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j. Soc. Cosmet. Chem., 46, 117-127 (March/April 1995) In vitro skin absorption and metabolism of Padimate-O and a nitrosamine formed in Padimate-O-containing cosmetic products G. E. KENNEY,• A. SAKR, J. L. LICHTIN, H. CHOU, and R. L. BRONAUGH 2, Hill Top Research, Miamiville, OH 45147 (G. E. K, ), College of Pharmacy, University of Cincinnati, Cincinnati, OH 45221 (A.S., J.L.L.), and Food and Drug Administration, Laurel, MD 20708 (H.C., R.L.B.). Received August 5, 1994, Synopsis 2-Ethylhexyl p-(N,N-dimethylamino) benzoic acid (Padimate-O) has been a popular sunscreen agent. In 1988 it was reported by the U.S. Food and Drug Administration to sometimes contain a nitrosamine contaminant, 2oethylhexyl p-(N-methyl-N-nitrosamino) benzoic acid (NMPABAO). The nitrosamine was initially reported to be mutagenic in the Ames test, but this finding was not confirmed by others. The in vitro percutaneous absorption and metabolism of NMPABAO and Padimate-O were determined in hairless guinea pig and human skin. The viability of excised skin was maintained for 24 h in flow-through diffusion cells. The percutaneous absorption of Padimate-O was almost fourfold greater from a volatile vehicle (ethanol) than from a lotion vehicle. Substantial amounts of the absorbed compound were hydrolyzed by esterase enzymes in skin. The percentages of the applied dose of NMPABAO absorbed (lotion vehicle) were 5.2 (hairless guinea pig) and 2.3 (human skin). About 26% (hairless guinea pig) and 85% (human) of the NMPABAO absorbed into the receptor fluid were hydrolyzed to p-(N-methyl-N-nitrosamino) benzoic acid (NMPABA). In some experiments, NMPABAO applied to hairless guinea pig skin was immediately irradiated with UVA and UVB light from a solar simulator. The amount of NMPABAO absorbed was reduced 17-fold as a result of the instability of the nitrosamine in UV light. However, UV instability generally cannot be considered a safety factor because many sunscreen users apply these products on a regular basis regardless of whether exposure to the sun is expected. INTRODUCTION 2-Ethylhexyl p-(N,N-dimethylamino) benzoic acid (Padimate-O), a tertiary amine de- rivative ofp-aminobenzoic acid (PABA), is a UV-absorbing chemical used in cosmetics • Results submitted as partial fulfillment of requirements for the M.S. degree in Cosmetic Science, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45221. 2 Reprint requests should be addressed to R. L. Bronaugh, Food and Drug Administration, HFS-128, Office of Cosmetics and Colors, 8301 Muirkirk Road, Laurel, MD 20708. 117