CATMoS: Collaborative Acute Toxicity Modeling Suite.


Journal

Environmental health perspectives
ISSN: 1552-9924
Titre abrégé: Environ Health Perspect
Pays: United States
ID NLM: 0330411

Informations de publication

Date de publication:
04 2021
Historique:
entrez: 30 4 2021
pubmed: 1 5 2021
medline: 26 11 2021
Statut: ppublish

Résumé

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. The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop 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. 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 CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for

Sections du résumé

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.
OBJECTIVES
The U.S. Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) Acute Toxicity Workgroup organized an international collaboration to develop
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
DISCUSSION
CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for

Identifiants

pubmed: 33929906
doi: 10.1289/EHP8495
pmc: PMC8086800
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

47013

Subventions

Organisme : NIEHS NIH HHS
ID : R43 ES031038
Pays : United States
Organisme : NIEHS NIH HHS
ID : HHSN273201500010C
Pays : United States
Organisme : NIGMS NIH HHS
ID : R44 GM122196
Pays : United States
Organisme : NIEHS NIH HHS
ID : R15 ES023148
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES016465
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES031080
Pays : United States

Commentaires et corrections

Type : ErratumIn
Type : ErratumIn

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Auteurs

Kamel Mansouri (K)

Integrated Laboratory Systems, LLC, Morrisville, North Carolina, USA.
National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Research Triangle Park, North Carolina, USA.

Agnes L Karmaus (AL)

Integrated Laboratory Systems, LLC, Morrisville, North Carolina, USA.

Jeremy Fitzpatrick (J)

ScitoVation, Research Triangle Park, North Carolina, USA.

Grace Patlewicz (G)

Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.

Prachi Pradeep (P)

Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Oak Ridge Institute for Science and Education (ORISE) Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.

Domenico Alberga (D)

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, Italy.

Nathalie Alepee (N)

L'Oréal Research & Innovation, Aulnay-sous-Bois, France.

Timothy E H Allen (TEH)

Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, UK.

Dave Allen (D)

Integrated Laboratory Systems, LLC, Morrisville, North Carolina, USA.

Vinicius M Alves (VM)

Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
Laboratory for Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiania, Brazil.

Carolina H Andrade (CH)

Laboratory for Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiania, Brazil.

Tyler R Auernhammer (TR)

The Dow Chemical Company, Midland, Michigan, USA.

Davide Ballabio (D)

Milano Chemometrics & QSAR Research Group, Department of Earth and Environmental Sciences, University of Milano-Bicocca, Milan, Italy.

Shannon Bell (S)

Integrated Laboratory Systems, LLC, Morrisville, North Carolina, USA.

Emilio Benfenati (E)

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Sudin Bhattacharya (S)

Institute for Quantitative Health Science and Engineering, Department of Biomedical Engineering, Michigan State University, East Lansing, Michigan, USA.

Joyce V Bastos (JV)

Laboratory for Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiania, Brazil.

Stephen Boyd (S)

Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, Michigan, USA.

J B Brown (JB)

Kyoto University Graduate School of Medicine, Kyoto, Japan.

Stephen J Capuzzi (SJ)

Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.

Yaroslav Chushak (Y)

Aeromedical Research Department, Force Health Protection, USAFSAM, Dayton, Ohio, USA.
Henry M Jackson Foundation for the Advancement of Military Medicine, Dayton, Ohio, USA.

Heather Ciallella (H)

Center for Computational and Integrative Biology, Rutgers University, Camden, New Jersey, USA.

Alex M Clark (AM)

Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina, USA.

Viviana Consonni (V)

Milano Chemometrics & QSAR Research Group, Department of Earth and Environmental Sciences, University of Milano-Bicocca, Milan, Italy.

Pankaj R Daga (PR)

Simulations Plus, Inc., Lancaster, California, USA.

Sean Ekins (S)

Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina, USA.

Sherif Farag (S)

Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.

Maxim Fedorov (M)

Skoltech, Skolkovo Institute of Science and Technology, Moscow, Russia.

Denis Fourches (D)

Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.
Bioinformatics Research Center, North Carolina State University, Raleigh, North Carolina, USA.

Domenico Gadaleta (D)

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Feng Gao (F)

Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, Michigan, USA.

Jeffery M Gearhart (JM)

Aeromedical Research Department, Force Health Protection, USAFSAM, Dayton, Ohio, USA.
Henry M Jackson Foundation for the Advancement of Military Medicine, Dayton, Ohio, USA.

Garett Goh (G)

Pacific Northwest National Laboratory, Richland, Washington, USA.

Jonathan M Goodman (JM)

Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, UK.

Francesca Grisoni (F)

Milano Chemometrics & QSAR Research Group, Department of Earth and Environmental Sciences, University of Milano-Bicocca, Milan, Italy.

Christopher M Grulke (CM)

Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.

Thomas Hartung (T)

Underwriters Laboratories, Northbrook, Illinois, USA.

Matthew Hirn (M)

Department of Computational Mathematics, Science & Engineering, Department of Mathematics, Michigan State University, East Lansing, Michigan, USA.

Pavel Karpov (P)

Institute of Structural Biology, Helmholtz Zentrum München (GmbH), Neuherberg, Germany.

Alexandru Korotcov (A)

Science Data Software, LLC, Rockville, Maryland, USA.

Giovanna J Lavado (GJ)

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Michael Lawless (M)

Simulations Plus, Inc., Lancaster, California, USA.

Xinhao Li (X)

Department of Chemistry, North Carolina State University, Raleigh, North Carolina, USA.

Thomas Luechtefeld (T)

Underwriters Laboratories, Northbrook, Illinois, USA.

