National Academies Press: OpenBook

Environmental Neurotoxicology (1992)

Chapter: Front Matter

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

Environmental Neurotoxicology

Committee on Neurotoxicology and Models for Assessing Risk

Board on Environmental Studies and Toxicology

Commission on Life Sciences

National Research Council

NATIONAL ACADEMY PRESS
Washington, D.C.
1992

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

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 competencies and with regard for appropriate balance.

This report has been reviewed by a group other than the authors according to procedures approved by a Report Review Committee consisting of members of the National Academy of Sciences, the National Academy of Engineering, and the Institute of 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. Frank Press 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. Robert M. White 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 Shine is president of the Institute of Medicine.

Environmental neurotoxicology / Committee on Neurotoxicology and Models for Assessing Risk, Commission on Life Sciences, National Research Council

p. cm.

Includes bibliographical references and index.

ISBN 0-309-04531-2

1. Neurotoxicology. 2. Environmental monitoring. 3. Health risk assessment. I. National Research Council (U.S.). Committee on Neurotoxicology and Models for Assessing Risk.

[DNLM: 1. Environmental Exposure. 2. Nervous System--drug effects. WL 100 E61]

RC347.5.E58 1991

615.9--dc20

DNLM/DLC

for Library of Congress 91-43537

CIP

Additional copies of this report are available from the
National Academy Press,
2101 Constitution Avenue, N.W., Washington, D.C. 20418

S538

Printed in the United States of America

First Printing, January 1992

Second Printing, August 1992

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

Committee on Neurotoxicology and Models for Assessing Risk

PHILIP J. LANDRIGAN, Chairman,

Mt. Sinai School of Medicine, New York

DOYLE G. GRAHAM, Vice Chairman,

Duke University Medical Center, Durham, North Carolina

W. KENT ANGER,

Oregon Health Sciences University, Portland

JEFFERY BARKER,

National Institutes of Health, Bethesda, Maryland

TERRI DAMSTRA,

National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina

DALE HATIIS,

Massachusetts Institute of Technology, Cambridge

WILLIAM LANGSTON,

California Parkinson Foundation, San Jose

HERBERT E. LOWNDES,

Rutgers University, Piscataway, New Jersey

JOE MARWAH,

National Institutes of Health, Bethesda, Maryland

PIERRE MORELL,

University of North Carolina, Chapel Hill

TOSHIO NARASHI,

Northwestern University Medical School, Chicago

PHILLIP P. NELSON,

National Institutes of Health, Bethesda, Maryland

LAWRENCE W. REITER,

U.S. Environmental Protection Agency, Research Triangle Park, North Carolina

PATRICIA RODIER,

University of Rochester, Rochester, New York

JOSEPH RODRICKS,

Environ Corporation, Arlington, Virginia

ELLEN K. SILBERGELD,

University of Maryland at Baltimore, Baltimore

PETER S. SPENCER,

Oregon Health Sciences University, Portland

BERNARD WEISS,

University of Rochester, Rochester, New York

RONALD WYZGA,

Electric Power Research Institute, Palo Alto, California

DONALD MATTISON,

Liaison, Board on Environmental Studies and Toxicology

JOHN L. EMMERSON,

Liaison, Board on Environmental Studies and Toxicology

Staff

RICHARD D. THOMAS, Program Director

KATHLEEN R. STRATTON, Project Director

MARY B. PAXTON, Senior Staff Officer

MARVIN A. SCHNEIDERMAN, Senior Staff Scientist

ANDREW M. POPE, Senior Staff Officer

NORMAN GROSSBLATT, Editor

ANNE M. SPRAGUE, Information Specialist

GARY J. BENNETT, Technical Adviser

IAN C.T. NISBET, Technical Adviser

HUGH TILSON, Technical Adviser

LINDA V. LEONARD, Senior Project Assistant

Sponsor

Agency for Toxic Substances and Disease Registry, U.S. Public Health Service

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

Board on Environmental Studies and Toxicology

PAUL G. RISSER (Chairman),

University of New Mexico, Albuquerque

GILBERT S. OMENN (Immediate Past Chairman),

University of Washington, Seattle

FREDERICK R. ANDERSON,

Washington School of Law, American University

JOHN C. BAILAR, III,

McGill University School of Medicine, Montreal

LAWRENCE W. BARNTHOUSE,

Oak Ridge National Laboratory, Oak Ridge

GARRY D. BREWER,

Yale University, New Haven

EDWIN H. CLARK,

Department of Natural Resources & Environmental Control, State of Delaware, Dover

