-------
RECOGNITION AND
MANAGEMENT OF
PESTICIDE POISONINGS
Fifth Edition, 1999
J. Routt Reigart, M.D.
Professor of Pediatrics, Medical University of South Carolina
James R. Roberts, M.D., M.P.H.
Assistant Professor of Pediatrics, Medical University of South Carolina
Support for this publication was provided by:
Certification and Worker Protection Branch
Field and External Affairs Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
401 M Street SW (7506C)
Washington, DC 20460
For additional copies or more information:
Tel: 703-305-7666
Fax:703-308-2962
The manual is available in electronic format on the Internet at:
http://www.epa.gov/pesticides/safety/healthcare
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Acknowledgments
We are grateful to the Office of Pesticide Programs, Environmental Protection Agency, for giving us the
opportunity to collaborate on this new edition. Our thanks go to Kevin Keaney, Acting Branch Chief, for
his support and vision, and for giving this publication priority attention. Particular mention should also be
made of the efforts of Jerome M. Blondell, Ph.D., M.P.H., and Ameesha Mehta, M.P.H., whose oversight
and constant assistance were invaluable in moving this project forward. Ana Maria Osorio, M.D., M.P.H.,
contributed Chapter 3, Environmental and Occupational History, to this manual.
Experts in clinical toxicology conducted critical reviews of draft material. We are greatly appreciative
of the time and effort of the following reviewers:
Jeffery Lloyd Burgess, M.D., M.P.H.
Assistant Professor
Environmental Occupational Health Unit
University of Arizona Prevention Center
Matthew C. Keifer, M.D., M.P.H.
Assistant Professor
Department of Medicine/Environmental Health
University of Washington
Wayne R. Snodgrass, M.D, Ph.D.
Professor and Head
Clinical Pharmacology-Toxicology
Texas Poison Center
Sheldon L.Wagner, M.D.
Professor of Clinical Toxicology
Oregon State University
Many other individuals contributed their time and skill to this publication. We are very appreciative
of the tireless efforts of Patricia Clark, our administrative assistant, who spent endless hours in text
review, securing references, communicating with reviewers, and otherwise making the revision process
possible and easier than anticipated. Gilah Langner of Stretton Associates, Inc., provided editorial super-
vision. Will Packard and Sarah Carter of Free Hand Press, Inc. were responsible for the format and
layout of the manual.
Cover photographs by Steve Delaney, EPA.
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CONTENTS
Section I: General Information
1 Introduction 2
2 General Principles in the Management of Acute Pesticide Poisonings 10
3 Environmental and Occupational History 17
Section II: Insecticides
4 Organophosphate Insecticides 34
5 N-Methyl Carbamate Insecticides 48
6 Solid Organochlorine Insecticides 55
7 Biologicals and Insecticides of Biological Origin 63
8 Other Insecticides, Acaricides, and Repellents 74
Section III: Herbicides
9 Chlorophenoxy Herbicides 94
10 Pentachlorophenol 99
11 Nitrophenolic and Nitrocresolic Herbicides 104
12 Paraquat and Diquat 108
13 Other Herbicides 118
Section IV: Other Pesticides
14 Arsenical Pesticides 126
15 Fungicides 137
16 Fumigants 156
17 Rodenticides 169
18 Miscellaneous Pesticides, Solvents, and Adjuvants 183
19 Disinfectants 196
Section V
Index of Signs and Symptoms 210
Index of Pesticide Products 223
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List of Tables
Dosage Tables
Sorbitol 12
Activated Charcoal 13
Syrup of Ipecac 14
Diazepam 14
Lorazepam 15
Atropine 42
Pralidoxime 43
Atropine 51
Diazepam 58
Atropine Sulfate 68, 72
Calcium Gluconate 84
Lorazepam 102
Bentonite and Fuller's Earth 113
Morphine Sulfate 115
BAL (Dimercaprol) 130
D -penicillamine 131
DMSA (Succimer) 131
DMPS 131
Cyanide Antidotes 166
Supplemental Sodium Nitrite and Sodium Thiosulfate 167
Phytonadione 171
Aquamephyton* 172
Calcium Gluconate 178
Tables
Pesticides Most Often Implicated in Symptomatic Illnesses, 1996 5
California Occupational Illnesses Due to Pesticides, 1991-1995 6
Screening Questions for Occupational and Environmental Exposures 18
Adult Interview for Occupational and Environmental Exposures 26
Steps in Investigating a Disease Outbreak 26
Approximate Lower Limits of Normal Plasma and
Red Cell Cholinesterase Activities in Humans 39
Toxicity of Common Herbicides 119
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Section I
GENERAL INFORMATION
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CHAPTER 1
Introduction
This fifth edition of Recognition and Management of Pesticide Poisonings is an up-
date and expansion of the 1989 fourth edition. The Office of Pesticide Pro-
grams of the United States Environmental Protection Agency has sponsored
the series since 1973. The purpose of the manual is to provide health profes-
sionals with recently available information on the health hazards of pesticides
currently in use, and current consensus recommendations for management of
poisonings and injuries caused by them.
Pesticide poisoning is a commonly under-diagnosed illness in America to-
day. Despite recommendations by the Institute of Medicine and others urging
the integration of environmental medicine into medical education, health care
providers generally receive a very limited amount of training in occupational
and environmental health, and in pesticide-related illnesses, in particular.'The
updating of this manual is part of a larger initiative of the U.S. Environmental
Protection Agency, in conjunction with numerous federal agencies, associa-
tions of health professionals, and related organizations to help health care
providers become better aware, educated, and trained in the area of pesticide-
related health concerns. This larger initiative, entitled Pesticides and National
Strategies for Health Care Providers, was launched in April 1998.
As with previous updates, this new edition incorporates new pesticide prod-
ucts that are not necessarily widely known among health professionals. The
accumulated "use experience" of formulators, applicators, and field workers
provides an expanding basis for judging safety and identifying the environmen-
tal and workplace hazards of old and new pesticides. Major episodes of adverse
health effects reported in medical and scientific periodicals have been taken
into account. This literature also contributes importantly to improved under-
standing of toxic mechanisms. Clinical toxicology is a dynamic field of medi-
cine; new treatment methods are developed regularly, and the effectiveness of
old as well as new modalities is subject to constant critical review.
There is general agreement that prevention of pesticide poisoning remains a
much surer path to safety and health than reliance on treatment. In addition to
the inherent toxicity of pesticides, none of the medical procedures or drugs
used in treating poisonings is risk-free. In fact, many antidotes are toxic in their
own right, and such apparently simple procedures as gastric intubation incur
substantial risk. The clinical toxicologist must often weigh the hazards of vari-
ous courses of actionsometimes including no treatment at allagainst the
risks of various interventions, such as gastric emptying, catharsis, administration
2 INTRODUCTION
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of intravenous fluids, or administration of an antidote, if available. Clinical man-
agement decisions have to be made promptly and, as often as not, on the basis
of limited scientific and medical information. The complex circumstances of
human poisonings rarely allow precise comparisons of alternative management.
In no sense, then, are the treatment recommendations in this book infallible
guides to successful outcomes.They are no more than consensus judgments of
the best available clinical management options.
This manual deals almost entirely with short-term (acute) harmful effects
of pesticides. Although obviously important, the subject of chronic effects is
too complex to deal with exhaustively in a manual designed as guidance for
emergency management. Nonetheless, appropriate treatment of serious expo-
sures to pesticides represents an important step in avoiding chronic as well as
acute disease.
The pesticides and commercial products mentioned in this manual do not
represent the universe of pesticide products in existence. They were selected
based on frequency of use and exposure, severity of toxicity, and prior experi-
ence with acute poisonings. Products are discussed in this manual that have
been discontinued or whose U.S. pesticide registration has been revoked but
are judged to still be of risk due to use elsewhere or where there is a probability
of residual stocks. Agents long out of use in the U.S. and elsewhere were not
included in the manual.
The amount of pesticide absorbed is a critical factor in making treatment
decisions, and estimation of dosage in many circumstances of pesticide expo-
sure remains difficult.The terms "small amount" and "large amount" used in
this book are obviously ambiguous, but the quality of exposure information
obtained rarely justifies more specific terminology.
Sometimes the circumstances of exposure are a rough guide to the amount
absorbed. Exposure to spray drift properly diluted for field application is not
likely to convey a large dose unless exposure has been prolonged. Spills of
concentrated technical material onto the skin or clothing may well represent a
large dose of pesticide unless the contamination is promptly removed. Brief
dermal exposure to foliage residues of cholinesterase-inhibiting pesticides is
not likely to lead to poisoning, but prolonged exposures may well do so. Sui-
cidal ingestions almost always involve "large amounts," requiring the most ag-
gressive management. Except in children, accidental pesticide ingestions are
likely to be spat out or vomited. Ingestions of pesticides by children are the
most difficult to evaluate. The therapist usually must base clinical management
decisions on "worst case" assumptions of dosage. Childhood poisonings are still
further complicated by the greater vulnerability of the very young, not only to
pesticides themselves, but also to drugs and treatment procedures. The nature
of neurological development in children entails an additional level of risk that
is not present in adults. Some adult groups such as farmwrokers with poor
nutrition and high exposure may also be at increased risk.
INTRODUCTION 3
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Key Principles
General methods of managing pesticide poisonings are presented in Chap-
ter 2 and reflect a broad base of clinical experience. The following key points
deserve emphasis. The need to protect the airway from aspiration of vomitus
cannot be overstated. Death has occasionally resulted from this complication,
even following ingestions of substances having relatively low toxic potential. In
poisonings by agents that depress central nervous system function or cause
convulsions, early placement of a cuffed endotracheal tube (even when this
requires light general anesthesia) may be life saving. Maintenance of adequate
pulmonary gas exchange is another essential element of poisoning manage-
ment that deserves constant reemphasis.
Gastric intubation, with aspiration and lavage, remains a useful method for
removing poisons from the stomach shortly after they have been swallowed,
but the time after ingestion during which lavage is likely to be beneficial is
shorter than many clinical toxicologists have thought. Rarely are significant
amounts of swallowed toxicants recovered more than 1-2 hours after ingestion,
and, in many instances, the bulk of swallowed material passes into the duode-
num and beyond in 15-30 minutes. In addition, the majority of controlled
studies evaluating the effectiveness of gastric emptying procedures are done for
ingestions of solid material (pills) rather than liquids.
Full advantage should be taken of new highly adsorbent charcoals that are
effective in binding some pesticides in the gut. Unfortunately, charcoal does
not adsorb all pesticides, and its efficiency against many of them is not known.
In poisonings caused by large intakes of pesticide, hemodialysis and
hemoperfusion over adsorbents continue to be tested as methods for reducing
body burdens. Against some toxicants, these procedures appear valuable. Over-
all effectiveness appears to depend not only on efficiency of clearance from the
blood, but also on the mobility of toxicant already distributed to tissues before
the extracorporeal blood-purification procedure is started.The volume of dis-
tribution and avidity of tissue binding are important considerations in making
such decisions. The critical determinant of success in using these systems may
well be the speed with which they can be put into operation before tissue-
damaging stores of toxicant have accumulated.
There remains a need for systematic reporting of pesticide poisonings to a
central agency so that accurate statistics describing the frequency and circum-
stances of poisoning can be compiled, and efforts to limit these occurrences can
be properly directed. In some countries there has been an increase in the use of
pesticides as instruments of suicide and even homicide. Producers are now
devoting considerable effort to modifying formulation and packaging to deter
these misuses.This work is important because suicidal ingestions are often the
most difficult pesticide poisonings to treat successfully.
4 INTRODUCTION
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Common Pesticide Poisonings
The pesticides most often implicated in poisonings, injuries, and illnesses,
according to 1996 data from the American Association of Poison Control Centers
Toxic Exposure Surveillance System, are listed below.
The list is based on symptomatic cases classified as minor, moderate, major,
or fatal outcome for unintentional cases involving a single product. Numbers
of cases are reported for both children under six years of age and for adults and
older children. Suicide/homicide (intentional) cases have been excluded. Cases
listed as organophosphates (and the other categories as well) may also include
other insecticides such as carbamates and organochlorines in a single product.
PESTICIDES MOST OFTEN IMPLICATED IN SYMPTOMATIC
ILLNESSES, 1996
Rank
1
2
3
4
5
6
7
8
9
10
Pesticide or Pesticide Class
Organophosphates
Pyrethrins and pyrethroids**
Pine oil disinfectants
Hypochlorite disinfectants
Insect repellents
Phenol disinfectants
Carbamate insecticides
Organochlorine insecticides
Phenoxy herbicides
Anticoagulant rodenticides
All Other Pesticides
Total all pesticides/disinfectants
* Totals include a small number of cases with
** Rough estimate: includes some veterinary
Source:
System,
Child
< 6 years
700
1100
1336
808
1081
630
202
229
63
176
954
7279
Adults
6-19yrs.
3274
2850
903
1291
997
405
817
454
387
33
3604
15,015
Total*
4002
3950
2246
2109
2086
1040
1030
685
453
209
4623
22,433
unknown age.
products not classified by chemical type.
American Association of Poison Control Centers, Toxic
1996 data.
Exposure
Surveillance
Approximately 90% of symptomatic cases involve only minor symptoms of
the type that could typically be treated at home with dilution or just observation.
However, seven of the top ten categories listed in the table above (organo-
phosphates, py re thr ins/pyre thro ids, hypochlorite disinfectants, carbamates,
organochlorines, phenoxy herbicides, and anticoagulant rodenticides) are much
more likely to require medical attention.
This list cannot be considered representative of all symptomatic poisonings
because it only shows cases reported to Poison Control Centers. However, it does
give a sense of the relative frequency and risk of poisoning from various agents or
classes of agents. The relative frequency of cases generally reflects how widely a
product is used in the environment. For example, a number of disinfectants occur
in the top ten partly because they are far more commonly found in the home and
work environment than other pesticides (see also the table of occupational cases
INTRODUCTION
-------
below). Denominator information on the population at risk (numbers exposed)
would be needed to better understand the relative risk of different pesticides.
However, the main purpose of these tables is to give physicians a sense of what
types of cases they are most likely to see in their practice.
Although suicide cases make up roughly 3% of pesticide-related calls to
Poison Control Centers, they may account for nearly 10% of the cases seen in
a health care facility. The leading types of products involved in suicidal cases
include anticoagulant rodenticides (20% of total suicide attempts), pine oil dis-
infectants (14%),organophosphates (ll%),pyrethrins/pyrethroids (6%),unknown
rodenticides (5%), carbamate insecticides (4%), and phenol disinfectants
CALIFORNIA OCCUPATIONAL ILLNESSES LIKELY DUE TO
PESTICIDES, 1991-1995
Rank Pesticide
1 Sodium hypochlorite
2 Quaternary ammonia
3 Chlorine
4 Glutaraldehyde
5 Chlorpyrifos
6 Sulfur
7 Glyphosate
8 Propargite
9 Metam sodium**
10 Cyanuric acid
All Other
Total all pesticides/disinfectants
* Topical includes skin, eye, and respiratory
** Train derailment led to a cluster of cases
Systemic
167
9
112
38
113
48
9
3
64
14
1149
1726
effects.
due to metam
Topical*
858
348
124
118
39
69
94
96
33
76
1089
2944
sodium in 1991.
Source: Louise Mehler, M.S., California Pesticide Illness Surveillance Program
Environmental Protection Agency.
Total
1025
357
236
156
152
117
103
99
97
90
2238
4670
California
Poison Control Centers are best at capturing pesticide exposures which
occur in residential environments. However, occupational exposures are not as
well covered. California's Pesticide Illness Surveillance Program is generally
regarded as the best in the country. The table above presents the number of
occupationally-related cases in California reported from 1991 through 1995
where a pesticide was considered a probable or definite cause of the resulting
illness. Pesticide combinations, where the primary pesticide responsible for the
illness could not be identified, are not included in this table. Among persons
who encounter pesticides in the course of their occupational activities, dermal
and eye injuries, rather than systemic poisonings, are more common. Systemic
poisonings, however, are likely to be more severe.
6 INTRODUCTION
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Format of this Manual
An effort has been made to format this book for quick reference by thor-
ough indexing and minimal references to other pages or chapters. However,
many different agents commonly require similar procedures in treating poison-
ings and it is not practical to repeat these protocols in every chapter. General
principles for management of pesticide poisoning, including skin and eye de-
contamination, gastrointestinal decontamination, and control of convulsions
are considered in Chapter 2, General Principles. These principles are refer-
enced throughout.
Changes in this reformatted edition include: tabular listings of Commercial
Products in each chapter, the addition of a new chapter on Disinfectants (Chapter
19), and the addition of a chapter on Environmental and Occupational History
(Chapter 3), which places pesticide poisonings in the context of other environ-
mental and occupational exposures, provides questionnaires designed to elicit ex-
posure information, discusses resources available to the practitioner, and provides a
list of governmental and non-government contacts and Web sites for more infor-
mation. In addition, each chapter is referenced to key references in readily accessible
current literature. Most references were selected as primary references in peer
review journals, although some review papers are also included.
The contents of this book have been derived from many sources: published
texts, current medical, toxicological, and pesticide product literature, and direct
communications with experts in clinical toxicology and pesticide toxicology and
environmental and occupational health specialists. A list of the major text sources
follows this introduction.
Reference
1. Institute of Medicine. Role of the Primary Care Physician in Occupational and Environ-
mental Medicine, Washington, DC: Institute of Medicine, 1988.
Texts and Handbooks on Pesticides,
Pesticide Toxicology, and Clinical Toxicology
Agricultural Chemicals Books I, II, III, IV
W.T.Thomson
Thomson Publications, Fresno, CA, 1994-95
Agrochemicals Desk Reference: Environmental Data
John H. Montgomery
Lewis Publishers, Boca Raton, FL, 1995
The Agrochemicals Handbook, 3rd Edition
The Royal Society of Chemistry, Cambridge, England, 1994
INTRODUCTION 7
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Biological Monitoring Methods for Industrial Chemicals,
2nd Edition
Randall C. Baselt
Biomedical Publications, Davis, CA, 1988
Casarett and Doull's Toxicology, 5th Edition
John Doull, Curtis D. Klaassen, and Mary O. Amdur
Macmillan Publishing Company, New York, NY, 1996
Chemicals Identified in Human Biological Media: A Data Base
Compiled by M.Virginia Cone, Margaret F. Baldauf, Fay M. Martin, and John
T. Ensminger
Oak Ridge National Laboratory, 1980
Clinical Toxicology of Agricultural Chemicals
Sheldon L.Wagner, M.D.
Oregon State University Press, Corvallis, OR, 1981
Clinical Toxicology of Commercial Products, 5th Edition
Robert E. Gosselin, Roger P. Smith and Harold C. Hodge, with assistance of
Jeannette E. Braddock
Williams and Wilkins, Baltimore, MD, 1984
Farm Chemicals Handbook
Charlotte Sine, Editorial Director
Meister Publishing Company, Willoughby, Ohio, 1998
Handbook of Pesticide Toxicology
Wayland J. Hayes, Jr. and Edward R. Laws, Jr., Editors
Academic Press, San Diego, CA 1991
Handbook of Poisoning: Prevention, Diagnosis and Treatment,
12th Edition
Robert H. Dreisbach and William O. Robertson
Appleton and Lange, East Norwalk, CT, 1987
Herbicide Handbook, 7th Edition
Weed Science Society of America, 1994
Medical Toxicology: Diagnosis and Treatment of Human Poisoning
Matthew J. Ellenhorn and Donald G. Barceloux
Elsevier, New York, NY, 1988
8 INTRODUCTION
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The Merck Index, llth Edition
Martha Windholz and Susan Budavari, Editors
Merck and Company, Inc., Rahway, NJ, 1989
Patty's Industrial Hygiene and Toxicology, 4th Revised Edition
George D. Clayton and Florence E. Clayton
Wiley Interscience, New York, NY, 1991-95
Pesticide Manual, llth Edition
CDS Tomlin
The British Crop Protection Council, Farnham, Surrey, United Kingdom, 1997
Pesticide Pro files :Toxi city, Environmental Impact, and Fate
Michael A. Kamrin (Editor)
Lewis Publishers, Boca Raton, FL, 1997
The Pharmacological Basis of Therapeutics, 8th Edition
Louis S. Goodman and Alfred Gilman
Pergamon Press, New York, NY, 1990
POISINDEXฎ System
Barry H. Rumack, N.K. Sayre, and C.R. German, Editors
Micromedex, Englewood, CO, 1974-98
Poisoning: A Guide to Clinical Diagnosis and Treatment, 2nd Edition
W. F Von Oettingen
W. B. Saunders Company, Philadelphia, PA, 1958
INTRODUCTION 9
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CHAPTER 2
General Principles in
the Management of
Acute Pesticide Poisonings
This chapter describes basic management techniques applicable to most acute
pesticide poisonings. Where special considerations and treatments are required
for a particular pesticide, they are addressed separately in the appropriate chapter.
Skin Decontamination
Decontamination must proceed concurrently with whatever resuscitative
and antidotal measures are necessary to preserve life. Shower patient with soap
and water, and shampoo hair to remove chemicals from skin and hair. If there
are any indications of weakness, ataxia, or other neurologic impairment, cloth-
ing should be removed and a complete bath and shampoo given while the
victim is recumbent. The possibility of pesticide sequestered under fingernails
or in skin folds should not be overlooked.
Flush contaminating chemicals from eyes with copious amounts of clean
water for 10-15 minutes. If eye irritation is present after decontamination, oph-
thalmologic consultation is appropriate.
Persons attending the victim should avoid direct contact with heavily con-
taminated clothing and vomitus. Contaminated clothing should be promptly
removed, bagged, and laundered before returning. Shoes and other leather items
cannot usually be decontaminated and should be discarded. Note that pesti-
cides can contaminate the inside surfaces of gloves, boots, and headgear. De-
contamination should especially be considered for emergency personnel such
as ambulance drivers at the site of a spill or contamination. Wear rubber gloves
while washing pesticide from skin and hair of patient. Latex and other surgical
or precautionary gloves usually will not always adequately protect from pesti-
cide contamination, so only rubber gloves are appropriate for this purpose.
Airway Protection
Ensure that a clear airway exists. Suction any oral secretions using a large
bore suction device if necessary. Intubate the trachea if the patient has respira-
tory depression or if the patient appears obtunded or otherwise neurologically
10 GENERAL PRINCIPLES
-------
impaired. Administer oxygen as necessary to maintain adequate tissue oxygen-
ation. In severe poisonings, it may be necessary to mechanically support pul-
monary ventilation for several days.
Note on Specific Pesticides: There are several special considerations
with regard to certain pesticides. In organophosphate and carbamate poi-
soning, adequate tissue oxygenation is essential prior to administering atropine.
As important, in paraquat and diquat poisoning, oxygen is contraindicated
early in the poisoning because of progressive oxygen toxicity to the lung tissue.
See specific chapters for more details.
Gastrointestinal Decontamination
A joint position statement has recently been released by the American
Academy of Clinical Toxicology and the European Association of Poisons Centres
and Clinical Toxicologists on various methods of gastrointestinal decontamina-
tion. A summary of the position statement accompanies the description of
each procedure.
1. Gastric Lavage
If the patient presents within 60 minutes of ingestion, lavage may be con-
sidered. Insert an orogastric tube and follow with fluid, usually normal saline.
Aspirate back the fluid in an attempt to remove any toxicant. If the patient is
neurologically impaired, airway protection with a cuffed endotracheal tube is
indicated prior to gastric lavage.
Lavage performed more than 60 minutes after ingestion has not proven to
be beneficial and runs the risk of inducing bleeding, perforation, or scarring
due to additional trauma to already traumatized tissues. It is almost always nec-
essary first to control seizures before attempting gastric lavage or any other
method of GI decontamination.
Studies of poison recovery have been performed mainly with solid mate-
rial such as pills.There are no controlled studies of pesticide recovery by these
methods. Reported recovery of material at 60 minutes in several studies was
8%-32%.''2 There is further evidence that lavage may propel the material into
the small bowel, thus increasing absorption.3
Note on Specific Pesticides: Lavage is contraindicated in hydrocarbon
ingestion, a common vehicle in many pesticide formulations.
Position Statement: Gastric lavage should not be routinely used in the
management of poisons. Lavage is indicated only when a patient has ingested a
potentially life-threatening amount of poison and the procedure can be done
within 60 minutes of ingestion. Even then, clinical benefit has not been con-
firmed in controlled studies.4
GENERAL PRINCIPLES 11
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2. Catharsis
Sorbitol and magnesium citrate are commonly used cathartic agents. Be-
cause magnesium citrate has not been studied as much, its use is not described
here. Sorbitol is often included in charcoal formulations. It will increase gut
motility to improve excretion of the charcoal-poison complex. The dosage of
sorbitol is 1-2 g/kg as a one-time dose. Repeat doses of cathartics may result in
fluid and electrolyte imbalances, particularly in children, and are therefore not
recommended. Sorbitol is formulated in 70% and 35% solutions and usually
packaged in 100 mL bottles. The gram dosage of sorbitol in a 100 mL bottle
can be calculated by multiplying 100 (mL) x 0.7 (for 70% solution) x 1.285 g
sorbitol/mL.Therefore the dose in mL is as follows:
Dosage of Sorbitol:
Adults: 70% sorbitol, 1-2 mL/kg.
Children:35% sorbitol, 1.5-2.3 mL/kg (maximum dosage: 50 g).
Note on Specific Pesticides: Significant poisoning with organophos-
phates, carbamates, and arsenicals generally results in a profuse diarrhea. Poi-
soning with diquat and to a lesser extent paraquat results in an ileus.The use of
sorbitol is not recommended in any of the above pesticide poisonings.
Position Statement: The administration of a cathartic alone has no role
in the management of the poisoned patient. There are no definite indications
for the use of cathartics in the management of the poisoned patient. Data are
conflicting with regard to use in combination with activated charcoal, and its
routine use is not endorsed. If a cathartic is used, it should be as a single dose in
order to minimize adverse effects. There are numerous contraindications,
including absent bowel sounds, abdominal trauma or surgery, or intestinal
perforation or obstruction. It is also contraindicated in volume depletion,
hypotension, electrolyte imbalance, or the ingestion of a corrosive substance.5
3. Activated Charcoal Adsorption
Activated charcoal is an effective absorbent for many poisonings.Volunteer
studies suggest that it will reduce the amount of poison absorbed if given within
60 minutes.6 There are insufficient data to support or exclude its use if time
from ingestion is prolonged, although some poisons that are less soluble may be
adsorbed beyond 60 minutes. Clinical trials with charcoal have been done with
poisons other than pesticides. There is some evidence that paraquat is well
adsorbed by activated charcoal.7'8 Charcoal has been anecdotally successful with
other pesticides.
12 GENERAL PRINCIPLES
-------
Dosage of Activated Charcoal:
Adults and children over 12years: 25-100 g in 300-800 mL water.
Children under 12years: 25-50 g per dose.
Infants and toddlers under 20 kg. I g per kg body weight.
Many activated charcoal formulations come premixed with sorbitol. Avoid giv-
ing more than one dose of sorbitol as a cathartic in infants and children due to
the risk of rapid shifts of intravascular fluid.
Encourage the victim to swallow the adsorbent even though spontaneous vom-
iting continues. Antiemetic therapy may help control vomiting in adults or older
children. As an alternative, activated charcoal may be administered through an
orogastric tube or diluted with water and administered slowly through a nasogastric
tube. Repeated administration of charcoal or other absorbent every 2-4 hours may
be beneficial in both children and adults, but use of a cathartic such as sorbitol
should be avoided after the first dose. Repeated doses of activated charcoal should
not be administered if the gut is atonic.The use of charcoal without airway protec-
tion is contraindicated in the neurologically impaired patient.
Note on Specific Pesticides: The use of charcoal without airway pro-
tection should be used with caution in poisons such as organophosphates, car-
bamates, and organochlorines if they are prepared in a hydrocarbon solution.
Position Statement: Single-dose activated charcoal should not be used
routinely in the management of poisoned patients. Charcoal appears to be most
effective within 60 minutes of ingestion and may be considered for use for this
time period. Although it may be considered 60 minutes after ingestion, there is
insufficient evidence to support or deny its use for this time period. Despite
improved binding of poisons within 60 minutes, only one study exists9 to suggest
that there is improved clinical outcome. Activated charcoal is contraindicated in
an unprotected airway, a GI tract not anatomically intact, and when charcoal
therapy may increase the risk of aspiration of a hydrocarbon-based pesticide.6
4. Syrup of Ipecac
Ipecac has been used as an emetic since the 1950s. In a pediatric study,
administration of ipecac resulted in vomiting within 30 minutes in 88% of
children.10 However, in light of the recent review of the clinical effectiveness of
ipecac, it is no longer recommended for routine use in most poisonings.
Most clinical trials involve the use of pill form ingestants such as aspirin,2'11
acetaminophen,12 ampicillin,1 and multiple types of tablets.13 No clinical trials
have been done with pesticides. In 1996, more than 2 million human exposures
to a poisonous substances were reported to American poison centers. Ipecac
was recommended for decontamination in only 1.8% of all exposures.14
GENERAL PRINCIPLES 13
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Dosage of Syrup of Ipecac:
Adolescents and adults: 15-30 mL followed immediately with 240 mL
of water.
Children 1-12 years: 15 mL preceded or followed by 120 to 240
mL of water.
Infants 6 months to 12 months: 5-10 mL preceded or followed by 120
to 240 mL of water.
Dose may be repeated in all age groups if emesis does not occur within
20-30 minutes.
Position Statement: Ipecac syrup should not be administered routinely
in poisoned patients. If ipecac is used, it should be administered within 60
minutes of the ingestion. Even then, clinical studies have demonstrated no ben-
efit from its use. It should be considered only in an alert conscious patient who
has ingested a potentially toxic ingestion. Contraindications to its use include
the following: patients with diminished airway protective reflexes, the ingestion
of hydrocarbons with a high aspiration potential, the ingestion of a corrosive
substance, or the ingestion of a substance in which advanced life support may
be necessary within the next 60 minutes.15
5. Seizures
Lorazepam is increasingly being recognized as the drug of choice for status
epilepticus, although there are few reports of its use with certain pesticides.
One must be prepared to assist ventilation with lorazepam and any other medi-
cation used to control seizures. See dosage table on next page.
For organochlorine compounds, use of lorazepam has not been reported
in the literature. Diazepam is often used for this, and is still used in other pesti-
cide poisonings.
Dosage of Diazepam:
Adults: 5-10 mg IV and repeat every 5-10 minutes to maximum of
30 mg.
Children: 0.2-0.5 mg/kg IV every 5 minutes to maximum of 10 mg
in children over 5 years and 5 mg in children under 5 years.
14
GENERAL PRINCIPLES
-------
Dosage of Lorazepam:
Adults:2-4 mg/dose given IV over 2-5 minutes. Repeat if necessary
to a maximum of 8 mg in a 12 hour period.
Adolescents: Same as adult dose, except maximum dose is 4 mg.
Children under 12years: 0.05-0.10 mg/kg IV over 2-5 minutes. Re-
peat if necessary .05 mg/kg 10-15 minutes after first dose, with a
maximum dose of 4 mg.
Caution: Be prepared to assist pulmonary ventilation mechanically if
respiration is depressed, to intubate the trachea if laryngospasm occurs,
and to counteract hypotensive reactions.
Phenobarbital is an additional treatment option for seizure control. Dos-
age for infants, children, and adults is 15-20 mg/kg as an IV loading
dose. An additional 5 mg/kg IV may be given every 15-30 minutes to a
maximum of 30 mg/kg. The drug should be pushed no faster than 1 mg/
kg/minute.
For seizure management, most patients respond well to usual management
consisting of benzodiazepines, or phenytoin and phenobarbital.
References
1. Tenenbein M, Cohen S, and Sitar DS. Efficacy of ipecac-induced emesis, orogastric lavage,
and activated charcoal for acute drug overdose. Ann EmergMed 1987;16:838- 41.
2. Danel V, Henry IA, and Glucksman E. Activated charcoal, emesis, and gastric lavage in aspi-
rin overdose. Br Med J 1988;296:1507.
3. Saetta IP, March S, Gaunt ME, et al. Gastric emptying procedures in the self-poisoned pa-
tient: Are we forcing gastric content beyond the pylorus? ]R Soc Med 1991;84:274-6.
4 American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical
Toxicologists. Position statement: Gastric lavage. JToxicol Clin Toxicol 1997;35:711-9.
5. American Academy of Clinical Toxicology, European Association of Poisons Centres and
Clinical Toxicologists. Position statement: Cathartics. JToxicol Clin Toxicol 1997;35:743-52.
6. American Academy of Clinical Toxicology, European Association of Poisons Centres and
ClinicalToxicologists. Position statement: Single-dose activated charcoal. JToxicol Clin Toxicol
1997:35:721-41.
7. Gaudreault P, Friedman PA, and Lovejoy FH Ir. Efficacy of activated charcoal and magne-
sium citrate in the treatment of oral paraquat intoxication. Ann Emerg Med 1985;14:123-5.
8. Terada H, MiyoshiT, Imaki M, et al. Studies on in vitro paraquat and diquat removal by
activated carbon. JExp Med 1994;41:31-40.
9. Merigian KS,Woodward M, Hedges IR, et al. Prospective evaluation of gastric emptying in
the self-poisoned patient. Am J Emerg Med 1990;8:479-83.
GENERAL PRINCIPLES 15
-------
10. Robertson W Syrup of ipecac: A slow or fast emetic? AJDC 1962;103:136-9.
11. Curtis RA, Barone J, and Giacona N. Efficacy of ipecac and activated charcoal/cathartic.
Arch Intern Med 1984; 144:48-52.
12. McNamara RM, Aaron CK, Gemborys M, et al. Efficacy of charcoal cathartic versus ipecac in
reducing serum acetaminophen in a simulated overdose. Ann Emerg Med 1989;18:934-8.
13. Neuvonen PJ.Vartiainen M, and Tokola O. Comparison of activated charcoal and ipecac
syrup in prevention of drug absorption. Eur J Clin Pharmacol 1983;24:557-62.
14. Litovitz RL, Smilkstein M, Felberg L, et al. 1996 Annual Report of the American
Association of Poison Control CentersToxic Exposure Surveillance System. Am J Emerg Med
1997:15:447-500.
15. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical
Toxicologists. Position statement: Ipecac syrup. JToxicol ClinToxicol 1997;35:699-709.
16 GENERAL PRINCIPLES
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CHAPTER 3
Environmental and
Occupational History
Pesticide poisonings may go unrecognized because of the failure to take a proper
exposure history. This chapter is intended to remedy this often overlooked area
by providing basic tools for taking a complete exposure history. In some situ-
ations where exposures are complex or multiple and/or symptoms atypical, it is
important to consider consultation with clinical toxicologists or specialists in
environmental and occupational medicine. Local Poison Control Centers should
also be considered when there are questions about diagnosis and treatment.
Although this manual deals primarily with pesticide-related diseases and
injury, the approach to identifying exposures is similar regardless of the specific
hazard involved. It is important to ascertain whether other non-pesticide ex-
posures are involved because of potential interactions between these hazards
and the pesticide of interest (e.g., pesticide intoxication and heat stress in agri-
cultural field workers) .Thus, the following section on pesticide exposures should
be seen in the context of an overall exposure assessment.
Most pesticide-related diseases have clinical presentations that are similar
to common medical conditions and display nonspecific symptoms and physical
signs. Knowledge of a patient's exposure to occupational and environmental
factors is important for diagnostic, therapeutic, rehabilitative and public health
purposes.Thus, it is essential to obtain an adequate history of any environmen-
tal or occupational exposure which could cause disease or exacerbate an exist-
ing medical condition.
In addition to the appropriate patient history-taking, one must also con-
sider any other persons that may be similarly exposed in the home, work or
community environment. Each environmental or occupational disease identi-
fied should be considered a potential sentinel health event which may require
follow-up activities to identify the exposure source and any additional cases. By
identifying and eliminating the exposure source, one can prevent continued
exposure to the initial patient and any other individuals involved.
Patients with these types of diseases may be seen by health care providers
that are not familiar with these conditions. If an appropriate history is obtained
and there appears to be a suspect environmental or occupational exposure, the
health care provider can obtain consultation with specialists (e.g., industrial
hygienists, toxicologists, medical specialists, etc.) in the field of environmental
and occupational health. For the more severe sentinel health events and those
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 17
-------
that involve numerous exposed individuals, additional assistance can be ob-
tained by contacting the state health department, state regulatory agency (e.g.,
the agriculture department in the case of pesticide illness and injury), or other
related organizations (see list at end of chapter). Furthermore, some states re-
quire reporting of certain environmental and occupational conditions (e.g.,
pesticide case reporting in Arizona, California, Florida, Oregon, Texas, and
Washington).
This chapter reviews the types of questions to be asked in taking an occupa-
tional and environmental history (for both adult and pediatric patients), discusses
legal, ethical, and public health considerations, and lists information resources.
Taking an Exposure History
Given the time constraints of most health care providers, a few screening
questions are likely to be preferable to a lengthy questionnaire in identifying
occupational or environmental hazards. The screening questions below could
be incorporated into an existing general health questionnaire or routine
patient interview.
SCREENING QUESTIONS FOR OCCUPATIONAL
AND ENVIRONMENTAL EXPOSURES*
For an adult patient:
After establishing the chief complaint and history of the presenting illness:
What kind of work do you do?
(if unemployed) Do you think your health problems are related to your home
or other location?
(if employed) Do you think your health problems are related to your work? Are
your symptoms better or worse when you are at home or at work?
Are you now or have you previously been exposed to pesticides, solvents, or
other chemicals, dusts, fumes, radiation, or loud noise?
For a pediatric patient (questions asked of parent or guardian):
Do you think the patient's health problems are related to the home, daycare,
school, or other location?
Has there been any exposure to pesticides, solvents or other chemicals, dusts,
fumes, radiation, or loud noise?
What kind of work do the parents or other household members engage in?
If the clinical presentation or initial medical history suggests a potential occu-
pational or environmental exposure, a detailed exposure interview is needed.
An extensive exposure history provides a more complete picture of pertinent
exposure factors and can take up to an hour. The detailed interview includes
questions on occupational exposure, environmental exposure, symptoms and
medical conditions, and non-occupational exposure potentially related to ill-
ness or injury. Although the focus is on pesticide exposures and related health
ENVIRONMENTAL AND
18 OCCUPATIONAL HISTORY
-------
effects, concurrent non-pesticide exposures need to be considered in the over-
all patient health assessment. Questions typical of a detailed interview are listed
on the next several pages, preceded by special concerns in addressing exposures
of children and agricultural workers. For further details on taking a history for
all types of occupational and environmental hazards, consult the ATSDR mono-
graph entitled "Taking an Exposure History"1 or a general occupational and
environmental medicine reference text.2
Special Patient Populations
Children
In comparison to adults, children may be at greater risk from pesticide
exposures due to growth and developmental factors. Consideration of fetal,
infant, toddler or child characteristics is helpful in an exposure evaluation: physical
location, breathing zones, oxygen consumption, food consumption, types of
foods consumed and normal behavioral development.3 Furthermore, transpla-
cental absorption and breast milk may pose additional routes of exposure. Al-
though environmental (and, at times, occupational) exposure to pesticides is
the focus of this chapter, the most significant hazard for children is uninten-
tional ingestion.4 Thus, it is very important to ask about pesticides used and
stored in the home, day care facility, school, and play areas.
Agricultural Workers
Data from California's mandatory pesticide poisoning reporting system would
imply an annual national estimate of 10,000-20,000 cases of farmworker poison-
ing.5 However, it is believed that these figures still represent serious underreporting
due to the lack of medical access for many farmworkers and misdiagnosis by
some clinicians. For these high-risk patients, the exposure history should include
specific questions about the agricultural work being done. For example:
Are pesticides being used at home or work?
Were the fields wet when you were picking?
Was any spraying going on while you were working in the fields?
Do you get sick during or after working in the fields?
The use of pesticides in the residence and taking home agricultural pesticides or
contaminated work clothes that are not properly separated from other clothes
may pose hazards for other household members as well.
Obtaining Additional Pesticide Information
In addition to the patient history, it is often helpful to obtain further infor-
mation on suspect pesticide products.Two documents are useful starting points
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 19
-------
DETAILED INTERVIEW FOR OCCUPATIONAL
AND ENVIRONMENTAL EXPOSURES
(Questions marked in bold type are especially important for a pesticide exposure history)
(1) Adult Patient
OCCUPATIONAL EXPOSURE
What is your occupation? (If unemployed, go to next section)
How long have you been doing this job?
Describe your work and what hazards you are exposed to (e.g., pesticides, solvents or other
chemicals, dust, fumes, metals, fibers, radiation, biologic agents, noise, heat, cold, vibration)
Under what circumstances do you use protective equipment? (e.g., work clothes, safety glasses,
respirator, gloves, and hearing protection)
Do you smoke or eat at the worksite?
List previous jobs in chronological order, include full and part-time, temporary, second jobs,
summer jobs, and military experience. (Because this question can take a long time to answer, one
option is to ask the patient to fill out a form with this question on it prior to the formal history taking by
the clinician. Another option is to take a shorter history by asking the patient to list only the prior jobs
that involved the agents of interest. For example, one could ask for all current and past jobs involving
pesticide exposure.)
ENVIRONMENTAL EXPOSURE HISTORY
Are pesticides (e.g., bug or weed killers, flea and tick sprays, collars, powders, or shampoos)
used in your home or garden or on your pet?
Do you or any household member have a hobby with exposure to any hazardous materials (e.g.,
pesticides, paints, ceramics, solvents, metals, glues)?
If pesticides are used:
Is a licensed pesticide applicator involved?
Are children allowed to play in areas recently treated with pesticides?
Where are the pesticides stored?
Is food handled properly (e.g., washing of raw fruits and vegetables)?
Did you ever live near a facility which could have contaminated the surrounding area (e.g., mine,
plant, smelter, dump site)?
Have you ever changed your residence because of a health problem?
Does your drinking water come from a private well, city water supply, and/or grocery store?
Do you work on your car?
Which of the following do you have in your home: air conditioner/purifier, central heating (gas or oil), gas stove,
electric stove, fireplace, wood stove, or humidifier?
Have you recently acquired new furniture or carpet, or remodeled your home?
Have you weatherized your home recently?
Approximately what year was your home built?
SYMPTOMS AND MEDICAL CONDITIONS
(If employed)
Does the timing of your symptoms have any relationship to your work hours?
Has anyone else at work suffered the same or similar problems?
Does the timing of yoursymptoms have any relationship to environmental activities listed above?
Has any other household member or nearby neighbor suffered similar health problems?
ENVIRONMENTAL AND
20 OCCUPATIONAL HISTORY
-------
NON-OCCUPATIONAL EXPOSURES POTENTIALLY RELATED TO ILLNESS OR INJURY
Do you use tobacco? If yes, in what forms (cigarettes, pipe, cigar, chewing tobacco)? About how many
do you smoke or how much tobacco do you use per day? At what age did you start using tobacco? Are
there other tobacco smokers in the home?
Do you drink alcohol? How much per day or week? At what age did you start?
What medications or drugs are you taking? (Include prescription and non-prescription uses)
Has anyone in the family worked with hazardous materials that they might have brought home
(e.g., pesticides, asbestos, lead)? (If yes, inquire about household members potentially exposed.)
(2) PedJatrJC Patient (questions asked of parent or guardian)
OCCUPATIONAL EXPOSURE
What is your occupation and that of other household members? (If no employed individuals, goto
next section)
Describe your work and what hazards you are exposed to (e.g., pesticides, solvents or other
chemicals, dust, fumes, metals, fibers, radiation, biologic agents, noise, heat, cold, vibration)
ENVIRONMENTAL EXPOSURE HISTORY
Are pesticides (e.g., bug or weed killers, flea and tick sprays, collars, powders, or shampoos)
used in your home or garden or on your pet?
Do you or any household member have a hobby with exposure to any hazardous materials (e.g.,
pesticides, paints, ceramics, solvents, metals, glues)?
If pesticides are used:
Is a licensed pesticide applicator involved?
Are children allowed to play in areas recently treated with pesticides?
Where are the pesticides stored?
Is food handled properly (e.g., washing of raw fruits and vegetables)?
Has the patient ever lived near a facility which could have contaminated the surrounding area
(e.g., mine, plant, smelter, dump site)?
Has the patient ever changed residence because of a health problem?
Does the patient's drinking water come from a private well, city water supply, and/or grocery
store?
Which of the following are in the patient's home: air conditioner/purifier, central heating (gas or oil), gas stove,
electric stove, fireplace, wood stove, or humidifier?
Is there recently acquired new furniture or carpet, or recent home remodeling in the patient's home?
Has the home been weatherized recently?
Approximately what year was the home built?
SYMPTOMS AND MEDICAL CONDITIONS
Does the timing of symptoms have any relationship to environmental activities listed above?
Has any other household member or nearby neighbor suffered similar health problems?
NON-OCCUPATIONAL EXPOSURES POTENTIALLY RELATED TO ILLNESS OR INJURY
Are there tobacco smokers in the home? If yes, in what forms (cigarettes, pipe, cigar, chewing tobacco)?
What medications or drugs is the patient taking? (Include prescription and non-prescription uses)
Has anyone in the family worked with hazardous materials that they might have brought home
(e.g., pesticides, asbestos, lead)? (If yes, inquire about household members potentially exposed.)
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY
21
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in the identification and evaluation of the pesticide exposure: the material safety
data sheet (MSDS) and the pesticide label.
Material Safety Data Sheet (MSDS). Under OSHA's Hazard
Communications Standard (29 CFR 1910.1200), all chemical manu-
facturers are required to provide an MSDS for each hazardous chemi-
cal they produce or import. Employers are required to keep copies
of MSDSs and make them available to the workers. The following
items are contained in an MSDS:
- Material identification
- Ingredients and occupational exposure limits
- Physical data
- Fire and explosion data
- Reactivity data
- Health hazard data
- Spill, leak, and disposal procedures
- Special protection data
- Special precautions and comments.
These documents tend to have very limited information on health
effects and some of the active ingredients may be omitted due to
trade secret considerations. One cannot rely solely on an MSDS in
making medical determinations.
Pesticide label. EPA requires that all pesticide products bear labels
that provide certain information.This information can help in evalu-
ating pesticide health effects and necessary precautions. The items
covered include the following:
- Product name
- Manufacturer
- EPA registration number
- Active ingredients
- Precautionary statements:
i. Human hazard signal words "Danger" (most hazardous),
"Warning," and "Caution" (least hazardous)
ii. Child hazard warning
iii. Statement of practical treatment (signs and symptoms of
poisoning, first aid, antidotes, and note to physicians in the
event of a poisoning)
iv. Hazards to humans and domestic animals
v. Environmental hazards
vi. Physical or chemical hazards
ENVIRONMENTAL AND
22 OCCUPATIONAL HISTORY
-------
- Directions for use
- Name and address of manufacturer
- Net contents
- EPA registration number
- EPA establishment number
- Worker Protection Standard (WPS) designation, including re-
stricted entry interval and personal protection equipment required
(see WPS description on page 25).
The EPA registration number is useful when contacting EPA for infor-
mation or when calling the National Pesticide Telecommunications
Network hotline (see page 29). Pesticide labels may differ from one
state to another based on area-specific considerations. Also, different
formulations of the same active ingredients may result in different label
information.The pesticide label lists information only for active ingre-
dients (not for inert components) and rarely contains information on
chronic health effects (e.g., cancer and neurologic, reproductive, and
respiratory diseases) .6 Although further pesticide information is often
needed, these documents should be considered as the first step in iden-
tifying and understanding the health effects of a given pesticide.
For the agricultural worker patient, the health care provider has
two legal bases the EPA Worker Protection Standard and USDA
regulations under the 1990 Farm Bill for obtaining from the
employer the pesticide product name to which the patient was ex-
posed.When requesting this information, the clinician should keep
the patient's name confidential whenever possible.
Assessing the Relationship of
Work or Environment to Disease
Because pesticides and other chemical and physical hazards are often asso-
ciated with nonspecific medical complaints, it is very important to link the
review of systems with the timing of suspected exposure to the hazardous agent.
The Index of Signs and Symptoms in Section V provides a quick reference to
symptoms and medical conditions associated with specific pesticides. Further
details on the toxicology, confirmatory tests, and treatment of illnesses related
to pesticides are provided in each chapter of this manual. A general understand-
ing of pesticide classes and some of the more common agents is helpful in
making a pesticide related disease diagnoses.
In evaluating the association of a given pesticide exposure in the workplace
or environment and a clinical condition, key factors to consider are:
Symptoms and physical signs appropriate for the pesticide being
considered
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 23
-------
Co-workers or others in the environment who are ill
Timing of the problems
Confirmation of physical exposure to the pesticide
Environmental monitoring data
Biomonitoring results
Biological plausibility of the resulting health effect
Ruling out non-pesticide exposures or pre-existing illnesses.
A concurrent non-pesticide exposure can either have no health effect, ex-
acerbate an existing pesticide health effect, or solely cause the health effect in a
patient. In the more complicated exposure scenarios, assistance should be sought
from specialists in occupational and environmental health (see Information Re-
sources on page 27).
Legal, Ethical, and Public Health Considerations
Following are some considerations related to government regulation of
pesticides, ethical factors, and public health concerns that health care providers
should be aware of in assessing a possible pesticide exposure.
Reporting Requirements
When evaluating a patient with a pesticide-related medical condition, it
is important to understand the state-specific reporting requirements for the
workers' compensation system (if there has been an occupational exposure)
or surveillance system. Reporting a workers' compensation case can have
significant implications for the worker being evaluated. If the clinician is not
familiar with this system or is uncomfortable evaluating work-related health
events, it is important to seek an occupational medicine consultation or make
an appropriate referral.
At least six states have surveillance systems within their state health depart-
ments that cover both occupational and environmental pesticide poisonings: Cali-
fornia, Florida, New York, Oregon, Texas, and Washington. These surveillance
systems collect case reports on pesticide-related illness and injury from clinicians
and other sources; conduct selected interviews, field investigations, and research
projects; and function as a resource for pesticide information within their state. In
some states, as noted earlier, pesticide case reporting is legally mandated.
Regulatory Agencies
Since its formation in 1970, EPA has been the lead agency for the regula-
tion of pesticide use under the Federal Insecticide, Fungicide and Rodenticide
Act. EPA's mandates include the registration of all pesticides used in the United
States, setting restricted entry intervals, specification and approval of label in-
ENVIRONMENTALAND
24 OCCUPATIONAL HISTORY
-------
formation, and setting acceptable food and water tolerance levels. In addition,
EPA works in partnership with state and tribal agencies to implement two field
programs the certification and training program for pesticide applicators
and the agricultural worker protection standard to protect workers and
handlers from pesticide exposures. EPA sets national standards for certification
of over 1 million private and commercial pesticide applicators.
The authority to enforce EPA regulations is delegated to the states. For
example, calls concerning non-compliance with the worker protection stan-
dard can typically be made to the state agricultural department. In five states,
the department of the environment or other state agency has enforcement
authority. Anonymous calls can be made if workers anticipate possible retalia-
tory action by management. It should be noted that not all state departments of
agriculture have similar regulations. In California, for instance, employers are
required to obtain medical supervision and biological monitoring of agricul-
tural workers who apply pesticides containing cholinesterase-inhibiting com-
pounds. This requirement is not found in the federal regulations.
Outside the agricultural setting, the Occupational Safety and Health
Administration (OSHA) has jurisdiction over workplace exposures. All workers
involved in pesticide manufacturing would be covered by OSHA. OSHA sets
permissible exposure levels for selected pesticides. Approximately half the states
are covered by the federal OSHA; the rest have their own state-plan OSHA.
Individual state plans may choose to be more protective in setting their workplace
standards. Anonymous calls can also be made to either state-plan or federal
OSHA agencies.
For pesticide contamination in water, EPA sets enforceable maximum
containment levels. In food and drug-related outbreaks, EPA works jointly with
the Food and Drug Administration (FDA) and the U.S. Department of
Agriculture (USDA) to monitor and regulate pesticide residues and their
metabolites. Tolerance limits are established for many pesticides and their
metabolites in raw agricultural commodities.
In evaluating a patient with pesticide exposure, the clinician may need
to report a pesticide intoxication to the appropriate health and/or regulatory
agency.
Worker Protection Standard
EPA s Worker Protection Standard (WPS) became fully effective in 1995.
The intent of the regulation is to eliminate or reduce pesticide exposure, mitigate
exposures that occur, and inform agricultural workers about the hazards of
pesticides. The WPS applies to two types of workers in the farm, greenhouse,
nursery, and forest industries: (1) agricultural pesticide handlers (mixer, loader,
applicator, equipment cleaner or repair person, and flagger), and (2) field workers
(cultivator or harvester).
The WPS includes requirements that agricultural employers notify workers
about pesticide treatments in advance, offer basic pesticide safety training, provide
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 25
-------
personal protective equipment for direct work with pesticides, and observe
restricted entry interval (REI) times. (The REI is a required waiting period before
workers can return to areas treated with pesticides.) Of special interest to health
care providers, the WPS also requires agricultural employers to:
Post an emergency medical facility address and phone number in a
central location.
Arrange immediate transport from the agricultural establishment to
a medical facility for a pesticide-affected worker.
Supply the affected worker and medical personnel with product name,
EPA registration number, active ingredient, label medical information,
a description of how the pesticide was used, and exposure information.
Ethical Considerations
Attempts to investigate an occupational pesticide exposure may call for ob-
taining further information from the worksite manager or owner. Any contact
with the worksite should be taken in consultation with the patient because of the
potential for retaliatory actions (such as loss of job or pay cuts). Ideally, a request
for a workplace visit or more information about pesticide exposure at the work-
place will occur with the patients agreement. In situations where the health
hazard is substantial and many individuals might be affected, a call to a state
pesticide surveillance system (if available), agricultural health and safely center (if
nearby), can provide the National Institute for Occupational Safety and Health
(NIOSH) or state agricultural agency the assistance needed for a disease out-
break investigation.
Similarly, the discovery of pesticide contamination in a residence, school,
daycare setting, food product, or other environmental site or product can have
public health, financial, and legal consequences for the patient and other indi-
viduals (e.g., building owner, school district, food producer). It is prudent to
discuss these situations and follow-up options with the patient as well as a knowl-
edgeable environmental health specialist and appropriate state or local agencies.
Public Health Considerations
Health care providers are often the first to identify a sentinel health event that
upon further investigation develops into a full-blown disease outbreak. A disease
outbreak is defined as a statistically elevated rate of disease among a well-defined
population as compared to a standard population. For example, complaints about
infertility problems among workers at a dibromochloropropane (DBCP) manufac-
turing plant in California led to diagnoses of azoospermia (lack of sperm) or oli-
gospermia (decreased sperm count) among a handful of otherwise healthy young
men working at the plant.7 An eventual disease outbreak investigation resulted in the
first published report of a male reproductive toxicant in the workplace. At the time,
DBCP was used as a nematocide; it has since been banned in the United States.
Disease outbreak investigations are conducted for all kinds of exposures
ENVIRONMENTAL AND
26 OCCUPATIONAL HISTORY
-------
and health events, not only those in the occupational and environmental area.
Usually, assistance from government or university experts is needed in the in-
vestigation, which may require access to information, expertise, and resources
beyond that available to the average clinician. The steps involved in such an
investigation and the types of information typically gathered in the preliminary
clinical stages are outlined below.The clinician must be aware that an outbreak
investigation may be needed when a severe and widespread exposure and dis-
ease scenario exists. For more information on disease outbreak investigations,
consult the literature.8'9
STEPS IN INVESTIGATING A DISEASE OUTBREAK
Confirm diagnosis of initial case reports (the "index" cases)
Identify other unrecognized cases
Establish a case definition
Characterize cases by person, place, and time characteristics (e.g., age, race, ethnicity, gen-
der, location within a company or a neighborhood, timeline of exposure and health events)
Create plot of case incidence by time (an epidemic curve)
Determine if a dose-response relationship exists (i.e., more severe clinical case presen-
tation for individuals with higher exposures)
Derive an attack rate and determine if statistical significance is achieved (divide num-
ber of incident cases by number of exposed individuals and multiply by 100 to obtain
attack rate percentage)
Information Resources
Government Agencies:
EPA Office of Pesticide Programs
Overall pesticide regulation with special programs on agricultural workers and
pesticide applicators. Specific programs include the promotion of the reduc-
tion of pesticide use, establishment of tolerance levels for food, and investiga-
tion of pesticide releases and exposure events.
Address: EPA - Office of Pesticide Programs
401 M Street SW (7501C)
Washington, DC 20460
Telephone: 703-305-7090
Web site: www.epa.gov/pesticides
EPA - Certification and Worker Protection Branch
Within the Office of Pesticide Programs, the Certification and Worker Protec-
tion Branch addresses worker-related pesticide issues and pesticide applicator
certification activities. Special emphasis is placed on the adequate training of
farm workers, pesticide applicators, and health care providers. Various training
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 27
-------
materials in several languages are available.
Address: EPA - OPP
401 M Street SW (7506C)
Washington, DC 20460
Telephone: 703-305-7666
Web site: www.epa.gov/pesticides/safety
Occupational Safety and Health Administration (OSHA)
More than 100 million workers and 6.5 million employers are covered under
the Occupational Safety and Health Act, which covers workers in pesticide
manufacturing as well as other industries. OSHA and its state partners have
approximately 2100 inspectors, plus investigators, standards writers, educators,
physicians, and other staff in over 200 offices across the country. OSHA sets
protective workplace standards, enforces the standards, and offers employers
and employees technical assistance and consultation programs. Note that some
states have their own OSHA plan.
Address: OSHA - US DDL
Room N3647
Constitution Ave NW
Washington, DC 20210
Telephone: 202-219-8021
Web site: www.osha.gov
Food and Drug Administration (FDA)
Drug and food pesticide issues.
Address: FDA
National Center for Toxicological Research
5600 Fishers Lane
Rockville, MD 20857
Telephone: 301-443-3170
Internet: gopher.nctr.fda.gov
USDA Extension Service
USDA's Extension Service works with its university partners, the state land-
grant system, to provide farmers and ranchers information to reduce and
prevent agricultural-related work incidents. The Pesticide Applicator Training
program trains applicators in the safe use of pesticides and coordinates
pesticide-related safety training programs.
Address: USDA
14th & Independence SW
Washington, DC 20250
Telephone: 202-720-2791
Web site: www.reeusda.gov
ENVIRONMENTAL AND
28 OCCUPATIONAL HISTORY
-------
National Center for Environmental Health (NCEH),
Centers for Disease Control (CDC)
NCEH provides expertise in environmental pesticide case surveillance and dis-
ease outbreak investigations.
Address: NCEH, CDC
Mailstop F29
4770 Buford Highway NE
Atlanta, GA 30341
Tel: 770-488-7030
Web site: www.cdc.gov/nceh/ncehhome.htm
National Institute for Occupational Safety and Health (NIOSH),
Centers for Disease Control (CDC)
NIOSH is the federal agency responsible for conducting research on occupational
disease and injury. NIOSH may investigate potentially hazardous working condi-
tions upon request, makes recommendations on preventing workplace disease and
injury, and provides training to occupational safely and health professionals.
Address: NIOSH
Humphrey Building, Room 715H
200 Independence Ave SW
Washington, DC 20201
Hotline: 1-800-356-4674
Web site: www.cdc.gov/niosh/homepage.html
NIOSH Agricultural Health and Safety Centers
NIOSH has funded eight Agricultural Health and Safety Centers throughout
the country which involve clinicians and other health specialists in the area of
pesticide-related illness and injury.The NIOSH-supported centers are:
University of California Agricultural
Health and Safety Center
Old Davis Road
University of California
Davis, CA 95616
Tel: 916-752-4050
High Plains Intermountain Center
for Agricultural Health and Safety
Colorado State University
Fort Collins, CO 80523
Tel: 970-491-6152
Great Plains Center for Agricultural
Health
University of Iowa
Iowa City, IA 52242
Tel: 319-335-4415
Southeast Center for Agricultural
Health and Injury Prevention
University of Kentucky
Department of Preventive Medicine
Lexington, KY 40536
Tel: 606-323-6836
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 29
-------
Northeast Center for Agricultural
and Occupational Health
One Atwell Road
Cooperstown, NY 13326
Tel: 607-547-6023
Southwest Center for Agricultural
Health, Injury and Education
University of Texas
Health Center at Tyler
PO Box 2003
Tyler,TX 75710
Tel: 903-877-5896
Pacific Northwest Agricultural Safety
and Health Center
University of Washington
Department of Environmental Health
Seattle, WA 98195
Tel: 206-543-0916
Midwest Center for Agricultural
Research, Education and Disease and
Injury Prevention
National Farm Medicine Center
Marshfield,WI 54449-5790
Tel: 715-389-3415
Non-Governmental Organizations:
National Pesticide Telecommunications Network
The National Pesticide Telecommunications Network (NPTN) is based at
Oregon State University and is cooperatively sponsored by the University and
EPA. NPTN serves as a source of objective, science-based pesticide informa-
tion on a wide range of pesticide-related topics, such as recognition and man-
agement of pesticide poisonings, safety information, health and environmental
effects, referrals for investigation of pesticide incidents and emergency treat-
ment for both humans and animals, and cleanup and disposal procedures.
A toll-free telephone service provides pesticide information to callers in
the continental United States, Puerto Rico, and the Virgin Islands. Additionally,
pesticide questions and comments can be sent to an e-mail address. The Web
site has links to other sites and databases for further information.
NPTN hotline: 1-800-858-7378
Hours of operation: 9:30 am - 7:30 pm E.S.T daily except holidays
Web site: http://ace.orst.edu/info/nptn/
E-mail address: nptn@ace.orst.edu
Farmworker Justice Fund
The Farmworker Justice Fund can provide an appropriate referral to a network of
legal services and nonprofit groups which represent farmworkers for free.
Address:
Telephone:
E-mail address:
Farmworker Justice Fund
1111 19th Street, NW, Suite 1000
Washington, DC 20036
202-776-1757
fjf@nclr.org
ENVIRONMENTAL AND
30 OCCUPATIONAL HISTORY
-------
American Farm Bureau Federation
The AFBF is the nation's largest general farm organization. Information on how
to contact individual state-based farm bureaus is available on their Web site.
Web site: www.fb.com
Association of Occupational and Environmental Clinics (AOEC)
This association is a network of 63 clinics representing more than 250 specialists.
Address: AOEC
1010 Vermont Ave, NW, Suite 513
Washington, DC 20005
Telephone: 202-347-4976
Web site: http://152.3.65.120/oem/aoec.htm
Poison Control Centers
For a list of state and regional poison control centers, or the nearest location,
consult the NPTN Web site (http://ace.orst.edu/info/nptn).
Pesticide Information Databases:
Extension Toxicology Network (EXTOXNET)
http://ace.ace. orst. edu/info/extoxnet
The Extension Service's Toxicology Network, EXTOXNET, provides science-
based information about pesticides to health care providers treating pesticide-
related health concerns. Pesticide toxicological information is developed
cooperatively by the University of California-Davis, Oregon State University,
Michigan State University, Cornell University, and the University of Idaho.
IRIS
www. epa.go v/ngispgm 3/iris
The Integrated Risk Information System - IRIS - is an electronic database, main-
tained by EPA, on human health effects that may result from exposure to various
chemicals in the environment. IRIS is intended for those without extensive training
in toxicology, but with some knowledge of health sciences. It provides hazard iden-
tification and dose-response assessment information. Combined with specific expo-
sure information, the data in IRIS can be used for characterization of the public
health risks of a chemical in a particular situation that can lead to a risk management
decision designed to protect public health. Extensive supporting documentation
available online.
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 31
-------
Agency for Toxic Substances and Disease Registry
http://atsdTl.atsdT.cdc.goV.8080/toxfaq.html
ATSDR (part of the Department of Human Health and Services) publishes
fact sheets and other information on pesticides and other toxic substances.
California Pesticide Databases
http://www. cdpr. ca.gov/docs/database/database.htm
Includes Pesticidal Chemical Ingredients Queries, links to EPA s Officeof Pesticide
Programs chemical dictionary, Product/Label Database Queries (updated nightly),
a current listing of California's Section 18 Emergency Exemptions, and more.
References
1. Frank A and Balk S. ATSDR Case Studies in Environmental Medicine #26, Taking an
Exposure History. Atlanta: Agency forToxic Substances and Disease Registry, Oct. 1992.
2. LaDou J. Approach to the diagnosis of occupational illness. In: LaDou J (ed). Occupational
and Environmental Medicine, 2nd ed. Stamford, CT: Appleton and Lange, 1997.
