Abstract
Generally, the blood and skin concentration profiles and steady-state skin concentration of topically applied or exposed chemicals can be calculated from the in vitro skin permeation profile. However, these calculation methods are particularly applicable to chemicals for which the main pathway is via the stratum corneum. If the contribution of hair follicles to the total skin permeation of chemicals can be obtained in detail, their blood and skin concentrations can be more precisely predicted. In the present study, the contribution of the hair follicle pathway to the skin permeation of topically applied or exposed chemicals was calculated from the difference between their permeability coefficients through skin with and without hair follicle plugging, using an in vitro skin permeation experiment. The obtained results reveal that the contribution of the hair follicle pathway can be predicted by using the chemicals’ lipophilicity. For hydrophilic chemicals (logarithm of n-octanol/water partition coefficient (log Ko/w) < 0), a greater reduction of permeation due to hair follicle plugging was observed than for lipophilic chemicals (log Ko/w ≥ 0). In addition, the ratio of this reduction was decreased with an increase in log Ko/w. This consideration of the hair follicle pathway would be helpful to investigate the efficacy and safety of chemicals after topical application or exposure to them because skin permeation and disposition should vary among skins in different body sites due to differences in the density of hair follicles.
Highlights
The body is exposed to many chemical compounds in daily life
Reductions of the p value of around 50% were observed observed for fluorescein isothiocyanate-dextran 4 kDa (FD-4), calcein sodium salt (Ca-Na), Fluorescein sodium salt (FL-Na), ionized Lidocaine hydrochloride (LC), ionized AMP and isosorbide mononitrate (ISMN), whereas no or only slight for FD-4, Ca-Na, FL-Na, ionized LC, ionized AMP and ISMN, whereas no or only slight reductions reductions in p value were observed for non-ionized Butyl paraben (BP), non-ionized IP and non(less than 20%) in p value were observed for non-ionized BP, non-ionized IP and non-ionized LC
Permeation of FD-4 or FL-Na was observed through three-dimensional cultured human skin models no permeation of FD-4 or FL-Na was observed through three-dimensional cultured human skin models in our study [8]
Summary
The body is exposed to many chemical compounds in daily life. These chemicals are mainly absorbed via oral, pulmonary and dermal routes, as well as through other mucosa. The dermal pathway is more accessed by chemicals than the other pathways because skin is the outermost tissue covering the whole body and has a large surface area [1]. The skin is focused on as the site of application of drugs and cosmetics. The pathway for the permeation of therapeutic and cosmeceutical chemicals through the skin is very important to evaluate their effects. In the case of either skin application or skin exposure, skin permeation and the concentration of chemicals in skin should be investigated to evaluate their effects and/or toxicities
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