Search

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: Recent work in our laboratory shows that it is possible to measure the minute weight changes of skin during exposure to chemical vapor using the thermogravimetric analysis (TGA) method. Further, the TGA weight curves can be analyzed with a two-compartment diffusion model, yielding two sets of diffusion and skin:air partition coefficients. In this study, the dermal diffusion of six chemical vapors (n-butanol, cyclohexanone, ethyl benzene, n-hexane, styrene and m-xylene) were studied by the TGA method using neonatal pig skin. The penetration of the six substances was also studied using conventional Franz diffusion cells and neat, liquid chemical. A combined analysis of the data, along with previously published data on four additional substances (n-butyl acetate, methanol, 2-propanol and toluene) suggest a good agreement between the TGA and the Franz cell methods with respect to diffusion coefficients. An interesting observation is that correction of the TGA-derived diffusion coefficients by the octanol:water partition coefficient improves the agreement with the Franz cell-derived coefficients. TGA-data for seven of the substances were further compared with dermal diffusion studies on chemical vapor reported by other investigators. The comparisons show good agreement with respect to permeability as well as skin:air partition coefficients. In conclusion, it appears that good estimates of diffusion coefficients as well as skin:air and permeability coefficients can be derived for volatile chemicals with the TGA technique. [Copyright &y& Elsevier]