Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model

Marie Frederiksen, Heather M Stapleton, Katrin Vorkamp, Thomas F Webster, Niels Martin Jensen, Jens Ahm Sørensen, Flemming Nielsen, Lisbeth E Knudsen, Lars S Sørensen, Per Axel Clausen, Jesper B Nielsen

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Resumé

Organophosphate esters (OPEs) are used as flame retardants, plasticizers, and as hydraulic fluids. They are present in indoor environments in high concentrations compared with other flame retardants, and human exposure is ubiquitous. In this study we provide data for estimating dermal uptake for eight OPEs and ranking in OPEs risk assessment. Dermal uptake and percutaneous penetration of the OPEs were studied in a Franz diffusion cell system using human skin dosed with a mixture of OPEs in an ethanol:toluene (4:1) solution. Large variation in penetration profiles was observed between the OPEs. The chlorinated OPEs tris(2-chloroisopropyl) phosphate (TCIPP), and in particular tris(2-chloroethyl) phosphate (TCEP), penetrated the skin quite rapidly while tris(1,3-dichlor-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) tended to build up in the skin tissue and only smaller amounts permeated through the skin. For tris(isobutyl) phosphate (TIBP), tris(n-butyl) phosphate (TNBP), and tris(methylphenyl) phosphate (TMPP) the mass balance was not stable over time indicating possible degradation during the experimental period of 72 h. The rates at which OPEs permeated through the skin decreased in the order TCEP > TCIPP ≥ TBOEP > TIBP ≥ TNBP > TDCIPP > TPHP > TMPP. Generally, the permeation coefficient, kp, decreased with increasing log Kow, whereas lag time and skin deposition increased with log Kow. The present data indicate that dermal uptake is a non-negligible human exposure pathway for the majority of the studied OPEs.

OriginalsprogEngelsk
TidsskriftChemosphere
Vol/bind197
Sider (fra-til)185-192
ISSN0045-6535
DOI
StatusUdgivet - apr. 2018

Fingeraftryk

organophosphate
ester
skin
penetration
phosphate
toluene
ranking
ethanol
mass balance
risk assessment
hydraulics
degradation
fluid

Citer dette

Frederiksen, Marie ; Stapleton, Heather M ; Vorkamp, Katrin ; Webster, Thomas F ; Jensen, Niels Martin ; Sørensen, Jens Ahm ; Nielsen, Flemming ; Knudsen, Lisbeth E ; Sørensen, Lars S ; Clausen, Per Axel ; Nielsen, Jesper B. / Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model. I: Chemosphere. 2018 ; Bind 197. s. 185-192.
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title = "Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model",
abstract = "Organophosphate esters (OPEs) are used as flame retardants, plasticizers, and as hydraulic fluids. They are present in indoor environments in high concentrations compared with other flame retardants, and human exposure is ubiquitous. In this study we provide data for estimating dermal uptake for eight OPEs and ranking in OPEs risk assessment. Dermal uptake and percutaneous penetration of the OPEs were studied in a Franz diffusion cell system using human skin dosed with a mixture of OPEs in an ethanol:toluene (4:1) solution. Large variation in penetration profiles was observed between the OPEs. The chlorinated OPEs tris(2-chloroisopropyl) phosphate (TCIPP), and in particular tris(2-chloroethyl) phosphate (TCEP), penetrated the skin quite rapidly while tris(1,3-dichlor-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) tended to build up in the skin tissue and only smaller amounts permeated through the skin. For tris(isobutyl) phosphate (TIBP), tris(n-butyl) phosphate (TNBP), and tris(methylphenyl) phosphate (TMPP) the mass balance was not stable over time indicating possible degradation during the experimental period of 72 h. The rates at which OPEs permeated through the skin decreased in the order TCEP > TCIPP ≥ TBOEP > TIBP ≥ TNBP > TDCIPP > TPHP > TMPP. Generally, the permeation coefficient, kp, decreased with increasing log Kow, whereas lag time and skin deposition increased with log Kow. The present data indicate that dermal uptake is a non-negligible human exposure pathway for the majority of the studied OPEs.",
keywords = "Journal Article, Plasticizers, OPE, Human exposure, Flame retardants, OPFR, PFR, Environmental Monitoring, Skin/metabolism, Humans, Middle Aged, Esters/metabolism, Plasticizers/metabolism, Skin Absorption/physiology, Organophosphates/metabolism, Phosphines/metabolism, Flame Retardants/metabolism, Halogenation, Adult, Female, Organophosphorus Compounds/metabolism",
author = "Marie Frederiksen and Stapleton, {Heather M} and Katrin Vorkamp and Webster, {Thomas F} and Jensen, {Niels Martin} and S{\o}rensen, {Jens Ahm} and Flemming Nielsen and Knudsen, {Lisbeth E} and S{\o}rensen, {Lars S} and Clausen, {Per Axel} and Nielsen, {Jesper B}",
note = "Copyright {\circledC} 2018 Elsevier Ltd. All rights reserved.",
year = "2018",
month = "4",
doi = "10.1016/j.chemosphere.2018.01.032",
language = "English",
volume = "197",
pages = "185--192",
journal = "Chemosphere",
issn = "0045-6535",
publisher = "Pergamon Press",

}

Frederiksen, M, Stapleton, HM, Vorkamp, K, Webster, TF, Jensen, NM, Sørensen, JA, Nielsen, F, Knudsen, LE, Sørensen, LS, Clausen, PA & Nielsen, JB 2018, 'Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model', Chemosphere, bind 197, s. 185-192. https://doi.org/10.1016/j.chemosphere.2018.01.032

Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model. / Frederiksen, Marie; Stapleton, Heather M; Vorkamp, Katrin; Webster, Thomas F; Jensen, Niels Martin; Sørensen, Jens Ahm; Nielsen, Flemming; Knudsen, Lisbeth E; Sørensen, Lars S; Clausen, Per Axel; Nielsen, Jesper B.

