Percutaneous penetration and dermal metabolism of triclosan (2,4,4′-trichloro-2′-hydroxydiphenyl ether)

triclosan is widely used in many products that contact the skin of consumers. This study compares in vivo and in vitro skin absorption of triclosan and determines the potential of skin to metobolize it prior to entering the blood stream. After in vivo topical application of a 64.5 mM alcoholic solution of [H-3]triclosan to rat skin, 12% radioactivity was recovered in the faeces, 8% in the carcass 1% in the urine, 30% in the stratum corneum and 26% was rinsed from the skin surface at 24 hours after application. Free triclosan and the glucuronide and sulfate conjugates of triclosan mere found in urine and faeces, triclosan penetrated rat skin more rapidly and extensively than human skin in vitro. 23% of the dose had penetrated completely through rat skin into the receptor fluid by 24 hours, whereas penetration through human skin tvas only 6.3% of the dose. Chromatographic analysis of the receptor solutions showed that triclosan was metabolized to the glucuronide, and to a lesser extent to the sulfate, during passage through the skin, triclosan glucuronide appeared rapidly in the receptor fluid whereas triclosan sulfate remained in the skin, Although the major site of metabolism was the li,er, conjugation of triclosan in skin was also demonstrated in vitro and in vivo, particularly to the glucuronide conjugate which was more readily removed from the skin. The in vitro system provides a reasonable estimate of dermal absorption in rho for the rat. Therefore by extrapolation of the comparative in vitro data for human and rat skin it is reasonable to deduct that dermal absorption in human of triclosan applied at the same dose is about one-third of that in the rat in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved.