Hayes' Handbook of Pesticide Toxicology, Two-Volume Set, Third Edition volume 1 & 2

2392 Pages·2010·98.14 MB·English

by  Robert Krieger

Hayes’ Handbook of Pesticide Toxicology
(c) 2011 Elsevier Inc. All Rights Reserved.
Hayes ’ Handbook
of Pesticide Toxicology
Third Edition
VOLUME 1 & 2
EDITED BY
Robert Krieger
University of California,
Riverside
ASSOCIATE EDITORS:
John Doull
Joop van Hemmen†
Ernest Hodgson
Howard Maibach
Lawrence Reiter
Leonard Ritter
John Ross
William Slikker
EDITORIAL ASSISTANT:
Helen Vega
†Deceased
AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS
SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO
Academic Press is an imprint of Elsevier
(c) 2011 Elsevier Inc. All Rights Reserved.
Academic Press is an imprint of Elsevier
32 Jamestown Road, London NW1 7BY, UK
30 Corporate Drive, Suite 400, Burlington, MA 01803, USA
525 B Street, Suite 1800, San Diego, CA 92101-4495, USA

First edition 1991
Second edition 2001
Third edition 2010

Copyright © 1991, 2001, 2010 Elsevier Inc. All rights reserved with the exception of
Chapter 2 © 2009 American Chemical Society.
Chapters 18, 34 and 61 in the Public Domain.
Chapters 31, 49, 58, 63, 72, 78, 82, 86, 91, 92 and 107 © 2001 Elsevier Inc. All rights reserved.

No part of this publication may be reproduced, stored in a retrieval system or transmitted in any form or by any means
electronic, mechanical, photocopying, recording or otherwise without the prior written permission of the publisher.
Permissions may be sought directly from Elsevier’s Science & Technology Rights Department in Oxford, UK: phone
( (cid:2) 44) (0) 1865 843830; fax ( (cid:2) 44) (0) 1865 853333; email: [email protected] . Alternatively, visit the Science
and Technology Books website at www.elsevierdirect.com/rights for further information

Notice
No responsibility is assumed by the publisher for any injury and/or damage to persons or property as a matter of
products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas
contained in the material herein. B ecause of rapid advances in the medical sciences, in particular, independent verification
of diagnoses and drug dosages should be made

British Library Cataloguing-in-Publication Data
A catalogue record for this book is available from the British Library
Library of Congress Cataloging-in-Publication Data
A catalog record for this book is available from the Library of Congress

ISBN: 978-0-12-374367-1 set
ISBN: 978-0-12-374481-4 volume 1
ISBN: 978-0-12-374482-1 volume 2

For information on all Academic Press publications
visit our website at www.elsevierdirect.com
Typeset by Macmillan Publishing Solutions
www.macmillansolutions.com

