Modernising cosmetic chemical safety assessment: an updated workflow

We present an updated workflow for safety assessment of human systemic toxicity of cosmetic chemicals that is exposure-led and hypothesis driven and adapted from that proposed by the SEURAT-1 European program, taking account of day-to-day realities faced by cosmetic ingredient risk assessors. The workflow utilizes pre-existing legacy in vivo toxicity data for target chemicals and chemically and biologically suitable analogues. These are considered alongside human exposure data and are complemented by data provided by in silico and in vitro new-approach methodologies, when needed to build confidence in the safety decision or when legacy in vivo toxicity data are unavailable. The workflow specifies three consecutive Tiers. Tier 0 involves problem formulation and collection of existing data; if this provides sufficient certainty in a safety decision, further work is not needed. Tier 1 focuses on further hypothesis generation, plus data generation to explore (and potentially generate) hypotheses and quantify points of departure. Tier 2 encompasses further refinement activities that may be required if activities undertaken in Tiers 0 and 1 are insufficient. The workflow differs from existing frameworks by providing clear exit points, explicit integration of new approach methodologies-supported read-across and a practical structure for systemic toxicity decision making without new animal data generation. We have highlighted aspects that will benefit from further development and improvement - most notably, Tier 2 refinement. Case studies are presented that illustrate how the updated workflow is ready for practical use in cosmetic chemical safety assessments. We recommend its adoption in future cosmetic ingredient regulatory submissions.