National Academies Press: OpenBook
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

REVIEW OF THE ENVIRONMENTAL PROTECTION
AGENCY’S STATE-OF-THE-SCIENCE EVALUATION OF
NONMONOTONIC
DOSE-RESPONSE
RELATIONSHIPS

AS THEY APPLY TO
ENDOCRINE DISRUPTORS

Committee to Review EPA’s State of the Science Paper
on Nonmonotonic Dose Response

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. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

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 EP-C-09-003 between the National Academy of Sciences and the US Environmental Protection Agency. 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: 978-0-309-29754-7

International Standard Book Number-10: 0-309-29754-0

Additional copies of this report are available for sale from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu/.

Copyright 2014 by the National Academy of Sciences. All rights reserved.

Printed in the United States of America

Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

THE NATIONAL ACADEMIES

Advisers to the Nation on Science, Engineering, and Medicine

The National Academ 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 achieve ents of engineers. Dr. C. D. Mote, Jr., 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. C. D. Mote, Jr., are chair and vice chair, respectively, of the National Research Council.

www.national-academies.org

Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

This page intentionally left blank.

Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

COMMITTEE TO REVIEW EPA’S DRAFT STATE OF THE SCIENCE PAPER ON NONMONOTONIC DOSE RESPONSE

Members

DAVID A. SAVITZ (Chair), Brown University, Providence, RI

ANDREA BACCARELLI, Harvard School of Public Health, Boston, MA

ROBERT E. CHAPIN, Pfizer, Inc., Groton, CT

RICHARD A. CORLEY, Pacific Northwest National Laboratory, Richland, WA

GEORGE P. DASTON, Procter and Gamble Company, Mason, OH

RUSS B. HAUSER, Harvard School of Public Health, Boston, MA

AMY H. HERRING, University of North Carolina, Chapel Hill, NC

ANDREAS KORTENKAMP, Brunel University, Uxbridge, United Kingdom

HEATHER B. PATISAUL, North Carolina State University, Raleigh, NC

ELIZABETH N. PEARCE, Boston University, Boston, MA

TRACEY J. WOODRUFF, University of California San Francisco, CA

LAUREN ZEISE, California Environmental Protection Agency, Oakland, CA

YILIANG ZHU, University of South Florida, Tampa, FL

Staff

SUSAN N.J. MARTEL, Project Director

KERI STOEVER, Research Associate

NORMAN GROSSBLATT, Senior Editor

MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center

RADIAH ROSE, Manager, Editorial Projects

TAMARA DAWSON, Program Associate

Sponsor

US Environmental Protection Agency

Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Members

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

PRAVEEN AMAR, Clean Air Task Force, Boston, 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, HealthRisk Strategies, Washington, DC

DOMINIC M. DI TORRO, 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, George Washington University, Washington, DC

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

WILLIAM E. HALPERIN, Rutgers University, 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

SAMUEL KACEW, University of Ottawa, Ontario, ON, Canada

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, Boulder, CO

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, Bellevue, WA

Senior Staff

JAMES J. REISA, Director

DAVID J. POLICANSKY, Scholar

RAYMOND A. WASSEL, Senior Program Officer for Environmental Studies

ELLEN K. MANTUS, Senior Program Officer for Risk Analysis

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

MIRSADA KARALIC-LONCAREVIC, Manager, Technical Information Center

RADIAH ROSE, Manager, Editorial Projects

Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

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

Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

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)

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 (seventeen volumes, 2000-2014)

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. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

Preface

Potential health effects of endocrine-disrupting chemicals raise an environmental health concern about the chemicals’ ability to interfere with normal hormone function in humans and wildlife. Some research on endocrine-disrupting chemicals has identified dose–response relationships that have nonmonotonic curves; that is, lower doses are not always associated with smaller responses, nor higher doses with larger responses. Nonmonotonic dose–response (NMDR) curves have been a subject of debate in regulatory toxicology because of their implications for how chemicals should be tested and for how risks posed by such chemicals should be assessed. The debate has focused on whether standard toxicity-testing protocols assess relevant health effects for such chemicals, on the degree to which such tests might miss low-dose effects of NMDR relationships (false-negative results), and on the implications of the evidence on NMDR curves for current risk-assessment practices. To help to address those issues, the US Environmental Protection Agency (EPA) developed a draft State of the Science Evaluation: Nonmonotonic Dose Responses as They Apply to Estrogen, Androgen, and Thyroid Pathways and EPA Testing and Assessment Procedures. EPA asked the National Research Council to conduct an independent review of its evaluation to ensure that it is scientifically sound and of high quality.