Printed and bound in United States of America

10 11 12 13 10 9 8 7 6 5 4 3 2 1

(c) 2011 Elsevier Inc. All Rights Reserved.
Dedication
Wayland Jackson “ Jack ” Hayes, Jr. made endur- large amounts, that are known to have caused poisoning
ing contributions to pesticide science. H ayes ’ Handbook relatively frequently, or that are of special interest for some
of Pesticide Toxicology , third edition, carries his name other reason. ” The subjects of clinical studies included: (1)
to recognize his profound commitment to “ improve the persons with “ heavy occupational exposure ” —i ncluding
knowledge of toxicology, in general, the epidemiology malaria control spray operators, farmers, orchardists, spray
of pesticide poisoning, and the medical management of pilots, and pest control operators; (2) volunteers who take
cases.” He wrote and spoke often of the importance of part in strictly controlled experimental investigations; and
the first principles of toxicology as Chief Toxicologist at (3) patients who are sick from accidental over-exposure to
Centers for Disease Control, Atlanta, Georgia, and later as pesticides. In the preface to his next major work and the
Professor of Toxicology, School of Medicine, Vanderbilt first edition in the present series, he called attention to the
University, Nashville, Tennessee. need for basic toxicology education. P esticides Studied in
Hayes contributed his first volume to the toxicological Man (1982) and T he Handbook of Pesticide Toxicology rep-
literature as the Clinical Handbook on Economic Poisons resent his commitment to the collection and dissemination
(1963), replacing “ C linical Memoranda on Economic of critical research and clinical experience in Hayes’ career
Poisons ” first issued in March 1950 as separate releases on as a leader in pesticide science.
several new insecticides. The booklet described the diagno- Widespread use of the C linical Handbook on Economic
sis and treatment of persons who may have had extensive Poisons and active participation in public debate concern-
or intensive exposure to economic poisons. It was prepared ing pesticide use encouraged Hayes to write of the general
primarily for the guidance of physicians and other public importance of principles of toxicology. In Toxicology of
health professionals. The 1963 booklet concerned use of Pesticides (1975) and his subsequent books he retained the
organophosphorous insecticides and acute toxicities asso- strong clinical content but offered much expanded coverage
ciated with pesticides such as “ arsenic, thallium, phospho- of principles of toxicology, the conditions of exposure, the
rous, and kerosene” because they were “l eading causes of effects on human health, problems of diagnosis and treat-
deaths associated with pesticides.” Hayes acknowledged ment, the means to prevent injury, and even brief outlines on
the great potential value of the materials used as pesticides the impact of pesticides on domestic animals and wildlife.
and urged the careful collection of clinical data and related In the public arena, Hayes spoke out on an expanding
information concerning poisoning, a theme that became role of toxicology to address issues of public and environ-
much clearer in the expanded T oxicology of Pesticides mental health related to pesticide use that became criti-
(1975). Toxicology of Pesticides and his works that followed cal during the 1960s and 1970s following publication of
gave attention to “ those materials that are manufactured in Rachel Carson’s polemic Silent Spring (1962). Concerning
v
(c) 2011 Elsevier Inc. All Rights Reserved.
vi Dedication
the resulting intense public debate about pesticides, Hayes biochemistry and experimental toxicology, and description
wrote in the Preface to T oxicology of Pesticides : of the human experience with pesticides.
Hayes’ admonition to physicians to collect quantitative
“T he pesticide problem is not merely one concerning the
