CATMoS: Collaborative acute toxicity modeling suite

Kamel Mansouri, Agnes L. Karmaus, Jeremy Fitzpatrick, Grace Patlewicz, Prachi Pradeep, Domenico Alberga, Nathalie Alepee, Timothy E.H. Allen, Dave Allen, Vinicius M. Alves, Carolina H. Andrade, Tyler R. Auernhammer, Davide Ballabio, Shannon Bell, Emilio Benfenati, Sudin Bhattacharya, Joyce V. Bastos, Stephen Boyd, J. B. Brown, Stephen J. CapuzziYaroslav Chushak, Heather Ciallella, Alex M. Clark, Viviana Consonni, Pankaj R. Daga, Sean Ekins, Sherif Farag, Maxim Fedorov, Denis Fourches, Domenico Gadaleta, Feng Gao, Jeffery M. Gearhart, Garett Goh, Jonathan M. Goodman, Francesca Grisoni, Christopher M. Grulke, Thomas Hartung, Matthew Hirn, Pavel Karpov, Alexandru Korotcov, Giovanna J. Lavado, Michael Lawless, Xinhao Li, Thomas Luechtefeld, Filippo Lunghini, Giuseppe F. Mangiatordi, Gilles Marcou, Dan Marsh, Todd Martin, Andrea Mauri, Eugene N. Muratov, Glenn J. Myatt, Dac Trung Nguyen, Orazio Nicolotti, Reine Note, Paritosh Pande, Amanda K. Parks, Tyler Peryea, Ahsan H. Polash, Robert Rallo, Alessandra Roncaglioni, Craig Rowlands, Patricia Ruiz, Daniel P. Russo, Ahmed Sayed, Risa Sayre, Timothy Sheils, Charles Siegel, Arthur C. Silva, Anton Simeonov, Sergey Sosnin, Noel Southall, Judy Strickland, Yun Tang, Brian Teppen, Igor V. Tetko, Dennis Thomas, Valery Tkachenko, Roberto Todeschini, Cosimo Toma, Ignacio Tripodi, Daniela Trisciuzzi, Alexander Tropsha, Alexandre Varnek, Kristijan Vukovic, Zhongyu Wang, Liguo Wang, Katrina M. Waters, Andrew J. Wedlake, Sanjeeva J. Wijeyesakere, Dan Wilson, Zijun Xiao, Hongbin Yang, Gergely Zahoranszky-Kohalmi, Alexey V. Zakharov, Fagen F. Zhang, Zhen Zhang, Tongan Zhao, Hao Zhu, Kimberley M. Zorn, Warren Casey, Nicole C. Kleinstreuer

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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. In silica models built using existing data facilitate rapid acute tox- icity predictions without using animals. Objkctivks: The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organ- ized an international collaboration to develop in silica models for predicting acute oral toxicity based on five different end points: Lethal Dose 50 (LD50 value, U.S. Environmental Protection Agency hazard (four) categories, Globally Harmonized System for Classification and Labeling hazard (five) categories, very toxic chemicals [LD50 (LD50 ≤ 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). Mkthods: 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 in viva results. Discussion: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in viva 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/EHP8495l.

Original languageEnglish (US)
Article number047013
JournalEnvironmental Health Perspectives
Volume129
Issue number4
DOIs
StatePublished - 2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Fingerprint

Dive into the research topics of 'CATMoS: Collaborative acute toxicity modeling suite'. Together they form a unique fingerprint.

Cite this