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Laboratory (In Vitro) Test Method for Determining the Disposition of Chemicals in Contact with the Skin
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A wide variety of chemicals come in contact with the skin, either intentionally in the case of drugs to treat topical or systemic disease, or unintentionally as a result of occupational or environmental exposures. Animal (in vivo) models, notably the rat, have traditionally been used to determine the extent of skin absorption. However, significant progress has been made to develop in vitro models using excised skin that reduce or eliminate animal use, offer greater experimental control, and provide more information at lower cost. We wish to report on the progress made with one such model that simultaneously measured both evaporation and skin penetration. The test system employed conditions to maintain skin viability and to control temperature and air flow over the skin. Using radiolabeled compounds spanning a wide range of physical properties, comparative in vitro/in vivo studies with skin from four different species confirmed that when properly conducted, in vitro skin penetration values accurately reflected those obtained in vivo. While skin penetration values are useful for risk assessments for environmental hazards or efficacy of topical drugs, the evaporative process is important to measure, as it affects skin penetration or may, in the case of insect repellents, be responsible for efficacy. In conclusion, in vitro studies have proven valuable for evaluating the skin disposition of formulated products, for which skin absorption and disposition data are seldom available.
in vitro, skin, percutaneous absorption, evaporation, pesticides
Reifenrath, William G.
Stratacor, Inc., Richmond, CA