Neurobehavioral Toxicology: Neurological and Neuropsychological Perspectives, Volume I

Foundations and Methods

Stanley Berent, James W. Albers

• Publisher: Taylor & Francis
• Year: 2012
• ISBN:
  9781135421137
• Edition: 1
• Topic: Psychology
• Subtopic: History & Theory in Psychology
• Index: Psychology

This book, the first of three volumes, provides a thorough background to the emerging field of neurobehavioral toxicology by looking at current clinical approaches and tests, as well as assessing current clinical research. The analysis of the impact of toxins on the human nervous system is particularly pertinent given the ongoing expansion of pharmaceuticals, industrial hazards, biological warfare and global pollution.

A comprehensive introduction to neurobehavioral toxicology, this work will be of interest to practicing neurologists and neuropsychologists, as well as to occupational medicine physicians and medical toxicologists.

1 Introduction to neurobehavioral toxicology

Introduction

Volume I of this three-volume book introduces an emerging field, Clinical Neurobehavioral Toxicology, one which we believe will become a primary vehicle when addressing important questions related to the effects of toxins on the nervous system and behavior. There is at present no single, recognized field that encompasses all relevant aspects of this problem area, but there is general recognition that a multidisciplinary response is indicated. Our writings will reflect a multidisciplinary approach to Neurobehavioral Toxicology, with an emphasis on the independent and collaborative contributions of Neurology and Neuropsychology to this endeavor. The present chapter begins with a brief historical perspective and some conceptual considerations. It then focuses on one important biological aspect of the nervous system – neurotransmission – as a way of discussing biological vulnerability and, more specifically, neurotoxicology. Case-related material at times is presented to illustrate the complexity of this area of human understanding.¹ Finally, and since almost nothing occurs in isolation, we conclude the chapter with a discussion of the importance of individual and contextual factors in determining the impact of toxicant-induced damage to the individual.

Many substances affect the human nervous system and its various functions, both positively and negatively. Some are seen as beneficial, while others are considered detrimental or toxic. Interestingly, the amount of a specified substance often determines its characterization as one or the other. Some substances, endogenous (i.e., intrinsic to the organism) as well as exogenous (i.e., extrinsic to the organism), have been hypothesized to play a causative role in a host of specific as well as non-specific disorders. These disorders include progressive neurodegenerative conditions such as Alzheimer disease, Parkinson disease, and motor neuron disease, as well as depression, anxiety, and other neurobehavioral disorders (Grunhaus, Dilsaver, Greden, & Carroll, 1983; Forno, 1992). To complicate matters or, depending on one's viewpoint, to make them more interesting, compounds that are potentially pathogenic exist naturally in the environment. The popular view is often one that considers toxic materials limited to the careless waste of an industrial society or the agents of individual or of mass destruction. In actuality, toxicity is a relative concept that earns its precise definition by consequence. The same agent that is toxic in one circumstance might be non-toxic in another (Cooper, Bloom, & Roth, 1996). Even when toxic, these substances play important roles in nature, e.g., as naturally occurring pesticides and herbicides that aid in plant survival, as animal defenses, and as aids in human and animal neurogenesis and neurotransmission (Goetz, 1985; Cooper, Bloom, & Roth, 1996; Siegel, Agranoff, Albers, Fisher, & Uhler, 1999).

