title: An in silico skin absorption model for fragrance materials.
abstract: 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 Jmax ranges. This conservative SAM may be applied when fragrance material lack skin absorption data.
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA. Electronic address: lkromidas@rifm.org.
authors.forename: Lambros
authors.initials: L
authors.lastname: Kromidas
authors.affiliation: College of Veterinary Medicine, The University of Tennessee, 2407 River Dr., Knoxville, TN 37996, USA.
authors.forename: Terry
authors.initials: T
authors.lastname: Schultz
authors.affiliation: Research Institute for Fragrance Materials, Inc., 50 Tice Blvd., Woodcliff Lake, NJ 07677, USA.
authors.forename: Sneha
authors.initials: S
authors.lastname: Bhatia
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D062126:Databases, Chemical; D006801:Humans; D008954:Models, Biological; D010476:Perfume / Q000737:chemistry / Q000493:pharmacokinetics*; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results; D012869:Skin Absorption / Q000502:physiology*; D012995:Solubility
chemical_list: D010476:Perfume
keywords: Computational; Dermal; QSAR; Safety; Topical; Toxicology