In vitro studies—how good are they at replacing in vivo studies for measurement of skin absorption?

Abstract

Measures of percutaneous penetration are required for risk assessment of exposure of man to chemicals. In vitro approaches and QSAR predictions can be used and reduce the use of in vivo animal experiments. The OECD Guidelines on in vitro dermal absorption studies were recently accepted but progress was hampered by a lack of direct in vitro/in vivo comparisons in humans or in rodents. Either flow through diffusion or static cell systems with full thickness, dermatomed skin or membranes can be used. In a study of the robustness of in vitro techniques, inter-skin variability was greater than inter-laboratory or between cell variability. Recent studies with a number of chemicals have shown a reasonably good prediction but the difference between in vitro and in vivo results was greater for lipophilic molecules as lipophilic molecules which were retained in the stratum corneum. The experimental flux obtained in vitro using conditions that reflect the potential occupational exposure may be the most appropriate figure for risk assessment purposes. A database of in vitro and in vivo dermal penetration has been established. Dermal absorption data using infinite doses has been combined in a number of databases used for predictive QSAR modelling approaches to dermal absorption. However, absorption values derived from QSAR may over estimate the actual absorption from a finite dose.