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Toxicological Effects of Methylmercury (2000)

Chapter:Front Matter

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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Toxicological Effects of Methylmercury

Committee on the Toxicological Effects of Methylmercury

Board on Environmental Studies and Toxicology

Commission on Life Sciences

National Research Council

NATIONAL ACADEMY PRESS
Washington, DC

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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NATIONAL ACADEMY PRESS
2101 Constitution Ave., N.W. Washington, D.C.20418

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 Grant Agreement No. X 827238-01 between the National Academy of Sciences and the 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.

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Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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THE NATIONAL ACADEMIES

National Academy of Sciences

National Academy of Engineering

Institute of Medicine

National Research Council

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. Bruce M. Alberts 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. William A. Wulf 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. Kenneth I. Shine 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. Bruce M. Alberts and Dr. William A. Wulf are chairman and vice chairman, respectively, of the National Research Council.

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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COMMITTEE ON THE TOXICOLOGICAL EFFECTS OF METHYLMERCURY

ROBERT A. GOYER (Chair),

University of Western Ontario (Professor, Emeritus), Chapel Hill, North Carolina

H. VASKEN APOSHIAN,

University of Arizona, Tucson, Arizona

LENORE ARAB,

University of North Carolina, Chapel Hill, North Carolina

DAVID C. BELLINGER,

Harvard Medical School, Boston, Massachusetts

THOMAS M. BURBACHER,

University of Washington, Seattle, Washington

THOMAS A. BURKE,

The Johns Hopkins University, Baltimore, Maryland

JOSEPH L. JACOBSON,

Wayne State University, Detroit, Michigan

LYNDA M. KNOBELOCH,

State of Wisconsin Bureau of Environmental Health, Madison, Wisconsin

LOUISE M. RYAN,

Dana-Farber Cancer Institute, Boston, Massachusetts

ALAN H. STERN,

New Jersey Department of Environmental Protection, Trenton, New Jersey

Staff

CAROL A. MACZKA, Director,

Toxicology and Risk Assessment Program

MICHELLE C. CATLIN, Research Associate

RUTH E. CROSSGROVE, Editor

MIRSADA KARALIC-LONCAREVIC, Information Specialist

JUDITH L. ESTEP, Senior Program Assistant

LAURA T. HOLLIDAY, Senior Program Assistant

STEPHANIE K. PARKER, Graphics and Layout

Sponsor

U.S. ENVIRONMENTAL PROTECTION AGENCY

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
×

BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

GORDON ORIANS (Chair),

University of Washington, Seattle, Washington

DONALD MATTISON (Vice Chair),

March of Dimes, White Plains, New York

DAVID ALLEN,

University of Texas, Austin, Texas

INGRID C. BURKE,

Colorado State University, Fort Collins, Colorado

WILLIAM L. CHAMEIDES,

Georgia Institute of Technology, Atlanta, Georgia

JOHN DOULL,

The University of Kansas Medical Center, Kansas City, Kansas

CHRISTOPHER B. FIELD,

Carnegie Institute of Washington, Stanford, California

JOHN GERHART,

University of California, Berkeley, California

J. PAUL GILMAN,

Celera Genomics, Rockville, Maryland

BRUCE D. HAMMOCK,

University of California, Davis, California

MARK HARWELL,

University of Miami, Miami, Florida

ROGENE HENDERSON,

Lovelace Respiratory Research Institute, Albuquerque, New Mexico

CAROL HENRY,

Chemical Manufacturers Association, Arlington, Virginia

BARBARA HULKA,

University of North Carolina, Chapel Hill, North Carolina

JAMES F. KITCHELL,

University of Wisconsin, Madison, Wisconsin

DANIEL KREWSKI,

University of Ottawa, Ottawa, Ontario

JAMES A. MACMAHON,

Utah State University, Logan, Utah

MARIO J. MOLINA,

Massachusetts Institute of Technology, Cambridge, Massachusetts

CHARLES O'MELIA,

Johns Hopkins University, Baltimore, Maryland

WILLEM F. PASSCHIER,

Health Council of the Netherlands

KIRK SMITH,

University of California, Berkeley, California

MARGARET STRAND,

Oppenheimer Wolff Donnelly & Bayh, LLP, Washington, D.C.

TERRY F. YOSIE,

Chemical Manufacturers Association, Arlington, Virginia

Senior Staff

JAMES J. REISA, Director

DAVID J. POLICANSKY, Associate Director and Senior Program Director for Applied Ecology

CAROL A. MACZKA, Senior Program Director for Toxicology and Risk Assessment

RAYMOND A. WASSEL, Senior Program Director for Environmental Sciences and Engineering

KULBIR BAKSHI, Program Director for the Committee on Toxicology

LEE R. PAULSON, Program Director for Resource Management

ROBERTA M. WEDGE, Program Director for Risk Analysis

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
×

COMMISSION ON LIFE SCIENCES

MICHAEL T. CLEGG (Chair),

University of California, Riverside, California

PAUL BERG (Vice Chair),

Stanford University, Stanford, California

FREDERICK R. ANDERSON,

Cadwalader, Wickersham & Taft, Washington, D.C.