information on the effects of different dosages is consistent
chemical industry and professional farmers, foresters, and
with his high regard for the fullest possible data concern-
applicators, or one concerning only those who wish to
ing the human experience with pesticides. Throughout his
protect wildlife, or those responsible for control of malaria
career Hayes shaped a vision of modern toxicology as an
and other vector-borne diseases of man and his livestock.
Rather, the pesticide problem concerns every person who important means to achieve rational use of chemicals in the
wants food at a reasonable price and who wants his home environment, much in the spirit of Paracelsus who wrote,
free from vermin. The problem can be solved only on the “ … whenever I went I eagerly and diligently investigated
basis of sound toxicological principles. Knowledge of these and sought after the tested and reliable arts of medicine. I
principles permits agreement and a cooperative approach went not only to the doctors, but also to barbers, bathkeep-
on the part of persons professionally responsible for pro- ers, learned physicians, women, and magicians who pursue
tection of our food, our health, and our wildlife, respec-
the art of healing. ”
tively. Ignorance of these principles limits some other
Wayland Hayes was born in Charlottesville, Virginia, on
persons to a partisan approach that may be dangerous to
April 29, 1917. He graduated in 1938 from the University
the common good. ”
of Virginia, received an M. A. degree and a Ph. D. from the
In dedicating Toxicology of Pesticides to Paracelsus, University of Wisconsin where he specialized in zoology
Hayes sought to bring attention to the “ d ecisive importance and physiological chemistry. He returned to the University
of dosage ” in determining the effect of exposure. He urged of Virginia where he received the M. D. in 1946. He
recognition of “ tolerated doses ” as well as information on interned in the Public Health Service Hospital in Staten
doses or blood levels that have produced harm. He clearly Island, New York, and entered the regular corps of the ser-
viewed modern toxicology as a predictive, interdisciplinary vice from 1948 to 1968. He became Chief Toxicologist of
science with great capacity to contribute to chemical safety the Pesticides Program of the Centers for Disease Control
evaluation. in Savannah and Atlanta, Georgia. Hayes joined Vanderbilt
His Pesticides Studied in Man (1982) assumed the University as Professor of Biochemistry, School of
reader’s mastery of the basic principles of toxicology and Medicine, in 1968 becoming emeritus in 1982 but remain-
offered more in-depth coverage of those pesticides with ing active in university affairs until 1991. He died January
direct information concerning their effects in humans. The 4, 1993. His wife, Barnita Donkle Hayes, of 50 years and a
information came from reports of poisoning, from observa- son, Wayland J. Hayes III; and four daughters, Marie Royce
tion of workers or volunteers, or from persons who received Hayes, Maryetta Hayes Hacskaylo, Lula Turner McCoy and
certain compounds as drugs. Sections were organized in Roche Del Moser; and 10 grandchildren, survived him. In
three parts. The first gave a concise summary of the chem- his family and community, he was revered as a parent, gar-
istry and use of the pesticide. The second part concerned dener, artist, philosopher and humorist.
the fate and basic animal toxicity data that contributed to Hayes had a full professional life of national and interna-
determining important dose-response relationships. The tional service. He was a consultant on the toxicology of pes-
third section reported the human experience with the pesti- ticides to the World Health Organization, the Pan American
cide. The present edition of H ayes ’ Handbook of Pesticide Sanitary Bureau, the American Medical Association, the
Toxicology applies this basic scheme more loosely in the U. S. Department of Agriculture/Environmental Protection
