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j. Soc. Cosmet. Chem., 35, 95-102 (March/April 1984) Permeability and reactivity of skin as related to aoe FRANCIS N. MARZULLI, National Academy of Sciences, Washington, DC, and HOWARD I. MAIBACH, University of California Received November 14, 1983. Presented at the IFSCC/SCC Joint Conj•rence on Skin, San Francisco, September 1983. Synopsis This report reviews the literature on skin permeability in humans, from infancy to old age. The site of the major barrier function, the stratum corneum, is identified. Its physiologic function is described differences in chemical and physical properties that may affect penetration pathways are reviewed as well as complexities of the problem and limitations in available information. Finally, the world's literature on the subject is examined with the tentative conclusion that the skin's capacity for penetration, with minor variations, remains relatively constant throughout life. The main physical and physiological changes occur immediately prior to birth, during the formation of horny barrier structure which then remains essentially constant during its process of shedding the outer layers and renewing itself from below. Future studies, conducted with different chemicals than those reported, and on different sites, may make modifications in these general conclusions. INTRODUCTION Claude Bernard, renowned physiologist and experimentalist of the 19th century, ex- pressed the view that "the condition of life is the constancy of the internal milieu." Many organs including skin are directed toward maintaining the constancy of the internal milieu. Skin appears to perform its contribution to this important function unencumbered by energy requirements, and with remarkable consistency. Physiological and biochemical changes occur in humans from infancy, through youth, adolescence, maturity, and old age. As the individual ages, there is at first a decrease in metabolic rate, accompanied by an increase in endogenous processing enzymes, as the body encounters new substances in the environment. On approaching maturity there is an increase in physical performance and finally a decline with increasing age. The permeability of skin, in contradistinction to other of life's processes, appears more tied to a relatively consistent physical function rather than to changing physiological or biochemical events. The major barrier to skin penetration resides in the stratum corneum (1-2), a tissue that, once formed, may remain relatively constant thereafter, despite the fact that it is involved in a continuous process of shedding and renewal. In the normal individual, shedding and renewal are in balance, and the barrier capacity, 95