Partition coefficient and diffusion coefficient determinations of 50 compounds in human intact skin, isolated skin layers and isolated stratum corneum lipids

• Published in: Toxicology in vitro Vol. 69; p. 104990
• Main Authors: Ellison, Corie A., Tankersley, Kevin O., Obringer, Cindy M., Carr, Greg J., Manwaring, John, Rothe, Helga, Duplan, Hélène, Géniès, Camille, Grégoire, Sébastien, Hewitt, Nicola J., Jamin, Carine Jacques, Klaric, Martina, Lange, Daniela, Rolaki, Alexandra, Schepky, Andreas
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.12.2020; Elsevier Science Ltd
• Subjects: Bioavailability; Chemical partition; Correlation analysis; Cosmetics; Dermis; Diffusion coefficient; Diffusion layers; Epidermis; Infinite dose; Lipids; Partition coefficient; Physicochemical properties; Radioactivity; Regression analysis; Skin; Skin absorption; Skin penetration; Stratum corneum; Skin penetration; percent coefficient of variation; maximum steady state flux; Partition coefficient; molecular weight; polyethersulfone; lag time to steady state; quantitative structure activity relationships; stratum corneum; flux at steady state; skin permeability coefficient; viable epidermis; Skin absorption; aqueous boundary layer; Infinite dose; Diffusion coefficient; bovine serum albumin
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2020.104990

A standard protocol was used to determine partition (K) and diffusion (D) coefficients in dermatomed human skin and isolated human skin layers for 50 compounds relevant to cosmetics ingredients. K values were measured in dermatomed skin, isolated dermis, whole epidermis, intact stratum corneum (SC), delipidized SC and SC lipids by direct measurements of the radioactivity in the tissue layers/lipid component vs. buffer samples. D determinations were made in dermatomed skin, isolated dermis, whole epidermis and intact SC using a non-linear regression of the cumulative receptor fluid content of radiolabeled compound, fit to the solution of Fick's 2nd Law. Correlation analysis was completed between K, D, and physicochemical properties. The amount of interindividual (donor) and intraindividual (replicate) variability in the K and D data was characterized for each skin layer and chemical. These data can be further used to help inform the factors that influence skin bioavailability and to help improve in silico models of dermal penetration. •One of the biggest in vitro skin penetration datasets produced in a dedicated project.•Partition & Diffusion coefficients determined in intact & isolated human skin layers for 50 compounds.•New Partition & Diffusion coefficient data will improve mechanistic understanding of skin absorption.