An in silico skin absorption model for fragrance materials

• Published in: Food and chemical toxicology 2014-12, Vol.74, p.164-176
• Main Authors: Shen, Jie, Kromidas, Lambros, Schultz, Terry, Bhatia, Sneha
• Format: Article
• Language: English
• Subjects: Algorithms; Assessments; Biological and medical sciences; Coefficients; Computational; Computer Simulation; Cosmetics; Databases, Chemical; Dermal; Estimates; Fittings; Food toxicology; Fragrances; Humans; Ingredients; Mathematical models; Medical sciences; Models, Biological; Perfume - chemistry; Perfume - pharmacokinetics; QSAR; Quantitative Structure-Activity Relationship; Reproducibility of Results; Safety; Skin Absorption - physiology; Solubility; Topical; Toxicology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2014.09.015

[Display omitted] •The current practice is to use 100% skin absorption default value when experimental data is lacking.•An in silico skin absorption model tailored for fragrances, assigns absorption values of 10%, 40%, or 80% based on Jmax.•The model may be used confidently for non-fragrance material provided they meet certain specified criteria.•A hypothetical example on the application of this skin absorption model in the safety assessment is presented. Fragrance materials are widely used in cosmetics and other consumer products. The Research Institute for Fragrance Materials (RIFM) evaluates the safety of these ingredients and skin absorption is an important parameter in refining systemic exposure. Currently, RIFM's safety assessment process assumes 100% skin absorption when experimental data are lacking. This 100% absorption default is not supportable and alternate default values were proposed. This study aims to develop and validate a practical skin absorption model (SAM) specific for fragrance material. It estimates skin absorption based on the methodology proposed by Kroes et al. SAM uses three default absorption values based on the maximum flux (Jmax) – namely, 10%, 40%, and 80%. Jmax may be calculated by using QSAR models that determine octanol/water partition coefficient (Kow), water solubility (S) and permeability coefficient (Kp). Each of these QSAR models was refined and a semi-quantitative mechanistic model workflow is presented. SAM was validated with a large fragrance-focused data set containing 131 materials. All resulted in predicted values fitting the three-tiered absorption scenario based on Jmax ranges. This conservative SAM may be applied when fragrance material lack skin absorption data.