Eckert Elisabeth, Jäger Thomas, Leibold Edgar, Bader Michael, Göen Thomas, Hiller Julia
Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Bavarian Health and Food Safety Authority, Erlangen, Germany.
Arch Toxicol. 2025 Mar;99(3):1095-1103. doi: 10.1007/s00204-024-03938-5. Epub 2024 Dec 24.
2-Phenoxyethanol (PhE) is an amphiphilic organic compound frequently used as a broad-spectrum preservative in cosmetic products and other consumer goods. PhE is also used as a biocidal component in occupational settings. A previous volunteer study by our working group following oral exposure to PhE showed that PhE is almost completely taken up into the human body followed by an extensive metabolization and fast urinary elimination. However, with respect to the importance of transdermal uptake, we now conducted another volunteer study applying dermal PhE exposure: five volunteers were dermally exposed with 0.4 mg/kg body weight of PhE each on a specified 800 cm skin area using non-occlusive conditions. Subsequently, blood and urine samples were collected up to 48 h post-exposure. The present study illustrates the fast transdermal uptake of PhE. Following systemic resorption, PhE was extensively metabolized and rapidly eliminated in urine mainly in form of the metabolites PhAA (phenoxyacetic acid) and 4-OH-PhAA (4-hydroxyphenoxyacetic acid) accounting together for over 99% of the renally excreted PhE dose. The absolute urinary recovery rate of PhE was observed to be significantly lower following dermal exposure compared to oral uptake indicating a dermal resorption rate of PhE of about 45% in humans. The present study provides for the first time detailed insights into human biotransformation and toxicokinetics of PhE after dermal exposure, thus establishing a reliable strategy for human biomonitoring of PhE. The here presented results may thus be useful for further toxicokinetic modeling and forward dosimetry.
2-苯氧乙醇（PhE）是一种两亲性有机化合物，常用于化妆品和其他消费品中作为广谱防腐剂。PhE也被用作职业环境中的杀生物成分。我们工作组之前的一项志愿者研究表明，口服PhE后，PhE几乎完全被人体吸收，随后进行广泛代谢并快速经尿液排出。然而，考虑到经皮吸收的重要性，我们现在进行了另一项志愿者研究，对皮肤进行PhE暴露：五名志愿者在特定的800平方厘米皮肤区域，在非封闭条件下，每人以0.4毫克/千克体重的剂量进行皮肤PhE暴露。随后，在暴露后48小时内采集血液和尿液样本。本研究表明PhE经皮吸收迅速。经全身吸收后，PhE被广泛代谢，并主要以代谢产物苯氧乙酸（PhAA）和4-羟基苯氧乙酸（4-OH-PhAA）的形式迅速经尿液排出，这两种代谢产物占经肾脏排泄的PhE剂量的99%以上。与口服吸收相比，皮肤暴露后PhE的绝对尿回收率显著降低，表明人体中PhE的皮肤吸收率约为45%。本研究首次详细深入地了解了皮肤暴露后PhE在人体中的生物转化和毒代动力学，从而建立了一种可靠的PhE人体生物监测策略。因此，这里呈现的结果可能有助于进一步的毒代动力学建模和前瞻性剂量测定。
