New approach methods: The in vitro Bhas 42 cell transformation assay's current acceptance and utility in a weight-of-evidence approach for carcinogenicity testing

UKEMS 2023 -- The Bhas 42 cell promoter transformation assay is a sensitive short-term system for predicting chemical carcinogenicity related to transformation promotion activity. Bhas 42 cells were established from BALB/c 3T3 A31-1-1 cells by the transfection of v‑Ha‑ras gene. Tumour formation is a multi-stage process including an initiation stage (genomic level) and a promotion stage (cellular level). Of the available cell transformation assays (CTAs), the in vitro Bhas 42 CTA uses a cell line that is already considered to be initiated (as a result of its selection process); therefore, this version of the CTA only needs to follow the promotor protocol. CTAs have been used for nearly 60 years and over that time, they have gone through development and international scrutiny for evaluating if "fit-for-purpose" by OECD. That led to rejection of a potential Test Guideline, but did lead to method improvement through revision and acceptance for Guidance Documents. An OECD workgroup has be