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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

Application of
Modern Toxicology Approaches
for Predicting Acute Toxicity
for Chemical Defense

Committee on Predictive-Toxicology Approaches for
Military Assessments of Acute Exposures

Committee on Toxicology

Board on Environmental Studies and Toxicology

Board on Life Sciences

Division on Earth and Life Studies

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THE NATIONAL ACADEMIES PRESS

Washington, DC

www.nap.edu

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

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This project was supported by Contract W81K04-11-D-0017, TO#8 between the National Academies of Sciences, Engineering, and Medicine and the US Department of Defense. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

International Standard Book Number-13: 978-0-309-37666-2
International Standard Book Number-10: 0-309-37666-1.

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Suggested citation: The National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press.

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

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The National Academy of Sciences was established in 1863 by an Act of Congress, signed by President Lincoln, as a private, nongovernmental institution to advise the nation on issues related to science and technology. Members are elected by their peers for outstanding contributions to research. Dr. Ralph J. Cicerone is president.

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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

COMMITTEE ON PREDICTIVE-TOXICOLOGY APPROACHES FOR MILITARY ASSESSMENTS OF ACUTE EXPOSURES

Members

DAVID C. DORMAN (Chair), North Carolina State University, Raleigh, NC

WEIHSUEH A. CHIU, Texas A&M University, College Station, TX

HAIYAN HUANG, University of California, Berkeley, CA

ANDY NONG, Health Canada, Ottawa, ON

GRACE PATLEWICZ, US Environmental Protection Agency, Research Triangle Park, NC

DAVID REIF, North Carolina State University, Raleigh, NC

JOHN WADE, Battelle, Arlington, VA

KATRINA WATERS, Pacific Northwest National Laboratories, Richland, WA

BARBARA A. WETMORE, The Hamner Institutes for Health Sciences, Research Triangle Park, NC

YVONNE WILL, Pfizer, Groton, CT

Staff

ELLEN K. MANTUS, Project Director

MARILEE SHELTON-DAVENPORT, Senior Program Officer

KERI STOEVER, Research Associate

NORMAN GROSSBLATT, Senior Editor

MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center

RADIAH ROSE-CRAWFORD, Manager, Editorial Projects

IVORY CLARKE, Senior Program Assistant

Sponsor

US DEPARTMENT OF DEFENSE

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

COMMITTEE ON TOXICOLOGY

Members

GARY P. CARLSON (Chair), Purdue University (retired), West Lafayette, IN

LAWRENCE S. BETTS, Eastern Virginia Medical School, Norfolk

DEEPAK K. BHALLA, Wayne State University, Detroit, MI

DEBORAH A. CORY-SLECHTA, University of Rochester School of Medicine and Dentistry, Rochester, NY

MARY E. DAVIS, West Virginia University, Morgantown

DAVID C. DORMAN, North Carolina State University, Raleigh

MARGARET M. MACDONELL, Argonne National Laboratory, Argonne, IL

IVAN RUSYN, Texas A&M University, College Station

KENNETH R. STILL, Portland State University, Portland, OR

JOYCE S. TSUJI, Exponent, Inc., Bellevue, WA

Staff

SUSAN N.J. MARTEL, Senior Program Officer for Toxicology

ELLEN K. MANTUS, Scholar and Director of Risk Assessment

MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center

RADIAH ROSE, Manager, Editorial Projects

TAMARA DAWSON, Program Associate

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1

Members

ROGENE F. HENDERSON (Chair), Lovelace Respiratory Research Institute, Albuquerque, NM

PRAVEEN AMAR, Independent Consultant, Lexington, MA

RICHARD A. BECKER, American Chemistry Council, Washington, DC

MICHAEL J. BRADLEY, M.J. Bradley & Associates, Concord, MA

JONATHAN Z. CANNON, University of Virginia, Charlottesville, VA

GAIL CHARNLEY ELLIOTT, HealthRisk Strategies, Washington, DC

DOMINIC M. DITORO, University of Delaware, Newark, DE

DAVID C. DORMAN, North Carolina State University, Raleigh, NC

CHARLES T. DRISCOLL, JR., Syracuse University, Syracuse, NY

WILLIAM H. FARLAND, Colorado State University, Fort Collins, CO

LYNN R. GOLDMAN, The George Washington University, Washington, DC

LINDA E. GREER, Natural Resources Defense Council, Washington, DC

WILLIAM E. HALPERIN, University of Medicine and Dentistry of New Jersey, Newark, NJ

