National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

TOXICITY-PATHWAY-BASED RISK ASSESSMENT

PREPARING FOR PARADIGM CHANGE

A Symposium Summary

Ellen Mantus, Rapporteur

Standing Committee on Risk Analysis Issues and Reviews

Board on Environmental Studies and Toxicology

Division on Earth and Life Studies

NATIONAL RESEARCH COUNCIL
OF THE NATIONAL ACADEMIES

THE NATIONAL ACADEMIES PRESS

Washington, D.C.
www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

THE NATIONAL ACADEMIES PRESS
500 Fifth Street, NW
Washington, DC 20001

NOTICE: The project that is the subject of this report was approved by the Governing Board of the National Research Council, whose members are drawn from the councils of the National Academy of Sciences, the National Academy of Engineering, and the Institute of Medicine. The members of the committee responsible for the report were chosen for their special competences and with regard for appropriate balance.

This project was supported by Contract No. EP-C-06-057 between the National Academy of Sciences and the U.S. Environmental Protection Agency. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the author(s) and do not necessarily reflect the view of the organizations or agencies that provided support for this project.

International Standard Book Number-13: 978-0-309-15422-2

International Standard Book Number-10: 0-309-15422-7

Additional copies of this report are available from

The National Academies Press

500 Fifth Street, NW Box 285 Washington, DC 20055 800-624-6242 202-334-3313 (in the Washington metropolitan area) http://www.nap.edu

Copyright 2010 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine


The National Academy of Sciences is a private, nonprofit, self-perpetuating society of distinguished scholars engaged in scientific and engineering research, dedicated to the furtherance of science and technology and to their use for the general welfare. Upon the authority of the charter granted to it by the Congress in 1863, the Academy has a mandate that requires it to advise the federal government on scientific and technical matters. Dr. Ralph J. Cicerone is president of the National Academy of Sciences.


The National Academy of Engineering was established in 1964, under the charter of the National Academy of Sciences, as a parallel organization of outstanding engineers. It is autonomous in its administration and in the selection of its members, sharing with the National Academy of Sciences the responsibility for advising the federal government. The National Academy of Engineering also sponsors engineering programs aimed at meeting national needs, encourages education and research, and recognizes the superior achievements of engineers. Dr. Charles M. Vest is president of the National Academy of Engineering.


The Institute of Medicine was established in 1970 by the National Academy of Sciences to secure the services of eminent members of appropriate professions in the examination of policy matters pertaining to the health of the public. The Institute acts under the responsibility given to the National Academy of Sciences by its congressional charter to be an adviser to the federal government and, upon its own initiative, to identify issues of medical care, research, and education. Dr. Harvey V. Fineberg is president of the Institute of Medicine.


The National Research Council was organized by the National Academy of Sciences in 1916 to associate the broad community of science and technology with the Academy’s purposes of furthering knowledge and advising the federal government. Functioning in accordance with general policies determined by the Academy, the Council has become the principal operating agency of both the National Academy of Sciences and the National Academy of Engineering in providing services to the government, the public, and the scientific and engineering communities. The Council is administered jointly by both Academies and the Institute of Medicine. Dr. Ralph J. Cicerone and Dr. Charles M. Vest are chair and vice chair, respectively, of the National Research Council.


www.national-academies.org

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

This page intentionally left blank.

