Table Of Content

Contributors Michael E. Adams Robert B. Koch Richard W. Beeman Frances Leighton William S. Bowers Terrance Leighton Joel R. Coats A. E. Lund Laurence K. Cutkomp Philip S. Magee Durisala Desaiah Thomas A. Magee James R. Heitz Edwin P. Marks Clive A. Henrick Fumio Matsumura R. M. Hollingworth Thomas A. Miller Charles O. Knowles Hideo Ohkawa Insecticide Mode of Action Edited by JOEL R. COATS Department of Entomology Iowa State University Ames, Iowa 1982 ACADEMIC PRESS A Subsidary of Harcourt Brace Jovanovich, Publishers New York London Paris San Diego San Francisco Sao Paulo Sydney Tokyo Toronto COPYRIGHT © 1982, BY ACADEMIC PRESS, INC. ALL RIGHTS RESERVED. NO PART OF THIS PUBLICATION MAY BE REPRODUCED OR TRANSMITTED IN ANY FORM OR BY ANY MEANS, ELECTRONIC OR MECHANICAL, INCLUDING PHOTOCOPY, RECORDING, OR ANY INFORMATION STORAGE AND RETRIEVAL SYSTEM, WITHOUT PERMISSION IN WRITING FROM THE PUBLISHER. ACADEMIC PRESS, INC. Ill Fifth Avenue, New York, New York 10003 United Kingdom Edition published by ACADEMIC PRESS, INC. (LONDON) LTD. 24/28 Oval Road, London NW1 7DX Library of Congress Cataloging in Publication Data Main entry under title: Insecticide mode of action. Includes index. 1. Insecticides—Physiological effect. I. Coats, Joel R. SB951.5.I58 1982 632 \ 951 82-8781 ISBN 0-12-177120-2 AACR2 PRINTED IN THE UNITED STATES OF AMERICA 82 83 84 85 9 8 7 6 5 4 3 2 1 Contributors Numbers in parentheses indicate the pages on which the authors' contributions begin. Michael E. Adams (3), Research Laboratory, Zoecon Corporation, Palo Alto, California 94304 Richard W. Beeman (229), U.S. Grain Marketing Research Laboratory, USDA-SEA, ARS, Manhattan, Kansas 66502 William S. Bowers (403), Department of Entomology, New York State Agricultural Experiment Station, Cornell University, Geneva, New York 14456 Joel R. Coats (29), Department of Entomology, Iowa State University, Ames, Iowa 50011 Laurence K. Cutkomp (45), Department of Entomology, Fisheries, and Wildlife, University of Minnesota, St. Paul, Minnesota 55108 Durisala Desaiah (45), Department of Neurology, University of Missis sippi Medical Center, Jackson, Mississippi 39216 James R. Heitz (429), Department of Biochemistry, Mississippi State Uni versity, Mississippi State, Mississippi 39762 Clive A. Henrick (315), Research Laboratory, Zoecon Corporation, Palo Alto, California 94304 R. M. Hollingworth (189), Department of Entomology, Purdue Uni- veristy, West Lafayette, Indiana 47907 Charles O. Knowles (243), Department of Entomology, University of Missouri, Columbia, Missouri 65211 Robert B. Koch (45), Department of Biochemistry, Mississippi State Uni versity, Mississippi State, Mississippi 39762 Frances Leighton (281), Department of Microbiology and Immunology, University of California, Berkeley, California 94720 ix X Contributors Terrance Leighton (281), Department of Microbiology and Immunology, University of California, Berkeley, California 94720 A. E. Lund (189), Biochemicals Department, DuPont Experimental Sta tion, Wilmington, Delaware 19898 Philip S. Magee (101), Agricultural Chemicals Division, Chevron Chemi cal Company, Richmond, California 94804 Thomas A. Magee (71), T. R. Evans Research Center, Diamond Sham rock Corporation, Painesville, Ohio 44077 Edwin P. Marks (281), Metabolism and Radiation Research Lab, ARS- USDA, Fargo, North Dakota 58102 Fumio Matsumura (229), Pesticide Research Center, Michigan State Uni versity, East Lansing, Michigan 48824 Thomas A. Miller (3), Department of Entomology, Division of Toxicology and Physiology, University of California, Riverside, California 92521 Hideo Ohkawa (163), Institute for Biological Science, Sumitomo Chemi cal Company Ltd., Takarazuka, Hyogo 665, Japan Preface Recent advances in research on insecticide mode of action research have been published in a plethora of scientific journals. This volume at tempts to consolidate significant results for researchers, teachers, and regulatory personnel concerned with the biological activity of insecti cides. Thirteen chapters, authored by eminent leaders in the field, cover a broad range of insecticide classes, each developed in considerable detail. The first section presents