description of the toxicology of agents. Agency, the American Conference of Governmental
As Professor of Biochemistry, School of Medicine, Industrial Hygienists and the National Academy of Sciences-
Vanderbilt University, Hayes teamed with his colleague National Research Council. He served on numerous govern-
Edward R. Laws, Jr., Department of Neurological Surgery, mental committees and editorial boards. He was a charter
George Washington School of Medicine, Washington, D. member of the Society of Toxicology in 1961 and served as
C. to edit the first edition of the H andbook of Pesticide its eleventh president 1971– 72. As president of the Society,
Toxicology . It was published by Academic Press in three he staunchly defended the integrity of toxicologists in regu-
volumes and updated and revised both T oxicology of latory affairs (Science 174: 545– 5 46, 1971) and launched
Pesticides and P esticides Studied in Man . The Preface criticism of the USEPA’s dismissal of the recommendation
again champions the potential role of toxicology in reso- of its own Scientific Advisory Committee in response to
lution of controversy regarding pesticide use and reiterates “ external pressure. ” As president, Hayes made a strong plea
the importance of the study of dose-response relationships for the inclusion of toxicology in textbooks of biology, zool-
in diagnosis of poisoning. The book follows familiar orga- ogy, hygiene, and general science (Toxicology and Applied
nization including exposition of principles of toxicology Pharmacology 19, i – ii, 1971). Both subjects are topical
and sections featuring the chemistry and uses of pesticides, today. Other society memberships included the American
(c) 2011 Elsevier Inc. All Rights Reserved.
Dedication vii
Society of Pharmacology and Experimental Therapeutics and Hayes clearly recognized the difficulties associated with
the American Society of Tropical Medicine and Hygiene. collecting meaningful dosage-response information. He
He became a Diplomat of The Academy of Toxicological suggested that failure to collect such valuable data might
Sciences in 1989. result from lack of recognition of its importance in diag-
Wayland Hayes was a sought after expert witness par- nostics. He closed on a theme that has shaped his career
ticularly in cases involving pesticides. His commanding and that remains central to the spirit and content of the cur-
and distinguished presence, his southern accent and gra- rent volumes now dedicated to his life and career saying,
cious manner coupled with his encyclopedic knowledge “ Clinicians who attend patients poisoned by a pesticide
rarely failed to win the case. However, there was one case or by any other material are urged to be alert to the possi-
in Wisconsin where he was unable to convince the jury bility of getting new information on dosage. ”
that DDT was not a potent poison. Finally, he walked over
to the evidence table, picked up the bottle of DDT and
ingested a teaspoon of the evidence. When asked about
how that worked out, he replied, “ well I may have walked Robert I. Krieger, Ph.D.
a little funny, but we won the case” . John W. Doull, M.D., Ph.D.
(c) 2011 Elsevier Inc. All Rights Reserved.
Contents of Volume 1
Contributors xxiii 1.5.7 Species and Strain Differences 64
Foreword xxix 1.5.8 Discussion of Factors Influencing
Preface xxxvii Toxicity 88
Section I 2. P est Toxicology: The Primary
Pesticide Uses Mechanisms of Pesticide Action 103
2.1 Introduction 103
1. D ose and Time Determining, and 2.2 Primary targets 103
Other Factors Infl uencing, Toxicity 3 2.3 Secondary targets 105
2.4 C ommon target for structurally
1.1 Introduction 3 diverse pesticides 105
1.1.1 Dose and Time as Fundamental 2.5 Resistance as a limiting factor 105
Variables of Toxicity 3 2.6 Nerve (Table 2.1, Figure 2.2) 106
1.1.2 Definition of Dose and Time 6 2.7 P hotosynthesis and pigment synthesis
