Comparison of the thermogravimetric analysis (TGA) and Franz cell methods to assess dermal diffusion of volatile chemicals

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.