Principles of skin permeability relevant to chemical exposure.
Guy RH; Hadgraft J
Dermal and ocular toxicology: fundamentals and methods. Hobson DW, ed. Boca Raton, FL: CRC Press, 1991 Jan; :221-246
The biological and physicochemical aspects of dermal penetration after chemical exposure were reviewed. The basic structure of the skin and possible routes of penetration (transcellular, intercellular, appendageal) were discussed. Dermal absorption studies conducted during the past 10 to 15 years have indicated that intercellular transport is the major route of absorption. Physicochemical factors that influence the extent of skin penetration were considered. The degree of skin penetration is inversely proportional to the melting point of the chemical. Chemicals having log octanol/water partition coefficients between 1 and 2 are well absorbed. Slightly soluble materials are not well absorbed. Chemicals that can hydrogen bond diffuse more slowly through the skin than those that cannot. Structure activity relationships involved in the percutaneous absorption of n-alkanols, phenols, phenylboronic acids, steroids, nicotinic acid esters, alkanoic acids, polynuclear aromatic compounds, and nonsteroidal antiinflammatory drugs were discussed. Procedures for calculating the degree of systemic exposure from skin absorption data were reviewed. Using animal models to predict human absorption was discussed. Studies using rats and rabbits or other small animals have usually yielded penetration values that are much higher than those seen in humans. Rhesus-monkeys appear to be the most suitable in-vivo model for predicting human percutaneous absorption. Newer animal models using weanling pigs, micro-pigs or mini-pigs, and human skin grafted rats appear to be viable alternatives to the use of rhesus-monkeys.
NIOSH-Grant; Dermatitis; Skin-absorption; Skin-exposure; In-vivo-studies; Laboratory-animals; Anatomy; Diffusion-analysis; Mathematical-models; Risk-analysis; Chemical-structure; Physical-properties; Chemical-properties
Pharmacy University of California 926 Medical Sciences Building San Francisco, Calif 94143
Dermal and ocular toxicology: fundamentals and methods
University of California San Francisco, San Francisco, California