Toxicity is a complex topic. For most of history it has been dealt with intellectually through anecdote and subjective reasoning and, emotionally, with fear and anxiety. While to some extent these tendencies continue, a number of fields have directed scientific attention to the problems associated with toxicity. These include the scientifically based disciplines of Medicine, Psychology, Toxicology, Chemistry, Physiology, Neuroscience, and others. Some of the specialties within these disciplines that have an interest in toxicity include Developmental Psychology, Neuropsychology, Epidemiology, Internal Medicine, Neurology, Nuclear Medicine, Occupational Medicine, Pediatrics, Psychiatry, and the various subspecialties of Toxicology. The approaches to the study of toxicants have become sophisticated, and the knowledge base has become substantial. At the same time, considerable misunderstanding persists, especially amongst the lay population, but also among scientists and other professionals. Also, there is some fragmentation in scientific understanding that appears to result from the fact that there is no one field that encompasses the various discipline- and specialty-specific methodologies applied to the study of toxicants. The multidisciplinary effort represented by Neurobehavioral Toxicology is an attempt to enhance collaboration between these various specialties. Through didactic and case-related material, we will describe in the present volume concepts and methods that we view as particularly relevant to the field. While, as mentioned above, Neurobehavioral Toxicology is a multidisciplinary topic, emphasis will be on two professions, Neuropsychology and Neurology, and how these disciplines interact and complement one another in their approach to this topic. The present work will emphasize methodology, with the inclusion of specific toxicants and clinical entities that relate to the nervous system as needed for illustration.

The approach taken in this work is largely, although not entirely, empirical in nature. That is, the approach is based on observation. However, to the extent possible, we attempt to make our observations verifiable through citation or experiment. We will at times refer to ‘science’ and the ‘scientific method,’ and we claim that the fields of Neurology, Neuropsychology, Neurobehavioral Toxicology, and related disciplines are empirical and based on a scientific foundation. While science is empirical, scientific method refers to a specific approach to problem-solving, as discussed further below. We recognize that limits of our knowledge will also limit what can be concluded in a given case. Diagnosis of a medical or neuropsychological condition frequently can be specified even when etiology cannot. For instance, we do not yet know what causes Alzheimer disease, but there are criteria for its diagnosis. While theory plays an important role in the development of such criteria, our developing knowledge requires that adjustments to these criteria be made periodically. Rather than focusing on specific substances, we have chosen to emphasize a science-based, problem-solving approach that will be applied to a variety of neurotoxicological problems. We view such an approach as the best way to address the various clinical and scientific challenges that the professional must meet in order to determine the adverse effects a substance might have, or might have had, on human behavior and the nervous system. When specific compounds are mentioned, we focus primarily on those agents that adversely effect the nervous system, directly or indirectly, with some regularity. The effects of toxic substances must be determined within a framework of differentiation from potentially competing contributions to the clinical picture or scientific problem (i.e., in the form of the differential diagnosis in clinical practice and by control of nuisance variables, or confounders, in research). Because of this, we will also discuss some of the factors that serve to obscure accurate conclusions.

The neurobehavioral approach strives for an objective and scientific analysis of the topic. By scientific, we mean more than the application of the experimental method. Mounting concerns for the environment have led to diverse opinions and sometimes conflicting methodologies about how best to address the issue – from legal and regulatory branches of government, industry, and science to vested interest groups and the lay public. We see these problems as calling for objective and multidisciplinary solutions. To be effective, however, the knowledge base upon which decisions are to be made must be accurate. There is need for a common language and, where possible, consensus in decision-making. Science, it seems to us, represents the best model upon which to base the methods of neurobehavioral toxicology. While the science may not appear to be manifest in all of the clinical approaches and examples described in the various sections that follow, we attempt to remain objective and maintain an empirical approach that relies on scientifically derived information in reaching our conclusions.

Some conceptual considerations

The word ‘toxin’ has crept into common parlance and is often used to mean something that is poisonous. Strictly speaking, the word ‘toxicant’ is more correct since toxin has a more technically restricted definition, often referring to substances produced by living organisms and which are injurious to bodily tissue (Merriam-Webster, 1993). Both terms, toxin and toxicant, derive from the ancient Greek word for bow and, later, for the poison in which the arrow was dipped (Merriam-Webster, 1993; Shipley, 1995). The word ‘poison’ itself has very interesting origins. From Old French and originally Latin (potare, to drink), the word was used until medieval times to refer only to an alcoholic drink. With the practice of adding lethal substances to a person's drink for purposes of assassination, the word took on its more sinister meaning (Shipley, 1995). Vestiges of the earlier meaning are still found in everyday English (e.g., ‘Name your poison’).

