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In Silico Estimation of Skin Concentration Following the Dermal Exposure to Chemicals

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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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The authors declare that there are no conflicts of interest.

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Correspondence to Kenji Sugibayashi.

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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

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