3. Bearer C. Chapter 10: Pediatric developmental toxicology. In: Brooks SM, Gochfield M.Herzstein
J, et al. Environmental Medicine. St. Louis, MO: Mosby Yearbook, 1995, pp. 115-28.
4. Jackson RJ. Chapter 31: Hazards of pesticides to children. Ibid, pp. 377-82.
5. Blondell JM. Epidemiology of pesticide poisonings in the United States, with special refer-
ence to occupational cases. In: Keifer MC (ed). Human Health Effects of Pesticides, Occu-
pational Medicine: State of the Art Reviews, Philadelphia: Hanley & Belfus, Inc., 1997.
6. Keifer MC (ed). Ibid.
7. Osorio, AM. Chapter 26: Male reproductive toxicology. In: LaDou J (ed), op. cit.
8. Brooks SM, Gochfield M, Herzstein J, et al. Environmental Medicine. St. Louis, MO: Mosby
Yearbook, 1995.
9. Steenland K. Case Studies in Occupational Epidemiology. New York: Oxford University
Press, 1993.
ENVIRONMENTAL AND
32 OCCUPATIONAL HISTORY
-------
Section II
INSECTICIDES
-------
CHAPTER 4
HIGHLIGHTS
Acts through
phosphorylation of the
acetylcholinesterase enzyme
at nerve endings
Absorbed by inhalation,
ingestion, and skin
penetration
Muscarinic, nicotinic & CNS
effects
Signs and Symptoms:
Headache, hypersecretion,
muscle twitching, nausea,
diarrhea
Respiratory depression,
seizures, loss of
consciousness
Miosis is often a helpful
diagnostic sign
Treatment:
Clear airway, improve tissue
oxygenation
Administer atropine sulfate
intravenously
Pralidoxime may be
indicated
Proceed concurrently with
decontamination
Contraindicated:
Morphine, succinylcholine,
theophylline,
phenothiazines, reserpine
Organophosphate Insecticides
Since the removal of organochlorine insecticides from use, organophosphate
insecticides have become the most widely used insecticides available today. More
than forty of them are currently registered for use and all run the risk of acute
and subacute toxicity. Organophosphates are used in agriculture, in the home,
in gardens, and in veterinary practice. All apparently share a common mecha-
nism of cholinesterase inhibition and can cause similar symptoms. Because they
share this mechanism, exposure to the same organophosphate by multiple routes
or to multiple Organophosphates by multiple routes can lead to serious additive
toxicity. It is important to understand, however, that there is a wide range of
toxicity in these agents and wide variation in cutaneous absorption, making
specific identification and management quite important.
Toxicology
Organophosphates poison insects and mammals primarily by phosphory-
lation of the acetylcholinesterase enzyme (AChE) at nerve endings.The result
is a loss of available AChE so that the effector organ becomes overstimulated by
the excess acetylcholine (ACh, the impulse-transmitting substance) in the nerve
ending.The enzyme is critical to normal control of nerve impulse transmission
from nerve fibers to smooth and skeletal muscle cells, glandular cells, and
autonomic ganglia, as well as within the central nervous system (CNS). Some
critical proportion of the tissue enzyme mass must be inactivated by phospho-
rylation before symptoms and signs of poisoning become manifest.
At sufficient dosage, loss of enzyme function allows accumulation of ACh
peripherally at cholinergic neuroeffector junctions (muscarinic effects), skeletal
nerve-muscle junctions, and autonomic ganglia (nicotinic effects), as well as
centrally. At cholinergic nerve junctions with smooth muscle and gland cells,
high ACh concentration causes muscle contraction and secretion, respectively.
At skeletal muscle junctions, excess ACh may be excitatory (cause muscle twitch-
ing), but may also weaken or paralyze the cell by depolarizing the end-plate. In
the CNS, high ACh concentrations cause sensory and behavioral disturbances,
incoordination, depressed motor function, and respiratory depression. Increased
pulmonary secretions coupled with respiratory failure are the usual causes of
death from organophosphate poisoning. Recovery depends ultimately on gen-
eration of new enzyme in all critical tissues.
34
ORGANOPHOSPHATES
-------
ace p hate
Orthene
azinphos- methyl*
Gusathion
Guthion
bensulide
Betasan
Lescosan
bomyl*
Swat
bromophos
Nexion
bromophos-ethyl
Nexagan
cadusafos
Apache
Ebufos
Rugby
carbophenothion*
Trithion
chlorethoxyfos
Fortress
chlorfenvinphos
Apachlor
Birlane
chlormephos*
Dotan
chlorphoxim
Baythion-C
chlorpyrifos
Brodan
Dursban
Lorsban
chlorthiophos*
Celathion
coumaphos*
Asuntol
Co-Ral
crotoxyphos
Ciodrin
Cypona
crufomate
Ruelene
cyanofenphos*
Surecide
cyanophos
Cyanox
cythioate
Cyflee
Proban
DBF
De-Green
E-Z-Off D
demeton*
systox
demeton-S-methyl
Duratox
Metasystoxl
dialifor*
Torak
diazinon
dichlorofenthion
COMMERCIAL
VC-13 Nemacide
dichlorvos
DDVP
Vapona
dicrotophos*
Bidrin
dimefos*
Hanane
Pestox XIV
dimethoate
Cygon
DeFend
dioxathion*
Delnav
disulfoton*
Disyston
ditalimfos
edifenphos
endothion*
EPBP
S-Seven
EPN+
ethion
Ethanox
ethoprop
Mocap
ethyl parathion*
E605
Parathion
thiophos
etrimfos
Ekamet
famphur
Bash
Bo-Ana
Famfos
fenamiphos*
Nemacur
fenitrothion
Accothion
Agrothion
Sumithion
fenophosphon*
Agritox
trichloronate
fensulfothion*
Dasanit
fenthion
Baytex
Entex
Tiguvon
fonofos*
Dyfonate
N-2790
formothion
Anthio
fosthietan*
Nem-A-Tak
heptenophos
Hostaquick
hiometon
Ekatin
PRODUCTS
hosalone
Zolone
IBP
Kitazin
iodofenphos
Nuvanol-N
isazofos
Brace
Miral
Triumph
isofenphos*
Amaze
Oftanol
isoxathion
E-48
Karphos
leptophos
Phosvel
malathion
Cythion
mephosfolan*
Cytrolane
merphos
Easy off-D
Folex
methamidophos*
Monitor
methidathion*
Supracide
Ultracide
methyl parathion*
E601
Penncap-M
methyl trithion
mevinphos*
Duraphos
Phosdrin
mipafox*
Isopestox
Pestox XV
monocrotophos*
Azodrin
naled
Dibrom
oxydemeton- methyl
Metasystox-R
oxydeprofos
Metasystox-S
phencapton
G 28029
phenthoate
dimephenthoate
Phenthoate
phorate*
Rampart
Thimet
phosalone
Azofene
Zolone
phosfolan*
Cylan
Cyolane
phosmet
Imidan
Prolate
phosphamidon*
Dimecron
phostebupirim
Aztec
phoxim
Baythion
pirimiphos-ethyl
Primicid
pirimiphos-methyl
Actellic
profenofos
Curacron
propetamphos
Safrotin
propyl thiopyro-
phosphate*
Aspon
prothoate
Fac
pyrazophos
Afugan
Curamil
pyridaphenthion
Ofunack
quinalphos
Bayrusil
ronnel
Fenchlorphos
Korlan
schradan*
OMPA
sulfotep*
Bladafum
Dithione
Thiotepp
sulprofos
Bolster
Helothion
temephos
Abate
Abathion
terbufos
Contraven
Counter
tetrachlorvinphos
Gardona
Rabon
tetraethyl pyrophos-
phate*
TEPP
triazophos
Hostathion
trichlorfon
Dipterex
Dylox
Neguvon
Proxol
+ Indicates high toxicity. Highly
toxic organophosphates have
listed oral LD50 values (rat) less
than or equal to 50 mg/kg body
weight. Most other organo-
phosphates included in this table
are considered moderately toxic,
with LD50 values in excess of 50
mg/kg and less than 500 mg/kg.
ORGANOPHOSPHATES 35
-------
Organophosphates are efficiently absorbed by inhalation, ingestion, and skin
penetration. There is considerable variation in the relative absorption by these
various routes. For instance, the oral LD5Q of parathion in rats is between 3-8 mg/
kg, which is quite toxic,1-2 and essentially equivalent to dermal absorption with
an LD5Q of 8 mg/kg.2 On the other hand, the toxicity of phosalone is much
lower from the dermal route than the oral route, with rat LD5Qs of 1500 mg/kg
and 120 mg/kg, respectively.2 In general, the highly toxic agents are more likely
to have high-order dermal toxicity than the moderately toxic agents.
Chemical Classes: To some degree, the occurrence of poisoning depends
on the rate at which the pesticide is absorbed. Breakdown occurs chiefly by
hydrolysis in the liver; rates of hydrolysis vary widely from one compound to
another. In the case of certain Organophosphates whose breakdown is relatively
slow, significant temporary storage in body fat may occur. Some Organophos-
phates such as diazinon and methyl parathion have significant lipid solubility,
allowing fat storage with delayed toxicity due to late release.3 Delayed toxicity
may also occur atypically with other Organophosphates, specifically
dichlorofenthion and demeton-methyl.4 Many organothiophosphates readily
undergo conversion from thions (P=S) to oxons (P=O). Conversion occurs in
the environment under the influence of oxygen and light, and in the body,
chiefly by the action of liver microsomes. Oxons are much more toxic than
thions, but oxons break down more readily. Ultimately, both thions and oxons
are hydrolyzed at the ester linkage, yielding alkyl phosphates and leaving groups,
both of which are of relatively low toxicity. They are either excreted or further
transformed in the body before excretion.
The distinction between the different chemical classes becomes important
when the physician interprets tests from reference laboratories.This can be espe-
cially important when the lab analyzes for the parent compound (i.e., chlorpyrifos
in its thiophosphate form) instead of the metabolite form (chlorpyrifos will be
completely metabolized to the oxon after the first pass through the liver).
Within one or two days of initial organophosphate binding to AChE, some
phosphorylated acetylcholinesterase enzyme can be de-phosphorylated (reac-
tivated) by the oxime antidote pralidoxime. As time progresses, the enzyme-
phosphoryl bond is strengthened by loss of one alkyl group from the phosphoryl
adduct, a process called aging. Pralidoxime reactivation is therefore no longer
possible after a couple of days,5 although in some cases, improvement has still
been seen with pralidoxime administration days after exposure.6
OPIDN: Rarely, certain Organophosphates have caused a different kind of
neurotoxicity consisting of damage to the afferent fibers of peripheral and cen-
tral nerves and associated with inhibition of "neuropathy target esterase" (NTE).
This delayed syndrome has been termed organophosphate-induced delayed
neuropathy (OPIDN), and is manifested chiefly by weakness or paralysis and
paresthesia of the extremities.7 OPIDN predominantly affects the legs and may
36 ORGANOPHOSPHATES
-------
persist for weeks to years.These rare occurrences have been found shortly after
an acute and often massive exposure, but in some cases, symptoms have per-
sisted for months to years. Only a few of the many organophosphates used as
pesticides have been implicated as causes of delayed neuropathy in humans.
EPA guidelines require that organophosphate and carbamate compounds which
are candidate pesticides be tested in susceptible animal species for this neuro-
toxic property.
Three epidemiologic studies with an exposed group and a control group
also suggest that a proportion of patients acutely poisoned from any organo-
phosphate can experience some long-term neuropsychiatric sequelae. The
findings show significantly worse performance on a battery of neurobehavioral
tests, including memory, concentration, and mood, and compound-specific
peripheral neuropathy in some cases.These findings are subtle and may some-
times be picked up only on neuropsychologic testing rather than on a neuro-
logic exam.8"10 Follow-ups of case series have occasionally found some
individuals reporting persistent headaches, blurred vision, muscle weakness,
depression, memory and concentration problems, irritability, and/or develop-
ment of intolerance to selected chemical odors.11"15
Intermediate Syndrome: In addition to acute poisoning episodes and
OPIDN, an intermediate syndrome has been described.This syndrome occurs
after resolution of the acute cholinergic crisis, generally 24-96 hours after ex-
posure. It is characterized by acute respiratory paresis and muscular weakness,
primarily in the facial, neck, and proximal limb muscles. In addition, it is often
accompanied by cranial nerve palsies and depressed tendon reflexes. Like OPIDN,
this syndrome lacks muscarinic symptomatology, and appears to result from a
combined pre- and post-synaptic dysfunction of neuromuscular transmission.
Symptoms do not respond well to atropine and oximes; therefore treatment is
mainly supportive.16'17 The most common compounds involved in this syn-
drome are methyl parathion, fenthion, and dimethoate, although one case with
ethyl parathion was also observed.17
Other specific properties of individual organophosphates may render them
more hazardous than basic toxicity data suggest. By-products can develop in long-
stored malathion which strongly inhibit the hepatic enzymes operative in malathion
degradation, thus enhancing its toxicity. Certain organophosphates are exception-
ally prone to storage in fat tissue, prolonging the need for antidote for several days
as stored pesticide is released back into the circulation. Animal studies have demon-
strated potentiation of effect when two or more organophosphates are absorbed
simultaneously; enzymes critical to the degradation of one are inhibited by the
other. Animal studies have also demonstrated a protective effect from phenobar-
bital which induces hepatic degradation of the pesticide.1 Degradation of some
compounds to a trimethyl phosphate can cause restrictive lung disease.18
ORGANOPHOSPHATES 37
-------
Signs and Symptoms of Poisoning
Symptoms of acute organophosphate poisoning develop during or after
exposure, within minutes to hours, depending on the method of contact. Ex-
posure by inhalation results in the fastest appearance of toxic symptoms, fol-
lowed by the gastrointestinal route and finally the dermal route. All signs and
symptoms are cholinergic in nature and affect muscarinic, nicotinic, and central
nervous system receptors.5The critical symptoms in management are the respi-
ratory symptoms. Sufficient muscular fasciculations and weakness are often
observed as to require respiratory support; respiratory arrest can occur sud-
denly. Likewise, bronchorrhea and bronchospasm may often impede efforts at
adequate oxygenation of the patient.
Bronchospasm and bronchorrhea can occur, producing tightness in the
chest, wheezing, productive cough, and pulmonary edema. A life threatening
severity of poisoning is signified by loss of consciousness, incontinence, con-
vulsions, and respiratory depression. The primary cause of death is respiratory
failure, and there usually is a secondary cardiovascular component. The classic
cardiovascular sign is bradycardia which can progress to sinus arrest. However,
this may be superseded by tachycardia and hypertension from nicotinic (sym-
pathetic ganglia) stimulation.19 Toxic myocardiopathy has been a prominent
feature of some severe organophosphate poisonings.
Some of the most commonly reported early symptoms include headache,
nausea, dizziness, and hypersecretion, the latter of which is manifested by sweat-
ing, salivation, lacrimation, and rhinorrhea. Muscle twitching, weakness, tremor,
incoordination, vomiting, abdominal cramps, and diarrhea all signal worsening of
the poisoned state. Miosis is often a helpful diagnostic sign and the patient may
report blurred and/or dark vision. Anxiety and restlessness are prominent, as are a
few reports of choreaform movements. Psychiatric symptoms including depres-
sion, memory loss, and confusion have been reported.Toxic psychosis, manifested
as confusion or bizarre behavior, has been misdiagnosed as alcohol intoxication.
Children will often present with a slightly different clinical picture than adults.
Some of the typical cholinergic signs of bradycardia, muscular fasciculations, lac-
rimation, and sweating were less common. Seizures (22%-25%) and mental status
changes including lethargy and coma (54%-96%) were common.20'21 In com-
parison, only 2-3% of adults present with seizures. Other common presenting
signs in children include flaccid muscle weakness, miosis, and excessive salivation.
In one study, 80% of cases were transferred with the wrong preliminary diagno-
sis.20 In a second study, 88% of the parents initially denied any exposure history.21
See the preceding Toxicology section for information regarding the fea-
tures of the intermediate syndrome and OPIDN.
38 ORGANOPHOSPHATES
-------
Confirmation of Poisoning
If poisoning is probable, treat the patient immediately. Do not wait
for laboratory confirmation.
Blood samples should be drawn to measure plasma pseudocholinesterase
and red blood cell AChE levels. Depressions of plasma pseudocholinesterase
and/or RBC acetylcholinersterase enzyme activities are generally available bio-
chemical indicators of excessive organophosphate absorption. Certain organo-
APPROXIMATE LOWER LIMITS OF NORMAL PLASMA
AND RED CELL CHOLINESTERASE ACTIVITIES IN HUMANS*
Methods Plasma RBC
pH (Michel) 0.45 0.55
pH Stat (Nabb-Whitfield) 2.3 8.0
BMC Reagent Set
(Ellman-Boehringer) 1,875
DupontACA <8
Garry-Routh (Micro)
Technicon 2.0 8.0
Blood
3,000
Male 7.8
Female 5.8
Whole units
ApH per ml per hr
|iM per ml per min
mU per ml per min
Units per ml
HM-SH per 3mL per min
|iM per ml per min
* Because measurement technique varies among laboratories, more accurate estimates of
minimum normal values are usually provided by individual laboratories.
phosphates may selectively inhibit either plasma pseudocholinesterase or RBC
acetylcholinesterase.22 A minimum amount of organophosphate must be ab-
sorbed to depress blood cholinesterase activities, but enzyme activities, espe-
cially plasma pseudocholinesterase, may be lowered by dosages considerably
less than are required to cause symptomatic poisoning.The enzyme depression
is usually apparent within a few minutes or hours of significant absorption of
organophosphate. Depression of the plasma enzyme generally persists several
days to a few weeks.The RBC enzyme activity may not reach its minimum for
several days, and usually remains depressed longer, sometimes 1 -3 months, until
new enzyme replaces that inactivated by organophosphate. The above table
lists approximate lower limits of normal plasma and RBC cholinesterase activi-
ties of human blood, measured by several methods. Lower levels usually in-
dicate excessive absorption of a cholinesterase-inhibiting chemical.
ORGANOPHOSPHATES 39
-------
In certain conditions, the activities of plasma and RBC cholinesterase are
depressed in the absence of chemical inhibition. About 3% of individuals have
a genetically determined low level of plasma pseudocholinesterase. These
persons are particularly vulnerable to the action of the muscle-paralyzing drug
succinylcholine (often administered to surgical patients), but not to organo-
phosphates. Patients with hepatitis, cirrhosis, malnutrition, chronic alcoholism,
and dermatomyositis exhibit low plasma cholinesterase activities. A number of
toxicants, notably cocaine, carbon disulfide, benzalkonium salts, organic mer-
cury compounds, ciguatoxins, and solanines may reduce plasma pseudocho-
linesterase activity. Early pregnancy, birth control pills, and metoclopramide
may also cause some depression. The RBC acetylcholinesterase is less likely
than the plasma enzyme to be affected by factors other than organophosphates.
It is, however, reduced in certain rare conditions that damage the red cell mem-
brane, such as hemolytic anemia.
The alkyl phosphates and phenols to which organophosphates are hydro-
lyzed in the body can often be detected in the urine during pesticide absorp-
tion and up to about 48 hours thereafter.These analyses are sometimes useful in
identifying and quantifying the actual pesticide to which workers have been
exposed. Urinary alkyl phosphate and phenol analyses can demonstrate orga-
nophosphate absorption at lower dosages than those required to depress cho-
linesterase activities and at much lower dosages than those required to produce
symptoms and signs. Their presence may simply be a result of organophos-
phates in the food chain.
Detection of intact organophosphates in the blood is usually not possible
except during or soon after absorption of a substantial amount. In general,
organophosphates do not remain unhydrolyzed in the blood for more than a
few minutes or hours, unless the quantity absorbed is large or the hydrolyzing
liver enzymes are inhibited.
Treatment
Caution: Persons attending the victim should avoid direct contact with heavily contami-
nated clothing and vomitus. Wear rubber gloves while washing pesticide from skin and
hair. Vinyl gloves provide no protection.
1. Airway protection. Ensure that a clear airway exists. Intubate the patient
and aspirate the secretions with a large-bore suction device if necessary.
Administer oxygen by mechanically assisted pulmonary ventilation if respiration
is depressed. Improve tissue oxygenation as much as possible before
administering atropine, so as to minimize the risk of ventricular
fibrillation. In severe poisonings, it may be necessary to support pulmonary
ventilation mechanically for several days.
40 ORGANOPHOSPHATES
-------
2. Atropine sulfate. Administer atropine sulfate intravenously, or intramuscu-
larly if intravenous injection is not possible. Remember that atropine can be
administered through an endotracheal tube if initial IV access is difficult to
obtain. Depending on the severity of poisoning, doses of atropine ranging from
very low to as high as 300 mg per day may be required,23 or even continuous
infusion.24-25 (See dosage on next page.)
The objective of atropine antidotal therapy is to antagonize the effects of
excessive concentrations of acetylcholine at end-organs having muscarinic re-
ceptors. Atropine does not reactivate the cholinesterase enzyme or accelerate
disposition of organophosphate. Recrudescence of poisoning may occur if tis-
sue concentrations of organophosphate remain high when the effect of atro-
pine wears off. Atropine is effective against muscarinic manifestations, but it is
ineffective against nicotinic actions, specifically muscle weakness and twitch-
ing, and respiratory depression.
Despite these limitations, atropine is often a life-saving agent in organophos-
phate poisonings. Favorable response to a test dose of atropine (1 mg in adults,
0.01 mg/kg in children under 12 years) can help differentiate poisoning by anti-
cholinesterase agents from other conditions. However, lack of response, with no
evidence of atropinization (atropine refractoriness) is typical of more severe poi-
sonings.The adjunctive use of nebulized atropine has been reported to improve
respiratory distress, decrease bronchial secretions, and increase oxygenation.26
3. Glycopyrolate has been studied as an alternative to atropine and found to
have similar outcomes using continuous infusion. Ampules of 7.5 mg of
glycopyrolate were added to 200 mL of saline and this infusion was titrated to the
desired effects of dry mucous membranes and heart rate above 60 beats/mm.
During this study, atropine was used as a bolus for a heart rate less than 60 beats/
min.The other apparent advantage to this regimen was a decreased number of
respiratory infections. This may represent an alternative when there is a concern
for respiratory infection due to excessive and difficult to control secretions, and in
the presence of altered level of consciousness where the distinction between
atropine toxicity or relapse of organophosphate poisoning is unclear.27
4. Pralidoxime. Before administration of pralidoxime, draw a blood sample
(heparinized) for cholinesterase analysis (since pralidoxime tends to reverse the
cholinesterase depression).Administer pralidoxime (Protopam, 2-PAM) a cho-
linesterase reactivator, in cases of severe poisoning by organophosphate pesti-
cides in which respiratory depression, muscle weakness, and/or twitching are
severe. (See dosage table on page 43.) When administered early (usually less
than 48 hours after poisoning), pralidoxime relieves the nicotinic as well as the
muscarinic effects of poisoning. Pralidoxime works by reactivating the cho-
linesterase and also by slowing the "aging" process of phosphorylated cho-
linesterase to a non-reactivatable form.
Note: Pralidoxime is of limited value and may actually be hazardous in poi-
sonings by the cholinesterase-inhibiting carbamate compounds (see Chapter 5).
ORGANOPHOSPHATES 41
-------
Dosage of Atropine:
In moderately severe poisoning (hypersecretion and other end-organ
manifestations without central nervous system depression), the follow-
ing dosage schedules have been used:
Adults and children over 12years: 2.0-4.0 mg, repeated every 15 min-
utes until pulmonary secretions are controlled, which may be ac-
companied by other signs of atropinization, including flushing, dry
mouth, dilated pupils, and tachycardia (pulse of 140 per minute).
Warning: In cases of ingestion of liquid concentrates of organo-
phosphate pesticides, hydrocarbon aspiration may complicate these
poisonings. Pulmonary edema and poor oxygenation in these cases
will not respond to atropine and should be treated as a case of acute
respiratory distress syndrome.
Children under 12years: 0.05-0.1 mg/kg body weight, repeated ev-
ery 15 minutes until atropinization is achieved.There is a minimum
dose of 0.1 mg in children. Maintain atropinization by repeated
doses based on recurrence of symptoms for 2-12 hours or longer
depending on severity of poisoning.
Maintain atropinization with repeated dosing as indicated by clinical
status. Crackles in the lung bases nearly always indicate inadequate
atropinization. Pulmonary improvement may not parallel other signs
of atropinization. Continuation of, or return of, cholinergic signs indi-
cates the need for more atropine. When symptoms are stable for as
much as six hours, the dosing may be decreased.
Severely poisoned individuals may exhibit remarkable tolerance to at-
ropine; two or more times the dosages suggested above may be needed.
The dose of atropine may be increased and the dosing interval de-
creased as needed to control symptoms. Continuous intravenous infu-
sion of atropine may be necessary when atropine requirements are
massive. The desired end-point is the reversal of muscarinic
symptoms and signs with improvement in pulmonary status
and oxygenation, without an arbitrary dose limit. Preservative-free
atropine products should be used whenever possible.
Note: Persons not poisoned or only slightly poisoned by organophos-
phates may develop signs of atropine toxicity from such large doses.
Fever, muscle fibrillations, and delirium are the main signs of atropine
toxicity. If these appear while the patient is fully atropinized, atropine
administration should be discontinued, at least temporarily, while the
severity of poisoning is reevaluated.
42 ORGANOPHOSPHATES
-------
Dosage of Pralidoxime:
Adults and children over 12years: 1.0-2.0 g by intravenous infusion at a
rate of no more than 0.2 g per minute. Slow administration of pralidoxime
is strongly recommended and may be achieved by administering the
total dose in 100 mL of normal saline over 30 minutes, or longer.
Children under 12 years: 20-50 mg/kg body weight (depending on
severity of poisoning) intravenously, mixed in 100 mL of normal
saline and infused over 30 minutes.
Dosage of pralidoxime may be repeated in 1-2 hours, then at 10-12 hour inter-
vals if needed. In very severe poisonings, dosage rates may be doubled. Repeated
doses of pralidoxime are usually required. In cases that involve continuing ab-
sorption of organophosphate (as after ingestion of large amount), or continuing
transfer of highly lipophilic organophosphate from fat into blood, it may be nec-
essary to continue administration of pralidoxime for several days beyond the 48
hour post-exposure interval usually cited as the limit of its effectiveness. Pralidoxime
may also be given as a continuous infusion of approximately 500 mg/hour based
on animal case studies and adult patient reports.28-29
Blood pressure should be monitored during administration because of the
occasional occurrence of hypertensive crisis. Administration should be slowed
or stopped if blood pressure rises to hazardous levels. Be prepared to assist
pulmonary ventilation mechanically if respiration is depressed during or after
pralidoxime administration. If intravenous injection is not possible, pralidoxime
may be given by deep intramuscular injection.
5. Skin decontamination. In patients who have been poisoned by organo-
phosphate contamination of skin, clothing, hair, and/or eyes, decontamination
must proceed concurrently with whatever resuscitative and antidotal measures
are necessary to preserve life. Flush the chemical from the eyes with copious
amounts of clean water. If no symptoms are evident in a patient who remains
alert and physically stable, a prompt shower and shampoo may be appropriate,
provided the patient is carefully observed to insure against any sudden appear-
ance of poisoning. If there are any indications of weakness, ataxia, or other
neurologic impairment, clothing should be removed and a complete bath and
shampoo given while the victim is recumbent, using copious amounts of soap
and water. Attendants should wear rubber gloves as vinyl provides no protec-
tion against skin absorption. Surgical green soap is excellent for this purpose,
but ordinary soap is about as good. Wash the chemical from skin folds and from
under fingernails.
ORGANOPHOSPHATES 43
-------
Contaminated clothing should be promptly removed, bagged, and laundered
before returning. Contaminated leather shoes should be discarded. Note that the
pesticide can contaminate the inside surfaces of gloves, boots, and headgear.
6. Gastrointestinal decontamination. If organophosphate has been ingested
in quantity probably sufficient to cause poisoning, consideration should be given
to gastrointestinal decontamination, as outlined in Chapter 2, General Prin-
ciples. If the patient has already vomited, which is most likely in serious expo-
sures, further efforts at GI decontamination may not be indicated. In significant
ingestions, diarrhea and/or vomiting are so constant that charcoal adsorption
and catharsis are not indicated.
7. Observation. Observe patient closely for at least 72 hours to ensure that
symptoms (sweating, visual disturbances, vomiting, diarrhea, chest and abdomi-
nal distress, and sometimes pulmonary edema) do not recur as atropinization is
withdrawn. In very severe poisonings by ingested organophosphates, particu-
larly the more lipophilic and slowly hydrolyzed compounds, metabolic dispo-
sition of toxicant may require as many as 5-14 days. In some cases, this slow
elimination may combine with profound cholinesterase inhibition to require
atropinization for several days or even weeks. As dosage is reduced, the lung
bases should be checked frequently for crackles. If crackles are heard, or if there
is a return of miosis, bradycardia, sweating, or other cholinergic signs, atropin-
ization must be re-established promptly.
8. Furosemide may be considered if pulmonary edema persists in the lungs
even after full atropinization. It should not be used until the maximum benefit of
atropine has been realized. Consult package insert for dosage and administration.
9. Pulmonary ventilation. Particularly in poisonings by large ingested doses
of organophosphate, monitor pulmonary ventilation carefully, even after recov-
ery from muscarinic symptomatology, to forestall respiratory failure. In some
cases, respiratory failure has developed several days following organophosphate
ingestion, and has persisted for days to weeks.
10. Hydrocarbon aspiration may complicate poisonings that involve inges-
tion of liquid concentrates of organophosphate pesticides. Pulmonary edema
and poor oxygenation in these cases will not respond to atropine and should be
treated as a case of acute respiratory distress syndrome.
11. Cardiopulmonary monitoring. In severely poisoned patients, monitor
cardiac status by continuous EGG recording. Some organophosphates have sig-
nificant cardiac toxicity.
44 ORGANOPHOSPHATES
-------
12. Seizure control. Rarely, in severe organophosphate poisonings, convul-
sions occur despite therapy with atropine and pralidoxime. Insure that causes
unrelated to pesticide toxicity are not responsible: head trauma, cerebral anoxia,
or mixed poisoning. Drugs useful in controlling convulsions are discussed in
Chapter 2. The benzodiazepines (diazepam or lorazepam) are the agents of
choice as initial therapy.
13. Contraindications. The following drugs are contraindicated in nearly all
organophosphate poisoning cases: morphine, succinylcholine, theophylline,
phenothiazines, and reserpine. Adrenergic amines should be given only if there
is a specific indication, such as marked hypotension.
14. Re-exposures. Persons who have been clinically poisoned by organo-
phosphate pesticides should not be re-exposed to cholinesterase-inhibiting
chemicals until symptoms and signs have resolved completely and blood cho-
linesterase activities have returned to at least 80 percent of pre-poisoning levels.
If blood cholinesterase was not measured prior to poisoning, blood enzyme
activities should reach at least minimum normal levels (see table on page 39)
before the patient is returned to a pesticide-contaminated environment.
15. Do not administer atropine or pralidoxime prophylactically to workers
exposed to organophosphate pesticides. Prophylactic dosage with either atropine
or pralidoxime may mask early signs and symptoms of organophosphate poison-
ing and thus allow the worker to continue exposure and possibly progress to
more severe poisoning. Atropine itself may enhance the health hazards of the
agricultural work setting: impaired heat loss due to reduced sweating and im-
paired ability to operate mechanical equipment due to blurred vision. This can
be caused by mydriasis, one of the effects of atropine.
General Chemical Structure
R is usually either ethyl or methyl. The insecticides with a double bonded sulfur are
organothiophosphates, but are converted to organophosphates in the liver. Phosphonate
contains an alkyl (R-) in place of one alkoxy group (RO-). "X" is called the "leaving
group " and is the principal metabolite for a specific identification.
RO^ 4, S (or 0)
P
no' ^ o
[Leaving Group|
ORGANOPHOSPHATES 45
-------
References
1. DuBois KP. The toxicity of organophosphorous compounds to mammals. Bull World Health
Organ 1971;44:233-40.
2. Pasquet J, Mazuret A, Fournel J, et al. Acute oral and percutaneous toxicity of phosalone in the
rat, in comparison with azinphosmethyl and parathion. Toxicol Appl Pharmacol 1976;37:85-92.
3. Garcia-Repetto R, Martinez D, and Repetto M. Coefficient of distribution of some organo-
phosphorus pesticides in rat tissue. Vet Hum Toxicol 1995;37:226-9.
4. Gallo MA and Lawryk NJ. Organic phosphorus pesticides. In: Haves WJ and Laws ER (eds),
Handbook of Pesticide Toxicology, vol 2, Classes of Pesticides. San Diego, CA: Academic
Press Inc., 1991.
5. Taylor R Anticholinesterase agents. In: Gilman AG and Goodman LS (eds), The Pharmaco-
logical Basis of Therapeutics. New York: Macmillan Publishing Co. Inc.; 1985, pp. 110-28.
6. De Kort WL, Kiestra SH, and Sangster B.The use of atropine and oximes in organophos-
phate intoxications: A modified approach. Clin Toxicol 1988;26:199-208.
7. Jamal JA. Neurological syndromes of organophosphorus compounds. Adverse Drug React
Toxicol Rev 1997;16(3): 133-70.
8. Steenland K, Jenkins B.Ames RG, et al. Chronic neurological sequelae to organophosphate
poisoning. Am J Public Health 1994;84:731-6.
9. Savage E, KeefeT, Mounce L, et al. Chronic neurological sequelae of acute organophosphate
pesticide poisoning. Arch Environ Health 1988;43:38-45.
10. Rosenstock L, Keifer M, Daniell VV et al. Chronic central nervous system effects of acute
organophosphate pesticide intoxication. Lancet 1991;338:223-7.
11. Gershon S and Shaw FH. Psychiatric sequelae of chronic exposure to organophosphorus
insecticides. Lancet 1961; 1:1371-4.
12. Metcalf DR and Holmes JH. EEG, psychological, and neurological alterations in humans
with organophosphorus exposure. Ann NYAcad Sci 1969;160:357-65.
13. Holmes JH and Gaon MD. Observations on acute and multiple exposure to anticholinest-
erase agents. Trans Am Clin Climatol Assoc 1957; 68:86-103.
14. Hirshberg A and Lerman Y Clinical problems in organophosphate insecticide poisoning:The
use of a computerized information system. Fundam Appl Toxicol 1984; 4:S209-14.
15. Miller CS and Mitzel HC. Chemical sensitivity attributed to pesticide exposure versus re-
modeling. Arch Environ Health 1995; 50:119-29.
16. DeBleeker J.Willems J,Van Den Neucker K, et al. Prolonged toxicity with intermediate
syndrome after combined parathion and methyl parathion poisoning. Clin Toxicol
1992;30:333-45.
17. DeBleecker J,Van Den Neucker K, and Colardyn F. Intermediate syndrome in organo-
phosphorous poisoning:A prospective study. Crit Care Med 1993;21:1706-11.
18. Aldridge WN and Nemery B. Toxicology of trialkylphosphorothioates with particular
reference to lung toxicity. Fundam Appl Toxicol 1984; 4:5215-23.
19. Bardin PG.Van Eeden SF, Moolman JA, et al. Organophosphate and carbamate poisoning.
Arch Intern Med 1994; 154:1433-41.
20. Zwiener RJ and Ginsburg CM. Organophosphate and carbamate poisoning in infants and
children. Pediatrics 1988;81:121-683.
21. Sofer S.Tal A, and Shahak E. Carbamate and organophosphate poisoning in early childhood.
PediatrEmerg Care 1989;5(4):222-5.
46 ORGANOPHOSPHATES
-------
22. Sullivan JB and Blose J. Organophosphate and carbamate insecticides. In: Sullivan JB and
Krieger GR (eds), Hazardous Materials Toxicology. Baltimore, MD: Williams and Wilkins,
1992, pp. 1015-26.
23. Goswamy R, Chaudhuri A, and Mahashur AA. Study of respiratory failure in organophos-
phate and carbamate poisoning. Heart Lung 1994;23:466-72.
24. LeBlanc FN, Benson BE, and Gilg AD. A severe Organophosphate poisoning requiring the
use of an atropine drip. Clin Toxicol 1986;24:69-76.
25. DuToit PW, Muller FO, Van Tender WM, et al. Experience with the intensive care manage-
ment of Organophosphate insecticide poisoning. S Afr Med J 1981;60:227-9.
26. Shockley LW. The use of inhaled nebulized atropine for the treatment of malathion poison-
ing. ClinToxicol 1989;27:183-92.
27. Bardin PG and van Eeden SE Organophosphate poisoning: Grading the severity and compar-
ing treatment between atropine and glycopyrrolate. Crit Care Med 1990; 18:956-60.
28. Thompson DF, Thompson GD, Greenwood RB, et al. Therapeutic dosing of pralidoxime
chloride. Drug Intell Clin Pharm 1987;21:590-2.
29. Tush GM and Anstead MI. Pralidoxime continuous infusion in the treatment of Organo-
phosphate poisoning. Ann Pharmawther 1997;31:441-4.
ORGANOPHOSPHATES 47
-------
CHAPTER 5
HIGHLIGHTS
Cause reversible
carbamylation of AChE
Muscarinic, nicotinic, CNS
effects
Signs and Symptoms:
Malaise, muscle weakness,
dizziness, sweating
Headache, salivation,
nausea, vomiting,
abdominal pain, diarrhea
CNS depression, pulmonary
edema in serious cases
Treatment:
Clear airway, improve tissue
oxygenation
Administer atropine sulfate
intravenously
Proceed immediately with
decontamination
procedures
N-Methyl Carbamate
Insecticides
N-Methyl carbamate insecticides are widely used in homes, gardens, and agri-
culture. They share with organophosphates the capacity to inhibit cholinest-
erase enzymes and therefore share similar symptomatology during acute and
chronic exposures. Likewise, exposure can occur by several routes in the same
individual due to multiple uses, and there is likely to be additive toxicity with
simultaneous exposure to organophosphates. However, due to the somewhat
different affinity for cholinesterases, as compared to organophosphates, these
poisonings are often somewhat easier to treat, as discussed later in this chapter.
Toxicology
The N-methyl carbamate esters cause reversible carbamylation of the ace-
tylcholinesterase enzyme, allowing accumulation of acetylcholine, the
neuromediator substance, at parasympathetic neuroeffector junctions (muscar-
inic effects), at skeletal muscle myoneural junctions and autonomic ganglia (nico-
tinic effects), and in the brain (CNS effects).The carbamyl-acetylcholinesterase
combination dissociates more readily than the phosphoryl-acetylcholinesterase
complex produced by organophosphate compounds. This lability has several
important consequences: (1) it tends to limit the duration of N-methyl car-
bamate poisonings, (2) it accounts for the greater span between symptom-
producing and lethal doses than in most organophosphate compounds, and (3)
it frequently invalidates the measurement of blood cholinesterase activity as a
diagnostic index of poisoning (see below).
N-methyl carbamates are absorbed by inhalation and ingestion and some-
what by skin penetration, although the latter tends to be the less toxic route. For
example, carbofuran has a rat oral LD50 of 5 mg/kg, compared to a rat dermal
LD5Q of 120 mg/kg, which makes the oral route approximately 24 times more
toxic when ingested.1 N-methyl carbamates are hydrolyzed enzymatically by the
liver; degradation products are excreted by the kidneys and the liver.
At cholinergic nerve junctions with smooth muscle and gland cells, high
acetylcholine concentration causes muscle contraction and secretion, respec-
tively. At skeletal muscle junctions, excess acetylcholine may be excitatory (cause
muscle twitching), but may also weaken or paralyze the cell by depolarizing the
end-plate. In the brain, elevated acetylcholine concentrations may cause sen-
48 N-METHYL CARBAMATES
-------
sory and behavioral disturbances, incoordination, and depressed motor func-
tion (rarely seizures), even though the N-methyl carbamates do not penetrate
the central nervous system very efficiently. Respiratory depression combined
with pulmonary edema is the usual cause of death from poisoning by N-me-
thyl carbamate compounds.
Signs and Symptoms of Poisoning
As with organophosphate poisoning, the signs and symptoms are based on
excessive cholinergic stimulation. Unlike organophosphate poisoning, carbamate
poisonings tend to be of shorter duration because the inhibition of nervous tissue
AchE is reversible, and carbamates are more rapidly metabolized.2 Bradycardia and
seizures are less common than in organophosphate poisonings. However, blood
cholinesterase levels may be misleading due to in vitro reactivation of a
carbamylated enzyme.3'4 A falsely "normal" level can make the diagnosis more
difficult in the acute presentation in the absence of an exposure history.
The primary manifestations of serious toxicity are central nervous system
depression, as manifested by coma, seizures, and hypotonicity, and nicotinic
effects including hypertension and cardiorespiratory depression. Dyspnea, bron-
chospasm, and bronchorrhea with eventual pulmonary edema are other seri-
ous signs. Recent information indicates that children and adults differ in their
clinical presentation. Children are more likely than adults to present with the
CNS symptoms above. While children can still develop the classic muscarinic
signs, the absence of them does not exclude the possibility of carbamate poi-
soning in the presence of CNS depression.5
Malaise, muscle weakness, dizziness, and sweating are commonly reported
early symptoms. Headache, salivation, nausea, vomiting, abdominal pain, and
diarrhea are often prominent. Miosis with blurred vision, incoordination, muscle
twitching, and slurred speech are reported.
Confirmation of Poisoning
If there are strong clinical indications of acute N-methyl carbam-
ate poisoning, and/or a history of carbamate exposure, treat the pa-
tient immediately. Do not wait for laboratory confirmation.
Blood for plasma pseudocholinesterase and RBC AChE should be ob-
tained. Be advised that unless a substantial amount of N-methyl carbamate has
been absorbed and a blood sample is taken within an hour or two, it is unlikely
that blood cholinesterase activities will be found depressed. Even under the
above circumstances, a rapid test for enzyme activity must be used to detect an
effect, because enzyme reactivation occurs in vitro as well as in vivo. See the table
on page 39 for methods of measurement of blood cholinesterase activities, if
circumstances appear to warrant performance of the test.
Commercial Products
aldicarb*
Temik
aminocarb*
Matacil
bendiocarb*
Dycarb
Ficam
Multamat
Niomil
Tattoo
Turcam
bufencarb
Bux
metalkamate
carbaryl
Dicarbam
Sevin
carbofuran*
Crisfuran
Curaterr
Furadan
cloethocarb*
Lance
dimetan
Dimethan
dioxacarb
Elecron
Famid
fenoxycarb
Torus
formetanate hydrochloride*
Carzol
isolan*
Primin
isoprocarb
Etrofolan
MIPC
methiocarb*
Draza
Mesurol
methomyl*
Lannate
Lanox
Nudrin
mexacarbate
Zectran
oxamyl*
DPX1410
Vydate L
pirimicarb
Abol
Aficida
Aphox
Fernos
Pirimor
Rapid
(Continued on the next page)
N-METHYL CARBAMATES 49
-------
Commercial Products
(Continued)
promecarb
Carbamult
propoxur
aprocarb
Baygon
thiodicarb
Larvin
trimethacarb
Broot
Landrin
+ Indicates high toxicity.
Highly toxic N-methyl
carbamates have listed oral
LD50 values (rat) less than or
equal to 50 mg/kg body
weight. Most other
carbamates included in this
table are considered
moderately toxic, with LD50
values in excess of 50 mg/
kg and less than 500 mg/kg.
Absorption of some N-methyl carbamates can be confirmed by analysis of
urine for unique metabolites: alpha-naphthol from carbaryl, isopropoxyphenol
from propoxur, carbofuran phenol from carbofuran, and aldicarb sulfone, sul-
foxide, and nitrile from aldicarb.These complex analyses, when available, can be
useful in identifying the responsible agent and following the course of carbam-
ate disposition.
Treatment
Caution: Persons attending the victim should avoid direct contact with
heavily contaminated clothing and vomitus.Wear rubber gloves while washing
pesticide from skin and hair. Vinyl gloves provide no protection.
1. Airway protection. Ensure that a clear airway exists. Intubate the patient
and aspirate the secretions with a large-bore suction device if necessary. Ad-
minister oxygen by mechanically assisted pulmonary ventilation if respiration is
depressed. Improve tissue oxygenation as much as possible before ad-
ministering atropine, to minimize the risk of ventricular fibrillation.
In severe poisonings, it may be necessary to support pulmonary ventilation
mechanically for several days.
2. Atropine. Administer atropine sulfate intravenously, or intramuscularly if
intravenous injection is not possible. Remember that atropine can be adminis-
tered through an endotracheal tube if initial IV access is difficult to obtain.
Carbamates usually reverse with much smaller dosages of atropine than those
required to reverse organophosphates.6 (See dosage on next page.)
The objective of atropine antidotal therapy is to antagonize the effects of
excessive concentrations of acetylcholine at end-organs having muscarinic re-
ceptors. Atropine does not reactivate the cholinesterase enzyme or accelerate
excretion or breakdown of carbamate. Recrudescence of poisoning may occur
if tissue concentrations of toxicant remain high when the effect of atropine
wears off. Atropine is effective against muscarinic manifestations, but is ineffec-
tive against nicotinic actions, specifically, muscle weakness and twitching, and
respiratory depression.
Despite these limitations, atropine is often a life-saving agent in N-methyl
carbamate poisonings. Favorable response to a test dose of atropine (1 mg in
adults, 0.01 mg/kg in children under 12 years) given intravenously can help
differentiate poisoning by anticholinesterase agents from other conditions such
as cardiogenic pulmonary edema and hydrocarbon ingestion. However, lack of
response to the test dose, indicating no atropinization (atropine refractoriness),
is characteristic of moderately severe to severe poisoning and indicates a need
for further atropine. If the test dose does not result in mydriasis and drying of
secretions, the patient can be considered atropine refractory.
50 N-METHYL CARBAMATES
-------
Dosage of Atropine:
In moderately severe poisoning (hypersecretion and other end-organ
manifestations without central nervous system depression), the follow-
ing dosage schedules have proven effective:
Adults and children over 12years: 2.0-4.0 mg, repeated every 15 min-
utes until pulmonary secretions are controlled, which may be ac-
companied by other signs of atropinization, including flushing, dry
mouth, dilated pupils, and tachycardia (pulse of 140 per minute).
Warning: In cases of ingestion of liquid concentrates of carbamate
pesticides, hydrocarbon aspiration may complicate these poisonings.
Pulmonary edema and poor oxygenation in these cases will not
respond to atropine and should be treated as a case of acute respira-
tory distress syndrome.
Children under 12years: 0.05-0.1 mg/kg body weight, repeated every
15 minutes until pulmonary secretions are controlled, which may be
accompanied by other signs of atropinization as above (heart rates
vary depending on age of child with young toddlers having a rate
approaching 200).There is a minimum dose of 0.1 mg in children.
Maintain atropinization by repeated doses based on recurrence of symp-
toms for 2-12 hours or longer depending on severity of poisoning. Crack-
les in the lung bases nearly always indicate inadequate atropinization and
pulmonary improvement may not parallel other signs. Continuation or
return of cholinergic signs indicates the need for more atropine.
Severely poisoned individuals may exhibit remarkable tolerance to at-
ropine; two or more times the dosages suggested above may be needed.
Reversal of muscarinic manifestations, rather than a specific dosage, is
the object of atropine therapy. However, prolonged intensive intrave-
nous administration of atropine sometimes required in organophos-
phate poisonings is rarely needed in treating carbamate poisoning.
Note: Persons not poisoned or only slightly poisoned by N-methyl
carbamates may develop signs of atropine toxicity from such large doses.
Fever, muscle fibrillations, and delirium are the main signs of atropine
toxicity. If these signs appear while the patient is fully atropinized, atro-
pine administration should be discontinued, at least temporarily, while
the severity of poisoning is reevaluated.
N-METHYL CARBAMATES 51
-------
3. Skin decontamination. In patients with contaminated skin, clothing, hair,
and/or eyes, decontamination must proceed concurrently with what-
ever resuscitative and antidotal measures are needed to preserve life.
Flush the chemical from eyes with copious amounts of clean water. For asymp-
tomatic individuals who are alert and physically able, a prompt shower and
shampoo may be appropriate for thorough skin decontamination, provided the
patient is carefully observed to insure against sudden appearance of poisoning.
If there are any indications of weakness ataxia or other neurologic impairment,
clothing should be removed and a complete bath and shampoo given while the
victim is recumbent, using copious amounts of soap and water. Attendants should
wear rubber gloves as vinyl provides no protection against skin absorption.
Wash the chemical from skin folds and from under fingernails.
Contaminated clothing should be promptly removed, bagged, and laundered
before returning. Contaminated leather shoes should be discarded. Note that the
pesticide can contaminate the inside surfaces of gloves, boots, and headgear.
4. Gastrointestinal decontamination. If N-methyl carbamate has been ingested
in a quantity probably sufficient to cause poisoning, consideration should be given
to gastrointestinal decontamination as outlined in Chapter 2. If the patient has
presented with a recent ingestion and is still asymptomatic, adsorption of poison
with activated charcoal may be beneficial. In significant ingestions, diarrhea and/or
vomiting are so constant that charcoal adsorption and catharsis are not indicated.
Attention should be given to oxygen, airway management, and atropine.
5. Urine sample. Save a urine sample for metabolite analysis if there is need to
identify the agent responsible for the poisoning.
6. Pralidoxime is probably of little value in N-methyl carbamate poisonings,
because atropine alone is effective. Although not indicated in isolated carbam-
ate poisoning, pralidoxime appears to be useful in cases of mixed carbamate/
organophosphate poisonings, and cases of an unknown pesticide with muscar-
inic symptoms on presentation.7'8 See Chapter 4,Treatment section, p. 41.
7. Observation. Observe patient closely for at least 24 hours to ensure that symp-
toms (sweating, visual disturbances, vomiting, diarrhea, chest and abdominal distress,
and sometimes pulmonary edema) do not recur as atropinization is withdrawn.The
observation period should be longer in the case of a mixed pesticide ingestion,
because of the prolonged and delayed symptoms associated with organophosphate
poisoning. As the dosage of atropine is reduced over time, check the lung bases
frequently for crackles. Atropinization must be re-established promptly, if crackles
are heard, or if there is a return of miosis, sweating, or other signs of poisoning.
8. Furosemide may be considered for relief of pulmonary edema if crackles
persist in the lungs even after full atropinization. It should not be considered
52 N-METHYL CARBAMATES
-------
until the maximum effect of atropine has been achieved. Consult package in-
sert for dosage and administration.
9. Pulmonary ventilation. Particularly in poisonings by large doses of N-
methyl carbamates, monitor pulmonary ventilation carefully, even after recov-
ery from muscarinic symptomatology, to forestall respiratory failure.
10. Cardiopulmonary monitoring. In severely poisoned patients, monitor
cardiac status by continuous EGG recording.
11. Contraindications. The following drugs are probably contraindicated in
nearly all N-methyl carbamate poisoning cases: morphine, succinlycholine, theo-
phylline, phenothiazines, and reserpine. Adrenergic amines should be given
only if there is a specific indication, such as marked hypotension.
12. Hydrocarbon aspiration may complicate poisonings that involve inges-
tion of liquid concentrates of some carbamates that are formulated in a petro-
leum product base. Pulmonary edema and poor oxygenation in these cases will
not respond to atropine and should be treated as cases of acute respiratory
distress syndrome.
13. Do not administer atropine prophylactically to workers exposed to
N-methyl carbamate pesticides. Prophylactic dosage may mask early symptoms
and signs of carbamate poisoning and thus allow the worker to continue expo-
sure and possibly progress to more severe poisoning. Atropine itself may en-
hance the health hazards of the agricultural work setting: impaired heat loss
due to reduced sweating and impaired ability to operate mechanical equip-
ment due to blurred vision (mydriasis).
General Chemical Structure
References
1. Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety
and Health, Cincinnati, OH. (CD-ROMVersion, Micromedex, Inc. Englewood, CA 1991.)
2. Ecobichon DJ. Toxic effect of pesticides. In: Klaassen CD (ed), Casarett & Doull's Toxicol-
ogy: The Basic Science of Poisons, 5th ed. New York: McGraw-Hill, 1996, p. 659.
3. Rotenberg M and Almog S. Evaluation of the decarbamylation process of cholinesterase
during assay of enzyme activity. Clin ChimActa 1995;240:107-16.
N-METHYL CARBAMATES 53
-------
4. Jokanovic M and Maksimovic M. Abnormal cholinesterase activity: Understanding and in-
terpretation. EurJ Clin Chem Clin Biochem 1997;35:11-6.
5. Lifshitz M, Shahak E.BolotinA.et al. Carbamate poisoning in early childhood and in adults.
Ota Toxto/1997:35:25-7.
6. Goswarny R et al. Study of respiratory failure in organophosphate and carbamate poisoning.
Heart Lung 1994;23:466-72.
7. Lifshitz M.Totenberg M, Sofer S, et al. Carbamate poisoning and oxime treatment in chil-
dren: A clinical and laboratory study. Pediatrics 1994;93:652-5.
8. Kurtz PH. Pralidoxime in the treatment of carbamate intoxication. AmJEmerg Med 1990,8:68-70.
54 N-METHYLCARBAMATES
-------
CHAPTER 6
Solid Organochlorine Insecticides
EPA has sharply curtailed the availability of many organochlorines, particularly
DDT, aldrin, dieldrin, heptachlor, mirex, chlordecone, and chlordane. Others,
however, remain the active ingredients of various home and garden products
and some agricultural, structural, and environmental pest control products.
Hexachlorobenzene is a fungicide used as a seed protectant and is discussed
further in Chapter 15, Fungicides.
Technical hexachlorocyclohexane (misnamed benzene hexachloride, BHC)
includes multiple stereoisomers; only the gamma isomer (lindane) is insecticidal.
Lindane is the active ingredient of some pest control products used in the home
and garden, on the farm, and in forestry and animal husbandry. It is also the active
agent in the medicine Kwell*, used for human ectoparasitic disease. Lindane has
been reported on numerous occasions to be associated with acute neurological
toxicity either from ingestion or in persons treated for scabies or lice.1"6
Toxicology
In varying degrees, organochlorines are absorbed from the gut and also by
the lung and across the skin. The efficiency of dermal absorption is variable.
Hexachlorocyclohexane, including lindane, the cyclodienes (aldrin, dieldrin,
endrin, chlordane, heptachlor), and endosulfan are efficiently absorbed across
the skin, while dermal absorption efficiencies of DDT, dicofol, marlate, tox-
aphene, and mirex are substantially less.7 Lindane has a documented 9.3% der-
mal absorption rate,8 and is absorbed even more efficiently across abraded skin. '-9
This becomes especially important when taking into account its use on chil-
dren with severe dermatitis associated with scabies. Fat and fat solvents enhance
gastrointestinal, and probably dermal, absorption of organochlorines. While most
of the solid organochlorines are not highly volatile, pesticide-laden aerosol or
dust particles trapped in respiratory mucous and subsequently swallowed may
lead to significant gastrointestinal absorption.
Following exposure to some organochlorines (notably DDT), a significant
part of the absorbed dose is stored in fat tissue as the unchanged parent com-
pound. Most organochlorines are in some degree dechlorinated, oxidized, then
conjugated. The chief route of excretion is biliary, although nearly all orga-
nochlorines yield measurable urinary metabolites. Unfortunately, many of the
unmetabolized pesticides are efficiently reabsorbed by the intestine (enterohepatic
circulation), substantially retarding fecal excretion.
HIGHLIGHTS
Signs and Symptoms:
Absorbed dose is stored in
fat tissue
Sensory disturbances:
hyperesthesia and
paresthesia, headache,
dizziness, nausea,
hyperexcitable state
Convulsions
Treatment:
Anticonvulsants
(benzodiazepines)
Administer oxygen
Cardiopulmonary
monitoring
Contraindicated:
Epinephrine, other
adrenergic amines, atropine
Animal or vegetable oils or
fats taken orally
SOLID ORGANOCHLORINES 55
-------
Commercial Products
aldrin*
benzene hexachloride (BHC)*
HCH
hexachlor
hexachloran
chlordane*
(multiple trade names)
chlordecone*
Kepone
chlorobenzilate
DDT*
(multiple trade names)
dicofol
Kelthane
(multiple trade names)
dieldrin*
Dieldrite
dienochlor
Pentac
endosulfan
(multiple trade names)
endrin*
Hexadrin
heptachlor**
(multiple trade names)
hexacholorobenzene*
lindane
gamma BHC or HCH
Kwell
(multiple trade names)
methoxychlor
Marlate
mirex*
terpene polychlorinates*
Strobane
toxaphene*
* All U.S. registrations have
been cancelled.
** Registered in the United
States only for
underground use in
power lines for fire ants.
Metabolic dispositions of DDT and DDE (a DDT degradation product), the
beta isomer of hexachlorocyclohexane, dieldrin, heptachlor epoxide, and mirex
tend to be slow, leading to storage in body fat. Storable lipophilic compounds are
likely to be excreted in maternal milk.6-10-11 On the other hand, rapid metabolic
dispositions of lindane, methoxychlor, dienochlor, endrin, chlorobenzilate, dicofol,
toxaphene, perthane, and endosulfan reduce the likelihood that these organochlo-
rines will be detected as residues in body fat, blood, or milk.
The chief acute toxic action of organochlorine pesticides is on the nervous
system, where these compounds induce a hyperexcitable state in the brain.12
This effect is manifest mainly as convulsions, sometimes limited to myoclonic
jerking, but often expressed as violent seizures. Convulsions caused by cyclodienes
may recur over periods of several days. Other less severe signs of neurologic
toxicity such as paresthesias, tremor, ataxia, and hyperreflexia are also characteristic
of acute organochlorine poisoning. Agents such as DDT and methoxychlor
tend to cause the less severe effects, while the cyclodienes, mirex, and lindane
are associated with the more severe seizures and fatalities.7 Convulsions may
cause death by interfering with pulmonary gas exchange and by generating
severe metabolic acidosis.
High tissue concentrations of organochlorines increase myocardial irritability,
predisposing to cardiac arrhythmia.When tissue organochlorine concentrations
drop below threshold levels, recovery from the poisoning occurs.
Organochlorines are not cholinesterase inhibitors.
High tissue levels of some organochlorines (notably DDT, DDE, and cy-
clodienes) have been shown to induce hepatic microsomal drug-metabolizing
enzymes.13 This tends to accelerate excretion of the pesticides themselves, but
may also stimulate biotransformation of critical natural substances, such as ste-
roid hormones and therapeutic drugs, occasionally necessitating re-evaluation
of required dosages in persons intensively exposed to organochlorines. Human
absorption of organochlorine sufficient to cause enzyme induction is likely to
occur only as a result of prolonged intensive exposure.
Ingestion of hexachlorobenzene-treated wheat has been associated with
human dermal toxicity diagnosed as porphyria cutanea tarda.The skin blisters,
becomes very sensitive to sunlight, and heals poorly, resulting in scarring and
contracture formation.14 Unlike other organochlorine compounds, there have
been no reported cases of convulsions caused by the fungicide hexachloro-
benzene. Lindane and chlordane have rarely been associated anecdotally with
certain hematological disorders, including aplastic anemia and megaloblastic
anemia.15'16
There has been considerable interest recently in the interaction of orga-
nochlorines with endocrine receptors, particularly estrogen and androgen
receptors. In vitro studies and animal experimentation have supported the view
that the function of the endocrine system may be altered by these interac-
tions.17'18 This in turn may alter the reproductive development and success of
animals and humans. In addition, some organochlorines may inhibit lactation
and may also be developmental toxicants.10 Due to evidence of carcinogenic
56 SOLID ORGANOCHLORINES
-------
potential, some organochlorines have lost registration for use in the United
States or had their uses restricted. Although these effects are important, they are
beyond the scope of this manual.
Signs and Symptoms of Poisoning
Early manifestations of poisoning by some organochlorine pesticides, par-
ticularly DDT, are often sensory disturbances: hyperesthesia and paresthesia of
the face and extremities. Headache, dizziness, nausea, vomiting, incoordination,
tremor, and mental confusion are also reported. More severe poisoning causes
myoclonic jerking movements, then generalized tonic-clonic convulsions. Coma
and respiratory depression may follow the seizures.
Poisoning by the cyclodienes and toxaphene is more likely to begin with
the sudden onset of convulsions, and is often not preceded by the premonitory
manifestations mentioned above. Seizures caused by cyclodienes may appear as
long as 48 hours after exposure, and then may recur periodically over several
days following the initial episode. Because lindane and toxaphene are more
rapidly biotransformed in the body and excreted, they are less likely than diel-
drin, aldrin, and chlordane to cause delayed or recurrent seizures.
Confirmation of Poisoning
Organochlorine pesticides and/or their metabolites can sometimes be iden-
tified in blood by gas-liquid chromatographic examination of samples taken
within a few days of significant pesticide absorption. Such tests are performed
by a limited number of government, university, and private laboratories, which
can usually be contacted through poison control centers or health departments.
Some organochlorine pesticides or their products (notably DDT, dieldrin, mirex,
heptachlor, epoxide, chlordecone) persist in tissues and blood for weeks or
months after absorption, but others are likely to be excreted in a few days,
limiting the likelihood of detection. Blood levels tend to correlate more with
acute toxicity, while levels found in adipose tissue and breast milk usually re-
flect more long-term and historic exposure.19
Chromatographic methods make possible detection of most organochlo-
rines at concentrations much lower than those associated with symptoms of
toxicity. Therefore, a positive finding in a blood sample does not, of itself Justify
a diagnosis of acute poisoning. Lindane appears in the literature more frequently
than other compounds.The time of acquisition of the blood level in relation to
exposure time must be taken into account when interpreting blood levels. In
one study, lindane levels were measured at 10.3 ng/mL in healthy volunteers
three days after application to the skin.20
In a study with childhood dermal absorption using children with scabies
and a non-affected control group, lindane peaked at 28 ng/mL 6 hours after
application in the affected group, and at 24 ng/mL in the control group. At 48
SOLID ORGANOCHLORINES 57
-------
hours, levels were 6 ng/mL and 5 ng/mL respectively. Findings from this study
also provide evidence for increased absorption across abraded skin.9 A child
with severely abraded skin was treated for scabies and developed seizures.Three
days after exposure, his lindane level was 54 ng/mL.1 Most reports of acute
toxicity from lindane involve blood levels of 130 ng/mL or greater, with the
most severe and fatal cases involving levels exceeding 500 ng/mL.2
DDT, DDE, and a few other organochlorines are still found at very low
levels in blood samples from the general U.S. population, presumably due to
past and/or current low-level contamination of food by these environmentally
persistent pesticides.
In the absence of corresponding elevations of blood levels, the amount of
stored pesticides is not likely to be of clinical significance. Measurements of uri-
nary metabolites of some organochlorine pesticides can be useful in monitoring
occupational exposures; however, the analytical methods are complex, and are
not likely to detect amounts of metabolites generated by minimal exposures.
Treatment
1. Observation. Persons exposed to high levels of organochlorine pesticides
by any route should be observed for sensory disturbances, incoordination, speech
slurring, mental aberrations, and involuntary motor activity that would warn of
imminent convulsions.
2. Convulsions. If convulsions occur, place the victim in the left lateral decu-
bitus position with the head down. Move away furniture or other solid objects
that could be a source of injury. If jaw movements are violent, place padded
tongue blades between the teeth to protect the tongue. Whenever possible,
remove dentures and other removable dental work. Aspirate oral and pharyn-
geal secretion, and when possible, insert an oropharyngeal airway to maintain
an open passage unobstructed by the tongue. Minimize noise and any manipu-
lation of the patient that may trigger seizure activity.
Dosage of Diazepam:
Adults'. 5-10 mg IV and repeat every 5-10 minutes to maximum of 30 mg.
Children: 0.2 to 0.5 mg/kg every 5 minutes to maximum of 10 mg in
children over 5 years, and maximum of 5 mg in children under 5 years.
Although lorazepam is widely accepted as a treatment of choice for
status epilepticus, there are no reports of its use for organochlorine
intoxication. Some cases have required aggressive seizure management
including the addition of phenobarbital and the induction of pento-
barbital coma.
58 SOLID ORGANOCHLORINES
-------
Seizures in patients caused by organochlorine toxicity are likely to be pro-
longed and difficult to control. Status epilepticus is common. For this reason,
patients with seizures that do not respond immediately to anticonvulsants should
be transferred as soon as possible to a trauma center and will generally require
intensive care admission until seizures are controlled and neurologic status is
improved. Initial therapy with benzodiazepines should be instituted.
