RECOGNITION AND

MANAGEMENT O F

PESTICIDE P OISONINGS

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
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 supervision. 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.
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

CONTENTS
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
Section I

GENERAL INFORMATION
2 • INTRODUCTION

CHAPTER 1

Introduction

This fifth edition of Recognition and Management of Pesticide Poisonings is an update and expansion of the 1989 fourth edition. The Office of Pesticide Programs of the United States Environmental Protection Agency has sponsored

the series since 1973. The purpose of the manual is to provide health professionals 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 today. 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.1

 The

updating of this manual is part of a larger initiative of the U.S. Environmental

Protection Agency, in conjunction with numerous federal agencies, associations of health professionals, and related organizations to help health care

providers become better aware, educated, and trained in the area of pesticiderelated 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 products 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 environmental 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 understanding of toxic mechanisms. Clinical toxicology is a dynamic field of medicine; 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 various courses of action—sometimes including no treatment at all—against the

risks of various interventions, such as gastric emptying, catharsis, administration
INTRODUCTION • 3

of intravenous fluids, or administration of an antidote, if available. Clinical management 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 exposures 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 experience 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 exposure 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. Suicidal ingestions almost always involve “large amounts,” requiring the most aggressive 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.
4 • INTRODUCTION

Key Principles

General methods of managing pesticide poisonings are presented in Chapter 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 management 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 duodenum 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. Overall 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 distribution 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 tissuedamaging 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 circumstances 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.
INTRODUCTION • 5

Common Pesticide Poisonings

The pesticides most often implicated in poisonings, injuries, and illnesses,

according to 1996 data from the American Association of Poison Control Center’s

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 Pesticide or Pesticide Class Child Adults Total*

< 6 years 6-19 yrs.

1 Organophosphates 700 3274 4002

2 Pyrethrins and pyrethroids** 1100 2850 3950

3 Pine oil disinfectants 1336 903 2246

4 Hypochlorite disinfectants 808 1291 2109

5 Insect repellents 1081 997 2086

6 Phenol disinfectants 630 405 1040

7 Carbamate insecticides 202 817 1030

8 Organochlorine insecticides 229 454 685

9 Phenoxy herbicides 63 387 453

10 Anticoagulant rodenticides 176 33 209

All Other Pesticides 954 3604 4623

Total all pesticides/disinfectants 7279 15,015 22,433

* Totals include a small number of cases with unknown age.

** Rough estimate: includes some veterinary products not classified by chemical type.

Source: American Association of Poison Control Centers, Toxic Exposure Surveillance

System, 1996 data.

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 (organophosphates, pyrethrins/pyrethroids, 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
6 • 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 disinfectants (14%), organophosphates (11%), pyrethrins/pyrethroids (6%), unknown

rodenticides (5%), carbamate insecticides (4%), and phenol disinfectants (3%).

CALIFORNIA OCCUPATIONAL ILLNESSES LIKELY DUE TO

PESTICIDES, 1991-1995

Rank Pesticide Systemic Topical* Total

1 Sodium hypochlorite 167 858 1025

2 Quaternary ammonia 9 348 357

3 Chlorine 112 124 236

4 Glutaraldehyde 38 118 156

5 Chlorpyrifos 113 39 152

6 Sulfur 48 69 117

7 Glyphosate 9 94 103

8 Propargite 3 96 99

9 Metam sodium** 64 33 97

10 Cyanuric acid 14 76 90

All Other 1149 1089 2238

Total all pesticides/disinfectants 1726 2944 4670

* Topical includes skin, eye, and respiratory effects.

** Train derailment led to a cluster of cases due to metam sodium in 1991.

Source: Louise Mehler, M.S., California Pesticide Illness Surveillance Program, California

Environmental Protection Agency.