YORAM COHEN,

University of California, Los Angeles

JOHN L. EMMERSON,

Lilly Research Laboratories, Greenfield, Indiana

ROBERT L HARNESS,

Monsanto Agricultural Company, St. Louis

ALFRED G. KNUDSON,

Fox Chase Cancer Center, Philadelphia

GENE E. LIKENS,

The New York Botanical Garden, Millbrook

PAUL J. LIOY,

UMDNJ-Robert Wood Johnson Medical School, Piscataway, New Jersey

JANE LUBCHENCO,

Oregon State University, Corvallis

DONALD MATTISON,

University of Pittsburgh, Pittsburgh

GORDON ORIANS,

University of Washington, Seattle

NATHANIEL REED,

Hobe Sound, Florida

MARGARET M. SEMINARIO,

AFL/CIO, Washington, DC

I. GLENN SIPES,

University of Arizona, Tucson

WALTER J. WEBER, JR.,

University of Michigan, Ann Arbor

Staff

JAMES J. REISA, Director

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

RICHARD D. THOMAS, Associate Director and Program Director for Human Toxicology and Risk Assessment

LEE R. PAULSON, Program Director for Information Systems and Statistics

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

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

Commission on Life Sciences

BRUCE M. ALBERTS (Chairman),

University of California, San Francisco

BRUCE N. AMES,

University of California, Berkeley

J. MICHAEL BISHOP,

Hooper Research Foundation, University of California Medical Center, San Francisco

MICHAEL T. CLEGG,

University of California, Riverside

GLENN A. CROSBY,

Washington State University, Pullman

LEROY E. HOOD,

California Institute of Technology, Pasadena

DONALD F. HORNIG,

Harvard School of Public Health, Boston

MARIAN E. KOSHLAND,

University of California, Berkeley

RICHARD E. LENSKI,

University of California, Irvine

STEVEN P. PAKES,

Southwestern Medical School, University of Texas, Dallas

EMIL A. PFITZER,

Hoffman-LaRoche, Inc., Nutley, New Jersey

THOMAS D. POLLARD,

Johns Hopkins Medical School, Baltimore

JOSEPH E. RALL,

National Institutes of Health, Bethesda, Maryland

RICHARD D. REMINGTON,

University of Iowa, Iowa City

PAUL G. RISSER,

University of New Mexico, Albuquerque

HAROLD M. SCHMECK, JR.,

Armonk, New York

RICHARD B. SETLOW,

Brookhaven National Laboratory, Upton, New York

CARLA J. SHATZ,

Stanford University School of Medicine, Stanford

TORSTEN N. WIESEL,

Rockefeller University, New York, NY

JOHN E. BURRIS, Executive Director

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

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. Frank Press and Dr. Robert M. White are chairman and vice chairman, respectively, of the National Research Council.

The project was supported by the Environmental Protection Agency; the National Institute of Environmental Health Sciences; and the Comprehensive Environmental Response, Compensation, and Liability Act Trust Fund through cooperative agreement with the Agency for Toxic Substances and Disease Registry, U.S. Public Health Service, Department of Health and Human Services.

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

Preface

There is convincing evidence that chemicals in the environment can alter the function of the nervous system. The number of people afflicted with neurotoxic disease can only be estimated, because the number of neurotoxic substances is unknown but probably plentiful, and the effects on the nervous system are many and varied. Despite increasing attention to neurotoxicity in recent years, much work still needs to be done.

The Board on Environmental Studies and Toxicology of the National Research Council's Commission on Life Sciences convened the Committee on Neurotoxicology and Models for Assessing Risk. Support was provided by the Agency for Toxic Substances and Disease Registry of the U.S. Public Health Service. The charge to the committee was to 1) assess the biologic bases of neurotoxicity with regard to establishing underlying principles relevant to risk assessment and extrapolation across species; 2) review existing models and indicators of neurotoxic action and disease, including structure-activity relationships, with respect to their efficacy in identifying neurotoxicants from environmental, occupational, and other potential sources; and 3) develop critical hypotheses for future research in neurotoxicology, particularly research that will lead to models for assessing the risks of neurotoxic disease. Committee members represented the breadth of disciplines involved in environmental neurotoxicology. Their expertise served the committee well as it endeavored to meet its charge.

The committee met seven times over 2 years. It focused on the magnitude of the problem, the use of biologic markers, neurotoxicity testing, surveillance and epidemiology, and risk assessment. This report presents the views of the committee members, and the conclusions and recommendations reflect the committee's deliberations. The committee concluded that research is needed to improve understanding of the mechanisms of neurotoxic action and the extent of neurotoxic disease. The committee encouraged the development of a coherent, tiered testing strategy and the improvement of surveillance programs.