3. Oxygen. Administer oxygen by mask. Maintain pulmonary gas exchange by
mechanically assisted ventilation whenever respiration is depressed.
4. Skin decontamination. Skin decontamination should be done thoroughly,
as outlined in Chapter 2.
5. Gastrointestinal decontamination. If organochlorine has been ingested
in a quantity sufficient to cause poisoning and the patient presents within an
hour, consideration should be given to gastric decontamination procedures, as
outlined in Chapter 2. If the patient presents more than an hour after ingestion,
activated charcoal may still be beneficial. If the victim is convulsing, it is almost
always necessary first to control seizures before attempting gastric decontami-
nation. Activated charcoal administration has been advocated in such poison-
ings, but there is little human or experimental evidence to support it.
6. Respiratory failure. Particularly in poisonings by large doses of
organochlorine, monitor pulmonary ventilation carefully to forestall
respiratory failure. Assist pulmonary ventilation mechanically with oxygen
whenever respiration is depressed. Since these compounds are often formulated
in a hydrocarbon vehicle, hydrocarbon aspiration may occur with ingestion of
these agents. The hydrocarbon aspiration should be managed in accordance
with accepted medical practice as a case of acute respiratory distress syndrome
which will usually require intensive care management.
7. Cardiac monitoring. In severely poisoned patients, monitor cardiac status
by continuous EGG recording to detect arrhythmia.
8. Contraindications. Do not give epinephrine, other adrenergic amines, or
atropine unless absolutely necessary because of the enhanced myocardial irrita-
bility induced by chlorinated hydrocarbons, which predisposes to ventricular
fibrillation. Do not give animal or vegetable oils or fats by mouth. They en-
hance gastrointestinal absorption of the lipophilic organochlorines.
9. Phenobarbital. To control seizures and myoclonic movements that some-
times persist for several days following acute poisoning by the more slowly
excreted organochlorines, phenobarbital given orally is likely to be effective.
SOLID ORGANOCHLORINES 59
-------
Dosage should be based on manifestations in the individual case and on infor-
mation contained in the package insert.
10. Cholestryamine resin accelerates the biliary-fecal excretion of the more
slowly eliminated organochlorine compounds.21 It is usually administered in 4
g doses, 4 times a day, before meals and at bedtime.The usual dose for children
is 240 mg/kg/24 hours, divided Q 8 hours. The dose may be mixed with a
pulpy fruit or liquid. It should never be given in its dry form and must always
be administered with water, other liquids or a pulpy fruit. Prolonged treatment
(several weeks or months) may be necessary.
11. Convalescence. During convalescence, enhance carbohydrate, protein, and
vitamin intake by diet or parenteral therapy.
General Chemical Structures
s=o
Cl Cl
Heptachlor
OCH,
yCI-C-Clv
Cl
Methoxychlor
Endosulfan
Cl Cl
Cl Cl
Cl Cl Cl Cl
Dienochlor
60 SOLID ORGANOCHLORINES
-------
Cl Cl
Cl
Cl
Mirex
Chlordecone
References
1. Friedman SJ. Lindane neurotoxic reaction in nonbullous congenital ichthyosiform erythro-
derma. Arch Dermatol 1987;123:1056-8.
2. Aks SE, Krantz A, Hryhorczuk DO, et al. Acute accidental lindane ingestion in toddlers. Ann
EmergMed 1995;25(5):647-51.
3. Tenenbein M. Seizures after lindane therapy. J Am Geriatr Soc 1991;39(4):394-5.
4. Solomon BA, Haut SR, Carr EM, and Shalita AR. Neurotoxic reaction to lindane in an HIV-
seropositive patient: An old medication's new problem. /Fam Pract 1995;40(3):291-6.
5. FischerTE Lindane toxicity in a 24-year-old woman. Ann EmergMed 1994;24(5):972-4.
6. Solomon LM.Fahrner L,and West DP Gamma benzene hexachloride toxicity. Arch Dermatol
1977:113:353-7.
7. Echobichon DJ.Toxic effects of pesticides. In Klaassen CD (ed), Casarett & Doull'sToxicol-
ogy: The Basic Science of Poisons, 5th ed. New York: McGraw-Hill, 1996, pp. 649-55.
8. Feldmann RJ and Maibach HI. Percutaneous penetration of some pesticides and herbicides
in man. Toxicol andAppl Pharmacol 1974;28:126-32.
9. Ginsburg CM, Lowry W, and Reisch JS. Absorption of lindane (gamma benzene hexachlo-
ride) in infants and children. /Pediatr 1997;91(6):998-1000.
10. RoganWJ. Pollutants in breast milk. Arch PediatrAdolesc Med 1996;150:981-90.
11. Stevens MF, Ebell GF, and Psaila-Savona P. Organochlorine pesticides in Western Australian
nursing mothers. MedJAust 1993;158(4):238-41.
12. Joy RM.The effects of neurotoxicants on kindling and kindled seizures. FundamApplToxicol
1985;5:41-65.
13. Hunter J, Maxwell JD, Stewart DA, et al. Increased hepatic microsomal enzyme activity from
occupational exposure to certain organochlorine pesticides. Nature 1972;237:399-401.
14. Booth NH and McDowell JR. Toxicity of hexachlorobenzene and associated residues in
edible animal tissues. J Am Vet Med Assoc 1975;166(6):591-5.
15. RauchAE.Kowalsky SF, LesarTS.et al. Lindane (Kwell)-induced aplastic anemia. Arch Intern
Med 1990; 150:2393-5.
16. Furie B andTrubowitz S. Insecticides and blood dyscrasias. Chlordane exposure and self-
limited refractory megaloblastic anemia. JAMA 1976;235(16):1720-2.
17. Vonier PM, Grain DA, McLachlan JA, et al. Interaction of environmental chemicals with the
estrogen and progesterone receptors from the oviduct of the American alligator. Environ
Health Perspect 1996;104(12): 1318-22.
SOLID ORGANOCHLORINES 61
-------
18. Fry DM. Reproductive effects in birds exposed to pesticides and industrial chemicals. Environ
Health Perspect 1995;103(Suppl 7):165-71.
19. Frank R, Rasper J, Srnout MS, and Braun HE. Organochlorine residues in adipose tissues,
blood and milk from Ontario residents, 1976-1985. Can J Public Health 1988;79:150-8.
20. Hosier J.Tschan C, Hignite CE, et al. Topical application of lindane cream (Kwell) and
antipyrine metabolism. /Invest Dermatol 1980;74:51-3.
21. Cohn WJ, Boylan JJ, Blanke RV, et al. Treatment of chlordecone (Kepone) toxicity with
cholestyramine. NewEngl JMed 1978;298(5):243-8.
62 SOLID ORGANOCHLORINES
-------
CHAPTER 7
Biologicals and Insecticides
of Biological Origin
This chapter covers several widely-used insecticidal products of natural origin, as
well as certain agents often identified as biological control agents. Of the many
living control agents, only the bacterial agent Bacillus thuringiensis will be discussed
in detail, since it is one of the most widely used. Many other agents, such as
parasitic wasps and insects, are so host-specific that they pose little or no risk to
human health.The agents are discussed in this chapter in alphabetic order.
AZADIRACHTIN
This biologically-obtained insecticide is derived from the Neem tree
(Azadirachta indica). It is an insect growth regulator that interferes with the
molting hormone ecdysone.
Toxicology
Azadirachtin causes severe dermal and gastrointestinal irritation. Central
nervous system stimulation and depression have been seen.This agent is prima-
rily used and manufactured in India; little use or exposures are expected in the
United States.
HIGHLIGHTS
Derived from living systems
Bacillus thuringensis is the
most important live agent
Generally of low order
toxicity
Signs and Symptoms:
Highly variable based on
specific agents
Several cause
gastrointestinal irritation
Nicotine and rotenone may
have serious CNS effects
Nicotine and sabadilla may
have cardiovascular effects
Treatment:
Specific to the agent
Skin, eye, and Gl
decontamination may be
indicated
Nicotine, rotenone, and
sabadilla require aggressive
support
Treatment
1. Skin decontamination. If skin exposure occurs, the skin should be thor-
oughly washed with soap and water.
2. Gastrointestinal decontamination. Due to the severe gastrointestinal ir-
ritation, gastric emptying and catharsis are not indicated. Consideration should
be given to administration of activated charcoal as outlined in Chapter 2.
BIOLOGICALS 63
-------
Commercial Products
BACILLUS THURINGIENSIS
azadirachtin
Align
Azatin
Bollwhip
Neemazad
Neemazal
Neemix
Turplex
Bacillus thuringiensis
Variety aizawai:
Agree
Design
Mattch
XenTari
Variety israelensis:
Aquabac
Bactimos
Gnatrol
Skeetal
Teknar
Vectobac
Vectocide
Variety kurstaki:
Bactospeine
Bactur
Dipel
Future
Sok-Bt
Thuricide
Tribactur
Variety morrisoni
Variety tenebrionis:
Novodor
eugenol
gibberellicacid (GA3)
Activol
Berelex
Cekugib
Gibberellin
Gibrel
Grocel
Pro-Gibb
Pro-Gibb Plus
Regulex
nicotine
Black Leaf 40
Nico Soap
pyrethrins
rotenone
Chem-Fish
Noxfire
Noxfish
Nusyn-Foxfish
Prenfish
(Continued on the next page)
Several strains of Bacillus thuringiensis are pathogenic to some insects. The
bacterial organisms are cultured, then harvested in spore form for use as insec-
ticide. Production methods vary widely. Proteinaceous and nucleotide-like toxins
generated by the vegetative forms (which infect insects) are responsible for the
insecticidal effect.The spores are formulated as wettable powders, flowable con-
centrates, and granules for application to field crops and for control of mosqui-
toes and black flies.
Toxicology
The varieties of Bacillus thuringiensis used commercially survive when in-
jected into mice, and at least one of the purified insecticidal toxins is toxic to
mice. Infections of humans have been extremely rare. A single case report of
ingestion by volunteers of Bacillus thuringiensis var. galleriae resulted in fever and
gastrointestinal symptoms. However, this agent is not registered as a pesticide.
B. thuringiensis products are exempt from tolerance on raw agricultural com-
modities in the United States. Neither irritative nor sensitizing effects have
been reported in workers preparing and applying commercial products.
Treatment
1. Skin decontamination. Skin contamination should be removed with soap
and water. Eye contamination should be flushed from the eyes with clean water
or saline. If irritation persists, or if there is any indication of infection, treatment
by a physician should be obtained.
A single case of corneal ulcer caused by a splash of B. thuringiensis suspen-
sion into the eye was successfully treated by subconjunctival injection of gen-
tamicin (20 mg) and cefazolin (25 mg).1
2. Gastrointestinal decontamination. If a B. thuringiensis product has been
ingested, the patient should be observed for manifestations of bacterial gastro-
enteritis: abdominal cramps, vomiting, and diarrhea. The illness is likely to be
self-limited if it occurs at all.The patient should be treated symptomatically and
fluid support provided as appropriate.
EUGENOL
This compound is derived from clove oil. It is used as an insect attractant.
64 BIOLOGICALS
-------
Toxicology
Eugenol is similar in its clinical effects to phenol. Although it works as an
anesthetic, in large doses it can cause burns to epithelial surfaces.2 Sloughing of
mucous membranes has occurred as an allergic reaction to a small dose applied
topically in the mouth.3 Gastric mucosal lesions have been reported in animals,
but no lesions were seen on endoscopy after clove oil ingestion.4 Large doses
may result in coma and liver dysfunction.5
Treatment
Treatment is primarily supportive as there is no antidote. If mucosal burns
are present, consider endoscopy to look for other ulcerations.
Commercial Products
(Continued)
Rotacide
Rotenone Solution FK-11
Sypren-Fish
sabadilla
streptomycin
Agri-Mycin 17
Paushamycin, Tech.
Plantomycin
*Discontinued in the U.S.
GIBBERELLIC ACID (Gibberellin, GA3)
Gibberellic acid is not a pesticide, but it is commonly used in agricultural
production as a growth-promoting agent. It is a metabolic product of a cul-
tured fungus, formulated in tablets, granules, and liquid concentrates for appli-
cation to soil beneath growing plants and trees.
Toxicology
Experimental animals tolerate large oral doses without apparent adverse
effect. No human poisonings have been reported. Sensitization has not been
reported, and irritant effects are not remarkable.
Treatment
1. Skin decontamination. Wash contamination from skin with soap and
water. Flush contamination from eyes with clean water or saline. If irritation
occurs, obtain medical treatment.
2. Gastrointestinal decontamination. If gibberellic acid has been swallowed,
there is no reason to expect adverse effects.
NICOTINE
Nicotine is an alkaloid contained in the leaves of many species of plants,
but is usually obtained commercially from tobacco. A 14% preparation of the
free alkaloid is marketed as a greenhouse fumigant. Significant volatilization of
nicotine occurs. Commercial nicotine insecticides have long been known as
Black Leaf 40. This formulation was discontinued in 1992. Other currently
BIOLOGICALS 65
-------
available formulations include dusts formulated with naphthalene and dried
blood used to repel dogs and rabbits. Be aware of Green Tobacco Syndrome
from dermal absorption.Very little nicotine insecticide is currently used in the
United States, although old preparations of nicotine insecticides may still be
found on occasion.6 Today, most nicotine poisonings are the result of ingestion
of tobacco products and incorrect use of nicotine skin patches.
Toxicology
Nicotine alkaloid is efficiently absorbed by the gut, lung, and skin. Exten-
sive biotransformation occurs in the liver with 70-75% occurring as a first pass
effect.7 Both the liver and kidney participate in the formation and excretion of
multiple end-products, which are excreted within a few hours. Estimates of the
half-life of nicotine range from about one hour in smokers to as much as two
hours in non-smokers.8'9
Toxic action is complex. At low doses, autonomic ganglia are stimulated.
Higher doses result in blockade of autonomic ganglia and skeletal muscle neuro-
muscular junctions, and direct effects on the central nervous system. Paralysis and
vascular collapse are prominent features of acute poisoning, but death is often due
to respiratory paralysis, which may ensue promptly after the first symptoms of
poisoning. Nicotine is not an inhibitor of the cholinesterase enzyme.
Signs and Symptoms of Poisoning
Early and prominent symptoms of poisoning include salivation, sweating,
dizziness, nausea, vomiting, and diarrhea. Burning sensations in the mouth and
throat, agitation, confusion, headache, and abdominal pain are reported. If dos-
age has been high, vascular collapse with hypotension, bradycardia or other
arrythmias, dyspnea then respiratory failure, and unconsciousness may ensue
promptly.6'10'11'12 In some cases, hypertension and tachycardia may precede hy-
potension and bradycardia, with the latter two signs leading to shock.11'12 Sei-
zures may also occur.6'11 In one case of ingestion of a large dose of nicotine
alkaloid pesticide, the patient developed asystole within two minutes. He later
developed seizures and refractory hypotension.6
Confirmation of Poisoning
Urine content of the metabolite cotinine can be used to confirm absorp-
tion of nicotine.
66 BIOLOGICALS
-------
Treatment
1. Skin decontamination. If liquid or aerosol spray has come in contact with
skin, wash the area thoroughly with soap and water. If eyes have been contami-
nated, flush them thoroughly with clean water or saline. If irritation persists,
obtain specialized medical treatment.
If symptoms of poisoning appear during exposure to an airborne nicotine
insecticide, remove the person from the contaminated environment immediately,
wash any skin areas that may be contaminated, then transport the victim to the
nearest treatment facility. Although mild poisoning may resolve without treat-
ment, it is often difficult to predict the ultimate severity of poisoning at the onset.
2. Pulmonary ventilation. If there is any indication of loss of respiratory
drive, maintain pulmonary ventilation by mechanical means, using supplemen-
tal oxygen if available, or mouth-to-mouth or mouth-to-nose methods if nec-
essary. Toxic effects of nicotine other than respiratory depression are usually
survivable.The importance of maintaining adequate gas exchange is therefore
paramount.
3. Gastrointestinal decontamination. If a nicotine-containing product has
been ingested recently, immediate steps must be taken to limit gastrointestinal
absorption. If the patient is fully alert, immediate oral administration of acti-
vated charcoal as outlined in Chapter 2 is probably the best initial step in man-
agement. Repeated administration of activated charcoal at half or more the
initial dosage every 2-4 hours may be beneficial. Since diarrhea is often a part
of this poisoning, it is usually not necessary or appropriate to administer a
cathartic. Do not administer syrup of ipecac.
4. Cardiac monitoring. Monitor cardiac status by electrocardiography and
measure blood pressure frequently. Cardiopulmonary resuscitation may
be necessary. Vascular collapse may require administration of norepinephrine
and/or dopamine. Consult package inserts for dosages and routes of adminis-
tration. Infusions of electrolyte solutions, plasma, and/or blood may also be
required to combat shock.
5. Atropine sulfate. There is no specific antidote for nicotine poisoning. Se-
vere hypersecretion (especially salivation and diarrhea) or bradycardia may be
treated with intravenous atropine sulfate. See dosage on next page.
BIOLOGICALS 67
-------
Dosage of Atropine Sulfate:
Adults and children over 12years:OA-0.5 mg slowly IV, repeated every
5 minutes if necessary.
Children under 12years:0.01 mg/kg body weight, slowly IV, repeated
every 5 minutes if necessary.There is a minimum dose of 0.1 mg.
6. Convulsions should be controlled as outlined in Chapter 2. If the patient
survives for four hours, complete recovery is likely.
PYRETHRUM AND PYRETHRINS
Pyrethrum is the oleoresin extract of dried chrysanthemum flowers. The
extract contains about 50% active insecticidal ingredients known as pyrethrins.
The ketoalcoholic esters of chrysanthemic and pyrethroic acids are known as
pyrethrins, cinerins, and jasmolins. These strongly lipophilic esters rapidly pen-
etrate many insects and paralyze their nervous systems. Both crude pyrethrum
extract and purified pyrethrins are contained in various commercial products,
commonly dissolved in petroleum distillates. Some are packaged in pressurized
containers ("bug-bombs"), usually in combination with the synergists piperonyl
butoxide and n-octyl bicycloheptene dicarboximide.The synergists retard enzy-
matic degradation of pyrethrins. Some commercial products also contain
organophosphate or carbamate insecticides.These are included because the rapid
paralytic effect of pyrethrins on insects ("quick knockdown") is not always lethal.
Pyrethrum and pyrethrin products are used mainly for indoor pest control.
They are not sufficiently stable in light and heat to remain as active residues on
crops. The synthetic insecticides known as pyrethroids (chemically similar to
pyrethrins) do have the stability needed for agricultural applications. Pyrethroids
are discussed separately in Chapter 8.
Toxicology
Crude pyrethrum is a dermal and respiratory allergen, probably due mainly
to non-insecticidal ingredients. Contact dermatitis and allergic respiratory re-
actions (rhinitis and asthma) have occurred following exposures.13'14 Single cases
exhibiting anaphylactic15 and pneumonitic manifestations16 have also been re-
ported. The refined pyrethrins are probably less allergenic, but appear to retain
some irritant and/or sensitizing properties.
Pyrethrins are absorbed across the gut and pulmonary membrane, but only
slightly across intact skin.They are very effectively hydrolyzed to inert products
by mammalian liver enzymes.This rapid degradation combined with relatively
68 BIOLOGICALS
-------
poor bioavailability probably accounts in large part for their relatively low mam-
malian toxicity. Dogs fed extraordinary doses exhibit tremor, ataxia, labored
breathing, and salivation. Similar neurotoxicity rarely, if ever, has been observed
in humans, even in individuals who have used pyrethrins for body lice control
(extensive contact) or pyrethrum as an anthelmintic (ingestion).
In cases of human exposure to commercial products, the possible role of
other toxicants in the products should be kept in mind.The synergists pipero-
nyl butoxide and n-octyl bicycloheptene dicarboximide have low toxic poten-
tial in humans, but organophosphates or carbamates included in the product
may have significant toxicity. Pyrethrins themselves do not inhibit cholinest-
erase enzyme.
Confirmation of Poisoning
There are at present no practical tests for pyrethrin metabolites or pyrethrin
effects on human enzymes or tissues that can be used to confirm absorption.
Treatment
1. Antihistamines are effective in controlling most allergic reactions. Severe
asthmatic reactions, particularly in predisposed persons, may require adminis-
tration of inhaled B2-agonists and/or systemic corticosteroids. Inhalation ex-
posure should be carefully avoided in the future.
2. Anaphylaxis-type reactions may require sub-cutaneous epinephrine,
epinepherine, and respiratory support.15
3. Contact dermatitis may require extended administration of topical corti-
costeroid preparations. This should be done under the supervision of a physi-
cian. Future contact with the allergen must be avoided.
4. Eye contamination should be removed by flushing the eye with large
amounts of clean water or saline. Specialized ophthalmologic care should be
obtained if irritation persists.
5. Other toxic manifestations caused by other ingredients must be treated ac-
cording to their respective toxic actions, independent of pyrethrin-related effects.
6. Gastrointestinal decontamination. Even though most ingestions of pyre-
thrin products present little risk, if a large amount of pyrethrin-containing
material has been ingested and the patient is seen within one hour, consider
gastric emptying. If the patient is seen later, or if gastric emptying is performed,
consider administration of activated charcoal as described in Chapter 2.
BIOLOGICALS 69
-------
ROTENONE
Although this natural substance is present in a number of plants, the source
of most rotenone used in the United States is the dried derris root imported
from Central and South America. It is formulated as dusts, powders, and sprays
(less than 5% active ingredient) for use in gardens and on food crops. Many
products contain piperonyl butoxide as synergist, and other pesticides are in-
cluded in some commercial products. Rotenone degrades rapidly in the envi-
ronment. Emulsions of rotenone are applied to lakes and ponds to kill fish.
Toxicology
Although rotenone is toxic to the nervous systems of insects, fish, and birds,
commercial rotenone products have presented little hazard to humans over
many decades. Neither fatalities nor systemic poisonings have been reported in
relation to ordinary use. However, there is one report of a fatality in a child
who ingested a product called Gallocide, which contains rotenone and etheral
oils, including clove oil. She developed a gradual loss of consciousness over two
hours and died of respiratory arrest.17
Numbness of oral mucous membranes has been reported in workers who
got dust from the powdered derris root in their mouths. Dermatitis and respira-
tory tract irritation have also been reported in occupationally exposed persons.
When rotenone has been injected into animals, tremors, vomiting, incoor-
dination, convulsions, and respiratory arrest have been observed.These effects
have not been reported in occupationally exposed humans.
Treatment
1. Skin decontamination. Skin contamination should be removed by wash-
ing with soap and water. Eye contamination should be removed by flushing the
eye thoroughly with clean water or saline. Dust in the mouth should be washed
out. If irritation persists, medical treatment should be obtained.
2. Gastrointestinal decontamination. If a large amount of a rotenone-con-
taining product has been swallowed and retained and the patient is seen within
an hour of exposure, consideration should be given to gastric emptying. Whether
or not gastric emptying is performed, consider use of activated charcoal as
outlined in Chapter 2.
3. Respiratory support should be used as necessary if mental status changes
and/or respiratory depression occurs.
70 BIOLOGICALS
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SABADILLA (Veratrum alkaloid)
Sabadilla consists of the powdered ripe seeds of a South American lily. It is
used as dust, with lime or sulfur, or dissolved in kerosene, mainly to kill ecto-
parasites on domestic animals and humans. Insecticidal alkaloids are those of
the veratrum type. The concentration of alkaloids in commercial sabadilla is
usually less than 0.5%. Little or no sabadilla is used in the United States today,
but some is probably used in other countries. Most toxic encounters with ver-
atrum alkaloid occur from the inadvertent ingestion of the plant.18
Toxicology
Sabadilla dust is very irritating to the upper respiratory tract, causing sneez-
ing, and is also irritating to the skin.Veratrin alkaloids are apparently absorbed
across the skin and gut, and probably by the lung as well. Veratrin alkaloids have a
digitalis-like action on the heart muscles (impaired conduction and arrhythmia).
Although poisoning by medicinal veratrum preparations may have occurred
in the past, systemic poisoning by sabadilla preparations used as insecticides has
been very rare. The prominent symptoms of veratrum alkaloid poisoning are
severe nausea and vomiting, followed by hypotension and bradycardia. Other
arrythmias or A-V block may occur.18'19
Treatment
1. Skin decontamination. Contaminated skin should be washed thoroughly
with soap and water. If eyes are affected, they should be flushed with copious
amounts of clean water or saline. If skin or eye irritation persists, medical treat-
ment should be obtained.
2. Gastrointestinal decontamination. If a large amount of sabadilla pesticide
product has been ingested in the past hour and retained, consider gastric empty-
ing.This may be followed by administration of charcoal. If only a small amount of
sabadilla pesticide has been ingested and retained, or if treatment is delayed, and if
the patient remains fully alert, immediate oral administration of activated char-
coal probably represents reasonable management, as outlined in Chapter 2.
3. Cardiac monitoring. If there is a suspicion that significant amounts of
sabadilla alkaloids have been absorbed, EGG monitoring of cardiac activity for
arrhythmia and conduction defects is appropriate. Bradycardia may be treated
with atropine.18'19 See dosage on next page.
BIOLOGICALS 71
-------
Dosage of Atropine Sulfate:
Adults and children over 12years: 0.4-0.5 mg slowly IV repeated ev-
ery 5 minutes if necessary.
Children under 12years:0.01 mg/kg body weight, slowly IV, repeated
every 5 minutes if necessary. (There is a minimum dose of 0.1 mg).
STREPTOMYCIN
Streptomycin sulfate and nitrate are used as pesticides for the control of a
variety of commercially important bacterial plant pathogens. Streptomycin is
an antibiotic derived from the growth of Streptomyces griseus.
Toxicology
This antibiotic shares a toxic profile with the aminoglycoside antibiotics
commonly used to treat human diseases. Its major modes of toxicity are neph-
rotoxicity and ototoxicity. Fortunately, it is poorly absorbed from the gastrointes-
tinal tract, so systemic toxicity is unlikely with ingestion.
Treatment
If a large amount of streptomycin has been ingested within one hour of the
patient's receiving care, gastric emptying should be considered. Administration
of activated charcoal, as outlined in Chapter 2, should be considered.
References
1. Samples JR and Buettner H. Corneal ulcer caused by a biological insecticide (Bacillus
thuringiensis). Am J Ophthalmol 1983;95:258.
2. Isaacs G. Permanent local anesthesia and anhydrosis after clove oil spillage. Lancet 1983; 1:882.
3. Barkin ME, Boyd JP, and Cohen S. Acute allergic reaction to eugenol. Oral Surg Oral Med Oral
Pathol 1984;57:441-2.
4. Lane BW, Ellenhorn MJ, HulbertTV, et al. Clove oil ingestion in an infant. Hum Exp Toxicol
1991;10:291-4.
5. Hartnoll G, Moore D, and Douek D. Near fatal ingestion of oil of cloves. Arch Dis Child
1993:69:392-3.
6. Lavoie FW and HarrisTM. Fatal nicotine ingestion. ]Emerg Med 1991;9:133-6.
7. Svensson CK. Clinical pharmacokinetics of nicotine. Clin Pharm 1987; 12:30-40.
72 BIOLOGICALS
-------
8. Kyerematen MS, Damiano MD, Dvorchik BH, et al. Smoking-induced changes in nicotine
disposition: Application of a new HPLC assay for nicotine and its metabolites. Clin Pharmacol
Ther 1982:32:769-80.
9. Feyerabend C, Ings RMJ, and Russell MAH. Nicotine pharmacokinetics and its application
to intake from smoking. BrJ Clin Pharmacol 1985;19:239-47.
10. Woolf A, Burkhart K, CaraccioT, et al. Self-poisoning among adults using multiple transdermal
nicotine patches. JToxicol Clin Toxicol 1996;34:691-8.
11. Sanchez P, Ducasse JL, Lapeyre-Mestre M, et al. Nicotine poisoning as a cause of cardiac
arrest? (letter). JToxicol Clin Toxicol 1996;34:475-6.
12. Malizia E, Andreucci G, Alfani F, et al. Acute intoxication with nicotine alkaloids and can-
nabinoids in children from ingestion of cigarettes. HumToxicol 1983;2:315-6.
13. Moretto A. Indoor spraying with the pyrethroid insecticide lambda-cyhalothrin: Effects on
spraymen and inhabitants of sprayed houses. Bull World Health Organ 1991; 69:591-4.
14. Newton JG and Breslin ABX. Asthmatic reactions to a commonly used aerosol insect killer.
MedJAust 1983; 1:378-80.
15. Culver CA, Malina JJ, and Talbert RL. Probable anaphylactoid reaction to a pyrethrin
pediculocide shampoo. Clin Pharm 1988;7:846-9.
16. Carlson JE and Villaveces JW Hypersensitivity pneumonitis due to pyrethrum. JAMA
1977:237:1718-9.
17. DeWilde AR. A case of fatal rotenone poisoning in a child. ]Forensic Sci 1986;31 (4): 1492-8.
18. Jaffe AM, Gephardt D, and Courtemanche L. Poisoning due to ingestion of veratrum viride
(false hellebore). JEmerg Med 1990;8:161-7.
19. Quatrehomme G, Bertrand F, Chauvet C, et al. Intoxication from veratrum album. Hum Exp
Toxicol 1993;12:lll-5.
BIOLOGICALS 73
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CHAPTERS
HIGHLIGHTS
Multiple agents, with
widely varying toxicity
Careful history will usually
reveal exposure history
Agents of particular
concern due to wide use
are pyrethroids,
diethyltoluamide, and
borates
Signs and Symptoms:
Variable and highly related
to the specific agent
Boric acid causes severe
erythematous and
exfoliative rash (boiled
lobster appearance)
Agents such as boric acid,
diethyltoluamide, and
pyrethroids should be
suspected in cases of
unusual nervous system
symptoms
Treatment:
Specific to the agents
Skin and Gl
decontamination
Severe CNS symptoms may
require intensive care
management
Other Insecticides,
Acaricides, and Repellents
This chapter discusses insecticides, acaricides, and repellents that have toxico-
logic characteristics distinct from the insecticides discussed in previous chap-
ters. Pesticides reviewed include: alkyl phthalates, benzyl benzoate, borates,
chlordimeform, chlorobenzilate, cyhexatin, diethyltoluamide, fluorides,
haloaromatic urea compounds, methoprene, propargite, pyrethroids, and sulfur.
ALKYL PHTHALATES
Dimethyl phthalate has been widely used as an insect repellent applied
directly to the skin. Dibutylphthalate is impregnated into fabric for the same
purpose. It is more resistant to laundering than dimethyl phthalate.
Toxicology
Dimethyl phthalate is strongly irritating to the eyes and mucous membranes.
It has caused little or no irritation when applied to skin, and dermal absorption is
apparently minimal. It has not caused sensitization.Tests in rodents have indicated
low systemic toxicity, but large ingested doses cause gastrointestinal irritation,
central nervous system depression, coma, and hypotension.
Treatment
No antidote is available. Supportive measures (hydration, oxygen if needed)
are probably adequate to manage all but the most severe poisonings.
BENZYL BENZOATE
Toxicology
Incorporated into lotions and ointments, this agent has been used for many
years in veterinary and human medicine against mites and lice. Apart from
occasional cases of skin irritation, adverse effects have been few.The efficiency
74
OTHER INSECTICIDES
-------
of skin absorption is not known. Absorbed benzyl benzoate is rapidly
biotransformed to hippuric acid which is excreted in the urine.When given in
large doses to laboratory animals, benzyl benzoate causes excitement, incoordi-
nation, paralysis of the limbs, convulsions, respiratory paralysis, and death. No
human poisonings have been reported.
Treatment
1. Skin decontamination. If significant irritant effect appears, medications
should be discontinued and the skin cleansed with soap and water. Eye con-
tamination should be treated by prolonged flushing with clean water or saline.
2. Gastrointestinal decontamination. If a potentially toxic amount has been
swallowed and retained and the patient is seen soon after exposure, gastrointes-
tinal decontamination should be considered as outlined in Chapter 2.
3. Seizures. If seizures occur, control may require anticonvulsant medication
as outlined in Chapter 2.
BORIC ACID AND BORATES
Boric acid is formulated as tablets and powder to kill larvae in livestock
confinement areas and cockroaches, ants, and other insects in residences. Rarely,
solutions are sprayed as a nonselective herbicide.
Toxicology
Boric acid powders and pellets scattered on the floors of homes do present
a hazard to children. Their frequent use for roach control increases access for
ingestion. A series of 784 patients has been described with no fatalities and
minimum toxicity. Only 12% of these patients had symptoms of toxicity, mostly
to the gastrointestinal tract.' However, there have been some recent reports of
fatal poisonings,2'3 and a great many poisonings of newborns which occurred
in the 1950s and 1960s often ended in death.4'5 Historically, many poisonings
have resulted from injudicious uses in human medicine aimed at suppressing
bacterial growth, such as compresses for burns, powders for diaper rash, and
irrigation solutions.6'7 With the increased use of boric acid for roach control,
suicidal or accidental ingestion is still likely to occur.3'7
Borax dust is moderately irritating to skin. Inhaled dust caused irritation of
the respiratory tract among workers in a borax plant. Symptoms included nasal
irritation, mucous membrane dryness, cough, shortness of breath, and chest
tightness.8'9
Commercial Products
ALKYL PHTHALATES
dibutylphthalate
dimethyl phthalate
DMP
BENZYL BENZOATE
BORIC ACID AND BORATES
boric acid
sodium polyborates
Polybor 3
sodium tetraborate
decahydrate
Borax
CHLORDIMEFORM (nr)
CHLOROBENZILATE (nr)
Acaraben
Akar
Benzilan
Folbex
CYHEXATIN (nr)
Acarstin
Metaran
Oxotin
Pennstyl
Plictran
DIETHYLTOLUAMIDE (DEET)
Auton
Detamide
Metadelphene
MGK
Muskol
Off!
Skeeter Beater
Skeeter Cheater
Skintastic for Kids
FLUORIDES
sodium fluoride (wood
protection only)
sodium fluosilicate (sodium
silico fluoride) (nr)
Prodan
Safsan
sodium fluoaluminate
Cryolite
Kryocide
Prokil
(Continued on the next page)
OTHER INSECTICIDES 75
-------
Commercial Products
(Continued)
HALOAROMATIC
SUBSTITUTED UREAS
diflubenzuron
Dimilin
Micromite
Vigilante
teflubenzuron
Dart
Diaract
Nomolt
METHOPRENE
Altosid
Apex
Diacon
Dianex
Kabat
Minex
Pharorid
Precor
PROPARGITE
Comite
Fenpropar
Omite
Ornamite
Mightikill
PYRETHROIDS
allethrin
Pynamin
barthrin (nr)
bioallethrin
D-trans
biopermethrin (nr)
bioresmethrin (nr)
cismethrin (nr)
cyfluthrin
Baythroid
cypermethrin
Ammo
Barricade
CCN52
Cymbush
Cymperator
Cynoff
Cyperkill
Cyrux
(Continued on the next page)
When determining toxicity to boric acid from ingestion, it is important to
distinguish between acute and chronic exposure. Chronic ingestion is more
likely to cause significant toxicity than acute exposure.1'2 Borates are well ab-
sorbed by the gut and by abraded or burned skin, but not by intact skin.6 The
kidney efficiently excretes them.The residence half-life in humans averages 13
hours, in a range of 4-28 hours.1
The gastrointestinal tract, skin, vascular system, and brain are the principal
organs and tissues effected. Nausea, persistent vomiting, abdominal pain, and
diarrhea reflect a toxic gastroenteritis.1'2'7 Lethargy and headache may occur,
but are more infrequent.1 In severe poisonings, a beefy red skin rash, most often
affecting palms, soles, buttocks, and scrotum, has been described. It has been
characterized as a "boiled lobster appearance." The intense erythema is fol-
lowed by extensive exfoliation.2'5'10 This may be difficult to distinguish from
staphylcoccal scalded skin syndrome.10
Headache, weakness, lethargy, restlessness, and tremors may occur, but are
less frequent than gastrointestinal effects.1 Seven infants who were exposed to a
mixture of borax and honey on their pacifiers developed seizures.11 Uncon-
sciousness and respiratory depression signify life-threatening brain injury. Cy-
anosis, weak pulse, hypotension, and cold clammy skin indicate shock, which is
sometimes the cause of death in borate poisoning.2'3'7
Acute renal failure (oliguria or anuria) may be a consequence of shock, of
direct toxic action on renal tubule cells, or both. It occurs in severe borate
poisoning.2'3'5'10 Metabolic acidosis may be a consequence of the acid itself, of
seizure activity, or of metabolic derangements.2 Fever is sometimes present in
the absence of infection.
Confirmation of Poisoning
Borate can be measured in serum by colorimetric methods, as well by
high-temperature atomic spectrometric methods. Urine borate concentrations
in non-exposed individuals are in the range of 0.004-.66 mg/dL. Normal se-
rum levels range up to 0.2 mg/dL in adults, and in children to 0.125 mg/dL.7
Levels reported in toxic incidents have varied widely, and it is felt that serum
levels are of little use in guiding therapy.'
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
2. Gastrointestinal decontamination. In acute poisonings, if a large amount
76
OTHER INSECTICIDES
-------
has been ingested and the patient is seen within one hour of exposure, gas-
trointestinal decontamination should be considered as outlined in Chapter 2. It
is important to keep in mind that vomiting and diarrhea are common, and
severe poisoning may be associated with seizures.Therefore induction of erne-
sis by syrup of ipecac is probably contraindicated in these exposures. Catharsis
is not indicated if diarrhea is present.
3. Intravenous fluids. If ingestion of borate has been massive (several grams),
or has extended over several days, administer intravenous glucose and electro-
lyte solutions to sustain urinary excretion of borate. Monitor fluid balance and
serum electrolytes (including bicarbonate capacity) regularly. Monitor cardiac
status by EGG. Test the urine for protein and cells to detect renal injury, and
monitor serum concentration of borate. Metabolic acidosis may be treated with
sodium bicarbonate. If shock develops, it may be necessary to infuse plasma or
whole blood. Administer oxygen continuously. If oliguria (less than 25-30 mL
urine formed per hour) occurs, intravenous fluids must be slowed or stopped to
avoid overloading the circulation. Such patients should usually be referred to a
center capable of providing intensive care for critically ill patients.
4. Hemodialysis. If renal failure occurs, hemodialysis may be necessary to
sustain fluid balance and normal extracellular fluid composition. Hemodialysis
has had limited success in enhancing clearance of borates.1
5. Peritoneal dialysis has been performed in borate poisoning5-12 and is felt to
be as effective as, and safer than, exchange transfusion in removing borate. No
large study of efficacy has been done, but it is still used somewhat less fre-
quently than hemodialysis.1
6. Seizures should be controlled as recommended for other agents and out-
lined Chapter 2.
CHLORDIMEFORM
Chlordimeform is an ovicide and acaricide. Formulations are emulsifiable
concentrates and water-soluble powders.
Toxicology
In a reported episode of occupational exposure to chlordimeform, several
workers developed hematuria. Hemorrhagic cystitis, probably due to chloraniline
biodegradation products, was the source of the blood in the urine. Symptoms
reported by the affected workers included gross hematuria, dysuria, urinary
frequency and urgency, penile discharge, abdominal and back pain, a general-
Commercial Products
(Continued)
Demon
Flectron
Folcord
KafilSuper
NRDC149
Polytrin
Ripcord
Siperin
Ustadd
others
deltamethrin
Decis
DeltaDust
DeltaGard
Deltex
Suspend
dimethrin
fenothrin (nr)
fenpropanate (nr)
fenpropathrin
Danitol
Herald
Meothrin
Rody
fenvalerate
Belmark
Fenkill
Sumicidin
flucythrinate
Cybolt
Fluent
Payoff
fluvalinate
furethrin (nr)
permethrin
Ambush
Dragnet
Eksmin
Elimite
Kafil
Nix
Outflank
Permasect
Perthrine
Pounce
Pramex
Talcord
others
phthalthrin (nr)
resmethrin
Benzofuroline
Chrysron
Pynosect
(Continued on the next page)
OTHER INSECTICIDES 77
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Commercial Products
(Continued)
tetramethrin
Neopynamin
tralomethrin
SAGA
Tralex
SULFUR
many commercial products
nr = not registered or withdrawn
ized "hot" sensation, sleepiness, skin rash and desquamation, a sweet taste, and
anorexia. Symptoms persisted for 2-8 weeks after exposure was terminated.13
In a single case, methemoglobinemia was reported.14 Chlordimeform is not a
cholinesterase inhibitor. Chlordimeform has been voluntarily cancelled in the
U.S. due to concerns regarding increased bladder cancer incidence seen in
manufacturing workers.
Confirmation of Poisoning
Although methods do exist for measurement of urinary excretion prod-
ucts, these tests are not generally available.
Treatment
1. Precautions. Strenuous efforts should be made to protect against inhalation
and dermal contact with Chlordimeform because absorption is evidently effi-
cient.
2. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
3. Gastrointestinal decontamination. If Chlordimeform has been ingested
no more than an hour prior to treatment, consider gastrointestinal decontami-
nation as outlined in Chapter 2. Repeated doses of charcoal every 2-4 hours
may be beneficial.
4. Hydration. Because catharsis may cause serious dehydration and electrolyte
disturbances in young children, fluid balance and serum electrolytes should be
monitored. An adequate state of hydration should be maintained by oral and/
or intravenous fluids to support Chlordimeform excretion.
5. Urinary analysis. Repeated analyses of urine for protein and red cells
should be done to detect injury to the urinary tract. Disappearance of hema-
turia can ordinarily be expected in 2-8 weeks. Relief from other symptoms can
usually be expected earlier.
CHLOROBENZILATE
Chlorobenzilate is a chlorinated hydrocarbon acaricide, usually formulated
as an emulsion or wettable powder for application in orchards. Use in the
United States has been discontinued.
78 OTHER INSECTICIDES
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Toxicology
Chlorobenzilate is moderately irritating to the skin and eyes. Although struc-
turally similar to DDT, chlorobenzilate is much more rapidly excreted following
absorption, chiefly in the urine as the benzophenone and benzole acid deriva-
tives. Based on observation of dosed animals, extreme absorbed doses may cause
tremors, ataxia, and muscle weakness.There has been one case in humans of toxic
encephalopathy following spraying in a field for 14 days at 10 hours per day.The
patient did not wear a mask while spraying. His symptoms included muscle pain,
weakness, fever, and mental status changes progressing to a tonic-clonic seizure.
He recovered without sequelae within 6 days. Treatment included respiratory
support and seizure control with phenobarbital and phenytoin.15
Chlorobenzilate is not a cholinesterase inhibitor.
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
2. Gastrointestinal decontamination. If a large amount of chlorobenzilate
was ingested within a few hours prior to treatment, consider gastrointestinal
decontamination as outlined in Chapter 2. If the absorbed dose of chlorobenzilate
was small, if treatment is delayed, and if the patient is asymptomatic, oral ad-
ministration of activated charcoal and sorbitol may be indicated. Do not give
fats or oils.
3. Seizures. Any seizures should be treated as outlined in Chapter 2.
CYHEXATIN
Toxicology
Tricyclohexyl tin hydroxide is formulated as a 50% wettable powder for
control of mites on ornamentals, hops, nut trees, and some fruit trees. It is
moderately irritating, particularly to the eyes. While information on the sys-
temic toxicity of this specific tin compound is lacking, it should probably be
assumed that cyhexatin can be absorbed to some extent across the skin, and that
substantial absorbed doses would cause nervous system injury (see organotin
compounds in Chapter 15, Fungicides). Cyhexatin has been voluntarily can-
celled in the United States.
OTHER INSECTICIDES 79
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Treatment
1. Skin decontamination. Wash skin with soap and water. Remove contami-
nation from the eyes by prolonged flushing with clean water or saline.
2. Gastrointestinal decontamination. Management of poisonings by inges-
tion should proceed on the assumption that cyhexatin is toxic, even though
rodent LD5Q values are fairly high, and no human poisonings have been re-
ported. Treatment should be as with other organotin compounds.
DIETHYLTOLUAMIDE (DEBT)
This chemical is a widely-used liquid insect repellent, suitable for application
to skin or to fabrics. It comes in a wide range of concentrations from 5% (Off!,
Skintastic for KidsR) to 100% (MuskolR). Compared to the widespread use of the
product, there are relatively few cases of toxicity16 However, if used improperly,
ingested, or a very high concentration is used on children, especially repeatedly
over large skin surfaces, the potential for severe toxicity exists.17 DEET is formu-
lated with ethyl or isopropyl alcohol.
Toxicology
For many years, diethyltoluamide has been effective and generally well
tolerated as an insect repellent applied to human skin, although tingling, mild
irritation, and sometimes desquamation have followed repeated application. In
some cases, DEET has caused contact dermatitis and excerbation of pre-exist-
ing skin disease.18'19 It is very irritating to the eyes, but not corrosive.
Serious adverse effects have occurred when used under tropical condition,
when it was applied to areas of skin that were occluded during sleep (mainly
the antecubital and popliteal fossae). Under these conditions, the skin became
red and tender, then exhibited blistering and erosion, leaving painful weeping
denuded areas that were slow to heal. Severe scarring occasionally resulted
from some of these severe reactions.20
DEET is efficiently absorbed across the skin and by the gut. Blood concen-
trations of about 0.3 mg/dL have been reported several hours after dermal
application in the prescribed fashion.17 The amount absorbed increases as the
concentration of DEET rises. In addition, many commercial formulations are
prepared with ethanol as a solvent, which further increases absorption.21 Toxic
encephalopathic reactions have apparently occurred in rare instances following
dermal application, mainly in children who were intensively treated.22'23'24The
more frequent cause of systemic toxicity has been ingestion: deliberate in adults
and accidental in young children.16'17
80 OTHER INSECTICIDES
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Manifestations of toxic encephalopathy have been behavioral disorders in-
cluding headache, restlessness, irritability, ataxia, rapid loss of consciousness,
hypotension, and seizures. Some cases have shown flaccid paralysis and areflexia.
Deaths have occurred following very large doses.16-17-22 Blood levels of DEET
found in fatal systemic poisonings have ranged from 168 to 240 mg per liter.17
Interpretation of DEET toxicity in some fatal cases has been complicated by
effects of simultaneously ingested ethanol, tranquilizers, and other drugs. One
well-documented case of anaphylactic reaction to DEET has been reported.
One fatal case of encephalopathy in a child heterozygous for ornithine car-
bamoyl transferase deficiency resembled Reyes syndrome, but the postmortem
appearance of the liver was not characteristic of the syndrome.
Discretion should be exercised in recommending DEET for persons who have
acne, psoriasis, an atopic predisposition, or other chronic skin condition. It should
not be applied to any skin area that is likely to be opposed to another skin surface
for a significant period of time (antecubital and popliteal fossae, inguinal areas) ,22
Great caution should be exercised in using DEET on children. Avoid re-
peated application day after day. Applications should be limited to exposed
areas of skin, using as little repellent as possible and washing off after use. Do
not apply to eyes and mouth and, with young children, do not apply to their
hands. Low concentrations (10% or below) are effective and may be preferred
in most situations. There are formulations labeled for children that have
concentrations of 5 to 6.5% DEET25 If continuous repellent protection is
necessary, DEET should be alternated with a repellent having another active
ingredient. If headache or any kind of emotional or behavioral change occurs,
use of DEET should be discontinued immediately.
Confirmation of Poisoning
Methods exist for measurement of DEET in blood and tissues and of me-
tabolites in urine, but these are not widely available.
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of
the eye with copious amounts of clean water or saline. If irritation persists,
specialized medical treatment should be obtained. Topical steroids and oral
antihistamines have been used for severe skin reactions that occasionally
follow application of DEET21
2. Gastrointestinal decontamination. If a substantial amount of DEET
has been ingested within an hour of treatment, gastrointestinal decontami-
nation should be considered as outlined in Chapter 2. Induced emesis is
OTHER INSECTICIDES 81
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usually considered contraindicated in these poisonings due to the rapid
onset of seizures.
3. Seizures. Treatment is primarily supportive, with control of seizures by
anticonvulsants, as outlined in Chapter 2. Persons surviving poisoning by in-
gestion of DEET have usually recovered within 36 hours or less.16'17
FLUORIDES
Sodium fluoride is a crystalline mineral once widely used in the United
States for control of larvae and crawling insects in homes, barns, warehouses,
and other storage areas. It is highly toxic to all plant and animal life. The only
remaining use permitted is for wood treatement
Sodium fluosilicate (sodium silico fluoride) has been used to control ec-
toparasites on livestock, as well as crawling insects in homes and work build-
ings. It is approximately as toxic as sodium fluoride. All uses in the U.S. have
been cancelled.
Sodium fluoaluminate (Cryolite) is a stable mineral containing fluoride. It
is used as an insecticide on some vegetables and fruits. Cryolite has very low
water solubility, does not yield fluoride ion on decomposition, and presents
very little toxic hazard to mammals, including humans.
Hydrofluoric acid is an important industrial toxicant, but is not used as a
pesticide. Sulfuryl fluoride is discussed in Chapter 16, Fumigants.
Toxicology
Sodium fluoride and fluosilicate used as insecticides present a serious haz-
ard to humans because of high inherent toxicity, and the possibility that chil-
dren crawling on floors of treated dwellings will ingest the material.
Absorption across the skin is probably slight, and methods of pesticide use
rarely include a hazard of inhalation, but uptake of ingested fluoride by the gut
is efficient and potentially lethal. Excretion is chiefly in the urine. Within the
first 24 hours of intoxication, renal clearance of fluoride from the blood is
rapid. However, patients go on to continue to excrete large amounts of fluoride
for several days. This is thought to be due to a rapid binding of fluoride to a
body store, probably bone. The subsequent release of fluoride from bone is
gradual enough not to cause a recurrence of toxicity26'27 Large loads of ab-
sorbed fluoride may potentially poison renal tubule cells, resulting in acute
renal failure. Children will have greater skeletal uptake of fluoride than adults,
therefore limiting the amount the kidney needs to handle. Despite this, chil-
dren are still at great risk because of their smaller body mass compared to adults
in relation to the amount ingested.27
82 OTHER INSECTICIDES
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The toxic effects of fluoride in mammals are multiple, and all may threaten
life.The primary effects from fluoride result from an inhibition of critical intra-
cellular enzymes and the direct effect on ionized calcium in extra-cellular fluid.
Hypocalcemia commonly occurs.26'28-29-30
Ingested fluoride is transformed in the stomach to hydrofluoric acid, which
has a corrosive effect on the epithelial lining of the gastrointestinal tract.Thirst,
abdominal pain, vomiting, and diarrhea are usual symptoms. Hemorrhage in
the gastric mucosa, ulceration, erosions, and edema are common signs.31
Absorbed fluoride ion reduces extracellular fluid concentrations of
calcium and magnesium. Hypocalcemia sometimes results in tetany.30 Cardiac
arrhythmia and shock are often prominent features of severe poisoning.
Hypotension and severe arrhythmia, sometimes progressing to ventricular
fibrillation, may also occur.26-32 These probably result from combinations of
effects of fluid and electrolyte disturbances including hyperkalemia32 and direct
actions of fluoride on heart and vascular tissues. Fluoride may directly affect the
central nervous system, resulting in headache, muscle weakness, stupor,
convulsions, and coma.26'27'28 Respiratory failure and ventricular arrythmias are
common causes of death.26-27
Confirmation of Poisoning
A population drinking water with a concentration of 1 mg per liter will
have a plasma inorganic fluoride concentration between 0.01 and 0.03 mg per
liter28 and rarely above 0.10 mg per liter. In fatal cases of poisoning, plasma
levels of 3.5 mg per liter and higher have been recorded, although survival has
been reported in patients with levels as high as 14 mg per liter.26-28
Treatment: Fluoride Toxicosis
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
2. Gastrointestinal decontamination. If sodium fluoride or sodium
fluosilicate has been ingested, consider gastric decontamination as outlined in
Chapter 2.
If the victim is obtunded or if vomiting precludes oral administration, the
airway should be protected by endotracheal intubation, then the stomach should
be gently intubated and lavaged with several ounces of one of the liquids named
below. Activated charcoal is not likely to be of use because it does not bind the
fluoride ion well.
OTHER INSECTICIDES 83
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3. Calcium and magnesium. If the victim is fully alert, and if vomiting does
not totally prevent swallowing of a neutralizing agent, prompt oral administra-
tion of milk, calcium gluconate, or magnesium citrate will precipitate
fluoride ion in the gut and therefore may be life-saving.The milk provides the
calcium ions that will bind to fluoride, thereby reducing absorption. Magne-
sium-based antacids have also been used to neutralize the acid and facilitate the
production of poorly absorbed salts.26 There are no data on the optimum
amounts to be administered.
4. Blood analysis. A blood specimen should be drawn for serum electrolyte
analysis for sodium, potassium, calcium, magnesium, fluoride, and bicarbon-
ate capacity. Blood should also be drawn to type and cross match for blood
transfusion.
5. Intravenous fluids (initially 5% dextrose in 0.9% saline) should be started
to combat dehydration, shock, and metabolic acidosis. Fluid balance should be
monitored closely to forestall fluid overload if renal failure occurs. If metabolic
acidosis is detected, sodium bicarbonate should be administered to keep the
urine alkaline as this may hasten excretion.27 Intravenous fluids must be stopped
if anuria or oliguria (less than 25-30 mL per hour) develops.
6. Hemodialysis should be reserved for compromised renal function.26
7. Monitor cardiac status by continuous electrocardiography. Ventricular
arrhythmia may necessitate DC cardioversion.
S.Tetany. If overt or latent tetany occurs, or if hypocalcemia is demonstrated,
or if it appears likely that a significant amount of fluoride has been absorbed,
administer 10 mL of 10% calcium gluconate intravenously, at no more than
1 mL per minute.
Dosage of Calcium Gluconate:
Supplied as 100 mg/mL (10% solution)
Adults and children over 12years: 10 mL of 10% solution, given slowly,
intravenously. Repeat as necessary.
Children under 12 years: 200-500 mg/kg/24 hr divided Q6 hr. For
cardiac arrest, 100 mg/kg/dose. Repeat dosage as needed.
9. Oxygen by mask should be administered for hypotension, shock, cardiac
arrhythmia, or cyanosis. Shock may require administration of plasma or blood.
84 OTHER INSECTICIDES
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10. Acid Burns. Since these compounds can cause severe acid burns to the
esophagus and stomach, patients should be referred for surgical evaluation and
endoscopy. If burns are documented, treatment for acid burns should be con-
tinued by a surgeon or gastroenterologist.
Treatment: Sodium Fluoaluminate (Cryolite)
Cryolite is much less toxic than other fluorides. If a very large amount has
been ingested, it may be appropriate to measure serum calcium to insure that
hypocalcemia has not occurred. If so, intravenous 10% calcium gluconate would
be indicated (see 8 above). It is unlikely that treatment for fluoride toxicity
would be necessary following ingestion of sodium fluoaluminate.
HALOAROMATIC SUBSTITUTED UREAS
Diflubenzuron is a haloaromatic substituted urea which controls insects by
impairing chitin deposition in the larval exoskeleton. It is formulated in wet-
table powders, oil dispersible concentrate, and granules for use in agriculture
and forestry, for aerial application against gypsy moth, and in settings where fly
populations tend to be large, such as feedlots. Teflubenzuron is another
haloaromatic substituted urea insecticide with similar toxicologic properties.
Toxicology
There is limited absorption of diflubenzuron across the skin and intestinal
lining of mammals, after which enzymatic hydrolysis and excretion rapidly
eliminate the pesticide from tissues. Irritant effects are not reported and sys-
temic toxicity is low. Methemoglobinemia is a theoretical risk from chloraniline
formed hydrolytically, but no reports of this form of toxicity have been re-
ported in humans or animals from diflubenzuron exposure.Teflubenzuron also
shows low systemic toxicity.
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, obtain
specialized medical treatment. Sensitization reactions may require steroid therapy.
2. Gastrointestinal decontamination. If large amounts of propargite have
been ingested and the patient is seen within an hour, consider gastrointestinal
decontamination. For small ingestions, consider oral administration of activated
charcoal and sorbitol.
OTHER INSECTICIDES 85
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METHOPRENE
Methoprene is a long chain hydrocarbon ester active as an insect growth
regulator. It is effective against several insect species. Formulations include slow-
release briquets, sprays, foggers, and baits.
Toxicology
Methoprene is neither an irritant nor a sensitizer in humans or laboratory
animals. Systemic toxicity in laboratory animals is very low. No human poi-
sonings or adverse reactions in exposed workers have been reported.
Treatment
1. Skin decontamination. Wash contaminated skin with soap and water.
Flush contamination from eyes with copious amounts of clean water or saline.
If irritation persists, medical attention must be obtained.
2. Gastrointestinal decontamination. If a very large amount of methoprene
has been ingested, oral administration of charcoal may be considered.
PROPARGITE
Propargite is an acaricide with residual action. Formulations are wettable
powders and emulsifiable concentrates.
Toxicology
Propargite exhibits very little systemic toxicity in animals. No systemic
poisonings have been reported in humans. However, many workers having
dermal contact with this acaricide, especially during the summer months, have
experienced skin irritation and possibly sensitization in some cases.33 Eye irri-
tation has also occurred. For this reason, stringent measures should be taken to
prevent inhalation or any skin or eye contamination by propargite.
Confirmation of Poisoning
There is no readily available method for detecting absorption of propargite.
86 OTHER INSECTICIDES
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Treatment
Treatment of contamination and ingestions should proceed essentially as
outlined for haloaromatic substituted urea.
PYRETHROIDS
These modern synthetic insecticides are similar chemically to natural pyre-
thrins, but modified to increase stability in the natural environment. They are
now widely used in agriculture, in homes and gardens, and for treatment of
ectoparasitic disease.
Pyrethroids are formulated as emulsifiable concentrates, wettable powders,
granules, and concentrates for ultra low volume application.They may be com-
bined with additional pesticides (sometimes highly toxic) in the technical product
or tank-mixed with other pesticides at the time of application. AASTAR (dis-
continued 1992), for instance, was a combination of flucythrinate and phorate.
Phorate is a highly toxic organophosphate. Nix and Elimite are permethrin
creams applied to control human ectoparasites.
Toxicology
Certain pyrethroids exhibit striking neurotoxicity in laboratory animals when
administered by intravenous injection, and some are toxic by the oral route. How-
ever, systemic toxicity by inhalation and dermal absorption is low. Although lim-
ited absorption may account for the low toxicity of some pyrethroids, rapid
biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is
probably the major factor responsible for this phenomenon.34 Most pyrethroid
metabolites are promptly excreted, at least in part, by the kidney.
The most severe, although more uncommon, toxicity is to the central ner-
vous system. Seizures have been reported in severe cases of pyrethroid intoxica-
tion. Of 573 cases reviewed in China, there were 51 cases with disturbed
consciousness and 34 cases with seizures. Of those, only 5 were from occupa-
tional exposure.35 Seizures are more common with exposure to the more toxic
cyano-pyrethroids, which include fenvalerate, flucythrinate, cypermethrin,
deltapermethrin, and fluvalinate.34 There are no reports in the literature of sei-
zures in humans from exposure to permethrin.
Apart from central nervous system toxicity, some pyrethroids do cause dis-
tressing paresthesias when liquid or volatilized materials contact human skin.
Again, these symptoms are more common with exposure to the pyrethroids
whose structures include cyano-groups.34 Sensations are described as stinging,
burning, itching, and tingling, progressing to numbness.35<36<37 The skin of the
face seems to be most commonly affected, but the face, hands, forearms, and
neck are sometimes involved. Sweating, exposure to sun or heat, and applica-
OTHER INSECTICIDES 87
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tion of water enhance the disagreeable sensations. Sometimes the effect is noted
within minutes of exposure, but a 1-2 hour delay in appearance of symptoms is
more common.36'37Sensations rarely persist more than 24 hours. Little or no
inflammatory reaction is apparent where the paresthesia are reported; the effect
is presumed to result from pyrethroid contact with sensory nerve endings in
the skin.The paresthetic reaction is not allergic in nature, although sensitization
and allergic responses have been reported as an independent phenomenon with
pyrethroid exposure. Neither race, skin type, nor disposition to allergic disease
affects the likelihood or severity of the reaction.
Persons treated with permethrin for lice or flea infestations sometimes ex-
perience itching and burning at the site of application, but this is chiefly an
exacerbation of sensations caused by the parasites themselves, and is not typical
of the paresthetic reaction described above.
Other signs and symptoms of toxicity include abnormal facial sensation, diz-
ziness, salivation, headache, fatigue, vomiting, diarrhea, and irritability to sound
and touch. In more severe cases, pulmonary edema and muscle fasciculations can
develop.35 Due to the inclusion of unique solvent ingredients, certain formula-
tions of fluvalinate are corrosive to the eyes. Pyrethroids are not cholinesterase
inhibitors. However, there have been some cases in which pyrethroid poisoning
has been misdiagnosed as organophosphate poisoning, due to some of the similar
presenting signs, and some patients have died from atropine toxicity35
Treatment
1. Skin decontamination. Wash skin promptly with soap and water as out-
lined in Chapter 2. If irritant or paresthetic effects occur, obtain treatment by a
physician. Because volatilization of pyrethroids apparently accounts for pares-
thesia affecting the face, strenuous measures should be taken (ventilation, pro-
tective face mask and hood) to avoid vapor contact with the face and eyes.
Vitamin E oil preparations (dL-alpha tocopheryl acetate) are uniquely effective
in preventing and stopping the paresthetic reaction.37'38They are safe for appli-
cation to the skin under field conditions. Corn oil is somewhat effective, but
possible side effects with continuing use make it less suitable. Vaseline is less
effective than corn oil. Zinc oxide actually worsens the reaction.
2. Eye contamination. Some pyrethroid compounds can be very corrosive
to the eyes. Extraordinary measures should be taken to avoid eye contamina-
tion. The eye should be treated immediately by prolonged flushing of the eye
with copious amounts of clean water or saline. If irritation persists, obtain pro-
fessional ophthalmologic care.
3. Gastrointestinal decontamination. If large amounts of pyrethroids, espe-
cially the cyano-pyrethroids, have been ingested and the patient is seen soon
OTHER INSECTICIDES
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after exposure, consider gastrointestinal decontamination as outlined in Chap-
ter 2. Based on observations in laboratory animals34 and humans,35 large ingestions
of allethrin, cismethrin, fluvalinate, fenvalerate, or deltamethrin would be the
most likely to generate neurotoxic manifestations.
If only small amounts of pyrethroid have been ingested, or if treatment
has been delayed, oral administration of activated charcoal and cathartic prob-
ably represents optimal management. Do not give cathartic if patient has
diarrhea or an ileus.
4. Other treatments. Several drugs are effective in relieving the pyrethroid
neurotoxic manifestations observed in deliberately poisoned laboratory animals,
but none has been tested in human poisonings. Therefore, neither efficacy nor
safety under these circumstances is known. Furthermore, moderate neurotoxic
symptoms and signs are likely to resolve spontaneously if they do occur.
5. Seizures. Any seizures should be treated as outlined in Chapter 2.
SULFUR
Elemental sulfur is an acaricide and fungicide widely used on orchard,
ornamental, vegetable, grain, and other crops. It is prepared as dust in various
particle sizes and applied as such, or it may be formulated with various minerals
to improve flowability, or applied as an aqueous emulsion or wettable powder.
Toxicology
Elemental sulfur is moderately irritating to the skin and is associated with
occupationally related irritant dermatitis.39 Airborne dust is irritating to the
eyes and the respiratory tract. In hot sunny environments, there may be some
oxidation of foliage-deposited sulfur to gaseous sulfur oxides, which are very
irritating to the eyes and respiratory tract.
Ingested sulfur powder induces catharsis, and has been used medicinally
(usually with molasses) for that purpose. Some hydrogen sulfide is formed in
the large intestine and this may present a degree of toxic hazard.The character-
istic smell of rotten eggs may aid in the diagnosis. An adult has survived inges-
tion of 200 grams.40
Ingested colloidal sulfur is efficiently absorbed by the gut and is promptly
excreted in the urine as inorganic sulfate.
OTHER INSECTICIDES 89
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Treatment
1. Skin decontamination. Wash skin with soap and water. Contamination of
the eyes should be removed by prolonged flushing with clean saline or water. If
eye irritation persists, obtain ophthamologic care.
2. Gastrointestinal decontamination. Unless an extraordinary amount of
sulfur (several grams) has been ingested shortly prior to treatment, there is
probably no need for gastrointestinal decontamination. Adsorbability of sulfur
on activated charcoal has not been tested.
