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Percutaneous absorption is highly variable between chemicals but also within chemicals depending on exposure conditions and experimental set up. We tested a larger number of organic solvents with the same experimental set up, using skin from new-born piglets and static diffusion cells. Thirty-six common organic solvents were studied neat (and 31 of them also in water dilution): acetone, acetonitrile, n-butanol 2-butanone 2-butoxyethanol, 1-butoxy-2-propanol, n-butyl acetate, butyl acrylate, cyclohexane, cyclohexanone, 1,2-dichloroethane, dichloromethane, ethanol, 2-ethoxyethanol, ethyl acetate, ethyl acrylate, ethylbenzene, furfuryl alcohol, n-hexane, 2-hexanone, 2-isopropoxyethanol, methanol, 1-methoxy-2-propanol, methyl acrylate, 3-methyl-1-butanol, methyl tertiary butyl ether, 4-metyl-2-pentanol, methyl methacrylate, 2-propanol, 2-propen-1-ol, 2-propoxyethanol, 1-propoxy-2-propanol, styrene, trichloromethane, toluene and m-xylene. In addition, a mixture of 2-methylbutyl acetate and n-pentyl acetate was tested. For most of the solvents, little or no percutaneous absorption data have been published. Lag times, steady-state fluxes and apparent permeability coefficients were obtained from the time courses of solvent appearance in the receptor medium, as measured by gas chromatography. The use of the same methodology and kind of skin resulted in small variability within experiments, underlining the need for consistent methodology for useful results for developing predictive models. Furthermore, a comparison of the neat and diluted data shows that water dilution affects all these variables and that the direction and magnitude of the effects vary between chemicals. This comparison strongly supports that prediction of percutaneous absorption of neat and water diluted chemicals requires different models. [ABSTRACT FROM AUTHOR]

Abstract: The focus of this review is on the systemic absorption of vapours via skin, including experimental data as well as regression and pharmacokinetic models. Dermal contribution ratios (DCR), i.e. amount absorbed through skin relative to total intake (skin and inhalation) at specified conditions, could be identified or calculated from published data for 33 chemical vapours. The ratios vary from ~0.0002 (vinyl chloride) to ~0.8 (2-butoxyethanol), with hydrophilic chemicals having a higher ratio than lipophilic ones. Multiple regression analysis of these data suggests that the DCR is largely explained by the octanol:water partition coefficient, vapour pressure and molecular weight (R2 =0.69). Several physiologically-based pharmacokinetic models were identified; however, all describe the absorption of single substances. Regarding predictive models, only two models were found. In conclusion, dermal uptake of chemical vapours needs more attention, as such exposures are common, data are scarce and few predictive models exist. [Copyright &y& Elsevier]

Abstract: Potential health hazards of dermal exposure, variability in reported dermal absorption rates and potential losses from the skin by evaporation indicate a need for a simple, inexpensive and standardized procedure to measure dermal absorption and desorption of chemical substances. The aim of this study was to explore the possibility to measure dermal absorption and desorption of volatile chemicals using a new gravimetric technique, namely thermal gravimetric analysis (TGA), and trypsinated stratum corneum from pig. Changes in skin weight were readily detected before, during and after exposure to vapours of water, 2-propanol, methanol and toluene. The shape and height of the weight curves differed between the four chemicals, reflecting differences in diffusivity and partial pressure and skin:air partitioning, respectively. As the skin weight is highly sensitive to the partial pressure of volatile chemicals, including water, this technique requires carefully controlled conditions with respect to air flow, temperature, chemical vapour generation and humidity. This new technique may help in the assessment of dermal uptake of volatile chemicals. Only a small piece of skin is needed and skin integrity is not necessary, facilitating the use of human samples. The high resolution weight–time curves obtained may also help to elucidate the characteristics of absorption, desorption and diffusion of chemicals in skin. [Copyright &y& Elsevier]