title: Disposition and pharmacokinetics of a lubricant contaminant, 2,6-di-tert-butyl 4-nitrophenol, in grafted human skin.
abstract: Disposition and uptake/elimination profiles of topical 2,6-di-t-butyl, 4-nitrophenol (DBNP), the nitrated metabolite of an antioxidant additive of lubricant and hydraulic fluids was quantified in human skin grafted on athymic mice after a single topical 75 microg dose in corn oil. DBNP was quantified throughout the stratum corneum (SC), epidermis (E) and dermis (D) in punch biopsies collected from treated skin 0.5, 1, 2, 4, 8 and 24 h after application. SC samples were harvested from the treated skin with 20 adhesive discs. E and D were generated from the biopsy using a manual sectioning method. Detectable DBNP concentrations were measured in all skin compartments at all time points investigated. The Cmax of DBNP in SC was 1663 +/- 602 microg cm(-3), and approximately 30 and approximately 300 fold greater than the Cmax for E and D, respectively. Tmax occurred at 1.0, 0.5 and 1.0 in the SC, E and D, respectively. Over a 24 h interval (AUC0-24 h) there was 52 and 520 fold more DBNP in the SC than E and D, respectively. The elimination half-life of DBNP was 11 h from the SC and 9 h from both E and D. Thus, DBNP was quickly absorbed into the outermost layer of skin and established a steep concentration profile through human skin. The data are consistent with the vast majority of DBNP remaining on the surface (77%) or within human skin (15%) in vivo with only 0.2% of the DBNP dose quantified in the systemic blood circulation.
authors.affiliation: Department of Dermatology, University of Utah, Salt Lake City, UT 84132, USA. Lynn.Pershing@hsc.utah.edu
authors.forename: Lynn K
authors.initials: LK
authors.lastname: Pershing
authors.forename: Joel L
authors.initials: JL
authors.lastname: Nelson
authors.forename: Judy L
authors.initials: JL
authors.lastname: Corlett
authors.forename: G Bruce
authors.initials: GB
authors.lastname: Briggs
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Still
authors.forename: Warren W
authors.initials: WW
authors.lastname: Jederberg
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009596:Nitrophenols / Q000493:pharmacokinetics* / Q000633:toxicity; D018570:Risk Assessment; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D016038:Skin Transplantation; D013366:Submarine Medicine; D014183:Transplantation, Heterologous
chemical_list: C480798:2,6-di-tert-butyl-4-nitrophenol; D000393:Air Pollutants; D009596:Nitrophenols