title: The influence of water mixtures on the dermal absorption of glycol ethers.
abstract: Glycol ethers are solvents widely used alone and as mixtures in industrial and household products. Some glycol ethers have been shown to have a range of toxic effects in humans following absorption and metabolism to their aldehyde and acid metabolites. This study assessed the influence of water mixtures on the dermal absorption of butoxyethanol and ethoxyethanol in vitro through human skin. Butoxyethanol penetrated human skin up to sixfold more rapidly from aqueous solution (50%, 450 mg/ml) than from the neat solvent. Similarly penetration of ethoxyethanol was increased threefold in the presence of water (50%, 697 mg/ml). There was a corresponding increase in apparent permeability coefficient as the glycol ether concentration in water decreased. The maximum penetration rate of water also increased in the presence of both glycol ethers. Absorption through a synthetic membrane obeyed Fick's Law and absorption through rat skin showed a similar profile to human skin but with a lesser effect. The mechanisms for this phenomenon involves disruption of the stratum corneum lipid bilayer by desiccation by neat glycol ether micelles, hydration with water mixtures and the physicochemical properties of the glycol ether-water mixtures. Full elucidation of the profile of absorption of glycol ethers from mixtures is required for risk assessment of dermal exposure. This work supports the view that risk assessments for dermal contact scenarios should ideally be based on absorption data obtained for the relevant formulation or mixture and exposure scenario and that absorption derived from permeability coefficients may be inappropriate for water-miscible solvents.
authors.affiliation: Toxicology Unit, Institute for Research on Environment and Sustainability and Medical School, University of Newcastle upon Tyne, Newcastle NE1 7RU, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Traynor
authors.forename: Simon C
authors.initials: SC
authors.lastname: Wilkinson
authors.forename: Faith M
authors.initials: FM
authors.lastname: Williams
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D015194:Diffusion Chambers, Culture; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000493:pharmacokinetics; D005026:Ethylene Glycols / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008823:Micelles; D051381:Rats; D012869:Skin Absorption / Q000187:drug effects*; D012997:Solvents; D014867:Water / Q000494:pharmacology*
chemical_list: D004987:Ethers; D005026:Ethylene Glycols; D008823:Micelles; D012997:Solvents; D014867:Water; C017096:n-butoxyethanol; C021296:2-ethoxyethanol