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

PLANNING COMMITTEE FOR A SYMPOSIUM ON TOXICITY-PATHWAY-BASED RISK ASSESSMENT

Members

LORENZ RHOMBERG (Chair),

Gradient Corporation, Cambridge, MA

ELAINE FAUSTMAN,

University of Washington, Seattle

LYNN GOLDMAN,

Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

MICHAEL LAWTON,

Pfizer Global Research and Development, Groton, CT

GEORGE LEIKAUF,

University of Pittsburgh, Pittsburgh, PA

JOEL POUNDS,

Pacific Northwest National Laboratory, Richland, WA

JOYCE TSUJI,

Exponent, Inc., Bellevue, WA

LAUREN ZEISE,

California Environmental Protection Agency, Oakland

Staff

ELLEN MANTUS, Project Director

NORMAN GROSSBLATT, Senior Editor

HEIDI MURRAY-SMITH, Associate Program Officer

KEEGAN SAWYER, Associate Program Officer

JOHN BROWN, Program Associate

Sponsor

U.S. ENVIRONMENTAL PROTECTION AGENCY

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

STANDING COMMITTEE ON RISK ANALYSIS ISSUES AND REVIEWS

Members

BERNARD GOLDSTEIN (Chair),

University of Pittsburgh, Pittsburgh, PA

FREDERÍC BOIS,

Institut National de l’Environnement Industriel et des Risques, France

MICHAEL BRAUER,

University of British Columbia, Vancouver, Canada

RICHARD CORLEY,

Pacific Northwest National Laboratory, Richland, WA

LINDA COWAN,

University of Oklahoma, Oklahoma City

KENNETH CRUMP,

Environ, Ruston, LA

LYNN GOLDMAN,

Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

PHILIP LANDRIGAN,

Mount Sinai School of Medicine, New York, NY

THOMAS LOUIS,

Johns Hopkins Bloomberg School of Public Health, Baltimore, MD

NU-MAY RUBY REED,

California Environmental Protection Agency, Sacramento

LORENZ RHOMBERG,

Gradient Corporation, Cambridge, MA

JOYCE TSUJI,

Exponent, Inc., Bellevue, WA

Staff

ELLEN MANTUS, Project Director

HEIDI MURRAY-SMITH, Associate Program Officer

KEEGAN SAWYER, Associate Program Officer

JOHN BROWN, Program Associate

Sponsor

U.S. ENVIRONMENTAL PROTECTION AGENCY

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY1

Members

ROGENE F. HENDERSON (Chair),

Lovelace Respiratory Research Institute, Albuquerque, NM

RAMÓN ALVAREZ,

Environmental Defense Fund, Austin, TX

TINA BAHADORI,

American Chemistry Council, Arlington, VA

MICHAEL J. BRADLEY,

M.J. Bradley & Associates, Concord, MA

DALLAS BURTRAW,

Resources for the Future, Washington, DC

JAMES S. BUS,

Dow Chemical Company, Midland, MI

JONATHAN Z. CANNON,

University of Virginia, Charlottesville

GAIL CHARNLEY,

HealthRisk Strategies, Washington, DC

RUTH DEFRIES,

Columbia University, New York, NY

RICHARD A. DENISON,

Environmental Defense Fund, Washington, DC

H. CHRISTOPHER FREY,

North Carolina State University, Raleigh

J. PAUL GILMAN,

Covanta Energy Corporation, Fairfield, NJ

RICHARD M. GOLD,

Holland & Knight, LLP, Washington, DC

LYNN R. GOLDMAN,

Johns Hopkins University, Baltimore, MD

JUDITH A. GRAHAM (retired),

Pittsboro, NC

HOWARD HU,

University of Michigan, Ann Arbor

ROGER E. KASPERSON,

Clark University, Worcester, MA

TERRY L. MEDLEY,

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

JANA MILFORD,

University of Colorado at Boulder, Boulder

DANNY D. REIBLE,

University of Texas, Austin

JOSEPH V. RODRICKS,

ENVIRON International Corporation, Arlington, VA

ROBERT F. SAWYER,

University of California, Berkeley

KIMBERLY M. THOMPSON,

Harvard School of Public Health, Boston, MA

MARK J. UTELL,

University of Rochester Medical Center, Rochester, NY

Senior Staff

JAMES J. REISA, Director

DAVID J. POLICANSKY, Scholar

RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies

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

ELLEN K. MANTUS, Senior Program Officer for Risk Analysis

EILEEN N. ABT, Senior Program Officer

RUTH E. CROSSGROVE, Senior Editor

MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center

RADIAH ROSE, Manager, Editorial Projects

1

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

Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

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)

Atlantic Salmon in Maine (2004)

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

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

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 (seven volumes, 2000-2009)

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 Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

This page intentionally left blank.

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

Preface

In 2007, the National Research Council (NRC) released a report titled Toxicity Testing in the 21st Century: A Vision and a Strategy. That report proposed a new paradigm for toxicity testing that envisioned evaluation of biologically significant perturbations in key toxicity pathways by using new methods in molecular biology, bioinformatics, and computational toxicology and a comprehensive array of in vitro tests based primarily on human biology. The revolution in toxicity testing is under way, and a large influx of new data is anticipated. The U.S. Environmental Protection Agency will need to be able to interpret the new data and therefore asked the Standing Committee on Risk Analysis Issues and Reviews to convene a symposium to stimulate discussion on the application of the new approaches and data in risk assessment. This summary provides an overview of the presentations and discussions that took place at that symposium.

This summary has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the NRC’s 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 summary as sound as possible and to ensure that the summary 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 summary: Cynthia A. Afshari, Amgen, Inc.; Jonathan H. Freedman, Duke University; William B. Mattes, PharmPoint Consulting; and Joyce S. Tsuji, Exponent, Inc.

Although the reviewers listed above have provided many constructive comments and suggestions, they did not see the final draft of the summary before its release. The review of the summary was overseen by David L. Eaton, University of Washington. Appointed by the NRC, he was responsible for making certain that an independent examination of the summary was carried out in accordance with institutional procedures and that all review comments were

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

carefully considered. Responsibility for the final content of the summary rests entirely with the author and the institution.