JOANNA BURGER,

Rutgers University, Piscataway, New Jersey

JAMES E. CLEAVER,

University of California, San Francisco, California

DAVID EISENBERG,

University of California, Los Angeles, California

JOHN EMMERSON,

Fishers, Indiana

NEAL FIRST,

University of Wisconsin, Madison, Wisconsin

DAVID J. GALAS,

Keck Graduate Institute of Applied Life Science, Claremont, California

DAVID V. GOEDDEL,

Tularik, Inc., South San Francisco, California

ARTURO GOMEZ-POMPA,

University of California, Riverside, California

COREY S. GOODMAN,

University of California, Berkeley, California

JON W. GORDON,

Mount Sinai School of Medicine, New York, New York

DAVID G. HOEL,

Medical University of South Carolina, Charleston, South Carolina

BARBARA S. HULKA,

University of North Carolina, Chapel Hill, North Carolina

CYNTHIA KENYON,

University of California, San Francisco, California

BRUCE R. LEVIN,

Emory University, Atlanta, Georgia

DAVID LIVINGSTON,

Dana-Farber Cancer Institute, Boston, Massachusetts

DONALD R. MATTISON,

March of Dimes, White Plains, New York

ELLIOT M. MEYEROWITZ,

California Institute of Technology, Pasadena, California

ROBERT T. PAINE,

University of Washington, Seattle, Washington

RONALD R. SEDEROFF,

North Carolina State University, Raleigh, North Carolina

ROBERT R. SOKAL,

State University of New York, Stony Brook, New York

CHARLES F. STEVENS,

The Salk Institute, La Jolla, California

SHIRLEY M. TILGHMAN,

Princeton University, Princeton, New Jersey

RAYMOND L. WHITE,

University of Utah, Salt Lake City, Utah

Staff

WARREN R. MUIR, Executive Director

JACQUELINE K. PRINCE, Financial Officer

BARBARA B. SMITH, Administrative Associate

LAURA T. HOLLIDAY, Senior Project Assistant

Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
×

OTHER REPORTS OF THE BOARD ON ENVIRONMENTAL STUDIES AND TOXICOLOGY

Strengthening Science at the U.S. Environmental Protection Agency: Research Management and Peer Review Practices (2000)

Scientific Frontiers in Developmental Toxicology and Risk Assessment (2000)

Modeling Mobile-Source Emissions (2000)

Copper in Drinking Water (2000)

Ecological Indicators for the Nation (2000)

Waste Incineration and Public Health (1999)

Hormonally Active Agents in the Environment (1999)

Research Priorities for Airborne Particulate Matter: I. Immediate Priorities and a Long-Range Research Portfolio (1998); II. Evaluating Research Progress and Updating the Portfolio (1999)

Ozone-Forming Potential of Reformulated Gasoline (1999)

Risk-Based Waste Classification in California (1999)

Arsenic in Drinking Water (1999)

Brucellosis in the Greater Yellowstone Area (1998)

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

Toxicologic Assessment of the Army's Zinc Cadmium Sulfide Dispersion Tests (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 (5 reports, 1989-1995)

Review of EPA's Environmental Monitoring and Assessment Program (3 reports, 1994-1995)

Science and Judgment in Risk Assessment (1994)

Ranking Hazardous Waste Sites for Remedial Action (1994)

Pesticides in the Diets of Infants and Children (1993)

Issues in Risk Assessment (1993)

Setting Priorities for Land Conservation (1993)

Protecting Visibility in National Parks and Wilderness Areas (1993)

Dolphins and the Tuna Industry (1992)

Hazardous Materials on the Public Lands (1992)

Science and the National Parks (1992)

Animals as Sentinels of Environmental Health Hazards (1991)

Assessment of the U.S. Outer Continental Shelf Environmental Studies Program, Volumes I-IV (1991-1993)

Human Exposure Assessment for Airborne Pollutants (1991)

Monitoring Human Tissues for Toxic Substances (1991)

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
×

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 Academy Press

(800) 624-6242

(202) 334-3313

www.nap.edu

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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PREFACE

