Only about 3% of the ethylhexanol was excreted unchanged.

4. Ethylhexanol was a competitive inhibitor of yeast alcohol dehydrogenase, but a good substrate for horse alcohol dehydrogenase.

5. Other relationships between metabolism and toxicity of 2-ethylhexanol are discussed.