Structure - penetration relationships in percutaneous absorption.
Departments of Pharmacy and Pharmaceutical Chemistry, Schools of Pharmacy and Medicine, University of California, San Francisco, California, 1987 Dec; :1-19
An attempt was made to predict the kinetics and extent of percutaneous penetration of the skin by a chemical in-vivo from the physicochemical and pharmacokinetic properties of the chemical in question. If this is possible, then one should be able to determine the risk of toxicity arising from dermal exposure to pesticide formulations. Penetration data were gathered for a series of barbiturates, nicotinates, phenols, steroids, and a selection of other compounds. For these experiments excised skin and artificial membranes were used. Particular attention was given to the utility of various organic aqueous partition coefficients as rank order indicators of transdermal flux and on the predictability of the different model systems investigated. In most cases membrane permeability increased with increasing organic aqueous partition coefficients. The researchers conclude that for a structurally related series of chemicals, measurement of a simple lipid water partition coefficient and selected permeabilities through a model membrane composed of the lipid can accurately predict rank order transport rates across the skin. This approach should allow one to select a chemical which demonstrates high potency for its proposed utilization as a pesticide but presents a low risk with respect to worker toxicity resulting from dermal exposure.
NIOSH-Grant; Dermatitis; Skin-exposure; Agricultural-chemicals; Chemical-structure; Skin-absorption; In-vitro-studies
Pharmacy University of California 926 Medical Sciences Building San Francisco, Calif 94143
Final Grant Report
NTIS Accession No.
Departments of Pharmacy and Pharmaceutical Chemistry, Schools of Pharmacy and Medicine, University of California, San Francisco, California
University of California San Francisco, San Francisco, California