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.

摘要

1. 乙二醇 2-乙基己基醚 (EGEHE) 是一种用于各种应用的溶剂。

2. 我们报告了在大鼠和小鼠体内以及体外大鼠肝细胞中单次灌胃或皮肤给药 50、150 或 500 mg/kg [ ^{14 C]EGEHE 后 EGEHE 的分布和代谢。}

3. EGEHE 在大鼠肝细胞中迅速清除（半衰期约 4 分钟），没有性别差异。

4. EGEHE 分别在口服（大鼠：80-96%，小鼠：91-95%）和皮肤应用（大鼠：25-37%，小鼠：22-24%）后被良好和中度吸收，并在体内迅速排泄尿。

5. [ ¹⁴ C]EGEHE 衍生的放射性分布到组织（口服：2.3-7.2%，皮肤：0.7-2.2%），肝脏和肾脏在这两个物种中含量最高。

6. EGEHE 被广泛代谢，尿液中几乎没有检测到母体。未检测到之前已显示可介导其他短链乙二醇醚毒性的烷氧基乙酸代谢物。

7. EGEHE 的分布和代谢没有明显的剂量、物种​​或性别差异，除了与大鼠 (<2%) 相比，小鼠 (19-20%) 呼出的挥发性化合物更多。

8. 这些研究解决了科学文献中的一个关键空白，并提供了数据，这些数据将为未来旨在评估 EGEHE 毒性的研究提供信息。