The most serious consequence of sulfur ingestion is likely to be that of
catharsis, resulting in dehydration and electrolyte depletion, particularly in chil-
dren. If diarrhea is severe, oral or intravenous administration of glucose and/or
electrolyte solutions may be appropriate.
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toxicity in a series of 784 boric acid ingestions. Am JEmerg Med 1988;6(3):209- 13.
2. Restuccio A, Mortensen ME, and Kelley MT. Fatal ingestion of boric acid in an adult. Am J
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1985-1989. ClinToxicol 1994;32:1.
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taining insect repellents. JAMA 1987;258:1509.
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19. Wantke B, Bocke M, Hemmer W, et al. Generalized urticaria induced by a diethyltoluamide-
containing insect repellent in a child. Contact Dermatitis 1996;35(3): 186.
20. Reuveni H.andYagupsky B. Diethyltoluamide-containing insect repellent: Adverse effects in
worldwide use. Arch Dermatol 1982;! 18:582.
21. Stinecipher J and Shaw J. Bercutaneous permeation of N,N-diethyl-m-toluamide (DEBT)
from commercial mosquito repellents and the effect of solvent. / Toxicol Environ Health
1997;52:119.
22. Bipscomb JW, Kramer JE, and Beikin JB. Seizure following brief exposure to the insect
repellent N,N-diethyl-m-toluamide. Ann Emerg Med 1992;21(3):315-17.
23. Zadikoff CM. Toxic encephalopathy associated with use of insect repellent. / Pediatr
1979:95:140-2.
24. Bronczuk de Garbino J and Baborda A.Toxicity of an insect repellent: N,N- diethyltoluamide.
Vet Hum Toxicol 1983;25:422-3.
25. Hebert AA and Carlton S. Getting bugs to bug off: A review of insect repellents. Contemp
Pediatr 1998; 15:85-95.
26. YolkenR.Konecny Band McCarthy B. Acute fluoride poisoning. Pediatrics 1976;58(l):90-3.
27. Heifetz SB and Horowitz HS. Amounts of fluoride in self-administered dental products:
Safety considerations for children. Pediatrics 1986;77(6):876-82.
28. Gessner BD, Beler M, Middaugh JB, and Whitford GM. Acute fluoride poisoning from a
public water system. NewEngl JMed 1994;330(2):95-9.
29. Swanson B, Bilandrinos DT, Shevlin JM, and Willett JR. Death from accidental ingestion of
an ammonium and sodium bifluoride glass etching compound. Vet Hum Toxicol 1993; 35 (4): 351.
30. Harchelroad B and Goetz C. Systemic fluoride intoxication with leukocytosis and pyrexia.
Vet Hum Toxicol 1993;35(4):351.
31. Spak CJ, Sjostedt S, Eleborg B, et al. Tissue response of gastric mucosa after ingestion of
fluoride. Br Med J 1989;298:1686-7.
32. Baltazar RD, Mower MM, Reider R, et al. Acute fluoride poisoning leading to fatal hyper-
kalemia. Chest 1980;78:660.
33. Saunders BD, Ames RG, Knaak JB, et al. Outbreak of omite-cr-induced dermatitis among
orange pickers inTulare County, California. / Occup Med 1987;29:409-13.
34. Dorman DC and BeasleyVR. Neurotoxicology of pyrethrin and the pyrethroid insecticides.
VetHumTaxto/1991;33(3):238-43.
35. He B, Wang S, Bui B, et al. Clinical manifestations and diagnosis of acute pyrethroid poison-
ing. ArchToxicol 1989;63:54-8.
36. Tucker SB and Blannigan SA. Cutaneous effects from occupational exposure to fenvalerate.
Arch Toxicol 1983;54:195-202.
37. Blannigan SA,Tucker SB, Key MM, et al. Synthetic pyrethroid insecticides: Adermatological
evaluation. Br J Ind Med 1985;42:363-72.
OTHER INSECTICIDES 91
-------
38. Tucker SB, Flannigan SA, and Ross CE. Inhibitions of cutaneous paresthesia resulting from
synthetic pyrethroid exposure. Int JDermatol 1984;10:686-9.
39. O'Malley MA. Skin reactions to pesticides. Occup Med 1997; 12:327-45.
40. Schwartz SM, Carroll HM, and Scharschmidt LA. Sublimed (inorganic) sulfur ingestion - A
cause of life-threatening metabolic acidosis with a high anion gap. Arch Intern Med
1986;146:1437-8.
92 OTHER INSECTICIDES
-------
Section III
HERBICIDES
-------
CHAPTER 9
HIGHLIGHTS
Signs and Symptoms:
Irritating to skin and
mucous membranes
Vomiting, diarrhea,
headache, confusion,
bizarre or aggressive
behavior, peculiar odor on
breath
Metabolic acidosis, renal
failure, tachycardia
Treatment:
Washing, Gl
decontamination
Administer IV
Forced alkaline diuresis
Chlorophenoxy Herbicides
Chlorophenoxy compounds are sometimes mixed into commercial fertilizers
to control growth of broadleaf weeds. Several hundred commercial products
contain Chlorophenoxy herbicides in various forms, concentrations, and com-
binations. In some cases, the same name is used for products with different
ingredients. The exact composition must therefore be determined from the
product label. Sodium, potassium, and alkylamine salts are commonly formu-
lated as aqueous solutions, while the less water-soluble esters are applied as
emulsions. Low molecular weight esters are more volatile than the acids, salts,
or long-chain esters.
Toxicology
Some of the Chlorophenoxy acids, salts, and esters are moderately irritating
to skin, eyes, and respiratory and gastrointestinal linings. In a few individuals,
local depigmentation has apparently resulted from protracted dermal contact
with Chlorophenoxy compounds.
Chlorophenoxy compounds are well absorbed from the gastrointestinal
tract.1 They are less well absorbed from the lung. Cutaneous absorption appears
to be minimal.2 The compounds are not significantly stored in fat. Excretion
occurs almost entirely by way of urine. Apart from some conjugation of the
acids, there is limited biotransformation in the body.1'2 The compounds are
highly protein bound.2 The average residence half-life of 2,4-D in humans is
between 13 and 39 hours,1'3'4'5 while that of 2,4,5-T is about 24 hours. Excre-
tion is greatly enhanced in alkaline urine,4'5'6 and with a half-life as prolonged
as 70-90 hours with acidic urine.6 Half-life is also longer with large doses and
prolonged exposure.
Given in large doses to experimental animals, 2,4-D causes vomiting, diar-
rhea, anorexia, weight loss, ulcers of the mouth and pharynx, and toxic injury
to the liver, kidneys, and central nervous system. Myotonia (stiffness and inco-
ordination of hind extremities) develops in some species and is apparently due
to CNS damage: demyelination has been observed in the dorsal columns of the
cord, and EEC changes have indicated functional disturbances in the brains of
heavily-dosed experimental animals.
Ingestion of large amounts of Chlorophenoxy acids has resulted in severe
metabolic acidosis in humans. Such cases have been associated with electrocar-
CHLOROPHENOXY
94 HERBICIDES
-------
diographic changes, myotonia, muscle weakness, myoglobinuria, and elevated
serum creatine phosphokinase, all reflecting injury to striated muscle.
Chlorophenoxy acids are weak uncouplers of oxidative phosphorylation; there-
fore, extraordinary doses may produce hyperthermia from increased produc-
tion of body heat.5
In the manufacture of some of these herbicides, other more toxic sub-
stances can be formed at excessive temperatures. These include chlorinated
dibenzo dioxin (CDD) and chlorinated dibenzo furan (CDF). The 2,3,7,8-
tetra CDD form is extraordinarily toxic to multiple mammalian tissues; it is
formed only in the synthesis of 2,4,5-T Hexa-, hepta-, and octa-compounds
exhibit less systemic toxicity, but are the likely cause of chloracne (a chronic,
disfiguring skin condition) seen in workers engaged in the manufacture of
2,4,5-T and certain other chlorinated organic compounds.7 Although toxic
effects, notably chloracne, have been observed in manufacturing plant workers,
these effects have not been observed in formulators or applicators regularly
exposed to 2,4,5-T or other chlorophenoxy compounds. All uses of 2,4,5-T in
the U.S. have been cancelled.
The medical literature contains reports of peripheral neuropathy following
what seemed to be minor dermal exposures to 2,4-D8 It is not certain that
exposures to other neurotoxicants were entirely excluded in these cases. Single
doses of 5 mg/kg body weight of 2,4-D and 2,4,5-T have been administered to
human subjects without any adverse effects. One subject consumed 500 mg of
2,4-D per day for 3 weeks without experiencing symptoms or signs of illness.
Commercial Products
2,4-dichlorophenoxyacetic acid
(2,4-D)
2,4-dichlorophenoxypropionic
acid (2,4-DP)
dichlorprop
2,4-dichlorophenoxybutyric
acid (2,4-DB)
2,4,5-trichlorophenoxy acetic
acid (2,4,5-T)
MCPA
MCPB
mecoprop (MCPP)
2-methyl-3, 6 dichlorobenzoic
acid
Banvel
Dicamba
Signs and Symptoms of Poisoning
Chlorophenoxy compounds are moderately irritating to skin and mucous
membranes. Inhalation of sprays may cause burning sensations in the nasophar-
ynx and chest, and coughing may result. Prolonged inhalation sometimes causes
dizziness. Adjuvant chemicals added to enhance foliage penetration might ac-
count for the irritant effects of some formulations.
Manifestations of systemic toxicity of chlorophenoxy compounds are known
mainly from clinical experience with cases of deliberate suicidal ingestion of
large quantities. Most reports of fatal outcomes involve renal failure, acidosis,
electrolyte imbalance, and a resultant multiple organ failure.3'6'9 The agents most
often involved in these incidents have been 2,4-D and mecoprop. The toxic
effects of other chlorophenoxy compounds are probably similar but not identical.
Patients will present within a few hours of ingestion with vomiting, diar-
rhea, headache, confusion, and bizarre or aggressive behavior. Mental status
changes occur with progression to coma in severe cases.4'5'6 A peculiar odor is
often noticed on the breath. Body temperature may be moderately elevated,
but this is rarely a life-threatening feature of the poisoning. The respiratory
drive is not depressed. Conversely, hyperventilation is sometimes evident, prob-
CHLOROPHENOXY
HERBICIDES
95
-------
ably secondary to the metabolic acidosis that occurs. Muscle weakness and
peripheral neuropathy have been reported after occupational exposure.6 Con-
vulsions occur very rarely. With effective urinary excretion of the toxicant,
consciousness usually returns in 48-96 hours.4'5-6
As mentioned above, chlorophenoxy compounds cause significant meta-
bolic changes. Metabolic acidosis is manifest as a low arterial pH and bicarbon-
ate content. The urine is usually acidic. Skeletal muscle injury, if it occurs, is
reflected in elevated creatine phosphokinase, and sometimes myoglobinuria.
Moderate elevations of blood urea nitrogen and serum creatinine are com-
monly found as the toxicant is excreted. Cases of renal failure are reported,
often with an accompanying hyperkalemia or hypocalcemia that was thought
to result in the cardiovascular instability that led to death.3-9Tachycardia is com-
monly observed, and hypotension has also been reported.3-4-6T-wave flattening
has also been observed.5 Mild leukocytosis and biochemical changes indicative
of liver cell injury have been reported.
Myotonia and muscle weakness may persist for months after acute poison-
ing.5 Electromyographic and nerve conduction studies in some recovering pa-
tients have demonstrated a mild proximal neuropathy and myopathy.
Confirmation of Poisoning
Gas-liquid chromatographic methods are available for detecting
chlorophenoxy compounds in blood and urine. These analyses are useful in
confirming and assessing the magnitude of chlorophenoxy absorption. Poison-
ing characterized by unconsciousness has shown initial blood chlorophenoxy
concentrations ranging from 80 to more than 1000 mg per liter.4 Urine samples
should be collected as soon as possible after exposure because the herbicides
may be almost completely excreted in 24-72 hours under normal conditions.
Urine samples can also confirm overexposure. In a study of asymptomatic her-
bicide applicators, their urinary excretion of chlorophenoxy compounds rarely
exceeded 1-2 mg/L.10The half-life may be much longer in cases of intoxica-
tion depending on the extent of absorption and urine pH.
Analyses can be performed at special laboratories usually known to local poi-
son control centers. If the clinical scenario indicates that excessive exposure to
chlorophenoxy compounds has occurred, initiate appropriate treatment measures
immediately. Do not wait for chemical confirmation of toxicant absorption.
Treatment
1. Precautions. Individuals with chronic skin disease or known sensitivity to
these herbicides should either avoid using them or take strict precautions to
avoid contact (respirator, gloves, etc.).
CHLOROPHENOXY
96 HERBICIDES
-------
2. Respiratory protection. If any symptoms of illness occur during or fol-
lowing inhalation of spray, remove victim from contact with the material for at
least 2-3 days. Allow subsequent contact with chlorophenoxy compounds only
if effective respiratory protection is practiced.
3. Skin decontamination. Flush contaminating chemicals from eyes with
copious amounts of clean water for 10-15 minutes. If irritation persists, an
ophthalmologic examination should be performed.
4. Gastrointestinal decontamination. If substantial amounts of chlorophenoxy
compounds have been ingested, spontaneous emesis may occur. Gastric decon-
tamination procedures may be considered, as outlined in Chapter 2.
5. Intravenous fluids. Administer intravenous fluids to accelerate excretion of
the chlorophenoxy compound, and to limit concentration of the toxicant in
the kidney. A urine flow of 4-6 mL/minute is desirable. Intravenous saline/
dextrose has sufficed to rescue comatose patients who drank 2,4-D and mecoprop
several hours before hospital admission.
Caution: Monitor urine protein and cells, BUN, serum creatinine, serum
electrolytes, and fluid intake/output carefully to insure that renal function re-
mains unimpaired and that fluid overload does not occur.
6. Diuresis. Forced alkaline diuresis has been used successfully in management
of suicidal ingestions of chlorophenoxy compounds, especially when initiated
early.4'5'6 Alkalinizing the urine by including sodium bicarbonate (44-88 mEq
per liter) in the intravenous solution accelerates excretion of 2,4-D dramati-
cally and mecoprop excretion substantially. Urine pH should be maintained
between 7.6 and 8.8. Include potassium chloride as needed to offset increased
potassium losses: add 20-40 mEq of potassium chloride to each liter of intrave-
nous solution. It is crucial to monitor serum electrolytes carefully, especially
potassium and calcium.
There may possibly be some hazard to the kidneys when urine concentra-
tions of toxicant are very high, so the integrity of renal function and fluid
balance should be monitored carefully as the chlorophenoxy compound is ex-
creted. Renal failure has occurred in patients with severe intoxication during
alkaline diuresis. In one case, the diuresis was begun 26 hours after ingestion,6
and the other two were initiated a couple days after poisoning.3'9
7. Hemodialysis is not likely to be of significant benefit in poisonings by
chlorophenoxy compounds. It has been used in four patients who survived
intoxication.11 However, given the highly protein-bound nature of these herbi-
cides and lack of any other evidence, hemodialysis is not recommended.2
CHLOROPHENOXY
HERBICIDES 97
-------
8. Follow-up clinical examination should include electromyographic and
nerve conduction studies to detect any neuropathic changes and neuromuscu-
lar junction defects.
General Chemical Structure
Cl (orCH3)
References
1. Kohli JD, Khanna RN, Gupta BN, et al. Absorption and excretion of 2,4-dichlorophenoxy-
acetic. Xenobiotica 1974;4(2):97-100.
2. Arnold EK, Beasley MS, and Beasley VR. The pharmacokinetics of chlorinated phenoxy
acid Herbicides:A literature review. Vet Hum Toxicol 1989;31(2):121-5.
3. KellerT, Skopp G,Wu M, et al. Fatal overdose of 2,4-dichlorophenoxyacetic acid (2,4-D).
Forensic Sci Int 1994;65:13-8.
4. Friesen EG, Jones GR, andVaughan D. Clinical presentation and management of acute 2,4-
D oral ingestion. Drug Saf 1990;5(2): 155-90.
5. Prescott LF, Park J, and Darrien I.Treatment of severe 2,4-D and mecoprop intoxication
with alkaline diuresis. En journal of Clinical Pharmacology 1979;7:111-116.
6. Flanagan RJ, Meredith TJ, Ruprah M, et al. Alkaline diuresis for acute poisoning with
chlorophenoxy herbicides and ioxynil. Lancet 1990;335:454-8.
7. Poskitt LB, Duffill MB, and Rademaker M. Chloracne, palmoplantar keratoderma and local-
ized scleroderma in a weed sprayer. Clin and Exp Dermatol 1994; 19:264-7.
8. O'Reilly JE Prolonged coma and delayed peripheral neuropathy after ingestion of
phenoxyacetic acid weedkillers. Postgrad Med Journal 1984;60:76-7.
9. Kancir CB, Anderson C, and Olesen AS. Marked hypocalcemia in a fatal poisoning with
chlorinated phenoxy acid derivatives. Clin Toxicol 26(3&4):257-64.
10. Kolmodin-Hedman B, Hoglund S, and Akerblom M. Studies on phenoxy acid herbicides, I,
Field study: Occupational exposure to phenoxy acid herbicides (MCPA, dichlorprop,
mecoprop,and 2,4-D) in agriculture. ArchToxicol 1983;54:257-65.
11. Durakovic Z, Durakovic A, Durakovic S, et al. Poisoning with 2,4- dichlorophenoxyacetic
acid treated by hemodialysis. ArchToxicol 1992;66:518-21.
CHLOROPHENOXY
98 HERBICIDES
-------
CHAPTER 10
Pentachlorophenol
Pentachlorophenol (PCP) is currently registered in the United States only as
a restricted use pesticide for use as a wood preservative. PCP has been used as
an herbicide, algacide, defoliant, wood preservative, germicide, fungicide, and
molluscicide.1 As a wood preservative, it is commonly applied as a 0.1% solu-
tion in mineral spirits, No. 2 fuel oil, or kerosene. It is used in pressure treat-
ment of lumber at 5% concentration. Weed killers have contained higher
concentrations.
Pentachlorophenol volatilizes from treated wood and fabric. It has a signifi-
cant phenolic odor, which becomes quite strong when the material is heated.
Excessively treated interior surfaces may be a source of exposure sufficient to
cause irritation of eyes, nose, and throat.
Technical PCP contains lower chlorinated phenols (4-12%) plus traces of
chlorobenzodioxins, chlorobenzofurans, and chlorobenzenes. Incomplete com-
bustion of PCP-treated wood may lead to the formation of these compounds.
Toxicology
PCP is readily absorbed across the skin, the lungs, and the gastrointestinal
lining. In animals, the dermal LD50 is of the same order of magnitude as the
oral. With acute exposure it is rapidly excreted, mainly in the urine, as un-
changed PCP and as PCP glucuronide. In chronic exposures, the elimination
half-life has been reported to be very long, up to 20 days.2 In another study,
three volunteers took consecutive oral doses of PCP, and a half-life of 20 days
was also found.The long half-life was attributed to the low urinary clearance
because of high protein binding.3 In the blood, a large fraction of absorbed
PCP is protein-bound. It is widely distributed to other tissues in the body,
including kidney, heart, and adrenal glands.
At certain concentrations, PCP is irritating to mucous membranes and
skin. Contact dermatitis is common among workers having contact with PCP.
In a study of employees involved in the manufacture of PCP, chloracne was
found in 7% of the workers, and the risk was significantly higher among em-
ployees with documented skin contact compared to employees without skin
contact.4 Urticaria has also been reported as an uncommon response in ex-
posed persons.
HIGHLIGHTS
Absorbed by skin, lung, Gl
lining
Fatalities reported,
associated with intensive
exposure in hot
environments
Signs and Symptoms:
Irritation of the nose,
throat, and eyes
Hyperthermia, muscle
spasm, tremor, labored
breathing, and chest
tightness indicate serious
poisoning
Treatment:
No specific antidote
Control fever, replace fluids,
oxygen
Decontaminate eyes, skin,
hair, clothing
Monitor cardiac status,
control agitation
Contraindicated:
Salicylates for fever control
PENTACHLOROPHENOL 99
-------
Commercial Products
Chlorophen
PCP
Penchlorol
Penta
Pentacon
Penwar
Sinituho
The sodium salt is sodium
pentachlorophenate.
The primary toxicological mechanism is increased cellular oxidative me-
tabolism resulting from the uncoupling of oxidative phosphorylation. Heat pro-
duction is increased and leads to clinical hyperthermia.This clinical state may
mimic the signs and symptoms found in hyperthyroidism. Internally, large doses
are toxic to the liver, kidneys, and nervous system.
Based on laboratory experimentation on animals, PCP has been reported
to have fetotoxic and embrotoxic properties and to bind to various hormone
receptors.5'6 Epidemiological evidence suggests exposed persons may be at risk
for miscarriages, reduced birth weight, and other malformations.7-8
Albuminuria, glycosuria, aminoaciduria, and elevated BUN reflect renal
injury. Liver enlargement, anemia, and leukopenia have been reported in some
intensively exposed workers. Elevated serum alkaline phosphatase, AST, and
LDH enzymes indicate significant insult to the liver, including both cellular
damage and some degree of biliary obstruction.
Signs and Symptoms of Poisoning
The most common effects of airborne PCP include local irritation of the
nose, throat, and eyes, producing a stuffy nose, scratchy throat, and tearing.
Dermal exposure is also common and may lead to irritation, contact dermatitis,
or more rarely, diffuse urticaria or chloracne. Individual cases of exfoliative
dermatitis of the hands and diffuse urticaria and angioedema of the hands have
been reported in intensively exposed workers. Several infant deaths occurred in
a nursery where a PCP-containing diaper rinse had been used.
Severe poisoning and death have occurred as a result of intensive PCP
exposure. Acute poisoning occurs with systemic absorption which can occur
by any route of sufficient dosage. Most occupational poisonings occur through
dermal contact. Hyperthermia, muscle spasm, tremor, labored breathing, and
chest tightness indicate serious poisoning. The patient may also complain of
abdominal pain, and exhibit vomiting, restlessness, and mental confusion. Ta-
chycardia and increased respiratory rate are usually apparent. Other commonly
reported signs and symptoms of systemic poisoning include profuse sweating,
weakness, dizziness, anorexia, and intense thirst. Workers exposed over long
periods may experience weight loss.
Most adult fatalities have occurred in persons working in hot environ-
ments where hyperthermia is poorly tolerated. Cases of aplastic anemia and
leukemia have been reported which were associated temporally with PCP ex-
posure. Causal relationships in these cases were not established.9 Peripheral neu-
ropathies have also been reported in some cases of long-term occupational
exposure; however, a causal relationship has not been supported by longitudi-
nal studies.10
100 PENTACHLOROPHENOL
-------
Confirmation of Poisoning
If poisoning is strongly suspected on the basis of exposure, symptoms, and
signs, do not postpone treatment until diagnosis is confirmed.
PCP can be measured in blood, urine, and adipose tissue by gas-liquid
chromatography. Plasma levels can be much greater than urine levels (ratio of
blood to urine is 1.0 to 2.5) so care must be taken in interpreting results.10'11
There is no clear-cut determination of what constitutes an abnormally high
level of PCP, and there is great variability among different references. Most
information on the extent of serum levels in relation to toxicity is based on
individual cases or small series of patients. Reports exist of asymptomatic in-
fants with serum levels as high as 26 parts per million (ppm).11'12 However, most
reports of non-occupational exposure in the general public involve levels in the
parts per billion range.1-13"15 Food is probably the main source of this nano-
gram-level dosage.1 Serum levels among occupationally exposed persons often
exceed 1 ppm.1 A report of a lethal case describes a plasma level of 16 ppm,16
but most cases generally involve serum levels in the range of 100 ppm or
higher.11-17 It is reasonable to assume that levels greater than 1 ppm are consis-
tent with an unusual exposure and that levels approaching 100 ppm are cause
for great concern.
Treatment
1. Supportive treatment and hyperthermia control. There is no specific
antidote to the poisoning; therefore treatment is supportive in nature including
oxygen, fluid replacement, and most importantly, fever control.
Reduce elevated body temperature by physical means. Administer sponge
baths and use fans to increase evaporation.18 In fully conscious patients, admin-
ister cold, sugar-containing liquids by mouth as tolerated. Cooling blankets and
ice packs to body surfaces may also be used.
Antipyretic therapy with salicylates is strongly contraindicated as salicy-
lates also uncouple oxidative phosphorylation. Other antipyretics are thought
to be of no use because of the peripherally mediated mechanism of hyperther-
mia in poisoning of this nature. Neither the safety nor the effectiveness of the
other antipyretics has been tested.
Administer oxygen continuously by mask to minimize tissue anoxia. Un-
less there are manifestations of cerebral or pulmonary edema or of inadequate
renal function, administer intravenous fluids to restore hydration and support
physiologic mechanisms for heat loss and toxicant disposition. Monitor serum
electrolytes, adjusting IV infusions to stabilize electrolyte concentrations. Fol-
low urine contents of albumin and cells, and keep an accurate hourly record of
intake/output to forestall fluid overload if renal function declines.
Caution: In the presence of cerebral edema and/or impaired renal func-
tion, intravenous fluids must be administered very cautiously to avoid increased
PENTACHLOROPHENOL 101
-------
intracranial pressure and pulmonary edema. Central monitoring of venous and
pulmonary wedge pressures may be indicated. Such critically ill patients should
be treated in an intensive care unit.
2. Skin decontamination. Flush the chemical from eyes with copious amounts
of clean water. Perform skin decontamination as described in Chapter 2.
3. Cardiopulmonary monitoring. In severe poisonings, monitor pulmo-
nary status carefully to insure adequate gas exchange, and monitor cardiac sta-
tus by EGG to detect arrhythmias. The toxicant itself and severe electrolyte
disturbances may predispose to arrhythmias and myocardial weakness.
4. Neurological. To reduce production of heat in the body, control agitation and
involuntary motor activity with sedation. Lorazepam or other benzodiazepines
should be effective, although use of these drugs in these poisonings has not been
reported. If lorazepam is chosen, administer slowly, intravenously.
Dosage of Lorazepam:
Adults: 2-4 mg/dose IV given over 2-5 minutes. Repeat if necessary
to a maximum of 8 mg in a 12-hour period.
Adolescents: Same as adult dose, except maximum dose is 4 mg.
Children under 12years: 0.05-0.10 mg/kg IV over 2-5 minutes. Re-
peat if necessary 0.05 mg/kg 10-15 minutes after first dose, with a
maximum dose of 4 mg.
Caution: Be prepared to assist pulmonary ventilation mechanically if
respiration is depressed, to intubate the trachea if laryngospasm occurs,
and to counteract hypotensive reactions.
5. Gastrointestinal decontamination. If PGP has been ingested in a quan-
tity sufficient to cause poisoning and the patient presents within one hour,
consider gastric decontamination as outlined in Chapter 2.
6. Nutrition. During convalescence, administer a high-calorie, high-vitamin
diet to restore body fat and carbohydrates. Discourage subsequent contact with
the toxicant for 4-8 weeks (depending on severity of poisoning) to allow full
restoration of normal metabolic processes.
102 PENTACHLOROPHENOL
-------
Chemical Structure
Cl
References
1. Jorens PG and Schepens PJC. Human pentachlorophenol poisoning. Hum Exp Toxicol
1993;479-95.
2. Kalman DA and Horstman SW Persistence of tetrachlorophenol and pentachlorophenol in
exposed woodworkers. JToxicol ClinToxicol 1983;20:343.
3. Uhl S, Schrnid P and Schlatter C. Pharmacokinetics of pentachlorophenol in man. Arch
Toxicol \986;58:182-6.
4. O'Malley MA, Carpenter AV, Sweeney MH, et al. Chloracne associated with employment in
the production of pentachlorophenol. Am ]Ind Med 1990;17:411-21.
5. Danzo BJ. Environmental xenobiotics may disrupt normal endocrine function by interfer-
ing with the binding of physiological ligands to steroid receptors and binding proteins.
Environ Health Perspect 1997:105:294-301.
6. Tran DQ.KlotzDM.Ladlie BL.et al. Inhibition of progesterone receptor activity in yeast by
synthetic chemicals. Biochem Biophys Res Commun 1996;229:518-23.
7. Dimich-Ward H, Hertzman C.Teschke K, et al. Reproductive effects of paternal exposure to
chlorophenate wood preservatives in the sawmill industry. Scand J Work Environ Health
1996;22:267-73.
8. DeMaeyer J, Schepens PJ, Jorens PG, andVerstaete R. Exposure to pentachlorophenol as a
possible cause of miscarriages. BrJ Obstet Gynaecol 1995;102:1010-1.
9. Roberts HJ.Aplastic anemia due to pentachlorophenol. NewEngl]Med 1981;305:1650-1.
10. Casarett LJ, Bevenue A.Yauger WL, and Whalen SA. Observations on pentachlorophenol in
human blood and urine. Am Ind HygAssoc J 1969;30:360-6.
11. Clayton GD and Clayton FE (eds). Patty's Industrial Hygiene and Toxicology, vol 2B, 4th ed.
New York: John Wiley & Sons, 1994, pp. 1605-13.
12. Robson AM, Kissane JM, Elvick WH, et al. Pentachclorophenol poisoning in a nursery for
newborn infants: Clinical features and treatment. /Pediatr 1969;75:309-16.
13. Gomez-Catalan J,To-Figueras J, Planas J, et al. Pentachlorophenol and hexachlorobenzene in
serum and urine of the population of Barcelona. Hum Toxicol 1987;6:397-400.
14. Wylie JA, Gabica J, Benson WW, and Yoder J. Exposure and contamination of the air and
employees of a pentachlorophenol plant, Idaho-1972. Pest Monit J 1975;9:150-3.
15. Wagner SL. Pentachlorophenol. In: Clinical Toxicology of Agricultural Chemicals. Corvallis,
OR: Oregon State University Press, 1981, pp. 131-7.
16. Wood S, Rom WN, White GL, and Logan DC. Pentachlorophenol poisoning. / Occup Med
1983:25:527-30.
17. Gray RE, Gilliland RD, Smith EE, et al. Pentachlorophenol intoxication: Report of a fatal
case, with comments on the clinical course and pathologic anatomy. Arch Environ Health
1985:40:161-4.
18. Graham BS, Lichtenstein MJ, Hinson JM, et al. Nonexertional heatstroke: Physiologic man-
agement and cooling in 14 patients. Arch Intern Med 1986; 146:87-90.
PENTACHLOROPHENOL 103
-------
CHAPTER 11
HIGHLIGHTS
Highly toxic herbicides
Affect hepatic, renal, and
nervous systems
Signs and Symptoms:
Sweating, thirst, fever,
headache, confusion,
malaise, and restlessness
Hyperthermia, tachycardia,
tachypnea in serious cases
Characteristic bright yellow
staining of skin and hair
often present with topical
exposure
Treatment:
No specific antidote
Replace oxygen and fluids,
control temperature
Decontaminate skin, hair,
clothing
Contraindicated:
Antipyretic therapy with
salicylates
Atropine
Nitrophenolic and
Nitrocresolic Herbicides
These highly toxic chemicals have many uses in agriculture worldwide, as her-
bicides (weed-killing and defoliation), acaricides, nematocides, ovicides, and
fungicides. Relatively insoluble in water, most technical products are dissolved
in organic solvents and formulated for spray application as emulsions. There are
some wettable powder formulations. Only dinocap continues to have active
registrations in the United States.
Toxicology
Nitroaromatic compounds are highly toxic to humans and animals with
LD5Qs in the range of 25 to 50 mg/kg.1 Most nitrophenols and nitrocresols are
well absorbed by the skin, gastrointestinal tract, or lung when fine droplets are
inhaled.2 Fatal poisonings have occurred as a result of dermal contamination;
more common is a moderate irritation of the skin and mucous membranes.
Nitrophenols and nitrocresols undergo some biotransformation in humans,
chiefly reduction (one nitro group to an amino group) and conjugation at the
phenolic site. Although nitrophenols and metabolites appear consistently in
the urine of poisoned individuals, hepatic excretion is probably the main route
of disposition. Elimination is slow with a documented half-life in humans be-
tween 5 and 14 days.1 Blood and tissue concentrations tend to increase pro-
gressively if an individual is substantially exposed on successive days.
The basic mechanism of toxicity is stimulation of oxidative metabolism in
cell mitochondria, by the uncoupling of oxidative phosphorylation.This leads
to hyperthermia, tachycardia, headache, malaise, and dehydration, and in time,
depletes carbohydrate and fat stores. The major systems prone to toxicity are
the hepatic, renal, and nervous systems. The nitrophenols are more active as
uncouplers than chlorophenols such as pentachlorophenol (described in chap-
ter 10). Hyperthermia and direct toxicity on the brain cause restlessness and
headache, and in severe cases, seizures, coma, and cerebral edema. The higher
the ambient temperature, such as in an outdoor agricultural environment, the
more difficult it is to dissipate the heat.1'2 Liver parenchyma and renal tubules
show degenerative changes. Albuminuria, pyuria, hematuria, and azotemia are
signs of renal injury.
NITROPHENOLS &
104 NITROCRESOLS
-------
Cataracts occur in laboratory animals given nitrophenols, and have oc-
curred in humans, both as a result of ill-advised medicinal use and as a conse-
quence of chronic, occupational exposure.3 Cataract formation is sometimes
accompanied by glaucoma.
Signs and Symptoms of Poisoning
Most patients present within a few hours of exposure with generalized
non-specific signs and symptoms including profuse sweating, thirst, fever, head-
ache, confusion, malaise, and restlessness.The skin may appear warm and flushed
as hyperthermia develops, along with tachycardia, and tachypnea, all of which
indicate a serious degree of poisoning. Apprehension, anxiety, manic behavior,
seizures, and coma reflect cerebral injury; seizures and coma signify an immedi-
ately life-threatening intoxication. Labored breathing and cyanosis are conse-
quences of the stimulated metabolism and tissue anoxia. Renal failure may
occur early in cases of severe exposure. Liver damage is first manifested by
jaundice, and cell death can occur within 48 hours and is dose-dependent.4
Death may occur within 24 to 48 hours after exposure in cases of severe poi-
soning.2 In cases of survival of severe poisoning, complete resolution of symp-
toms may be slow due to the toxicant's long half-life.1-5
A characteristic bright yellow staining of skin and hair is often present with
topical exposure and can be an important diagnostic clue to the clinician.1'2'5
Yellow staining of the sclerae and urine indicates absorption of potentially
toxic amounts. Weight loss occurs in persons continually exposed to relatively
low doses of nitrophenols or nitrocresols.1'3
Confirmation of Poisoning
If poisoning is probable, do not await confirmation before beginning treatment.
Save urine and blood specimens on ice at temperature below 20ฐ C in the event
confirmation is necessary later on. Unmetabolized nitrophenols and nitrocresols
can be identified spectrophotometrically, or by gas-liquid chromatography in the
serum at concentrations well below those that have been associated with acute
poisonings.The data on exposure and systemic levels of compounds in this group
are limited, and most reports specify the compound dinitro-ortho-cresol. In general,
blood levels of 10 mcg/dL or greater are usually seen when systemic toxicity is
evident.1'6 One fatal case occured with a level of 75 mcg/dL.6 Blood analysis is
useful in confirming the cause of poisoning. Monitoring of levels should be done
routinely during acute intoxication in order to establish a decay curve to determine
when therapy can be safely discontinued.
Commercial Products
dinitrocresol*
Chemsect DNOC
DNC
DNOC
Elgetol 30
Nitrador
Selinon
Sinox
Trifocide
dinitrophenol*
Chermox PE
dinobuton*
Acrex
Dessin
Dinofen
Drawinol
Talan
dinocap
Crotothane
Karathane
dinopenton
dinoprop*
dinosam*
Chemox General
DNAP
dinoseb*
Basanite
Caldon
Chemox General
Chemox PE
Chemsect DNBP
Dinitro
Dinitro-3
Dinitro General Dynamyte
Dinitro Weed Killer 5
DNBP
Elgetol 318
Gebutox
Hel-Fire
Kiloseb
Nitropone C
Premerge 3
Snox General
Subitex
UnicropDNBP
Vertac
Vertac General Weed Killer
Vertac Selective Weed Killer
dinoseb acetate*
Aretit
dinoseb methacrylate*
Acricid
Am box
binapacryl
(Continued on the next page)
NITROPHENOLS &
NITROCRESOLS 105
-------
Commercial Products
(Continued)
Dapacryl
Endosan
FMC 9044
Hoe 002784
Morrocid
NIA 9044
dinosulfon*
dinoterb acetate*
dinoterb salts*
dinoterbon*
* All U.S. registrations have
been cancelled
Treatment
1. Supportive treatment and hyperthermia control. There is no specific
antidote to poisoning with nitrophenolic or nitrocresolic herbicides.Treatment
is supportive in nature and includes oxygen, fluid replacement, and tempera-
ture control.
Reduce elevated body temperature by physical means. Administer
sponge baths and ice packs, and use a fan to promote air flow and evaporation.7
In fully conscious patients, administer cold, sugar-containing liquids by mouth
as tolerated.
2. Contraindications. Antipyretic therapy with salicylates is strongly
contraindicated as salicylates also uncouple oxidative phosphorylation. Other
antipyretics are thought to be of no use because of the peripherally mediated
mechanism of hyperthermia in poisoning of this nature. Neither the safety nor
the effectiveness of other antipyretics has been tested.
Atropine is also absolutely contraindicated! It is essential not to con
fuse the clinical signs for dinitrophenol with manifestations for cholinesterase
inhibition poisoning.2
3. Skin decontamination. If poisoning has been caused by contamination of
body surfaces, bathe and shampoo contaminated skin and hair promptly and
thoroughly with soap and water, or water alone if soap is not available. Wash the
chemical from skin folds and from under fingernails. Care should be taken to
prevent dermal contamination of hospital staff. See Chapter 2.
4. Other Treatment. Other aspects of treatment are identical to management
of pentachlorophenol poisoning, detailed in Chapter 10.
General Chemical Structure
02N{' \)0-H or
(ALKYL) (ALKYL)
References
1. Leftwich RB, Floro IF, Neal RA, et al. Dinitrophenol poisoning: A diagnosis to consider in
undiagnosed fever. South Med J 1982;75:182-5.
2. Finkel AJ. Herbicides: Dinitrophenols. In: Hamilton and Hardy's IndustrialToxicology, 4th ed.
Boston: lohn Wright PSG, Inc., 1983, pp. 301-2.
3. Kurt TL, Anderson R, Petty C, et al. Dinitrophenol in weight loss:The poison center and
public safety. Vet Hum Toxicol 1986;28:574-5.
NITROPHENOLS &
106 NITROCRESOLS
-------
4. Palmeira CM, Moreno AJ, and Madeira VM. Thiols metabolism is altered by the herbicides
paraquat,dinoseb,and 2.4-D:A study in isolated hepatocytes. ToxicolLett 1995;81:115-23.
5. Smith WD. An investigation of suspected dinoseb poisoning after agricultural use of a herbi-
cide. Practitioner 1981;225:923-6.
6. NIOSH. Criteria document: Occupational exposure to dinitro-orthocresol. Cincinnati: NIOSH,
1978.
7. Graham BS, Lichtenstein MJ, Hinson JM, et al. Nonexertional heatstroke: Physiologic man-
agement and cooling in 14 patients. Arch Intern Med 1986; 146:87-90.
NITROPHENOLS &
NITROCRESOLS 107
-------
CHAPTER 12
HIGHLIGHTS
Life-threatening effects on
Gl tract, kidney, liver, heart,
other organs
Pulmonary fibrosis is the
usual cause of death in
paraquat poisoning (but not
diquat)
Signs and Symptoms:
Paraquat and diquat
(ingestion): burning pain in
the mouth, throat, chest,
upper abdomen; pulmonary
edema, pancreatitis, other
renal, CNS effects
Paraquat (dermal): dry and
fissured hands, horizontal
ridging or loss of fingernails,
ulceration and abrasion
Diquat: neurologic toxicity
Treatment:
Immediate Gl
decontamination with
Bentonite, Fuller's Earth, or
activated charcoal
Maintain urinary output by
administering IV, but
monitor fluids in case of
renal failure
Decontaminate eyes and
skin
Contraindicated:
No supplemental oxygen
unless patient develops
severe hypoxemia
Paraquat and Diquat
The dipyridyl compounds paraquat and diquat are non-selective contact
herbicides that are relatively widely-used, primarily in agriculture and by
government agencies and industries for control of weeds. While paraquat is a
restricted-use pesticide in most forms for most uses in the United States, its
wide usage leads to significant potential for misuse and accidental and inten-
tional poisonings. In the past few decades, paraquat has been a popular agent
for suicide, but recent experience indicates a decline in such intentional
poisonings. Paraquat and diquat are highly toxic compounds and management
of poisonings requires a great deal of skill and knowledge of proper manage-
ment procedures.
PARAQUAT
Toxicology
When ingested in adequate dosage (see below), paraquat has life-threaten-
ing effects on the gastrointestinal tract, kidney, liver, heart, and other organs.
The LD5Q in humans is approximately 3-5 mg/kg, which translates into as little
as 10-15 ml of a 20% solution.1'2
The lung is the primary target organ of paraquat, and pulmonary effects
represent the most lethal and least treatable manifestation of toxicity. However,
toxicity from inhalation is rare.The primary mechanism is through the genera-
tion of free radicals with oxidative damage to lung tissue.1'2 While acute pul-
monary edema and early lung damage may occur within a few hours of severe
acute exposures,3'4 the delayed toxic damage of pulmonary fibrosis, the usual
cause of death, most commonly occurs 7-14 days after the ingestion.5 In pa-
tients who ingested a very large amount of concentrated solution (20%), some
have died more rapidly (within 48 hours) from circulatory failure.5
Both types I and II pneumatocytes appear to selectively accumulate paraquat.
Biotransformation of paraquat in these cells results in free-radical production
with resulting lipid peroxidation and cell injury.1'2'4 Hemorrhage proteinaceous
edema fluid and leukocytes infiltrate the alveolar spaces, after which there is rapid
proliferation of fibroblasts.There is a progressive decline in arterial oxygen tension
and CO2 diffusion capacity. Such a severe impairment of gas exchange causes
progressive proliferation of fibrous connective tissue in the alveoli and eventual
death from asphyxia and tissue anoxia.6 One prospective study of survivors suggests
108 PARAQUAT & DIQUAT
-------
that some of the fibrous toxic damage may be reversible as evidence exists of
markedly improved pulmonary function three months after survival.7
Local skin damage includes contact dermatitis. Prolonged contact will pro-
duce erythema, blistering, abrasion and ulceration, and fingernail changes.8-9
Although absorption across intact skin is slow, abraded or eroded skin allows
efficient absorption.
The gastrointestinal (GI) tract is the site of initial or phase I toxicity to the
mucosal surfaces following ingestion of the substance.This toxicity is manifested
by swelling, edema, and painful ulceration of the mouth, pharynx, esophagus,
stomach, and intestine. With higher levels, other GI toxicity includes centrizonal
hepatocellular injury which can cause elevated bilirubin, and hepatocellular en-
zymes such as AST, ALT, and LDH.
Damage to the proximal renal tubule is often more reversible than the
destruction to lung tissue. However, impaired renal function may play a critical
role in determining the outcome of paraquat poisoning. Normal tubule cells
actively secrete paraquat into the urine, efficiently clearing it from the blood.
However, high blood concentrations poison the secretory mechanism and may
destroy the cells. Diquat poisoning typically results in greater renal injury com-
pared to paraquat.
Focal necrosis of the myocardium and skeletal muscle are the main features
of toxicity to any type of muscle tissue, and typically occur as a second phase.
Ingestion has also been reported to cause cerebral edema and brain damage.10
Although much concern has been expressed about the effects of smoking
paraquat-contaminated marijuana, toxic effects caused by this mechanism have
been either very rare or nonexistent. Most paraquat that contaminates marijuana
is pyrolyzed during smoking to dipyridyl, which is a product of combustion of
the leaf material itself (including marijuana) and presents little toxic hazard.
Signs and Symptoms of Poisoning
Initial clinical signs depend upon the route of exposure. Early symptoms
and signs of poisoning by ingestion are burning pain in the mouth, throat,
chest, and upper abdomen, due to the corrosive effect of paraquat on the mu-
cosal lining. Diarrhea, which is sometimes bloody, can also occur. Giddiness,
headache, fever, myalgia, lethargy, and coma are other examples of CNS and
systemic findings. Pancreatitis may cause severe abdominal pain. Proteinuria,
hematuria, pyuria, and azotemia reflect renal injury. Oliguria/anuria indicate
acute tubular necrosis.
Because the kidney is almost the exclusive route of paraquat elimination
from body tissues, renal failure fosters a build-up of tissue concentrations, in-
cluding those in the lung. Unfortunately, this pathogenic sequence may occur
in the first several hours following paraquat ingestion, generating lethal con-
centrations of paraquat in lung tissue before therapeutic measures to limit ab-
sorption and enhance disposition have taken effect. It is probably for this reason
Commercial Products
Paraquat
Liquid Concentrates:
Cekuquat
Crisquat
Dextrone
Esgram
Goldquat
Gramocil
Gramonol
Gramoxone
In combination with other
herbicides:
With diquat:
Actor
Preeglone
Preglone
Weedol (a 2.5% soluble
granule formulation)
With diuron:
Dexuron
Gramuron
Para-col
Tota-col
With monolinuron:
Gramonol
With simazine:
Pathclear
Terraklene
Diquat
Aquacide
Dextrone
Ortho Diquat
Reglone
PARAQUAT & DIQUAT 109
-------
that methods for enhancing paraquat disposition several hours following inges-
tion have had little effect on mortality.
Cough, dyspnea, and tachypnea usually appear 2-4 days following paraquat
ingestion, but may be delayed as long as 14 days. Progressive cyanosis and dys-
pnea reflect deteriorating gas exchange in the damaged lung. In some cases, the
coughing up of frothy sputum (pulmonary edema) is the early and principal
manifestation of paraquat lung injury.
Clinical experience has offered a rough dose-effect scale on which to base
prognosis in cases of paraquat ingestion:9
Less than 20 rng paraquat ion per kg body weight (less than 7.5
mL of 20% [w/v] paraquat concentrate): No symptoms or only
gastrointestinal symptoms occur. Recovery is likely.
Twenty to 40 mg paraquat ion per kg body weight (7.5-15.0 mL
of 20% [w/v] paraquat concentrate): Pulmonary fibroplasia ensues.
Death occurs in most cases, but may be delayed 2-3 weeks.
More than 40 mg paraquat ion per kg body weight (more than
15.0 mL of 20% [w/v] paraquat concentrate): Multiple organ
damage occurs as in class II, but is more rapidly progressive. Often
characterized by marked ulceration of the oropharynx. Mortality is
essentially 100% in 1-7 days.
Dermal signs are common among agriculture workers with acute paraquat
toxicity. Particularly in concentrated form, paraquat causes localized injury to
tissues with which it comes into contact. Fatal poisonings are reported to
have occurred as a result of protracted dermal contamination by paraquat, but
this is likely to occur only when the skin is abraded, eroded, or diseased,
when more efficient systemic absorption can occur. With an intact dermal
barrier, paraquat leaves the skin of the hands dry and fissured, can cause hori-
zontal ridging of the fingernails, and may even result in the loss of fingernails.
Prolonged contact with skin will create ulceration and abrasion, sufficient to
allow systemic absorption.
In addition, some agriculture workers can be exposed through prolonged
inhalation of spray droplets, and develop nosebleeds due to local damage.
However, inhalation has not resulted in systemic toxicity, due to the low
vapor pressure and lower concentration of paraquat field formulations. Eye
contamination with diquat concentrate or stronger solutions results in severe
conjunctivitis and sometimes protracted corneal opacification.
The hepatic injury from paraquat may be severe enough to cause jaun-
dice, which signifies severe injury. However, hepatotoxicity is rarely a major
determinant to clinical outcome. No other hepatic signs or symptoms are
present other than the abnormal laboratory values mentioned in the Toxicol-
ogy section.
110 PARAQUAT & DIQUAT
-------
DIQUAT
Toxicology
Diquat poisoning is much less common than paraquat poisoning, so that
human reports and animal experimental data for diquat poisoning are less ex-
tensive than for paraquat. Systemically absorbed diquat is not selectively con-
centrated in lung tissue, as is paraquat, and pulmonary injury by diquat is less
prominent. In animal studies, diquat causes mild, reversible injury to type I
pneumatocytes, but does not injure the type II cells. No progressive pulmonary
fibrosis has been noted in diquat poisoning.11"13
However, diquat has severe toxic effects on the central nervous system that
are not typical of paraquat poisoning.12-13 While laboratory experimentation has
suggested that diquat is not directly neurotoxic, there have been relatively con-
sistent pathologic brain changes noted in reported fatal cases of diquat poison-
ing.These consist of brain stem infarction, particularly involving the pons.12 It
is not clear whether these post-mortem changes represent direct toxicity or
secondary effects related to the systemic illness and therapy. (See Signs and
Symptoms section for CNS clinical effects.)
There is probably significant absorption of diquat across abraded or ulcer-
ated skin.
Signs and Symptoms of Poisoning
In many human diquat poisoning cases, clinical signs of neurologic toxicity
are the most important. These include nervousness, irritability, restlessness, com-
bativeness, disorientation, nonsensical statements, inability to recognize friends
or family members, and diminished reflexes. Neurologic effects may progress to
coma, accompanied by tonic-clonic seizures, and result in the death of the
patient.12'13 Parkinsonism has also been reported following dermal exposure to
diquat.14
Except for the CNS signs listed in the preceding paragraph, early symp-
toms of poisoning by ingested diquat are similar to those from paraquat, reflect-
ing its corrosive effect on tissues. They include burning pain in the mouth,
throat, chest, and abdomen, intense nausea and vomiting, and diarrhea. If the
dosage was small, these symptoms may be delayed 1-2 days. Blood may appear
in the vomitus and feces. Intestinal ileus, with pooling of fluid in the gut, has
characterized several human poisonings by diquat.
The kidney is the principal excretory pathway for diquat absorbed into the
body. Renal damage is therefore an important feature of poisonings. Proteinuria,
hematuria, and pyuria may progress to renal failure and azotemia. Elevations of
serum alkaline phosphatase, AST, ALT, and LDH reflect liver injury. Jaundice
may develop.
PARAQUAT & DIQUAT -111
-------
If the patient survives several hours or days, circulatory function may fail
due to dehydration. Hypotension and tachycardia can occur, with shock result-
ing in death. Other cardiorespiratory problems may develop, such as toxic car-
diomyopathy or a secondary infection such as bronchopneumonia.
Diquat is somewhat less damaging to the skin than paraquat, but irritant
effects may appear following dermal contamination with the concentrate. There
is probably significant absorption of diquat across abraded or ulcerated skin.
The great majority of poisonings by paraquat and diquat (discussed below)
have been caused by ingestion with suicidal intent in most cases, particularly in
Japan11 and many developing countries. Since 1987, there has been a decline in
most countries in the total numbers of suicidal deaths attributed to paraquat
and diquat. Nearly all of the few poisonings caused by occupational exposure
have been survived, but the mortality rate among persons who have swallowed
paraquat or diquat remains high.1'5 Avoidance of this mortality will probably
have to rely on preventive strategies or on stopping gastrointestinal absorption
very soon after the toxicant has been ingested.
Even though intestinal absorption of dipyridyls is relatively slow, lethal
uptake by critical organs and tissues apparently occurs within 18 hours, and
possibly within 6 hours, following ingestion of toxic quantities of paraquat or
diquat. Bipyridyls have large volumes of distribution. Once distribution to tis-
sues has occurred, measures to remove bipyridyls from the blood are very inef-
ficient in reducing the total body burden.
Several strategies are being tested to reduce the frequency of these occur-
rences. These include the addition of emetics, stenching agents, gelling sub-
stances, and bittering agents such as sodim denatonium.
Confirmation of Poisoning: Paraquat and Diquat
At some treatment facilities, a simple colorimetric test is used to identify
paraquat and diquat in the urine, and to give a rough indication of the magni-
tude of absorbed dose. To one volume of urine, add 0.5 volume of freshly
prepared 1% sodium dithionite (sodium hydrosulfite) in one normal sodium
hydroxide (1.0 N NaOH). Observe color at the end of one minute. A blue
color indicates the presence of paraquat in excess of 0.5 mg per liter. Both
positive and negative controls should be run to ensure that the dithionite has
not undergone oxidation in storage.
When urine collected within 24 hours of paraquat ingestion is tested, the
dithionite test appears to have some prognostic value: concentrations less than
one milligram per liter (no color to light blue) generally predict survival, while
concentrations in excess of one milligram per liter (navy blue to dark blue)
often foretell a fatal outcome.
Diquat in urine yields a green color with the dithionite test. Although
there is less experience with this test in diquat poisonings, the association of
bad prognosis with intense color is probably similar.
112 PARAQUAT & DIQUAT
-------
Paraquat and diquat can be measured in blood and urine by spectrophoto-
metric, gas chromatographic, liquid chromatographic, and radioimmunoassay
methods. These tests are available in numerous clinical reference laboratories
and sometimes by the manufacturing company. Survival is likely if plasma con-
centrations do not exceed 2.0, 0.6, 0.3, 0.16, and 0.1 mg per liter at 4, 6, 10, 16,
and 24 hours, respectively, after ingestion.15
Treatment
1. Skin and eye decontamination. Flush skin immediately with copious
amounts of water. Material splashed in the eyes must be removed by pro-
longed irrigation with clean water. Eye contamination should thereafter be
treated by an ophthalmologist. Mild skin reactions usually respond if there is no
further contact with the pesticide, but the irritation may take several weeks to
resolve. Severe injuries with inflammation, cracking, secondary infection, or
nail injury should be treated by a dermatologist.
2. Gastrointestinal decontamination. If paraquat or diquat have been in-
gested, immediate administration of adsorbent is the one therapeutic
measure most likely to have a favorable effect. Bentonite (7.5% suspension)
and Fuller's Earth (15% suspension) are highly effective, but sometimes not
available.
Dosage of Bentonite and Fuller's Earth:
Adults and children over 12years: 100-150 g.
Children under 12 years: 2 gm/kg body weight.
Caution: Hypercalcemia and fecaliths have sometimes occurred fol-
lowing administration of Fuller's Earth.
Activated charcoal is nearly as effective, and is widely available. See Chapter
2 for dosage of charcoal and further information on gastric decontamination.
Lavage has not been shown to be effective and should not be performed
unless the patient is seen within an hour of ingestion. Later lavage runs the risk
of inducing bleeding, perforation, or scarring due to additional trauma to al-
ready traumatized tissues. Repeated administration of charcoal or other absor-
bent every 2-4 hours may be beneficial in both children and adults, but use of
a cathartic such as sorbitol should be avoided after the first dose. Cathartics and
repeat doses of activated charcoal should not be administered if the gut is atonic.
Check frequently for bowel sounds. Ileus occurs commonly in diquat
poisoning, less often in paraquat poisoning.
PARAQUAT & DIQUAT 113
-------
3. Samples. Secure a blood sample as soon as possible for paraquat analysis, and
urine samples for either paraquat and/or diquat. Serial samples of urine for either
agent and plasma for paraquat may be followed for prognostic information.
4. Respiration. Do not administer supplemental oxygen until the pa
tient develops severe hypoxemia. High concentrations of oxygen in the lung
increase the injury induced by paraquat, and possibly by diquat as well.There
may be some advantage in placing the patient in a moderately hypoxic envi-
ronment, i.e., 15%-16% oxygen, although the benefit of this treatment measure
has not been established empirically in human poisonings. Inhalation of nitric
oxide has been suggested as a method to maintain tissue oxygenation at low
inspired oxygen concentrations, but its efficacy is unproven. When the lung
injury is so far advanced that there is no expectation of recovery, oxygen may
be given to relieve air hunger.
5. Intensive care. In serious poisonings, care should be provided in an inten-
sive care setting, to allow proper monitoring of body functions and skilled
performance of necessary invasive monitoring and procedures.
6. Fluids. It is essential to maintain adequate urinary output.4 Administer in-
travenous fluids: isotonic saline, Ringer's solution, or 5% glucose in water.This
is highly advantageous early in poisonings as a means of correcting dehydra-
tion, accelerating toxicant excretion, reducing tubular fluid concentrations of
paraquat, and correcting any metabolic acidosis. However, fluid balance must
be monitored carefully to forestall fluid overload if renal failure develops. Monitor
the urine regularly for protein and cells, to warn of impending tubular necrosis.
Intravenous infusions must be stopped if renal failure occurs, and extracorpo-
real hemodialysis is indicated. Hemodialysis is not effective in clearing paraquat
or diquat from the blood and tissues.
7. Hemoperfusion over cellophane-coated activated charcoal may be consid-
ered. The procedure has been used in many paraquat poisonings because the
adsorbent does efficiently remove paraquat from the perfused blood. However,
recent reviews of effectiveness have failed to show any reduction in mortality as
a result of hemoperfusion.1'4 The apparent reason for this is the very small
proportion of paraquat body burden carried in the circulating blood even when
only a few hours have elapsed after ingestion. Theoretically, a patient who can
be hemoperfused within 10 hours of paraquat ingestion may derive some mar-
ginal benefit, but this has not been demonstrated.
If hemoperfusion is attempted, blood calcium and platelet concentrations
must be monitored. Calcium and platelets must be replenished if these con-
stituents are depleted by the procedure.
114 PARAQUAT & DIQUAT
-------
8. Seizure control. Convulsions and psychotic behavior sometimes encoun-
tered in diquat poisoning may be best controlled by lorazepam, given slowly
intravenously, as outlined in Chapter 2. Control convulsions as outlined in
Chapter 2.
9. Other drugs. Many drugs have been tested in animals or given in human
bipyridyl poisonings without clear evidence of benefit or harm: corticoster-
oids, superoxide dismutase, propranolol, cyclophosphamide, vitamin E, ribofla-
vin, niacin, ascorbic acid, clofibrate, desferrioxamine, acetylcysteine, and terpin
hydrate. However, recent evidence regarding the use of cyclophosphamide
and methylprednisolone may be effective in reducing the mortality associ-
ated with moderate to severe paraquat poisoning.Two studies found a reduced
mortality associated with the treatment, while one study found no difference.16
The dosages used for cyclophosphamide and methylprednisolone were 1 gram
daily for two days and 1 gram daily for three days respectively, and were given
after hemoperfusion. Each drug was administered as a two hour infusion, and
white cell counts, serum creatinine levels, chest radiography, and liver function
tests were monitored.16
10. Pain management. Morphine sulfate is usually required to control the
pain associated with deep mucosal erosions of the mouth, pharynx, and esophagus,
as well as abdominal pain from pancreatitis and enteritis. Mouthwashes, cold
fluids, ice cream, or anesthetic lozenges may also help to relieve pain in the
mouth and throat.
Dosage of Morphine Sulfate:
Adults and children over 12 years: 10-15 mg subcutaneously every 4
hours.
Children under 12years: 0.1-0.2 mg /kg body weight every 4 hours.
11. Transplantation. With severe pulmonary toxicity, recovery of the patient
may only be accomplished by lung transplantation. However, the transplanted
lung is susceptible to subsequent damage due to redistribution of paraquat.17
PARAQUAT & DIQUAT 115
-------
General Chemical Structures
ci
Cl
CK +N
\
\_
7\
fci ^-
Paraquat
N CH3
2CI
/
CH2 CH2 2 Br"
Diquat
References
1. Pond SM. Manifestations and management of paraquat poisoning. MedJAust 1990; 152:256-9.
2. Giulivi C, Lavagno CC, Lucesoli F, et al. Lung damage in paraquat poisoning and hyper-
baric oxyen exposure: superoxide-mediated inhibition of phospholipase A2. Free Radic
BiolMed 1995; 18:203-13.
3. Nordquist RE, Nguyen H, Poyer JL, et al. The role of free radicals in paraquat-induced
corneal lesions. Free Radic Res 1995;23:61-71.
4. Honore P, Hantson P Fauville JP et al. Paraquat poisoning: State of the art. Acta Clin Belg
1994;49:220-8.
5. Bismuth C, Gamier R, Dally S, et al. Prognosis and treatment of paraquat poisoning: A
review of 28 cases. JToxicol ClinToxicol 1982; 19:461-74.
6. Harsanyi L, Nemeth A, and Lang A. Paraquat (gramoxone) poisoning in south-west Hun-
gary, 1977-1984. Am JForensic Med Pathol 1987;8:131-4.
7. Lee CC, Lin JL, and Liu L. Recovery of respiratory function in survivors with paraquat
intoxication (abstract). Ann EmergMed 1995;26:721-2.
8. Tungsanga K, Chusilp S, Israsena S, et al. Paraquat poisoning: Evidence of systemic toxicity
after dermal exposure. Postgrad Med J 1983;59:338-9.
9. Vale JA, MeredithTJ, and Buckley BM. Paraquat poisoning: Clinical features and immediate
general management. HumToxicol 1987;6:41-7.
10. Hughes JT. Brain damage due to paraquat poisoning: A fatal case with neuropathological
examination of the brain. Neurotoxicology 1988;9:243-8.
11. Lam HF, Azawa J, Gupta BN, et al. A comparison of the effects of paraquat and diquat on
lung compliance, lung volume, and single-breath diffusing capacity in the rat. Toxicology
1980;18:lll-23.
12. Vanholder R, Colardyn F, DeReuck J, et al. Diquat intoxication: Report of two cases and
review of the literature. Am J Med 1981;70:1267-71.
13. Olson KR. Paraquat and diquat. In: Olson KR et al. (eds), Poisoning and Drug Overdose, 2nd
ed. Norwalk CT: Appelton and Lange, 1994, pp. 245-6.
14. Sechi GP, AgnettiV, Piredda M, et al. Acute and persistent Parkinsonism after use of diquat.
Neurology 1992;42:261-3.
15. Proudfoot AT, Stewart MS, LevittT, et al. Paraquat poisoning: Significance of plasma-paraquat
concentrations. Lancet 1979;2:330-2.
116 PARAQUAT & DIQUAT
-------
16. Lin JL, Wei MC, and LiuYC. Pulse therapy with cyclophosphamide and methyprednislone
in patients with moderate to severe paraquat poisoning: A preliminary report. Thorax
1996;51:661-3.
17. Toronto Lung Transplant Group. Sequential bilateral lung transplantation for paraquat poi-
soning. A case report. JThoracic Cardiovas Surg 1985;89:734-42.
PARAQUAT & DIQUAT 117
-------
CHAPTER 13
Other Herbicides
Many herbicides are now available for use in agriculture and for lawn and
garden weed control. This chapter discusses herbicides other than the
chlorophenoxys, nitrophenols and chlorophenols, arsenicals, and dipyridyls, which
are the subjects of separate chapters. Many modern herbicides kill weeds selec-
tively by impairing metabolic processes that are unique to plant life. For this
reason, their systemic toxicities in mammals are generally low. Nonetheless,
some herbicides pose a significant risk of poisoning if handled carelessly, and
many are irritating to eyes, skin, and mucous membranes.
For several good reasons, all of the herbicides mentioned in this chapter
should be handled and applied only with full attention to safety measures that
minimize personal contact. Many formulations contain adjuvants (stabilizers,
penetrants, surfactants) that may have significant irritating and toxic effects. A
number of premixed formulations contain two or more active ingredients; the
companion pesticides may be more toxic than the principal herbicide. Good
hygienic practice should not be disregarded just because a pesticide is reported
to have a high LD50 in laboratory rodents.
Health professionals who may need to assess the consequences of prior
exposure should understand the fate of these compounds after absorption by
humans.The water-soluble herbicides are not retained in body tissues for long
periods, as were the old lipophilic organochlorine insecticides, such as DDT.
Most are excreted, mainly in the urine, within one to four days.
Toxicology
The table on the following pages lists the more commonly used herbicides
not discussed elsewhere in this manual. The rat acute oral LD5Q is given as a
rough index of potential lethal toxicity. (If several values are reported by various
sources, the lowest is recorded here.) The adverse effect information is drawn
from many sources, including product labels, textbooks, published case histo-
ries, and some unpublished reports.The listing cannot be considered inclusive,
either of herbicide products or of effects.
