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Disposition and pharmacokinetics of a lubricant contaminant, 2,6‐di‐ tert ‐butyl 4‐nitrophenol, in grafted human skin
Author(s) -
Pershing Lynn K.,
Nelson Joel L.,
Corlett Judy L.,
Briggs G. Bruce,
Still Kenneth R.,
Jederberg Warren W.
Publication year - 2006
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.1153
Subject(s) - stratum corneum , human skin , metabolite , chemistry , pharmacokinetics , dermis , toxicokinetics , epidermis (zoology) , chromatography , in vivo , permeation , skin biopsy , pharmacology , biopsy , anatomy , biochemistry , pathology , medicine , biology , genetics , microbiology and biotechnology , membrane
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 µg 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 C max of DBNP in SC was 1663 ± 602 µg cm −3 , and ∼30 and ∼300 fold greater than the C max for E and D, respectively. T max occurred at 1.0, 0.5 and 1.0 in the SC, E and D, respectively. Over a 24 h interval ( AUC 0−24 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. Copyright © 2006 John Wiley & Sons, Ltd.