Comparison of in vivo and in vitro experimental models to predict percutaneous penetration of chemicals
A. Capt*, O. Blanck, R. Bars
Bayercropscience Research Center, Sophia Antipolis, France
Percutaneous penetration is a critical factor in risk assessments for agricultural workers exposed to agrochemicals via the skin. Currently available animal models tend to over-estimate percutaneous absorption in humans and therefore it is crucial to develop more predictive models in order to refine human risk assessments.
The dermal penetration potential of three insecticides: malathion, lindane and cypermethrin, and two reference compounds: testosterone and benzoic acid (representing a range of logPs from 2.4 to 6.6) were compared using human in vitro, rat in vivo, rat in vitro, and a new in vivo mouse (HuSki) model for which penetration is measured through human skin grafted onto nude mice. The skin penetration data obtained from these models were compared to each other and to human in vivo absorption data published in the literature.
Our results indicate that the HuSki mouse model provides a more accurate prediction of human skin absorption than any of the other in vivo or in vitro alternatives which all tended to overestimate human absorption. In particular, the HuSki mouse model allows a precise investigation of the fate of the substances which tend to accumulate within the skin compartment. As such, this innovative model should be a useful tool for predicting the human skin absorption of agrochemicals and for improving the quality of worker risk assessments.
Content last modified: 21 May 2005
