title: Linking existing in vitro dermal absorption data to physicochemical properties: Contribution to the design of a weight-of-evidence approach for the safety evaluation of cosmetic ingredients with low dermal bioavailability.
abstract: To characterize the risk of cosmetic ingredients when threshold toxicity is assumed, often the "margin of safety" (MoS) is calculated. This uncertainty factor is based on the systemic no observable (adverse) effect level (NO(A)EL) which can be derived from in vivo repeated dose toxicity studies. As in vivo studies for the purpose of the cosmetic legislation are no longer allowed in Europe and a validated in vitro alternative is not yet available, it is no longer possible to derive a NO(A)EL value for a new cosmetic ingredient. Alternatively, cosmetic ingredients with a low dermal bioavailability might not need repeated dose data, as internal exposure will be minimal and systemic toxicity might not be an issue. This study shows the possibility of identifying compounds suspected to have a low dermal bioavailability based on their physicochemical properties (molecular weight, melting point, topological polar surface area and log P) and their in vitro dermal absorption data. Although performed on a limited number of compounds, the study suggests a strategic opportunity to support the safety assessor's reasoning to omit a MoS calculation and to focus more on local toxicity and mutagenicity/genotoxicity for ingredients for which limited systemic exposure is to be expected.
authors.affiliation: Department of In Vitro Toxicology and Dermato-cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: Gamze.Ates@vub.ac.be.
authors.forename: Gamze
authors.initials: G
authors.lastname: Ates
authors.affiliation: QSAR and Modelling Group, School of Pharmacy and Biomolecular Sciences Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, England, United Kingdom.
authors.forename: Fabian P
authors.initials: FP
authors.lastname: Steinmetz
authors.affiliation: Unit of Toxicology, Scientific Institute of Public Health (IPH), Juliette Wytsmanstraat 14, B-1050, Brussels, Belgium.
authors.forename: Tatyana Yordanova
authors.initials: TY
authors.lastname: Doktorova
authors.affiliation: QSAR and Modelling Group, School of Pharmacy and Biomolecular Sciences Liverpool John Moores University, Byrom Street, Liverpool, L3 3AF, England, United Kingdom.
authors.forename: Judith C
authors.initials: JC
authors.lastname: Madden
authors.affiliation: Department of In Vitro Toxicology and Dermato-cosmetology, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Rogiers
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D001682:Biological Availability; D003257:Consumer Product Safety; D003358:Cosmetics / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D019055:No-Observed-Adverse-Effect Level; D018570:Risk Assessment; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption; D013329:Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D003358:Cosmetics
keywords: Bioavailability; Cosmetic ingredient; Dermal absorption; In silico prediction; Modelling; Physicochemical properties; Risk assessment; Safety evaluation