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Kirsenko V. V., Yastrub T. O.


State Institution "Institute for Occupational Health of the National Academy of Medical Sciences of Ukraine", Kyiv

Full article (PDF), UKR

Introduction. Permeability of chemicals through the skin is a prerequisite of risk assessment of this route of entry of hazardous factors to the working zone (pesticides, organic solvents) and the environment (air pollutants, soil and water pollutants), effectiveness of medicines (transdermal therapeutic systems, ointments, liniment) and cosmetics. A mathematical modeling is the most fruitful way of overcoming many uncertainties, accompanying this complex process and the most developed and relatively simple base of such modeling is to use Fick’s laws on diffusion. Despite the enormous amount of information on this problem available in the literature there is still no any holistic view on this problem, which could help experts in solving urgent problems in practical spheres (hygienic standardization, classifications, algorithms for search studies, etc) and there is lack information on the above problem in Ukraine. There is hope, that this review, composed mainly on materials of the Scientific Advisory Council of the Environmental Protection Agency (US EPA) will be able, to some extent, to fill gaps, available in the national literature and to help in solution of these problems. The overview is built on the notion of the coefficient of penetration as a cornerstone of the diffusion model and on approaches to its definition in the mathematical apparatus, being not overloaded by complex theoretical interpretations.

Purpose. To develop an algorithm for practical use of the theory of diffusion (diffusion models) in the biological problem, related to the permeability of chemicals through biological membranes (skin) and to use this theory for practical application, based on a literature review.

Materials and methods. An analytical review of scientific publications on the theory of diffusion (analytical equations and correlations) and of the coefficient of permeability of chemicals through biological membranes as a system­producing factor in the problem of dermal absorption of chemical substances.

Results. The ways of development of a diffusion penetration model of chemicals through the skin are presented, beginning from theoretical bases to a simplified definition of the main model parameter – the coefficient of penetration, by using the Potts’s and Guy’s equation: log Kwp(est) = ­2,72 + 0,71 log Ko/w – 0,0061 MW, where Kwp(est) – an estimated coefficient of penetration through the skin from an aqueous solution; Ko/w – a partition coefficient "octanol­water"; MW – molecular mass of a substance, which penetrates through the skin, as well as methods of determining empirical equations of permeability coefficients for organic chemical solvents and pure liquids from the stratum corneum to the viable epidermis, from the air and skin. A definition of the absorbed dose as a criterion of risk assessment in percutaneous way of exposure to xenobiotics is discussed. Conclusion. The coefficient of penetration through the biological membrane (skin) is the main parameter which characterizes a complex process of distribution of a penetrant between skin and water (solvent) and diffusion in thick membranes (stratum corneum) up to the inner surface membrane (of epidermis, vascular layer of the skin). The diffusion model of permeability of biological membranes, despite a large number of conventions and uncertainties, is the most suitable way to describe this complex process, and the coefficient of permeability is the most effective tool in solving the applied problems, related to estimation of the absorbed amount of chemical substances (pesticides, medicines, cosmetic products, etc.).

Key words: skin penetration, Fick’s diffusion laws, mathematics on diffusion, coefficient of diffusion, coefficient on penetration, diffusion models, statistic models


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