Evaluation of in-vivo animal and in-vitro models for prediction of dermal absorption in man.
Risk assessment of dermal exposure to chemicals requires percutaneous absorption data to link the external exposure to the systemic uptake. The most reliable data on percutaneous absorption are obtained from in-vivo human volunteer studies. In addition to ethical constrains, the conduct of these studies is not feasible for the large number of industrial chemicals in use today. Therefore, there is an increasing need for alternative methods to determine percutaneous absorption such as in-vitro assays and methods performed in vivo in experimental animals. In this article, recent comparative in-vitro and in-vivo studies on percutaneous absorption have been addressed with emphasis on the factors that may affect the predictive value of the in-vitro models. Furthermore, the use of animal models, in particular the rat skin, in prediction of percutaneous absorption in the human skin has been reviewed. In-vitro assays showed to be largely influenced by the experimental circumstances, such as type and thickness of the skin, receptor fluid, and the way in which percutaneous absorption is calculated. Rat skin showed consistently to be more permeable than human skin. However, the difference between human and rat skin does not show a consistent pattern between chemicals hampering prediction of human percutaneous absorption. To increase predictive value of in-vitro and animal models, the influence of experimental factors on the percutaneous absorption should be systematically investigated by comparison with human in-vivo data, resulting in more prescriptive guidelines.
Jakasa
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Academic Medical Center, Coronel Institute of Occupational Health, University of Amsterdam, Amsterdam, The Netherlands.
Kezic
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S
D000279:Administration, Cutaneous; D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D023421:Models, Animal; D011237:Predictive Value of Tests; D018570:Risk Assessment / Q000379:methods*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism; D012869:Skin Absorption / Q000187:drug effects*; D015262:Xenobiotics / Q000008:administration & dosage / Q000633:toxicity*
D015262:Xenobiotics