文献类型：期刊文献

英文题名：CATMoS: Collaborative Acute Toxicity Modeling Suite

作者：Mansouri, Kamel[1,41];Karmaus, Agnes L.[1];Fitzpatrick, Jeremy[2];Patlewicz, Grace[3];Pradeep, Prachi[3,4];Alberga, Domenico[5];Alepee, Nathalie[6];Allen, Timothy E. H.[7];Allen, Dave[1];Alves, Vinicius M.[8,9];Andrade, Carolina H.[9];Auernhammer, Tyler R.[10];Ballabio, Davide[11];Bell, Shannon[1];Benfenati, Emilio[12];Bhattacharya, Sudin[13];Bastos, Joyce, V[9];Boyd, Stephen[14];Brown, J. B.[15];Capuzzi, Stephen J.[8];Chushak, Yaroslav[16,17];Ciallella, Heather[18];Clark, Alex M.[19];Consonni, Viviana[11];Daga, Pankaj R.[20];Ekins, Sean[19];Farag, Sherif[8];Fedorov, Maxim[21];Fourches, Denis[22,23];Gadaleta, Domenico[12];Gao, Feng[14];Gearhart, Jeffery M.[16,17];Goh, Garett[24];Goodman, Jonathan M.[7];Grisoni, Francesca[11];Grulke, Christopher M.[3];Hartung, Thomas[25];Hirn, Matthew[26];Karpov, Pavel[27];Korotcov, Alexandru[28];Lavado, Giovanna J.[12];Lawless, Michael[20];Li, Xinhao[22];Luechtefeld, Thomas[25];Lunghini, Filippo[29];Mangiatordi, Giuseppe F.[5];Marcou, Gilles[29];Marsh, Dan[25];Martin, Todd[30];Mauri, Andrea[31];Muratov, Eugene N.[8,9];Myatt, Glenn J.[32];Dac-Trung Nguyen[33];Nicolotti, Orazio[5];Note, Reine[6];Pande, Paritosh[24];Parks, Amanda K.[10];Peryea, Tyler[33];Polash, Ahsan H.[15];Rallo, Robert[24];Roncaglioni, Alessandra[12];Rowlands, Craig[25];Ruiz, Patricia[34];Russo, Daniel P.[18];Sayed, Ahmed[35];Sayre, Risa[3,4];Sheils, Timothy[33];Siegel, Charles[24];Silva, Arthur C.[9];Simeonov, Anton[33];Sosnin, Sergey[21];Southall, Noel[33];Strickland, Judy[1];Tang, Yun[36];Teppen, Brian[14];Tetko, Igor, V[27,37];Thomas, Dennis[24];Tkachenko, Valery[28];Todeschini, Roberto[11];Toma, Cosimo[12];Tripodi, Ignacio[38];Trisciuzzi, Daniela[5];Tropsha, Alexander[8];Varnek, Alexandre[29];Vukovic, Kristijan[12];Wang, Zhongyu[39];Wang, Liguo[39];Waters, Katrina M.[24];Wedlake, Andrew J.[7];Wijeyesakere, Sanjeeva J.[10];Wilson, Dan[10];Xiao, Zijun[39];Yang, Hongbin[36];Zahoranszky-Kohalmi, Gergely[33];Zakharov, Alexey, V[33];Zhang, Fagen F.[10];Zhang, Zhen[40];Zhao, Tongan[33];Zhu, Hao[18];Zorn, Kimberley M.[19];Casey, Warren[41];Kleinstreuer, Nicole C.[41]

