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.

Explaining skin permeation of 2-butoxyethanol from neat and aqueous solutions

“…Finally, flux from neat BE is substantially smaller (Region III) than from the 50% solutions and similar to that from the 10% BE solution. Similar observations have also been reported for other glycol ethers (Dugard et al, 1984;Traynor et al, 2007a;Venier et al, 2004;Wilkinson and Williams, 2002). It is important to note that the flux numbers presented in Fig.…”

Influence of water dilution on percutaneous absorption of N-vinyl-2-pyrrolidone in vivo and ex vivo in rats and ex vivo in humans

“…In both species, the absorption flux obtained with 50 % nVP was twofold higher than with neat nVP. This was expected as results published by Traynor et al (2007) for human skin exposed in vitro to neat or aqueous mixtures of 2-be revealed percutaneous absorption of 2-be to be fivefold higher for a 50 % solution compared to neat 2-be (2.26 and 0.39 mg/ cm 2 /h, respectively; 200 µl/cm 2 applied). When the solution was applied at 20 µl/cm 2 , there was still a fourfold difference (0.19 ± 0.03 and 0.04 ± 0.01 mg/cm 2 /h, respectively).…”

“…similarly, for many other amphiphilic compounds, skin permeation was enhanced for aqueous solutions compared to neat compounds. For example, the absorption fluxes for ethoxyethanol (Traynor et al 2007), diethylene glycol (mono) butyl ether acetate (Venier et al 2004) andisopropanol (korinth et al 2012) were found to be between threeand more than tenfold higher for diluted solutions compared to their neat counterparts. For Frasch et al (2014), this phenomenon of neat absorption rates being less than absorption rates for dilute solutions is caused by dehydratation of skin, which is related to the specific concentration dependence of the thermodynamic activity of water for the compound in water.…”

Enhanced Skin Absorption and Fly Toxicity of Permethrin in Emulsion Formulation

“…These results parallel the poor mammalian skin absorption characteristics of permethrin in a dry formulation (Minugel 200), and high absorption in emulsion formulation. Traynor et al (2007) showed that butoxyethanol penetrated excised human skin up to six fold more rapidly from aqueous solution (50%) than from the neat solvent. Likewise, ethoxyethanol penetration increased threefold in the presence of water (50%).…”