Flavour and Fragrance Models: Skin Absorption Modelling
Fragrance materials are widely used in cosmetics and other consumer products. The safety assessment of these ingredients includes skin absorption as this is an important parameter in estimating systemic exposure. In the current safety assessment process a compound is assumed as having 100% skin absorption when experimental data are lacking. Hence better estimates for absorption will help provide a better assessment of new fragrances and topically applied chemicals.
A model has been created with reference to published work from Shen et al directed at predicting Jmax (a theoretically achieved dose based on Fick’s first law of diffusion) where Jmax = Kp * Cwater on a data set of fragrance-like molecules. The 131 Jmax values are skewed but LogJmax are more normally distributed and so LogJmax modelled in Auto-Modeller using an 80:10:10% split of the data.
The values of LogCwater and LogK(oct/water) from the paper can be modelled successfully with the LogS and LogP models (available within StarDrop and ADME QSAR module). The Kp value in the paper is derived from a consensus of 7 models for LogK(oct/water), this property can be calculated directly. The Shen paper contains experimental and estimated values for Kp and was combined with Kp data derived from Alves et al to give a data set of 202 compounds. This set was split in 70:15:15% to generate a model for LogKp.
The best performing model for LogJmax was generated using the Gaussian Process methodology with rescaled forward variable selection (GP-RFVS).
The best performing model for LogKp was generated using a GA-RBF model
Jie Shen, Lambros Kromidas, Terry Schultz, Sneha Bhatia, An in silico skin absorption model for fragrance materials., Food and Chemical Toxicology 74 (2014) 164–176 (http://dx.doi.org/10.1016/j.fct.2014.09.015).
Alves, V.M., Muratov, E.N., Fourches, D., Strickland, J., Kleinstreuer, N., Andrade, C.H., Tropsha, A., Predicting chemically-induced skin reactions. Part I: QSAR models of skin sensitization and their application to identify potentially hazardous compounds. Toxicol. Appl. Pharmacol. 2015. (http://dx.doi.org/10.1016/j.taap.2014.12.014.).
Alves, V.M., et al., Predicting chemically-induced skin reactions. Part II: QSAR models of skin permeability and the relationships between skin permeability, Toxicol. Appl. Pharmacol. 2015. (http://dx.doi.org/10.1016/j.taap.2014.12.013).
Using the Models
The models can be downloaded for use within StarDrop from the following links:
To use these within StarDrop, download and save these files in a convenient place. Load them into StarDrop using the button on the Models tab. Alternatively, the directory in which the model files have been saved can be added to the paths from which models are automatically loaded when StarDrop starts by selecting the File->Preference menu option and adding the directory under Models in the File Locations tab.