1.1.3 Dose and Time Relationships 6 (Table 2.2, Figure 2.3) 107
1.1.4 Analogy to Thermodynamics 8 2.8 Biosynthesis 108
1.2 Kinds of toxicity 10 2.8.1 Herbicides (Table 2.3, Figure 2.4) 108
1.2.1 Nature of the Injury 10 2 .8.2 Fungicides and Insecticides
1.2.2 Duration of the Injury 10 (Table 2.4, Figure 2.5) 109
1.3 Q uantitation of dosage–response 2.9 Respiration (Table 2.5, Figure 2.6) 111
relationships 12 2.10 Growth regulators (Table 2.6,
1.3.1 ED 50 or LD 50 13 Figure 2.7) 112
1.3.2 Measurement of Cumulative 2.11 U nknown, nonspecific and other
Effects 23 targets (Table 2.7) 112
1.3.3 Time Relationships 27 2.12 Overview (Table 2.8) 113
1.3.4 Problem of Measuring Effect of 2.13 Conclusion 116
2.14 Postscript 116
Dispersed Toxicants 33
Acknowledgments 116
1.3.5 Measurement of Graded
Responses 33
1.3.6 Dosage at the Tissue Level 33
3. P est Control Agents from Natural
1.3.7 Statistical Considerations 34
Products 119
1.4 D osage–response relationships in
different kinds of toxicity or change 47 3.1 Introduction 119
1.4.1 Toxicity (Sensu Stricto) 47 3.2 Insect control agents 120
1.4.2 Neurotoxicity 47 3.2.1 Botanical Insecticides 120
1.4.3 Teratogenesis 47 3.2.2 Microbial Insecticides 154
1.4.4 Carcinogenesis 48 3.2.3 Semiochemicals 167
1.4.5 Mutagenesis 50 3.3 Disease control agents 173
1.4.6 Hypersensitivity and Allergy 50 3.3.1 Fungicides 173
1.4.7 Induction of Enzymes 50 3.3.2 Bactericides 180
1.4.8 Metabolism and Storage 51 3.4 Herbicides 183
1.5 Factors influencing toxicity of any kind 53 3.4.1 Bilanafos (Bialaphos) 183
1.5.1 Dosage 53 3.4.2 Glufosinate 184
1.5.2 Compound 54 3.5 Rodenticides 188
1.5.3 Interaction of Compounds 56 3.5.1 Strychnine 188
1.5.4 Schedule of Dosage 61 3.5.2 Red Squill and Scilliroside 193
1.5.5 Duration of Dosage 62 3.5.3 Ricin 196
1.5.6 Route of Exposure 63 3.5.4 Salmonella Bacteria 200
ix
(c) 2011 Elsevier Inc. All Rights Reserved.
x Contents of Volume 1
4. Public Health Pesticides 231 7. P esticide Use and Associated
Morbidity and Mortality in
4.1 Introduction 231
4.2 Definition of terms in vector-borne Veterinary Medicine 285
diseases 231
7.1 Introduction 285
4.3 Impact of arthropods on human
7.2 Formulations 286
health 237
7.3 Species sensitivities 286
4.4 I ntegrated pest management and
7.4 Pesticide use in domestic animals 287
vector management 238
7.5 R egulation of pesticides used in
4.4.1 Noninsecticidal Methods in
veterinary medicine 287
Vector Management 240
7.6 Violative residues 289
4.4.2 Chemicals in Vector 7.7 Frequency of intoxication 289
Management 241 7.8 Scenarios of concern 290
Conclusion 250
7.8.1 Acute Intoxication 290
7.8.2 Chronic Intoxication 290
5. T he Changing Role of Insecticides 7.8.3 Pesticide Use and Cancer in
in Structural Pest Control 257 Animals 291
7.8.4 Pesticide Use and Exposure of
5.1 Introduction 257
People in Contact with Animals 291
5.2 Pest problems: real or perceived 257
7.9 Major pesticide categories 292
5.3 Environmental and health concerns 258
7.9.1 Cholinesterase Inhibitors: Organ-
5.4 Insecticide applications 260
ophosphoruses and Carbamates 292
5.4.1 Nonresidual Insecticides 260
7.9.2 Pyrethrins and Pyrethroids 292
5.4.2 Residual Insecticides 261
7.9.3 Natural Products Used for
5.5 Soil treatments for subterranean
Flea Control 293
termites 263
7.9.4 Macrocyclic Lactones 294
5.6 Baits and baiting 265
5.7 Future directions 266 7.9.5 Neonicotinoids: Imidacloprid
Conclusion 266 and Nitenpyram 294
7.9.6 Fipronil 295
7.9.7 Amitraz 295
6. V ertebrate Pest Control Chemicals
7.9.8 Insect Growth Regulators 295
and Their Use in Urban and Rural
7.9.9 Synergists and Repellants 295
Environments 271
7.9.10 Rodenticides 296
6.1 Introduction 271 7.9.11 Metaldehyde 296
6.2 Vertebrate pests: what are they? 271 7.9.12 Paraquat 296
6.3 Management restrictions 272 7.10 Diagnosis of intoxication 296
6.4 Problems created by vertebrates 272 7.11 Treatment of intoxication 297
6.5 Nonlethal management without Conclusion 298
pesticides 272