The committee acknowledges the tireless efforts of those without whom the report would never have been completed. The committee thanks Hugh Tilson for his expertise and insight. The committee also acknowledges NRC staff for their work in organizing and managing this undertaking. Devra Davis was instrumental in conceptualizing the study initially. James Reisa, director of the Board on Environmental Studies and Toxicology, provided much welcomed guidance and encouragement. In addition to his contributions as program director, Richard

Page viii Cite
Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

Thomas served as interim project director and gave invaluable support to the committee and staff. The committee thanks senior staff officers Andrew Pope and Mary Paxton for their work in the formative stages of the committee process and in helping with early drafts of the report, and Kathleen Stratton for seeing the report through its final stages. The committee recognizes the tireless efforts of Anne Sprague of the Toxicology Information Center and Linda Leonard, project assistant. Norman Grossblatt and Lee Paulson served as editors.

On behalf of the committee, I thank all who assisted in completing this report.

Philip J. Landrigan, Chairman

Committee on Neurotoxicology and Models for and Assessing Risk

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

Tables and Figures

TABLES

1-1

 

Partial List of Neurotoxicants

 

10

1-2

 

Human and Animal Neurobehavioral Effects Attributed to at Least 25 Chemicals

 

11

1-3

 

Selected Major Neurotoxicity Events

 

12

2-1

 

Nonneuronal (Glial) Cells of the Nervous System and Their Function

 

22

2-2

 

Neuron Type Classified by Neurochemical Released for Synaptic Transmission

 

27

3-1

 

Examples of Characteristics of Exogenous; Agents, Organisms, or Targets That Influence Choice of Biologic Marker

 

44

3-2

 

Selected Markers of Neurotoxicity in Nervous System

 

45

4-1

 

In Vitro Neurobiologic Test Systems

 

62

4-2

 

Markers for Assessing Neurotoxicity in In Vitro Systems

 

63

4-3

 

Proposed Protocol for Developing and In Vitro Neurotoxicity Screening System

 

65

4-4

 

Neurotoxic Effects of Representative Agents in Humans and Animals

 

67

4-5

 

Examples of Behavioral Measures of Functional Neurotoxicity

 

69

4-6

 

End Points That Might be Included in a Functional Observational Battery

 

71

4-7

 

Areas of the Nervous System to be Used in Neuropathologic Evaluation

 

81

4-8

 

Tissues of the Nervous System to be Used in Neuropathologic Evaluation

 

82

4-9

 

Tests Used in NCTR Collaborative Study

 

83

4-10

 

Proposed Components for Evaluating In Vitro Neurotoxicity Screening Tests

 

92

5-1

 

Characteristics of Responses to Exposure to Some Neurotoxicants

 

98

5-2

 

Components of Clinical Neurologic Examination

 

100

5-3

 

Test Batteries

 

102

6-1

 

Some Neurotoxicants That Act on Receptors

 

118

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
×

FIGURES

2-1

 

Diagrammatic representation of neuronal structure

 

23

2-2

 

Events in chemical synaptic transmission

 

26

2-3

 

Structures of type I and type II pyrethroids

 

34

2-4

 

Metabolism of hexane

 

37

2-5

 

Diagram of MPTP toxicity

 

39

3-1

 

Simplified classification of biologic markers

 

46

4-1

 

Biologic markers in the stages between formation and degneration of neural circuits

 

91

6-1

 

Effect of a shift in mean IQ score on the population distribution

 

113

6-2

 

Estimated developmental scores at various ages for three blood-level concentrations

 

115

6-3

 

Percentage of severe mental retardation among those exposed in utero by dose and gestational age in Hiroshima and Nagasaki

 

119

Suggested Citation:"Front Matter." National Research Council. 1992. Environmental Neurotoxicology. Washington, DC: The National Academies Press. doi: 10.17226/1801.
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Environmental Neurotoxicology Get This Book
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Scientists agree that exposure to toxic agents in the environment can cause neurological and psychiatric illnesses ranging from headaches and depression to syndromes resembling parkinsonism. It can even result in death at high exposure levels. The emergence of subclinical neurotoxicity--the concept that long-term impairments can escape clinical detection--makes the need for risk assessment even more critical.

This volume paves the way toward definitive solutions, presenting the current consensus on risk assessment and environmental toxicants and offering specific recommendations.

The book covers:

  • The biologic basis of neurotoxicity.
  • Progress in the application of biologic markers.
  • Reviews of a wide range of in vitro and in vivo testing techniques.
  • The use of surveillance and epidemiology to identify neurotoxic hazards that escape premarket screening.
  • Research needs.

This volume will be an important resource for policymakers, health specialists, researchers, and students.

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