IN 1997, the U.S. Environmental Protection Agency (EPA) issued two reports to the U.S. Congress on mercury (Hg) and its effects on public health. The first of these reports, the Mercury Study Report to Congress, assessed the source and amount of Hg emissions in the United States, the detrimental effects of Hg on humans and wildlife, and the feasibility of control technologies. The second report, the Utility Hazardous Air Pollutant Report to Congress, looked specifically at emissions from utility companies and cited Hg as a major contaminant, especially in emissions from coal-fired power plants. Once in the environment, Hg can be converted to methylmercury (MeHg), which bioaccumulates up the food chain. Such bioaccummulation can lead to high concentrations of MeHg in predatory fish. Because of concerns about MeHg exposure levels in the United States from the consumption of contaminated fish, particularly among sensitive populations, questions have arisen among federal agencies over what is an acceptable level of exposure to MeHg. Because of gaps in the scientific data regarding Hg toxicity, particularly MeHg, the potentially widespread implications for human health, and the high financial costs and feasibility problems associated with further regulating Hg emissions, Congress directed EPA in the House Appropriations Report for EPA's Fiscal 1999 funding to contract with the National Research Council (NRC) to prepare recommendations on the appropriate reference dose for Hg exposure.

In this report, the Committee on the Toxicological Effects of Methylmercury of the NRC independently reviewed the reference dose

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
×

for MeHg. The committee reviewed the available toxicological, epidemiological, and exposure data (from food and water) and determined the appropriateness of the critical study, end points of toxicity, and uncertainty factors used by EPA in the derivation of the reference dose for MeHg. The committee was also asked to identify data gaps and make recommendations for future research.

This report has been reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise in accordance with procedures approved by the NRC's Report Review Committee for reviewing NRC and Institute of Medicine reports. The purpose of this independent review is to provide candid and critical comments that will assist the NRC in making the published report as sound as possible and to ensure that the report meets institutional standards for objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscripts remain confidential to protect the integrity of the deliberative process. The committee wishes to thank the following individuals, who are neither officials nor employees of the NRC, for their participation in the review of this report: Melvin Andersen, Colorado State University; Michael Aschner, Wake Forest University; Kenny Crump, ICF Consulting; Kim Dietrich, University of Cincinnati; Johanna Dwyer, New England Medical Center; John Emmerson, Eli Lilly (retired); Susan Miller, University of California at San Francisco; Charles Poole, University of North Carolina; Jonathan Samet, Johns Hopkins University; Ellen Silbergeld, University of Maryland; Christopher Whipple, Environ International Corporation; James Woods, University of Washington.

The individuals listed above have provided many constructive comments and suggestions. It must be emphasized, however, that responsibility for the final content of this report rests entirely with the authoring committee and the NRC.

The committee gratefully acknowledges the following individuals for providing background information and for making presentations to the committee: Richard Duffy of the office of Senator Patrick Leahy (Vermont); Lee Alman of the office of Congressman Alan Mollohan (West Virginia); George Lucier, National Institute of Environmental Health Sciences; William Farland, EPA; Michael Bolger, Food and Drug Administration; Christopher DeRosa, Agency for Toxic Substances and Disease Registry; E. Spencer Garrett, National Oceanic and Atmospheric Administration, Fran Sharples, Office of Science and Technology; Michael Bender, Mercury Policy Project; Jane Williams, California

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Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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Communities Against Toxics; Eric Uram, Sierra Club-Great Lakes Program; Greg Schaefer, Arch Coal, Inc.; Leonard Levin, Electric Power Research Institute; and David Michaud, Wisconsin Electric Power Company. The committee also heard from a number of researchers actively investigating issues related to MeHg exposure. Those researchers are Tord Kjellstrom, University of Auckland, New Zealand; Donna Mergler, University of Quebec at Montreal; Kenny Crump, ICF Kaiser; Ellen Silbergeld, University of Maryland; Philippe Grandjean, University of Southern Denmark; Neils Keiding and Esben Budtz-Jøergensen, both from the University of Copenhagen; and Thomas Clarkson, Christopher Cox, Gary Myers, Philip Davidson, and Mark Moss, all from the University of Rochester. In addition, the committee wants to give special thanks to individuals and groups who provided further analyses and information at the request of the committee. Those are Wayne Rosamond, University of North Carolina; Philippe Grandjean; Neils Keiding; Esben Budtz-Jørgensen; Thomas Clarkson; Christopher Cox; Tord Kjellstrom; Harvey Clewell III; Jeffrey Swartout; Cynthia Van Landingham; and Kenny Crump. The committee also gratefully acknowledges input from individuals representing the Environmental Working Group, the Dental Amalgam Mercury Syndrome (DAMS) organization and the Mercury Free Press.

The committee is grateful for the assistance of the NRC staff in preparing the report. Staff members who contributed to this effort are Carol A. Maczka, senior program director for the Toxicology and Risk Assessment Program; Michelle Catlin, research associate; Ruth E. Crossgrove, editor; Laura Holliday and Judy Estep, senior project assistants; and Mirsada Karalic-Loncarevic, information specialist.

Finally, I would like to thank all the members of the committee for their dedicated efforts throughout the development of this report.