118 OTHER HERBICIDES
-------
TOXICITY OF COMMON HERBICIDES
Chemical Class
Acetamides
Aliphatic acids
Anilides
Benzamide
Benzoic,
anisic acid
derivatives
Benzonitriles
Benzothiadiazinone
dioxide
Carbamates and
Thiocarbamates
(herbicidal)
Generic Name
metolachlor
trichloroacetic
acid
dichloropropionic
acid (dalapon)
alachlor
propachlor
propanil
pronamide
trichlorobenzoic
acid
dicamba
dichlobenil
bentazone
asulam
terbucarb
butylate
cycloate
pebulate
vernolate
EPTC
dial late
triallate
thiobencarb
Proprietary
Names
Dual, Pennant,
others
TCA
Dalapon,
Revenge
Lasso, Alanox
Ramrod, Bexton,
Prolex
DPA, Chem
Rice, Propanex,
Riselect, Stam,
Stampede
Kerb, Rapier
TCBA, Tribac,
2,3,6-TBA
Banvel
Casoron,
Dyclomec, Barrier
Basagran
Asulox
Azac, Azar
Sutan
Ro-Neet
Tillam, PEBC
Vernam
Eptam, Eradicane
Di-allate
Far-go
Bolero, Saturn
Acute Oral LD50
mg/kg
2,780
5,000
970
1,800
710
>2,500
8,350
1,500
2,700
>4,460
>1,000
>5,000
>34,000
3,500
2,000
921
1,800
1,630
395
1,675
1,300
Known or
Suspected
Adverse Effects
Irritating
to eyes
and skin.
Irritating to
skin, eyes,
and respiratory
tract.
Mild irritant.
Dermal irritant
and sensitizer.
Irritating to skin,
eyes, and
respiratory tract.
Moderately
irritating to eyes
Moderately
irritating to skin
and respiratory
tract.
Minimal toxic,
irritant effects
Irritating to eyes
and respiratory
tract.
Some are
irritating to
eyes, skin, and
respiratory tract,
particularly in
concentrated
form.
Some may be
weak inhibitors
of cholinesterase.
OTHER HERBICIDES 119
-------
TOXICITY OF COMMON HERBICIDES
Chemical Class
Carbanilates
Chloropyridinyl
Cyclohexenone
derivative
Dinitroamino-
benzene
derivative
Fluorodinitro-
toluidine
compounds
Isoxazolidinone
Nicotinic acid
isopropylamine
derivative
Oxadiazolinone
Phosphonates
Generic Name
chlorpropham
triclopyr
sethoxydim
butralin
pendimethalin
oryzalin
benfluralin
dinitramine
ethalfluralin
fluchloralin
profluralin
trifluralin
clomazone
imazapyr
oxadiazon
glyphosate
fosamine
ammonium
Proprietary
Names
Sprout-Nip
Chloro-IPC
Garlon, Turflon
Poast
Amex
Tarn ex
Prowl, Stomp,
Accotab,
Herbodox,
Go-Go-San,
Wax Up
Surflan, Dirimal
Benefin, Balan,
Balfin, Quilan
Cobex
Sonalan
Basalin
Tolban
Treflan
Command
Arsenal
Ronstar
Roundup,
Glyfonox
Krenite
Acute Oral LD50
mg/kg
3,800
630
3,125
12,600
>5,000
2,250
>1 0,000
>1 0,000
3,000
>1 0,000
1,550
1,808
>1 0,000
1,369
>5,000
>3,500
4,300
>5,000
Known or
Suspected
Adverse Effects
Skin irritants.
May generate
methemoglobin
at high dosage.
Irritating to skin
and eyes.
Irritating to skin
and eyes.
May be
moderately
irritating.
These herbicides
do not uncouple
oxidative
phosphorylation
or generate
methemoglobin.
May be mildly
irritating. These
herbicides do not
uncouple
oxidative
phosphorylation
or generate
methemoglobin.
May be
moderately
irritating.
Irritating to eyes
and skin. Does
not contain
arsenic.
Minimal toxic
and irritant
effects.
Irritating to eyes,
skin, and upper
respiratory tract.
Irritating to eyes,
skin, and upper
respiratory tract.
120 OTHER HERBICIDES
-------
TOXICITY OF COMMON HERBICIDES
Chemical Class
Phthalates
Picolinic acid
compound
Triazines
Triazole
Generic Name
chlorthaldimethyl
endothall
picloram
ametryn
atrazine
cyanazine
desmetryn
metribuzin
prometryn
propazine
simazine
terbuthylazine
tertutryn
prometon
amitrole,
aminotriazole
Proprietary
Names
Dachthal, DCPA
Aquathol
Tordon, Pinene
Ametrex, Evik,
Gesapax
Aatrex, Atranex,
Crisazina
Bladex, Fortrol
Semeron
Sencor, Lexone,
Sencoral, Sencorex
Caparol, Gesagard,
Prometrex
Milo-Pro,
Primatol, Prozinex
Gesatop, Princep,
Caliber 90
Gardoprim,
Primatol M
Ternit, Prebane,
Terbutrex
Gesafram 50
Pramitol 25E
Amerol, Azolan,
Azole, Weedazol
Acute Oral LD50
mg/kg
>1 0,000
51
8,200
1,750
1,780
288
1,390
1,100
5.235
>7,000
>5,000
2,000
2,500
2,980
>1 0,000
Known or
Suspected
Adverse Effects
Moderately
irritating to eyes.
Free acid is highly
toxic. Irritating to
skin, eyes and
respiratory tract.
See Chapter 18.
Irritating to skin,
eyes, and
respiratory tract.
Low systemic
toxicity.
Systemic
toxicity
is unlikely
unless large
amounts
have been
ingested.
Some
triazines
are moderately
irritating to
the eyes,
skin, and
respiratory
tract.
This particular
formulation of
prometon is
strongly irritating
to eyes, skin, and
respiratory tract.
Minimal systemic
toxicity. Slight
irritant effect.
OTHER HERBICIDES 121
-------
TOXICITY OF COMMON HERBICIDES
Known or
Chemical Class
Uracils
Urea
derivatives
Generic Name
bromacil
lenacil
terabacil
chlorimuron
ethyl
chlorotoluron
diuron
flumeturon
isoproturon
linuron
methabenz-
thiazuron
metobromuron
metoxuron
monolinuron
monuron
neburon
siduron
sulfemeturon-
methyl
Proprietary
Names
Hyvar
Venzar
Sinbar
Classic
Dicuran, Tolurex
Cekiuron,
Crisuron, Dailon,
Direx, Diurex,
Diuron,
Karmex, Unidron,
Vonduron
Cotoran,
cottonex
Alon, Arelon,
IP50, Tolkan
Afalon, Linex,
Linorox, Linurex,
Lorox, Sarclex
Tribunil
Pattonex
Deftor, Dosaflo,
Purivel, Sulerex
Ares in
Monuron
Granurex,
Neburex
Tupersan
Oust
Acute Oral LD50
mg/kg
5,200
>1 1,000
>5,000
>4,000
>1 0,000
>5,000
8,900
1,826
1,500
5,000
2,000
3,200
2,100
3,600
>1 1,000
>7,500
>5,000
Suspected
Adverse Effects
Irritant to skin,
eyes, and
respiratory tract.
Moderately
irritating.
Systemic
toxicity is
unlikely unless
large amounts
have been
ingested.
Many
substituted
ureas are
irritating to
eyes, skin, and
mucous
membranes.
tebuthiuron
Spike, Tebusan 644
122 OTHER HERBICIDES
-------
Confirmation of Poisoning
Although there are analytical methods for residues of many of the herbi-
cides mentioned in this chapter and for some of the mammalian metabolites
generated from them, these procedures are not generally available to confirm
human absorption of the chemicals. Exposure must be determined from a re-
cent history of occupational contact or accidental or deliberate ingestion.
Treatment
1. Skin decontamination. Skin contamination should be treated promptly
by washing with soap and water. Contamination of the eyes should be treated
immediately by prolonged flushing of the eyes with large amounts of clean
water. If dermal or ocular irritation persists, medical attention should be ob-
tained without delay. See Chapter 2.
2. Gastrointestinal decontamination. Ingestions of these herbicides are likely
to be followed by vomiting and diarrhea due to their irritant properties. Man-
agement depends on: (1) the best estimate of the quantity ingested, (2) time
elapsed since ingestion, and (3) the clinical status of the subject.
Activated charcoal is probably effective in limiting irritant effects and
reducing absorption of most or all of these herbicides. Aluminum hydroxide
antacids may be useful in neutralizing the irritant actions of more acidic agents.
Sorbitol should be given to induce catharsis if bowel sounds are present and if
spontaneous diarrhea has not already commenced. Dehydration and electrolyte
disturbances may be severe enough to require oral or intravenous fluids.
There are no specific antidotes for poisoning by these herbicides. In the
case of suicidal ingestions, particularly, the possibility must always be kept in
mind that multiple toxic substances may have been swallowed.
If large amounts of herbicide have been ingested and the patient is seen
within an hour of the ingestion, gastrointestinal decontamination should be
considered, as outlined in Chapter 2.
If the amount of ingested herbicides was small, if effective emesis has al-
ready occurred, or if treatment is delayed, administer activated charcoal and
sorbitol by mouth.
3. Intravenous fluids. If serious dehydration and electrolyte depletion have
occurred as a result of vomiting and diarrhea, monitor blood electrolytes and
fluid balance and administer intravenous infusions of glucose, normal saline, Ringers
solution, or Ringer's lactate to restore extracellular fluid volume and electrolytes.
Follow this with oral nutrients as soon as fluids can be retained.
OTHER HERBICIDES 123
-------
4. Supportive measures are ordinarily sufficient for successful management
of excessive exposures to these herbicides (endothall is an exceptionsee Chap-
ter 18, p. 187). If the patient's condition deteriorates in spite of good supportive
care, the operation of an alternative or additional toxicant should be suspected.
124 OTHER HERBICIDES
-------
Section IV
OTHER PESTICIDES
-------
CHAPTER 14
HIGHLIGHTS
Life-threatening effects
on CNS, blood vessels,
kidney, liver
Signs and Symptoms:
In acute cases, garlic odor
of the breath and feces,
metallic taste in mouth,
adverse Gl symptoms
In chronic cases, muscle
weakness, fatigue,
weight loss,
hyperpig mentation,
hyperkeratosis, Mees
lines
Treatment:
Gl decontamination
Chelation therapy
Dimercaprol (BAL) or
DMPS to accelerate
arsenic excretion
Arsenical Pesticides
Many arsenic compounds have been discontinued in the United States as a
result of government regulations. However, arsenical pesticides are still widely
available in some countries, and many homes and farms have leftover supplies
that continue to represent some residual risk.
Arsine gas is discussed separately on page 132.
Toxicology
Arsenic is a natural element that has both metal and nonmetal physical/
chemical properties. In some respects, it resembles nitrogen, phosphorus, anti-
mony, and bismuth in its chemical behavior. In nature, it exists in elemental,
trivalent (-3 or +3), and pentavalent (+5) states. It binds covalently with most
nonmetals (notably oxygen and sulfur) and with metals (for example, calcium
and lead). It forms stable trivalent and pentavalent organic compounds. In bio-
chemical behavior, it resembles phosphorus, competing with phosphorus ana-
logs for chemical binding sites.
Toxicity of the various arsenic compounds in mammals extends over a
wide range, determined in part by the unique biochemical actions of each
compound, but also by absorbability and efficiency of biotransformation and
disposition. Overall, arsines present the greatest toxic hazard, followed closely
by arsenites (inorganic trivalent compounds). Inorganic pentavalent compounds
(arsenates) are somewhat less toxic than arsenites, while the organic (methy-
lated) pentavalent compounds represent the least hazard of the arsenicals that
are used as pesticides.1
The pentavalent arsenicals are relatively water soluble and absorbable across
mucous membranes.Trivalent arsenicals, having greater lipid solubility, are more
readily absorbed across the skin.2 However, poisonings by dermal absorption of
either form have been extremely rare. Ingestion has been the usual basis of
poisoning; gut absorption efficiency depends on the physical form of the com-
pound, its solubility characteristics, the gastric pH, gastrointestinal motility, and
gut microbial transformation. Arsine exposure occurs primarily through inha-
lation, and toxic effects may also occur with other arsenicals through inhalation
of aerosols.
Once absorbed, many arsenicals cause toxic injury to cells of the nervous
system, blood vessels, liver, kidney, and other tissues. Two biochemical mecha-
126 ARSENICALS
-------
nisms of toxicity are recognized: (1) reversible combination with thiol groups
contained in tissue proteins and enzymes, and (2) substitution of arsenic anions
for phosphate in many reactions, including those critical to oxidative phosphory-
lation. Arsenic is readily metabolized in the kidney to a methylated form, which
is much less toxic and easily excreted. However, it is generally safest to manage
cases of arsenical pesticide ingestion as though all forms are highly toxic.
The unique toxicology of arsine gas is described later in this chapter.
Signs and Symptoms of Poisoning
Manifestations of acute poisoning are distinguishable from those of chronic
poisoning.
Acute arsenic poisoning: Symptoms and signs usually appear within
one hour after ingestion, but may be delayed several hours. Garlic odor of the
breath and feces may help to identify the toxicant in a severely poisoned pa-
tient.There is often a metallic taste in the mouth. Adverse gastrointestinal (GI)
effects predominate, with vomiting, abdominal pain, and rice-water or bloody
diarrhea being the most common. Other GI effects include inflammation, vesicle
formation and eventual sloughing of the mucosa in the mouth, pharynx, and
esophagus.3 These effects result from the action of an arsenical metabolite on
blood vessels generally, and the splanchnic vasculature in particular, causing
dilation and increased capillary permeability.
The central nervous system is also commonly affected during acute expo-
sure. Symptoms may begin with headache, dizziness, drowsiness, and confusion.
Symptoms may progress to include muscle weakness and spasms, hypothermia,
lethargy, delirium, coma, and convulsions.1 Renal injury is manifest as pro-
teinuria, hematuria, glycosuria, oliguria, casts in the urine, and, in severe poi-
soning, acute tubular necrosis. Cardiovascular manifestations include shock,
cyanosis, and cardiac arrhythmia,4-5 which are due to direct toxic action and
electrolyte disturbances. Liver damage may be manifested by elevated liver en-
zymes and jaundice. Injury to blood-forming tissues may cause anemia, leuko-
penia, and thrombocytopenia.
Death usually occurs one to three days following onset of symptoms and is
often the result of circulatory failure, although renal failure also may contrib-
ute.1 If the patient survives, painful paresthesias, tingling, and numbness in the
hands and feet may be experienced as a delayed sequela of acute exposure.This
sensorimotor peripheral neuropathy, which may include muscle weakness and
spasms, typically begins 1-3 weeks after exposure.6 The muscle weakness may
be confused with Guillain-Barre syndrome.7
Chronic arsenic poisoning from repeated absorption of toxic amounts
generally has an insidious onset of clinical effects and may be difficult to diag-
nose. Neurologic, dermal, and nonspecific manifestations are usually more promi-
nent than the gastrointestinal effects that characterize acute poisoning. Muscle
Commercial Products
(Many have been discontinued)
arsenic acid
Hi-Yield DessicantH-10
Zotox
arsenic trioxide
cacodylic acid (sodium
cacodylate)
Bolate
Bolls-Eye
Bophy
Dilie
Kack
Phytar 560
Rad-E-Cate 25
Salvo
calcium acid methane arsonate
(CAMA)
Calar
Super Crab-E-Rad-Calar
Super Dal-E-Rad
calcium arsenate
Spra-cal
tricalcium arsenate
Turf-Cal
calcium arsenite
London purple
mono-calcium arsenite
copper acetoarsenite
Emerald green
French green
Mitis green
Paris green
Schweinfurt green
copper arsenite (acid copper
arsenite)
disodium methane arsonate
Ansar 8100
Arrhenal
Arsinyl
Crab-E-Rad
Di-Tac
DMA
DSMA
Methar 30
Sodar
Weed-E-Rad 360
lead arsenate
Gypsine
Soprabel
methane arsonic acid (MAA)
monoammonium methane
arsonate (MAMA)
monosodium methane arsonate
(MSMA)
Ansar 170
(Continued on the next page)
ARSENICALS 127
-------
Commercial Products
(Continued)
Arsonate Liquid
Bueno 6
Daconate 6
Dal-E-Rad
Drexar 530
Herbi-AII
Merge 823
Mesamate
Target MSMA
Trans-Vert
Weed-E-Rad
Weed-Hoe
sodium arsenate
disodium arsenate
Jones Ant Killer
sodium arsenite
Prodalumnol Double
Sodanit
zinc arsenate
weakness and fatigue can occur, as can anorexia and weight loss. Hyperpig-
mentation is a common sign, and tends to be accentuated in areas that are
already more pigmented, such as the groin and areola. Hyperkeratosis is an-
other very common sign, especially on the palms and soles.8-9 Subcutaneous
edema of the face, eyelids, and ankles, stomatitis, white striations across the nails
(Mees lines), and sometimes loss of nails or hair are other signs of chronic,
continuous exposure.1-9 On occasion, these hyperkeratotic papules have under-
gone malignant transformation.8 Years after exposure, dermatologic findings
include squamous cell and basal cell carcinoma, often in sun-protected areas.
Neurologic symptoms are also common with chronic exposure. Peripheral
neuropathy, manifested by paresthesia, pain, anesthesia, paresis, and ataxia, may
be a prominent feature. It may often begin with sensory symptoms in the lower
extremities and progress to muscular weakness and eventually paralysis and
muscle wasting. Although less common, encephalopathy can develop with speech
and mental disturbances very much like those seen in thiamine deficiency
(Wernicke's syndrome).
Other organ systems are affected with arsenic toxicity. Liver injury reflected
in hepatomegaly and jaundice may progress to cirrhosis, portal hypertension,
and ascites. Arsenic has direct glomerular and tubular toxicity resulting in oliguria,
proteinuria, and hematuria. Electrocardiographic abnormalities (prolongation
of the Q-T interval) and peripheral vascular disease have been reported. The
latter includes acrocyanosis, Raynaud's phenomenon, and frank gangrene.1-10
Hematologic abnormalities include anemia, leukopenia, and thrombocytopenia.1
Late sequelae of protracted high intakes of arsenic include skin cancer as described
above and an increased risk of lung cancer.1-8
Confirmation of Poisoning
Measurement of 24-hour urinary excretion of arsenic (micrograms per
day) is the most common way to confirm excessive absorption and is the
preferred method to follow serial levels and evaluate chronic exposure.1-11
Spot urine arsenic analysis expressed as a ratio with urinary creatinine is the
recommended method to evaluate occupational exposures.12 Methods to de-
termine blood arsenic concentration are available; however blood levels tend
to poorly correlate with exposure except in the initial acute phase.11-13 Spe-
cial metal-free acid-washed containers should be used for sample collection.
Arsenic excretion above 100 meg per day should be viewed with suspicion
and the test should be repeated.
Excretions above 200 meg per day reflect a toxic intake, unless seafood was
ingested.11-13-14-15 Diets rich in seafood, primarily shellfish in the previous 48
hours, may generate 24-hour urine excretion levels as high as 200 meg per day
and sometimes more.3'14 The majority of marine arsenic that is excreted is in
the methylated form (arsenobetaine) and is not considered acutely toxic. How-
128 ARSENICALS
-------
ever, a recent study supports that some of the arsenic released from mussels may
contain higher amounts of arsenic trioxide than previously thought.14 Urinary
arsenic may be speciated into inorganic and organic fractions to help deter-
mine the source of the exposure and to help guide treatment.
Concentrations of arsenic in blood, urine, or other biologic materials can be
measured by either wet or dry ashing, followed by colorimetric or atomic ab-
sorption spectrometric analysis.The latter method is preferred. Blood concentra-
tions in excess of about 100 meg per liter probably indicate excessive intake or
occupational exposure, provided that seafood was not ingested before the sample
was taken.3-11'13-15 Blood samples tend to correlate with urine samples during the
early stages of acute ingestion,11 but because arsenic is rapidly cleared from the
blood, the 24-hour urine sample remains the preferred method for detection and
for ongoing monitoring.1'11'13 Hair has been used for evaluation of chronic expo-
sure. Levels in unexposed people are usually less than 1 mg/kg; levels in individu-
als with chronic poisoning range between 1 and 5 mg/kg.15 Hair samples should
be viewed with caution because external environmental contamination such as
air pollution may artificially elevate arsenic levels.
Special tests for arsine toxicosis are described on page 132 under "Arsine
Gas."
Treatment
The following discussion applies principally to poisonings by arsenicals in
solid or dissolved form. Treatment of poisoning by arsine gas requires special
measures described below on page 132.
1. Skin decontamination. Wash arsenical pesticide from skin and hair with
copious amounts of soap and water. Flush contaminant from eyes with clean
water. If irritation persists, specialized medical treatment should be obtained.
See Chapter 2.
2. Gastrointestinal decontamination. If arsenical pesticide has been in-
gested within the first hour of treatment, consideration should be given to GI
decontamination, as outlined in Chapter 2. Because poisoning by ingested ar-
senic almost always results in profuse diarrhea, it is generally not appropriate to
administer a cathartic.
3. Intravenous fluids. Administer intravenous fluids to restore adequate hy-
dration, support urine flow, and correct electrolyte imbalances. Monitor in-
take/output continuously to guard against fluid overload. If acute renal failure
occurs, monitor blood electrolytes regularly. Blood transfusions and oxygen by
mask may be needed to combat shock.
ARSENICALS 129
-------
4. Cardiopulmonary monitoring. Monitor cardiac status by EGG to detect
ventricular arrhythmias including prolonged Q-T interval and ventricular ta-
chycardia, and toxic myocardiopathy (T wave inversion, long S-T interval).
5. Chelation therapy. Administration of Dimercaprol (BAL) is usually indi-
cated in symptomatic arsenic poisonings, although DMPS, where available, may
prove to be a better antidote.The following dosage schedule has proven to be
effective in accelerating arsenic excretion.
Monitor urinary arsenic excretion while any chelating agent is being ad-
ministered. When 24-hour excretion falls below 50 meg per day, it usually is
advisable to discontinue the chelation therapy.
RECOMMENDED INTRAMUSCULAR DOSAGE OF BAL
(DIMERCAPROL) IN ARSENIC POISONING
1st day
2nd day
3rd day
Each of the following
days for 10 days, or
until recovery
Severe Poisoning
3.0 mg/kg q4h
(6 injections)
3.0 mg/kg q4h
(6 injections)
3.0 mg/kg q6h
(4 injections)
3.0 mg/kg q1 2 hr
(2 injections)
Mild Poisoning
2.5 mg/kg q6h
(4 injections)
2.5 mg/kg q6h
(4 injections)
2.5 mg/kg q1 2h
(2 injections)
2.5 mg/kg qd
(1 injection)
BAL is provided as a 100 mg/mL solution in oil. Dosages in the table are in terms of BAL
itself, not of the solution. Dosages for children are consistent with the "Mild Poisoning"
schedule and can be between 2.5 and 3.0 mg/kg per dose.16
Caution: Disagreeable side effects often accompany the use of BAL: nausea,
headache, burning and tingling sensations, sweating, pain in the back and abdo-
men, tremor, restlessness, tachycardia, hypertension, and fever. Coma and con-
vulsions occur at very high dosage. Sterile abscesses may form at injection sites.
Acute symptoms usually subside in 30-90 minutes. Antihistamine drugs or an
oral dose of 25-50 mg ephedrine sulfate or pseudoephedrine provide relief.
These are more effective if given a few minutes before the injection of BAL.
BAL may potentially have other adverse effects. In rabbits, treatment of arsenite
exposure with BAL increased brain arsenic levels.17
6. Oral treatments. After the gastrointestinal tract is reasonably free of arsenic,
oral administration of d-penicillamine, Succimer (DMSA), or DMPS should
probably replace BAL therapy. However, d-penicillamine has demonstrated lim-
ited effectiveness for arsenic exposure in experimental models.18
130 ARSENICALS
-------
Dosage of d-penicillamine:
Adults and children over 12 years: 0.5 g every 6 hours, given 30-60
minutes before meals and at bedtime for about 5 days.
Children under 12years:O.I g/kg body weight, every 6 hours, given
30-60 minutes before meals and at bedtime for about 5 days. Not to
exceed 1.0 g per day.
Caution: Adverse reactions to short-term therapy are rare. However,
persons allergic to penicillin should not receive d-penicillamine
as they may suffer allergic reactions to it.
Succimer (DMSA) has been shown to be an effective chelator of arsenic,
though it is not labeled for this indication.19 In Europe, DMPS has been used
successfully in treatment of arsenic poisoning. In light of the lack of effective-
ness of d-penicillamine, coupled with the low toxicity and high therapeutic
index of DMPS and DMSA, it appears that the latter two agents may be the
preferred method for chronic toxicity or when oral chelation is acceptable.18-19
Dosage of DMSA (Succimer):
Adults and Children: 10 mg/kg every 8 hours for 5 days, followed by
10 mg/kg every 12 hours for an additional 14 days. (Maximum 500
mg per dose). Should be given with food.
Dosage of DMPS:
Adults: 100 mg every 8 hours for 3 weeks to 9 months.
7. Hemodialysis. Extracorporeal hemodialysis, used in combination with
BAL therapy, has limited effectiveness in removing arsenic from the blood.
Hemodialysis is clearly indicated to enhance arsenic elimination and main-
tain extracellular fluid composition if acute renal failure occurs.
8. Renal function. In patients with intact renal function, alkalinization of
the urine by sodium bicarbonate to maintain urine pH >7.5 may help pro-
tect renal function in the face of hemolysis occurring as part of the acute
poisoning.
ARSENICALS 131
-------
HIGHLIGHTS
Signs and Symptoms:
Malaise, dizziness, nausea,
abdominal pain
Hemoglobinuria and
jaundice.
Treatment:
Supportive
Exchange transfusion may
be considered
132 ARSENICALS
ARSINE GAS
Arsine is not used as a pesticide. However, some poisonings by arsine
have occurred in pesticide manufacturing plants and metal refining op-
erations when arsenicals came into contact with mineral acids or strong
reducing agents.
Toxicology
Arsine is a powerful hemolysin, a toxic action not exhibited by other
arsenicals. In some individuals, very little inhalation exposure is required to
cause a serious hemolytic reaction. Exposure times of 30 minutes at 25-50
parts per million are considered lethal.20 Symptoms of poisoning usually
appear 1-24 hours after exposure: headache, malaise, weakness, dizziness,
dyspnea, nausea, abdominal pain, and vomiting. Dark red urine (hemoglo-
binuria) is often passed 4-6 hours after exposure. Usually 1-2 days after
hemoglobinuria appears, jaundice is evident. Hemolytic anemia, sometimes
profound, usually provides diagnostic confirmation and can cause severe
weakness. Abdominal tenderness and liver enlargement are often apparent.
Basophilic stippling of red cells, red cell fragments, and ghosts are seen in
the blood smear. Methemoglobinemia and methemoglobinuria are evi-
dent. Elevated concentrations of arsenic are found in the urine, but these
are not nearly as high as are found in poisonings by solid arsenicals. Plasma
content of unconjugated bilirubin is elevated.
Renal failure due to direct toxic action of arsine and to products of
hemolysis represents the chief threat to life in arsine poisoning.21
Polyneuropathy and a mild psycho-organic syndrome are reported to
have followed arsine intoxication after a latency of 1-6 months.
Treatment
1. Remove the victim to fresh air.
2. Administer intravenous fluids to keep the urine as dilute as possible and to
support excretion of arsenic and products of hemolysis. Include sufficient
sodium bicarbonate to keep the urine alkaline (pH greater than 7.5).
Caution: Monitor fluid balance carefully to avoid fluid overload if
renal failure supervenes. Monitor plasma electrolytes to detect disturbances
(particularly hyperkalemia) as early as possible.
3. Monitor urinary arsenic excretion to assess severity of poisoning. The
amount of arsine that must be absorbed to cause poisoning is small, and
therefore high levels of urinary arsenic excretion may not always occur,
even in the face of significant poisoning.21'22
4. If poisoning is severe, exchange blood transfusion may be considered.
It was successful in rescuing one adult victim of arsine poisoning.
5. Extracorporeal hemodialysis may be necessary to maintain normal extra-
cellular fluid composition and to enhance arsenic elimination if renal failure
occurs, but it is not very effective in removing arsine carried in the blood.
-------
General Chemical Structures
INORGANIC TRIVALENT
Arsenic trioxide
O
/ \
As-O-As
"White arsenic." Arsenous oxide. Has been
discontinued but still may be available
from prior registrations.
Sodium arsenite
Na-0-As = 0
Sodanit, Prodalumnol Double. All uses
discontinued in the U.S.
Calcium arsenite
O As=O
I
Ca (approx.)
I
OAs=0
Mono-calcium arsenite, London purple.
Flowable powder for insecticidal use on
fruit. All uses discontinued in the U.S.
Copper arsenite
(Acid copper arsenite)
HO-Cu-O-As = O
Wettable powder, for use as insecticide,
wood preservative. All uses discontinued
in the U.S.
Copper acetoarsenite
O
Cu-(O-C-CH3)2
3Cu-(O-As=O)2
Insecticide. Paris green, Schweinfurt green,
Emerald green, French green, Mitis green.
No longer used in the U.S.; still used
outside U.S.
Arsine
H
H
Not a pesticide. Occasionally generated
during manufacture of arsenicals.
\
As
I
H
INORGANIC PENTAVALENT
Arsenic acid
OH
HO
\ I
As=O
Hi-Yield Dessicant H-10, Zotox. Water
solutions used as defoliants, herbicides, and
wood preservatives.
HO
Sodium arsenate
NaO OH
Disodium arsenate. Jones Ant Killer. All
uses discontinued, but may still be
encountered from old registration.
As=0
NaO
ARSENICALS 133
-------
Calcium arsenate
O O
O O O O
x \ // ^ x \
Ca As O Ca O As Ca the U S
\ x \ x
O O
Tricalcium arsenate, Spra-cal,Turf-Cal.
Flowable powder formulations used
against weeds, grubs. No longer used in
Lead arsenate
O OH
x \
Pb As = O
\ /
O
Gypsine, Soprabel. Limited use in the
U.S.; wettable powder used as insecticide
outside the U.S.
O
x \ ,
In As
\ x
O
Zinc arsenate
O 00
5- ^ x \
O In O As In
\ x
O
Powder once used in U.S. as insecticide
on potatoes and tomatoes.
ORGANIC (PENTAVALENT)
Cacodylic acid (sodium cacodylate) Non-selective herbicide, defoliant,
silvicide. Bolate, Bolls-Eye, Bophy, Dilic,
6Q> Rad_E_Cate 25; Salvo.
As
OH
(or Na)
Methane arsonic acid
CH3 OH
\ x
As
MAA. Non-selective herbicide.
O
OH
Monosodium methane arsonate
CH3 OH
\ x
As
-
O
OH
MSMA. Non-selective herbicide,
defoliant, silvicide. Ansar 170, Arsonate
Liquid, Bueno 6, Daconate 6, Dal-E-Rad,
Drexar 530, Herbi-All, Merge 823,
Mesamate.Target MSMA,Trans-Vert,
Weed-E-Rad, Weed-Hoe.
Disodium methane arsonate
CH3 ONa
\ x
As
x \
O ONa
DSMA. Selective post-emergence
herbicide, silvicide. Ansar 8100, Arrhenal,
Arsinyl, Crab-E-Rad, Di-Tac, DMA,
Methar 30, Sodar, Weed-E-Rad 360.
Monoammonium methane arsonate MAMA. Selective post-emergence
CH3 ONH4 herbicide. No longer used in the U.S.
\ X
As
OH
134 ARSENICALS
-------
Calcium acid methane arsonate CAMA. Selective post-emergence
r*u /-ILJ LJ/-I ^u herbicide. Calar, Super Crab-E-Rad-
UM3 Un HU UM3 ,-,,-,
\ X \ / Calar, Super Dal-E-Rad.
As As
^ \ / ^
O O - Ca - O O
References
1. Malachowski ME. An update on arsenic. Clln Lab Med 1990; 10(3):459-72.
2. Ellenhorn, MJ. Arsenic: Metals and related compounds. In: Ellenhorn's Medical Toxicology,
Diagnosis and Treatment of Human Poisoning, 2nd ed. Baltimore: Williams & Wilkins,
1997, p. 1540.
3. Campbell JP and Alvarez JA. Acute arsenic intoxication. Am Fam Physician 1989; 40(6):93-7.
4. St. Petery J, Gross C, and Victorica BE. Ventricular fibrillation caused by arsenic poisoning.
AJDC 1970; 120:367-71.
5. Goldsmith S and From AHL. Arsenic-induced atypical ventricular tachycardia. New Engl J
Med 1980; 303(19). 1096-8.
6. Heyman A, Pfeiffer JB Jr., Willett RW, et al. Peripheral neuropathy caused by arsenical in-
toxication. A study of 41 cases with observations on the effects of BAL (2,3-dimercapto-
propanol). N Engl J Med 1956;254:401-9.
7. Donofrio PD.WilbournAJ.AlbersJW, etal. Acute arsenic intoxication presenting as Guillain-
Barre-like syndrome. Muscle Nerve 1987; 10:114-20.
8. Maloney ME. Arsenic in dermatology. Dermatol Surg 1996;22:301-4.
9. Navarro B, Sayas MJ, Atienza A, and Leon R An unhappily married man with thick soles.
Lancet 1996;347:1596.
10. LinTH, Huang YL, and Wang MY. Arsenic species in drinking water, hair, fingernails, and
urine of patients with blackfoot disease. JToxicol Environ Health 1998;53A:85-93.
11. Fesmire FM, Schauben JL, and Roberge RJ. Survival following massive arsenic ingestion.
AmJEmergMed, 1998;6(6):602-6.
12. ACGIH. 1997TLVs and BEIs.Threshold limit values for chemical substances and physical
agents. Biological exposure indices. Cincinnati, 1997.
13. Wagner SL and Weswig P. Arsenic in blood and urine of forest workers. Arch Environ Health
1974; 28:77-9.
14. Buchet JP, Pauwels J, and Lauwerys R. Assessment of exposure to inorganic arsenic follow-
ing ingestion of marine organisms by volunteers. Environ Res 1994;66:44-51.
15. Baselt RA and Cravey RH. Arsenic. In: Disposition ofToxic Drugs and Chemicals in Men,
3rd ed. Chicago, IL: Year Book Medical Publishers, 1990, pp. 65-9.
16. Barone MA. Drug doses; Dimercaprol. In:The Harriet Lane Handbook, 14th ed. Baltimore:
Mosby, 1996, p. 525.
17. Hoover TD and Aposhian HV. BAL increased the arsenic-74 content of rabbit brain. Toxicol
Appl Pharmacol 1983; 70:160-2.
ARSENICALS 135
-------
18. Kreppel H, Reichl FX, Forth W, and Fichtl B. Lack of effectiveness of d-penicillamine in
experimental arsenic poisoning. Vet Hum Toxicol 1989;31:l-5.
19. Muckter H, Liebl B, Beichl FX, et al. Are we ready to replace dimercaprol (BAL) as an
arsenic antidote? Hum Exp Toxicol 1997;16:460-5.
20. Blackwell M and Robbins A. NIOSH Current Intelligence Bulletin #32,Arsine (arsenic
hydride) poisoning in the workplace. Am Ind HygAssoc J 1979;40:A56-61.
21. Fowler BA andWeissberg JB.Arsine poisoning. New Engl JMed 1974;291:1171-4.
22. Rathus E, Stingon RG, and Putrnan JL. Arsine poisoning, country style. MedJAust 1979;!: 163-6.
136 ARSENICALS
-------
CHAPTER 15
Fungicides
Fungicides are extensively used in industry, agriculture, and the home and gar-
den for a number of purposes, including: protection of seed grain during stor-
age, shipment, and germination; protection of mature crops, berries, seedlings,
flowers, and grasses in the field, in storage, and during shipment; suppression of
mildews that attack painted surfaces; control of slime in paper pulps; and pro-
tection of carpet and fabrics in the home.
Fungicides vary enormously in their potential for causing adverse effects in
humans. Historically, some of the most tragic epidemics of pesticide poisoning
occurred because of mistaken consumption of seed grain treated with organic
mercury or hexachlorobenzene. However, most fungicides currently in use are
unlikely to cause frequent or severe systemic poisonings for several reasons.
First, many have low inherent toxicity in mammals and are inefficiently ab-
sorbed. Second, many fungicides are formulated as suspensions of wettable pow-
ders or granules, from which rapid, efficient absorption is unlikely. And third,
methods of application are such that relatively few individuals are intensively
exposed. Apart from systemic poisonings, fungicides as a class are probably re-
sponsible for a disproportionate number of irritant injuries to skin and mucous
membranes, as well as dermal sensitization.
The following discussion covers the recognized adverse effects of widely
used fungicides. For fungicides that have caused systemic poisoning, recom-
mendations for management of poisonings and injuries are set forth. For fungi-
cides not known to have caused systemic poisonings in the past, only general
guidelines can be offered.
The discussion of fungicide-related adverse effects proceeds in this order:
Substituted Benzenes
Thiocarbamates
Ethylene Bis Dithiocarbamates
Thiophthalimides
Copper Compounds
Organomercury Compounds
Organotin Compounds
Cadmium Compounds
Miscellaneous Organic Fungicides
HIGHLIGHTS
Numerous fungicides in use
with varying levels of
toxicity
Other than organomercury
compounds, most
fungicides are unlikely to be
absorbed enough to cause
systemic poisonings
Signs and Symptoms:
Variable
Treatment:
Dermal and eye
decontamination
Gl decontamination
Intravenous fluids
Contraindicated:
Atropine. Fungicides are
not cholinesterase
inhibitors
FUNGICIDES 137
-------
Commercial Products
SUBSTITUTED BENZENES
SUBSTITUTED BENZENES
chloroneb
Terraneb SP
chlorothalonil
Bravo
Clorto Caffaro
Clortosip
Daconil 2787
Exotherm Termil
Tuffcide
others
dicloran
Allisan
Clortran
DCNA
hexachlorobenzene*
Anticarie
Ceku C.B.
HCB
No Bunt
pentachloronitrobenzene
Avicol
Earthcide
Folosan
Kobu
Kobutol
PCNB
Pentagen
quintozene
Tri-PCNB
others
* Discontinued in the U.S.
Toxicology
Chloroneb is supplied as wettable powder for treatment of soil and seed.
This agent exhibits very low oral toxicity in mammals. It may be moderately
irritating to skin and mucous membranes. The metabolite dichloromethoxy-
phenol is excreted in the urine. No cases of systemic poisoning in humans have
been reported.
Chlorothalonil is available as wettable powder, water dispersible granules,
and flowable powders. Chlorothalonil has caused irritation of skin and mucous
membranes of the eye and respiratory tract on contact. Cases of allergic contact
dermatitis have been reported.There is one report of immediate anaphylactoid
reaction to skin contact.' It is apparently poorly absorbed across the skin and
the gastrointestinal lining. No cases of systemic poisoning in humans have been
reported.
Dicloran is a broad-spectrum fungicide widely used to protect perishable
produce. It is formulated as wettable powder, dusts, and flowable powders.
Dicloran is absorbed by occupationally exposed workers, but it is promptly
eliminated, at least partly in the urine. Biotransformation products include
dichloroaminophenol, which is an uncoupler of oxidative phosphorylation (en-
hances heat production). Extraordinary doses of dicloran given to laboratory
animals cause liver injury and corneal opacities.
Based on laboratory animal studies and effects of similar compounds, large
doses might be expected to cause liver injury, pyrexia, corneal opacities, and
possibly methemoglobinemia. None of these have been observed in humans
exposed to DCNA.
Hexachlorobenzene.Principal formulations are dusts and powders.
Hexachlorobenzene differs chemically and toxicologically from hexachlorocy-
clohexane,the gamma isomer of which (lindane) is still a widely-used insecticide.
Although this seed protectant fungicide has only slight irritant effects and
relatively low single-dose toxicity, long-term ingestion of HCB-treated grain
by Turkish farm dwellers in the late 1950s caused several thousand cases of
toxic porphyria resembling porphyria cutanea tarda.2This condition was due
to impaired hemoglobin synthesis, leading to toxic end-products (porphyrins)
in body tissues.The disease was characterized by excretion of red-tinged (por-
phyrin-containing) urine, bullous lesions of light-exposed skin, scarring and
atrophy of skin with overgrowth of hair, liver enlargement, loss of appetite,
arthritic disease, and wasting of skeletal muscle mass. Although most adults
ultimately recovered after they stopped consuming the HCB-treated grain, some
infants nursed by affected mothers died.
Hexachlorobenzene is effectively dechlorinated and oxidized in humans;
trichlorophenols are the major urinary excretion products. Disposition is suffi-
ciently prompt that occupationally exposed workers usually show only slight
138 FUNGICIDES
-------
elevation of blood HCB concentrations. HCB is sometimes present in blood
specimens from "non-occupationally exposed" persons in concentrations of up
to 5 meg per liter. Residues in food are the probable cause.
Pentachloronitrobenzene is used to dress seed and treat soil. Formula-
tions include emulsifiable concentrates, wettable powders, and granules.
Hexachlorobenzene is a minor contaminant to technical PCNB.
High concentrations in prolonged contact with skin have caused sensitiza-
tion in some tested volunteers, but neither irritation nor sensitization has been
reported in occupationally exposed workers. One case of conjunctivitis and keratitis
occurred following eye contamination.This resolved slowly but completely.
Systemic poisonings have not been reported. Clearance in laboratory ani-
mals is slow, probably due to enterohepatic recirculation. Excretion is chiefly
biliary, with some conversion to pentachloroaniline, pentachlorophenol, and
other metabolites in the liver. Although a methemoglobinemic effect might be
suspected (as from nitrobenzene), this has not been reported in humans or
animals, nor has toxic porphyria (as from hexachlorobenzene) been reported.
Confirmation of Poisoning
Hexachlorobenzene (HCB) can be measured in blood by gas chromatog-
raphy. Chlorophenol metabolites can be measured in the urine. Although in-
herited disease and a number of exogenous agents may cause porphyrins to
appear in the urine, a test for porphyrins may be useful for toxicological diag-
nosis if there has been a known exposure to HCB or if a patient exhibits signs
suggestive of porphyria cutanea tarda.
Gas chromatography can be used to measure PCNB and metabolites,
chlorothalonil, and chloroneb, but the analysis is not widely available. Methods
have also been described for analysis of dicloran, but they are not widely available.
Treatment
1. Skin decontamination. Dermal contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water. If irritation persists, specialized medical care should be obtained. See
Chapter 2.
2. Gastrointestinal decontamination. If a large amount of the fungicide has
been ingested in the last few hours, and if copious vomiting has not already
occurred, it may be reasonable to consider GI decontamination. Activated char-
coal can be used along with the addition of the cathartic sorbitol to the char-
coal slurry. If sorbitol is given separately, it should be diluted with an equal
volume of water before administration. No more than one dose of sorbitol is
recommended and it should be used with caution in children and the elderly.
See Chapter 2 for appropriate dosages.
FUNGICIDES 139
-------
Commercial Products
THIOCARBAMATES
ferbam
Carbamate WDG
Ferbam
Ferberk
Hexaferb
Knockmate
Trifungol
metam-sodium
A7 Vapam
Busan 1020
Karbation
Maposol
Metam-Fluid BASF
Nemasol
Solasan 500
Sometam
Trimaton
Vapam
VPM
thiram
Aules
Chipco Thiram 75
Fermide 850
Fernasan
Hexathir
Mercuram
Nomersam
Polyram-Ultra
Pomarsol forte
Spotrete-F
Spotrete WP 75
Tetrapom
Thimer
Thioknock
Thiotex
Thiramad
Thirasan
Thiuramin
Tirampa
TMTD
Tram eta n
Tripomol
Tuads
ziram
Cuman
Hexazir
Mezene
Tricarbamix
Triscabol
Vancide MZ-96
Zincmate
Ziram F4
Ziram Technical
Zirberk
Zirex 90
Ziride
Zitox
If contact with the toxicant has been minimal (for example, oral contami-
nation only, promptly flushed out of the mouth), administration of charcoal
without a cathartic, followed by careful observation of the patient, probably
represents optimal management.
3. Porphyria. Persons affected by porphyria should avoid sunlight, which ex-
acerbates the dermal injury by porphyrins.
THIOCARBAMATES
Thiocarbamates are commonly formulated as dusts, wettable powders, or water
suspensions. They are used to protect seeds, seedlings, ornamentals, turf, veg-
etables, fruit, and apples. Unlike the N-methyl carbamates (Chapter 5),
thiocarbamates have very little insecticidal potency. A few exhibit weak anti-
cholinesterase activity, but most have no significant effect on this enzyme. Overall,
they are less of a threat to human health than the insecticidal carbamates. Fun-
gicidal thiocarbamates are discussed in this section, while those used as herbi-
cides are considered in Chapter 13.
METAM-SODIUM
Metam-sodium is formulated in aqueous solutions for application as a soil
biocide and fumigant to kill fungi, bacteria, weed seeds, nematodes, and insects.
All homeowner uses have been cancelled in the United States.
Toxicology
Metam-sodium can be very irritating to the skin. Poisonings by ingestion
of metam-sodium have not been reported. Although animal feeding studies do
not indicate extraordinary toxicity of metam-sodium by ingestion, its decom-
position in water yields methyl isothiocyanate, a gas that is extremely irritating
to respiratory mucous membranes, to the eyes, and to the lungs. Inhalation of
methyl isothiocyanate may cause pulmonary edema (severe respiratory distress,
coughing of bloody, frothy sputum). For this reason, metam-sodium is consid-
ered a fumigant. It must be used in outdoor settings only, and stringent precau-
tions must be taken to avoid inhalation of evolved gas.
Theoretically, exposure to metam-sodium may predispose the individual
to Antabuse reactions if alcohol is ingested after exposure. (See Thiram.) How-
ever, no such occurrences have been reported.
140 FUNGICIDES
-------
Confirmation of Poisoining
No tests for metam-sodium or its breakdown products in body fluids are
available.
Treatment
1. Skin decontamination. Skin contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water to avoid burns and corneal injury. If dermal or eye irritation persists,
specialized medical treatment should be obtained. See Chapter 2.
2. Gastrointestinal decontamination. If a large amount has been ingested
recently, consider gastric emptying or charcoal and cathartic. See Chapter 2 for
appropriate dosages.
3. Pulmonary edema. If pulmonary irritation or edema occur as a result of
inhaling methyl isothiocyanate, transport the victim promptly to a medical fa-
cility. Treatment for pulmonary edema should proceed as outlined in Chapter
16, Fumigants.
4. Contraindicated: Metam-sodium is not a cholinesterase inhibitor. Atro-
pine is not an antidote.
THIRAM
Thiram is a common component of latex and possibly responsible for
some of the allergies attributed to latex.
Toxicology
Thiram dust is moderately irritating to human skin, eyes, and respiratory
mucous membranes. Contact dermatitis has occurred in occupationally ex-
posed workers. A few individuals have experienced sensitization to thiram.3
Systemic human poisonings by thiram itself have been very few, probably
due to limited absorption in most circumstances involving human exposure.
Those which have been reported have been similar clinically to toxic reactions
to disulfiram (Antabuse), the ethyl analogue of thiram which has been exten-
sively used in alcohol aversion therapy.3 In laboratory animals, thiram at high
dosage has effects similar to those of disulfiram (hyperactivity, ataxia, loss of
muscle tone, dyspnea, and convulsions), but thiram appears to be about 10
times as toxic as disulfiram.
FUNGICIDES 141
-------
Neither thiram nor disulfiram are cholinesterase inhibitors. Both, however,
inhibit the enzyme acetaldehyde dehydrogenase, which is critical to the
conversion of acetaldehyde to acetic acid. This is the basis for the "Antabuse
reaction" that occurs when ethanol is consumed by a person on regular disulfiram
dosage. The reaction includes symptoms of nausea, vomiting, pounding headache,
dizziness, faintness, mental confusion, dyspnea, chest and abdominal pain, profuse
sweating, and skin rash. In rare instances, Antabuse reactions may have occurred
in workers who drank alcohol after previously being exposed to thiram.
Confirmation of Poisoning
Urinary xanthurenic acid excretion has been used to monitor workers
exposed to thiram.The test is not generally available.
Treatment: Thiram Toxicosis
1. Skin decontamination. Wash thiram from the skin with soap and water.
Flush contamination from the eyes with copious amounts of clean water. If irri-
tation of skin or eyes persists, specialized medical treatment should be obtained.
2. Gastrointestinal decontamination. If a large amount of thiram has been
swallowed within 60 minutes of presentation, and effective vomiting has not
already occurred, the stomach may be emptied by intubation, aspiration, and
lavage, taking all precautions to protect the airway from aspiration of vomitus.
Lavage should be followed by instillation of activated charcoal and cathartic. If
only a small amount of thiram has been ingested and/or treatment has been
delayed, oral administration of activated charcoal and cathartic probably repre-
sents optimal management.
3. Intravenous fluids. Appropriate IV fluids should be infused, especially if
vomiting and diarrhea are severe. Serum electrolytes and glucose should be
monitored and replaced as needed.
Treatment: Acetaldehyde Toxicosis (Antabuse Reaction)
1. Immediate management. Oxygen inhalation, Trendelenburg position-
ing, and intravenous fluids are usually effective in relieving manifestations of
Antabuse reactions.
2. Alochol avoidance. Persons who have absorbed any significant amount of
thiocarbamates must avoid alcoholic beverages for at least three weeks. Dispo-
sition of thiocarbamates is slow, and their inhibitory effects on enzymes are
slowly reversible.
142 FUNGICIDES
-------
ZIRAM AND FERBAM
These are formulated as flowable and wettable powders, used widely on
fruit and nut trees, apples, vegetables, and tobacco.
Toxicology
Dust from these fungicides is irritating to the skin, respiratory tract, and
eyes. Prolonged inhalation of ziram is said to have caused neural and visual
disturbances, and, in a single case of poisoning, a fatal hemolytic reaction.Theo-
retically, exposure to ziram or ferbam may predispose the individual to Antabuse
reactions if alcohol is ingested after exposure. (SeeThiram.) However, no such
occurrences have been reported.
Confirmation of Poisoning
No tests for these fungicides or their breakdown products in body fluids
are available.
Treatment
1. Skin decontamination. Skin contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water. If dermal or eye irritation persists, specialized medical treatment should
be obtained. See Chapter 2.
2. Gastrointestinal decontamination. If substantial amounts of ferbam or
ziram have been ingested recently, consideration should be given to gastric
emptying. If dosage was small and/or several hours have elapsed since inges-
tion, oral administration of charcoal and a cathartic probably represents optimal
management.
3. Hemolysis. If hemolysis occurs, intravenous fluids should be administered,
and induction of diuresis considered.
FUNGICIDES 143
-------
Commercial Products
ETHYLENE BIS
DITHIOCARBAMATES
(EBDC COMPOUNDS)
mancozeb
Dithane
Mancozin
manzeb
Manzin
Nemispor
Penncozeb
Ziman-Dithane
maneb
Kypman 80
Maneba
Manex
Manex 80
M-Diphar
Sopranebe
Trimangol
nabam
Chem Bam
DSE
Parzate
Spring Bak
zineb
Aspor
Dipher
Hexathane
Kypzin
Parzate C
Tritoftorol
Zebtox
ETHYLENE BIS DITHIOCARBAMATES
(EBDC COMPOUNDS)
MANEB, ZINEB, NABAM, AND MANCOZEB
Maneb and zineb are formulated as wettable and flowable powders. Nabam
is provided as a soluble powder and in water solution. Mancozeb is a coordina-
tion product of zinc ion and maneb. It is formulated as a dust and as wettable
and liquid flowable powders.
Toxicology
These fungicides may cause irritation of the skin, respiratory tract, and eyes.
Both maneb and zineb have apparently been responsible for some cases of chronic
skin disease in occupationally exposed workers, possibly by sensitization.
Although marked adverse effects may follow injection of EBDC compounds
into animals, systemic toxicity by oral and dermal routes is generally low. Nabam
exhibits the greatest toxicity, probably due to its greater water solubility and
absorbability. Maneb is moderately soluble in water, but mancozeb and zineb
are essentially water insoluble. Absorption of the latter fungicides across skin
and mucous membranes is probably very limited. Systemic poisonings of humans
have been extremely rare. However, zineb apparently precipitated an episode of
hemolytic anemia in one worker predisposed by reason of multiple red cell
enzyme deficiencies.4 Maneb exposure has been reported in one person who
developed acute renal failure and was treated with hemodialysis.5 Another person
developed behavioral and neurological symptoms including tonic-clonic seizures
after handling maneb. He recovered uneventfully with supportive care.6
The EBDC compounds are not inhibitors of cholinesterase or of acetalde-
hyde dehydrogenase.They do not induce cholinergic illness or "Antabuse" re-
actions.
Confirmation of Poisoining
No tests for these fungicides or their breakdown products in body fluids
are available.
Treatment
See Treatment for Substituted Benzenes, p. 139.
144 FUNGICIDES
-------
THIOPHTHALIMIDES
Commercial Products
CAPTAN, CAPTAFOL, AND FOLPET
These agents are widely used to protect seed, field crops, and stored pro-
duce.They are formulated as dusts and wettable powders. Captafol is no longer
registered for use in the United States.
Toxicology
All of these fungicides are moderately irritating to the skin, eyes, and
respiratory tract. Dermal sensitization may occur; captafol appears to have been
responsible for several episodes of occupational contact dermatitis.7'8 No systemic
poisonings by thiophthalimides have been reported in humans, although captafol
has been reported to have exacerbated asthma after occupational exposure.9
Laboratory animals given very large doses of captan exhibit hypothermia,
irritability, listlessness, anorexia, hyporeflexia, and oliguria, the latter with
glycosuria and hematuria.
Confirmation of Poisoning
Captan fungicides are metabolized in the body to yield two metabolites
that can be measured in the urine.10
Treatment
See Treatment for Substituted Benzenes, p. 139.
COPPER COMPOUNDS
INORGANIC AND ORGANIC COMPOUNDS
Insoluble compounds are formulated as wettable powders and dusts. Soluble
salts are prepared as aqueous solutions. Some organometallic compounds are
soluble in mineral oils.
A great many commercial copper-containing fungicides are available. Some
are mixtures of copper compounds. Others include lime, other metals, and
other fungicides. Compositions of specific products can usually be provided by
manufacturers or by poison control centers.
Copper-arsenic compounds such as Paris green may still be used in agri-
culture outside the U.S. Toxicity of these compounds is chiefly due to arsenic
content (see Chapter 14, Arsenical Pesticides).
THIOPHTHALIMIDES
captafol*
Crisfolatan
Difolatan
Foltaf
Haipen
Merpafol
Mycodifol
Sanspor
captan
Captaf
Captanex
Merpan
Orthocide
Vondcaptan
folpet
Folpan
Fungitrol II
Phaltan
Thiophal
COPPER COMPOUNDS
Inorganic Copper Compounds
copper acetate
copper ammonium carbonate
copper carbonate, basic
copper hydroxide
copper lime dust
copper oxychloride
copper potassium sulfide
copper silicate
copper sulfate
cupric oxide
cuprous oxide
tribasic
Bordeaux Mixture
Organic Copper Compunds
copper linoleate
copper naphthenate
copper oleate
copper phenyl salicylate
copper quinolinolate
copper resinate
* Discontinued in the U.S.
FUNGICIDES 145
-------
Toxicology
The dust and powder preparations of copper compounds are irritating to the
skin, respiratory tract, and particularly to the eyes. Soluble copper salts (such as
the sulfate and acetate) are corrosive to mucous membranes and the cornea.
Limited solubility and absorption probably account for the generally low sys-
temic toxicity of most compounds. The more absorbable organic copper com-
pounds exhibit the greatest systemic toxicity in laboratory animals. Irritant effects
from occupational exposures to copper-containing fungicides have been fairly
frequent. Most of what is known about mammalian toxicity of copper com-
pounds has come from veterinary toxicology (livestock seem uniquely vulner-
able) and poisonings in humans due to deliberate ingestion of copper sulfate or to
consumption of water or food that had been contained in copper vessels.
Early signs and symptoms of copper poisoning include a metallic taste,
nausea, vomiting, and epigastric pain. In more severe poisonings, the gastrointes-
tinal irritation will worsen with hemetemesis and melanotic stools. Jaundice
and hepatomegaly are common.n'12Hemolysis can occur, resulting in circula-
tory collapse and shock. Methemoglobinemia has been reported in these
cases.11'13'14 Acute renal failure with oliguria can also occur. Shock is a primary
cause of death early in the course, and renal failure and hepatic failure contrib-
ute to death more than 24 hours after poisoning.15
Treatment
Management of poisonings by ingestion of copper-containing fungicides
depends entirely on the chemical nature of the compound: the strongly ionized
salts present the greatest hazard; the oxides, hydroxides, oxychloride, and
oxysulfate are less likely to cause severe systemic poisoning.
1. Skin decontamination. Dust and powder should be washed from the skin
with soap and water. Flush the eyes free of irritating dust, powder, or solution,
using clean water or saline. If eye or dermal irritation persists, specialized medi-
cal treatment should be obtained. Eye irritation may be severe. See Chapter 2.
2. Anti-corrosive. Give water or milk as soon as possible to dilute the toxicant
and mitigate corrosive action on the mouth, esophagus, and gut.
3. Gastrointestinal decontamination. Vomiting is usually spontaneous in
acute copper ingestion. Further induction of emesis is contraindicated because
the corrosive nature of some copper salts can cause further damage to the
esophagus. Further GI decontamination should be determined on a case-by-
case basis, as outlined in Chapter 2. Gastric lavage may cause further damage.15
Charcoal has not been widely studied in metal poisonings as an effective
adsorbant.
146 FUNGICIDES
-------
Caution: Gastric intubation may pose a serious risk of esophageal perfo-
ration if corrosive action has been severe. In this event, it may be best to avoid
gastric intubation.
4. Intravenous fluids. If indications of systemic illness appear, administer in-
travenous fluids containing glucose and electrolytes. Monitor fluid balance, and
correct blood electrolyte concentrations as needed. If shock develops, give blood
transfusions and vasopressor amines, as required.
5. Hemolysis. Monitor plasma for evidence of hemolysis (free hemoglobin)
and the red cells for methemoglobin. If hemolysis occurs, alkalinize the urine
to about pH 7.5 by adding sodium bicarbonate to the intravenous infusion
fluid. Also, mannitol diuresis may be considered. If methemoglobinemia is se-
vere (> 30%), or the patient is cyanotic, administer methylene blue.The dosage
for adults/child is 1-2 mg/kg/dose, given as a slow IV push over a few minutes,
every 4 hours as needed.15
6. Pain management. Severe pain may require the administration of mor-
phine.
7. Chelating agents. The value of chelating agents in copper poisoning has
not been established.16 However, BAL appears to accelerate copper excretion
and may alleviate illness. D-penicillamine is the treatment for Wilson's disease
due to chronic copper toxicity; however, in the context of severe vomiting
and/or mental status changes from an acute ingestion, BAL would be a more
likely initial choice.13'15 For a recommended schedule of dosage for initial therapy
with BAL and subsequent penicillamine administration, see Chapter 14, Ar-
senical Pesticides.
Commercial Products
ORGANOMERCURY
COMPOUNDS
Methyl Mercury
Compounds
methyl mercury acetate
propionate
quinolinolate
Methoxyethyl Mercury
Compounds
methoxyethyl mercury acetate
MEMA
Panogen
Panogen M
methoxyethyl mercury chloride
Ceresan
Emisan 6
MEMC
Phenyl mercuric Acetate
Agrosan
Setrete
Gallotox
PMAA
Shimmer-ex
Tag HE 331
Unisan
8. Hemodialysis. Although hemodialysis is indicated for patients with renal
failure, copper is not effectively removed in the dialysate.11
ORGANOMERCURY COMPOUNDS
METHYL MERCURY AND METHOXYETHYL
MERCURY COMPOUNDS, PHENYLMERCURIC ACETATE
These fungicides have been formulated as aqueous solutions and dusts.
They have been used chiefly as seed protectants. Use of alkyl mercury fungicides
in the United States has been virtually prohibited for several years. Phenyl-
mercuric acetate is no longer permitted to be used in the United States.
FUNGICIDES 147
-------
Toxicology
The mercurial fungicides are among the most toxic pesticides ever
developed, for both chronic and acute hazards. Epidemics of severe, often fatal,
neurologic disease have occurred when indigent residents of less developed
countries consumed methyl mercury-treated grain intended for planting of
crops.17'18 Poisoning has also occurred from eating meat from animals fed
mercury-treated seed.19 Most of what is known of poisoning by organic mercurial
fungicides has come from these occurrences.
Organic mercury compounds are efficiently absorbed across the gut and
possibly across the skin.Volatile organic mercury is readily taken up across the
pulmonary membrane. Methyl mercury is selectively concentrated in the tissue
of the nervous system, and also in red blood cells. Other alkyl mercury com-
pounds are probably distributed similarly. Excretion occurs almost entirely by
way of the bile into the bowel. The residence half-life of methyl mercury in
humans is about 65 days.20 There is significant conversion of organic mercury
to inorganic mercury in the red cell.
Early symptoms of poisoning are metallic taste in the mouth, numbness
and tingling of the digits and face, tremor, headache, fatigue, emotional lability,
and difficulty thinking. Manifestations of more severe poisoning are incoordi-
nation, slurred speech, loss of position sense, hearing loss, constriction of visual
fields, spasticity or rigidity of muscle movements, and deterioration of mental
capacity. Many poisonings caused by ingestion of organic mercurials have ter-
minated fatally, and a large percentage of survivors have suffered severe perma-
nent neurologic damage.17"19
Phenylmercuric acetate is not as extremely toxic as the alkyl mercury com-
pounds. It is not as efficiently absorbed from the gut as methyl mercury21 Phenyl-
mercuric acetate had been used to prevent fungal growth in latex paint. There
have been reports of acrodynia in persons exposed to mercury vapor from use of
interior latex paint. Symptoms include fever, erythema and desquamation of hands
and feet, muscular weakness, leg cramps, and personality changes.22 Phenyl-
mercuric compounds have since been banned from latex paint.20
Confirmation of Poisoning
Mercury content of blood and tissues can be measured by atomic absorp-
tion spectrometry. Blood levels of 5 mcg/dL or greater are considered elevated
for acute exposure.21 Special procedures are needed for extraction and mea-
surement of organic mercury compounds specifically.
148 FUNGICIDES
-------
Treatment
Commercial Products
Every possible precaution should be taken to avoid exposure to organic
mercury compounds. Ingestion of an organic mercury compound, even at low
dosage, is life threatening, and management is difficult.Very little can be done
to mitigate neurologic damage caused by organic mercurials.
Persons experiencing symptoms (metallic taste in mouth) after inhalation of
volatile organic mercury compounds (methyl mercury is the most volatile) should
be removed promptly from the contaminated environment and observed closely
for indications of neurologic impairment. Following are the basic steps in man-
agement of poisoning:
1. Skin decontamination. Skin and hair contaminated by mercury-contain-
ing dust or solution should be cleansed with soap and water. Flush contamina-
tion from the eyes with clean water. If irritation persists, specialized medical
care should be obtained. See Chapter 2.
2. Gastrointestinal decontamination. Consider gastrointestinal decontami-
nation as outlined in Chapter 2.
3. Chelation is an essential part of the management of mercury poisoning. For
dosages of specific agents, see Chapter 14, Arsenical Pesticides. Succimer (DMSA)
appears to be the most effective agent available in the United States. Dimerca-
prol (BAL) is contraindicated in these poisonings due to its potential to in-
crease brain levels of mercury.20 EDTA is apparently of little value in poisonings
by organic mercury. D-penicillamine is probably useful, is available in the United
States, and has proven effective in reducing the residence half-life of methyl
mercury in poisoned humans.20 2,3-dimercaptopropane-l-sulfonate acid
(DMPS) and N-acetyl-D,L-penicillamine (NAP) are probably also useful but
are not currently approved for use in the United States.
4. Hemodialysis. Extracorporeal hemodialysis and hemoperfusion may be
considered, although experience to date has not been encouraging.
ORGANOTIN
COMPOUNDS
fentin acetate*
Batasan
Brestan
Phenostat-A
Phentinoacetate
Suzu
TPTA
fentin chloride*
Tinmate
fentin hydroxide
Super Tin
Suzu-H
Tubotin
triphenyl tin
* Discontinued in the U.S.
ORGANOTIN COMPOUNDS
These compounds are formulated as wettable and flowable powders for use
mainly as fungicides to control blights on field crops and orchard trees. Fentin
chloride was also prepared as an emulsifiable concentrate for use as a mollusci-
cide (Aquatin 20 EC, discontinued 1995).Tributyltin salts are used as fungi-
cides and antifouling agents on ships. They are somewhat more toxic by the
oral route than triphenyltin, but toxic actions are otherwise probably similar.
