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New Framework for a Non-Animal Approach Adequately Assures the Safety of Cosmetic Ingredients – A Case Study on Caffeine

Bury, D, Alexander-White, C, Clewell, H, Cronin, MTD, Desprez, B, Detroyer, A, Efremenko, A, Firman, JW, Hack, E, Hewitt, NJ, Kenna, G, Klaric, M, Lester, C, Mahoney, C, Ouédraogo, G, Paini, A and Schepky, A New Framework for a Non-Animal Approach Adequately Assures the Safety of Cosmetic Ingredients – A Case Study on Caffeine. Regulatory Toxicology and Pharmacology. ISSN 0273-2300 (Accepted)

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Abstract

This case study on the model substance caffeine demonstrates the viability of a 10-step read across (RAX) framework in practice. New approach methodologies (NAM), including RAX and physiologically-based kinetic (PBK) modelling were used to assess the consumer safety of caffeine. Appropriate animal systemic toxicity data were used from the most relevant RAX analogue while assuming that no animal toxicity data were available for caffeine. Based on structural similarities, three primary metabolites of the target chemical caffeine (theophylline, theobromine and paraxanthine) were selected as its most relevant analogues, to estimate a point of departure in order to support a next generation risk assessment (NGRA). On the basis of the pivotal mode of action (MOA) of caffeine and other methylxanthines, theophylline appeared to be the most potent and suitable analogue. A worst-case aggregate exposure assessment determined consumer exposure to caffeine from different sources, such as cosmetics and food/drinks. Using a PBK model to estimate human blood concentrations following exposure to caffeine, an acceptable Margin of Internal Exposure (MOIE) of 27-fold was derived on the basis of a RAX using theophylline animal data, which suggests that the NGRA approach for caffeine is sufficiently conservative to protect human health.

Item Type: Article
Uncontrolled Keywords: 1115 Pharmacology and Pharmaceutical Sciences
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Elsevier
Date Deposited: 14 Apr 2021 10:06
Last Modified: 04 Sep 2021 05:36
URI: https://researchonline.ljmu.ac.uk/id/eprint/14795

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