In response to EPA’s request, the National Research Council convened the Committee to Review EPA’s Draft State of the Science Paper on Nonmonotonic Dose Response, which prepared this report. The members of the committee were selected for their expertise in reproductive and developmental toxicology, endocrinology, epidemiology, environmental epigenetics, toxicogenomics, mechanistic toxicology, physiologically based pharmacokinetic modeling, risk assessment, and biostatistics. Biographic information on the committee members is presented in Appendix A.

The committee’s report has been reviewed in draft form by persons chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the National Research Council’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 report as sound as possible and to ensure that the report meets institutional standards of objectivity,

Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×

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 the report: Sandra Baird, Massachusetts Department of Environmental Protection; Niladri Basu, McGill University; Jan-Åke Gustafsson, University of Houston; Sangtae Kim, Purdue University; M. Sue Marty, The Dow Chemical Company; Shyamal Peddada, National Institute of Environmental Health Sciences; Gail Prins, University of Illinois at Chicago; Justin Teeguarden, Pacific Northwest National Laboratory; Rochelle Tyl, RTI International; John Vandenbergh, North Carolina State University; and R. Thomas Zoeller, University of Massachusetts Amherst.

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 Linda McCauley, Emory University, and Martin Philbert, University of Michigan. Appointed by the National Research Council, 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 author committee and the institution.

The committee is grateful for the assistance of National Research Council staff in preparing the report. It particularly wishes to acknowledge with deep gratitude the support of Project Director Susan Martel, who coordinated the project and contributed to the committee’s report. Other staff members who contributed to this effort are James Reisa, director of the Board on Environmental Studies and Toxicology; Keri Stoever, research associate; Tamara Dawson, program associate; Norman Grossblatt, senior editor; and Mirsada Karalic-Loncarevic, manager of the Technical Information Center.

Finally, I thank all the members of the committee for their efforts throughout the development of this report. Their varied expertise attests to the complexity of this topic, and the committee’s ability to synthesize that expertise into a clear consensus is much appreciated.

David A. Savitz, PhD, Chair
Committee to Review EPA’s Draft State
of the Science Paper on Nonmonotonic
Dose Response

Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R1
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R2
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R3
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R4
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R5
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R6
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R7
Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R8
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R9
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R10
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R11
Suggested Citation:"Front Matter." National Research Council. 2014. Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors. Washington, DC: The National Academies Press. doi: 10.17226/18608.
×
Page R12
Next: Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as They Apply to Endocrine Disruptors »
Review of the Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response Relationships as they Apply to Endocrine Disruptors Get This Book
×
Buy Paperback | $33.00 Buy Ebook | $26.99
MyNAP members save 10% online.
Login or Register to save!
Download Free PDF

Potential health effects from chemicals that disrupt endocrine function pose an environmental health concern because of their ability to interfere with normal hormone function in human and wildlife populations. The endocrine system regulates biological processes throughout the body and is sensitive to small changes in hormone concentrations. Endocrine-disruptor research has focused primarily on chemicals that affect three hormone pathways that play important roles in reproduction and development - the estrogen, androgen, and thyroid hormone pathways. Some of this research has identified dose-response relationships that have nonmonotonic curves. Nonmonotonic dose-response curves (NMDRs) are of concern because they do not follow the usual assumption made in toxicology that as dose decreases the response also decreases.

The existence of NMDRs has been a controversial topic for decades, and there has been considerable debate about their implications for how chemicals are tested and for how risks from such chemicals are assessed. Toxicity tests are designed to identify hazards and to characterize dose-response relationships, so tests are aimed at finding a (high) dose that elicits a response, and dose-response is explored by testing lower doses spaced to identify statistically a no- or lowest-observed-adverse-effect level. The concern for NMDRs is that such studies, as currently designed, might not detect the inflection of the dose-response curve if only a few doses are tested or if the change in inflection occurs below the range of doses tested. Another concern is that some NMDRs are found for biological effects that are not usually evaluated in toxicity tests. If current testing strategies are inadequate to account for NMDRs, changes to risk assessment practices might be necessary. To help address these issues, the U.S. Environmental Protection Agency (EPA) developed a draft State-of-the-Science Evaluation: Nonmonotonic Dose Responses as they Apply to Estrogen, Androgen, and Thyroid Pathways and EPA Testing and Assessment Procedures. EPA asked the National Research Council to conduct an independent review of this evaluation to ensure that it is scientifically sound and of high quality.

Review of Environmental Protection Agency's State-of-the-Science Evaluation of Nonmonotonic Dose-Response as they Apply to Endocrine Disrupters evaluates whether EPA's evaluation presents a scientifically sound and high-quality analysis of the literature on NMDRs. This report reviews how well the EPA evaluation described how the assessment was performed, whether consistent methods and criteria were applied in the analysis of different evidence streams, and whether appropriate methods were applied to evaluating the evidence. The report makes recommendations to improve EPA's process and strengthen the evaluation.

  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!