Introduction

The Cosmetics Europe (CosEche) ADME Task Force aims to evaluate and develop in silico skin penetration models using relevant measured values. Since there are widely differing opinions on different in silico models, we have evaluated 3 open source and 3 commercial models in order to identify 1-2 that will be investigated further as part of the CosEu Long Range Science Strategy. Models varied in complexity (see “Model features”) but were primarily based on physical chemistry of diffusion, with different degrees of physiological relevance built in. The models were built to simulate different scenarios (e.g. in vivo pharmacokinetics of drugs, finite application to in vitro skin etc); however, we used all of them to simulate the cutaneous distribution of 25 chemicals that were run in ex vivo human skin penetration studies. The chemicals varied in molecular weight (110-290), LogP (-0.07- 4.8), melting point (-90-104°C), boiling point (200-489°C), vapor pressure (2.4×10-8-0.7 mmHg at 25°C) and water solubility (0.04-504 mg/l). Each partner was provided with the same set of input parameters, including physicochemical properties and details of the skin penetration protocol e.g., dose applied, application surface area, as well as the mass balance. The models were evaluated based on several aspects (see below).

Society of Toxicology 57th Annual Meeting and ToxExpo, March 11-15, 2018, San Antonio, Texas