A proposed evaluation of new approach methodologies for dermal toxicity assessment of botanicals

Background Botanicals are widely used in topical formulations for cosmetics, hair care, and personal care products, reflecting consumer interest in plant-derived materials. Their complex and variable composition, presents challenges for traditional toxicological approaches developed for single chemicals. Although many botanicals are well tolerated, reports of skin irritation, sensitization, and phototoxicity highlight the need for reliable approaches to identify dermal hazards and evaluate risk. Established in silico, in chemico, and in vitro test methods, often referred to as New Approach Methodologies (NAMs), may offer efficient and mechanistically informed tools.Objective The Dermal Working Group within the Botanical Safety Consortium (BSC) developed a strategy for evaluating existing NAMs for assessing dermal toxicity endpoints in botanicals, using literature evidence and data-rich botanicals to inform assay selection and anticipated performance. This narrative review describes the literature-based considerations used to select candidate assays and characterized reference botanicals for subsequent experimental evaluation.Methods This narrative review describes considerations in the selection and application of in vitro and in chemico assays addressing skin irritation (OECD TG 439), phototoxicity (OECD TG 432), and skin sensitization (OECD TG 442 C, 442D, and 442E), together with in silico approaches.Results & Discussion A set of reference botanicals spanning a range of expected outcomes, from botanicals not expected to have effects to known irritants, sensitizers, and phototoxicants, was chosen to provide a foundation for evaluating assay performance and identifying technical considerations.Conclusion This manuscript describes the botanicals and assays being evaluated as part of the BSC’s planned dermal toxicity work. The goal of this work is to investigate the utility of NAMs for dermal safety evaluations of botanicals.