Skin permeation and metabolism of di(2-ethylhexyl) phthalate (DEHP)

•DEHP is extensively metabolized in vitro in human viable skin.•DEHP pass readily through human skin when emulsified in aqueous solution.•Percutaneous permeation of DEHP should be considered in risk assessments. Phthalates are suspected to be endocrine disruptors. Di(2-ethylhexyl) phthalate (DEHP) i...

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Vydáno v:	Toxicology letters Ročník 224; číslo 1; s. 47 - 53
Hlavní autoři:	Hopf, N.B., Berthet, A., Vernez, D., Langard, E., Spring, P., Gaudin, R.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Netherlands Elsevier Ireland Ltd 03.01.2014
Témata:	117-81-7 DEHP Di(2-ethylhexyl) phthalate Diethylhexyl Phthalate - metabolism Human Humans Percutaneous permeation Permeability Skin Skin - metabolism 117-81-7 τ MEHP Kp DiNP J EFSA SC 5cx-MEPP BSA DiDP DBP GHS OECD DEHP TDI 5OH-MEHP ESI MBP 5oxo-MEHP HPLC Human TEWL DAD 2cx-MMHP Percutaneous permeation EU HGP Di(2-ethylhexyl) phthalate CV EPA Skin HMWP permeation coefficient permeation rate a high-performance liquid chromatograph stratum corneum mono-(2-ethylhexyl) phthalate diisononyl phthalate High-molecular-weight phthalates European Food Safety Authority diethyl hexyl phthalate mono-(2-ethyl-5-hydroxyhexyl) phthalate mono-(2-ethyl-5-carboxypentyl) phthalate mono(2-(carboxymethyl)hexyl) phthalate mono-butyl phthalate bovine serum albumin US Environmental Protection Agency Tolerable Daily Intake trans epidermal water loss diisodecyl phthalate coefficients of variation globally harmonized system of classification and labelling of chemicals di-butyl phthalate mono-(2-ethyl-5-oxohexyl) phthalate dermally absorbed dose lag time hairless guinea pig European Union electrospray interface Organisation for Economic Co-operation and Development
ISSN:	0378-4274, 1879-3169, 1879-3169
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Shrnutí:	•DEHP is extensively metabolized in vitro in human viable skin.•DEHP pass readily through human skin when emulsified in aqueous solution.•Percutaneous permeation of DEHP should be considered in risk assessments. 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 (800μm) and mounted on flow-through diffusion cells (1.77cm2) 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 (166μg/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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0378-4274 1879-3169 1879-3169
DOI:	10.1016/j.toxlet.2013.10.004