STEVEN P. HAMBURG, Environmental Defense Fund, New York, NY

ROBERT A. HIATT, University of California, San Francisco, CA

PHILIP K. HOPKE, Clarkson University, Potsdam, NY

SAMEUL KACEW, University of Ottawa, Ontario

H. SCOTT MATTHEWS, Carnegie Mellon University, Pittsburgh, PA

THOMAS E. MCKONE, University of California, Berkeley, CA

TERRY L. MEDLEY, E. I. du Pont de Nemours & Company, Wilmington, DE

JANA MILFORD, University of Colorado at Boulder, Boulder, CA

MARK A. RATNER, Northwestern University, Evanston, IL

JOAN B. ROSE, Michigan State University, East Lansing, MI

GINA M. SOLOMON, California Environmental Protection Agency, Sacramento, CA

PETER S. THORNE, University of Iowa, Iowa City, IA

JOYCE S. TSUJI, Exponent, Inc., Bellevue, WA

Senior Staff

JAMES J. REISA, Senior Director

ELLEN K. MANTUS, Scholar and Director of Risk Assessment

RAYMOND A. WASSEL, Scholar and Director of Environmental Studies

DAVID J. POLICANSKY, Scholar

SUSAN N.J. MARTEL, Senior Program Officer for Toxicology

MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center

RADIAH ROSE-CRAWFORD, Manager, Editorial Projects

__________________

1This study was planned, overseen, and supported by the Board on Environmental Studies and Toxicology.

Page viii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Review of California’s Risk-Assessment Process for Pesticides (2015)

Sustainability Concepts in Decision Making, Tools and Approaches for the US Environmental Protection Agency (2014)

Rethinking the Components, Coordination, and Management of US Environmental Protection Agency Laboratories (2014)

Review of the Formaldehyde Assessment in the National Toxicology Program 12th Report on Carcinogens (2014)

Review of the Styrene Assessment in the National Toxicology Program 12th Report on Carcinogens (2014)

Review of EPA’s Integrated Risk Information System (IRIS) Process (2014)

Review of the Environmental Protection Agency’s State-of-the-Science Evaluation of Nonmonotonic Dose–Response Relationships as They Apply to Endocrine Disruptors (2014)

Assessing Risks to Endangered and Threatened Species from Pesticides (2013)

Science for Environmental Protection: The Road Ahead (2012)

Exposure Science in the 21st Century: A Vision and A Strategy (2012)

A Research Strategy for Environmental, Health, and Safety Aspects of Engineered Nanomaterials (2012)

Macondo Well–Deepwater Horizon Blowout: Lessons for Improving Offshore Drilling Safety (2012)

Feasibility of Using Mycoherbicides for Controlling Illicit Drug Crops (2011)

Improving Health in the United States: The Role of Health Impact Assessment (2011)

A Risk-Characterization Framework for Decision-Making at the Food and Drug Administration (2011)

Review of the Environmental Protection Agency’s Draft IRIS Assessment of Formaldehyde (2011)

Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change (2010)

The Use of Title 42 Authority at the U.S. Environmental Protection Agency (2010)

Review of the Environmental Protection Agency’s Draft IRIS Assessment of Tetrachloroethylene (2010)

Hidden Costs of Energy: Unpriced Consequences of Energy Production and Use (2009)

Contaminated Water Supplies at Camp Lejeune—Assessing Potential Health Effects (2009)

Review of the Federal Strategy for Nanotechnology-Related Environmental, Health, and Safety Research (2009)

Science and Decisions: Advancing Risk Assessment (2009)

Phthalates and Cumulative Risk Assessment: The Tasks Ahead (2008)

Estimating Mortality Risk Reduction and Economic Benefits from Controlling Ozone Air Pollution (2008)