FUNGICIDES 149
-------
Commercial Products
CADMIUM
COMPOUNDS
cadmium chloride*
Caddy
cadmium succinate*
Cadminate
cadmium sulfate*
Cad-Trete
Crag Turf Fungicide
Kromad
Miller 531
* Discontinued in the U.S.
Toxicology
These agents are irritating to the eyes, respiratory tract, and skin. They are
probably absorbed to a limited extent by the skin and gastrointestinal tract. Manifes-
tations of toxicity are due principally to effects on the central nervous system:
headache, nausea, vomiting, dizziness, and sometimes convulsions and loss of
consciousness. Photophobia and mental disturbances occur. Epigastric pain is
reported, even in poisoning caused by inhalation. Elevation of blood sugar, suffi-
cient to cause glycosuria, has occurred in some cases. The phenyltin fungicides
are less toxic than ethyltin compounds, which have caused cerebral edema,
neurologic damage, and death in severely poisoned individuals who were
exposed dermally to a medicinal compound of this type.23 No deaths and very
few poisonings have been reported as a result of occupational exposures to phenyltin
compounds.
Treatment
1. Skin decontamination. Skin contamination should be removed by wash-
ing with soap and water. Flush contaminants from the eyes with clean water or
saline. If irritation persists, specialized medical treatment should be obtained.
See Chapter 2.
2. Gastrointestinal decontamination. If large amounts of phenyltin com-
pound have been ingested in the past hour, measures may be taken to decon-
taminate the gastrointestinal tract, as outlined in Chapter 2.
3. Chelating agents. Neither BAL, penicillamine, nor other chelating agents
have been effective in lowering tissue stores of organotin compounds in ex-
perimental animals.
CADMIUM COMPOUNDS
Cadmium salts have been used to treat fungal diseases affecting turf and the
bark of orchard trees.They were formulated as solutions and emulsions. Miller
531 and Crag Turf Fungicide 531 were complexes of cadmium, calcium, cop-
per, chromium, and zinc oxides.They are now marketed as a generic fungicide.
Kromad is a mixture of cadmium sebacate, potassium chromate, and thiram.
Cad-Trete is a mixture of cadmium chloride and thiram. All cadmium fungi-
cides in the U.S. have been discontinued.
150 FUNGICIDES
-------
Toxicology
Cadmium salts and oxides are very irritating to the respiratory and gas-
trointestinal tracts. Inhaled cadmium dust or fumes can cause respiratory toxic-
ity after a latency period of several hours, including a mild, self-limited illness
of fever, cough, malaise, headaches, and abdominal pain, similar to metal fume
fever. A more severe form of toxicity includes chemical pneumonitis, and is
associated with labored breathing, chest pain, and a sometimes fatal hemor-
rhagic pulmonary edema.24-25 Symptoms may persist for weeks.
Ingested cadmium causes nausea, vomiting, diarrhea, abdominal pain, and
tenesmus. Relatively small inhaled and ingested doses produce serious symp-
toms. Protracted absorption of cadmium has led to renal damage (proteinuria
and azotemia), anemia, liver injury (jaundice), and defective bone structure
(pathologic fractures) in chronically exposed persons. Prolonged inhalation of
cadmium dust has contributed to chronic obstructive pulmonary disease.26
Confirmation of Poisoning
Cadmium can be measured in body fluids by appropriate extraction, fol-
lowed by flame absorption spectrometry. It is reported that blood cadmium
concentrations tend to correlate with acute exposure and urine levels tend to
reflect total body burden. Blood levels exceeding 5 mcg/dL suggest excessive
exposure.25 Urinary excretion in excess of 100 meg per day suggests an unusu-
ally high body burden.
Treatment
1. Skin decontamination. Skin contamination should be removed by wash-
ing with soap and water. Flush contamination from the eyes with copious
amounts of clean water or saline. If irritation persists, specialized medical treat-
ment should be obtained. See Chapter 2.
2. Pulmonary edema. Respiratory irritation resulting from inhalation of
small amounts of cadmium dust may resolve spontaneously, requiring no
treatment. More severe reactions, including pulmonary edema and pneumonitis,
may require aggressive measures, including positive pressure mechanical
pulmonary ventilation, monitoring of blood gases, administration of diuretics,
steroid medications, and antibiotics.25 Codeine sulfate may be needed to control
cough and chest pain.
3. Gastrointestinal decontamination. The irritant action of ingested cadmium
products on the gastrointestinal tract is so strong that spontaneous vomiting
and diarrhea often eliminate nearly all unabsorbed cadmium from the gut. If
FUNGICIDES 151
-------
Commercial Products
MISCELLANEOUS
ORGANIC FUNGICIDES
anilazine*
Dyrene
benomyl
Benex
Ben I ate
Tersan 1991
cycloheximide*
naramycin
dodine
Carpene
Curitan
Melprex
Venture I
etridiazole
Aaterra
Ethazol
Koban
Pansoil
Terrazole
Truban
iprodione
Glycophene
Rovral
metalaxyl
Ridomil
Subdue
thiabendazole
Apl-Luster
Arbotect
Mertect
Tecto
Thibenzole
triadimefon
Amiral
Bayleton
triforine
Denarin
Funginex
Saprol
* Discontinued in the U.S.
retention of some cadmium in the lower GI tract is suspected, further
gastrointestinal decontamination may be considered, as outlined in Chapter 2.
4. Intravenous fluids may be required to overcome dehydration caused by
vomiting and diarrhea. Also, fluids limit cadmium toxicity affecting the kidneys
and liver. However, great care must be taken to monitor fluid balance and
blood electrolyte concentrations, so that failing renal function does not lead to
fluid overload.
5. Chelation therapy with calcium disodium EDTA may be considered for
acute poisoning, depending on measured cadmium in blood and urine, and the
status of renal function. Its therapeutic value in cadmium poisoning has not
been established, and use of the agent carries the risk that unduly rapid transfer
of cadmium to the kidney may precipitate renal failure. Urine protein and
blood urea nitrogen and creatinine should be carefully monitored during therapy.
The dosage should be 75 mg/kg/day in three to six divided doses for 5 days.
The total dose for the 5-day course should not exceed 500 mg/kg.27 Succimer
(DMSA) has also been used in this poisoning, but has not been demonstrated
to be efficacious.
6. Contraindications: Dimercaprol (BAL) is not recommended for treatment
of cadmium poisoning, chiefly because of the risk of renal injury by mobilized
cadmium.
7. Liver function. Monitor urine content of protein and cells regularly, and
perform liver function tests for indications of injury to these organs.
MISCELLANEOUS ORGANIC FUNGICIDES
Some modern organic fungicides are widely used. Reports of adverse ef-
fects on humans are few. Some of the known properties of these agents are
listed below.
Anilazine is supplied as wettable and flowable powders. Used on veg-
etables, cereals, coffee, ornamentals, and turf.This product has caused skin irri-
tation in exposed workers. Acute oral and dermal toxicity in laboratory animals
is low. Human systemic poisonings have not been reported.
Benomyl is a synthetic organic fungistat having little or no acute toxic
effect in mammals. No systemic poisonings have been reported in humans.
Although the molecule contains a carbamate grouping, benomyl is not a cho-
linesterase inhibitor. It is poorly absorbed across skin; whatever is absorbed is
promptly metabolized and excreted.
Skin injuries to exposed individuals have occurred, and dermal sensitiza-
tion has been found among agricultural workers exposed to foliage residues.
152 FUNGICIDES
-------
Cycloheximide is formulated as wettable powder, sometimes combined
with other fungicides. Cycloheximide is a product of fungal culture, effective
against fungal diseases of ornamentals and grasses. It is selectively toxic to rats,
much less toxic to dogs and monkeys. No human poisonings have been reported.
Animals given toxic doses exhibit salivation, bloody diarrhea, tremors, and
excitement, leading to coma and death due to cardiovascular collapse.
Hydrocortisone increases the rate of survival of deliberately poisoned rats.
Atropine, epinephrine, methoxyphenamine, and hexamethonium all relieved
the symptoms of poisoning, but did not improve survival.
Dodine is formulated as a wettable powder. It is commonly applied to
berries, nuts, peaches, apples, pears, and to trees afflicted with leaf blight. Dodine
is a cationic surfactant with antifungal activity. It is absorbed across the skin and
is irritating to skin, eyes, and gastrointestinal tract. Acute oral and dermal toxic-
ity in laboratory animals is moderate. Poisonings in humans have not been
reported. Based on animal studies, ingestion would probably cause nausea, vom-
iting, and diarrhea.
Iprodione is supplied as wettable powder and other formulations. It is
used on berries, grapes, fruit, vegetables, grasses, and ornamentals, and as a seed
dressing. Iprodione exhibits low acute oral and dermal toxicity in laboratory
animals. No human poisonings have been reported.
Metalaxyl is supplied as emulsifiable and flowable concentrates. It is used
to control soil-borne fungal diseases on fruit trees, cotton, hops, soybeans, pea-
nuts, ornamentals and grasses. Also used as seed dressing. Metalaxyl exhibits low
acute oral and dermal toxicity in laboratory animals. No human poisonings
have been reported.
Etridiazole is supplied as wettable powder and granules for application to
soil as a fungicide and nitrification inhibitor. Contact may result in irritation of
skin and eyes. Systemic toxicity is low. Human poisonings have not been re-
ported.
Thiabendazole is widely used as an agricultural fungicide, but most ex-
perience with its toxicology in humans has come from medicinal use against
intestinal parasites. Oral doses administered for this purpose are far greater than
those likely to be absorbed in the course of occupational exposure.Thiabenda-
zole is rapidly metabolized and excreted in the urine, mostly as a conjugated
hydroxy-metabolite. Symptoms and signs that sometimes follow ingestion are:
dizziness, nausea, vomiting, diarrhea, epigastric distress, lethargy, fever, flushing,
chills, rash and local edema, headache, tinnitus, paresthesia, and hypotension.
Blood enzyme tests may indicate liver injury. Persons with liver and kidney
disease may be unusually vulnerable to toxic effects. Adverse effects from use of
thiabendazole as a fungicide have not been reported.
Triadimefon is supplied as wettable powder, emulsifiable concentrate, sus-
pension concentrate, paste, and dry flowable powder. Used on fruit, cereals,
vegetables, coffee, ornamentals, sugarcane, pineapple, and turf, triadimefon ex-
hibits moderate acute oral toxicity in laboratory animals, but dermal toxicity is
FUNGICIDES 153
-------
low. It causes irritation if eyes are contaminated.Triadimefon is absorbed across
the skin. Overexposures of humans are said to have resulted in hyperactivity
followed by sedation.
Triforine is supplied as emulsifiable concentrate and wettable powder.
Used on berries, fruit, vegetables, and ornamentals, triforine exhibits low acute
oral and dermal toxicity in laboratory animals. Mammals rapidly excrete it
chiefly as a urinary metabolite. No human poisonings have been reported.
Confirmation of Poisoining
There are no generally available laboratory tests for these organic fungi-
cides or their metabolites in body fluids.
Treatment
See Treatment for Substituted Benzenes, p. 139.
References
1. Dannaker CJ, Maibach HI, and O'Malley M. Contact urticaria and anaphylaxis to the fun-
gicide chlorothalonil. Cutis 1993;52:3120-5.
2. Peters HA, Gocrnen A, Cripps DJ, et al. Epidemiology of hexachlorobenzene-induced por-
phyria in Turkey: Clinical and laboratory follow-up after 25 years. Arch Neural 1992;39:744-9.
3. Dalvi RR. Toxicology of thirarn (tetramethylthiuram disulfide): A review. Vet Hum Toxicol
1988;30:480-2.
4. Pinkhans J, Djaldetti M, Joshua H, et al. Sulfahemoglobinemia and acute hemolytic anemia
with Heinz bodies following contact with a fungicide-zinc ethylene bisdithiocarbamate in a
subject with glucose-6-phosphate dehydrogenase deficiency and hypocatalasemia. Blood
1963:21:484-93.
5. Koizumi A, Shiojima S, Omiya M, et al. Acute renal failure and maneb (manganouis
ethylenebis[dithiocarbamate]) exposure. JAMA 1979;242:2583-5.
6. Israeli R, Sculsky M, andTiberin P. Acute intoxication due to exposure to maneb and zineb:
A case with behavioral and central nervous system changes. Scand J Work Environ Health
1983;9:47-51.
7. Peluso AM.Tardio M, Adamo F, et al. Multiple sensitization due to bis-dithiocarbamate and
thiophthalimide pesticides. Contact Dermatitis 1991;25:327.
8. Vilaplana J and Romaguera C. Captan, a rare contact sensitizer in hairdressing. Contact Der-
matitis 1993:29:107.
9. Royce S, Wald P, Sheppard D, et al. Occupational asthma in a pesticides manufacturing
worker. Chest 1993; 103:295-6.
10. Krieger RI and Thongsinthusak T Captan metabolism in humans yields two biomarkers,
tetrahydrophthalimide (THPI) and thiazolidine-2-thione-4-carboxylic acid (TTCA) in urine.
Drug ChemToxicol 1993; 16:207-25.
154 FUNGICIDES
-------
11. Agarwal SK.Tiwari SC, and Dash SC. Spectrum of poisoning requiring haemodialysis in a
tertiary care hospital in India. Int JArtif Organs 1993;16:20-3.
12. Lament DL and Duflou JALC. Copper sulfate: Not a harmless chemical. Am J Forensic Med
Pathol 1988;9:226-7.
13. Chugh KS, Singhal PC, and Sharma BK. Methemoglobinemia in acute copper sulfate poi-
soning. Ann Intern Med 1975:82:226-9.
14. Jantsch W, Kulig K, and Rumack BH. Massive copper sulfate ingestion resulting in hepato-
toxicity. ClinToxicol 1984-85;22:585-8.
15. POISINDEXฎ: Copper poisoning. Englewood, CO: Micromedex, 1998.
16. Hantson P, Lievens M, and Mahieu P. Accidental ingestion of a zinc and copper sulfate
preparation. ClinToxicol 1996;34:725-30.
17. Bakir F, Rustam H.Tikritis S, et al. Clinical and epidemiological aspects of methylmercury
poisoning. Postgrad Med J 1980;56:1-10.
18. Grandjean P, Weihe P, and Nielsen JB. Methylmercury; Significance of intrauterine and
postnatal exposures. Clin Chem 1994;40:1395-1400.
19. Snyder RD. Congenital mercury poisoning. NewEngl]Med 1971;284:1014-5.
20. ClarksonTW. Mercury An element of mystery. New Engl J Med 1990;323:1137-8.
21. Agency for Toxic Substances and Disease Registry. Mercury toxicity Am Fam Physician
1992:46:1731-41.
22. Agocs MM, Etzel RA, Parrish RG, et al. Mercury exposure from interior latex paint. New
Engl J Med 1990:323:1096-100.
23. Colosio C.Tomasini M, Cairoli S, et al. Occupational triphenyltin acetate poisoning: A case
report. Br JInd Med 1991;48:136-9.
24. Barnhart S and Rosenstock L. Cadmium chemical pneumonitis. Chest 1984;86:789-91.
25. Ando Y, Shibata E.Tsuchiyama F, et al. Elevated urinary cadmium concentrations in a patient
with acute cadmium pneumonitis. Scand JWork Environ Health 1996;22:150-3.
26. Hendrick DJ. Occupational and chronic obstructive pulmonary disease (COPD). Thorax
1996:51:947-55.
27. Klaassen CD. Heavy metals and heavy metal antagonists. In: Gilman AG, RallTW, Niew AS,
et al (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics, 3rd ed. New
York: Pergamon Press, 1990, pp. 1605-6.
FUNGICIDES 155
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CHAPTER 16
HIGHLIGHTS
Easily absorbed in lung, gut,
skin
Signs and Symptoms:
Highly variable based on
agent
Many are irritants
Carbon disulfide,
chloroform, hydrogen
cyanide, and naphthalene
may have serious CNS
effects
Methyl bromide and
aluminum phosphide
(phosphine gas) cause
pulmonary edema
Hydrogen cyanide causes
severe hypoxia without
cyanosis in early stages
Treatment:
Skin and eye
decontamination
Oxygen and diuresis for
pulmonary edema
Specific measures needed
for various agents
Contraindicated:
Ipecac should not be used
in cyanide poisoning
Fumigants
Fumigants have remarkable capacities for diffusion, a property essential to their
function. Some readily penetrate rubber and neoprene personal protective gear,
as well as human skin. They are rapidly absorbed across the pulmonary mem-
brane, gut, and skin. Special adsorbents are required in respirator canisters to
protect exposed workers from airborne fumigant gases. Even these may not
provide complete protection when air concentrations of fumigants are high.
The packaging and formulation of fumigants are complex. Fumigants which
are gases at room temperature (methyl bromide, ethylene oxide, sulfur dioxide,
hydrogen cyanide, sulfuryl fluoride) are provided in compressed gas cylinders. Liq-
uids are marketed in cans or drums. Solids which sublime, such as naphthalene,
must be packaged so as to prevent significant contact with air before they are used.
Mixtures of fumigants have several advantages. Carbon tetrachloride re-
duces the explosiveness of carbon disulfide and acrylonitrile. Chloropicrin, having
a strong odor and irritant effect, is often added as a "warning agent" to other
liquid fumigants.
Liquid halocarbons and carbon disulfide evaporate into the air while naph-
thalene sublimes. Paraformaldehyde slowly depolymerizes to formaldehyde.
Aluminum phosphide slowly reacts with water vapor in the air to liberate phos-
phine, an extremely toxic gas. Metam sodium, also a fumigant, is covered under
thiocarbamates in Chapter 15, Fungicides.
(in alphabetical order)
Acrolein (acrylaldehyde) is an extremely irritating gas used as a fumigant
and an aquatic herbicide. The vapor causes lacrimation and upper respiratory
tract irritation, which may lead to laryngeal edema, bronchospasm, and delayed
pulmonary edema. The consequences of ingestion are essentially the same as
those that follow ingestion of formaldehyde. Contact with the skin may cause
blistering.
Acrylonitrile is biotransformed in the body to hydrogen cyanide.Toxic-
ity and mechanisms of poisoning are essentially the same as for cyanide (see
under hydrogen cyanide below), except that acrylonitrile is irritating to the
eyes and to the upper respiratory tract.
Carbon disulfide vapor is only moderately irritating to upper respiratory
membranes, but it has an offensive "rotten cabbage" odor. Acute toxicity is due
156 FUMIGANTS
-------
chiefly to effects on the central nervous system. Inhalation of high concentra-
tions for short periods has caused headache, dizziness, nausea, hallucinations,
delirium, progressive paralysis, and death from respiratory failure. More pro-
longed exposure to lesser amounts has lead to blindness, deafness, paresthesia,
painful neuropathy, and paralysis. Carbon disulfide is a potent skin irritant,
often causing severe burns. Long-term occupational exposures have been shown to
accelerate atherosclerosis, leading to ischemic myocardiopathy, polyneuropathy,
and gastrointestinal dysfunction.1 Toxic damage to the liver and kidneys may
result in severe functional deficits of these organs. Reproductive failure has
been noted.
Carbon tetrachloride is less toxic than chloroform as a central nervous
system depressant, but is much more severely hepatotoxic, particularly follow-
ing ingestion. Liver cell damage is apparently due to free radicals generated in
the process of initial dechlorination.2 Cardiac arrhythmias, progressing to
fibrillation, may follow inhalation of high concentrations of carbon tetra-
chloride or ingestion of the liquid. Kidney injury also occurs sometimes with
minimal hepatic toxicity.The kidney injury may be manifested by acute tubular
necrosis or by azotemia and general renal failure. Even topical exposure has
resulted in acute renal toxicity.3
Chloroform has an agreeable sweet odor and is only slightly irritating to
the respiratory tract. It is well absorbed from the lungs and is also absorbed
from the skin and gastrointestinal tract. It is a powerful central nervous system
depressant (in fact, an anesthetic).4 Inhalation of toxic concentrations in air
leads to dizziness, loss of sensation and motor power, and then unconsciousness.
Inhalation of large amounts causes cardiac arrhythmias, sometimes progressing
to ventricular fibrillation. Large absorbed doses damage the functional cells of
the liver and kidney. Ingestion is more likely to cause serious liver and kidney
injury than is inhalation of the vapor.
Chloropicrin is severely irritating to the upper respiratory tract, eyes, and
skin. Inhalation of an irritant concentration sometimes leads to vomiting. In-
gestion could be expected to cause a corrosive gastroenteritis.
Dibromochloropropane is irritating to skin, eyes, and the respiratory
tract. Eye damage has resulted from repeated exposure to the vapors. When
absorbed, it causes headache, nausea, vomiting, ataxia, and slurred speech. Liver
and kidney damage are prominent features of acute poisoning. Chronic
exposure to relatively low concentrations has led to temporary or permanent
sterility of workers in a manufacturing plant, by causing diffuse necrosis of
seminiferous tubule cells. Because it is much less odiferous than ethylene
dibromide, exposure of workers to toxic concentrations of DBCP is more likely.
Its use has been cancelled in the U.S.
Dichloropropene and dichloropropane are strongly irritating to the
skin, eyes, and respiratory tract. Bronchospasm may result from inhalation of
high concentrations. Liver, kidney, and cardiac toxicity are seen in animals, but
there are limited data in humans. It appears that risk of such toxicity is relatively
low for humans except via ingestion of large quantities.
Commercial Products
HALOCARBONS
carbon tetrachloride*
chloroform*
trichloromethane
chloropicrin
Aquinite
Dojyopicrin
Dolochlor
Larvacide
Pic-Clor
dibromochloropropane*
Nemafume
Nemanax
Nemaset
1,2-dichloropropane*
propylene dichloride
1,3-dichloropropene
D-D92
Telone II Soil Fumigant
ethylene dibromide*
Bromofume
Celmide
dibromoethane
E-D-Bee
EDB
Kopfume
Nephis
ethylene dichloride*
dichloroethane
EDC
methyl bromide
Celfume
Kayafume
Meth-0-Gas
MeBr
Sobrom 98
methylene chloride*
paradichlorobenzene
HYDROCARBONS
naphthalene
NITROGEN COMPOUNDS
acrylonitrile*
hydrogen cyanide*
hydrocyanic acid
prussic acid
(Continued on the next page)
FUMIGANTS 157
-------
Commercial Products
(Continued)
OXIDES AND ALDEHYDES
acrolein
Magnacide B
Magnacide H
1,2-epoxyethane
ethylene oxide
ETO
formaldehyde
oxirane
paraformaldehyde
PHOSPHORUS COMPOUNDS
phosphine (liberated from
aluminum phosphide or
magnesium phosphide)
Ag toxin
Alphos
Fumex
Fumitoxin
Phostoxin
Quickfos
Sanifume
Shaphos
others
SULFUR COMPOUNDS
carbon disulfide*
sulfur dioxide
sulfuryl fluoride
Vikane
* Discontinued in the U.S.
Ethylene dibromide is a severe irritant to skin, eyes, and respiratory tract.
The liquid causes blistering and erosion of skin, and is corrosive to the eyes.
Once absorbed, it may cause pulmonary edema and central nervous system
depression. Damage to testicular tissue has occurred in animals.5 Long-term
exposure may have some damaging effect on testicular tissue. Persons poisoned
by ingestion have suffered chemical gastroenteritis, liver necrosis, and renal tu-
bular damage. Death is usually due to respiratory or circulatory failure. A pow-
erful disagreeable odor is advantageous in warning occupationally exposed
workers of the presence of this gas.
Ethylene dichloride is moderately irritating to the eyes and respiratory
tract. Respiratory symptoms may have a delayed onset. It depresses the central
nervous system, induces cardiac arrhythmias, and damages the liver and kidney,
in much the same way as carbon tetrachloride. Symptoms and signs of poison-
ing include headache, nausea, vomiting, dizziness, diarrhea, hypotension, cy-
anosis, and unconsciousness.
Ethylene oxide and propylene oxide are irritants to all tissues they
contact. Aqueous solutions of ethylene oxide cause blistering and erosion of the
affected skin. The area of skin may thereafter be sensitized to the fumigant.
Inhalation of high concentrations is likely to cause pulmonary edema and car-
diac arrhythmias. Headache, nausea, vomiting, weakness, and a persistent cough
are common early manifestations of acute poisoning. Coughing of bloody, frothy
sputum is characteristic of pulmonary edema.
Airborne formaldehyde is irritating to the eyes and to membranes of the
upper respiratory tract. In some individuals, it is a potent sensitizer, causing aller-
gic dermatitis. In addition, it has been associated with asthma-like symptoms,
though there remains some controversy as to whether these represent true aller-
gic asthma caused by formaldehyde.6'7'8 High air concentrations may cause laryn-
geal edema, asthma, or tracheobronchitis, but apparently not pulmonary edema.
Aqueous solutions in contact with the skin cause hardening and roughness, due
to superficial coagulation of the keratin layer. Ingested formaldehyde attacks the
membrane lining of the stomach and intestine, causing necrosis and ulceration.
Absorbed formaldehyde is rapidly converted to formic acid.The latter is partly
responsible for the metabolic acidosis that is characteristic of formaldehyde poi-
soning. Circulatory collapse and renal failure may follow the devastating effects of
ingested formaldehyde on the gut, leading to death. Paraformaldehyde is a poly-
mer which slowly releases formaldehyde into the air. Toxicity is somewhat less
than that of formaldehyde, because of the slow evolution of gas.
Hydrogen cyanide gas causes poisoning by inactivating cytochrome oxi-
dase, the final enzyme essential to mammalian cellular respiration. The patient
will have signs of severe hypoxia, however, and in some cases may not appear
cyanotic. This is due to the failure of hemoglobin reduction in the face of loss
of cellular respiration. This will result in a pink or red color to the skin and
arteriolization of retinal veins. In addition to the suggestive physical findings,
158 FUMIGANTS
-------
one may also find an unusually high pO2 on a venous blood gas.9 Cyanosis is a
late sign and indicates circulatory collapse.
The cells of the brain appear to be the most vulnerable to cyanide action.
Presenting signs are nonspecific and can be found with many poisonings.
Unconsciousness and death may occur immediately following inhalation of a
high cyanide concentration, respiratory failure being the principal mechanism.
Metabolic acidosis is another common presenting sign. Lesser exposures cause
a constriction and numbness in the throat, stiffness of the jaw, salivation, nausea,
vomiting, lightheadedness, and apprehension. Worsening of the poisoning
is manifest as violent tonic or clonic convulsions. Fixed, dilated pupils,
bradycardia, and irregular gasping respiration (or apnea) are typical of profound
poisoning. The heart often continues to beat after breathing has stopped.9'10
A bitter almond odor to the breath or vomitus may be a clue to poisoning, but
not all individuals are able to detect this odor.9
Methyl bromide is colorless and nearly odorless, but is severely irritating
to the lower respiratory tract, sometimes inducing pulmonary edema, hemor-
rhage, or a confluent pneumonia. The onset of respiratory distress may be
delayed 4-12 hours after exposure. It is a central nervous system depressant, but
may also cause convulsions. Early symptoms of acute poisoning include
headache, dizziness, nausea, vomiting, tremor, slurred speech, and ataxia.The
more severe cases of poisoning exhibit myoclonic and generalized tonic clonic
seizures, which are sometimes refractory to initial therapy. Residual neurologi-
cal deficits including myoclonic seizures, ataxia, muscle weakness, tremors,
behavioral disturbances, and diminished reflexes may persist in more severely
poisoned patients.11'12 If liquid methyl bromide contacts the skin, severe
burning, itching, and blister formation occur. Skin necrosis may be deep and
extensive.
Methylene chloride is one of the less toxic halocarbons. It is absorbed by
inhalation and to a limited extent across the skin. Exposure to high concentra-
tions may cause central nervous system depression, manifested as fatigue,
weakness, and drowsiness. Some absorbed methylene chloride is degraded to
carbon monoxide in humans, yielding increased blood concentrations of
carboxyhemoglobin. However, concentrations are rarely high enough to cause
symptoms of carbon monoxide poisoning. Ingestion has caused death from
gastrointestinal hemorrhage, severe liver damage, coma, shock, metabolic
acidosis, and renal injury. In laboratory animals, extraordinary dosage has caused
irritability, tremor, and narcosis, leading to death. When heated to that point of
decomposition, one of the products is the highly toxic phosgene gas that has
caused a significant acute pneumonitis.13
Naphthalene is a solid white hydrocarbon long used in ball, flake, or cake
form as a moth repellent. It sublimes slowly.The vapor has a sharp, pungent odor
that is irritating to the eyes and upper respiratory tract. Inhalation of high con-
centrations causes headache, dizziness, nausea, and vomiting. Intensive prolonged
inhalation exposure, or ingestion or dermal exposure (from contact with heavily
FUMIGANTS 159
-------
treated fabric) may cause hemolysis, particularly in persons afflicted with glu-
cose-6-phosphate dehydrogenase deficiency.14 The inheritance of glucose-6-
phosphate dehydrogenase (G-6-PD) deficiency is by a sex-linked gene with
intermediate dominance. For this reason it is most commonly expressed in
heterozygous males. However, homozygous females, who are far less common,
will have a similar expression. Heterozygous females have only a mild depres-
sion of this enzyme. This illness is most common in non-white African and
African-American ethnic groups. It is also seen in some Mediterranean ethnic
populations.
It is actually the metabolites of naphthalene that are responsible for the hemoly-
sis. 15 Secondary renal tubular damage may ensue from the naphthol and from the
products of hemolysis. Convulsions and coma may occur, particularly in children.
In infants, high levels of hemoglobin, methemoglobin, and bilirubin in the plasma
may lead to encephalopathy. Kernicterus has been specifically described as a com-
plication of exposure to naphthalene with severe hemolysis and resulting hyper-
bilirubinemia. Some individuals exhibit dermal sensitivity to naphthalene.
Paradichlorobenzene is solid at room temperature, and is now widely
used as a moth repellent, air freshener, and deodorizer in homes and in public
facilities.The vapor is only mildly irritating to the nose and eyes. Liver injury
and tremor may occur following ingestion of large amounts. Although acci-
dental ingestions, especially by children, have been fairly common, symptom-
atic human poisonings have been rare. Other stereoisomers of dichlorobenzene
are more toxic than the para-isomer.
Phosphine gas is extremely irritating to the respiratory tract. It also pro-
duces severe systemic toxicity. It is used as a fumigant by placing solid aluminum
phosphide (phostoxin) near produce or in other storage spaces. Through hy-
drolysis, phosphine gas is slowly released. Most severe acute exposures have in-
volved ingestion of the solid aluminum phosphide, which is rapidly converted to
phosphine by acid hydrolysis in the stomach. Poisoning due to ingestion carries a
high mortality rate (50 to 90%).16'17 Mechanisms of toxicity are not well under-
stood. Extracellular magnesium levels have been found to be slightly elevated,
suggesting a depletion of intracellular magnesium from myocardial damage.18
Poisonings had become quite frequent during the late 1980s and early
1990s in some parts of India.16'17 The principal manifestations of poisoning are
fatigue, nausea, headache, dizziness, thirst, cough, shortness of breath, tachycar-
dia, chest tightness, paresthesia, and jaundice. Cardiogenic shock is present in
more severe cases. Pulmonary edema is a common cause of death. In other
fatalities, ventricular arrythmias, conduction disturbances, and asystole devel-
oped.16'19 Odor is said to resemble that of decaying fish.
Sulfur dioxide is a highly irritant gas, so disagreeable that persons inhal-
ing it are usually prompted to seek uncontaminated air as soon as possible.
However, laryngospasm and pulmonary edema have occurred, occasionally lead-
ing to severe respiratory distress and death. It is sometimes a cause of reactive
airways disease in occupationally exposed persons.
160 FUMIGANTS
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Sulfuryl fluoride has been used extensively for structural fumigation.
Although use experience has generally been good, some fatalities have oc-
curred when fumigated buildings have been prematurely reentered by unpro-
tected individuals.20 Since this material is heavier than air, fatal hypoxia may
follow early reentry. Manifestations of poisoning have been nose, eye, and throat
irritation, weakness, nausea, vomiting, dyspnea, cough, restlessness, muscle twitch-
ing, and seizures. Renal injury may induce proteinuria and azotemia.
Confirmation of Poisoning
There are no practical tests for absorbed alkyl oxides, aldehydes, or
phosphine that would be helpful in diagnosis of poisoning.
Carbon disulfide can be measured in urine by gas chromatography, but
the test is not generally available.
Cyanide ion from cyanide itself or acrylonitrile can be measured in
whole blood and urine by an ion-specific electrode or by colorimetry. Symp-
toms of toxicity may appear at blood levels above 0.10 mg per liter.10 Urine
cyanide is usually less than 0.30 mg per liter in nonsmokers, but as much as 0.80
mg per liter in smokers. Thiocyanate, the metabolite of cyanide, can also be
measured in blood and urine. It is elevated at blood levels exceeding 12 mg per
liter.10 Urine thiocyanate is usually less than 4 mg per liter in nonsmokers, but
may be as high as 17 mg per liter in smokers.
Methyl bromide yields inorganic bromide in the body. Methyl bromide
itself has a short half-life and is usually not detectable after 24 hours.The bromide
anion is slowly excreted in the urine (half-life about 10 days), and is the preferred
method of serum measurement.11 The serum from persons having no excep-
tional exposure to bromide usually contains less than 1 mg bromide ion per 100
mL.The possible contributions of medicinal bromides to elevated blood content
and urinary excretion must be considered, but if methyl bromide is the exclusive
source, serum bromide exceeding 6 mg per 100 mL probably means some ab-
sorption, and 15 mg per 100 mL is consistent with symptoms of acute poisoning.
Inorganic bromide is considerably less toxic than methyl bromide; serum con-
centrations in excess of 150 mg per 100 mL occur commonly in persons taking
inorganic bromide medications. In some European countries, blood bromide
concentrations are monitored routinely in workers exposed to methyl bromide.
Blood levels over 3 mg per 100 mL are considered a warning that personal pro-
tective measures must be improved. A bromide concentration over 5 mg per 100
mL requires that the worker be removed from the fumigant-contaminated envi-
ronment until blood concentrations decline to less than 3 mg per 100 mL.
Methylene chloride is converted to carbon monoxide in the body, gener-
ating carboxyhemoglobinemia, which can be measured by clinical laboratories.
Naphthalene is converted mainly to alpha naphthol in the body and promptly
excreted in conjugated form in the urine. Alpha naphthol can be measured by gas
FUMIGANTS 161
-------
chromatography. Many halocarbons can be measured in blood by gas chromato-
graphic methods. Some can be measured in the expired air as well.
Paradichlorobenzene is metabolized mainly to 2,5-dichlorophenol, which
is conjugated and excreted in the urine. This product can be measured chro-
matographically.
A serum fluoride concentration of 0.5 mg per liter was measured in one
fatality from sulfuryl fluoride fumigation. Serum fluoride in persons not
exceptionally exposed rarely exceeds 0.1 mg per liter.
Large industrial concerns sometimes monitor human absorption of
halocarbons by analysis of expired air. Similar technology is available in some
departments of anesthesiology These analyses are rarely needed to identify the
offending toxicant, because this is known from the exposure history. In managing
difficult cases of poisoning, however, it may be helpful to monitor breath concen-
trations of toxic gas to evaluate disposition of the fumigant. Testing of the urine
for protein and red cells is needed to detect renal injury. Free hemoglobin in
urine most likely reflects hemolysis, as from naphthalene. Elevations of alkaline
phosphatase, lactate dehydrogenase (LDH), serum GGT, ALT, AST, and certain
other enzymes are sensitive indices of insult to liver cells. More severe damage
increases plasma concentrations of bilirubin. The chest x-ray may be used to
confirm the occurrence of pulmonary edema. Electromyography may be useful
in evaluating peripheral nerve injury. Sperm counts may be appropriate for workers
exposed to dibromochloropropane and ethylene dibromide.
Some occupational health agencies now urge periodic neurologic and
neuropsychologic testing of workers heavily exposed to fumigants and solvents
to detect injury to the nervous system as early as possible.This would be par-
ticularly desirable in the case of exposures to such agents as methyl bromide
and carbon disulfide which have well-documented chronic neurotoxic effects.
Treatment
1. Skin decontamination. Flush contaminating fumigants from the skin and
eyes with copious amounts of water or saline for at least 15 minutes. Some
fumigants are corrosive to the cornea and may cause blindness. Specialized
medical treatment should be obtained promptly following decontamination.
Skin contamination may cause blistering and deep chemical burns. Absorption
of some fumigants across the skin may be sufficient to cause systemic poisoning
in the absence of fumigant inhalation. For all these reasons, decontamination of
eyes and skin must be immediate and thorough. See Chapter 2.
2. Physical placement. Remove victims of fumigant inhalation to fresh air
immediately. Even though initial symptoms and signs are mild, keep the victim
quiet, in a semi-reclining position. Minimum physical activity limits the likeli-
hood of pulmonary edema.
162 FUMIGANTS
-------
3. Respiration. If victim is not breathing, clear the airway of secretions and
resuscitate with positive pressure oxygen apparatus. If this is not available, use
chest compression to sustain respiration. If victim is pulseless, employ cardiac
resuscitation.
4. Pulmonary edema. If pulmonary edema is evident, there are several mea-
sures available to sustain life. Medical judgment must be relied upon, however,
in the management of each case. The following procedures are generally
recommended:
Put the victim in a sitting position with a backrest.
Use intermittent and/or continuous positive pressure oxygen to
relieve hypoxemia. (Do not give oxygen at greater concentrations
or longer periods than necessary, because it may exaggerate the fu-
migant injury to lung tissue. Monitor arterial pO2.)
Slowly administer furosemide, 40 mg, intravenously (0.5-1 mg/kg
in children up to 20 mg), to reduce venous load by inducing diure-
sis. Consult package insert for additional directions and warnings.
Some patients may benefit from careful administration of anxiolytic drugs.
Whenever possible, such patients should be managed by intensivists in an in-
tensive care center. Limit victim's physical activity for at least 4 weeks. Severe
physical weakness usually indicates persistent pulmonary injury. Serial pulmo-
nary function testing may be useful in assessing recovery.
5. Shock. Combat shock by placing victim in the Trendelenburg position and
administering plasma, whole blood, and/or electrolyte and glucose solutions
intravenously, with great care, to avoid pulmonary edema. Central venous pres-
sure should be monitored continuously. Vasopressor amines must be given with
great caution, because of the irritability of the myocardium.
6. Control convulsions. Seizures are most likely to occur in poisonings by
methyl bromide, hydrogen cyanide, acrylonitrile, phosphine, and carbon disul-
fide. See Chapter 2 for seizure management. In some cases of methyl bromide,
seizures have been refractory to benzodiazepines and diphenylhydantoin, and
the authors resorted to anesthesia using thiopental.11
7. Gastrointestinal decontamination. If a fumigant liquid or solid has been
ingested less than an hour prior to treatment, consider gastric emptying, fol-
lowed by activated charcoal, as suggested in Chapter 2.
8. Fluid balance should be monitored, and urine sediment should be checked
regularly for indications of tubular injury. Measure serum alkaline phosphatase,
LDH, ALT, AST, and bilirubin to assess liver injury.
FUMIGANTS 163
-------
9. Extracorporeal hemodialysis may be needed to regulate extracellular
fluid composition if renal failure supervenes. It is probably not very effective in
removing lipophilic fumigant compounds from blood, but it is, of course, effec-
tive in controlling extracellular fluid composition if renal failure occurs.
10. Specific fumigants. Certain specific measures are recommended in poi-
sonings by particular fumigants (carbon disulfide, carbon tetrachloride, naph-
thalene, phosphine gas, and hydrogen cyanide and acrylonitrile):
Carbon Disulfide: Mild poisonings by carbon disulfide inhalation
may be managed best by no more than careful observation, even
though sensory hallucinations, delirium, and behavioral aberrations
can be alarming. Severe poisonings may require specific measures. If
manic behavior threatens the safety of the victim, diazepam (5-10
mg in adults, 0.2-0.4 mg/kg in children), administered slowly, intra-
venously, may be helpful as a tranquilizer. Give as much as is neces-
sary to achieve sedation. Do not give catecholamine-releasing agents
such as reserpine and amphetamines.
Carbon Tetrachloride: For carbon tetrachloride poisoning, sev-
eral treatment measures have been suggested to limit the severity of
hepatic necrosis. Hyperbaric oxygen has been used with some suc-
cess.2 Oral administration of N-acetyl cysteine (MucomystR) may
be worthwhile as a means of reducing free radical injury.21 Dilute
the proprietary 20% product 1:4 in a carbonated beverage, and give
about 140 mg/kg body weight of the diluted solution as a loading
dose.Then give 70 mg/kg every 4 hours after the loading dose for a
total of 17 doses. (This dosage schedule is used for acetaminophen
poisonings.) Administration via duodenal tube may be necessary in
a few patients who cannot tolerate Mucomyst.22 Intravenous ad-
ministration of N-acetyl cysteine may be used; more information is
available through poison control centers.
Naphthalene: Naphthalene toxicosis caused by vapor inhalation
can usually be managed simply by removing the individual to fresh
air. Skin contamination should be removed promptly by washing
with soap and water. Eye contamination should be removed by flush-
ing with copious amounts of clean water. Eye irritation may be
severe, and if it persists, should receive ophthalmalogic attention.
Examine the plasma for evidence of hemolysis: a reddish-brown
tinge, especially in the blood smear for "ghosts" and Heinz bodies. If
present, monitor red blood cell count and hematocrit for anemia,
urine for protein and cells. Measure direct-and indirect-reacting bi-
164 FUMIGANTS
-------
lirubin in the plasma. Monitor fluid balance and blood electrolytes.
If possible, monitor urinary excretion of naphthol to assess severity
of poisoning and clinical progress.
If hemolysis is clinically significant, administer intravenous fluids
to accelerate urinary excretion of the naphthol metabolite and pro-
tect the kidney from products of hemolysis. Use Ringer's lactate or
sodium bicarbonate to keep urine pH above 7.5. Consider the use
of mannitol or furosemide to promote diuresis. If urine flow de-
clines, intravenous infusions must be stopped to prevent fluid over-
load and hemodialysis should be considered.15 If anemia is severe,
blood transfusions may be needed.
Phosphine Gas: Recent experience in India suggests that therapy
with magnesium sulfate may decrease the likelihood of a fatal out-
come.16'19'23 The mechanism is unclear, but may possibly be due to
the membrane stabilization properties of magnesium in protecting
the heart from fatal arrythmias. In one series of 90 patients, magne-
sium sulfate was found to decrease the mortality from 90% to 52%.16
Two controlled studies have been done, one of which showed a
reduction in mortality from 52% to 22%.23 The other study found
no effect on mortality.24 The dosage for magnesium sulfate is: 3
grams during the first 3 hours as a continous infusion, followed by 6
grams per 24 hours for the next 3 to 5 days.16
Hydrogen Cyanide and Acrylonitrile: Poisonings by hydrogen
cyanide and acrylonitrile gases or liquids are treated essentially the
same as poisoning by cyanide salts. Because cyanide is so promptly
absorbed following ingestion, treatment should commence with
prompt administration of oxygen and antidotes. Gastrointestinal
decontamination should be considered if the patient presents within
a short interval after ingestion, and only after the above life-saving
treatment has commenced. Ipecac should be avoided due to the
potential for rapid onset of loss of consciousness.
The three antidotes amyl nitrite, sodium nitrite, and sodium thio-
sulfate are available as a kit called the Lilly Cyanide Antidote Kit,
available from Eli Lilly and Company, Indianapolis, IN.The dosages
vary between adults and children and are outlined below.
FUMIGANTS 165
-------
Dosage of Cyanide Antidotes
Adults:
Administer oxygen continuously. Hyperbaric oxygen has been evalu-
ated as effective in this condition.25 If respiration fails, maintain pul-
monary ventilation mechanically.
Administer amyl nitrite ampules by inhalation for 15-30 seconds
of every minute, while a fresh solution of 3% sodium nitrite is being
prepared. This solution is ready prepared in commercial cyanide
antidote kits.
As soon as solution is available, inject intravenously 10 mL of 3%
sodium nitrite solution over a 5-minute interval, keeping the needle
in place.
Caution: Monitor pulse and blood pressure during administration of amyl
nitrite and sodium nitrite. If systolic blood pressure falls below 80 mm Hg,
slow or stop nitrite administration until blood pressure recovers.
Follow sodium nitrite injection with an infusion of 50 mL of 25%
aqueous solution of sodium thiosulfate administered over a 10-
minute period. Initial adult dose should not exceed 12.5 g.
If symptoms persist or recur, treatment by sodium nitrite and so-
dium thiosulfate should be repeated at half the dosages listed above.
Measure hemoglobin and methemoglobin in blood. If more than
50% of total hemoglobin has been converted to methemoglobin,
blood transfusion or exchange transfusion should be considered, be-
cause conversion back to normal hemoglobin proceeds slowly.
Children:
Give amyl nitrite, oxygen, and mechanical respiratory support as
recommended for adults. The following dosages of antidotes have
been recommended for children.26
Children over 25 kg body weight should receive adult dosages of
sodium nitrite and sodium thiosulfate.
Children less than 25 kg body weight should first have two 3-4 mL
samples of blood drawn and then, through the same needle, receive
0.15-0.33 mL/kg up to 10 mL of the 3% solution of sodium nitrite
injected over a 5-minute interval. Following sodium nitrite, admin-
ister an infusion of 1.65 mL/kg of 25% sodium thiosulfate at a rate
of 3-5 mL per minute.
... continued
166 FUMIGANTS
-------
At this point, determine the hemoglobin content of the pretreat-
ment blood sample. If symptoms and signs of poisoning persist or
return, give supplemental infusions of sodium nitrite and sodium
thiosulfate based on hemoglobin level, as presented in the table.These
recommended quantities are calculated to avoid life-threatening
methemoglobinemia in anemic children. They are aimed at con-
verting approximately 40% of circulating hemoglobin to methemo-
globin. If possible, monitor blood methemoglobin concentrations as
treatment proceeds.
RECOMMENDED DOSAGES OF SUPPLEMENTAL SODIUM
NITRITE AND SODIUM THIOSULFATE
HEMOGLOBIN
Initial
Hemoglobin
Concentration
g/100mL
14.0
12.0
10.0
8.0
LEVEL
Volume of 3%
Sodium Nitrite
ml/kg
0.20
0.16
0.14
0.11
BASED ON
Dose
25% Sodium
Thiosulfate
ml/kg
1.00
0.83
0.68
0.55
Although various cobalt salts, chelates, and organic combinations have shown
some promise as antidotes to cyanide, they are not generally available in the
United States. None has been shown to surpass the nitrite-thiosulfate regimen
in effectiveness.
References
1. Wilcosky TC and Tyroler HA. Mortality from heart disease among workers exposed to
solvents. / Occup Med 1983;25:879-85.
2. Truss C and Killenberg R Treatment of carbon tetrachloride poisoning with hyperbaric
3.
5.
oxygen. Gastroenterology 1982;82:767-9.
Perez AJ, Courel M, Sobrado J, et al. Acute renal failure after topical application of carbon
tetrachloride. Lancet 1987;l:515-6.
4. Dykes MH. Halogenated hydrocarbon ingestion. Intern Anesthesiol Clin 1970;8:357-68.
Amir D. The spermicidal effect of ethylene dibromide in bulls and rams. Mol Reprod Dev
1991;28:99-109.
FUMIGANTS 167
-------
6. Smedley J. Is formaldehyde an important cause of allergic respiratory disease? Clin Exp
Allergy 1996;26:247-9.
7. Krzyzanowski M, Quackenboss JJ, and Lebowitz MD. Chronic respiratory effects of indoor
formaldehyde exposure. Environ Res 1990;52:117-25.
8. Harving H, Korsgaard J, Pedersen OF, et al. Pulmonary function and bronchial reactivity in
asthmatics during low-level formaldehyde exposure. Lung 1990;168:15-21.
9. Johnson RP and Mellors JW Arteriolization of venous blood gases: A clue to the diagnosis of
cyanide poisoning. JEmerg Med 1988;6:401-4.
10. Yen D.TsaiJ.Wang LM.et al.The clinical experience of acute cyanide poisoning. Am J Emerg
Med 1995:13:524-8.
11. Hustinx WNM, van de Laar RTH, van Huffelen A, et al. Systemic effects of inhalational
methyl bromide poisoning: A study of nine cases occupationally exposed due to inadvertent
spread during fumigation. BrJIndMed 1993;50:155-9.
12. Deschamps FJ andTurpin JC. Methyl bromide intoxication during grain store fumigation.
OccupatMed 1996;48:89-90.
13. Snyder RW, Mishel HS, and Christensen GC. Pulmonary toxicity following exposure to
methylene chloride and its combustion product, phosgene. Chest 1992;101:860-1.
14. Shannon K and Buchanan GR. Severe hemolytic anemia in black children with glucose-6-
phosphate dehydrogenase deficiency. Pediatrics 1982;70:364-9.
15. Gosselin RE, Smith HC, and Hodge HC (eds). Naphthalene. In: Clinical Toxicology of
Commercial Products, 5th ed. Baltimore:Williams &Wilkins, 1984, pp. III-307-ll.
16. Katira R, Elhence GP, Mehrotra ML, et al. A study of aluminum phosphide poisoning with
special reference to electrocardiographic changes. JAssoc Physicians India 1990;38:471-3.
17. Singh S, Singh D, Wig N, et al. Aluminum phosphide ingestion: A clinico-pathologic study.
ClinToxicol 1996;34:703-6.
18. Singh RB, Singh RG, and Singh U. Hypermagnesemia following aluminum phosphide
poisoning. Int J Clin PharmacolTherToxicol 1991;29:82-5.
19. Gupta S and Ahlawat SK.Aluminum phosphide poisoning:A review. ClinToxicol 1995;33:19-24.
20. Scheuerman EH. Suicide by exposure to sulfuryl fluoride. J Forensic Sci 1986;31:1154-8.
21. Ruprah M, MantTGK, and Flanagan RJ. Acute carbon tetrachloride poisoning in 19 pa-
tients: Implications for diagnosis and treatment. Lancet 1985;l:1027-9.
22. Anker AL and Smilkenstein MJ. Acetaminophen: Concepts and controversies. Emerg Med
Clin North Am 1994;12:335-49.
23. Chugh SN, Kumar P Sharma A, et al. Magnesium status and parenteral magnesium sulphate
therapy in acute aluminum phosphide intoxication. Magnesium Res 1994;7:289-94.
24. Siwach SB, Singh P, Ahlawat S, et al. Serum and tissue magnesium content in patients of
aluminum phosphide poisoning and critical evaluation of high dose magnesium sulphate
therapy in reducing mortality. /Assoc Physicians India 1994;42:107-10.
25. Myers RAM and Schnitzer BM. Hyperbaric oxygen use: Update 1984. Postgrad Med
1984:76:83-95.
26. Mofenson HC, Greensher J, Horowitz R, and Berlin CM.Treatment of cyanide poisoning.
Pediatrics 1970:46:793-6.
168 FUMIGANTS
-------
CHAPTER 17
Rodenticides
A wide variety of materials are used as rodenticides.They pose particular risks for
accidental poisonings for several reasons. First, as agents specifically designed to
kill mammals, often their toxicity is very similar for the target rodents and for
humans. (Warfarin and other anticoagulant rodenticides were initially developed
to overcome this problem by creating compounds that were highly toxic to ro-
dents, particularly after repeated exposures, but much less toxic to humans.) Sec-
ond, since rodents usually share environments with humans and other mammals,
the risk of accidental exposure is an integral part of the placement of baits for the
rodents. Finally, as rodents have developed resistance to existing rodenticides, there
is a continuous need to develop new and potentially more toxic rodenticides. As
rodents have become resistant to warfarin baits, for example, the development of
"superwarfarins" has increased the risk to humans.1-2 It is important to be familiar
with use patterns and development of more toxic compounds and to make every
effort to identify the actual agent used in order to institute the most appropriate
management for these poisonings.
COUMARINS AND INDANDIONES
Toxicology
Warfarin and related compounds (coumarins and indandiones) are the most
commonly ingested rodenticides in the United States, with 13,345 exposures
reported in 1996.3 Gastrointestinal absorption of these toxicants is efficient.
Warfarin can be absorbed across the skin, but this has occurred only under
extraordinary circumstances.
Coumarins and indandiones depress the hepatic synthesis of vitamin K
dependent blood-clotting factors (II (prothrombin),VII, IX, and X).The anti-
prothrombin effect is best known, and is the basis for detection and assessment
of clinical poisoning.The agents also increase permeability of capillaries through-
out the body, predisposing the animal to widespread internal hemorrhage.This
generally occurs in the rodent after several days of warfarin ingestion due to the
long half-lives of the vitamin K dependent clotting factors,1-2 although lethal
hemorrhage may follow smaller doses of the modern, more toxic compounds.1
The lengthened prothrombin time (PT) from a toxic dose of coumarins or
indandiones may be evident within 24 hours, but usually reaches a maximum
HIGHLIGHTS
Newer "superwarfarins"
are widely available and
toxic at much lower doses
than conventional warfarin
Signs and Symptoms:
Variable depending on
agent
Warfarin compounds cause
bleeding
Pulmonary edema results
from phosphine gas (from
zinc phosphide)
Cardiovascular, Gl, and CNS
effects predominate with
thallium
Seizures are primary
manifestation of strychnine
and fluoroacetamide
Treatment:
Specific to agent
Vitamin K1 (phytonadione)
for warfarin-related
compounds
Control seizures
Proceed with
decontamination
concurrently with life-saving
measures
Contraindicated:
Neither Vitamins K3 nor K4
may be used as a substitute
for Vitamin K1
Chelating agents are not
effective in thallium
poisoning
RODENTICIDES 169
-------
Commercial Products
COUMARINS
brodifacoum
Havoc
Klerat
Ratak Plus
Talon
Volid
bromadiolone
Bromone,
Contrac
Maki
coumachlor
Famarin
coumatetralyl
Racumin
difenacoum
Frunax-DS
Ratak
warfarin
Co-Rax
coumafene
Cov-R-Tox
Kypfarin
Liqua-Tox
RAX
Tox-Hid
zoocoumarin
INDANDIONES
chlorophacinone
Caid
Liphadione
Microzul
Ramucide
Ratomet
Raviac
Rozol
Topitox
diphacinone
diphacin
Ditrac
Ramik
Tomcat
pivalyn*
pindone
pival
pivaldione
*Discontinued in the U.S.
in 36-72 hours.li4'5 Lengthened PT occurs in response to doses much lower
than that necessary to cause hemorrhage. There is concern that the more toxic
modern compounds, such as brodifacoum and difenacoum, may cause serious
poisoning of nontarget mammals, including humans, at much lower dosage.
Brodifacoum, one of the superwarfarins, is much more toxic, with a dose as low
as 1 mg in an adult or 0.014 mg/kg in a child sufficient to produce toxicity.1
Symptomatic poisoning, with prolonged symptoms due to the long half-
lives of superwarfarins, has been reported even with single exposures; however,
these are usually intentional and are large single dosages.2 Because of their
toxicity in relation to warfarin, patients may require higher dosages of vitamin
K and will require longer monitoring of their PT. One patient required vita-
min K for several months following discharge.6 Another patient was released
from the hospital with significant clinical improvement and only slightly el-
evated coagulation studies after brodifacoum ingestion.Two and a half weeks
later, he presented in a comatose state and was found to have massive intracra-
nial hemorrhage.7
Clinical effects of these agents usually begin several days after ingestion, due
to the long half-life of the factors. Primary manifestations include nosebleeds,
bleeding gums, hematuria, melena, and extensive ecchymoses.1'2'6'7-8 Patients may
also have symptoms of anemia, including fatigue and dyspnea on exertion.8 If the
poisoning is severe, the patient may progress to shock and death.
Unlike the coumarin compounds, some indandiones cause symptoms and
signs of neurologic and cardiopulmonary injury in laboratory rats leading to
death before hemorrhage occurs. These actions may account for the greater
toxicity of indandiones in rodents. Neither neurologic nor cardiopulmonary
manifestations have been reported in human poisonings.
Confirmation of Poisoning
Coumarin or indandione poisoning results in an increase in prothrombin
time, the result of reduced plasma prothrombin concentration. This is a reliable
test for absorption of physiologically significant doses. Detectable reduction in
prothrombin occurs within 24-48 hours of ingestion and persists for 1 -3 weeks.li4'5
The manufacturers can often measure blood levels of the more toxic coumarins.8
Treatment
1. Determine quantity ingested. If it is certain that the patient ingested no
more than a mouthful or two of warfarin- or indandione-treated bait, or a
single swallow or less of bait treated with the more toxic brodifacoum or
bromadiolone compounds, medical treatment is probably unnecessary.
170 RODENTICIDES
-------
2. Vitamin Kr A patient presenting within 24 hours after ingestion will likely
have a normal PT. However, in a study of 110 children who were poisoned by
superwarfarins, primarily brodifacoum, a child's PT was significantly more likely
to be prolonged at 48 hours after having a normal PT at 24 hours.5Therefore, for
suicidal ingestions with large amounts taken, if there is uncertainty about the
amount of bait ingested or the general health of the patient, phytonadione (vita-
min Kj) given orally protects against the anticoagulant effect of these rodenti-
cides, with essentially no risk to the patient. In accidental ingestions with healthy
children involving only a taste or single swallow, no medical treatment is re-
quired, but children should be observed for bleeding and bruising. If a larger
amount may have been ingested, PT should be monitored at 24 and 48 hours,
with phytonadione therapy initiated for elevated PT or clinical signs of bleeding.
Caution: Phytonadione, specifically, is required. Neither vitamin K3 (me-
nadione, HykinoneR) nor vitamin K4 (menadiol) is an antidote for these anti-
coagulants.
Dosage of Phytonadione (oral):
Adults and children over 12years: 15-25 mg.
Children under 12years: 5-10 mg.
Alternatively, a colloidal preparation of phytonadione, AquamephytonR,
may be given intramuscularly. For adults and children over 12 years,
give 5-10 mg; for children under 12, give 1-5 mg.
Ensure that patients (especially children) are carefully observed for
at least 4-5 days after ingestion.The indandiones and some of the more
recently introduced coumarins may have other toxic effects.
3. Gastrointestinal decontamination. If large amounts of anticoagulant
have been ingested within several hours prior to treatment, consider gastric
decontamination procedures as outlined Chapter 2.
4. Determine prothrombin time. If anticoagulant has been ingested any
time in the preceding 15 days, determination of the PT provides a basis for
judging the severity of poisoning. Patients who ingest large amounts, particu-
larly of the superwarfarin compounds, will likely have a very prolonged period
of decreased prothrombin activity. Patients may need to be treated for as long as
3 or 4 months.6-7
If the prothrombin time is significantly lengthened, give AquamephytonR
intramuscularly. See next page for dosage.
RODENTICIDES 171
-------
Dosage of AquamephytonR (intramuscular):
Adults and children over 12years: 5-10 mg.
Children under 12years: 1-5 mg.
Decide dose within these ranges according to the degree of prothrom-
bin time lengthening and, in children, the age and weight of the child.
Substantially higher doses of phytonadione (50 to 125 mg) have been
required in some poisonings with brodifacoum when bleeding and PT
elevation persisted despite therapy.6'7'9
Repeat prothrombin time in 24 hours. If it has not decreased from
the original value, repeat AquamephytonR dosage.
5. Bleeding. If victim is bleeding as a result of anticoagulant poisoning, ad-
minister AquamephytonR intravenously: up to 10 mg in adults and children
over 12 years, and up to 5 mg in children under 12 years. Initial dosage should
be decided chiefly on the basis of the severity of bleeding. Subsequent dosages
may need to be adjusted based on response, especially in the case of the
superwarfarins.6'7'9 Repeat intravenous AquamephytonR in 24 hours if bleeding
continues. Inject at rates not exceeding 5% of the total dose per minute. Intra-
venous infusion of the AquamephytonR diluted in saline or glucose solution is
recommended. Bleeding is usually controlled in 3-6 hours.
Caution: Adverse reactions, some fatal, have occurred from intravenous
phytonadione injections, even when recommended dosage limits and injection
rates were observed. For this reason, the intravenous route should be used only
in cases of severe poisoning. Flushing, dizziness, hypotension, dyspnea, and cy-
anosis have characterized adverse reactions.
Antidotal therapy in cases of severe bleeding should be supplemented with
transfusion of fresh blood or plasma. Use of fresh blood or plasma represents the
most rapidly effective method of stopping hemorrhage due to these anticoagu-
lants, but the effect may not endure.Therefore, the transfusions should be given
along with phytonadione therapy.
Determine PT and hemoglobin concentrations every 6-12 hours to assess
effectiveness of antihemorrhagic measures. When normal blood coagulation is
restored, it may be advisable to drain large hematomata.
Ferrous sulfate therapy may be appropriate in the recuperative period to
rebuild lost erythrocyte mass.
172 RODENTICIDES
-------
INORGANIC RODENTICIDES
Commercial Products
Toxicology
Thallium sulfate is well absorbed from the gut and across the skin. It
exhibits a very large volume of distribution (tissue uptake) and is distributed
chiefly to the kidney and liver, both of which participate in thallium excretion.
Most blood-borne thallium is in the red cells. Elimination half-life from blood
in the adult human is about 1.9 days. Most authors report the LD5Q in humans
to be between 10 and 15 mg/kg.10
Unlike other inorganic rodenticides like yellow phosphorus and zinc phos-
phide, thallium poisoning tends to have a more insidious onset with a wide
variety of toxic manifestations. Alopecia is a fairly consistent feature of thallium
poisoning that is often helpful diagnostically; however, it occurs two weeks or
more after poisoning and is not helpful early in the presentation.10-11 In addi-
tion to hair loss, the gastrointestinal system, central nervous system, cardiovas-
cular system, renal system, and skin are prominently affected by toxic intakes.
Early symptoms include abdominal pain, nausea, vomiting, bloody diar-
rhea, stomatitis, and salivation. Ileus may appear later on. Elevated liver enzymes
may occur, indicating tissue damage. Other patients experience signs of central
nervous system toxicity including headache, lethargy, muscle weakness,
paresthesias, tremor, ptosis, and ataxia.These usually occur several days to more
than a week after exposure.10'12 Extremely painful paraesthesias, either in the
presence or absence of gastrointestinal signs, may be the primary presenting
complaint.11'13 Myoclonic movements, convulsions, delirium, and coma reflect
more severe neurologic involvement. Fever is a bad prognostic indication of
brain damage.
Cardiovascular effects include early hypotension, due at least in part to a
toxic myocardiopathy.Ventricular arrythmias may occur. Hypertension occurs
later and is probably a result of vasoconstriction.The urine may show protein
and red cells. Patients may also develop alveolar edema and hyaline membrane
formation in the lungs, consistent with a diagnosis of Acute Respiratory Dis-
tress Syndrome.14 Death from thallium poisoning may be caused by respiratory
paralysis or cardiovascular collapse. Absorption of nonlethal doses of thallium
has caused protracted painful neuropathies and paresis, optic nerve atrophy,
persistent ataxia, dementia, seizures, and coma.11
Yellow phosphorus (also known as white phosphorus) is a corrosive agent
and damages all tissues it comes in contact with, including skin and the gut
lining. Initial symptoms usually reflect mucosal injury and occur a few minutes
to 24 hours following ingestion. The first symptoms include severe vomiting
and burning pain in the throat, chest, and abdomen.The emesis may be bloody
(either red, brown, or black)15 and on occasion may have a garlic smell.16'17 In
some cases, central nervous system signs such as lethargy, restlessness, and irrita-
INORGANICS
thallium sulfate
yellow phosphorus
zinc phosphide
Phosvin
Ridall-Zinc
Zinc-Tox
Yellow phosphorus is not sold
in the United States. Zinc
phosphide is still registered in
the United States, and can be
found in U.S. retail stores.
Thallium sulfate is no longer
registered for pesticidal use,
but is used by government
agencies only.
RODENTICIDES 173
-------
bility are the earliest symptoms, followed by symptoms of gastrointestinal in-
jury. Shock and cardiopulmonary arrest leading to death may occur early in
severe ingestions.17
If the patient survives, a relatively symptom-free period of a few hours or
days may occur, although this is not always the case.15The third stage of toxicity
then ensues with systemic signs indicating severe injury to the liver, myocar-
dium, and brain. This is due to phosphine gas (PH3) formed in and absorbed
from the gut. Nausea and vomiting recur. Hemorrhage occurs at various sites
reflecting a depression of clotting factor synthesis in the damaged liver. Also,
thrombocytopenia may contribute. Hepatomegaly and jaundice appear. Hypo-
volemic shock and toxic myocarditis may develop. Brain injury is manifested by
convulsions, delirium, and coma. Anuric renal failure commonly develops due
to shock and to the toxic effects of phosphorus products and accumulating
bilirubin on renal tubules.The mortality rate of phosphorus poisonings may be
as high as 50 percent.15
Zinc phosphide is much less corrosive to skin and mucous membranes
than yellow phosphorus, but inhalation of dust may induce pulmonary edema.
