Read Across:  Increasing Confidence and Consistency in Analogue Identification, Evaluation, and Assessment Through Case Study for Fragrance Chemicals Through Incorporation of NAMs into Read Across.

Using an exposure led approach, this project will explore the utility and limitation of NGRA with a focus on RAX and NAMs to investigate systemic toxicity, reproductive toxicity, and endocrine disruption for up to 4 fragrance chemical groups: Geraniol (CASRN 106-24-1), Anisaldehyde (p-Methoxybenzaldehyde) (CASRN 123-11-5), Hydroxycitronellal (CASRN No. 107-75-5), and Citronellylacetate (CASRN 150-84-5). We will link with the skin sensitization WG to explore the application of these 4 chemicals in sensitization NGRA case studies.

This project will use RAX informed by NAMs to:

1. Identify and rate chemical analogues using approaches/tools from the Cheminformatics WG to bring consistency, transparency, and toxicological relevance to RAX and identify biological/functional analogues based on MoA data as a parallel effort.
2. Underpin chemical/biological analogues with NAMs for defining common modes of action (MoA), taking account of potency differences and internal exposure through collaboration with Human Health and Human Exposure Delivery Teams to gain confidence and reduce uncertainty in the RAX hypothesis for safety assessment of relevant systemic toxicity and potentially skin sensitization endpoint(s).