Respiratory Diseases Research at NIOSH (2008)

Evaluating Research Efficiency in the U.S. Environmental Protection Agency (2008)

Hydrology, Ecology, and Fishes of the Klamath River Basin (2008)

Applications of Toxicogenomic Technologies to Predictive Toxicology and Risk Assessment (2007)

Models in Environmental Regulatory Decision Making (2007)

Toxicity Testing in the Twenty-first Century: A Vision and a Strategy (2007)

Sediment Dredging at Superfund Megasites: Assessing the Effectiveness (2007)

Environmental Impacts of Wind-Energy Projects (2007)

Scientific Review of the Proposed Risk Assessment Bulletin from the Office of Management and Budget (2007)

Assessing the Human Health Risks of Trichloroethylene: Key Scientific Issues (2006)

New Source Review for Stationary Sources of Air Pollution (2006)

Human Biomonitoring for Environmental Chemicals (2006)

Health Risks from Dioxin and Related Compounds: Evaluation of the EPA Reassessment (2006)

Fluoride in Drinking Water: A Scientific Review of EPA’s Standards (2006)

State and Federal Standards for Mobile-Source Emissions (2006)

Superfund and Mining Megasites—Lessons from the Coeur d’Alene River Basin (2005)

Health Implications of Perchlorate Ingestion (2005)

Air Quality Management in the United States (2004)

Endangered and Threatened Species of the Platte River (2004)

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

Atlantic Salmon in Maine (2004)

Endangered and Threatened Fishes in the Klamath River Basin (2004)

Cumulative Environmental Effects of Alaska North Slope Oil and Gas Development (2003)

Estimating the Public Health Benefits of Proposed Air Pollution Regulations (2002)

Biosolids Applied to Land: Advancing Standards and Practices (2002)

The Airliner Cabin Environment and Health of Passengers and Crew (2002)

Arsenic in Drinking Water: 2001 Update (2001)

Evaluating Vehicle Emissions Inspection and Maintenance Programs (2001)

Compensating for Wetland Losses Under the Clean Water Act (2001)

A Risk-Management Strategy for PCB-Contaminated Sediments (2001)

Acute Exposure Guideline Levels for Selected Airborne Chemicals (nineteen volumes, 2000-2015)

Toxicological Effects of Methylmercury (2000)

Strengthening Science at the U.S. Environmental Protection Agency (2000)

Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)

Ecological Indicators for the Nation (2000)

Waste Incineration and Public Health (2000)

Hormonally Active Agents in the Environment (1999)

Research Priorities for Airborne Particulate Matter (four volumes, 1998-2004)

The National Research Council’s Committee on Toxicology: The First 50 Years (1997)

Carcinogens and Anticarcinogens in the Human Diet (1996)

Upstream: Salmon and Society in the Pacific Northwest (1996)

Science and the Endangered Species Act (1995)

Wetlands: Characteristics and Boundaries (1995)

Biologic Markers (five volumes, 1989-1995)

Science and Judgment in Risk Assessment (1994)

Pesticides in the Diets of Infants and Children (1993)

Dolphins and the Tuna Industry (1992)

Science and the National Parks (1992)

Human Exposure Assessment for Airborne Pollutants (1991)

Rethinking the Ozone Problem in Urban and Regional Air Pollution (1991)

Decline of the Sea Turtles (1990)

Copies of these reports may be ordered from the National Academies Press (800) 624-6242 or (202) 334-3313 www.nap.edu