The committee gratefully acknowledges those who made presentations or served on discussion panels at the symposium (see Appendix C for a list of speakers and affiliations). The committee is also grateful for the assistance of the NRC staff in preparing this summary. Staff members who contributed to the effort are Ellen Mantus, project director; Norman Grossblatt, senior editor; Heidi Murray-Smith, associate program officer; Keegan Sawyer, associate program officer; and Radiah Rose, editorial projects manager. I thank especially all the members of the planning committee for their efforts in the development of the program and the conduct of the symposium.

Lorenz Rhomberg, Chair
Planning Committee for a Symposium on
Toxicity-Pathway-Based Risk Assessment

Page xiii Cite
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

Contents

TABLES AND FIGURES

TABLES

1

 

Options for Future Toxicity-Testing Strategies Considered by the NRC Committee on Toxicity Testing and Assessment of Environmental Agents,

 

7

2

 

Phased Development of ToxCast Program,

 

16

3

 

Types of ToxCast Assays,

 

17

FIGURES

1

 

Components of the vision described in the report, Toxicity Testing in the 21st Century: A Vision and a Strategy,

 

8

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×

2

 

Perturbation of cellular response pathway, leading to adverse effects,

 

8

3

 

DNA sequencing output,

 

11

4

 

Throughput potential for data acquisition as related to levels of biologic organization,

 

13

5

 

Illustration of bioactivity profiling using high-throughput technologies to screen chemicals,

 

14

6

 

Overview of chemical registration for REACH,

 

21

7

 

Integration of new approaches for toxicology,

 

22

8

 

Dosimetry considerations in cell systems,

 

28

9

 

What do cells see? Protein adsorption by nanomaterials is a universal phenomenon in biologic systems,

 

28

10

 

Example of gene ontology for DNA metabolism, a biologic process,

 

31

11

 

Framework for interpretation of dose- and time-dependent genomic data,

 

32

12

 

Integrated data provide more comprehensive and accurate network reconstruction,

 

36

13

 

Illustration of the development of modular network models,

 

37

14

 

Interaction network that can be used to associate environmental factors with toxicity pathways and associated human diseases,

 

43

Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R1
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R2
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R3
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R4
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R5
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R6
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R8
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R9
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R10
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R11
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R12
Page xiii Cite
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R13
Suggested Citation:"Front Matter." National Research Council. 2010. Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary. Washington, DC: The National Academies Press. doi: 10.17226/12913.
×
Page R14
Next: Summary of the Symposium »
Toxicity-Pathway-Based Risk Assessment: Preparing for Paradigm Change: A Symposium Summary Get This Book
×
Buy Paperback | $46.00 Buy Ebook | $36.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

In 2007, the National Research Council envisioned a new paradigm in which biologically important perturbations in key toxicity pathways would be evaluated with new methods in molecular biology, bioinformatics, computational toxicology, and a comprehensive array of in vitro tests based primarily on human biology. Although some considered the vision too optimistic with respect to the promise of the new science, no one can deny that a revolution in toxicity testing is under way. New approaches are being developed, and data are being generated. As a result, the U.S. Environmental Protection Agency (EPA) expects a large influx of data that will need to be evaluated. EPA also is faced with tens of thousands of chemicals on which toxicity information is incomplete and emerging chemicals and substances that will need risk assessment and possible regulation. Therefore, the agency asked the National Research Council to convene a symposium to stimulate discussion on the application of the new approaches and data in risk assessment.

The symposium was held on May 11-13, 2009, in Washington, DC, and included presentations and discussion sessions on pathway-based approaches for hazard identification, applications of new approaches to mode-of-action analyses, the challenges to and opportunities for risk assessment in the changing paradigm, and future directions.

  1. ×

    Welcome to OpenBook!

    You're looking at OpenBook, NAP.edu's online reading room since 1999. Based on feedback from you, our users, we've made some improvements that make it easier than ever to read thousands of publications on our website.

    Do you want to take a quick tour of the OpenBook's features?

    No Thanks Take a Tour »
  2. ×

    Show this book's table of contents, where you can jump to any chapter by name.

    « Back Next »
  3. ×

    ...or use these buttons to go back to the previous chapter or skip to the next one.

    « Back Next »
  4. ×

    Jump up to the previous page or down to the next one. Also, you can type in a page number and press Enter to go directly to that page in the book.

    « Back Next »
  5. ×

    Switch between the Original Pages, where you can read the report as it appeared in print, and Text Pages for the web version, where you can highlight and search the text.

    « Back Next »
  6. ×

    To search the entire text of this book, type in your search term here and press Enter.

    « Back Next »
  7. ×

    Share a link to this book page on your preferred social network or via email.

    « Back Next »
  8. ×

    View our suggested citation for this chapter.

    « Back Next »
  9. ×

    Ready to take your reading offline? Click here to buy this book in print or download it as a free PDF, if available.

    « Back Next »
Stay Connected!