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.
INTRODUCTION • 7

Format of this Manual

An effort has been made to format this book for quick reference by thorough indexing and minimal references to other pages or chapters. However,

many different agents commonly require similar procedures in treating poisonings and it is not practical to repeat these protocols in every chapter. General

principles for management of pesticide poisoning, including skin and eye decontamination, gastrointestinal decontamination, and control of convulsions

are considered in Chapter 2, General Principles. These principles are referenced 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 environmental and occupational exposures, provides questionnaires designed to elicit exposure information, discusses resources available to the practitioner, and provides a

list of governmental and non-government contacts and Web sites for more information. 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 Environmental 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
8 • INTRODUCTION

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
INTRODUCTION • 9

The Merck Index, 11th 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, 11th Edition

CDS Tomlin

The British Crop Protection Council, Farnham, Surrey, United Kingdom,1997

Pesticide Profiles: Toxicity, 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

POISINDEX® System

Barry H. Rumack, N.K. Sayre, and C.R. Gelman, 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
10 • GENERAL PRINCIPLES

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, clothing 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, ophthalmologic consultation is appropriate.

Persons attending the victim should avoid direct contact with heavily contaminated 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 pesticides can contaminate the inside surfaces of gloves, boots, and headgear. Decontamination 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 pesticide 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 respiratory depression or if the patient appears obtunded or otherwise neurologically
GENERAL PRINCIPLES • 11

impaired. Administer oxygen as necessary to maintain adequate tissue oxygenation. In severe poisonings, it may be necessary to mechanically support pulmonary ventilation for several days.

Note on Specific Pesticides: There are several special considerations

with regard to certain pesticides. In organophosphate and carbamate poisoning, 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 decontamination. 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 considered. 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 necessary 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 material 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%.1,2 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 confirmed in controlled studies.4
12 • GENERAL PRINCIPLES

2. Catharsis

Sorbitol and magnesium citrate are commonly used cathartic agents. Because 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 organophosphates, carbamates, and arsenicals generally results in a profuse diarrhea. Poisoning 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.
GENERAL PRINCIPLES • 13

Dosage of Activated Charcoal:

• Adults and children over 12 years: 25-100 g in 300-800 mL water.

• Children under 12 years: 25-50 g per dose.

• Infants and toddlers under 20 kg: 1 g per kg body weight.

Many activated charcoal formulations come premixed with sorbitol. Avoid giving 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 vomiting 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 protection is contraindicated in the neurologically impaired patient.

Note on Specific Pesticides: The use of charcoal without airway protection should be used with caution in poisons such as organophosphates, carbamates, 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
14 • GENERAL PRINCIPLES

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 benefit 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 medication 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 pesticide 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.
GENERAL PRINCIPLES • 15

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 12 years: 0.05-0.10 mg/kg IV over 2-5 minutes. Repeat 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. Dosage 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 Emerg Med 1987;16:838- 41.

2. Danel V, Henry JA, and Glucksman E. Activated charcoal, emesis, and gastric lavage in aspirin overdose. Br Med J 1988;296:1507.

3. Saetta JP, March S, Gaunt ME, et al. Gastric emptying procedures in the self-poisoned patient: Are we forcing gastric content beyond the pylorus? J 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. J Toxicol Clin Toxicol 1997;35:711-9.

5. American Academy of Clinical Toxicology, European Association of Poisons Centres and

Clinical Toxicologists. Position statement: Cathartics. J Toxicol Clin Toxicol 1997;35:743-52.

6. American Academy of Clinical Toxicology, European Association of Poisons Centres and

Clinical Toxicologists. Position statement: Single-dose activated charcoal. J Toxicol Clin Toxicol

1997;35:721-41.

7. Gaudreault P, Friedman PA, and Lovejoy FH Jr. Efficacy of activated charcoal and magnesium citrate in the treatment of oral paraquat intoxication. Ann Emerg Med 1985;14:123-5.

8. Terada H, Miyoshi T, Imaki M, et al. Studies on in vitro paraquat and diquat removal by

activated carbon. J Exp Med 1994;41:31-40.

