title: Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP).
abstract: Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) is assumed to have low dermal absorption; however, previous in vitro skin permeation studies have shown large permeation differences. Our aims were to determine DEHP permeation parameters and assess extent of skin DEHP metabolism among workers highly exposed to these lipophilic, low volatile substances. Surgically removed skin from patients undergoing abdominoplasty was immediately dermatomed (800 μm) and mounted on flow-through diffusion cells (1.77 cm(2)) operating at 32°C with cell culture media (aqueous solution) as the reservoir liquid. The cells were dosed either with neat DEHP or emulsified in aqueous solution (166 μg/ml). Samples were analysed by HPLC-MS/MS. DEHP permeated human viable skin only as the metabolite MEHP (100%) after 8h of exposure. Human skin was able to further oxidize MEHP to 5-oxo-MEHP. Neat DEHP applied to the skin hardly permeated skin while the aqueous solution readily permeated skin measured in both cases as concentration of MEHP in the receptor liquid. DEHP pass through human skin, detected as MEHP only when emulsified in aqueous solution, and to a far lesser degree when applied neat to the skin. Using results from older in vitro skin permeation studies with non-viable skin may underestimate skin exposures. Our results are in overall agreement with newer phthalate skin permeation studies.
authors.affiliation: IST, Institute for Work and Health, Universities of Lausanne and Geneva, Lausanne-Epalinges, Switzerland. Electronic address: Nancy.Hopf@hospvd.ch.
authors.forename: N B
authors.initials: NB
authors.lastname: Hopf
authors.forename: A
authors.initials: A
authors.lastname: Berthet
authors.forename: D
authors.initials: D
authors.lastname: Vernez
authors.forename: E
authors.initials: E
authors.lastname: Langard
authors.forename: P
authors.initials: P
authors.lastname: Spring
authors.forename: R
authors.initials: R
authors.lastname: Gaudin
mesh_terms: D004051:Diethylhexyl Phthalate / Q000378:metabolism*; D006801:Humans; D010539:Permeability; D012867:Skin / Q000378:metabolism*
chemical_list: D004051:Diethylhexyl Phthalate
keywords: 117-81-7; 2cx-MMHP; 5OH-MEHP; 5cx-MEPP; 5oxo-MEHP; BSA; CV; DAD; DBP; DEHP; Di(2-ethylhexyl) phthalate; DiDP; DiNP; EFSA; EPA; ESI; EU; European Food Safety Authority; European Union; GHS; HGP; HMWP; HPLC; High-molecular-weight phthalates; Human; J; Kp; MBP; MEHP; OECD; Organisation for Economic Co-operation and Development; Percutaneous permeation; SC; Skin; TDI; TEWL; Tolerable Daily Intake; US Environmental Protection Agency; a high-performance liquid chromatograph; bovine serum albumin; coefficients of variation; dermally absorbed dose; di-butyl phthalate; diethyl hexyl phthalate; diisodecyl phthalate; diisononyl phthalate; electrospray interface; globally harmonized system of classification and labelling of chemicals; hairless guinea pig; lag time; mono(2-(carboxymethyl)hexyl) phthalate; mono-(2-ethyl-5-carboxypentyl) phthalate; mono-(2-ethyl-5-hydroxyhexyl) phthalate; mono-(2-ethyl-5-oxohexyl) phthalate; mono-(2-ethylhexyl) phthalate; mono-butyl phthalate; permeation coefficient; permeation rate; stratum corneum; trans epidermal water loss; τ