Theoretically, anything in sufficient dose can be toxic, including seemingly benign substances such as water and oxygen. The word ‘toxicant’ in its various forms, however, is generally reserved for substances that have adverse effects in relatively small amounts. From a lay perspective, the concept of what is poisonous and what is not has been largely derived from historical experience. There are a variety of substances that are not included in the concept of toxicity at a given time, even though, in fact, they may later be seen as toxic. They were not included initially, perhaps because their adverse effects may have been too subtle, or because the effects may have occurred too rarely to be noted in historical experience. Sunlight is a fairly recent example of something that for many years was thought to be benign, even desirable, and which now is recognized as toxic, in sufficient doses. Agents that produced a dramatic effect, on the other hand, were more likely to be quickly labeled as ‘poisons.’ Also, the specific dose required to produce a toxic effect may change in response to new information. Lead is an example of a substance that over time has come to be seen as harmful at lower levels than was originally thought (Harte, Holdren, Schneider, & Shirley, 1991).

A lay understanding of toxicity rests on a historical knowledge base that has been derived, at least in part, serendipitously and, almost certainly, vicariously. Two people go into the forest to find mushrooms. One finds and eats a mushroom, becomes ill and dies. The other witnesses the event, avoids the same fate and brings the knowledge back to the community. Of course, the example just given is a gross oversimplification and almost certainly fails to give proper credit to the ingenuity and cleverness of people to derive increasingly sophisticated methodologies that involve more than simple observation and deductive logic for acquiring knowledge. Before the metal thallium found wide use as a rodenticide, for instance, it was used in the treatment of a variety of illnesses that included syphilis, gonorrhoea, and tuberculosis. The metal never found wide acceptance as a therapeutic agent, however, because of its adverse side-effects (Reed, Crawley, Faro, Pieper, & Kurland, 1963). Thallium was discovered in 1861 by Sir William Crooks and was suspected of being toxic by his contemporary, Claude August Lamy. Lamy tested his hypothesis that thallium was poisonous by feeding it to various animals, which all died within days of ingesting the metal (Reed et al., 1963). Despite such instances of prospective testing to confirm a ‘hypothesis,’ there is likely to be some element of accuracy in the earlier description of the hypothetical scenario that employed deductive reasoning following a chance experience, a method that is clearly not sufficient for an objective, scientific study of toxicants.

Although a cliché, it is true that when some of us were children, life seemed simpler than today. To us at that time the world contained things that were positive and some that were toxic or otherwise dangerous. We were taught, or learned, to avoid the dangers. There is no doubt that since that time, the world has experienced an increasingly expanding explosion of knowledge. Our previous, perhaps naive, notions of a manageable world, one in which the rules could be learned and dangers avoided by the ‘correct’ applications of these rules, has been challenged. The word ‘challenged’ is used purposely. An alternative word would be ‘lost.’ Since as individuals, and as a society, we can not afford to accept t...

Table of contents

• Front Cover
• Half Title
• STUDIES ON NEUROPSYCHOLOGY, NEUROLOGY, AND COGNITION
• Title Page
• Copyright
• Contents
• Contents of Volumes II and III
• From the Series Editor
• Acknowledgments
• Disclosures
• 1 INTRODUCTION TO NEUROBEHAVIORAL TOXICOLOGY
• 2 CLASSIFICATION AND MANAGEMENT OF TOXICANT-RELATED INFORMATION
• 3 CLINICAL AND CLINICAL RESEARCH CONSIDERATIONS
• 4 CLINICAL APPROACHES
• 5 THE NEUROPSYCHOLOGICAL APPROACH
• 6 THE NEUROLOGICAL APPROACH
• 7 CRITIQUE OF RELEVANT CLINICAL TESTS
• 8 CAUSALITY
• POSTSCRIPT
• Subject index