6.6 Population reduction without
8. P esticide Use Practices in
pesticides 273
Integrated Pest Management 303
6.7 Pesticides: repellents versus
lethal agents 274 8.1 Integrated pest management 304
6.8 Repellents 275 8.2 What is integrated pest
6.9 Immobilizing agents 277 manangement? 305
6.10 Lethal vertebrate pesticides 277 8.3 The IPM continuum 305
6.10.1 Poison Rodent Baits 277 8.4 Pesticides 306
6.10.2 Fumigants 281 8.5 Field scouting 306
6.10.3 Tracking Powders 281 8.5.1 Monitoring 306
6.10.4 Contraceptives 282 8.5.2 Decision Support 307
6.10.5 Glue Boards 282 8.6 Reduced-risk pesticides 307
6.10.6 Livestock Protection Collars 282 8.6.1 Behavioral Chemicals 307
6.10.7 Toxicant Ejector Device 283 8.6.2 Conventional Products and Risk 308
6.10.8 Flock Dispersal Agent 283 8.7 Cultural and physical suppression 308
6.10.9 Poison Bird Bait 283 8.8 Prevention 308
Conclusion 284 8.9 Avoidance 308
(c) 2011 Elsevier Inc. All Rights Reserved.
Contents of Volume 1 xi
8.10 Pesticides and biological controls 309 11. Genotoxicity of Pesticides 357
8.11 Advisory services 309
11.1 Introduction 357
Conclusion 311
11.2 Genotoxicity tests 358
11.2.1 Bacterial Reverse Mutation Assay 360
9. P roperties of Soil Fumigants and
11.2.2 In Vitro Mutation Assay in
Their Fate in the Environment 315 Mammalian Cells 361
11.2.3 In Vivo Cytogenetic Assay 361
9.1 Introduction 315
11.2.4 Micronucleus Assay 362
9.2 C hemical properties, application,
11.3 Genotoxicity testing of pesticides 362
and major environmental issues 317
11.4 Patterns of response 362
9.2.1 Fumigation Methods 318
11.4.1 Pesticides Exhibiting Both
9.2.2 Environmental Concerns 319
Genotoxicity and Carcinogenicity 362
9.3 P rocesses and factors affecting the
fate of fumigants in soil 319 11.4.2 Pesticides Exhibiting
Genotoxicity With Limited or
9.3.1 Volatilization 319
No Evidence of Carcinogenicity 365
9.3.2 Degradation 320
11.4.3 Pesticides Exhibiting
9.3.3 Adsorption 320
9.4 F umigant distribution in soil and Carcinogenicity Without
efficacy assessment 321 Appreciable Genotoxicity 366
9.5 Currently available soil fumigants 322 11.4.4 Nongenotoxic Agents Without
9.5.1 Methyl Bromide 322 Evidence of Carcinogenicity 367
9.5.2 Methyl Iodide (Iodomethane) 323 11.4.5 Pesticides Exhibiting Mixed Results
9.5.3 1,3-Dichloropropene 323 in Genotoxicity or Cancer Tests 367
9.5.4 Chloropicrin 324 11.5 Human biomonitoring 369
11.6 Genotoxicity and risk assessment 373
9.5.5 Methyl Isothiocyanate 324
Conclusion 374
9.5.6 Dimethyl Disulfide 325
9.5.7 Sodium Tetrathiocarbonate 325
9.6 Strategies to minimize emissions 326
9.6.1 Application Methods 326 12. Developmental and Reproductive
9.6.2 Plastic Films 326 Toxicology of Pesticides 381
9.6.3 Irrigation or Water Treatment 326
12.1 Introduction 381
9.6.4 Chemical Amendment 326
12.1.1 Developmental Toxicity 382
9.6.5 Organic Amendment 327
12.1.2 Reproductive Toxicity 383
9.6.6 Target Area Treatment 327
12.1.3 Epidemiology 383
9.6.7 Mass Balance of Fumigants
12.2 Exposure 384
Applied to Soil 327
12.2.1 Timing of Exposure 384
Conclusion 327
12.2.2 Prenatal Reproductive Toxicants 384
12.2.3 Prepubertal Reproductive
Toxicants 385
Section II 12.2.4 Adult Reproductive Toxicants 385
Toxicity and Safety Evaluation 12.3 Mechanisms of action 385
12.3.1 Direct-Acting 385
12.3.2 Indirect-Acting 385
Toxicity and Safety Evaluation of
12.4 Regulatory issues 385
Pesticides 333
12.4.1 History 386
12.4.2 Principles of Testing and
10. R isk Assessment for Acute Exposure
Evaluation 386
to Pesticides 337
12.4.3 Choice of Species in Testing 388
10.1 Introduction 337 12.4.4 Choice of Testing Doses 388
10.2 Toxicological data 337 12.4.5 Interpreting Effects 388
10.3 Exposure data 338 12.4.6 Statistical Evaluation 389
10.4 Examples 340 12.4.7 Exposure Assessment 389
10.4.1 Methyl Parathion 340 12.4.8 Impact of FQPA on
10.4.2 Methyl Bromide 344 Developmental and Reproductive
Conclusion 349 Toxic Effects of Pesticides 390
(c) 2011 Elsevier Inc. All Rights Reserved.