2026-10-12T22:40:26Z https://api.figshare.com/v2/oai

oai:figshare.com:article/34033335 2026-09-30T15:07:14Z category_4 category_13 category_14 category_272 category_873 category_734 category_64 category_69 portal_63 item_type_6 month_year_09_2026

Mapping ToxCast/Tox21 Assay Endpoints to Key Characteristics of Carcinogens to Support Cancer Hazard Evaluation Danila Cuomo (3178158) Agnes L. Karmaus (4866787) Bridgett N. Hill (8127153) Gwendolyn Osborne (8147796) Amy Wang (159932) Bevin Blake (25144572) William H. Bisson (189115) Gabrielle Rigutto (25144575) Cliona McHale (457144) Martyn T. Smith (68725) Caterina Facchin (15154575) Aline de Conti (665838) Federica Madia (264215) Nicole C Kleinstreuer (22750892) Weihsueh A. Chiu (7485812) Alexandre Borrel (1612594) Biochemistry Genetics Molecular Biology Environmental Sciences not elsewhere classified Chemical Sciences not elsewhere classified Biological Sciences not elsewhere classified Cancer Inorganic Chemistry nutrient supply ). driven consensus process cellular responses relevant causes immortalization ). cancer hazard evaluation novel tiering approach direct effect linked alters cell proliferation 838 assay endpoints throughput screening data tier b signifies ten key characteristics assay endpoints mapping different kccs depending tox21 assay endpoints incorporated response directionality mapped assay endpoints assay endpoints key characteristics assay ’ systematic approach downstream effect cell death comprehensive mapping systematically utilize structured framework risk assessors modulates receptor metabolically activated mediated effects mechanistic relevance mechanistic evidence interpreting high enables researchers crucial resource chemical prioritization 53 %) The Environmental Protection Agency’s Toxicity Forecaster (ToxCast) and the Toxicity Testing in the 21st Century federal consortium (Tox21) programs provide vast high-throughput screening data on thousands of chemicals, capturing a range of molecular and cellular responses relevant to toxicity. However, their application to cancer hazard identification requires a structured framework. The ten key characteristics of carcinogens (KCCs) offer a systematic approach for organizing this mechanistic evidence. We present an updated, comprehensive mapping of 1,570 ToxCast/Tox21 assay endpoints to the KCCs, developed through an expert-driven consensus process. A novel tiering approach was introduced to characterize each assay’s level of mechanistic relevance: Tier A indicates a direct effect linked to a KCC, while Tier B signifies an indirect or downstream effect. Additionally, we incorporated response directionality to correctly identify events contributing to, rather than merely associated with, a KCC. Of the 1,570 assay endpoints available in ToxCast/Tox21, 838 assay endpoints (53%) were mapped to the KCCs with some assay endpoints mapping to multiple KCCs. The majority of mapped assay endpoints were associated with KCC8 (modulates receptor-mediated effects) and KCC10 (alters cell proliferation, cell death, or nutrient supply). Some assay endpoints were mapped on different KCCs depending on the directionality of the response. No assay endpoints were mapped to KCC1 (is electrophilic or can be metabolically activated to electrophiles) or KCC9 (causes immortalization). This publicly available tiered mapping provides a crucial resource for interpreting high-throughput screening data in the context of carcinogenesis. It enables researchers and risk assessors to more systematically utilize such data for cancer hazard evaluation and chemical prioritization. 2026-09-30T00:00:00Z Text Journal contribution 10.1021/EHP.6c00478.s002 https://figshare.com/articles/journal_contribution/Mapping_ToxCast_Tox21_Assay_Endpoints_to_Key_Characteristics_of_Carcinogens_to_Support_Cancer_Hazard_Evaluation/34033335 CC BY-NC 4.0