9. Merigian KS, Woodward M, Hedges JR, et al. Prospective evaluation of gastric emptying in

the self-poisoned patient. Am J Emerg Med 1990;8:479-83.
16 • GENERAL PRINCIPLES

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 Centers Toxic 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. J Toxicol Clin Toxicol 1997;35:699-709.
• 17

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

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 situations 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 exposures are involved because of potential interactions between these hazards

and the pesticide of interest (e.g., pesticide intoxication and heat stress in agricultural 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 environmental or occupational exposure which could cause disease or exacerbate an existing medical condition.

In addition to the appropriate patient history-taking, one must also consider any other persons that may be similarly exposed in the home, work or

community environment. Each environmental or occupational disease identified 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
18 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

that involve numerous exposed individuals, additional assistance can be obtained 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 require 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 occupational 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 occupational 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 illness or injury. Although the focus is on pesticide exposures and related health
• 19

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

effects, concurrent non-pesticide exposures need to be considered in the overall 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 monograph 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, transplacental absorption and breast milk may pose additional routes of exposure. Although environmental (and, at times, occupational) exposure to pesticides is

the focus of this chapter, the most significant hazard for children is unintentional 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 poisoning.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 information on suspect pesticide products. Two documents are useful starting points
20 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

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 your symptoms have any relationship to environmental activities listed above?

• Has any other household member or nearby neighbor suffered similar health problems?
• 21

ENVIRONMENTAL AND

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) Pediatric Patient (questions asked of parent or guardian)

OCCUPATIONAL EXPOSURE

• What is your occupation and that of other household members? (If no employed individuals, go to

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.)
22 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

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 manufacturers are required to provide an MSDS for each hazardous chemical 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 evaluating 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
• 23

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

- Directions for use

- Name and address of manufacturer

- Net contents

- EPA registration number

- EPA establishment number

- Worker Protection Standard (WPS) designation, including restricted entry interval and personal protection equipment required

(see WPS description on page 25).

The EPA registration number is useful when contacting EPA for information 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 ingredients (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 identifying 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 exposed. 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 associated 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 understanding 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
24 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

• 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, exacerbate 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 Resources 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 departments that cover both occupational and environmental pesticide poisonings: California, 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 regulation 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-
• 25

ENVIRONMENTAL AND

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 standard 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 retaliatory 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 agricultural workers who apply pesticides containing cholinesterase-inhibiting compounds. 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
26 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

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 obtaining 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 workplace will occur with the patient’s 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 safety center (if

nearby), can provide the National Institute for Occupational Safety and Health

(NIOSH) or state agricultural agency the assistance needed for a disease outbreak 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 individuals (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 knowledgeable 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) manufacturing plant in California led to diagnoses of azoospermia (lack of sperm) or oligospermia (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
• 27

ENVIRONMENTAL AND

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 investigation, 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 disease 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, gender, 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 presentation for individuals with higher exposures)

• Derive an attack rate and determine if statistical significance is achieved (divide number 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 reduction of pesticide use, establishment of tolerance levels for food, and investigation 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 Protection 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
28 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

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 DOL

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 landgrant 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
• 29

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

National Center for Environmental Health (NCEH),

Centers for Disease Control (CDC)

NCEH provides expertise in environmental pesticide case surveillance and disease 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 conditions upon request, makes recommendations on preventing workplace disease and

injury, and provides training to occupational safety 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
30 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

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 information on a wide range of pesticide-related topics, such as recognition and management of pesticide poisonings, safety information, health and environmental

effects, referrals for investigation of pesticide incidents and emergency treatment 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: Farmworker Justice Fund

1111 19th Street, NW, Suite 1000

Washington, DC 20036

Telephone: 202-776-1757

E-mail address: fjf@nclr.org

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
• 31

ENVIRONMENTAL AND

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 sciencebased information about pesticides to health care providers treating pesticiderelated 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.gov/ngispgm3/iris

The Integrated Risk Information System – IRIS – is an electronic database, maintained 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 identification and dose-response assessment information. Combined with specific exposure 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.
32 •

ENVIRONMENTAL AND

OCCUPATIONAL HISTORY

Agency for Toxic Substances and Disease Registry

http://atsdr1.atsdr.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 for Toxic 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 reference to occupational cases. In: Keifer MC (ed). Human Health Effects of Pesticides, Occupational 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.
Section II

INSECTICIDES
34 • ORGANOPHOSPHATES

CHAPTER 4

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 mechanism 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 phosphorylation 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 phosphorylation 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 twitching), 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 generation of new enzyme in all critical tissues.