机构：[1]Integrated Lab Syst LLC, Morrisville, NC USA;[2]ScitoVation, Res Triangle Pk, NC USA;[3]US EPA, Ctr Computat Toxicol & Exposure, Res Triangle Pk, NC 27711 USA;[4]US EPA, Res Participat Program, Oak Ridge Inst Sci & Educ ORISE, Res Triangle Pk, NC 27711 USA;[5]Univ Bari Aldo Moro, Dipartimento Farm Sci Farmaco, Bari, Italy;[6]LOreal Res & Innovat, Aulnay Sous Bois, France;[7]Univ Cambridge, Ctr Mol Informat, Dept Chem, Cambridge, England;[8]Univ North Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Lab Mol Modeling, Chapel Hill, NC 27515 USA;[9]Univ Fed Goias, Fac Pharm, Lab Mol Modeling & Design, Goiania, Go, Brazil;[10]Dow Chem Co USA, Midland, MI 48674 USA;[11]Univ Milano Bicocca, Dept Earth & Environm Sci, Milano Chemometr & QSAR Res Grp, Milan, Italy;[12]Ist Ric Farmacol Mario Negri IRCCS, Lab Environm Chem & Toxicol, Dept Environm Hlth Sci, Milan, Italy;[13]Michigan State Univ, Dept Biomed Engn, Inst Quantitat Hlth Sci & Engn, E Lansing, MI 48824 USA;[14]Michigan State Univ, Dept Plant Soil & Microbial Sci, E Lansing, MI 48824 USA;[15]Kyoto Univ, Grad Sch Med, Kyoto, Japan;[16]USAFSAM, Aeromed Res Dept, Force Hlth Protect, Dayton, OH USA;[17]Henry M Jackson Fdn Adv Mil Med, Dayton, OH USA;[18]Rutgers State Univ, Ctr Computat & Integrat Biol, Camden, NJ USA;[19]Collaborat Pharmaceut Inc, Raleigh, NC USA;[20]Simulat Plus Inc, Lancaster, CA USA;[21]Skoltech, Skolkovo Inst Sci & Technol, Moscow, Russia;[22]North Carolina State Univ, Dept Chem, Raleigh, NC USA;[23]North Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC USA;[24]Pacific Northwest Natl Lab, Richland, WA 99352 USA;[25]Underwriters Labs, Northbrook, IL USA;[26]Michigan State Univ, Dept Math, Dept Computat Math Sci & Engn, E Lansing, MI 48824 USA;[27]Helmholtz Zentrum Munchen GmbH, Inst Struct Biol, Neuherberg, Germany;[28]Sci Data Software LLC, Rockville, MD USA;[29]Univ Strasbourg, Lab Chemoinformat, URM7140, Strasbourg, France;[30]US EPA, Ctr Computat Toxicol & Exposure, Cincinnati, OH USA;[31]Alvascience Srl, Lecce, Italy;[32]Leadscope Inc, Columbus, OH USA;[33]NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA;[34]Ctr Dis Control & Prevent, Off Innovat & Analyt, Agcy Tox Subst & Dis Registry, Atlanta, GA USA;[35]Rosettastein Consulting UG, Freising Weihenstephan, Germany;[36]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai, Peoples R China;[37]BIGCHEM GmbH, Unterschleissheim, Germany;[38]Univ Colorado, Comp Sci Interdisciplinary Quantitat Biol, Boulder, CO USA;[39]Dalian Univ Technol, Sch Environm Sci & Technol, Dalian, Liaoning, Peoples R China;[40]Dow Agrosci, Indianapolis, IN USA;[41]Interagcy Ctr Evaluat Alternat Toxicol Methods, Natl Toxicol Program, Res Triangle Pk, NC USA

年份：2021

卷号：129

期号：4

外文期刊名：ENVIRONMENTAL HEALTH PERSPECTIVES

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000662049200004)】；

基金：Acknowledgments The authors thank C. Sprankle for editorial assistance. This work was supported by the intramural research program of the NIEHS, NIH and NCATS, NIH. Technical support was provided by Integrated Laboratory Systems under NIEHS contract HHSN273201500010C.

语种：英文

摘要：BACKGROUND: Humans are exposed to tens of thousands of chemical substances that need to he 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 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 in silico 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 (live) categories, very toxic chemicals [LD50 (LD50 <= 50 mg/kg)], and nontoxic chemicals (LD50 > 2,000 mg/kg). 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 in vivo results. DISCUSSION: CATMoS is being evaluated by regulatory agencies for its utility and applicability as a potential replacement for in vivo 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.