The emetic effect of zinc released in the gut may provide a measure of protection;
however, phosphine will be produced in the gut and absorbed along with the
zinc. Nausea and vomiting, excitement, chills, chest tightness, dyspnea, and cough
may progress to pulmonary edema. Patients face many of the same systemic tox-
icities as encountered with yellow phosphorus, including hepatic failure with
jaundice and hemorrhage, delirium, convulsions, and coma (from toxic encepha-
lopathy), tetany from hypocalcemia, and anuria from renal tubular damage.Ven-
tricular arrythmias from cardiomyopathy and shock also occur and are another
common cause of death.16'18 Inhalation of phosphine gas from improper use of
phosphide rodenticides has resulted in pulmonary edema, myocardial injury, and
multisystem involvement.19 For more information about the effects of phosphine
gas poisoning, see the section on phosphine in Chapter 16, Fumigants.
Confirmation of Poisoning
Phosphorus and phosphides sometimes impart a foul rotten fish odor
to vomitus, feces, and sometimes the breath. Luminescence of vomitus or feces
is an occasional feature of phosphorus ingestion. Hyperphosphatemia and hy-
pocalcemia occur in some cases, but are not consistent findings.
Thallium can be measured in the serum, urine, and hair. Hair analysis is
likely to be useful only in establishing protracted prior absorption. Serum con-
centration does not exceed 30 meg per liter in non-exposed persons.The most
reliable method for diagnosis is considered a 24-hour urine excretion. The
normal value is less than 10 meg/liter per 24 hours.10-13
174 RODENTICIDES
-------
Treatment: Thallium Sulfate
1. Gastrointestinal decontamination. If thallium sulfate was swallowed less
than an hour prior to treatment, consider gastrointestinal decontamination as
outlined in Chapter 2. Multiple doses of activated charcoal may be helpful in
increasing thallium elimination.13
2. Electrolyte and glucose solutions should be given by intravenous infu-
sion to support urinary excretion of thallium by diuresis. Monitor fluid balance
carefully to insure that fluid overload does not occur. If shock develops, give
whole blood, plasma, or plasma expanders. Pressor amines must be used very
carefully in light of myocardial injury. Monitor EGG for arrhythmias.
3. Convulsions. Control seizures and myoclonic jerking as outlined in Chap-
ter 2.
4. Combined hemodialysis and hemoperfusion has proven moderately
effective in reducing the body burden of thallium in victims of severe poison-
ing. In one case, peritoneal dialysis was not effective.
5. Chelation therapy. Several methods for chelating and/or accelerating dis-
position of thallium have been tested and found either relatively ineffective or
hazardous. Chelating agents are not recommended in thallium poisoning. Po-
tassium chloride has been recommended. However it has been reported to
increase toxicity to the brain,11'14 and has not shown to increase elimination in
6. Potassium ferric ferrocyanide (Prussian Blue) orally enhances fecal
excretion of thallium by exchange of potassium for thallium in the gut. It is not
available or approved for use in humans in the United States. Reports of its use
in humans are anecdotal and do not strongly support its use.
Treatment: Yellow Phosphorus and Zinc Phosphide
1. Skin decontamination. Brush or scrape non-adherent phosphorus from
the skin. Wash skin burns with copious amounts of water. Make sure all par-
ticles of phosphorus have been removed. If burned area is infected, cover with
an antimicrobial creme. See Chapter 2.
2. Supportive management. Poisonings by ingested yellow phosphorus or
zinc phosphide are extremely difficult to manage. Treatment is basically sup-
portive and symptomatic. Control of airway and convulsions must be estab-
lished prior to considering gastrointestinal decontamination as described in
Chapter 2.
RODENTICIDES 175
-------
Caution: Highly toxic phosphine gas may evolve from emesis, lavage fluid,
and feces of victims of these poisons.The patient's room should be well venti-
lated. Persons attending the patient must wear gloves to avoid contact with the
phosphorus.
3. Lavage with 1:5000 potassium permanganate solution has been used in the
management of ingested phosphorus compounds in the past; however, there is
not sufficient evidence for its efficacy and we do not recommend it.
4. Catharsis is probably not indicated, but there may be some benefit in ad-
ministering mineral oil. Dosage is 100 mL for adults and children over 12 years,
and 1.5 mL/kg body weight in children under 12 years. Do not give vegetable
oils or fats.
5. Transfusions. Combat shock and acidosis with transfusions of whole blood
and appropriate intravenous fluids. Monitor fluid balance and central venous
pressure to avoid fluid overload. Monitor blood electrolytes, glucose, and pH to
guide choice of intravenous solutions. Administer 100% oxygen by mask or
nasal tube.
6. Oxygen. Combat pulmonary edema with intermittent or continuous posi-
tive pressure oxygen.
7. Renal protection. Monitor urine albumin, glucose, and sediment to detect
early renal injury. Extracorporeal hemodialysis will be required if acute renal
failure occurs, but it does not enhance excretion of phosphorus. Monitor EGG
to detect myocardial impairment.
8. Liver damage. Monitor serum alkaline phosphatase, LDH, ALT, AST, pro-
thrombin time, and bilirubin to evaluate liver damage. Administer
AquamephytonR (vitamin Kj) if prothrombin level declines.
9. Pain management. Morphine sulphate may be necessary to control pain.
Adult dose: 2-15 mg IM/IV/SC Q 2-6 hours prn. Child's dose: 0.1-0.2 mg/
kg/dose Q 2-4 hours.
10. Phosphine gas. For specific therapy due to phosphine gas, refer to the
treatment of phosphine poisoning in Chapter 16, Fumigants.
176 RODENTICIDES
-------
CONVULSANTS
Commercial Products
Toxicology
Crimidine is a synthetic chlorinated pyrimidine compound that, in adequate
dosage, causes violent convulsions similar to those produced by strychnine.
Sodium fluoroacetate and fluoroacetamide are readily absorbed by
the gut, but only to a limited extent across skin.The toxic mechanism is distinct
from that of fluoride salts.Three molecules of fluoroacetate or fluoroacetamide
are combined in the liver to form a molecule of fluorocitrate, which poisons
critical enzymes of the tricarboxylic acid (Krebs) cycle, blocking cellular
respiration. The heart, brain, and kidneys are the organs most prominently a
ffected.The effect on the heart is to cause arrhythmias, progressing to ventri-
cular fibrillation, which is a common cause of death. Metabolic acidosis, shock,
electrolyte imbalance, and respiratory distress are all poor prognostic signs.
Neurotoxicity is expressed as violent tonic-clonic convulsions, spasms, and
rigor, sometimes not occurring for hours after ingestion.21
Strychnine is a natural toxin (nux vomica) which causes violent convul-
sions by direct excitatory action on the cells of the central nervous system,
chiefly the spinal cord. Death is caused by convulsive interference with pulmo-
nary function, by depression of respiratory center activity, or both. Strychnine
is detoxified in the liver. Residence half-life is about 10 hours in humans. On-
set of symptoms is usually within 15-20 minutes of ingestion. Lethal dose in
adults is reported to be between 50 and 100 mg, although as little as 15 mg can
kill a child.22
CONVULSANTS
crimidine
Castrix
fluoroacetamide*
Compound 1081
sodium fluoroacetate
Compound 1080
strychnine
* Discontinued in the U.S.
Only specially trained
personnel are allowed to use
strychnine. Crimidine and
sodium fluoroacetate are no
longer registered for use as
pesticides.
Confirmation of Poisoning
There are no generally available tests to confirm poisoning by the convul-
sant rodenticides.
Treatment: Sodium Fluoroacetate and Fluoroacetamide
Poisonings by these compounds have occurred almost entirely as a result of
accidental and suicidal ingestions. If the poison was ingested shortly before
treatment and convulsions have not yet occurred, the first step in treatment is
to remove the toxicant from the gut. If the victim is already convulsing, how-
ever, it is necessary first to control the seizures before gastric lavage and cathar-
sis are undertaken.
1. Control seizures as outlined in Chapter 2. Seizure activity from these
compounds may be so severe that doses necessary for seizure control may para-
lyze respiration. For this reason, it is best to intubate the trachea as early as
RODENTICIDES 177
-------
possible in the course of seizure control, and support pulmonary ventilation
mechanically.This has the added advantage of protecting the airway from aspi-
ration of regurgitated gastric contents.
2. Gastrointestinal decontamination. If the patient is seen within an hour
of exposure and is not convulsing, consider gastrointestinal decontamination as
outlined in Chapter 2.
3. Administer intravenous fluids cautiously to support excretion of ab-
sorbed toxicant. It is especially important to avoid fluid overload in the pres-
ence of a weak and irritable myocardium.
4. Monitor electocardiogram for arrhythmias and, if detected, treat with an
appropriate antiarrhythmic drug. Facilities for electroshock cardioversion should
be at hand. Some victims of fluoroacetate poisoning have been rescued after
repeated cardioversions.
5. Calcium gluconate (10% solution) given slowly intravenously should be
given to relieve hypocalcemia. Care must be taken to avoid extravasation.
Dosage of Calcium Gluconate:
Supplied as 100 mg/mL (10% solution)
Adults and children over 12years: 10 mL of 10% solution, given slowly,
intravenously. Repeat as necessary.
Children under 12 years: 200-500 mg/kg/24 hr divided Q6 hr. For
cardiac arrest, 100 mg/kg/dose. Repeat dosage as needed.
6. Other therapies. Antidotal efficacy of glycerol monacetate and ethanol,
observed in animals, has not been substantiated in humans.These therapies are
not recommended in humans.
Treatment: Strychnine or Crimidine
Strychnine and crimidine cause violent convulsions shortly following in-
gestion of toxic doses. Both poisons are probably well adsorbed onto charcoal.
If the patient is seen fully conscious and not convulsing a few moments after
the ingestion, great benefit may derive from the immediate ingestion of acti-
vated charcoal. If the patient is already obtunded or convulsing, the involuntary
motor activity must be controlled before steps are taken to empty the gut and
limit toxicant absorption.
178 RODENTICIDES
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1. Control seizures as outlined in Chapter 2.
2. Gastrointestinal decontamination. Consider gastrointestinal decontami-
nation if patient is seen within an hour of ingestion.
3. Administer intravenous fluids to support excretion of absorbed toxi-
cants. Inclusion of sodium bicarbonate in the infusion fluid counteracts meta-
bolic acidosis generated by convulsions. Effectiveness of hemodialysis and
hemoperfusion has not been tested.
MISCELLANEOUS RODENTICIDES:
RED SQUILL AND CHOLECALCIFEROL
Toxicology
Red squill is a little-used rodenticide, consisting of the inner portions of a
small cabbage plant grown in eastern Mediterranean countries. Its toxic prop-
erties have been known since ancient times and are probably due to cardiac
glycosides. For several reasons, mammals other than rodents are unlikely to be
poisoned: (1) red squill is intensely nauseant, so that animals which vomit (ro-
dents do not) are unlikely to retain the poison; (2) the glycoside is not effi-
ciently absorbed from the gut; and (3) absorbed glycoside is rapidly excreted.
Injection of the glycosides leads to effects typical of digitalis: alterations in
cardiac impulse conduction and arrhythmias.
Cholecalciferol is the activated form of vitamin D (vitamin Dj). Its toxic
effect is probably a combination of actions on liver, kidney, and possibly the
myocardium, the last two toxicities being the result of hypercalcemia. Early symp-
toms and signs of vitamin D-induced hypercalcemia in humans are fatigue, weak-
ness, headache, and nausea. Polyuria, polydipsia, proteinuria, and azotemia result
from acute renal tubular injury by hypercalcemia.This is commonly the cause of
death. Prolonged hypercalcemia results ultimately in nephrolithiasis and nephro-
calcinosis. Azotemia occurs as renal tubular damage progresses.
Confirmation of Poisoning
Cholecalciferol intoxication is indicated by an elevated concentration of
calcium (chiefly the unbound fraction) in the serum. There are no generally
available tests for the other rodenticides or their biotransformation products.
Commercial Products
MISCELLANEOUS
Cholecalciferol
Muritan
Quintox
Rampage
red squill*
Dethdiet
Rodine
* Discontinued in the U.S.
RODENTICIDES 179
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Treatment: Red Squill
Red squill is unlikely to cause poisoning unless ingested at substantial dos-
age. The problem is usually self-correcting due to its intense emetic effect. If,
for some reason, the squill is retained, syrup of ipecac, followed by 1 -2 glasses of
water, should be administered to initiate vomiting. Monitor cardiac status elec-
trocardiographically.
Treatment: Cholecalciferol
Cholecalciferol at high dosage may cause severe poisoning and death.
Human poisonings from its use as a rodenticide have not been reported, but
vitamin D overdosage has occurred under clinical circumstances. Treatment is
directed at limiting gastrointestinal absorption, accelerating excretion, and
counteracting the hypercalcemic effect.
1. Gastrointestinal decontamination. If Cholecalciferol has been ingested
within an hour prior to treatment, consider gastric decontamination, as out-
lined in Chapter 2. Repeated administration of charcoal at half or more the
initial dosage every 2-4 hours may be beneficial.
2. Administer intravenous fluids (normal saline or 5% glucose) at moderate
rates to support excretory mechanisms and excretion. Monitor fluid balance to
avoid overload, and measure serum electrolytes periodically. Measure total and
ionized calcium levels in the blood 24 hours after Cholecalciferol ingestion to
determine severity of toxic effect. Monitor urine for protein, and red and white
cells to assess renal injury.
3. Furosemide (Lasix), 20-40 mg intravenously, or 40-120 mg daily by mouth
may be given to promote diuresis. Dosage for children under 12 is approximately
0.5-1.0 mg/kg body weight intravenously, 1.0-2.0 mg/kg body weight orally.
Monitor serum potassium after dosage; give potassium chloride if hypokalemia
occurs. Consult package insert for additional directions and warnings.
4. Predinisone and similar glucocorticoids reduce elevated blood calcium
levels in certain diseases. Although they have not been tested in Cholecalciferol
overdosage, it is possible that they would be beneficial. Dosage is approximately
1 mg per kilogram per day, to a maximum of 20 mg per day.
5. Calcitonin (salmon calcitonin, CalcimarR) is a logical antidote for Cholecal-
ciferol actions, but has only very limited use in human poisoning.23 In other
conditions, the usual dosage is 4 International Units per kg body weight every
12 hours, by intramuscular or subcutaneous injection, continued for 2-5 days.
180 RODENTICIDES
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The dose may be doubled if calcium-lowering effect is not sufficient. Calcium
gluconate for intravenous injection should be immediately available if indica-
tions of hypocalcemia (carpopedal spasm, cardiac arrhythmias) appear. Consult
package insert for additional directions and warnings.
6. Cholestryamine appears effective in the treatment of vitamin D toxicity in
animals.24 It has seen very limited use in humans.25-26
References
1. Mack RB. Not all rats have four legs: Superwarfarin poisoning. N C Med] 1994;55:554-6.
2. Katona B and Wason S. Superwarfarin poisoning. /Emerg Med 1989;7:627-31.
3. LitovitzTL,SrnilksteinM,FelbergL,et al. 1996 Annual Report of the American Association of
Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 1997;15:447-
500.
4. Burucoa C, Mura P, Robert R, et al. Chlorophacinone intoxication. ClinToxicol 1989;27:79-89.
5. Smolinske SC, Scherger DL, Kearns PS, et al. Superwarfarin poisoning in children: A pro-
spective study. Pediatrics 1989;84:490-4.
6. Lipton RA and Klass EM. Human ingestion of a 'superwarfarin' rodenticide resulting in a
prolonged anticoagulant effect. JAMA 1984;252:3004-5.
7. Helmuth RA, McCloskey DW, Doedens DJ, et al. Fatal ingestion of a brodifacoum-contain-
ing rodenticide. Lab Med 1989;20:25-7.
8. NorcrossWA, GaniatsTG, Ralph LP, et al. Accidental poisoning by warfarin-contaminated
herbal tea. West J Med 1993;159:80-2.
9. Kruse JA and Carlson RW Fatal rodenticide poisoning with brodifacoum. Ann Emerg Med
1992:21:331-6.
10. Mayfield SR, Morgan DP, and Roberts RJ. Acute thallium poisoning in a 3-year old child.
Clin Pediatr (Phila) 1983;23:461-2.
11. Bank WJ, Pleasure DE, Suzuki K, et al.Thallium poisoning. Arch Neurol 1972;26:456-64.
12. Fred HL and Accad ME Abdominal pain, leg weakness, and alopecia in a teenage boy. Hosp
Pract 1997:32:69-70.
13. MeggsWJ, Hoffman RS, Shih RD, et al.Thallium poisoning from maliciously contaminated
food. JToxicol Clin Toxicol 1994;32:723-30.
14. Roby DS, Fein AM, Bennett RH, et al. Cardiopulmonary effects of acute thallium poison-
ing. Chest 1984;85:236-40.
15. McMarron MM and Gaddis GR Acute yellow phosphorus poisoning from pesticide pastes.
ClinToxicol 1981;18:693-711.
16. Dipalma JR. Human toxicity from rat poison. Am Fam Physician 1981 ;24:186-9.
17. Simon FA and Pickering LK. Acute yellow phosphorus poisoning: Smoking stool syndrome.
JAMA 1976:235:1343-4.
18. Patial RK, Bansal SK, Kashyap S, et al. Hypoglycaemia following zinc phosphide poisoning.
JAssoc Physicians India 1990:38:306-7.
19. Schoonbroodt D, Guffens P, Jousten P, et al. Acute phosphine poisoning? A case report and
review. Acta Clin Belg 1992;47:280-4.
RODENTICIDES 181
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20. Koshy KM and Lovejoy FH.Thallium ingestion with survival: Ineffectiveness of peritoneal
dialysis and potassium chloride diuresis. Clin Toxicol 1981;18:521-5.
21. Chi CH, Chen KW, Chan SH, et al. Clinical presentation and prognostic factors in sodium
monofluoroacetate intoxication. ClinToxicol 1996;34:707-12.
22. Benomran FA and Henry JD. Homicide by strychnine poisoning. Med Sci Law 1996;36:271-3.
23. Buckle RM, GamlenTR, and Pullen IM.Vitamin D intoxication treated with procine calci-
tonin. BrMedJ 1972;3:205-7.
24. Queener SF and Bell NH. Treatment of experimental vitamin D3 intoxication in the rat
with cholestyramine. Clin Res 1976;24:583A.
25. Jibani M and Hodges NH. Prolonged hypercalcaemia after industrial exposure to vitamin D.
Br MedJ 1985;290:748-9.
26. Thomson RB and Johnson JK. Another family with acute vitamin D intoxication: Another
cause of familial hypercalcaemia. Postgrad Med] 1986;62:1025-8.
182 RODENTICIDES
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CHAPTER 18
Miscellaneous Pesticides,
Solvents, and Adjuvants
There are a variety of pesticides that do not fall into the broad categories
described in other chapters in this manual. Many of them are widely used and
are therefore associated with a high probability of human exposure. Some have
significant toxicity as well as a likelihood of human exposure, and are of real
concern. Many of the solvents and adjuvants used in the formulation of pesti-
cides also present a high likelihood of human exposure. Such exposures can
result in significant toxic effects that in many cases exceed the toxicity of the
active pesticide ingredient(s). Furthermore, it is sometimes more difficult to
obtain information about the solvents and adjuvants, complicating the issues of
diagnosis and management.
4-AMINOPYRIDINE
Toxicology
4-Aminopyridine is a highly toxic white powder used as a bird repellent. It
works by making one or two birds acutely ill, thus warning off the remaining
birds by cries of distress. It is toxic to all vertebrates.1 It is usually added to grain
baits in 0.5%-3.0% concentration, but 25% and 50% concentrates in powdered
sugar are available. Recent human exposure has come from its use as an inves-
tigational drug in the treatment of multiple sclerosis.2'3 It is rapidly absorbed by
the gut, less effectively across skin.The chief mechanism of toxicity is enhance-
ment of cholinergic transmission in the nervous system through the release of
acetylcholine both centrally and peripherally. Due to enhanced transmission at
neuromuscular junctions, severe muscle spasms may be a prominent manifesta-
tion of toxicity.2 4-Aminopyridine is rapidly metabolized and excreted.
No human poisonings have occurred as a result of ordinary use, but the
effects of ingestion of about 60 mg each by two adults have been reported.
Both experienced immediate abdominal discomfort, nausea and vomiting,
weakness, dizziness, and profuse diaphoresis, and one went on to develop a
tonic-clonic seizure and required ventilatory support. Acidosis was present in
both cases.1 Dizziness, giddiness, and gait disturbances are common, and sei-
zures may be severe, although recovery with supportive therapy and ventilatory
support has been the usual outcome.1'2-3
HIGHLIGHTS
Physicians may need to
actively seek information
from producers regarding
exact makeup of "inert
ingredients"
Signs and Symptoms:
Highly variable based on
agent
Many are irritants and
corrosives
Creosote (phenolic
compounds) give a smoky
color to urine
Methemoglobinemia may
occur with sodium
chlorate and creosote
poisoning
Sodium chlorate also
causes renal injury,
arrhythmia, shock, and
DIG
Pneumonitis occurs with
hydrocarbon aspiration
Treatment:
Skin, eye, and Gl
decontamination
Supportive care and
seizure control
Methylene blue for
methemoglobinemia
MISCELLANEOUS 183
-------
Commercial Products
Treatment
MISCELLANEOUS PESTICIDES
4-Aminopyridine
Avitrol
calcium cyanamide*
Cyanamide
nitrolime
creosote
endothall
Accelerate
Aquathol
Des-i-cate
Endothall Turf Herbicide
Herbicide 273
Hydrothol
metaldehyde
Antimilace
Cekumeta
Halizan
Metason
Namekil
others
sodium chlorate
Defol
De-Fol-Ate
Drop-Leaf
Fall
KM
Kusatol
Leafex
SYNERGISTS
piperonyl butoxide
SOLVENTS & ADJUVANTS
anticaking agents
dusts
emulsifiers
granular formations
penetrants
petroleum distillants
isopropanol
methanol
toluene
xylene
safeners
stickers and spreaders
*Discontinued in the U.S.
1. Skin decontamination. If skin or eye contamination has occurred, thor-
ough washing of the skin or eyes is indicated. See Chapter 2.
2. Gastrointestinal decontamination. If the patient is seen within an hour
of ingestion of a significant quantity of this compound, gastrointestinal decon-
tamination should be considered, as outlined in Chapter 2. If treatment is de-
layed, immediate oral administration of charcoal and sorbitol may represent
reasonable management.
3. Seizures may require anticonvulsant medication. See Chapter 2 for dosages.
4. Muscular spasms. Neuromuscular blockade with drugs such as d-
tubocuarine, metocurine and pancuronium bromide have been used sucessfully
to relieve the muscular spasms that occur with this agent. Such therapy must be
provided in an intensive care setting.1
5. Dehydration should be treated with intravenous fluids if oral fluids cannot
be retained.
CALCIUM CYANAMIDE
This synthetic compound is marketed as granules containing 44% calcium
cyanamide, yielding 19.5% nitrogen. It is incorporated into soil to serve as
fertilizer, fungicide, and herbicide. In contact with water, hydrogen cyanamide
is released. Acidic conditions accelerate this reaction. Hydrogen cyanamide is a
solid with considerable vapor pressure. It has toxic properties totally different
from those of cyanide, and it does not degrade to cyanide.
Toxicology
Calcium cyanamide is only moderately irritating to skin, but hydrogen
cyanamide is severely irritating and caustic to skin and the inhaled gas is strongly
irritating to mucous membranes.4 Dermal and mucosal lesions in the mouth,
tongue, and upper esophagus have occurred after exposure. No systemic symp-
toms from dermal exposure have been reported.5 Systemic poisonings have
followed inhalation of hydrogen cyanamide and ingestion of the salt. Manifes-
tations of poisoning include flushing, headache, vertigo, dyspnea, tachycardia,
and hypotension, sometimes progressing to shock.4 Because cyanamide is an
inhibitor of acetaldehyde dehydrogenase, ingestion of alcohol exaggerates the
symptoms. (A citrated form of cyanamide has been used in place of Antabuse in
alcohol aversion therapy.)
184 MISCELLANEOUS
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Treatment
1. Skin decontamination. Skin contamination with either the calcium salt
or the free form should be removed by washing with soap and water. Flush eyes
with copious amounts of clean water. If skin or eye irritation persists, medical
attention should be obtained promptly. See Chapter 2.
2. Gastrointestinal decontamination. If large doses have been ingested within
an hour of exposure, gastrointestinal decontamination should be considered. If
dosage was small or treatment is delayed, oral administration of activated charcoal
and sorbitol probably represents reasonable management. See Chapter 2 for doses.
3. Hypotension or Antabuse-type reactions should be treated by placing
the patient in the Trendelenburg position, giving intravenous fluids, including
plasma or blood, if needed, and, if necessary, vasopressor drugs parenterally.
4. Atropine is not antidotal.
CREOSOTE
Creosote is obtained by distillation of the tar formed by heating wood or
coal in the absence of oxygen. It is purified by extraction into oils. Creosote
from wood consists mainly of guaiacol (methoxy phenol) and cresol (methyl
phenol). Coal-derived creosote contains, in addition, some phenol, pyridine,
and pyridinol. Creosote is extensively used as a wood preservative, usually by
high-pressure impregnation of lumber. It has also been used as an animal dip
and disinfectant. Much of human exposure is in the form of various phenol
compounds.
Creosote is irritating to skin, eyes, and mucous membranes. Workers in
contact with technical creosote or with treated timbers sometimes develop
skin irritation, vesicular or papular eruptions, dermal pigmentation, and
occasionally gangrene and skin cancer.6 Photosensitization has been reported.
Eye contamination has resulted in conjunctivitis and keratitis, sometimes resulting
in corneal scarring.The constituents of creosote are efficiently absorbed across
the skin, but systemic poisonings following dermal absorption have occurred
very rarely. Absorption of ingested creosote from the gut occurs promptly, and
there may be significant absorption of vapor by the lung. Conjugates of absorbed
phenolic constituents are excreted mainly in the urine. Acute toxic effects are
similar to those of lysol, but the corrosive nature of creosote is somewhat less
because of greater dilution of phenol in the creosote.7 Irritation of the
gastrointestinal tract, toxic encephalopathy, and renal tubular injury are the
principal effects. A chronic toxicosis from continuing gastrointestinal absorption
(creosote used medicinally) has been described, consisting of gastroenteritis
and visual disturbances.
MISCELLANEOUS 185
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Manifestations of acute systemic poisoning are salivation, vomiting, dyspnea,
headache, dizziness, loss of pupillary reflexes, cyanosis, hypothermia, convulsions,
and coma. Death is due to multi-organ system failure as patients develop shock,
acidosis, respiratory depression, and anuric renal failure.
Confirmation of Poisoning
The presence of phenolic oxidation products imparts a dark, smoky color
to the urine.7 If there is suspicion of poisoning, addition of a few drops of ferric
chloride solution to the urine yields a violet or blue color, indicating the pres-
ence of phenolic compounds.
Treatment
1. Skin decontamination. Stringent measures should be taken to avoid con-
tamination of skin or eyes and inhalation of vapor. Skin contamination should
be promptly washed off with soap and water. Remove eye contamination by
washing with copious amounts of water, then obtain specialized medical atten-
tion promptly because corneal injury may be severe. See Chapter 2.
2. Gastrointestinal decontamination. If a significant amount of creosote has
been ingested and the patient is alert and able to swallow, immediately administer
a slurry of activated charcoal by mouth. Further efforts to limit absorption will
depend on whether there has been corrosive injury to the esophagus. If pharyn-
geal redness and swelling are evident, neither induced emesis nor gastric lavage is
advisable due to potential re-exposure of the esophagus to the creosote, or perfo-
ration of the esophagus from a gastric tube. For further information on gastric
decontamination, including charcoal dosing, see Chapter 2.
3. Maintain pulmonary ventilation mechanically with oxygen, if necessary.
4. Blood and urine samples. Draw a blood sample to test for methemoglo-
binemia, to measure BUN and blood electrolytes, and to check for signs of liver
injury (bilirubin, GGT, LDH, ALT, AST, and alkaline phosphatase). Examine
the urine for protein and cells, and for "smoky" phenolic excretion products.
5. Intravenous fluids. Give fluids intravenously to correct dehydration and
electrolyte disturbances. Include glucose to protect the liver and bicarbonate to
relieve metabolic acidosis, as necessary. Monitor fluid balance carefully to signal
discontinuation of intravenous fluids if renal failure occurs. Plasma or blood
transfusion may be needed to overcome shock.
6. Monitor ECG to detect arrhythmias and/or conduction defects that may
appear as manifestations of a toxic myocardiopathy.
186 MISCELLANEOUS
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7. Convulsions. Anticonvulsants may be needed to control seizures as out-
lined in Chapter 2.
8. Hemodialysis is not effective in accelerating disposition of phenol (or,
presumably, creosote), but hemoperfusion over charcoal probably is effective.8
This should be considered in severe creosote poisonings.
9. Methemoglobinemia is rarely severe, but intravenous administration of 1%
methylene blue may be considered if 25-30% of hemoglobin is converted. Dose
is 0.1 mL of 1% solution per kg body weight, given over no less than 10 minutes.
Nausea, dizziness, and a transient increase in blood pressure may occur.
ENDOTHALL
As the free acid or as sodium, potassium, or amine salts, endothall is used as
a contact herbicide, defoliant, aquatic herbicide, and algacide. It is formulated in
aqueous solutions and granules at various strengths.
Toxicology
Endothall is irritating to the skin, eyes, and mucous membranes. It is well
absorbed across abraded skin and from the gastrointestinal tract. Recognized
systemic toxic mechanisms in mammals are: corrosive effects on the gastrointes-
tinal tract (particularly from high concentrations of the free acid); cardiomy-
opathy and vascular injury leading to shock; and central nervous system injury,
causing convulsions and respiratory depression. A single case has been reported
of lethal poisoning in a previously healthy 21-year-old man who died after
ingestion of 7-8 grams of endothall. In this patient, hemorrhage and edema
were noted in the gastrointestinal tract and lungs.9 There are no standards for
levels, and they are not considered useful in management.
Treatment
1. Skin decontamination. Wash endothall from the skin with soap and water.
Flush contamination from the eyes with copious amounts of clean water. Ob-
tain medical attention if irritation of skin or eyes persists. See Chapter 2.
2. Gastrointestinal decontamination. If a large quantity has been ingested, the
patient is seen within an hour of exposure, and is fully alert and not convulsing,
gastrointestinal decontamination should be considered as outlined in Chapter 2.
Lavage is usually contraindicated due to the corrosive nature of this agent.
MISCELLANEOUS 187
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3. Intubation. If there are indications of corrosive effects in the pharynx,
gastric intubation should not be attempted because of the risk of esophageal
perforation.Treatment procedures appropriate for ingestions of corrosives (strong
acids and alkalis) may be necessary. Referral should be made to a surgeon or
gastroenterologist for consideration of endoscopy.
4. Oxygen should be given by mask. If respiratory drive is weak, pulmonary
ventilation may have to be supported mechanically.
5. Monitor blood pressure closely. Infusions of plasma, blood, other volume
expanders, and pressors may be needed to combat shock.
6. Administer intravenous fluids to correct dehydration, stabilize electro-
lytes, provide sugar, and support mechanisms for toxicant disposition. Give va-
soactive amines very carefully in light of possible myocardiopathy.
7. Convulsions. Seizures may require administration of diazepam and/or other
anticonvulsants.
8. Hemodialysis. It is not known whether hemodialysis or hemoperfusion
would be effective in removing endothall from the blood.This option should
be considered if the patient's condition deteriorates despite supportive care.
METALDEHYDE
Toxicology
Metaldehyde is a four-unit cyclic polymer of acetaldehyde which has long
been used to kill slugs and snails, which are attracted to it without the use of
bait. Occasional poisonings of animals and children have resulted from inges-
tion of pellets intended as molluscicide, but tablets designed as a combustible
fuel ("meta-fuel") have also been responsible for human poisonings.10 Another
form of exposure is "snow storm tablets," which the user places at the end of a
lighted cigarette to create snow. Toxicity occurs through inhalation of
metaldehyde fumes."The biochemical mechanism of poisoning is not known.
Both acetaldehyde and metaldehyde produced similar effects in dogs; however,
acetaldehyde was not detected in the plasma or urine of the metaldehyde-
poisoned dogs.12
Ingestion of a toxic dose is often followed shortly by nausea and vomiting.
The other primary features of toxicity are pyrexia, generalized seizures, and
mental status changes, sometimes leading to coma.10'13 Other signs and symp-
toms that may occur include hypersalivation, facial flushing, dizziness, tachyp-
nea, and acidosis.10'11 Pneumonitis has followed inhalational exposure to
188 MISCELLANEOUS
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metaldehyde.11 While most cases are dramatic with significant seizures and coma,
fatal events are infrequent.10-13 Poisoned animals show tremors, ataxia, hyperes-
thesia, salivation, ataxia, and seizures.12 Autopsy findings in fatal human poison-
ings indicate severe damage to liver cells and renal tubular epithelium.
Confirmation of Poisoning
Metaldehyde can be measured in the blood and urine, although there are
very few reports of levels among poisoned humans. One patient who had se-
vere tonic clonic seizures and was comatose had a metaldehyde level in the
serum of 125 mg/L with a half-life of 27 hours. This patient did not have
detectable acetaldehyde in the serum.13
Treatment
1. Gastrointestinal decontamination. If ingestion occurred within an hour
of treatment, consider gastrointestinal decontamination as outlined in Chapter 2.
Activated charcoal may well be useful against metaldehyde.
2. Convulsions. If seizures occur, sedative anticonvulsants must be adminis-
tered. See Chapter 2 for dosage.
3. Supportive treatment. Appropriate supportive treatment including intra-
venous fluids containing saline and glucose should be given. Sodium bicarbon-
ate may be considered in the event of severe metabolic acidosis. Fluid balance
and electrolytes must be monitored carefully to avoid fluid overload if renal
failure supervenes.
4. Renal failure. There is no specific antidote for metaldehyde poisoning.
Hemodialysis is probably not effective in removing metaldehyde, but must be
instituted if renal failure occurs. The effectiveness of hemoperfusion has not
been tested.
5. Liver function tests and urine sediment examination should be done to
assess liver and kidney injury in poisoned patients.
SODIUM CHLORATE
Sodium chlorate is used in agriculture as a defoliant, nonselective contact
herbicide, and semipermanent soil sterilant. Because of its explosive nature, it
must be formulated with water-soluble fire retardant material, such as sodium
metaborate, soda ash, magnesium chloride, or urea. It is usually applied in water
solution.
MISCELLANEOUS 189
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Toxicology
Sodium chlorate is irritating to skin, eyes, and mucous membranes of the
upper respiratory tract.14 Dermal absorption is slight. Even though gastrointes-
tinal absorption is also inefficient, severe (sometimes fatal) poisoning follows
ingestion of a toxic dose, estimated at about 20 grams in the adult human.
Excretion is chiefly in the urine. The principal mechanisms of toxicity are
hemolysis, methemoglobin formation, cardiac arrhythmia (partly secondary to
hyperkalemia), and renal tubular injury.14'15
The irritant action on the gut causes nausea, vomiting, and abdominal pain.
Once absorbed, hemoglobin is rapidly oxidized to methemoglobin, and intravas-
cular hemolysis occurs.14 Cyanosis is prominent if methemoglobinemia is severe
and may be the only presenting sign.15 Acute tubular necrosis and hemoglobin-
uria may result from the hemolysis or direct toxic injury. Plasma and urine are
dark brown from the presence of free hemoglobin and methemoglobin.14'15'16
Release of potassium from red cell destruction results in hyperkalemia which
may be severe enough to cause life-threatening arrythmias.16 The liver and spleen
are often enlarged due to uptake of hemolyzed erythrocytes.15 Hypoxemia may
lead to convulsions. Death may be the result of shock, tissue hypoxia, renal failure,
hyperkalemia, or disseminated intravascular coagulation (DIG).14'15'16
Confirmation of Poisoning
There are no widely available tests specifically for chlorate. Dark brown
staining of the plasma and urine indicates the action of a strong oxidizing agent
on hemoglobin. See Chapter 2.
Treatment
1. Skin decontamination. Skin contamination should be removed immedi-
ately by washing with soap and water. Medical attention should be sought if
irritation persists. Flush contamination from eyes with copious amounts of clean
water, then obtain specialized medical attention promptly, because irritant ac-
tion may be severe. See Chapter 2.
2. Gastrointestinal decontamination. If sodium chlorate has been ingested
within an hour prior to treatment, consider gastrointestinal decontamination as
outlined in Chapter 2.
3. Oxygen. If respiration is depressed, ventilatory support may be necessary.
4. Sodium thiosulfate has been recommended as an antidote against absorbed
sodium chlorate.Thiosulfate is thought to inactivate the chlorate ion to form the
190 MISCELLANEOUS
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less toxic chloride ion. It can be given orally or as an IV infusion over 60-90
minutes.The dose is 2-5 g dissolved in 200 mL of 5% sodium bicarbonate.14
5. Monitor blood pressure, fluid balance, blood electrolytes, BUN, methemo-
globin, and bilirubin, as well as urine protein, cells and free hemoglobin con-
tent, and EGG. Widening of the QRS complex and prolongation of the PR
interval indicate hyperkalemic cardiac toxicity.
6. Milk may be helpful in relieving the pain of gastric irritation.
7. Administer intravenous fluids to sustain chlorate excretion. Maintain
urine pH in the alkaline range by adding sodium bicarbonate to the infusion
fluid. Monitor urine production closely, so that intravenous fluids can be slowed
or discontinued if renal failure occurs. Blood transfusion may be needed if
hemolysis and methemoglobinemia are severe. Exchange transfusion has been
recommended to enhance clearance and treat DIG.16
8. Hemodialysis may be life-saving in severe poisoning. It is effective in re-
moving chlorate from the blood, provides a means to control hyperkalemia,
and makes possible the control of extracellular fluid volume and composition
while renal function remains impaired.
9. Methemoglobinemia. Administration of methylene blue to reverse meth-
emoglobinemia may be considered if as much as 25-30% of hemoglobin is
converted. Give intravenously 0.1 mL/kg body weight of a 1% solution over a
period of at least 10 minutes. An increase in blood pressure, nausea, and dizzi-
ness may occur, but these effects are usually transient. As the use of this agent in
chlorate poisoning has not proven beneficial in the past, it is still advisable to
proceed to exchange transfusion as stated in #7.
SYNERGISTS:
PIPERONYL BUTOXIDE
Synergists are chemical agents included in pesticide products to enhance
the killing power of the active ingredients.The widely-used insecticide syner-
gist, piperonyl butoxide, acts by inhibiting the enzymatic degradation of pyre-
thrins, rotenone, N-methyl carbamates, and possibly some other insecticides.
There is limited dermal absorption on contact. Inherent toxicity in mammals is
low. Large absorbed doses may theoretically enhance the toxic hazard of the
rapidly metabolized insecticides used today, although inhibition of human drug-
metabolizing enzymes by these agents has not actually been demonstrated.Their
presence in pesticide products to which humans are exposed does not change
MISCELLANEOUS 191
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the basic approach to management of poisoning, except that some possibility of
enhanced toxicity of the active insecticidal ingredients should be kept in mind.
SOLVENTS AND ADJUVANTS
Liquid materials in which pesticides are dissolved and the solids on which
they are adsorbed (sometimes called carriers or vehicles) are selected by pro-
ducers to achieve stability of the active ingredient, convenience in handling
and application, and maximum killing power following application. Often, the
particular solvents and adjuvants selected by pesticide manufacturers are re-
sponsible for giving their commercial products a competitive edge. For this
reason, their inclusion in marketed products is usually proprietary information,
not available to the general public except in emergencies. If a poisoning emer-
gency exists, pesticide companies will usually cooperate in supplying physicians
with information needed to provide treatment. Some companies will put the
inert ingredients on the Material Safety Data Sheet (MSDS). The physician
should seek this information to assist in evaluating all possible exposures. A
direct request to the producer is the quickest way to secure this information.
Physicians may also contact EPA directly for this information (tel: 703-305-
7090) if needed for proper management of a case.
Petroleum distillates are the most commonly used solvents for lipo-
philic pesticides. Most insecticides are lipophilic.The distillates are mixtures of
aliphatic and aromatic hydrocarbons and have low boiling points.
Sometimes specific hydrocarbons, such as toluene or xylene (strongly
odiferous), are added to stabilize the solution of insecticide or make it more
emulsifiable. Hydrocarbon-dissolved pesticides are usually diluted for applica-
tion by adding measured amounts of water to form emulsions. Some chlori-
nated hydrocarbons may be present in particular technical mixtures. A strong
odor lingering after application of a structural pest control spray is often due to
the solvent rather than the active ingredient.
Less lipophilic active ingredients are sometimes dissolved in mixtures of
alcohols, glycols, ethers, or various chlorinated solvents. It is possible that these
enhance the dermal absorbability of some pesticides. Some solvents, such as
methanol and isopropanol, may represent a significant toxic hazard if swallowed
in sufficient dosage.
Granular formulations utilize various clay materials which adsorb pesti-
cide, retain it in more or less stable form until application, then desorb the
material slowly into treated soil. There is some significant desorption when
granules are in contact with human skin and very substantial desorption into
gastrointestinal secretions if granules are swallowed. The clay materials them-
selves are not a toxic hazard.
Dusts are infrequently used today. Various forms of talc (silicatecarbonate
particles) have been used in the past to adsorb pesticides for application to
192 MISCELLANEOUS
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foliage. Particle sizes are such that these dusts are usually trapped in the upper
respiratory mucous when inhaled.When the mucous is swallowed, the particles
desorb pesticide into gastrointestinal secretions. Dust formulations may, there-
fore, release enough of some pesticides to cause systemic poisonings.
Stickers and spreaders (film extenders) are organic substances added to
formulations to disperse pesticide over treated foliage surfaces and enhance
adhesion.The availability and persistence of residue on the leaf surfaces is thereby
increased. Substances used include proteinaceous materials (milk products, wheat
flour, blood albumin, gelatin), oils, gums, resins, clays, polyoxyethylene glycols,
terpenes, and other viscid organics. Some also include sulfated alcohols, fatty
acid esters, and alkyl and petroleum sulfonates. For persons exposed in the
course of formulation or application of pesticides, these adjuvants probably add
little or no toxic hazard to that inherent in the active pesticidal ingredients.
Emulsifiers serve to stabilize water-oil emulsions formed when water is
added to technical hydrocarbon concentrates. Chemically, they resemble deter-
gents (one part of the molecule lipophilic, the other hydrophilic). Long-chain
alkyl sulfonate ethers of polyethylene glycol and polyoxyethylene oleate are
exemplary emulsifiers. They have low inherent mammalian toxicity, and their
presence probably has little effect on the overall toxicity of formulated products
which include them.
Penetrants facilitate the transfer of herbicide from foliage surface to the
interior tissues. Some are lipids while others are detergent (surfactant) in na-
ture. Substances used include heavy petroleum oils and distillates, polyol fatty
acid esters, polyethoxylated fatty acid esters, aryl alkyl polyoxyethylene glycols,
alkyl amine acetate, alkyl aryl sulfonates, polyhydric alcohols, and alkyl phos-
phates. Some of these are eye and skin irritants, and may account for the irritant
effects of particular herbicide formulations whose active ingredients do not
have this property.
Safeners are substances added to mixtures of fertilizers with pesticides (com-
monly herbicides) to limit the formation of undesirable reaction products. Some
substances used are alcohol sulfates, sodium alkyl butane diamate, polyesters of
sodium thiobutane dioate, and benzene acetonitrile derivatives. Some are mod-
erately irritating to the skin and eyes. Systemic toxicities are generally low.
Anticaking agents are added to granular and dust formulations to facili-
tate application by preventing cakes and clumps. Among several products used
are the sodium salt of mono- and di-methyl naphthalene sulfonate, and diato-
maceous earth. Diatomaceous earth has little adverse effect except a drying
action on the skin. Methyl naphthalenes are said to be skin irritants and photo-
sensitizers; whether their derivatives have this effect is not known.
MISCELLANEOUS 193
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Treatment
Petroleum distillates are mineral hydrocarbons which undergo limited ab-
sorption across the gut. In general, clinical toxicologists do not recommend in-
duced emesis or gastric lavage in treating ingestions of these materials, because of
the serious risk of hydrocarbon pneumonitis if even tiny amounts of the liquid
are aspirated into the lung. However, this injunction against emptying the stom-
ach may be set aside when the petroleum distillate is a vehicle for toxic pesticides
in significant concentration. In such cases, if the patient is seen within one hour
of exposure, gastrointestinal decontamination should be considered.
Rapid respiration, cyanosis, tachycardia, and low-grade fever are the usual
indications of frank hydrocarbon pneumonitis. Patients with presumed hydrocar-
bon pneumonitis, who are symptomatic, should usually be hospitalized, prefer-
ably in an intensive care setting. If the patient has pulmonary symptoms, a chest
x-ray should be taken to detect or confirm signs of pneumonitis. In addition, the
urine should be examined for protein, sugar, acetone, casts, and cells, and an EGG
should be examined for arrhythmias and conduction defects. Mechanically as-
sisted pulmonary ventilation with 100% oxygen may be required. Hydrocarbon
pneumonitis is sometimes fatal, and survivors may require several weeks for full
recovery. In milder cases, clinical improvement usually occurs within several days,
although radiographic findings will remain abnormal for longer periods.17
The presence of chlorinated solvents in some formulations may add sig-
nificantly to the toxic hazard, particularly if the product is ingested. Certain
adjuvants are irritants to skin, eyes, and mucous membranes, and may account
for the irritant properties of some products whose active ingredients do not
have this effect. With these exceptions, however, the presence of adjuvants in
most finished pesticide products probably does not enhance or reduce systemic
mammalian toxicity to any great extent.
References
1. Spyker DA, Lynch C, Shabanowitz J, et al. Poisoning with 4-aminopyridine: Report of three
cases. ClinToxicol 1980;16:487-97.
2. PickettTA and Enns R. Atypical presentation of 4-aminopyridine overdose. Ann Emerg Med
1996:27:382-5.
3. Stork CM and Hoffman RS. Characterization of 4-aminopyridine in overdose. Clin Toxicol
1994:32:583-7.
4. Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
NJ: Noyes Publications, 1991, pp. 316-7.
5. Torrelo A, Soria C, Rocamora A, et al. Lichen planus-like eruption with esophageal involve-
ment as a result of cyanamide. JAmAcad Dermatol 1990;23:1168-9.
6. Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
NJ: Noyes Publications, 1991, pp. 450-3.
7. Bowman CE, Muhleman MF, and Walters E. A fatal case of creosote poisoning. Postgrad Med
/1984;60:499-500.
194 MISCELLANEOUS
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8. Christiansen RG and Klaman JS. Successful treatment of phenol poisoning with charcoal
hemoperfusion. Vet Hum Toxicol 1996;38:27-8.
9. Allender WJ. Suicidal poisoning by endothall. ]Anal Toxicol 1983;7:79-82.
10. LongstrethWT and Pierson DJ. Metaldehyde poisoning from slug bait ingestion. West j Med
1982;137:134-7.
11. Jay MS, Kearns GL, StoneV, et al.Toxic pneumonitis in an adolescent following exposure to
snow storm tablets. J' Adolesc Health 1988;9:431-3.
12. Booze TF and Oehme FW An investigation of metaldehyde and acetaldehyde toxicities in
dogs. Fundam ApplToxicol 1986;6:440-6.
13. Moody JP and Inglis FG. Persistence of metaldehyde during acute molluscicide poisoning.
Hum Exp Toxicol 1992;ll:361-2.
14. Helliwell M and Nunn J. Mortality in sodium chlorate poisoning. Br MedJ 1979; 1:1119.
15. Steffen C and Seitz R. Severe chlorate poisoning: Report of a case. Arch Toxicol 1981;48:281-8.
16. Smith EA and Oehme FW A review of selected herbicides and their toxicities. Vet Hum
Toxicol \991:33:596-608.
17. Anas N, Namasonthi V, and Ginsburg CM. Criteria for hospitalizing children who have
ingested products containing hydrocarbons. JAMA 1981;246:840-3.
MISCELLANEOUS 195
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CHAPTER 19
HIGHLIGHTS
Compounds are registered
for medical or medicinal use
rather than as pesticides
Several are among the most
frequently reported human
poisonings in the U.S.
Iodine is well absorbed
through abraded or burned
skin
Disinfectants
A wide variety of disinfectant agents are used to destroy microorganisms and
they differ greatly in their toxic effects. Most disinfectants can conveniently be
grouped into a few categories, some of which are also represented in other
classes of pesticides. Many of these materials are not registered as pesticides, but
are registered for medical or medicinal use. This chapter reviews a few of the
more common or more severely toxic disinfectants.
Signs and Symptoms:
Highly variable based on
agent
Many are irritants and
Iodine causes neurological
symptoms, shock, renal
failure, and hyperkalemia
Pine oil can cause aspiration
pneumonia
Treatment:
Follow general principles of
decontamination and
supportive care
Contraindicated:
Gastric emptying and
decontamination
procedures are
contraindicated in
poisonings due to corrosive
agents and pine oil
ALCOHOLS
Alcohols have a long history of use as disinfectants. Often disinfectants are
mixtures, usually of ethanol and isopropyl alcohol (isopropanol). The alcohol
most commonly used in households as a disinfectant is isopropyl alcohol, com-
monly marketed as a 70% solution. It is a clear, colorless liquid with an odor
similar to ethanol.
Toxicology of Isopropyl Alcohol
Isopropyl alcohol is well and rapidly absorbed from the gastrointestinal tract.
It is also well absorbed by skin and by inhalation. It is considered to be more toxic
to the central nervous system than ethanol, with similar effects. Both ingestion
and inhalation at high concentrations can result in the rapid onset of CNS
depression with subsequent coma and death. Apnea commonly accompanies
this CNS depression.1'2 Similar neurological toxicity has been reported with
excessive topical exposure to the umbilicus of a neonate.3 Irritation of the
gastrointestinal tract results in gastritis and severe vomiting. Isopropyl alcohol may
also produce mild hepatic injury with acute exposures. Acute tubular necrosis has
been reported with this agent,1 but the renal toxicity is not as great as with
methanol poisonings. Ketosis without metabolic acidosis but prominent hypogly-
cemia is common.2'3 This ketosis is the result of direct metabolism of this
compound to acetone.1'3 Monitoring of isopropyl levels is useful, when available.
In addition, blood levels of acetone and glucose should be determined to aid
in management.
196 DISINFECTANTS
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Confirmation of Poisoning
Commercial Products
Isopropyl alcohol can be measured in the blood and urine. Serum acetone
can also be measured. Blood isopropyl alcohol levels of 128-200 mg/dL have
been associated with death.
Treatment: Isopropyl Alcohol
1. Gastrointestinal decontamination. Since the onset of coma is often rapid
with this poisoning, induced emesis is contraindicated, though spontaneous
vomiting often occurs. If the patient has ingested a large amount, has not vom-
ited, and is seen within one hour of exposure, consideration should be given to
gastric emptying by lavage as outlined in Chapter 2.
Isopropyl alcohol is well adsorbed to charcoal, so activated charcoal should
probably be administered, as outlined in Chapter 2.
2. Supportive care for hypotension and respiratory depression is critical to
survival and should be administered whenever possible in an intensive care
setting.
3. If hypoglycemia occurs, glucose administration is indicated in order to
maintain normoglycemia.
4. Hemodialysis has been reported to be beneficial in patients with severe
poisoning unresponsive to standard supportive therapy.1'4
ALDEHYDES
The two aldehydes most commonly used as disinfectants are formaldehyde
and glutaraldehyde. Formaldehyde is discussed in Chapter 17, Fumigants. Glu-
taraldehyde is very similar to formaldehyde in its toxicity and treatment, al-
though it is probably slightly less toxic. Glutaraldehyde is commonly prepared
as an aqueous solution at a 2% concentration, and is slightly alkaline in this
solution. It has been reported to cause respiratory irritation, resulting in rhini-
tis5-6 and occupational asthma.6'7-8 It has also resulted rarely in palpitations and
tachycardia in human subjects. At high dosage, given orally, it results in gas-
trointestinal irritation with diarrhea, which may be hemorrhagic. Due to the
irritant effects of glutaraldehyde, the wearing of personal protective equipment
is required for the protection of skin (29 CFR 1910.132), and eyes (29 CFR
1910.133). OSHA standards require the use of appropriate respirators by em-
ployees that may be exposed to glutaraldehyde during routine or emergency
work procedures (29 CFR 1910.134).
ALCOHOLS
Isopropyl alcohol
ALDEHYDES
formaldehyde
glutaraldehyde
CATIONIC DETERGENTS
benzalkonium chloride
cetrimide
cetylpyridium chloride
CHLORHEXIDINE
Hibiclens
Hibistat
Peridex
HYPOCHLORITES
calcium hypochlorite
sodium hypochlorite
IODINES
povidone-iodine
Betadine
loprep
Pharmadine
MERCURIALS
mercurobutol
mercurochrome
merthiolate
nitromersol
phenylmercuric acetate
phenylmercuric nitrate
thimerosol
PHENOLS
2-benzyl-4-chlorophenol
cresol
Lysol
hexachlorophene
Bilevon
Dermaadex
Exofene
Gamophen
Phisohex
Surgi-Cen
Surofene
Texosan
o-phenylphenol
phenol
4-tert-amylphenol
thymol
triclosan
PINE OIL
DISINFECTANTS 197
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Treatment: Glutaraldehyde
1. Gastrointestinal decontamination. If a large amount has been ingested
and retained, and the patient is seen within one hour of exposure, consider
gastric emptying as described in Chapter 2. Administration of activated char-
coal should be considered, as described in Chapter 2.
2. Oxygen. If patient has been in an area with strong odor of glutaraldehyde
due to vaporization, remove to fresh air area and administer oxygen as needed.
3. Skin decontamination. If skin irritation is noted, vigorous skin decon-
tamination is indicated. However, systemic toxicity from skin exposure appears
unlikely.
CATIONIC DETERGENTS
Several cationic detergents are used as disinfectants. All share the capacity,
in sufficient concentration, to behave as caustic agents, capable of causing rather
severe, caustic burns. It appears that concentrations greater than approximately
7.5% are necessary to produce significant caustic injuries. However, experience
with human exposures to these compounds is very limited. The three agents
most commonly used as detergent disinfectants are benzalkonium chloride,
cetrimide, and cetylpyridium chloride.
Though there are no cetrimide preparations available in the U.S., several
are available in European Union countries. Concentrated solutions are usually
only available in industrial settings, such as production of consumer products,
or for use in hospitals for disinfectant purposes.Therefore, acute poisonings are
uncommon.
Toxicology
In low-concentration solutions, these agents have been reported to cause
eye discomfort as well as skin rashes and irritation. In stronger concentrations,
they can cause severe corneal and skin burns. Likewise, strong concentrations
will result in caustic burns to lips, oral mucosa, esophagus, and stomach.9-10
Vomiting, diarrhea, and abdominal pain have been reported.11 Necrosis of the
gut, with peritonitis, has also been reported.12 In severe exposures, there are also
reports of CNS depression, liver injury, and pulmonary edema.9-11
Treatment
1. Skin decontamination. If a high-concentration solution has been applied
to skin, aggressive skin contamination and treatment of burns is appropriate. If
198 DISINFECTANTS
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a high concentration solution is in contact with the eyes, profuse washing of
the eyes is indicated followed by a careful exam of the corneas. If burns have
occurred, appropriate ophthalmologic care should be provided.
2. Gastrointestinal decontamination. Gastric emptying and other methods
of gastrointestinal decontamination are contraindicated in these poisonings.
Some experts recommend cautious dilution with small amounts of milk or
water.9'13 Acidic solutions such as juices should never be offered for dilution.
3. Endoscopy. If a highly concentrated solution was ingested or oral burns are
noted, the patient needs urgent endoscopy for grading of the caustic injury.The
endoscopy should be performed within 24 hours to minimize the risk of per-
foration from the procedure.12 A competent surgeon or gastroenterologist should
provide subsequent care.
4. Other agents. Although corticosteroids are commonly used to treat these
burns, their use remains controversial. Use of other agents, such as H2 antago-
nists and sulcralfate, has been reported but remains controversial at this time.
5. CNS, pulmonary and other systemic effects should be treated symptom-
atically, consistent with sound medical practice.
CHLORHEXIDINE
Chlorhexidine is a cationic biguanide, available in concentrations up to 4%
as a topical agent used as a skin cleanser and mouthwash. Skin preparations of
0.5%-4% are marketed under the trade names HibiclensR and HibistatR. It is
also marketed as a mouthwash in a 0.12% solution under the trade name PeridexR.
There is very little human experience with poisonings, as these concentrations
do not appear to be significantly toxic.
Toxicology
Chlorhexidine is poorly absorbed from skin or the gastrointestinal tract.
Therefore most effects noted have been primarily local. If a low concentration
solution is ingested or applied to the skin, mild local irritation can be seen.
Contact dermatitis, urticaria, and anaphylaxis have followed repeated skin ex-
posures to this agent.14'15 Corneal injuries have been described in several cases
after inadvertent exposure of the eyes to the 4% concentration.These injuries
have resulted in permanent corneal scarring.16 Esophageal burns have been
reported in a single case after ingestion of a large quantity of a 20% solution of
this agent.17 Ulcerative colitis has been described after an enema of the 4%
DISINFECTANTS 199
-------
solution mixed with tap water (10 mL in 2 liters water).18 Liver toxicity can
occur with large exposures.17
Treatment
1. Gastrointestinal decontamination. If ingestion of a large quantity has
occurred within an hour and the patient has not vomited, gastrointestinal de-
contamination as described in Chapter 2 should be considered. If a highly
concentrated solution has been ingested, manage as a caustic ingestion as de-
scribed in the cationic detergents, without gastrointestinal decontamination.
2. Liver injury panel should be performed with large ingestions.
3. Eye decontamination. If eye exposure has occurred, the eyes should be
vigorously irrigated and a careful ophthalmologic exam should be performed
for corneal injury. If an injury has occurred, an ophthalmologic consultation
should be obtained.
HYPOCHLORITES
Hypochlorites are implicated in a large proportion of the disinfectant
poisonings reported to poison control centers in the United States. Most are
solutions of sodium or calcium hypochlorite solutions. Chloramine, a disin-
fectant used by many municipal water supplies, is an infrequent cause of acute
poisonings. Sodium and calcium hypochlorite solutions are of relatively low
toxicity.They are mildly corrosive to the eyes,19 and mucous membrane burns
have been reported.20 Significant poisonings are very infrequent with these
agents in solution.21
When hypochlorite solutions are mixed with acids or ammonia solutions,
chlorine or chloramine gas is produced, resulting in an irritant with pulmonary
toxicity. Many brief exposures have led to transient symptoms requiring lim-
ited emergency department management.22 However, in cases of prolonged
exposure or exposure to high concentrations, there is the potential for severe
toxic pneumonitis.23 While severe injury may be the exception to the rule,
great efforts should be made to discourage mixing of these materials with acid
or ammonia.
Treatment
1. Gastric decontamination. After oral exposures, gastric emptying is not
indicated. If a granular material is ingested, and the patient has symptomatic
mucosal burns, referral to a surgeon or gastroenterologist for consideration of
endoscopy and management may be appropriate.
200 DISINFECTANTS
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2. Dilution with water or milk not to exceed approximately 15 mL/kg in a
child or 120-240 mL in an adult is probably appropriate if vomiting has not
occurred. Administration of acids is contraindicated, due to the risk or increas-
ing generation of chlorine gas.
3. Eye decontamination. If eyes were exposed, they should be irrigated
profusely with water or saline. If corneal burns are detected, referral to an
ophthalmologist is appropriate.
4. Skin decontamination. Skin exposure should also be managed by copi-
ous water dilutions. See Chapter 2.
5. Fresh air. If exposure to vapors or chlorine or chloramine gas has occurred,
patient should immediately be moved to fresh air. If symptoms occur or persist,
oxygenation should be assessed and oxygen should be administered as needed. If
persistent symptoms occur, a chest film should be obtained and hospital care
considered. Intensive care may need to be provided in severe inhalations.
IODINE
The most common iodine-containing disinfectant is povidone-iodine
(proviodine), in 7.5-10% solutions. Povidone-iodine is described as an iodophor,
which is a complex of iodine and polyvinylpyrrolidone, a solubilizing agent. It
is intended to liberate free iodine in solution for its effect. Although reported
concentrations of iodine in these solutions is only 80-120 ugm/dL, the total
available iodine is approximately 10% of the povidone-iodine.Therefore a 10%
solution will have in the range of 1% total available iodine.
Toxicology of Povidone-iodine
This compound is very poorly absorbed from the gastrointestinal tract, due
to the rapid conversion of free iodine to iodide in the stomach. Although
highly concentrated iodine solutions or iodine salts are corrosive to the gas-
trointestinal tract,24 solutions of povidone-iodine have little caustic potential.
Likewise, the compound is poorly absorbed from intact skin. All symptomatic
poisonings reported have occurred either after repeated exposure to burned
skin, or following irrigation of wounds, joints, or serosal surfaces such as the
mediastinum.25"28 The one exception was an infant who received an enema of
povidone-iodine in a polyethylene glycol solution, followed by whole bowel
irrigation with polyethylene glycol mixed with povidone-iodine. This child
died with severe hyperglycemia and very high iodine levels.24
In povidone-iodine exposures by these routes, the primary symptoms ini-
tially appear to be neurological, with headache, dizziness, delirium, hallucina-
DISINFECTANTS 201
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tions, and seizures.26 Hypotension, arrythmias, cyanosis, metabolic acidosis, shock,
and acute renal failure occur in severe cases.25<27<28 Hepatic injury, manifested by
elevated serum transaminase levels, has also been reported with very high level
exposures.27 Hyperkalemia has occurred, and the serum chloride may be falsely
elevated due to the presence of a second halide.25
Treatment: Povidone-lodine
1. Skin decontamination. Remove skin contamination by vigorous washing
with soap and water. See Chapter 2.
2. Gastrointestinal decontamination. If the patient is seen soon after a very
large ingestion, and vomiting has not occurred, consider gastrointestinal de-
contamination, as outlined in Chapter 2. Consider single dose charcoal.
3. Iodine clearance is apparently enhanced by procedures that enhance chlo-
ride excretion. Therefore, osmotic or choluretic diuresis is probably indicated
in these poisonings, if symptomatic.
4. Seizures. Treat seizures with anticonvulsants, as outlined in Chapter 2.
5. Monitor thyroid function following recovery to confirm euthyroid state.
MERCURIALS
A wide variety of organic mercurials have been used as disinfectants and as
preservatives. Nearly all uses have been banned in the United States. The tox-
icity and treatment of exposure to these compounds is described in detail in
Chapter 15, Fungicides, under organomercury compounds and will not be
repeated here.
PHENOLS
Several phenols are used as disinfectants. Cresol and thymol are alkyl de-
rivatives of phenol, while hexachlorophene and triclosan are chlorinated phenols.
Common commercial preparations are LysolR, a 50% solution of mixed cresols
in soap, and hexachlorophene, marketed under several trade names in soap bars
and some cosmetics. Cresols and hexachlorophene are discussed individually as
examples of these compounds that are familiar and for which there are some
human data.
202 DISINFECTANTS
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Toxicology of Cresols
Cresols, in common with phenol and other phenolic compounds, are highly
corrosive to all surfaces.With ingestion of concentrated forms they cause severe
corrosive injury to the mouth and upper gastrointestinal tract. Likewise, severe
eye and skin caustic injuries can occur with cresol exposure.29 Symptoms usu-
ally include nausea, vomiting, and diarrhea. Hypotension, myocardial failure,
pulmonary edema, and neurological changes may also occur.30 Liver and renal
toxicity, methemoglobinemia, and hemolysis have all been reported.30-31 After
long-term, repeated exposure, contact dermatitis may complicate these expo-
sures. These compounds are well absorbed from the gastrointestinal tract and
are also significantly absorbed from the skin and by inhalation.
Treatment: Cresols
1. Gastrointestinal decontamination. Due to the corrosive nature of these
compounds, gastrointestinal decontamination should not be attempted. Con-
sideration of dilution with milk or water is appropriate if vomiting has not
occurred.