discourses on groups of conventional insecti cides: chlorinated hydrocarbons, pyrethroids, carbamates, and organophosphorus chemicals. The carbamate chapter is an in-depth discussion of the oxime carbamates. Organophosphorus insecticides are considered in two specialized chapters, one on stereoselective activity and the other on phosphoramidates. A special section of the book examines the formamidines, an exciting group of pesticides that exhibit an unusual spectrum of activity. Numer ous types of toxic actions have been reported in biological systems, in cluding several modes of action of pharmacological significance as well as some important behavioral effects. The third section addresses groups of compounds that affect insect growth and development. Such chemicals typically demonstrate marked selectivity and represent more sophisticated strategies in the chemical control of insect pests. Two types of approaches to mode of action research are evident in this book. Investigations of specific biochemical or neurophysiological pro cesses broaden the understanding of toxic interactions between an insec ticide and a receptor site. Effects of changes in environmental conditions (e.g., temperature) can be assessed, and the kinetics of crucial toxic pro cesses can be determined. The structure-activity approach utilizes a series of closely related chem- XI xii Preface icals to evaluate the comparative influence of several types of physicoche- mical parameters on toxicity. Properties examined can be steric (e.g., size, shape, flexibility), electronic (e.g., e~ donating or withdrawing, field electronegativity), or lipophilic. Regression analysis can be employed to quantify the relative importance of several parameters or to examine the relationships singly. It is hoped that this volume will provide an update on the state of the science and will stimulate new and continued research efforts in insecti cide toxicology. I am very grateful to the authors who contributed their expertise toward the production of a worthwhile volume. I also appreciate the encouragement and advice I received from John Hathcock, Robert L. Metcalf, F. W. Plapp, and Paul Dahm. I am also indebted to the editorial staff of Academic Press for their assistance and patience. This book is de dicated to my parents, William Gilbert Coats and Catherine Elizabeth (Dodds) Coats. Joel R. Coats 1 Mode of Action of Pyrethroids THOMAS A. MILLER AND MICHAEL E. ADAMS I. Introduction 3 II. Structures 4 III. Symptoms of Pyrethroid Poisoning 6 IV. Neurophysiology of Pyrethroid Poisoning 8 A. Actions on Sensory Neurons 9 B. Actions on Motor Neurons 10 C. Actions on the Neuroendocrine System 13 D. Actions on the Central Nervous System 14 E. Ionic Mechanisms in Pyrethroid Poisoning 15 V. Mode of Action of Pyrethroids on Verebrates 16 VI. Resistance to Pyrethroid Insecticides 19 References 24 I. INTRODUCTION At present, pyrethroids appear to possess those characteristics that one would hope to find in more desirable insecticides. The natural and synthetic pyrethroids are relatively safe for mammals and extremely toxic to ar thropods, although intravenous doses of some of the compounds are rea sonably toxic to warm-blooded animals. [A lethal dose of deltamethrin* is 2-2.5 mg/kg intravenous to 10- to 12-week-old white rats (Barnes and Verschoyle, 1974), whereas an oral LD of deltamethrin in white rats is 50 greater than 60 mg/kg (Barnes and Verschoyle, 1974).] Problems of car- cinogenicity or mutagenicity have not been found with pyrethroids and, although it is a little early to determine the effects of long-term exposure, * Deltamethrin was previously named decamethrin; see Elliott's article (1980) for the Brit ish Standards common name and structure. 