title: In Silico Estimation of Skin Concentration Following the Dermal Exposure to Chemicals.
abstract: OBJECTIVE
  To develop an in silico method based on Fick's law of diffusion to estimate the skin concentration following dermal exposure to chemicals with a wide range of lipophilicity.
  
  
  METHODS
  Permeation experiments of various chemicals were performed through rat and porcine skin. Permeation parameters, namely, permeability coefficient and partition coefficient, were obtained by the fitting of data to two-layered and one-layered diffusion models for whole and stripped skin. The mean skin concentration of chemicals during steady-state permeation was calculated using the permeation parameters and compared with the observed values.
  
  
  RESULTS
  All permeation profiles could be described by the diffusion models. The estimated skin concentrations of chemicals using permeation parameters were close to the observed levels and most data fell within the 95% confidence interval for complete prediction. The permeability coefficient and partition coefficient for stripped skin were almost constant, being independent of the permeant's lipophilicity.
  
  
  CONCLUSIONS
  Skin concentration following dermal exposure to various chemicals can be accurately estimated based on Fick's law of diffusion. This method should become a useful tool to assess the efficacy of topically applied drugs and cosmetic ingredients, as well as the risk of chemicals likely to cause skin disorders and diseases.
authors.affiliation: Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan. tmmhtnk@tokai-u.jp.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Hatanaka
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Wesam R
authors.initials: WR
authors.lastname: Kadhum
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Todo
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan. sugib@josai.ac.jp.
authors.forename: Kenji
authors.initials: K
authors.lastname: Sugibayashi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003198:Computer Simulation; D004058:Diffusion; D005260:Female; D008297:Male; D008954:Models, Biological; D009930:Organic Chemicals / Q000493:pharmacokinetics*; D010539:Permeability; D051381:Rats; D054772:Rats, Hairless; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013552:Swine
chemical_list: D009930:Organic Chemicals
keywords: Fick’s law of diffusion; dermal exposure; in silico; skin concentration; skin permeation