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
ORGANOPHOSPHATES • 35

acephate

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

DEF

De-Green

E-Z-Off D

demeton

+

systox

demeton-S-methyl

Duratox

MetasystoxI

dialifor+

Torak

diazinon

dichlorofenthion

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

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

+

E 601

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 thiopyrophosphate+

Aspon

prothoate

Fac

pyrazophos

Afugan

Curamil

pyridaphenthion

Ofunack

quinalphos

Bayrusil

ronnel

Fenchlorphos

Korlan

schradan

+

OMPA

sulfotep

+

Bladafum

Dithione

Thiotepp

sulprofos

Bolstar

Helothion

temephos

Abate

Abathion

terbufos

Contraven

Counter

tetrachlorvinphos

Gardona

Rabon

tetraethyl pyrophosphate+

TEPP

triazophos

Hostathion

trichlorfon

Dipterex

Dylox

Neguvon

Proxol

COMMERCIAL PRODUCTS

+ Indicates high toxicity. Highly

toxic organophosphates have

listed oral LD50 values (rat) less

than or equal to 50 mg/kg body

weight. Most other organophosphates included in this table

are considered moderately toxic,

with LD50 values in excess of 50

mg/kg and less than 500 mg/kg.
36 • ORGANOPHOSPHATES

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 LD50 of parathion in rats is between 3-8 mg/

kg, which is quite toxic,1,2 and essentially equivalent to dermal absorption with

an LD50 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 LD50s 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 organophosphates 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 especially 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 (reactivated) by the oxime antidote pralidoxime. As time progresses, the enzymephosphoryl 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 central 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
ORGANOPHOSPHATES • 37

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 persisted 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 neurotoxic property.

Three epidemiologic studies with an exposed group and a control group

also suggest that a proportion of patients acutely poisoned from any organophosphate 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 sometimes be picked up only on neuropsychologic testing rather than on a neurologic 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 development 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 exposure. 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 syndrome 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 longstored malathion which strongly inhibit the hepatic enzymes operative in malathion

degradation, thus enhancing its toxicity. Certain organophosphates are exceptionally 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 demonstrated 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 phenobarbital which induces hepatic degradation of the pesticide.1

 Degradation of some

compounds to a trimethyl phosphate can cause restrictive lung disease.18
38 • ORGANOPHOSPHATES

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. Exposure by inhalation results in the fastest appearance of toxic symptoms, followed 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.5

 The critical symptoms in management are the respiratory symptoms. Sufficient muscular fasciculations and weakness are often

observed as to require respiratory support; respiratory arrest can occur suddenly. 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, convulsions, 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 (sympathetic 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 sweating, 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 depression, 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, lacrimation, and sweating were less common. Seizures (22%-25%) and mental status

changes including lethargy and coma (54%-96%) were common.20, 21 In comparison, 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 diagnosis.20 In a second study, 88% of the parents initially denied any exposure history. 21

See the preceding Toxicology section for information regarding the features of the intermediate syndrome and OPIDN.
ORGANOPHOSPHATES • 39

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 biochemical indicators of excessive organophosphate absorption. Certain organoAPPROXIMATE LOWER LIMITS OF NORMAL PLASMA

