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Lookup NU author(s): Emeritus Professor Faith Williams
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND).
Threshold of Toxicological Concern (TTC) aids assessment of human health risks from exposure to low levels of chemicals when toxicity data are limited. The objective here was to explore the potential refinement of exposure for applying the oral TTC to chemicals found in cosmetic products, for which there are limited dermal absorption data. A decision tree was constructed to estimate the dermally absorbed amount of chemical, based on typical skin exposure scenarios. Dermal absorption was calculated using an established predictive algorithm to derive the maximum skin flux adjusted to the actual 'dose' applied. The predicted systemic availability (assuming no local metabolism), can then be ranked against the oral TTC for the relevant structural class. The predictive approach has been evaluated by deriving the experimental/prediction ratio for systemic availability for 22 cosmetic chemical exposure scenarios. These emphasise that estimation of skin penetration may be challenging for penetration enhancing formulations, short application times with incomplete rinse-off, or significant metabolism. While there were a few exceptions, the experiment-to-prediction ratios mostly fell within a factor of 10 of the ideal value of 1. It can be concluded therefore, that the approach is fit-for-purpose when used as a screening and prioritisation tool. (C) 2016 International Life Sciences Institute Europe. Published by Elsevier Inc.
Author(s): Williams FM, Rothe H, Barrett G, Chiodini A, Whyte J, Cronin MTD, Monteiro-Riviere NA, Plautz J, Roper C, Westerhout J, Yang CH, Guy RH
Publication type: Article
Publication status: Published
Journal: Regulatory Toxicology and Pharmacology
Print publication date: 01/04/2016
Online publication date: 26/01/2016
Acceptance date: 07/01/2016
Date deposited: 08/07/2016
ISSN (print): 0273-2300
ISSN (electronic): 1096-0295
Publisher: Academic Press
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