2. Endoscopy. If a corrosive injury has occurred with burns to the mouth, or
if there is a clear history of gastrointestinal exposure, endoscopy should be
considered and a gastroenterologist or surgeon should be consulted for diagno-
sis and management.
3. Skin decontamination. If skin or eye contamination has occurred, copi-
ous irrigation should be performed. This should be followed by a careful eye
examination for corneal burns. If corneal burns are noted, ophthalmologic
consultation should be obtained.
4. Respiratory and circulatory support should be provided in accordance
with sound medical management. If severe systemic symptoms persist, the pa-
tient should be treated in an intensive care unit, if possible.
Toxicology of Hexachlorophene
Hexachlorophene is well absorbed orally and dermally. Dermal exposures
have led to severe toxicity and death in neonates, due to application to dam-
aged skin, or repeated or high-concentration skin exposures.32 Hexachlorophene
should never be used as a disinfectant on open wounds or abraded or inflamed
skin surfaces. In distinction to other phenolic compounds, this agent is not
significantly caustic and exposure does not result in the severe caustic injuries
seen with other phenolic chemicals.
DISINFECTANTS 203
-------
Hexachlorophene is a potent neurotoxicant. It causes brain edema and
spongy degeneration of white matter.33 This neurotoxicity can be seen after
acute or chronic exposures, either by skin absorption or ingestion.The nervous
system symptoms are complex. Lethargy is an early manifestation, followed by
muscular weakness, muscular fasciculation, irritability, cerebral edema, and pa-
ralysis, leading to coma and death. Seizures commonly occur in more severe
cases.32-34 Blindness and optic atrophy have been reported following exposure
to hexachlorophene.35
In addition to the neurological effects, common early symptoms of poison-
ing are vomiting, diarrhea, and anorexia.34 These findings have been accompa-
nied in animals by significant hepatotoxicity36 With skin exposure, an erythema-
tous desquamative rash is often noted at the site of exposure.34 With chronic
exposure, contact dermatitis may be noted. In severe poisonings, cardiovascular
symptoms, including hypotension and bradycardia, have been noted.37 In a single
case, repeated exposure to this compound led to asthma in a pediatric nurse.38
Treatment: Hexachlorophene
1. Gastrointestinal decontamination. Since this agent is not generally caustic,
consideration should be given to aggressive gastrointestinal decontamination. If
the patient has ingested a significant amount and is seen within one hour of
exposure, gastric emptying is likely to be useful, as described in Chapter 2.
Since hexachlorophene is thought to have an enterohepatic recirculation, it
is possible that repeated dosing of activated charcoal, as outlined in Chapter 2,
will enhance clearance of this compound. However, hexachlorophene does not
bind well to charcoal and there are no clinical trials of this therapy for this agent.
2. Other therapies. Though this compound is quite toxic systemically and
enhanced clearance methods would appear beneficial, there is no evidence to
support the efficacy of hemodialysis, peritoneal dialysis, hemoperfusion, or ex-
change transfusion.37
3. Skin decontamination. If exposure has occurred through the skin, aggres-
sive washing of skin with soap or detergent and water is probably beneficial, to
remove any residues still on the skin. Since hexachlorophene is not soluble in
water, water washing alone will provide no significant benefit. See Chapter 2.
4. Neurological support and control of seizures is critical to survival and
should be performed, when possible, in an intensive care setting. Seizure con-
trol should be in accordance with recommendations in Chapter 2.
5. Cardiovascular and respiratory support are also very important to sue
cess in treating severe poisonings with this agent and should be provided in an
intensive care unit in accordance with accepted medical practice.
204 DISINFECTANTS
-------
PINE OIL
Pine oil detergent and disinfectant solutions are among the most common
poisonings reported to poison control centers in the U.S. A relatively high
number of these are reported as serious or fatal. Pine oil is found in a variety of
household and commercial cleaners and disinfectants. It is a mixture of mono-
terpenes derived from the distillation of wood from various pine species, with
approximately 57% being alpha-pinene.39 Its most common side effects in smaller
dosage are irritation of mucous membranes, gastrointestinal irritation, mild res-
piratory and CNS depression, and renal toxicity Larger ingestions can result in
severe respiratory distress, cardiovascular collapse, and severe CNS effects. Re-
nal failure and myoglobinuria have also been reported in severe poisonings.40
Since even small ingestions can result in severe aspiration pneumonia, all
ingestions should be considered potentially hazardous.
While many of the reported effects of poisoning with this agent are related
to direct irritant effect on mucous membranes, gastrointestinal tract, and lung
(by aspiration), some reports suggest significant absorption from oral and rectal
exposures. Other reports suggest a lesser rate of absorption.39 While alpha-
terpineol can be measured in blood, there are no data relating levels to degree
of toxicity. Consequently, this measure is not considered useful in guiding
diagnosis and management.
Treatment
1. Gastrointestinal decontamination. Since there is a high risk of aspira-
tion pneumonia, induced emesis is usually considered contraindicated in these
poisonings. However, spontaneous emesis may occur due to direct irritation of
the gastric mucosa.
If the patient is seen within an hour of ingestion and a large amount has
been ingested, gastric emptying by intubation and lavage may be considered, as
described in Chapter 2. However, some studies have suggested greater rates of
complications with lavage than with ipecac-induced emesis.40
There is no evidence that activated charcoal is helpful in these poisonings.
Likewise, though a variety of enhanced elimination methods have been pro-
posed and tried, there is no evidence to support their efficacy.
2. Eye decontamination. If eye exposure has occurred, copious irrigation
of the eyes is appropriate.
3. Pulmonary symptoms. The patient should be observed for at least six
hours with any significant ingestion in order to observe the onset of any symp-
toms, particularly pulmonary symptoms. If any pulmonary symptoms are ob-
served, the patient should have a chest film and measurement of oxygenation,
DISINFECTANTS 205
-------
and hospitalization is appropriate. With severe pulmonary symptoms, transfer
to an intensive care unit is usually appropriate. With severe aspiration, manage-
ment should be handled as in any severe aspiration pneumonia, in accordance
with accepted medical practice. Other severe systemic effects should be treated
in accordance with accepted medical practice.
References
1. Lacouture PG.Wason S, Abrams A, et al. Acute isopropyl alcohol intoxication: Diagnosis and
management. Am JMed 1983;75:680-6.
2. Rich J, Scheife RT, Katz N, et al. Isopropyl alcohol intoxication. Arch Neural 1990;47:322-4.
3. Vivier PM, Lewander WJ, Martin HF, et al. Isopropyl alcohol intoxication in a neonate
through chronic dermal exposure: A complication of a culturally-based umbilical care prac-
tice. Pediatr Emerg Care 1994; 10:91-3.
4. Manring E, Meggs W, Pape G, et al.Toxicity of an intravenous infusion of isopropyl alcohol.
JToxicol Clin Toxicol 1997;35:503.
5. Norback D. Skin and respiratory symptoms from exposure to alkaline glutaraldehyde in
medical services. ScandJWork Environ Health 1988;14:366-71.
6. Corrado OJ, Osman J, and Davies RJ. Asthma and rhinitis after exposure to glutaraldehyde
in endoscopy units. HumToxicol 1986;5:325-8.
7. Chan-Yeung M, McMurrenT, Catonio-Begley F, et al. Occupational asthma in a technolo-
gist exposed to glutaraldehyde. JAllergy Clin Immunol 1993; 91(5):974-8.
8. Stenton SC, Beach JR, Dennis JH, et al. Glutaraldehyde, asthma, and work - a cautionary
tale. OccupMed 1994;44(2):95-8.
9. Mucklow ES. Accidental feeding of a dilute antiseptic solution (chlorhexidine 0.05% with
cetrimide 1%) to five babies. HumToxicol 1988;7:567-9.
10. Wilson JT and Burr IM. Benzaldonium chloride poisoning in infant twins. AJDC
1975;129:1208-9.
11. ChanTY. Poisoning due to savlon (cetrimide) liquid. Hum ExpToxicol 1994;13:681-2.
12. Zargar SA, Kochhar R, Mehta S, et al.The role of fiberoptic endoscopy in the management
of corrosive ingestion and modified endoscopic classification of burns. Gastrointest Endosc
1991;37:165-9.
13. Consensus: POISINDEXR Editorial Board consensus opinion poll, Irritants/Caustics Spe-
cialty Board. Englewood, CO: Micromedex, 1988.
14. WongWK, Goh CL.and Chan KW. Contact urticaria from chlorhexidine. Contact Dermatitis
1990;22:52.
15. Okano M, Nomura M, Hata S, et al. Anaphylactic symptoms due to chlorhexidine glucon-
ate. Arch Dermatol 1989:125:50-2.
16. Tabor E, Bostwick DC, and Evans CC. Corneal damage due to eye contact with chlorhexidine
gluconate. JAMA 1989;261:557-8.
17. Massano G, Ciocatto E, Rosabianca C, et al. Striking aminotransferase rise after chlorhexidine
self-poisoning. Lancet 1982;1:289.
18. Hardin RD andTedesco FJ. Colitis after hibiclens enema. / Clin Gastroenterol 1986;8:572-5.
19. Ingram TA. Response of the human eye to accidental exposure to sodium hypochlorite. /
Endod 1990; 16:235-8.
206 DISINFECTANTS
-------
20. French RJ.Tabb HJ, and Rutledge LJ. Esophogeal stenosis produced by ingestion of bleach.
South Med J 1970;63:1140-4.
21. Landau GD and SaundersWH.The effect of chlorine bleach on the esophagus. Arch Otolaryngol
1964:80:174-6.
22. Mrvos R, Dean BS, Krenzelok EP, et al. Home exposure to chlorine/chloramine gas: review
of 216 cases. South Med J 1993:86:654-7.
23. Reisz GR and Gammon RS. Toxic penumonitis from mixing household cleaners. Chest
1986:89:49-52.
24. KurtTL, HnilicaV, Bost R, et al. Fatal iatrogenic iodine toxicity in a 9-week old infant. Vet
Hum Toxicol \ 992:34:333.
25. Means LJ, Rescorla FJ, and Grosfield JL. Iodine toxicity: An unusual cause of cardiovascu-
lar collapse during anesthesia in an infant with Hirschsprung's Disease. / Pediatr Surg
1990:25:1278-9.
26. Ponn RB. Continuous povidone-iodine irrigation (letter). AnnThorac Surg 1987;43:239.
27. Pietsch J and Meakins JL. Complications of povidne-iodine absorption in topically treated
burn patients. Lancet 1976;7:280-2.
28. Campistol JM, Cipiano A, Nogue S, and Bertran A. Acute renal failure in a patient treated by
continuous povidone-iodine mediastinum irrigation. J Pediatr Surg 1988;29:410-2.
29. Pegg SP and Campbell DC. Children's burning due to cresol. Burns 1985;ll:294-6.
30. Arthus GJ.Wise CC, and Coles GA. Poisoning by cresol. Anaesthesia 1977;32:642-3.
31. ChanTK.Mak LW, and Ng RR Methemoglobinemia.heme bodies, and acute massive intra-
vascular hemolysis in lysol poisoning. Blood 1971;38:739-44.
32. Mullick FG. Hexachlorophene toxicity - Human experience at the Armed Forces Institute
of Pathology. Pediatrics 1973;51 (2)11:395-9.
33. Anderson JM, Cockburn F, Forfar J, et al. Neonatal spongioform myelinopathy after re-
stricted application of hexachlorophane skin disinfectant. / Clin Pathol 1981;34:25-9.
34. Martin-Bouyer G, Lebreton R.Toga M, et al. Outbreak of accidental hexachlorophene poi-
soning in France. Lancet 1982;l:91-5.
35. SlamovitzTL, Burde RM, and KlingeleTG. Bilateral optic atrophy caused by chronic oral
ingestion and topical application of hexachlorophene. Am J Ophthalmol 1980;89:676-9.
36. Prasad GV, Rajendra W, and Indira K. Brain ammonia metabolism in hexachlorophene-
induced encephalopathy Bull Environ Contam Toxicol 1987;38:561-4.
37. Boehm RM and Czajka PA. Hexachlorophene poisoning and the ineffectiveness of perito-
neal dialysis. JToxicol Clin Toxicol 1979;14(3);257-62.
38. Nagy Land Orosz M. Occupational asthma due to hexachlorophene. Thorax 1984;39:630-1.
39. Koppel C.Tenczer J.Tennesmann U, et al. Acute poisoning with pine oil - Metabolism of
monoterpenes. ArchToxicol 1981;49:73-8.
40. LitovitzTL, Schmidz BF Matyunas N, et al. 1987 Annual Report of the American Association of
Poison Control Centers National Data Collection System. Am JEmerg Med 1988;6:479-515.
DISINFECTANTS 207
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Index of Signs and Symptoms
Presented in this chapter are lists of pesticides reported to have caused particu-
lar symptoms and signs, or combinations thereof, in poisoned individuals.The
lists may help direct the attention of health professionals to possible toxic causes
of the various disease manifestations, prompting inquiry into likelihood of ex-
posure to the listed chemicals. If certain agents appear suspect, inquiry can then
be made into the presence of additional manifestations typical of poisoning by
those substances.
The limitations of this approach to diagnosis must be understood. First, all
manifestations of illness have multiple causes, pesticidal and nonpesticidal.
Second, there are no specific symptoms or signs that are invariably present in
poisonings by particular pesticides.Third, many poisonings are characterized by
unexpected manifestations.
Finally, neither route of exposure nor dosage of pesticide is taken into
account in this listing. For example, effects of high-dose ingestion are not
distinguished from effects of relatively low-dose dermal absorption, nor are
topical effects distinguished from systemic dermal manifestations. The lists of
pesticides can only be regarded as clues to prompt further inquiry by the inter-
viewing professional.
The term manifestation means either symptom or sign.The word "poison-
ing" is used loosely in these headings to include topical as well as systemic effects.
Pesticides which are relatively consistent in causing particular manifestations are
listed in the middle column, headed "Characteristic of These Agents." Pesticides
that have caused various conditions with less consistency, or are less prominent
features of poisoning, are listed in the right-hand column, headed "Occurs
withThese Agents." Obviously, the distinction is not clear-cut.
Some symptoms (malaise, fatigue, dizziness) occur so commonly in poi-
soned individuals that they have little or no value in differential diagnosis, and
are therefore not included in these tables.
210 SIGNS AND SYMPTOMS
-------
General
MANIFESTATION
Rotten egg odor
Hypothermia
Hyperthermia
(fever, pyrexia)
Chills
Hot sensations
Myalgia
Thirst
Anorexia
Alcohol intolerance
Sweet taste
in the mouth
Metallic taste in the
mouth
Salty, soapy taste
In the mouth
CHARACTERISTIC OF
THESE AGENTS
Sulfur
Creosote
Norbormide
Nitrophenols
Pentachlorophenol
Phosphine
Arsine
Nitrophenols
Chlordimeform
Paraquat
Chlorophenoxy compounds
Pentachlorophenol
Nitrophenois
Inorganic arsenicals
Phosphorus
Phosphides
Sodium fluoride
Cholecalciferol
Aminopyridine
Organophosphates
Carbamate insecticides
Nicotine
Pentachlorophenol
Hexachlorobenzene
Chlordimeform
Cholecalciferol
Thiram
Calcium cyanamide
Chlordimeform
Inorganic arsenicals
Organic mercury
Sodium fluoride
OCCURS WITH
THESE AGENTS
Borate
Thallium
Metaldehyde
Inorganic arsenicals
Chlorophenoxy compounds
Cadmium dusts
Naphthalene
Pentachlorophenol
Borate
Endothall
Halocarbon fumigants
Nitrophenols
Inorganic arsenicals
Aminopyridine
SIGNS AND SYMPTOMS -211
-------
Skin
MANIFESTATION
Irritation,
Rash,
Blistering, or
Erosion (without
sensitization)
Contact dermatitis
Flushing
Dermal sensitization
Beefy red palms, soles
Urticaria
Bullae
CHARACTERISTIC OF
THESE POISONINGS
Copper, organotin, cadmium
compounds
Metam sodium
Paraquat
Diquat
Sodium chlorate
Phosphorus
Sulfur
Glyphosate
Propargite
Sodium hypochlorite
Quaternary ammonia
Thiram
Chlordimeform
Cationic detergents
Hexachlorphene
Ethylene oxide
Formaldehyde
Aero le in
Methyl bromide
Ethylene dibromide
Dibromochloropropane
Dichloropropane
Endothall
Aliphatic acids
PCP
Paraquat
DEET
Chlorhexidine
Creosote
Hexachlorphine
Pyrethrins
Chlorothalonil
Thiram
Thiophthalimides
Cyanamide
Nitrophenols
Propachlor
Propargite
Ethylene oxide
Borate
Chlorhexidine
PCP
DEET
Liquid fumigants
OCCURS WITH
THESE AGENTS
Pentachlorophenol
Picloram
Chlorophenoxy compounds
Captan
Rotenone
Diethyltoluamide
Creosote
Fungicides
Herbicides with
irritant properties
Petroleum distillate
Thiram plus alcohol
Anflazine
Chlorothalonil
Barban
Captafol
Formaldehyde
Fluoride
Pentachlorophenol
Hexachlorobenzene
212 SIGNS AND SYMPTOMS
-------
Skin (continued)
MANIFESTATION
Pallor
Cyanosis
Yellow stain
Keratoses, brown
discoloration
Ecchymoses
Jaundice
Excessive hair growth
Loss of hair
Loss of fingernails
Brittle nails, white striations
Sweating, diaphoresis
CHARACTERISTIC OF
THESE POISONINGS
Organochlorines
Fumigants
Sodium fluoride
Creosote
Sodium chlorate
Paraquat
Cadmium dusts
Sodium fluoroacetate
Strychnine
Crimidine
Nicotine
Organochlorines
Nitrophenols
Inorganic arsenicals
Coumarins
Indandiones
Carbon tetrachloride
Chloroform
Phosphorus
Phosphides
Phosphine
Paraquat
Sodium chlorate
Thallium
Organophosphates
Carbamate insecticides
Nicotine
Pentachlorophenol
Naphthalene
Aminopyridine
OCCURS WITH
THESE AGENTS
Coumarins
Indandiones
Organophosphates
Carbamate insecticides
Agents that cause shock,
myocardiopathy, severe
arrhythmias or convulsions
Phosphorus
Phosphides
Inorganic arsenicals
Diquat
Copper compounds
Hexachlorobenzene
Inorganic arsenicals
Paraquat
Inorganic arsenicals
Inorganic arsenicals
Thallium
Copper compounds
SIGNS AND SYMPTOMS -213
-------
Eye
MANIFESTATION
Conjunctivitis
(irritation of mucous
membranes, tearing)
Tearing
Yellow schlerae
Keratitis
Ptosis
Diplopia
Photophobia
Constricted visual fields
Optic atrophy
Miosis
Dilated pupils
Unreactive pupils
CHARACTERISTIC OF
THESE POISONINGS
Copper compounds
Organotin compounds
Cadmium compounds
Metam sodium
Paraquat
Diquat
Aero le in
Chloropicrin
Sulfur dioxide
Naphthalene
Formaldehyde
Ethylene oxide
Methyl bromide
Endothall
Toluene
Xylene
Organophosphates
Carbamate insecticides
Chloropicrin
Aero le in
Nitrophenols
Paraquat
Thallium
Organophosphates
Carbamate insecticides
Nicotine
Organic mercury
Organophosphates
Carbamate insecticides
Cyanide
Fluoride
Cyanide
OCCURS WITH
THESE AGENTS
Thiophthalimides
Thiram
Thiocarbamates
Pentachlorophenol
Chlorophenoxy compounds
Chlorothalonil
Picloram
Creosote
Aliphatic acids
Pentachlorophenol
Pyrethrins
Agents that cause jaundice
(see above under Skin)
Organotin compounds
Thallium
Nicotine (early)
214 SIGNS AND SYMPTOMS
-------
Nervous System
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Paresthesia
(chiefly facial,
transitory)
Organophosphates
Cyanopyrethroids
Phosphides
Organochlorines
Thiabendazole
Nicotine (late)
Paresthesia of extremities
Inorganic arsenicals
Organic mercury
Sodium fluoroacetate
Carbon disulfide
Thallium
Pyrethroids (transitory)
Headache
Organophosphates
Carbamate insecticides
Nicotine
Inorganic arsenicals
Organic mercury
Cadmium compounds
Organotin compounds
Copper compounds
Thallium
Fluoride
Borates
Naphthalene
Phosphine
Halocarbon fumigants
Creosote
Diquat
Cholecalciferol
Cyanamide
Organochlorines
Nitrophenols
Thiram
Pentachlorophenol
Paraquat
Diethyltoluamide
Behavioral - mood
Disturbances
(confusion, excitement,
mania, disorientation,
emotional lability)
Organic mercury
Inorganic arsenicals
Organotin compounds
Thallium
Nicotine
Sodium fluoroacetate
Diquat
Cyanide
Nitrophenols
Aminopyridine
Carbon disulfide
Methyl bromide
Organophosphates
Carbamate insecticides
Pentachlorophenol
Sodium fluoride
Diethyltoluamide
Organochlorines
Depression, stupor, coma,
respiratory failure, often
without convulsions
Organophosphates
Carbamate insecticides
Sodium fluoride
Borate
Diquat
Inorganic arsenicals
Metaldehyde
Sulfuryl fluoride
Halocarbon fumigants
Phosphorus
Phosphine
Paraquat
Chlorophenoxy compounds
Diethyltoluamide
Alkyl phthalates
SIGNS AND SYMPTOMS -215
-------
Nervous System (continued)
MANIFESTATION
Seizures/Convulsions
(clonic-tonic) sometimes
leading to coma
Muscle twitching
Myotonia
Tetany, carpopedal spasms
Tremor
Incoordination
(including ataxia)
Paralysis
Paresis, muscle weakness
Hearing loss
CHARACTERISTIC OF
THESE POISONINGS
Organochlorines
Strychnine
Crimidine
Sodium fluoroacetate
Nicotine
Cyanide
Acrylonitrile
Metaldehyde
Thallium
DEBT
Chlorobenzilate
Carbon disulfide
Phosphine
Povidone-iodine
Hexachlorophene
Sodium chlorate
Creosote
Endothall
Fluoride
Organophosphates
Carbamate insecticides
Nicotine
Sulfuryl fluoride
Fluoride
Phosphides
Phosphorus
Organic mercury
Thallium
Organophosphates
Carbamate insecticides
Nicotine
Metaldehyde
Borates
Halocarbon fumigants
Organophosphates
Carbamate insecticides
Carbon disulfide
Nicotine
Thallium
Inorganic arsenicals
Organophosphates
Carbamate insecticides
Nicotine
Organic mercury
OCCURS WITH
THESE AGENTS
Nitrophenols
Pentachlorophenol
Inorganic arsenicals
Organotin compounds
Diquat
Borate
Sulfuryl fluoride
Methyl bromide
Chlorophenoxy compounds
Organophosphates
Carbamate insecticides
Aminopyridine
Organic mercury
Chlorophenoxy compounds
Chlorophenoxy compounds
Pentachlorophenol
Nitrophenole
Thiram
Organic mercury
Organochlorines
Organic mercury
Diethyltoluamide
216 SIGNS AND SYMPTOMS
-------
Nervous System (continued)
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Hypotension shock
Phosphorus
Phosphides
Phosphine
Sodium fluoride
Sodium chlorate
Borate
Thallium
Copper compounds
Endothall
Cyanamide
Inorganic arsenicals
Nicotine (late)
Creosote
Alkyl phthalate
Cycloheximide
Formaldehyde
Norbormide
Hypertension
Thallium (early)
Nicotine (early)
Organophosphates
Cardiovascular System
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Cardiac arrhythmias
Sodium fluoroacetate
Halocarbon fumigants
Nicotine
Sodium fluoride
Ethylene oxide
Sodium chlorate
Thallium-ventricular
Povidone-iodine
Veratrum alkaloid (sabadilla)
Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Organochlorines
Cyanide
Acrylonitrile
Fluoride
Bradycardia (sometimes to
asystole)
Cyanide
Organophosphates
Carbamate insecticides
Nicotine
Tachycardia
Nitrophenols
Pentachlorophenol
Cyanamide
Metaldehyde
Organophosphates
SIGNS AND SYMPTOMS -217
-------
Respiratory System
MANIFESTATION
Upper respiratory tract
irritation, rhinitis, scratchy
throat, cough
Sneezing
Runny nose
Pulmonary edema
(many chemicals come
packaged in a
hydrocarbon vehicle, well
known to cause
pulmonary edema)
Pulmonary consolidation
Dyspnea
CHARACTERISTIC OF
THESE POISONINGS
Naphthalene
Paraquat
Chloropicrin
Aero le in
Dichloropropene
Ethylene dibromide
Sulfur dioxide
Sulfuryl fluoride
Acrylonitrile
Formaldehyde
Cadmium dusts
ANTU
Sabadilla
Pyrethrins
Inorganic arsenicals
Organophosphates
Carbamate insecticides
Methyl bromide
Phosphine
Phosphorus
Phosphine
Ethylene oxide
Ethylene dibromide
Aero le in
Pyrethiods
Sulfur dioxide
Cationic detergents
Creosote
Methyl isothiocyanate
Cadmium
Paraquat
Cadmium dusts
Methyl bromide
Organophosphates
Carbamate insecticides
Nicotine
Paraquat
ANTU
Cadmium dusts
Cyanamide
Sulfuryl fluoride
Pentachlorophenol
Methyl bromide
Sulfur dioxide
Chloropicrin
OCCURS WITH
THESE AGENTS
Dry formulation of copper, tin,
zinc compounds
Dusts of thiocarbamate and
other organic pesticides
Chlorophenoxy compounds
Aliphatic acides
Rotenone
Dry formulation of copper, tin,
zinc compounds
Dusts of thiocarbamate and
other organic pesticides
Chlorophenoxy compounds
Aliphatic acides
Rotenone
Organophosphates
Carbamate insecticides
Paraquat
Phosphides
Diquat
Nitrophenols
Cyanide
Creosote
Pyrethins
218 SIGNS AND SYMPTOMS
-------
Gastrointestinal Tract and Liver
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Nausea, vomiting,
commonly followed by
diarrhea
Organophosphates
Carbamate insecticides
Nicotine
Arsenicals
Fluoride
Cadmium compounds
Organotin compounds
Copper compounds
Sodium chlorate
Borate
Cyanide
Chlorophenoxy compounds
Phosphorus
Phosphides
Phosphine
Carbon disulfide
Chloropicrin
Halocarbon fumigants
Endothall
Metaldehyde
Thallium
Red quill
Diquat
Naphthalene
Methyl bromide
Dibromochloropropane
Veratrum alkaloid
Thiram
Pentachlorophenol
B. thuringiensis
Cholecalciferol
Thiram
Ethylene dichloride
Propane
Ethylene oxide
Cresol
Many pesticides have some
irritant property
Diarrhea (first)
Organophosphates
Carbamates
Pyrethoids
Borates
Sulfur
Nicotine
B. thuringiensis
Thiram
Cadmium
Cationic detergents
Cresol
Hexachlorophene
Chlorophenoxy compounds
Diarrhea (bloody)
Fluoride
Paraquat
Diquat
Thallium
Coumarins
Indandiones
Endothall
Arsenicals
Phosphorus
Phosphides
Cycloheximide
SIGNS AND SYMPTOMS -219
-------
Gastrointestinal Tract and Liver (continued)
MANIFESTATION
Abdominal pain
Stomatitis
Salivation
Ileus
CHARACTERISTIC OF
THESE POISONINGS
Organophosphates
Carbamate insecticides
Paraquat
Diquat
Nicotine
Methaldehyde
Fluoride
Borate
Phosphorous
Phosphides
Inorganic arsenicals
Cadmium compounds
Copper compounds
Thallium
Organotin compounds
Inorganic arsenicals
Paraquat
Diquat
Copper compounds
Organophosphates
Carbamate insecticides
Nicotine
Aminopyridine
Sodium fluoride
Cyanide
Cadmium compounds
Thallium
Diquat
OCCURS WITH
THESE AGENTS
Chlorophenoxy compounds
Aliphatic acids
Sodium chlorate
Creosote
Endothall
Aminopyridine
Coumarins
Indandiones
Fumigants (ingested)
Cycloheximide
Thallium
Liver
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Enlargement
Copper compounds
Sodium chlorate
Phosphine
Carbon tetrachloride
Cholorform
Inorganic arsenicals
Hexachlorobenzene
Jaundice -
see section on Skin
220
SIGNS AND SYMPTOMS
-------
Kidney
MANIFESTATION
Proteinuria
Hematuria
Sometimes leading
to oliguria
Acute renal failure with
azote mia
Dysuria, hematuria, pyuria
Polyuria
Hemoglobinuria
Wine-red urine
(porphyrinuria
Smoky urine
Glycosuria
Ketonuria
CHARACTERISTIC OF
THESE POISONINGS
Inorganic arsenicals
Copper compounds
Sodium fluoride
Naphthalene
Borate
Nitrophenols
Pentacholorphenol
Sodium chlorate
Sulfuryl fluoride
Paraquat
Diquat
Arsine
Ethylene dibromide
Chlordimeform
Cholecalciferol
Naphthalene
Sodium chlorate
Arsine
Hexachlorobenzene
Creosote
OCCURS WITH
THESE AGENTS
Cadmium compounds
Phosphorus
Phosphides
Phosphine
Chlorophenoxy compounds
Creosote
Organotin compounds
Fluoride
Organotin compounds
Borate
Reproductive System
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Low sperm count
Dibromochloropropane
Kepone
SIGNS AND SYMPTOMS 221
-------
Blood
MANIFESTATION
Hemolysis
Methemoglobinemia
Hypoprothrombinemia
Hyperkalemia
Hypocalcemia
Hypercalcemia
Carboxyhemoglobinemia
Anemia
Leukopenia,
Thrombocytopenia
Elevated LDH
GOT, GPT,
alkaline phosphatase,
ALT, AST enzymes
Depressed RBC
Acetylcholinesterase and
plasma
pseudocholinesterase
CHARACTERISTIC OF
THESE POISONINGS
Naphthalene
Sodium chlorate
Arsine
Sodium chlorate
Creosote
Coumarins
Indandiones
Sodium chlorate
Naphthalene
Arsine
Fluoride
Cholecalciferol
Naphthalene
Sodium chlorate
Arsine
Inorganic arsenicals
Inorganic arsenicals
Carbon tetrachloride
Chloroform
Phosphine
Organosphosphates
OCCURS WITH
THESE AGENTS
Copper compounds
Cresol
Chlordimeform
Cyanide
Cresol
Copper
Arsine
Phosphorus
Phosphides
Carbon tetrachloride
Sodium fluoride
Thallium
Phosphorus
Phosphides
Organotin compounds
Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Sodium chlorate
Nitrophenols
Pentachlorophenol
Thallium
Organochlorines
Chlorophenoxy compounds
Carbamate insecticides
222 SIGNS AND SYMPTOMS
-------
Index of Pesticide Products
Symbols
1,2-dichloropropane 157
1,2-epoxyethane 158
1,3-dichloropropene 157
2-benzyl-4-chlorophenol 197
2-methyl-3, 6 dichlorobenzoic acid. 95
2,3,6-TBA 119
2,4-D 94-95,97-98
2,4-DB 95
2,4-dichlorophenoxyacetic acid . 95, 98
2,4-dichlorophenoxybutyric acid.... 95
2,4-dichlorophenoxypropionic acid 95
2,4-DP 95
2,4,5-T 94-95
2,4,5-trichlorophenoxy acetic acid.. 95
4-Aminopyridine 183-184, 194
4-tert-amylphenol 197
1080 177
1081 177
A7Vapam 140
Aaterra 152
Aatrex 121
Abate 35
Abathion 35
Abol 49
Acaraben 75
acaricides 74, 104
Acarstin 75
Accelerate 184
Accotab 120
Accothion 35
acephate 35
acetamides 119
Acrex 105
Acricid 105
acrolein 156, 158
acrylonitrile 156-157, 161, 163-165
Actellic 35
Activol 64
Actor 109
Afalon 122
Aficida 49
Afugan 35
Agree 64
Agri-Mycin 17 65
Agritox 35
Agrosan 147
Agrothion 35
Agtoxin 158
Akar 75
alachlor 119
Alanox 119
alcohols 192-193, 196-197
aldehydes 158, 161, 197
aldicarb 49, 50
aldrin 55-57
Align 64
alkyl phthalates 74-75
allethrin 76, 89
Allisan 138
Alon 122
Alphos 158
Altosid 76
Amaze 35
Ambox 105
Ambush 77
Amerol 121
Ametrex 121
ametryn 121
Amex 120
aminocarb 49
4-Aminopyridine 183-184, 194
aminotriazole 121
Amiral 152
amitrole 121
Ammo 76
anilazine 152
anilides 119
Ansar 170 127,134
AnsarSlOO 127,134
Anthio 35
anticaking agents 184, 193
Anticarie 138
anticoagulant rodenticides 5,6
Antimilace 184
Apache 35
Apachlor 35
Apex 76
Aphox 49
Apl-Luster 152
aprocarb 50
Aquabac 64
Aquacide 109
Aquathol 121, 184
Aquinite 157
Arbotect 152
Arelon 122
Aresin 122
Aretit 105
Arrhenal 127,134
Arsenal 120
INDEX OF PESTICIDES 223
-------
arsenic acid 127, 133
arsenic trioxide 127, 129, 133
arsenical pesticides .. 126, 145, 147, 149
arsinegas 126-127, 129,132
Arsinyl 127,134
Arsonate Liquid 128, 134
Aspon 35
Aspor 144
asulam 119
Asulox 119
Asuntol 35
Atranex 121
atrazine 121
Aules 140
Auton 75
Avicol 138
Avitrol 184
Azac 119
Azadirachtin 63-64
Azar 119
Azatin 64
azinphos-methyl 35
Azodrin 35
Azofene 35
Azolan 121
Azole 121
Aztec 35
B
Bacillus thuringiensis 64, 72
Bactimos 64
Bactospeine 64
Bactur 64
Balan 120
Balfin 120
Banvel 95,119
Barricade 76
Barrier 119
barthrin 76
Basagran 119
Basalin 120
Basanite 105
Bash 35
Batasan 149
Baygon 50
Bayleton 152
Bayrusil 35
Baytex 35
Baythion 35
Baythroid 76
Belmark 77
bendiocarb 49
Benefin 120
Benex 152
benfluralin 120
Benlate 152
benomyl 152
bensulide 35
bentazone 119
benzalkonium chloride 197-198
Benzamide 119
benzene hexachloride 56
Benzilan 75
Benzofuroline 77
Benzothiadiazinone dioxide 119
Benzyl benzoate 75
2-benzyl-4-chlorophenol 197
Berelex 64
Betadine 197
Betasan 35
Bexton 119
Bidrin 35
Bilevon 197
binapacryl 105
bioallethrin 76
Biologicals 63
biopermethrin 76
bioresmethrin 76
Birlane 35
Black Leaf 40 64-65
Bladafum 35
Bladex 121
Bo-Ana 35
Bolate 127,134
Bolero 119
Bolls-Eye 127,134
Bollwhip 64
Bolstar 35
bomyl 35
Bophy 127,134
borates 74-77
Borax 75-76,90
Bordeaux Mixture 145
boric acid 74-76, 90
Brace 35
Bravo 138
Brestan 149
Brodan 35
brodifacoum 170-172, 181
bromacil 122
bromadiolone 170
Bromofume 157
Bromone 170
bromophos 35
bromophos-ethyl 35
Broot 50
Bueno6 128,134
bufencarb 49
Busanl020 140
butralin 120
224
INDEX OF PESTICIDES
-------
butylate 119
Bux 49
cacodylic acid 127, 134
Cad-Trete 150
Caddy 150
Cadminate 150
cadmium chloride 150
cadmium compounds 137, 150
cadmium succinate 150
cadmium sulfate 150
cadusafos 35
Caid 170
Calar 127,135
calcium acid methane arsonate. 127, 135
calcium arsenate 127, 134
calcium arsenite 127, 133
calcium cyanamide 184
calcium hypochlorite 197, 200
Caldon 105
Caliber 90 121
CAMA 127,135
Caparol 121
Captaf 145
captafol 145
captan 145, 154
Captanex 145
CarbamateWDG 140
carbamates 5,12-13,49-50,
53,69,119,140
Carbamult 50
Carbanilates 120
carbaryl 49-50
carbofuran 48-50
carbon disulfide 40,156-158,
161-164
carbon tetrachloride 157-158, 164,
167-168
carbophenothion 35
Carpene 152
Carzol 49
Casoron 119
Castrix 177
cationic detergents 197-198, 200
CCN52 76
Cekiuron 122
CekuC.B 138
Cekugib 64
Cekumeta 184
Cekuquat 109
Celathion 35
Celfume 157
Celmide 157
Ceresan 147
cetrimide 197-198, 206
cetylpyridium chloride 197-198
Chem Bam 144
Chem-Fish 64
Chemox General 105
ChemoxPE 105
Chemsect DNBP 105
Chemsect DNOC 105
Chermox PE 105
ChipcoThiram75 140
chlordane 55-57, 61
chlordecone 55-57, 62
chlordimeform 74-75, 77-78
chlorethoxyfos 35
chlorfenvinphos 35
chlorhexidine 197-199, 206
chlorimuron 122
chlormephos 35
Chloro-IPC 120
chlorobenzilate .... 56, 74-75, 78-79, 91
chloroform 156-157
chloroneb 138-139
chlorophacinone 170, 181
Chlorophen 100
chlorophenoxy herbicides 94, 98
chloropicrin 156-157
chlorothalonil 138-139, 154
chlorotoluron 122
chlorphoxim 35
chlorpropham 120
chlorpyrifos 6, 35-36
chlorthaldimethyl 121
chlorthiophos 35
cholecalciferol 179-180
Chrysron 77
Ciodrin 35
cismethrin 76, 89
Classic 122
cloethocarb 49
clomazone 120
Clorto Caffaro 138
Clortosip 138
Clortran 138
Co-Ral 35
Co-Rax 170
Cobex 120
Comite 76
Command 120
Compound 1080 177
Compound 1081 177
Contrac 170
Contraven 35
convulsants 177
copper acetate 145
copper acetoarsenite 127, 133
INDEX OF PESTICIDES 225
-------
copper ammonium carbonate 145
copper arsenite
(acid copper arsenite) 127
copper carbonate, basic 145
copper compounds 137, 145-146
copper hydroxide 145
copper lime dust 145
copper linoleate 145
copper oxychloride 145
copper potassium sulfide 145
copper silicate 145
copper sulfate 145-146, 155
Cotoran 122
cottonex 122
coumachlor 170
coumafene 170
coumaphos 35
coumarins 169-171
coumatetralyl 170
Counter 35
Cov-R-Tox 170
Crab-E-Rad 127,134
CragTurf Fungicide 150
creosote 183-187, 194
cresol 105,185,197, 202-203, 207
crimidine 177-178
Crisazina 121
Crisfolatan 145
Crisfuran 49
Crisquat 109
Crisuron 122
Crotothane 105
crotoxyphos 35
crufomate 35
Cryolite 75,82,85
Cuman 140
cupric oxide 145
cuprous oxide 145
Curacron 35
Curamil 35
Curaterr 49
Curitan 152
cyanamide 184, 194
cyanazine 121
cyanofenphos 35
cyanophos 35
Cyanox 35
Cybolt 77
cycloate 119
cycloheximide 152-153
Cyflee 35
cyfluthrin 76
Cygon 35
cyhexatin 74-75,79-80
Cylan 35
Cymbush
Cymperator...
Cynoff
Cyolane
Cyperkill
cypermethrin
Cypona
Cyrux
76
76
76
35
76
76,87
35
76
cythioate 35
Cythion 35
Cytrolane 35
2,4-D 94-95,97-98
D-D92 157
D-trans 76
Dachthal 121
Daconate 6 128, 134
Daconil2787 138
Dailon 122
Dal-E-Rad 128,134
Dalapon 119
Danitol 77
Dapacryl 106
Dart 76
Dasanit 35
2,4-DB 95
DBCP 26,157
DCNA 138
DCPA 121
DDT 55-58,79,118
DDVP 35
De-Fol-Ate 184
De-Green 35
Decis 77
DEET 80-82,91
DEF 35
DeFend 35
Defol 184
Deftor 122
Delnav 35
DeltaDust 77
DeltaGard 77
deltamethrin 77, 89
Deltex 77
demeton 35
demeton-S-methyl 35
Demon 77
Denarin 152
Dermaadex 197
Des-i-cate 184
Design 64
desmetryn 121
Dessin 105
Detamide 75
226
INDEX OF PESTICIDES
-------
Dethdiet 179
Dextrone 109
Dexuron 109
Di-allate 119
Di-Tac 127,134
Diacon 76
dialifor 35
diallate 119
Dianex 76
Diaract 76
diatomaceous earth 193
diazinon 35-36
Dibrom 35
dibromochloropropane 26, 157, 162
dibromoethane 157
dibutylphthalate 74-75
dicamba 95, 119
Dicarbam 49
dichlobenil 119
dichloroethane 157
dichlorofenthion 35-36
2,4-dichlorophenoxyacetic acid .. 95,98
2,4-dichlorophenoxybutyric acid 95
2,4-dichlorophenoxypropionic acid . 95
1,2-dichloropropane 157
1,3-dichloropropene 157
dichloropropionic acid 119
dichlorprop 95, 98
dichlorvos 35
dicloran 138-139
dicofol 55-56
dicrotophos 35
Dicuran 122
dieldrin 55-57
Dieldrite 56
dienochlor 56
diethyltoluamide 74-75, 80, 91
difenacoum 170
diflubenzuron 76, 85
Difolatan 145
Dilie 127,134
Dimecron 35
dimefos 35
dimephenthoate 35
dimetan 49
Dimethan 49
dimethoate 35, 37
dimethrin 77
dimethyl phthalate 74, 75
Dimilin 76
dinitramine 120
Dinitro 105,107
Dinitro General Dynamyte 105
Dinitro Weed Killer 5 105
Dinitro-3 105
dinitrocresol 105
dinitrophenol 105-106
dinobuton 105
dinocap 104-105
Dinofen 105
dinopenton 105
dinoprop 105
dinosam 105
dinoseb 105, 107
dinoseb acetate 105
dinoseb methacrylate 105
dinosulfon 106
dinoterb acetate 106
dinoterb salts 106
dinoterbon 106
dioxacarb 49
dioxathion 35
Dipel 64
diphacin 170
diphacinone 170
Dipher 144
Dipterex 35
diquat 11-12,15,108-116
Direx 122
Dirimal 120
disinfectants 5-7, 196-199
disodium arsenate 128, 133
disodium methane arsonate ... 127, 134
disulfoton 35
Disyston 35
ditalimfos 35
Dithane 144
Dithione 35
Ditrac 170
Diurex 122
Diuron 122
diuron 109,122
DMA 127,134
DMP 75
DNAP 105
DNBP 105
DNC 105
DNOC 105
dodine 152
Dojyopicrin 157
Dolochlor 157
Dosaflo 122
Dotan 35
2,4-DP 95
DPA 119
DPX 1410 49
Dragnet 77
Drawinol 105
Draza 49
DrexarSSO 128,134
INDEX OF PESTICIDES 227
-------
Drop-Leaf 184
DSE 144
DSMA 127,134
Dual 119
Duraphos 35
Duratox 35
Dursban 35
dusts 18,66,70,90,138,
140,145,147,184,192-193
Dycarb 49
Dyclomec 119
Dyfonate 35
Dylox 35
Dyrene 152
E
E601 35
E-48 35
E-D-Bee 157
E-Z-OffD 35
E605 35
Earthcide 138
Easyoff-D 35
EBDC compounds 144
Ebufos 35
EDB 157
EDC 157
edifenphos 35
Ekamet 35
Ekatin 35
Eksmin 77
Elecron 49
Elimite 77
ElgetolSO 105
Elgetol318 105
Emerald green 127, 133
Emisan 6 147
emulsifiers 184, 193
Endosan 106
endosulfan 55, 56
endothall.. 121,124,184,187-188,195
Endothall Turf Herbicide 184
endothion 35
endrin 55-56
Entex 35
EPBP 35
EPN 35
1,2-epoxyethane 158
EPTC 119
Eradicane 119
Esgram 109
ethalfluralin 120
Ethanox 35
Ethazol 152
ethion 35
ethoprop 35
ethyl parathion 35, 37
ethylene dibromide .... 157-158, 162, 167
ethylene dichloride 157-158
ethylene oxide 156, 158
ETO 158
etridiazole 152-153
etrimfos 35
Etrofolan 49
Eugenol 64-65, 72
Evik 121
Exofene 197
ExothermTermil 138
Fac 35
Fall 184
Famarin 170
Famfos 35
Famid 49
famphur 35
Far-go 119
fenamiphos 35
Fenchlorphos 35
fenitrothion 35
Fenkill 77
fenophosphon 35
fenothrin 77
fenoxycarb 49
fenpropanate 77
Fenpropar 76
fenpropathrin 77
fensulfothion 35
fenthion 35, 37
fentin acetate 149
fentin chloride 149
fentin hydroxide 149
fenvalerate 77, 87, 89, 91
ferbam 140, 143
Ferberk 140
FermideSSO 140
Fernasan 140
Fernos 49
Ficam 49
Flectron 77
fluchloralin 120
flucythrinate 77, 87
Fluent 77
flumeturon 122
fluorides 74,82,85
fluoroacetamide 169, 177
fluvalinate 77,87-89
FMC9044 106
Folbex 75
Folcord 77
228
INDEX OF PESTICIDES
-------
Folex 35
Folosan 138
Folpan 145
folpet 145
Foltaf 145
fonofos 35
formaldehyde 156, 158, 168, 197
formetanate hydrochloride 49
formothion 35
Fortress 35
Fortrol 121
fosamine 120
fosthietan 35
French green 127, 133
Frunax-DS 170
Fumex 158
fumigants 82, 141, 156, 162,
164,174,176,197
Fumitoxin 158
fungicides 55,79,104,137,
143-150,152-154,156
Funginex 152
Fungitrol II 145
Furadan 49
furethrin 77
Futura 64
G 28029 35
GA3 64-65
Gallotox 147
gamma BHC or HCH 56
Gamophen 197
Gardona 35
Gardoprim 121
Garlon 120
Gebutox 105
Gesafram 50 121
Gesagard 121
Gesapax 121
Gesatop 121
gibberellic Acid 64-65
Gibberellin 64-65
Gibrel 64
glutaraldehyde 6, 197-198
Glycophene 152
Glyfonox 120
Glyphosate 6
glyphosate 120
Gnatrol 64
Go-Go-San 120
Goldquat 109
Gramocil 109
Gramonol 109
Gramoxone 109
gramoxone 116
Gramuron 109
granular formulations 192
Granurex 122
Grocel 64
Gusathion 35
Guthion 35
Gypsine 127,134
H
Haipen 145
Halizan 184
haloaromatic substituted ureas 85
halocarbon fumigants 156-157,
159,162
Hanane 35
Havoc 170
HCB 138-139
HCH 56
Hel-Fire 105
Helothion 35
heptachlor 55-57
heptenophos 35
Herald 77
Herbi-All 128,134
Herbicide 273 184
Herbodox 120
hexachlor 56
hexachloran 56
hexachlorobenzene 55-56, 61, 103,
137-139,154
hexachlorophene 197, 202-204, 207
Hexadrin 56
Hexaferb 140
Hexathane 144
Hexathir 140
Hexazir 140
Hi-Yield Dessicant H-10 127, 133
Hibiclens 197, 206
Hibistat 197
hiometon 35
Hoe 002784 106
hosalone 35
Hostaquick 35
Hostathion 35
hydrocyanic acid 157
hydrogen cyanide .... 156-158, 163-165
Hydrothol 184
hypochlorites 197,200
Hyvar 122
I
IBP 35
imazapyr 120
Imidan 35
INDEX OF PESTICIDES 229
-------
indandiones 169-171
inorganic copper compounds 145
Iodines 197
iodofenphos 35
loprep 197
IP50 122
iprodione 152-153
isazofos 35
isofenphos 35
isolan 49
Isopestox 35
isoprocarb 49
isopropanol 184, 192, 196
isopropyl alcohol 80, 196-197, 206
isoproturon 122
isoxathion 35
isoxazolidinone 120
Jones Ant Killer 128,133
K
Rabat 76
Rack 127,134
Kafil 77
KafilSuper 77
Karathane 105
Karbation 140
Karmex 122
Karphos 35
Kayafume 157
Kelthane 56
Kepone 56, 62
Kerb 119
Kiloseb 105
Kitazin 35
Klerat 170
Knockmate 140
Koban 152
Kobu 138
Kobutol 138
Kopfume 157
Korlan 35
Krenite 120
Kromad 150
Kryocide 75
Kusatol 184
Kwell 55-56,61-62
Kypfarin 170
KypmanSO 144
Kypzin 144
L
Lance ...
Landrin
49
50
Lannate 49
Lanox 49
Larvacide 157
Larvin 50
Lasso 119
Lead arsenate 134
lead arsenate 127
Leafex 184
lenacil 122
leptophos 35
Lescosan 35
Lexone 121
lindane 55-58, 61-62, 138
Linex 122
Linorox 122
Linurex 122
linuron 122
Liphadione 170
Liqua-Tox 170
London purple 127, 133
Lorox 122
Lorsban 35
Lysol 185,197,207
M
M-Diphar 144
MAA 127,134
Magnacide B 158
Magnacide H 158
Maki 170
malathion 35, 37, 47
MAMA 127,134
mancozeb 144
Mancozin 144
maneb 144, 154
Maneba 144
Manex 144
ManexSO 144
manzeb 144
Manzin 144
Maposol 140
Marlate 55-56
Matacil 49
Mattch 64
MCPA 95,98
MCPB 95
MCPP 95
MeBr 157
mecoprop 95, 97-98
Melprex 152
MEMA 147
MEMC 147
Meothrin 77
mephosfolan 35
Mercuram 140
230
INDEX OF PESTICIDES
-------
mercurials 148-149, 197, 202
mercurobutol 197
mercurochrome 197
Merge 823 128,134
Merpafol 145
Merpan 145
merphos 35
Mertect 152
merthiolate 197
Mesamate 128, 134
Mesurol 49
Metadelphene 75
metalaxyl 152-153
metaldehyde 184, 188-189, 195
metalkamate 49
Metam-Fluid BASF 140
metam-sodium 140-141
Metaran 75
Metason 184
Metasystox-R 35
Metasystox-S 35
Metasystoxl 35
Meth-O-Gas 157
methabenzthiazuron 122
methamidophos 35
methane arsonic acid 127, 134
methanol 184, 192, 196
MetharSO 127,134
methidathion 35
methomyl 49
methoprene 74, 76, 86
methoxychlor 56
methoxyethyl mercury acetate 147
methoxyethyl mercury chloride 147
methoxyethyl mercury compounds ..147
methyl bromide 156-157, 159,
161-163,168
2-methyl-3, 6 dichlorobenzoic acid ... 95
methyl mercury acetate 147
methyl mercury compounds 147
methyl naphthalenes 193
methyl parathion 35-37, 46
methyl trithion 35
methylene chloride. 157, 159, 161, 168
metobromuron 122
metolachlor 119
metoxuron 122
metribuzin 121
mevinphos 35
mexacarbate 49
Mezene 140
MGK 75
Micromite 76
Microzul 170
Mightikill 76
Miller 531 150
Milo-Pro 121
Minex 76
mipafox 35
MIPC 49
Miral 35
mirex 55-57
Mitis green 127, 133
Mocap 35
Monitor 35
mono-calcium arsenite 127, 133
monoammonium methane
arsonate 127, 134
monocrotophos 35
monolinuron 109, 122
monosodium methane
arsonate 127, 134
monuron 122
Morrocid 106
MSMA 127,134
Multamat 49
Muritan 179
Muskol 75
Mycodifol 145
N
N-2790 35
n-methyl carbamates 48-51,
53,140,191
nabam 144
naled 35
Namekil 184
naphthalene 66, 156-157, 159-162,
164,168,193
naphthenate 145
naramycin 152
Neburex 122
neburon 122
Neemazad 64
Neemazal 64
Neemix 64
Neguvon 35
Nem-A-Tak 35
Nemacur 35
Nemafume 157
Nemanax 157
Nemaset 157
Nemasol 140
Nemispor 144
Neopynamin 78
Nephis 157
Nexagan 35
Nexion 35
NIA9044 106
Nico Soap 64
INDEX OF PESTICIDES 231
-------
nicotine 63-67, 72-73
Niomil 49
Nitrador 105
nitrocresolic herbicides 104-105
nitrolime 184
nitromersol 197
nitrophenolic herbicides . 104-105, 118
Nitropone C 105
Nix 77
No Bunt 138
Nomersam 140
Nomolt 76
Novodor 64
Noxfire 64
Noxfish 64
NRDC 149 77
Nudrin 49
Nusyn-Foxfish 64
Nuvanol-N 35
o-phenylphenol.
Off!
Oftanol
Ofunack
197
75,80
35
35
oleate 145, 193
Omite 76,91
OMPA 35
organic copper compounds 146
organochlorines 5, 13, 55-59
organomercury compounds 137,
147,202
organophosphates .... 5-6, 12-13, 34-37,
39-40,42,44-45,
48,50,69
organotin compounds 79, 80, 137,
149-150
Ornamite 76
Orthene 35
Ortho Diquat 109
Orthocide 145
oryzalin 120
Oust 122
Outflank 77
Oxadiazolinone 120
oxadiazon 120
oxamyl 49
oxirane 158
Oxotin 75
oxydemeton-methyl 35
oxydeprofos 35
Panogen 147
Panogen M 147
Pansoil 152
Para-col 109
paradichlorobenzene 157, 160, 162
paraformaldehyde 156, 158
paraquat 11-12,15,107-117
Parathion 35, 46
Par is green 127,133,145
Parzate 144
ParzateC 144
Pathclear 109
Pattonex 122
Paushamycin.Tech 65
Payoff 77
PCNB 138-139
PCP 99,100-102
PEBC 119
pebulate 119
Penchlorol 100
pendimethalin 120
penetrants 118, 184, 193
Pennant 119
Penncap-M 35
Penncozeb 144
Pennstyl 75
Penta 100
Pentac 56
pentachloronitrobenzene 138-139
pentachlorophenol 99, 103-104,
106,139
Pentacon 100
Pentagen 138
Penwar 100
Peridex 197
Permasect 77
permethrin 77, 87-88
Perthrine 77
PestoxXIV 35
PestoxXV 35
petroleum distillates 68, 192, 194
Phaltan 145
Pharmadine 197
Pharorid 76
phencapton 35
phenol(s) 5-6, 40, 50, 65, 99,185,
187,195,197,202-203
Phenostat-A 149
Phenthoate 35
phenthoate 35
Phentinoacetate 149
phenyl salicylate 145
phenylmercuric acetate 197
phenylmercuric nitrate 197
phenylphenol 197
Phisohex 197
Phorate 87
232 INDEX OF PESTICIDES
-------
phorate 35, 87
phosalone 35-36, 46
Phosdrin 35
phosfolan 35
phosmet 35
phosphamidon 35
phosphine 156, 158, 160-161,
163-165,169,174,176,181
phostebupirim 35
Phostoxin 158
phostoxin 160
Phosvel 35
Phosvin 173
phoxim 35
phthalthrin 77
Phytar560 127,134
Pic-Clor 157
picloram 121
pindone 170
pine oil 5-6,196-197, 205, 207
Pinene 121
pinene 205
piperonyl butoxide 68-70, 184, 191
pirimicarb 49
pirimiphos-ethyl 35
pirimiphos-methyl 35
Pirimor 49
pival 170
pivaldione 170
pivalyn 170
Plantomycin 65
Plictran 75
PMAA 147
Poast 120
PolyborS 75
Polyram-Ultra 140
Polytrin 77
Pomarsol forte 140
Pounce 77
povidone-iodine 197, 201-202, 207
Pramex 77
Pramitol25E 121
Prebane 121
Precor 76
Preeglone 109
Preglone 109
Premerge 3 105
Prenfish 64
Primatol 121
PrimatolM 121
Primicid 35
Primin 49
Princep 121
Pro-Gibb 64
Pro-Gibb Plus 64
Proban 35
Prodalumnol Double 128, 133
Prodan 75
profenofos 35
profluralin 120
Prokil 75
Prolate 35
Prolex 119
promecarb 50
prometon 121
Prometrex 121
prometryn 121
pronamide 119
propachlor 119
Propanex 119
propanil 119
propargite 6, 74, 85-86
propazine 121
propetamphos 35
propionate 147
propoxur 50
propyl thiopyrophosphate 35
propylene dichloride 157
prothoate 35
Prowl 120
Proxol 35
Prozinex 121
prussic acid 157
Purivel 122
Pynamin 76
Pynosect 77
pyrazophos 35
pyrethrins 5-6, 68-69, 87, 191
pyrethroids 5-6, 68, 74, 76, 87-88
pyrethrum 68-69, 73
pyridaphenthion 35
Quickfos 158
Quilan 120
quinalphos 35
quinolinolate 145, 147
Quintox 179
quintozene 138
R
Rabon 35
Racumin 170
Rad-E-Cate 25 127,134
Ramik 170
Rampage 179
Rampart 35
Ramrod 119
Ramucide 170
Rapid 49, 194
INDEX OF PESTICIDES 233
-------
Rapier 119
Ratak 170
RatakPlus 170
Ratomet 170
Raviac 170
RAX 170
red squill 179
Reglone 109
Regulex 64
repellents 5, 74, 91
resinate 145
resmethrin 77
Revenge 119
Ridall-Zinc 173
Ridomil 152
Ripcord 77
Riselect 119
Ro-Neet 119
rodenticides 5-6, 169, 171,
173-174,177,179
Rodine 179
Rody 77
ronnel 35
Ronstar 120
Rotacide 65
rotenone 64, 70
Rotenone Solution FK-11 65
Roundup 120
Rovral 152
Rozol 170
Ruelene 35
Rugby 35
S-Seven 35
sabadilla 63, 65, 71
safeners 184,193
Safrotin 35
Safsan 75
SAGA 78
Salvo 127,134
Sanifume 158
Sanspor 145
Saprol 152
Sarclex 122
Saturn 119
schradan 35
Schweinfurt green 127, 133
Selinon 105
Semeron 121
Sencor 121
Sencoral 121
Sencorex 121
sethoxydim 120
Setrete 147
Sevin 49
Shaphos 158
Shimmer-ex 147
siduron 122
simazine 109, 121
Sinbar 122
Sinituho 100
Sinox 105
Siperin 77
Skeetal 64
Skeeter Beater 75
Skeeter Cheater 75
Skintastic for Kids 75
Snox General 105
Sobrom98 157
Sodanit 128,133
Sodar 127,134
sodium arsenate 128, 133
sodium arsenite 128, 133
sodium cacodylate 127, 134
sodium chlorate 183-184,
189-190,195
sodium fluoaluminate 75, 82, 85
sodium fluoride 75, 82-83
sodium fluoroacetate 177
sodium fluosilicate 75, 82-83
sodium hypochlorite 6, 197, 206
sodium polyborates 75
sodium silico fluoride 75, 82
sodium tetraborate decahydrate 75
Sok-Bt 64
SolasanSOO 140
solvents and adjuvants 183, 192
Sometam 140
Sonalan 120
Soprabel 127, 134
Sopranebe 144
Spike 122
SpotreteWP75 140
Spotrete-F 140
Spra-cal 127,134
Spring Bak 144
Sprout-Nip 120
Stam 119
Stampede 119
stickers and spreaders 184, 193
Stomp 120
streptomycin 65, 72
Strobane 56
strychnine 169, 177-178, 182
Subdue 152
Subitex 105
substituted benzenes 137-138,
144-145,154
Sulerex 122
234
INDEX OF PESTICIDES
-------
sulfemeturon-methyl 122
sulfotep 35
sulfur 6,71,74,78,89,90,92
sulfur dioxide 156, 158, 160
sulfuryl fluoride 82, 156, 158,
161-162,168
sulprofos 35
Sumicidin 77
Sumithion 35
Super Crab-E-Rad-Calar 127, 135
Super Dal-E-Rad 127, 135
Super Tin 149
Supracide 35
Surecide 35
Surflan 120
Surgi-Cen 197
Surofene 197
Suspend 77
Sutan 119
Suzu 149
Suzu-H 149
Swat 35
synergists 68-69, 184, 191
Sypren-Fish 65
systox 35
2,4,5-T 94-95
Tag HL 331 147
Talan 105
Talcord 77
Talon 170
Tamex 120
Target MSMA 128, 134
Tattoo 49
2,3,6-TBA 119
TCA 119
TCBA 119
Tebusan 122
tebuthiuron 122
Tecto 152
teflubenzuron 76, 85
Teknar 64
Telone II Soil Fumigant 157
temephos 35
Temik 49
TEPP 35
terabacil 122
terbucarb 119
terbufos 35
terbuthylazine 121
Terbutrex 121
Ternit 121
terpene polychlorinates 56
Terraklene 109
Terraneb SP 138
Terrazole 152
Tersan 1991 152
4-tert-amylphenol 197
tertutryn 121
tetrachlorvinphos 35
tetraethyl pyrophosphate 35
tetramethrin 78
Tetrapom 140
Texosan 197
thallium sulfate 173, 175
thiabendazole 152-153
Thibenzole 152
Thimer 140
thimerosol 197
Thimet 35
thiobencarb 119
thiocarbamate insecticides 137, 140,
142,156
thiocarbamate herbicides 119
thiodicarb 50
Thioknock 140
Thiophal 145
thiophos 35
thiophthalimides 137, 145
Thiotepp 35
Thiotex 140
thiram 140-143,150,154
Thiramad 140
Thirasan 140
Thiuramin 140
Thuricide 64
thymol 197,202
Tiguvon 35
Tillam 119
Tinmate 149
Tirampa 140
TMTD 140
Tolban 120
Tolkan 122
toluene 184,192
Tolurex 122
Tomcat 170
Topitox 170
Torak 35
Tordon 121
Torus 49
Tota-col 109
Tox-Hid 170
toxaphene 55-57
TPTA 149
Tralex 78
tralomethrin 78
Trametan 140
Trans-Vert 128,134
INDEX OF PESTICIDES 235
-------
Treflan 120
Tri-PCNB 138
triadimefon 152-154
triallate 119
triazines 121
Triazole 121
triazophos 35
Tribac 119
Tribactur 64
Tribunil 122
tricalcium arsenate 127, 134
Tricarbamix 140
trichlorfon 35
trichloroacetic acid 119
trichlorobenzoic acid 119
trichloromethane 157
trichloronate 35
2,4,5-trichlorophenoxy acetic acid ... 95
triclopyr 120
triclosan 197,202
trifluralin 120
Trifocide 105
Triforine 154
triforine 152, 154
Trifungol 140
Trimangol 144
Trimaton 140
trimethacarb 50
triphenyl tin 149
Tripomol 140
Triscabol 140
Trithion 35
Tritoftorol 144
Triumph 35
Truban 152
Tuads 140
Tubotin 149
Tuffcide 138
Tupersan 122
Turcam 49
Turf-Cal 127,134
Turflon 120
Turplex 64
u
Ultracide 35
Unicrop DNBP 105
Unidron 122
Unisan 147
uracils 122
Ustadd 77
V
Vancide MZ-96 140
Vapam 140
Vapona
VC-13Nemacide.
Vectobac
Vectocide
35
35
64
64
Venturol 152
Venzar 122
veratrum alkaloid 71
Vernam 119
vernolate 119
Vertac 105
Vertac General Weed Killer 105
Vertac Selective Weed Killer 105
Vigilante 76
Vikane 158
Volid 170
Vondcaptan 145
Vonduron 122
VPM 140
Vydate L 49
w
warfarin 169-170, 181
Wax Up 120
Weed-E-Rad 128, 134
Weed-E-Rad 360 127,134
Weed-Hoe 128,134
Weedazol 121
Weedol 109
X
XenTari 64
xylene 184,192
yellow phosphorus 173-175, 181
z
Zebtox 144
Zectran 49
Ziman-Dithane 144
zinc arsenate 128, 134
zinc phosphide 169, 173-175, 181
Zinc-Tox 173
Zincmate 140
zineb 144, 154
ziram 140,143
ZiramF4 140
Ziram Technical 140
Zirberk 140
Zirex90 140
Ziride 140
Zitox 140
Zolone 35
zoocoumarin 170
Zotox 127,133
236
INDEX OF PESTICIDES
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