Insecticides

Action and Metabolism

R. D. O'Brien

• Publisher: Academic Press
• Year: 2014
• Print ISBN: 9781483227382
• eBook ISBN: 9781483270685
• Topic: Technology & Engineering
• Subtopic: Biophysics
• Index: Technology & Engineering

Insecticides: Action and Metabolism provides a comprehensive review of the action of insecticides and a survey of their metabolism. This book discusses the toxicology of insecticides. Organized into 17 chapters, this book begins with an overview of the mechanisms whereby toxicants exert their effects. This text then discusses the insecticidal action of organophosphates, which is described as the toxic organic compounds containing phosphorus. Other chapters consider the mode of action of organophosphates by inhibiting cholinesterase with consequent disruption of nervous activity caused by accumulation of acetylcholine at nerve endings. This book discusses as well the erratic patterns of selective toxicity to insects of the carbamates. The final chapter deals with the real hazard to human health as well as the effects upon wild life of insecticides and chlorinated pesticides. This book is a valuable resource for organic and agricultural chemists, as well as biologists, agriculturists, neurophysiologists, environmental scientists, and research workers.

CHAPTER 1

Introduction

Publisher Summary

This chapter discusses the toxicology of insecticides. The majority of insecticides, and the majority of all poisons, kill by virtue of their effects on the nervous system. The reason lies in the special sensitivity of the nervous system, which is the part of the body showing, to the greatest extent, irreversible damage consequent on even transient blockade. Other poisons, whose primary target is elsewhere, commonly produce their ultimate effect upon the nervous system; thus, heart poisons and poisons that block the oxygen-carrying capacity of blood are lethal because of the brain damage that follows deprivation of the brain’s great oxygen requirement. There are two quite different modes of nerve impulse transmission in the nervous system. Axonic transmission conveys an impulse from its arrival point and then along the axon to the meeting place with another cell, which can be another neuron or can be a muscle, gland, or sensory receptor cell. Across the junction between cells, synaptic transmission occurs.

Toxicology

This book is about the toxicology of insecticides. The term toxicology is much abused; it is commonly applied in medical and veterinary usage to problems of analysis of food and organs for toxic substances. A recent two-volume treatise on toxicology is devoted almost entirely to this aspect. In agricultural schools, the term is often applied to work on the application of toxicants to animals and the evaluation of toxicity. In my view, “toxicology,” like any other “-ology,” should be reserved for a logical study of a body of knowledge, the subject matter in this case being the toxic effects of substances on organisms. From this viewpoint, toxicity testing and toxicant analysis are minor components of a subject whose central theme is the mechanism whereby toxicants exert their effects. Such mechanisms are the principal topics of this book.

In practice, toxicology is concerned with highly toxic substances, although it is recognized that even essential substances, such as sodium chloride, can be lethal in large excess. We are here concerned instead with compounds used in a dose range commonly of the order of 0.1–25 mg/kg,^* which might be better visualized as 0.1–25 parts per million (ppm) if evenly distributed. Such extreme effectiveness can only be achieved if the toxicant has considerable specificity, so that it avoids consuming its substance by combination with body components in great excess, and if it interferes specifically with a component which is not in excess and is vital for life. Usually, at doses which are just sufficient to kill, only one component will be “attacked.” At much larger doses, many other components with lesser affinities will become affected. The special mystery to be disentangled is why the toxicant has such special affinity; for example, why does nitrogen mustard preferentially alkylate the guanine of nucleic acids (2) or the organophosphates phosphorylate the serine of cholinesterase (p. 39), when the body contains billions of other alkylatable and phosphorylatable groups? The disentanglement is made very difficult by the existences of these less important reactions encountered at high concentrations. The older literature on organophosphates, and much of the literature on chlorinated hydrocarbons, is full of examples of effects which researchers have observed when extremely high concentrations of toxicant have been applied to tissue preparations, and such effects have often been “red herrings,” tempting one to believe a vital mechanism has been uncovered. It is not easy to say what concentrations are adequately low, but they should certainly be not more than 100 times larger than the concentration achieved by just-toxic doses in vivo, in cases where roughly equal distribution in the body may be assumed. This means that for a compound of molecular weight 250, whose LD₅₀ (dose which is lethal to 50% of the population of the organism) is 1 mg/kg, a concentration of 0.4mM is maximal and, to make a convincing case, one would like to see a concentration 100 times smaller. But the most convincing case of all is to show that, in an animal poisoned with an LD₅₀, the system under study is profoundly affected. Such a demonstration should be buttressed by showing that nontoxic close analogs at similar doses produce no effect on the particular system.

Modes of Killing

Organisms of any kind may be killed mechanically, physically, or chemically. All of these modes are forms of disruption. Living organisms are elaborately ordered arrays of organic and inorganic components, whose ability to carry on the essential life processes, such as the utilization of energy sources, the synthesis of body constituents, movement, and reproduction, depends upon the integrated activity of these ordered components. Organisms differ vastly in the ease with which disruption of this order is lethal; for instance, insects can survive decapitation or anoxia for days. But all organisms can be lethally disordered by the above three modes, and only by them.

This triple classification of modes is somewhat arbitrary, but convenient. By “mechanical” is meant gross destruction, by flyswatter, by fire, by squashing and entangling materials, such as Tanglefoot and polybutenes (7), and by mechanical abrasives, such as inert dusts. By “physical” is meant the action of agents which kill by interacting with body components, but not chemically. Examples would be those fumigants and organic solvents which we believe to act by modifying the physical properties of a poorly understood lipid biophase, and silica aerogels, which adsorb cuticular grease and lead to desiccation (6). The hallmarks of a physical toxicant are: little dependence of activity upon precise structure, little species specificity, common symptoms from very diverse groups of agents, usually a low order of toxicity, and often rather ready reversibility. Such compounds will be discussed in Chapters 2 and 13.

By far most interesting to the chemist and biologist are those agents which kill chemically, i.e., by reacting, usually specifically, with a body component. This class of compounds includes most of the insecticides. In some cases a clear-cut chemical reaction involving covalent bonding occurs, as with some hydrazides, which react with pyridoxal phosphate (vitamin B₆) to form a Schiff base, or as with the carbamates, which carbamylate cholinesterase. In other cases weaker bonding may be involved, such as ionic, van der Waals, or hydrogen bonding, but the molecular specificity of the reaction, and the fact that there is not merely a modification in the physical properties of a phase, allow us to classify the mode as chemical. Clear examples would be poisoning by reversible enzyme inhibitors such as malonate or organomercurials. There are cases which are difficult to classify, such as the chlorinated hydrocarbons, which seem to cause a specific modification of the electrical properties of a nerve component, and which show marked dependence of activity on struct...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Preface
• Chapter 1: Introduction
• Chapter 2: Physical Toxicants
• Chapter 3: Organophosphates: Chemistry and Inhibitory Activity
• Chapter 4: Organophosphates: Action, Therapy, and Metabolism
• Chapter 5: Carbamates
• Chapter 6: DDT and Related Compounds
• Chapter 7: Cyclodienes
• Chapter 8: Nicotinoids
• Chapter 9: Rotenoids
• Chapter 10: Pyrethroids
• Chapter 11: Fluorine Compounds
• Chapter 12: Lindane and Other Hexachlorocyclohexanes
• Chapter 13: Various Compounds
• Chapter 14: Synergism, Antagonism, and Other Interactions
• Chapter 15: Resistance
• Chapter 16: Selectivity; Penetration
• Chapter 17: Insecticides and Environmental Health
• Author Index
• Subject Index