TitleCATMoS: Collaborative Acute Toxicity Modeling Suite.
Publication TypeJournal Article
Year of Publication2021
AuthorsMansouri, K, Karmaus, AL, Fitzpatrick, J, Patlewicz, G, Pradeep, P, Alberga, D, Alepee, N, Allen, TEH, Allen, D, Alves, VM, Andrade, CH, Auernhammer, TR, Ballabio, D, Bell, S, Benfenati, E, Bhattacharya, S, Bastos, JV, Boyd, S, Brown, JB, Capuzzi, SJ, Chushak, Y, Ciallella, H, Clark, AM, Consonni, V, Daga, PR, Ekins, S, Farag, S, Fedorov, M, Fourches, D, Gadaleta, D, Gao, F, Gearhart, JM, Goh, G, Goodman, JM, Grisoni, F, Grulke, CM, Hartung, T, Hirn, M, Karpov, P, Korotcov, A, Lavado, GJ, Lawless, M, Li, X, Luechtefeld, T, Lunghini, F, Mangiatordi, GF, Marcou, G, Marsh, D, Martin, T, Mauri, A, Muratov, EN, Myatt, GJ, Nguyen, D-T, Nicolotti, O, Note, R, Pande, P, Parks, AK, Peryea, T, Polash, AH, Rallo, R, Roncaglioni, A, Rowlands, C, Ruiz, P, Russo, DP, Sayed, A, Sayre, R, Sheils, T, Siegel, C, Silva, AC, Simeonov, A, Sosnin, S, Southall, N, Strickland, J, Tang, Y, Teppen, B, Tetko, IV, Thomas, D, Tkachenko, V, Todeschini, R, Toma, C, Tripodi, I, Trisciuzzi, D, Tropsha, A, Varnek, A, Vukovic, K, Wang, Z, Wang, L, Waters, KM, Wedlake, AJ, Wijeyesakere, SJ, Wilson, D, Xiao, Z, Yang, H, Zahoranszky-Kohalmi, G, Zakharov, AV, Zhang, FF, Zhang, Z, Zhao, T, Zhu, H, Zorn, KM, Casey, W, Kleinstreuer, NC
JournalEnviron Health Perspect
Volume129
Issue4
Pagination47013
Date Published2021 04
ISSN1552-9924
KeywordsAnimals, Computer Simulation, Government Agencies, Rats, Toxicity Tests, Acute, United States, United States Environmental Protection Agency
Abstract

BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to be assessed for their potential toxicity. Acute systemic toxicity testing serves as the basis for regulatory hazard classification, labeling, and risk management. However, it is cost- and time-prohibitive to evaluate all new and existing chemicals using traditional rodent acute toxicity tests. models built using existing data facilitate rapid acute toxicity predictions without using animals.

OBJECTIVES: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 ( value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [ ()], and nontoxic chemicals ().

METHODS: An acute oral toxicity data inventory for 11,992 chemicals was compiled, split into training and evaluation sets, and made available to 35 participating international research groups that submitted a total of 139 predictive models. Predictions that fell within the applicability domains of the submitted models were evaluated using external validation sets. These were then combined into consensus models to leverage strengths of individual approaches.

RESULTS: The resulting consensus predictions, which leverage the collective strengths of each individual model, form the Collaborative Acute Toxicity Modeling Suite (CATMoS). CATMoS demonstrated high performance in terms of accuracy and robustness when compared with results.

DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for rat acute oral toxicity studies. CATMoS predictions for more than 800,000 chemicals have been made available via the National Toxicology Program's Integrated Chemical Environment tools and data sets (ice.ntp.niehs.nih.gov). The models are also implemented in a free, standalone, open-source tool, OPERA, which allows predictions of new and untested chemicals to be made. https://doi.org/10.1289/EHP8495.

DOI10.1289/EHP8495
Alternate JournalEnviron Health Perspect
PubMed ID33929906
PubMed Central IDPMC8086800
Grant ListR43 ES031038 / ES / NIEHS NIH HHS / United States
HHSN273201500010C / ES / NIEHS NIH HHS / United States
R44 GM122196 / GM / NIGMS NIH HHS / United States
R15 ES023148 / ES / NIEHS NIH HHS / United States
P42 ES016465 / ES / NIEHS NIH HHS / United States
R01 ES031080 / ES / NIEHS NIH HHS / United States