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

BOARD ON LIFE SCIENCES

Members

JAMES P. COLLINS (Chair), Arizona State University, Tempe, AZ

ENRIQUETA C. BOND, Burroughs Wellcome Fund, Marshall, VA

ROGER D. CONE, Vanderbilt University Medical Center, Nashville, TN

JOSEPH R. ECKER, Salk Institute for Biological Studies, LaJolla, CA

SEAN EDDY, HHMI Janelia Farm Research Campus, Ashburn, VA

SARAH C.R. ELGIN, Washington University, St. Louis, MO

DAVID R, FRANZ, Former Cdr USAMRIID, Consultant, Frederick, MD

STEPHEN FRIEND, Sage Bionetworks, Seattle, WA

ELIZABETH HEITMAN, Vanderbilt University Medical Center, Nashville, TN

RICHARD A. JOHNSON, Global Helix LLC, Washington, DC

JUDITH KIMBLE, University of Wisconsin, Madison, WI

MARY E. MAXON, Science Philanthropy Alliance, Palo Alto, CA

KAREN E. NELSON, J. Craig Venter Institute, Rockville, MD

ROBERT M. NEREM, Georgia Institute of Technology, Atlanta, GA

MARY E. POWER, University of California, Berkeley, CA

MARGARET RILEY, University of Massachusetts, Amherst, MA

LANA SKIRBOLL, Sanofi, Washington, DC

JANIS C. WEEKS, University of Oregon, Eugene, OR

MARY WOOLLEY, Research!America, Alexandria, VA

Staff

FRANCES E. SHARPLES, Director

JO L. HUSBANDS, Scholar/Senior Project Director

JAY B. LABOV, Senior Scientist/Program Director for Biology Education

LIDA ANESTIDOU, Senior Program Officer, ILAR

KATHERINE W. BOWMAN, Senior Program Officer

MARILEE K. SHELTON-DAVENPORT, Senior Program Officer

KEEGAN SAWYER, Program Officer

AUDREY THEVENON, Associate Program Officer

BETHELHEM M. MEKASHA, Financial Associate

ANGELA KOLESNIKOVA, Administrative Assistant

VANESSA LESTER, Research Associate

KANOKO MAEDA, Senior Program Assistant

JENNA OGILVIE, Senior Program Assistant

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

Preface

The US Department of Defense (DOD) is faced with an overwhelming task in evaluating chemicals that could potentially pose a threat to its deployed personnel. There are over 84,000 registered chemicals, and testing them with traditional toxicity-testing methods is not feasible in terms of time or money. In recent years, there has been a concerted effort to develop new approaches to toxicity testing that incorporate advances in systems biology, toxicogenomics, bioinformatics, and computational toxicology. Given the advances, DOD asked the National Research Council (NRC) to determine how DOD could use modern approaches for predicting chemical toxicity in its efforts to prevent debilitating, acute exposures to deployed personnel.

In this report, the Committee on Predictive-Toxicology Approaches for Military Assessments of Acute Exposures provides an overall conceptual approach that DOD could use to develop a predictive-toxicology system. It reviews the current state of computational and high-throughput approaches for predicting acute toxicity and suggests methods for integrating data and predictions. It concludes with lessons learned from current high-throughput screening programs and suggests some initial steps for DOD investment.

This report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the NRC Report Review Committee. The purpose of the independent review is to provide candid and critical comments that will assist the institution in making its published report as sound as possible and to ensure that the report meets institutional standards of objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process. We thank the following for their review of this report: Ellen Berg, BioSeek, Inc.; David Clapham, Harvard University; Mark Cronin, Liverpool John Moores University; Yvonne Dragan, DuPont; John Jenner, Defence Science and Technology Laboratory; Charles Santerre, Purdue University; Rusty Thomas, US Environmental Protection Agency; Ken Turtletaub, Lawrence Livermore National Laboratory; Daniel Wilson, The Dow Chemical Company; and Menghang Xia, National Center for Advancing Translational Sciences.

Although the reviewers listed above have provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations, nor did they see the final draft of the report before its release. The review of the report was overseen by the review coordinator, David Eaton, University of Washington, and the review monitor, Mark Cullen, Stanford University. Appointed by the NRC, they were responsible for making certain that an independent examination of the report was carried out in accordance with institutional procedures and that all review comments were carefully considered. Responsibility for the final content of the report rests entirely with the committee and the institution.

The committee gratefully acknowledges the following for their presentations to the committee during open sessions: Alison Director-Myska, Defense Threat Reduction Agency, and Keith Houck, US Environmental Protection Agency.

