Assessment of dermal absorption by thermogravimetric analysis: Development of a diffusion model based on Fick's second law.
Recent work in our laboratory shows that it is possible to reproducibly measure the weight change over time of a piece of porcine skin exposed to a chemical vapor by thermogravimetric analysis (TGA), that is, using a microbalance maintained at constant temperature and humidity. Here, we develop a diffusion model by which the TGA skin weight curve can be interpreted. A TGA-specific analytical solution for Fick's second law of diffusion was derived. The solution contains two chemical-dependent parameters; a diffusion coefficient (D) and a skin/air partition coefficient (P). The resulting function was fitted to weight curves from 83 experiments with 4 chemicals; n-butyl acetate, methanol, 2-propanol, and toluene. In most experiments, a single weight function could not adequately describe the shape of the weight curve, therefore up to five parallel compartments, each with its parameter set Di and Pi, were tested. A two-compartment model was adequate for 58% of the experiments according to the Akaike Information Criterion. Dermal penetration of the chemicals was also measured with Franz diffusion cells. The diffusion coefficients obtained by the two methods agreed well.
Rauma
Matias
M
Department of Work Environment Toxicology, Karolinska Institutet, S-171 77 Stockholm, Sweden. matias.rauma@ki.se
Johanson
Gunnar
G
D019840:2-Propanol / Q000737:chemistry / Q000493:pharmacokinetics; D000085:Acetates / Q000737:chemistry / Q000493:pharmacokinetics; D000279:Administration, Cutaneous; D000818:Animals; D000831:Animals, Newborn; D002102:Cadaver; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D006358:Hot Temperature; D000432:Methanol / Q000737:chemistry / Q000493:pharmacokinetics; D008956:Models, Chemical; D009929:Organ Size / Q000187:drug effects; D010539:Permeability; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D012997:Solvents / Q000737:chemistry; D034421:Sus scrofa; D013818:Thermogravimetry / Q000379:methods*; D014050:Toluene / Q000737:chemistry / Q000493:pharmacokinetics; D014835:Volatilization
D000085:Acetates; D012997:Solvents; D014050:Toluene; C006848:butyl acetate; D019840:2-Propanol; D000432:Methanol