Disposition and metabolism of ethylene glycol 2-ethylhexyl ether in Sprague Dawley rats, B6C3F1/N mice, and in vitro in rat hepatocytes

Abstract

1. Ethylene glycol 2-ethylhexyl ether (EGEHE) is a solvent used in a variety of applications.

2. We report disposition and metabolism of EGEHE following a single gavage or dermal administration of 50, 150 or 500 mg/kg [¹⁴C]EGEHE in rats and mice and in vitro in rat hepatocytes.

3. EGEHE was cleared rapidly in rat hepatocytes (half-life ∼4 min) with no sex difference.

4. EGEHE was well- and moderately absorbed following oral administration (rats: 80–96%, mice: 91–95%) and dermal application (rats: 25–37%, mice: 22–24%), respectively, and rapidly excreted in urine.

5. [¹⁴C]EGEHE-derived radioactivity was distributed to tissues (oral: 2.3–7.2%, dermal: 0.7–2.2%) with liver and kidney containing the highest levels in both species.

6. EGEHE was extensively metabolised with little to no parent detected in urine. The alkoxyacetic acid metabolite, which has previously been shown to mediate toxicities of other shorter-chain ethylene glycol ethers, was not detected.

7. There were no apparent dose, species or sex differences in disposition and metabolism of EGEHE, except that the exhaled volatile compounds were greater in mice (19–20%) compared with rats (<2%).

8. These studies address a critical gap in the scientific literature and provide data that will inform future studies designed to evaluate toxicity of EGEHE.

Keywords:

• Ethylene glycol 2-ethylhexyl ether
• EGEHE
• absorption
• distribution
• metabolism
• excretion
• glycol ether
• alkoxyacetic acid

Acknowledgements

The authors are grateful to Drs Esra Mutlu and Kelly Shipkowski for their review of this manuscript.

Disclosure statement

The authors have no real or perceived conflicts of interest to disclose.

Additional information

Funding

This work was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences, Intramural Research project ZIA ES103316-04, and performed for the National Toxicology Program, National Institute of Environmental Health Sciences, National Institutes of Health, U.S. Department of Health and Human Services, under contract HHSN291200775562 (LBERI, Albuquerque, NM).