Assessment of local and systemic safety of aqueous Eucommia ulmoides bark extract for a cosmetics ingredient utilizing in vitro, in silico, threshold of toxicological concern and history of safe use approaches

Abstract

As the cosmetic industry shifts toward sustainable botanical ingredients, ensuring the safety of plant extracts remains a regulatory challenge. Here, we assessed the safety of aqueous E. ulmoides bark extract for its use in cosmetics. First, skin and eye toxicity, and genotoxicity were evaluated for the whole extract using in vitro OECD test methods, all of which showed no concern. The skin sensitization potential was assessed through in silico prediction for chemical constituents using Derek Nexus. For the systemic safety, we employed the threshold of toxicological concern (TTC) approach by identifying the chemical constituents and their contents in the extract through literature search and instrumental analysis. All identified bioactive constituents were examined for their potential genotoxicity through in silico prediction using Chemtunes™ and literature search. It was confirmed that systemic exposure of all constituents through cosmetic use does not exceed each Cramer class threshold. We also employed the history of safe consumption approach to demonstrate that exposure to the extract is below those from its dietary intake. Comparison with the margin of safety estimation using existing repeated-dose toxicity data confirmed that both the TTC and history of safe consumption approaches are valid for the safety assessment of botanical extracts. © 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.