title: Absorption and metabolism of triclosan after application to the skin of B6C3F1 mice.
abstract: Triclosan is used as an antimicrobial agent in personal care products, household items, medical devices, and clinical settings. Humans can receive lifelong exposures to triclosan; however, data on the toxicity and carcinogenicity after topical application are lacking. This study determined the absorption, distribution, metabolism, and excretion of triclosan after application to the skin of B6C3F1 mice. [(14)C(U)]triclosan (10 or 100 mg triclosan/kg body weight) was administered topically to mice in two separate experiments: a vehicle selection experiment using propylene glycol, ethanol, and a generic cosmetic cream, and a toxicokinetic experiment. Mice were killed up to 72 h after triclosan administration, and excreta and tissues were analyzed for radioactivity. Ethanol had the best properties of the vehicles evaluated. Maximum absorption was obtained at approximately 12 h after dosing. Radioactivity appeared in the excreta and in all tissues examined, with the highest levels in the gall bladder and the lowest levels in the brain. Triclosan was metabolized to triclosan sulfate, triclosan glucuronide, 2,4-dichlorophenol, and hydroxytriclosan. The metabolite profile was tissue-dependent and the predominant route of excretion was fecal. The AUC(0-∞) and the Cmax of plasma and liver in females were greater than those in males. Slightly lower absorption was observed in mice with Elizabethan collars.
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, 72079, USA.
authors.forename: Jia-Long
authors.initials: JL
authors.lastname: Fang
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, 72079, USA.
authors.forename: Michelle
authors.initials: M
authors.lastname: Vanlandingham
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, 72079, USA.
authors.forename: Gonçalo Gamboa
authors.initials: GG
authors.lastname: da Costa
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicological Research, Food and Drug Administration, Jefferson, Arkansas, 72079, USA.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Beland
mesh_terms: D000327:Adsorption; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D056148:Chromatography, Reverse-Phase; D005243:Feces / Q000737:chemistry; D005260:Female; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D012372:ROC Curve; D012867:Skin / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D014018:Tissue Distribution; D014260:Triclosan / Q000032:analysis / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D014260:Triclosan
keywords: dermal toxicity; excretion; metabolism; tissue distribution; toxicokinetics; triclosan