Filippo Lunghini (F)

Laboratoire de Chemoinformatique, URM7140, Université de Strasbourg, Strasbourg, France.

Giuseppe F Mangiatordi (GF)

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, Italy.

Gilles Marcou (G)

Laboratoire de Chemoinformatique, URM7140, Université de Strasbourg, Strasbourg, France.

Dan Marsh (D)

Underwriters Laboratories, Northbrook, Illinois, USA.

Todd Martin (T)

Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency, Cincinnati, Ohio, USA.

Andrea Mauri (A)

Alvascience Srl, Lecco, Italy.

Eugene N Muratov (EN)

Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.
Laboratory for Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiania, Brazil.

Glenn J Myatt (GJ)

Leadscope Inc., Columbus, Ohio, USA.

Dac-Trung Nguyen (DT)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Orazio Nicolotti (O)

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, Italy.

Reine Note (R)

L'Oréal Research & Innovation, Aulnay-sous-Bois, France.

Paritosh Pande (P)

Pacific Northwest National Laboratory, Richland, Washington, USA.

Amanda K Parks (AK)

The Dow Chemical Company, Midland, Michigan, USA.

Tyler Peryea (T)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Ahsan H Polash (AH)

Kyoto University Graduate School of Medicine, Kyoto, Japan.

Robert Rallo (R)

Pacific Northwest National Laboratory, Richland, Washington, USA.

Alessandra Roncaglioni (A)

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Craig Rowlands (C)

Underwriters Laboratories, Northbrook, Illinois, USA.

Patricia Ruiz (P)

Office of Innovation and Analytics, Agency for Toxic Substances and Disease Registry, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Daniel P Russo (DP)

Center for Computational and Integrative Biology, Rutgers University, Camden, New Jersey, USA.

Ahmed Sayed (A)

Rosettastein Consulting UG, Freising, Germany.

Risa Sayre (R)

Center for Computational Toxicology and Exposure, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Oak Ridge Institute for Science and Education (ORISE) Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.

Timothy Sheils (T)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Charles Siegel (C)

Pacific Northwest National Laboratory, Richland, Washington, USA.

Arthur C Silva (AC)

Laboratory for Molecular Modeling and Design, Faculty of Pharmacy, Federal University of Goiás, Goiania, Brazil.

Anton Simeonov (A)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Sergey Sosnin (S)

Skoltech, Skolkovo Institute of Science and Technology, Moscow, Russia.

Noel Southall (N)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Judy Strickland (J)

Integrated Laboratory Systems, LLC, Morrisville, North Carolina, USA.

Yun Tang (Y)

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Brian Teppen (B)

Department of Plant, Soil, and Microbial Sciences, Michigan State University, East Lansing, Michigan, USA.

Igor V Tetko (IV)

Institute of Structural Biology, Helmholtz Zentrum München (GmbH), Neuherberg, Germany.
BIGCHEM GmbH, Unterschleissheim, Germany.

Dennis Thomas (D)

Pacific Northwest National Laboratory, Richland, Washington, USA.

Valery Tkachenko (V)

Science Data Software, LLC, Rockville, Maryland, USA.

Roberto Todeschini (R)

Milano Chemometrics & QSAR Research Group, Department of Earth and Environmental Sciences, University of Milano-Bicocca, Milan, Italy.

Cosimo Toma (C)

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Ignacio Tripodi (I)

Computer Science/Interdisciplinary Quantitative Biology, University of Colorado, Boulder, Colorado, USA.

Daniela Trisciuzzi (D)

Dipartimento di Farmacia-Scienze del Farmaco, Università degli Studi di Bari "Aldo Moro", Bari, Italy.

Alexander Tropsha (A)

Laboratory for Molecular Modeling, Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina, USA.

Alexandre Varnek (A)

Laboratoire de Chemoinformatique, URM7140, Université de Strasbourg, Strasbourg, France.

Kristijan Vukovic (K)

Laboratory of Environmental Chemistry and Toxicology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.

Zhongyu Wang (Z)

School of Environmental Sciences and Technology, Dalian University of Technology; Dalian, Liaoning, China.

Liguo Wang (L)

School of Environmental Sciences and Technology, Dalian University of Technology; Dalian, Liaoning, China.

Katrina M Waters (KM)

Pacific Northwest National Laboratory, Richland, Washington, USA.

Andrew J Wedlake (AJ)

Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Cambridge, UK.

Sanjeeva J Wijeyesakere (SJ)

The Dow Chemical Company, Midland, Michigan, USA.

Dan Wilson (D)

The Dow Chemical Company, Midland, Michigan, USA.

Zijun Xiao (Z)

School of Environmental Sciences and Technology, Dalian University of Technology; Dalian, Liaoning, China.

Hongbin Yang (H)

Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, China.

Gergely Zahoranszky-Kohalmi (G)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Alexey V Zakharov (AV)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Fagen F Zhang (FF)

The Dow Chemical Company, Midland, Michigan, USA.

Zhen Zhang (Z)

Dow Agrosciences, Indianapolis, Indiana, USA.

Tongan Zhao (T)

National Center for Advancing Translational Sciences, National Institutes of Health, Rockville, Maryland, USA.

Hao Zhu (H)

Center for Computational and Integrative Biology, Rutgers University, Camden, New Jersey, USA.

Kimberley M Zorn (KM)

Collaborations Pharmaceuticals, Inc., Raleigh, North Carolina, USA.

Warren Casey (W)

National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Research Triangle Park, North Carolina, USA.

Nicole C Kleinstreuer (NC)

National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, Research Triangle Park, North Carolina, USA.

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