Organic compounds percutaneous penetration in vivo in man: Relationship to mathematical predictive model

Human skin is a common pathway through which chemicals in our environment enter the body. To aid with risk management of environmental chemicals, the US EPA utilizes mathematical models to estimate percutaneous penetration when experimental data is not available. Here, the accuracy of predicted flux by the Potts and Guy model based on in vitro penetration is compared to human in vivo data of percutaneous absorption of various organic compounds. For most chemicals, the flux was over- or underestimated by a factor 10-100. In vitro flux was significantly correlated to experimental human in vivo flux; however, the physiochemical parameters used in the Potts and Guy equation, Kp, Koctanol, and molecular weight, did not correlate significantly with in vivo flux. We discuss possible explanations for why the computer model did not accurately predict in vivo flux. Further research is needed with different types of chemicals encountered in the environment, and/or as used in clinical practice. This manuscript discusses limitations to the mathematical models currently used, and why the models should be further refined for use.