3 INSECTICIDE MODE OF ACTION Copyright © 1982 by Academic Press, Inc. All rights of reproduction in any form reserved. ISBN 0-12-177120-2 4 Thomas A. Miller and Michael E. Adams as esters the compounds are biodegradable and appear to pose no serious residue problem (Elliott et ai, 1978). The overall characteristics of pyrethroids as insecticides are so favorable that they would approach the ideal were it not for resistance. The potential decrease in efficacy of pyrethroids brought about by any future development of resistance in pest species is difficult to predict. Although Elliott et al. (1978) offer a rather positive view for the long-term use of pyrethroids, with the possible exception of Egypt and Denmark, there is, unfortunately, no country in which legislation or registration restriction has been designed to counteract massive, continuing, indiscriminant use of pyrethroids, a prac tice that will surely shorten their useful life. Pyrethroid insecticides, together with DDT and DDT analogs, belong to a group of chemicals that are neurotoxic to insects. The modes of action of DDT and pyrethroids are similar, and together they are distinct from every other category of insecticide, including all other organochlorine com pounds such as lindane and dieldrin. Both DDT and pyrethroids act either on the central nervous system or on peripheral nerves such as motor axons or sensory axons at very low concentrations. The action on peripheral nerves is unique to this class of insecticide and complicates studies on mode of action because it is difficult to determine which site of action (central or peripheral) might be more important in toxicity. Most pyrethroids and DDT have negative temperature coefficients of toxicity; that is, they are more toxic at colder temperatures. The so-called kdr (knockdown resistance) factor confers cross-resistance on both DDT and pyrethroids, regardless of which compound is used for selective pres sure. The kdr factor appears to render the central and peripheral parts of the insect nervous system insensitive to the actions of DDT or pyrethroids when perfused at concentrations that would poison the nervous system of susceptible strains. II. STRUCTURES Synthetic pyrethroids are esters that have evolved from the natural prod uct pyrethrin I (I). Both dihalovinyl substitution in the acid moiety and incorporation of 3-phenoxybenzyl alcohols (see II) have improved the sta bility of the molecule to breakdown and metabolism. With the discovery of fenvalerate (III), the requirement for a cyclopropane moiety in the acid portion of the molecule was eliminated, and several 2,3-substituted butyrate esters with high insecticidal activity have been synthesized. It is now clear that the insecticidal activity of pyrethroids depends on 1 Mode of Action of Pyrethroids 5 structural conformation and that the activity of a particular optically pure isomer is often far greater than that of its enantiomer. For this reason, a knowledge of the chemical structure of pyrethroids is extremely important. The structure of pyrethrin I has three optical centers at carbons 1 and 3 of the cyclopropane ring and another at the cyclopentene moiety in the alcohol (in addition, the pentadiene side chain can be oriented cis or trans). Recent nomenclature has used R (rectus, Latin for "right") or S (sinister, Latin for "left") to denote the orientation of three of the bonds on a carbon atom when viewed across the atom from the bond of lowest priority. Prior ities are determined by the atoms bonded to the carbon, and the atoms of higher atomic number always take priority regardless of the sum of the atomic numbers of all attached atoms. For example, the a-carbon in deltamethrin (II) is marked S because when viewed toward the hydrogen atom that is below the plane of the paper with the bond depicted by a dashed line, the order of priority of the atoms attached to the carbon is — O, —CN, — phenyl, or counterclockwise (left). This notation system provides unambiguous expression of the three-dimensional structure of the pyrethroid molecules. Н,С НзС. .СНз H3C CHg <XS A o Br Br Pyrethrin I Deltamethrin (one isomer: S-cis) (I) (ID HSC. /Ca Fenvalerate (four isomers: R,R, R, S, S,R, S,S) (П1) Because optically active isomers are sometimes extremely difficult to resolve completely, a minor contaminant with high activity might have a significant effect on biological activity of the compound in hand. The name deltamethrin (II) applies specifically to the single isomer (S)- a-cyano-m-phenoxybenzyl (\R,3i?)-3-(2,2-dibromovinyl)-2,2-dimethylcy- clopropanecarboxylate, which is also named /-a-cyano-3-phenoxybenzyl