Ates, G and Steinmetz, FP and Doktorova, TY and Madden, JC and Rogiers, V (2016) 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. Regulatory Toxicology and Pharmacology, 76. pp. 74-78. ISSN 1096-0295
Ates_accepted_RTP_16.pdf - Accepted Version
Available under License Creative Commons Attribution Non-commercial No Derivatives.
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.
|Uncontrolled Keywords:||1115 Pharmacology And Pharmaceutical Sciences|
|Subjects:||R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
|Divisions:||Pharmacy & Biomolecular Sciences|
|Date Deposited:||11 Mar 2016 13:50|
|Last Modified:||22 Jan 2017 00:50|
|DOI or Identification number:||10.1016/j.yrtph.2016.01.015|
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