Toxicology of the Nervous System

In this chapter a brief introduction to the nervous system is presented and its functions are described. A discussion of some of the mechanisms of structural and functional neurotoxicant effects follows. These descriptions are not exhaustive, they are meant to illustrate the concepts of toxicant interaction with the nervous system. Finally some methods for testing toxicant effects in the nervous system are explored. 

Most multicellular animals possess a nervous system. In every case the function of the nervous system is to receive information about the external and internal environment, integrate the information, and then coordinate a response appropriate to the 

A Textbook of Modern Toxicology, Third Edition, edited by Ernest Hodgson ISBN 0-471 -26508-X Copyright 2004 John Wiley Sons, Inc. 

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Blake, B. L. Toxicology of the nervous system. In Hodgson E. (Ed.). A Textbook of Modem Toxicology, 3rd ed. John Wiley Sons, Hoboken, NJ, 2004, pp. 279-297. 

Anthony DC, Montine TJ, Graham DG. 1996. Toxic responses of the nervous system. In Wonsiewicz MJ, Sheinis EA, ed. Casarett and Doull s toxicology The basic science of poisons. New York, NY McGraw-Hill, 475-476. 

Problems associated with behavioral toxicology include the functional reserve and adaptability of the nervous system. Frequently behavior is maintained despite clearly observable injury. Other problems are the statistical ones associated with multiple tests, multiple measurements, and the inherently large variability in behavior. 

Behavioral toxicology is that scientific discipline which studies the effects of therapeutic drugs and other chemicals on behavior, the ultimate output of the nervous system, and also seeks to determine how such effects are caused. The impetus for such studies has come from multiple sources. Both human and experimental animal studies have been carried out to assess the behavioral consequences arising from exposures to chemicals used in the workplace as well as those dispersed in the environment. These efforts have been important in determining safe exposure and risk levels, as well as in furthering our understanding of these chemicals. A second force behind many such studies has been the need to screen newly synthesized chemicals for any potential adverse behavioral effects before their introduction into use, efforts which are obviously carried out only in experimental laboratory contexts. 

Psychology is the science that strives to understand, measure, and modify our behavior what we do, what we say, what we think, and what we feel. At its most basic level, behavior describes how we manipulate and respond to our environment. It is the ultimate output of the nervous system. Its domain ranges across the entire universe of human activities from simple reflexes to the creation of cosmological theories. Toxicology, however, at least in the formal sense, recognized the crucial role of behavioral neuroscience only recently. Perhaps behavior seemed somewhat exotic compared to the study and traditional endpoints of death and tissue damage. However, step back from the brink that these endpoints represent and toxicology swiftly becomes a more complex and subtle enterprise. 

A similar concern occurs when very sensitive in vitro studies indicate a chemical effect. In vitro studies take a cell or component of a cell out of the organism and maintain it alive in the laboratory. The effects of chemical exposure to these cells are then studied. This is a very sensitive and useful technique in toxicology when properly interpreted. For example, one could study the effects of chemicals on cells of the nervous system and detect potential effects. However, these same cells in the animal are very well protected by their location from ever coming into contact with this chemical. Secondly, some responses produced in isolated cells would be immediately counteracted by other cells in the intact animal. These tests have their place in toxicology. They can be used to probe the mechanism of action of an effect seen in animals, or be used as a screening tool to select compounds for further study in intact animals. 

Leo G. Abood, Ph D., was Professor of Pharmacology, Department of Pharmacology and Physiology, University of Rochester Medical Center until his death in January 1998. Dr. Abood was an expert on the biochemistry and physiology of the nervous system whose research focused on the isolation and characterization of neurotransmitter receptors from the mammalian brain, specifically nicotine, vasopressin, and opioid receptors. He previously served on the NRC Committee on Toxicology s Panel on Anticholinergic Compounds and the Chemical Weapons Stockpile Assessment Panel. 

Moser, V.C., Aschner, M., Richardson, R.J., et al., 2012. Toxic responses of the nervous system. In Klaassen, C. (Ed.), Casarett and DoulTs Toxicology The Basic Science of Poisons, eighth ed. McGraw-Hill Professional, New York,... 

Physiological Classifications of Contaminants. The physiological classification of air contaminants is difficult, because the type of action of many gases and vapors depends on concentrations (55). For example, a vapor at one concentration may exert its principal effect as an anesthetic but, at a lower concentration, the same vapor may iujure the nervous system, the hematopoietic (blood-forming) system, or some visceral organ (see Toxicology). 

In the 1960s and 1970s, the organophosphate and carbamate compounds replaced the chlorinated hydrocarbons as the most prominently used insecticides. These two families of insecticides share a common toxicological mechanism, the inhibition of cholinesterase enzymes in the nervous systems of... 

A particularly rapidly growing area of the science is behavioral toxicology. The nervous system serves a vast integrative function for the body, and various forms of behavior can be altered by response to substances that affect the nervous system in some way. We have already seen some examples of behavioral changes associated with exposure... 

Toxicology. Pentaborane is extremely toxic it affects the nervous system and causes signs of narcosis and hyperexcitation. 

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