AND RED CELL CHOLINESTERASE ACTIVITIES IN HUMANS*

Methods Plasma RBC Blood Whole units

pH (Michel) 0.45 0.55 ∆pH per mL per hr

pH Stat (Nabb-Whitfield) 2.3 8.0 μM per mL per min

BMC Reagent Set

(Ellman-Boehringer) 1,875 3,000 mU per mL per min

Dupont ACA <8 Units per mL

Garry-Routh (Micro) Male 7.8 μM-SH per 3mL per min

Female 5.8

Technicon 2.0 8.0 μM 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 absorbed to depress blood cholinesterase activities, but enzyme activities, especially 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 activities of human blood, measured by several methods. Lower levels usually indicate excessive absorption of a cholinesterase-inhibiting chemical.
40 • ORGANOPHOSPHATES

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 organophosphates. 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 mercury compounds, ciguatoxins, and solanines may reduce plasma pseudocholinesterase 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 membrane, such as hemolytic anemia.

The alkyl phosphates and phenols to which organophosphates are hydrolyzed in the body can often be detected in the urine during pesticide absorption 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 organophosphate absorption at lower dosages than those required to depress cholinesterase activities and at much lower dosages than those required to produce

symptoms and signs. Their presence may simply be a result of organophosphates 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 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.

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.
ORGANOPHOSPHATES • 41

2. Atropine sulfate. Administer atropine sulfate intravenously, or intramuscularly 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 receptors. Atropine does not reactivate the cholinesterase enzyme or accelerate

disposition of organophosphate. Recrudescence of poisoning may occur if tissue concentrations of organophosphate remain high when the effect of atropine wears off. Atropine is effective against muscarinic manifestations, but it is

ineffective against nicotinic actions, specifically muscle weakness and twitching, and respiratory depression.

Despite these limitations, atropine is often a life-saving agent in organophosphate 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 anticholinesterase agents from other conditions. However, lack of response, with no

evidence of atropinization (atropine refractoriness) is typical of more severe poisonings. 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/min.

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 cholinesterase reactivator, in cases of severe poisoning by organophosphate pesticides 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 cholinesterase and also by slowing the “aging” process of phosphorylated cholinesterase to a non-reactivatable form.

Note: Pralidoxime is of limited value and may actually be hazardous in poisonings by the cholinesterase-inhibiting carbamate compounds (see Chapter 5).
42 • ORGANOPHOSPHATES

Dosage of Atropine:

In moderately severe poisoning (hypersecretion and other end-organ

manifestations without central nervous system depression), the following dosage schedules have been used:

• Adults and children over 12 years: 2.0-4.0 mg, repeated every 15 minutes until pulmonary secretions are controlled, which may be accompanied 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 organophosphate 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 12 years: 0.05-0.1 mg/kg body weight, repeated every 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 indicates 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 atropine; two or more times the dosages suggested above may be needed.

The dose of atropine may be increased and the dosing interval decreased as needed to control symptoms. Continuous intravenous infusion 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 organophosphates 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.
ORGANOPHOSPHATES • 43

Dosage of Pralidoxime:

• Adults and children over 12 years: 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 intervals if needed. In very severe poisonings, dosage rates may be doubled. Repeated

doses of pralidoxime are usually required. In cases that involve continuing absorption of organophosphate (as after ingestion of large amount), or continuing

transfer of highly lipophilic organophosphate from fat into blood, it may be necessary 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 organophosphate 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 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. 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.
44 • ORGANOPHOSPHATES

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 Principles. If the patient has already vomited, which is most likely in serious exposures, 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 abdominal distress, and sometimes pulmonary edema) do not recur as atropinization is

withdrawn. In very severe poisonings by ingested organophosphates, particularly the more lipophilic and slowly hydrolyzed compounds, metabolic disposition 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, atropinization 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 recovery 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 ingestion 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 ECG recording. Some organophosphates have significant cardiac toxicity.
ORGANOPHOSPHATES • 45

12. Seizure control. Rarely, in severe organophosphate poisonings, convulsions 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 organophosphate pesticides should not be re-exposed to cholinesterase-inhibiting

chemicals until symptoms and signs have resolved completely and blood cholinesterase 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 poisoning 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 impaired 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.
46 • ORGANOPHOSPHATES

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 organophosphorus 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 P. Anticholinesterase agents. In: Gilman AG and Goodman LS (eds), The Pharmacological 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 organophosphate 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, Keefe T, 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 W, 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 NY Acad Sci 1969;160:357-65.

