Abstract
Purpose
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.
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Abbreviations
- \( {\overline{C}}_{ss} \) :
-
Mean concentration in stripped skin during steady-state permeation
- \( {\overline{C}}_{ws} \) :
-
Mean concentration in whole skin during steady-state permeation
- K sc :
-
Stratum corneum/donor vehicle partition coefficient
- K ss :
-
Stripped skin/donor vehicle partition coefficient
- P ss :
-
Permeability coefficient through stripped skin
- P ws :
-
Permeability coefficient through whole skin
- AMP:
-
Aminopyrine
- ANP:
-
Antipyrine
- BA:
-
Benzoic acid
- BP:
-
Butyl p-hydroxybenzoate
- B-PABA:
-
Butyl 4-aminobenzoate
- CAF:
-
Caffeine
- ClogP :
-
Calculated LogP
- Dopa:
-
Dopamine hydrochloride
- EP:
-
Ethyl p-hydroxybenzoate
- E-PABA:
-
Ethyl 4-aminobenzoate
- Epi:
-
Epinephrine hydrochloride
- LC:
-
Lidocaine hydrochloride
- LogP :
-
Logarithm of n-octanol/water partition coefficient
- MP:
-
Methyl p-hydroxybenzoate
- M-PABA:
-
Methyl 4-aminobenzoate
- PP:
-
Propyl p-hydroxybenzoate
- P-PABA:
-
Propyl 4-aminobenzoate
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Hatanaka, T., Yoshida, S., Kadhum, W.R. et al. In Silico Estimation of Skin Concentration Following the Dermal Exposure to Chemicals. Pharm Res 32, 3965–3974 (2015). https://doi.org/10.1007/s11095-015-1756-5
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DOI: https://doi.org/10.1007/s11095-015-1756-5