The committee is grateful for the assistance of the National Research Council staff in preparing this report. Staff members who contributed to the effort are Ellen Mantus, project director; Marilee Shelton-Davenport, senior program officer; Keri Stoever, research associate; James Reisa,

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

director of the Board on Environmental Studies and Toxicology; Norman Grossblatt, senior editor; Mirsada Karalic-Loncarevic, manager of the Technical Information Center; Radiah Rose-Crawford, manager of editorial projects; and Ivory Clarke, senior program assistant.

I especially thank the members of the committee for their efforts throughout the development of this report.

David Dorman, Chair

Committee on Predictive-Toxicology Approaches

for Military Assessments of Acute Exposures

Page xiii Cite
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×
Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
×

6 LESSONS LEARNED AND NEXT STEPS

Modern Approaches for the Assessment of Acute Chemical Toxicity

Implementation of the Committee’s Conceptual Model for Assessment of Acute Chemical Toxicity

Development of a Modern Tiered Approach for Predicting Acute Toxicity: Initial Steps

Other Considerations

Findings and Recommendations

References

APPENDIXES

A BIOGRAPHICAL INFORMATION ON THE COMMITTEE ON PREDICTIVE-TOXICOLOGY APPROACHES FOR MILITARY ASSESSMENTS OF ACUTE EXPOSURES

B AVAILABLE DATA OR DATABASES

BOXES, FIGURES, AND TABLES

BOXES

1-1 Statement of Task

2-1 Definitions of Relevant Terms

2-2 Tiered Approach to Predicting Toxicity

3-1 Definitions of Selected Nontesting Approaches

3-2 Primary Data Considered During a Preliminary Characterization of a Chemical of Interest

3-3 In Silico Approaches for Predicting Physicochemical Properties

4-1 ACuteTox Testing Strategy

5-1 Simplified Illustration of Integration and Decision-making

5-2 Example of Meta-Analytic Approach That Uses Irreproducible Discovery Rates to Integrate Categorization Decisions

6-1 An Example of an Integrated Testing Strategy for Predicting Drug-Induced Liver Injury

6-2 The Use of Computational Approaches for Evaluating Chemical-Induced Inhibition of Acetylcholinesterase

6-3 The Use of HTS Assays for Identifying Endocrine Disrupting Potential

6-4 The Use of the BALB/3T3 Neutral-Red Uptake Cytotoxicity Assay to Predict Acute Toxicity

6-5 The Use of HTS Assays to Evaluate Inhibition of Acetylcholinesterase

FIGURES

S-1 Conceptual framework and examples of databases, assays, models and tools for predicting acute chemical toxicity

S-2 Prioritization strategy based on a tiered approach for using predictive-toxicology models and tools to evaluate agents for acute toxicity

2-1 Conceptual framework and examples of databases, assays, models and tools for predicting acute chemical toxicity

2-2 Prioritization strategy based on a tiered approach for using predictive-toxicology models and tools to evaluate agents for acute toxicity

3-1 Conceptual framework for the future development of (Q)SARs

3-2 Key elements associated with evaluating the adequacy of a (Q)SAR model and its prediction as adapted from the REACH technical guidance

4-1 Intended target families and subfamilies for the ToxCast program

Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
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Suggested Citation:"Front Matter." National Academies of Sciences, Engineering, and Medicine. 2015. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense. Washington, DC: The National Academies Press. doi: 10.17226/21775.
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The US Department of Defense (DOD) is faced with an overwhelming task in evaluating chemicals that could potentially pose a threat to its deployed personnel. There are over 84,000 registered chemicals, and testing them with traditional toxicity-testing methods is not feasible in terms of time or money. In recent years, there has been a concerted effort to develop new approaches to toxicity testing that incorporate advances in systems biology, toxicogenomics, bioinformatics, and computational toxicology. Given the advances, DOD asked the National Research Council to determine how DOD could use modern approaches for predicting chemical toxicity in its efforts to prevent debilitating, acute exposures to deployed personnel. This report provides an overall conceptual approach that DOD could use to develop a predictive toxicology system. Application of Modern Toxicology Approaches for Predicting Acute Toxicity for Chemical Defense reviews the current state of computational and high-throughput approaches for predicting acute toxicity and suggests methods for integrating data and predictions. This report concludes with lessons learned from current high-throughput screening programs and suggests some initial steps for DOD investment.

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