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

• Published in: Regulatory toxicology and pharmacology 2016-04, Vol.76, p.74-78
• Main Authors: Ates, Gamze, Steinmetz, Fabian P., Doktorova, Tatyana Yordanova, Madden, Judith C., Rogiers, Vera
• Format: Article
• Language: English
• Subjects: Administration, Cutaneous; Animals; Bioavailability; Biological Availability; Consumer Product Safety; Cosmetic ingredient; Cosmetics - administration & dosage; Cosmetics - adverse effects; Cosmetics - chemistry; Cosmetics - pharmacokinetics; Dermal absorption; Dose-Response Relationship, Drug; Humans; In silico prediction; Modelling; Models, Molecular; Molecular Structure; No-Observed-Adverse-Effect Level; Physicochemical properties; Risk Assessment; Safety evaluation; Skin - metabolism; Skin Absorption; Structure-Activity Relationship; Toxicity Tests - methods
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2016.01.015

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. •Physicochemical features and dermal absorption of cosmetic ingredients were linked.•A ruleset was extracted to identify compounds with a low dermal bioavailability.•Sensitivity of predictions using the ruleset is 100% and specificity is 58%.•Compounds with low dermal bioavailability might not need in vivo repeated dose data.