I: Chemosphere, Bind 197, 04.2018, s. 185-192.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Dermal uptake and percutaneous penetration of organophosphate esters in a human skin ex vivo model

AU - Frederiksen, Marie

AU - Stapleton, Heather M

AU - Vorkamp, Katrin

AU - Webster, Thomas F

AU - Jensen, Niels Martin

AU - Sørensen, Jens Ahm

AU - Nielsen, Flemming

AU - Knudsen, Lisbeth E

AU - Sørensen, Lars S

AU - Clausen, Per Axel

AU - Nielsen, Jesper B

N1 - Copyright © 2018 Elsevier Ltd. All rights reserved.

PY - 2018/4

Y1 - 2018/4

N2 - Organophosphate esters (OPEs) are used as flame retardants, plasticizers, and as hydraulic fluids. They are present in indoor environments in high concentrations compared with other flame retardants, and human exposure is ubiquitous. In this study we provide data for estimating dermal uptake for eight OPEs and ranking in OPEs risk assessment. Dermal uptake and percutaneous penetration of the OPEs were studied in a Franz diffusion cell system using human skin dosed with a mixture of OPEs in an ethanol:toluene (4:1) solution. Large variation in penetration profiles was observed between the OPEs. The chlorinated OPEs tris(2-chloroisopropyl) phosphate (TCIPP), and in particular tris(2-chloroethyl) phosphate (TCEP), penetrated the skin quite rapidly while tris(1,3-dichlor-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) tended to build up in the skin tissue and only smaller amounts permeated through the skin. For tris(isobutyl) phosphate (TIBP), tris(n-butyl) phosphate (TNBP), and tris(methylphenyl) phosphate (TMPP) the mass balance was not stable over time indicating possible degradation during the experimental period of 72 h. The rates at which OPEs permeated through the skin decreased in the order TCEP > TCIPP ≥ TBOEP > TIBP ≥ TNBP > TDCIPP > TPHP > TMPP. Generally, the permeation coefficient, kp, decreased with increasing log Kow, whereas lag time and skin deposition increased with log Kow. The present data indicate that dermal uptake is a non-negligible human exposure pathway for the majority of the studied OPEs.

AB - Organophosphate esters (OPEs) are used as flame retardants, plasticizers, and as hydraulic fluids. They are present in indoor environments in high concentrations compared with other flame retardants, and human exposure is ubiquitous. In this study we provide data for estimating dermal uptake for eight OPEs and ranking in OPEs risk assessment. Dermal uptake and percutaneous penetration of the OPEs were studied in a Franz diffusion cell system using human skin dosed with a mixture of OPEs in an ethanol:toluene (4:1) solution. Large variation in penetration profiles was observed between the OPEs. The chlorinated OPEs tris(2-chloroisopropyl) phosphate (TCIPP), and in particular tris(2-chloroethyl) phosphate (TCEP), penetrated the skin quite rapidly while tris(1,3-dichlor-2-propyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP) tended to build up in the skin tissue and only smaller amounts permeated through the skin. For tris(isobutyl) phosphate (TIBP), tris(n-butyl) phosphate (TNBP), and tris(methylphenyl) phosphate (TMPP) the mass balance was not stable over time indicating possible degradation during the experimental period of 72 h. The rates at which OPEs permeated through the skin decreased in the order TCEP > TCIPP ≥ TBOEP > TIBP ≥ TNBP > TDCIPP > TPHP > TMPP. Generally, the permeation coefficient, kp, decreased with increasing log Kow, whereas lag time and skin deposition increased with log Kow. The present data indicate that dermal uptake is a non-negligible human exposure pathway for the majority of the studied OPEs.

KW - Journal Article

KW - Plasticizers

KW - OPE

KW - Human exposure

KW - Flame retardants

KW - OPFR

KW - PFR

KW - Environmental Monitoring

KW - Skin/metabolism

KW - Humans

KW - Middle Aged

KW - Esters/metabolism

KW - Plasticizers/metabolism

KW - Skin Absorption/physiology

KW - Organophosphates/metabolism

KW - Phosphines/metabolism

KW - Flame Retardants/metabolism

KW - Halogenation

KW - Adult

KW - Female

KW - Organophosphorus Compounds/metabolism

U2 - 10.1016/j.chemosphere.2018.01.032

DO - 10.1016/j.chemosphere.2018.01.032

M3 - Journal article

VL - 197

SP - 185

EP - 192

JO - Chemosphere

JF - Chemosphere

SN - 0045-6535

ER -