13. Holmes JH and Gaon MD. Observations on acute and multiple exposure to anticholinesterase 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 remodeling. 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 organophosphorous 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:S215-23.

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.

Pediatr Emerg Care 1989;5(4):222-5.
ORGANOPHOSPHATES • 47

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 organophosphate 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 Tonder WM, et al. Experience with the intensive care management 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 poisoning. Clin Toxicol 1989;27:183-92.

27. Bardin PG and van Eeden SF. Organophosphate poisoning: Grading the severity and comparing 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 organophosphate poisoning. Ann Pharmacother 1997;31:441-4.
48 • N-METHYL CARBAMATES

CHAPTER 5

N-Methyl Carbamate

Insecticides

N-Methyl carbamate insecticides are widely used in homes, gardens, and agriculture. They share with organophosphates the capacity to inhibit cholinesterase 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 acetylcholinesterase enzyme, allowing accumulation of acetylcholine, the

neuromediator substance, at parasympathetic neuroeffector junctions (muscarinic effects), at skeletal muscle myoneural junctions and autonomic ganglia (nicotinic 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 carbamate poisonings, (2) it accounts for the greater span between symptomproducing 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 somewhat 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

LD50 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, respectively. 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 senHIGHLIGHTS

• 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 CARBAMATES • 49

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+

DPX 1410

Vydate L

pirimicarb

Abol

Aficida

Aphox

Fernos

Pirimor

Rapid

(Continued on the next page)

sory and behavioral disturbances, incoordination, and depressed motor function (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-methyl 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, bronchospasm, and bronchorrhea with eventual pulmonary edema are other serious 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 poisoning 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 carbamate poisoning, and/or a history of carbamate exposure, treat the patient immediately. Do not wait for laboratory confirmation.

Blood for plasma pseudocholinesterase and RBC AChE should be obtained. 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.
50 • N-METHYL CARBAMATES

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, sulfoxide, and nitrile from aldicarb. These complex analyses, when available, can be

useful in identifying the responsible agent and following the course of carbamate 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. Administer oxygen by mechanically assisted pulmonary ventilation if respiration is

depressed. Improve tissue oxygenation as much as possible before administering 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 administered 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 receptors. 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 ineffective 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.

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.
N-METHYL CARBAMATES • 51

Dosage of Atropine:

In moderately severe poisoning (hypersecretion and other end-organ

manifestations without central nervous system depression), the following dosage schedules have proven effective:

• Adults and children over 12 years: 2.0-4.0 mg, repeated every 15 minutes until pulmonary secretions are controlled, which may be accompanied 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 respiratory distress syndrome.

• Children under 12 years: 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 symptoms for 2-12 hours or longer depending on severity of poisoning. Crackles 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 atropine; 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 intravenous administration of atropine sometimes required in organophosphate 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, atropine administration should be discontinued, at least temporarily, while

the severity of poisoning is reevaluated.
52 • N-METHYL CARBAMATES

3. Skin decontamination. In patients with contaminated skin, clothing, hair,

and/or eyes, decontamination must proceed concurrently with whatever resuscitative and antidotal measures are needed to preserve life.

Flush the chemical from eyes with copious amounts of clean water. For asymptomatic 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 carbamate poisoning, pralidoxime appears to be useful in cases of mixed carbamate/

organophosphate poisonings, and cases of an unknown pesticide with muscarinic 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 symptoms (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
N-METHYL CARBAMATES • 53

until the maximum effect of atropine has been achieved. Consult package insert for dosage and administration.

9. Pulmonary ventilation. Particularly in poisonings by large doses of Nmethyl carbamates, monitor pulmonary ventilation carefully, even after recovery from muscarinic symptomatology, to forestall respiratory failure.

