2-Phenoxyethanol (PhE) is an amphiphilic organic compound, that is used as a broad-spectrum preservative in cosmetic products as well as in other consumer goods, e.g., in disinfectant solutions, vaccine solutions or baby wipes. Its use is limited to a maximum concentration of 1% in cosmetic products in the European Union as stated by Regulation (EC) No. 1223/2009. According to the main areas of PhE application, it may be assumed that the general population is mainly exposed to PhE by the dermal exposure route. Furthermore, PhE has known applications in occupational settings, as it is also used as a biocidal component in metal working fluids for example (ECHA 2024; Hartwig and MAK Commission 2019). Apart from inhalative exposure to PhE at the workplace, dermal penetration of PhE may also play a substantial role in these settings (van Wendel de Joode et al. 2005). In several studies, the significance of dermal PhE absorption was already shown: In in vitro experiments using rat and human skin, mean dermal absorption rates of 64% and 85%, respectively, were observed (reviewed by SCCS 2016). Up to now, however, only one human volunteer study with dermal PhE exposure was described (albeit not sufficiently well): Howes (1988) collected urine samples from four hospitalized patients treated with various amounts of a topical ointment containing 1.2% of PhE (corresponding absolute PhE doses of 240–960 mg). In the urine samples, phenoxyacetic acid (PhAA), as main metabolite of PhE, was solely detected. Recovery in urine showed a high degree of variation and ranged from 8.5% to 42.1% of the applied dose up to 72 h post-exposure (Howes 1988).

As dermal exposure is assumed to be the most relevant route of PhE exposure for humans, SCCS (2016) selected a dermal study in rabbits (most sensitive species to PhE) as a key study for toxicological risk assessment with the critical toxicological effect identified as haematotoxicity, that was observed to be less pronounced in rats and mice. Based on an NOAEL (no observed adverse effect level) of 357 mg/kg body weight (bw) and day, the SCCS derived a health-based guidance value for humans of 14.28 mg/kg bw and day for dermal exposure to PhE.

Due to its widespread use and the potentially high exposure of consumers, PhE was selected as a chemical of interest in a collaboration project for the advancement of human biomonitoring between the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) and the German Chemical Industry Association (VCI) (Kolossa-Gehring et al. 2017). The basic goal of this project is to enable exposure assessment of the general population for substances of potential concern, e.g., due to their toxicity or their relevance for consumer exposure, by establishing reliable human biomonitoring methods and to investigate the biotransformation pathways including the main toxicokinetic parameters of the substances of interest. Thus, novel biomonitoring methods for the determination of PhE and its metabolites in human blood and urine were recently developed by our working group (Jäger et al. 2022, 2024). These procedures enable the determination of PhE in blood and urine as well as the quantification of three PhE metabolites in humans, namely PhAA, 4-hydroxyphenoxyacetic acid (4-OH-PhAA) and 4-hydroxyphenoxyethanol (4-OH-PhE). A former volunteer study conducted by our working group confirmed the suitability of the selected analytes as biomarkers of exposure for PhE: Following oral exposure to PhE with a single dose of 5 mg/kg bw to five volunteers, an average urinary excretion rate of 89.0 ± 11.8% up to 48 h post-exposure was observed, with PhAA and 4-OH-PhAA as the main renally excreted metabolites (Eckert et al. 2024). The almost complete recovery of the applied PhE dose in urine following oral exposure indicates that all relevant human metabolites of PhE have been considered. However, as the main exposure route for humans is assumed to be the dermal route, we now conducted another volunteer study applying dermal exposure to PhE using realistic conditions. In the present study, five volunteers were dermally exposed to PhE (non-occlusively) using a basic ointment containing PhE. The aim of the study was the investigation of PhE metabolism and toxicokinetics in humans following dermal exposure and, in particular, the assessment of the human dermal penetration rate of PhE.