Assessing the safety of cosmetic chemicals Consideration of a flux decision tree to predict dermally delivered systemic dose for comparison with oral TTC (Threshold of Toxicological Concern)
article
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. © 2016 International Life Sciences Institute Europe. Chemicals / CAS 2 methyl 4 isothiazolin 3 one, 2682-20-4; arbutin, 497-76-7; butyl paraben, 94-26-8; kojic acid, 501-30-4; phthalic acid diethyl ester, 84-66-2; pyrithione zinc, 13463-41-7; quercetin, 117-39-5; retinol, 68-26-8, 82445-97-4; triclocarban, 101-20-2; Cosmetics
Topics
Cosmetic chemicalDecision treeDermalFluxPredictionSystemic bioavailabilityThreshold of Toxicological Concern (TTC)2 methyl 4 isothiazolin 3 oneacid orangearbutinbasic blue 124butoxyethanolbutyl parabencosmetickojic acidmethylbenzylidene camphorphthalic acid diethyl esterpyrithione zincquercetinretinoltriclocarbanunclassified drugcosmeticArticlecosmetic industrydecision treehumanlong term exposuremathematical parameterspredictionpriority journalrisk assessmentskin absorptionskin permeabilityThreshold of Toxicological Concerntoxic concentrationtoxicity testingvalidation studyalgorithmanimalbioavailabilitybiological modelcutaneous drug administrationdecision treedose responseintestine absorptionmetabolismno-observed-adverse-effect leveloral drug administrationproceduresproduct safetyskintoxicity testingAdministration, CutaneousAdministration, OralAlgorithmsAnimalsBiological AvailabilityConsumer Product SafetyCosmeticsDecision TreesDose-Response Relationship, DrugHumansIntestinal AbsorptionModels, BiologicalNo-Observed-Adverse-Effect LevelRisk AssessmentSkinSkin AbsorptionToxicity Tests
TNO Identifier
954759
ISSN
02732300
Source
Regulatory Toxicology and Pharmacology, 76, pp. 174-186.
Pages
174-186
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