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.

Contents

• Committee on Neurotoxicology and Models for Assessing Risk
• Board on Environmental Studies and Toxicology
• Commission on Life Sciences
• Preface
• Executive Summary
• 1. Introduction: Defining the Problem of Neurotoxicity
  • Neurologic Responses to Environmental Toxicants
  • Magnitude of the Problem of Neurotoxicity
  • Detection and Control of Exposure to Neurotoxicants
  • Scope of this Report
• 2. Biologic Basis of Neurotoxicity
  • Cellular Anatomy and Physiology
  • General Aspects of Nervous System Structure and Function
  • Vulnerability of the Nervous System to Chemical Toxicants
  • Examples of Neurotoxic Mechanisms
  • MPTP
  • Summary
• 3. Biologic Markers in Neurotoxicology
  • Concepts and Definitions
  • Validation of Biologic Markers
  • Use of Biologic Markers in Risk Assessment
  • Summary
• 4. Testing for Neurotoxicity
  • Approach to Neurotoxicity Testing
  • Current Methods Based on Structure-Activity Relationships
  • Current in Vitro Procedures
  • Current In Vivo Procedures
  • Current Regulatory Approaches
  • Strategies for Improved Neurotoxicity Testing
• 5. Surveillance to Prevent Neurotoxicity in Humans
  • Need for Surveillance
  • Neurobehavioral Test Batteries
  • Current Exposure Surveillance Efforts
  • Current Disease-Surveillance Efforts
• 6. Risk Assessment
  • Approaches to Risk Assessment for Neurotoxicity
  • Curve-fitting in Risk Assessment for Neurotoxicity
  • Mechanistic Models for Risk Assessment for Neurotoxicity
  • Summary
• 7. Conclusions and Recommendations
• References

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.