Influence of the exposed anatomic sites on the human in vivo percutaneous absorption of the amphiphilic 2-phenoxyethanol

Percutaneous penetration is an important human exposure route, but it is influenced by multiple factors and can vary greatly between different substances and exposure conditions. Furthermore, skin characteristics such as thickness of different anatomic sites may have an effect on percutaneous absorption. Despite a potential relevance for safety measures, little is yet known for occupationally relevant skin sites, like hands. We conducted a human in vivo study aiming to identify the effect of anatomic sites on percutaneous absorption of 2-phenoxyethanol. Two human volunteers were dermally exposed to 2-phenoxyethanol (loading dose: 0.2 mg/cm² skin) at seven different anatomic skin sites with areas of 200 and 400 cm², respectively. Blood and urine samples were collected and analyzed for 2-phenoxyethanol and its two main metabolites up to 48 h post-exposure. Relative absorption ratios showed moderate site differences ranging from 0.89 to 1.64 (compared to the forearm) as the overall renal recovery was between 23 and 43% of applied 2-phenoxyethanol. Inter-individual variability was in a similar range. A notable influence of the exposed site could, however, be observed for the penetration speed which was highest at the forehead and neck, and slowest at the hand palms. Differing ratios of unmetabolized 2-phenoxyethanol and its main metabolite found in blood point to a site-depending intradermal metabolism. This study revealed major findings concerning the velocity of percutaneous penetration at different skin sites, which is relevant for adequate skin protection. The obtained data broaden the knowledge about site-related variations in percutaneous absorption and thus can improve future toxicological evaluations.