Robert A. Goyer

Chair, Committee on the Toxicological

Effects of Methylmercury

Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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 3

 

BIOLOGICAL VARIABILITY

 

72

   

 Age-Related Susceptibility,

 

72

   

 Gender Differences,

 

73

   

 Genetics,

 

74

   

 Mechanisms of Nutritional Influence on MeHg Health Effects,

 

75

   

 Toxicokinetic Variability,

 

83

   

 Conclusions,

 

95

   

 Recommendations,

 

96

   

 References,

 

98

 4

 

DOSE ESTIMATION

 

105

   

 Dietary Assessment,

 

105

   

 Biomarkers of Exposure,

 

111

   

 Analytical Error in Biomarker Measurements,

 

127

   

 Exposure and Dose Assessment in the Seychelles, Faroe Islands, and New Zealand Studies,

 

129

   

 Summary and Conclusions,

 

136

   

 Recommendations,

 

139

   

 References,

 

140

 5

 

HEALTH EFFECTS OF METHYLMERCURY

 

147

   

 Carcinogenicity,

 

149

   

 Genotoxicity,

 

154

   

 Immunotoxicity,

 

156

   

 Reproductive Effects,

 

161

   

 Renal Toxicity,

 

164

   

 Cardiovascular Effects,

 

168

   

 Hematological Effects,

 

173

   

 Developing Central-Nervous-System Toxicity,

 

174

   

 Adult Central-Nervous-System Toxicity,

 

221

   

 Conclusions,

 

228

   

 Recommendations,

 

231

   

 References,

 

232

 6

 

COMPARISON OF STUDIES FOR USE IN RISK ASSESSMENT

 

250

   

 Assessment of Prenatal Hg Exposure: Cord Blood Versus Maternal Hair and Timing of Exposure,

 

252

   

 Differences in the Neurobehavioral End Points Assessed and the Children 's Ages at Assessment,

 

255

   

 Stable Versus Episodic Pattern of Exposure,

 

258

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Suggested Citation:"Front Matter." National Research Council. 2000. Toxicological Effects of Methylmercury. Washington, DC: The National Academies Press. doi: 10.17226/9899.
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 Study Differences in Control for Confounders,

 

259

   

 Population Differences in Vulnerability,

 

264

   

 Random Variation in the Detectability of Effects at Low Exposures,

 

266

   

 Conclusions,

 

267

   

 Recommendations,

 

269

   

 References,

 

269

 7

 

DOSE-RESPONSE ASSESSMENT

 

271

   

 Risk Assessment for Non-Cancer End Points,

 

271

   

 Benchmark-Dose Calculations for Continuous Outcomes,

 

273

   

 Some Specific Considerations for MeHg,

 

277

   

 Comparing Benchmark Doses,

 

281

   

 Choosing a Critical Dose for a Point of Departure,

 

283

   

 An Integrative Analysis,

 

289

   

 Model Choice Issues,

 

293

   

 Summary and Conclusions,

 

298

   

 Recommendations,

 

300

   

 References,

 

301

 8

 

RISK CHARACTERIZATION AND PUBLIC HEALTH IMPLICATIONS

 

304

   

 The Current EPA Reference Dose,

 

305

   

 Evaluating the RfD–End Points of MeHg Toxicity,

 

307

   

 Selection of the End Point for the RfD,

 

311

   

 Examination of Critical Studies for the RfD,

 

311

   

 BMD Considerations: Selecting a Point of Departure,

 

314

   

 Selection of the Critical Study and Point of Departure for the Revised RfD,

 

317

   

 Sources of Uncertainty: Consideration for Uncertainty Factors,

 

318

   

 Implications for Public Health and Risk Management,

 

322

   

 Committee Findings and Recommendations,

 

326

   

 References,

 

329

 

 

APPENDIX TO CHAPTER 7

 

333

 

 

GLOSSARY

 

337

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Toxicological Effects of Methylmercury

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Mercury is widespread in our environment. Methylmercury, one organic form of mercury, can accumulate up the aquatic food chain and lead to high concentrations in predatory fish. When consumed by humans, contaminated fish represent a public health risk.

Combustion processes, especially coal-fired power plants, are major sources of mercury contamination in the environment. The U.S. Environmental Protection Agency (EPA) is considering regulating mercury emissions from those plants.

Toxicological Effects of Methylmercury reviews the health effects of methylmercury and discusses the estimation of mercury exposure from measured biomarkers, how differences between individuals affect mercury toxicity, and appropriate statistical methods for analysis of the data and thoroughly compares the epidemiological studies available on methylmercury. Included are discussions of current mercury levels on public health and a delineation of the scientific aspects and policy decisions involved in the regulation of mercury.

This report is a valuable resource for individuals interested in the public health effects and regulation of mercury. The report also provides an excellent example of the implications of decisions in the risk assessment process for a larger audience.

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