Relative absorption and dermal loading of chemical substances: Consequences for risk assessment

Quantification of skin absorption is an essential step in reducing the uncertainty of dermal risk assessment. Data from literature indicate that the relative dermal absorption of substances is dependent on dermal loading. Therefore, an internal exposure calculated with absorption data determined at a dermal loading not comparable to the actual loading may lead to a wrong assessment of the actual health risk. To investigate the relationship between dermal loading and relative absorption in a quantitative manner, 138 dermal publicly available absorption experiments with 98 substances were evaluated (87 in vitro, 51 in vivo; molecular weight between 40 and 950, log P between −5 and 13), with dermal loading ranging mostly between 0.001 and 10 mg/cm2. In 87 experiments (63%) an inverse relationship was observed between relative dermal absorption and dermal loading, with an average decrease of factor 33 ± 69. Known skin irritating and volatile substances less frequently showed an inverse relationship between dermal loading and relative absorption.