An in silico skin absorption model for fragrance materials

作者：Shen, Jie; Kromidas, Lambros^*; Schultz, Terry; Bhatia, Sneha

来源：Food and Chemical Toxicology, 2014, 74: 164-176.

DOI：10.1016/j.fct.2014.09.015

• Toxicology
• QSAR
• Computational
• Topical
• Safety
• Dermal

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 (J(max)) - namely, 10%, 40%, and 80%. J(max) may be calculated by using QSAR models that determine octanol/water partition coefficient (K-ow.), water solubility (S) and permeability coefficient (K-p). 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 J(max). ranges. This conservative SAM may be applied when fragrance material lack skin absorption data.

• 出版日期2014-12