10. Cardiopulmonary monitoring. In severely poisoned patients, monitor

cardiac status by continuous ECG recording.

11. Contraindications. The following drugs are probably contraindicated in

nearly all N-methyl carbamate poisoning cases: morphine, succinlycholine, theophylline, 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 ingestion of liquid concentrates of some carbamates that are formulated in a petroleum 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 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 impaired ability to operate mechanical equipment 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-ROM Version, Micromedex, Inc. Englewood, CA 1991.)

2. Ecobichon DJ. Toxic effect of pesticides. In: Klaassen CD (ed), Casarett & Doull’s Toxicology: 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 Chim Acta 1995;240:107-16.
54 • N-METHYL CARBAMATES

4. Jokanovic M and Maksimovic M. Abnormal cholinesterase activity: Understanding and interpretation. Eur J Clin Chem Clin Biochem 1997;35:11-6.

5. Lifshitz M, Shahak E, Bolotin A, et al. Carbamate poisoning in early childhood and in adults.

Clin Toxicol 1997;35:25-7.

6. Goswamy 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 children: A clinical and laboratory study. Pediatrics 1994;93:652-5.

8. Kurtz PH. Pralidoxime in the treatment of carbamate intoxication. Am J Emerg Med 1990;8:68-70.
SOLID ORGANOCHLORINES • 55

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

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, toxaphene, and mirex are substantially less.7

 Lindane has a documented 9.3% dermal absorption rate,8

 and is absorbed even more efficiently across abraded skin.1,9

This becomes especially important when taking into account its use on children 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 compound. Most organochlorines are in some degree dechlorinated, oxidized, then

conjugated. The chief route of excretion is biliary, although nearly all organochlorines yield measurable urinary metabolites. Unfortunately, many of the

unmetabolized pesticides are efficiently reabsorbed by the intestine (enterohepatic

circulation), substantially retarding fecal excretion.
56 • SOLID ORGANOCHLORINES

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 organochlorines 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 cyclodienes) 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 steroid 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 hexachlorobenzene. 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 organochlorines 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 interactions.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

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.
SOLID ORGANOCHLORINES • 57

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, particularly 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 dieldrin, aldrin, and chlordane to cause delayed or recurrent seizures.

Confirmation of Poisoning

Organochlorine pesticides and/or their metabolites can sometimes be identified 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 reflect more long-term and historic exposure.19

Chromatographic methods make possible detection of most organochlorines 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
58 • SOLID ORGANOCHLORINES

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 urinary 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 decubitus 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 pharyngeal secretion, and when possible, insert an oropharyngeal airway to maintain

an open passage unobstructed by the tongue. Minimize noise and any manipulation 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 pentobarbital coma.
SOLID ORGANOCHLORINES • 59

Seizures in patients caused by organochlorine toxicity are likely to be prolonged 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 decontamination. Activated charcoal administration has been advocated in such poisonings, 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 ECG recording to detect arrhythmia.

8. Contraindications. Do not give epinephrine, other adrenergic amines, or

atropine unless absolutely necessary because of the enhanced myocardial irritability induced by chlorinated hydrocarbons, which predisposes to ventricular

fibrillation. Do not give animal or vegetable oils or fats by mouth. They enhance gastrointestinal absorption of the lipophilic organochlorines.

9. Phenobarbital. To control seizures and myoclonic movements that sometimes persist for several days following acute poisoning by the more slowly

excreted organochlorines, phenobarbital given orally is likely to be effective.
60 • SOLID ORGANOCHLORINES

Dosage should be based on manifestations in the individual case and on information 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

H

CI

Lindane

CI

CI

H

H

H

CI

CI

H

H

CI

CI

CI

Chlordane

CI

CI

CI-C-CI

CI

CI

CI

CI

Dieldrin

CI

CI-C-CI H-C-H O

CI

CI

CI

CI

Dicofol

CI

OH

C

C

CI

CI

CI

Endosulfan

CI

C

C

O

O

CI-C-CI S=O

CI

CI

CI

Heptachlor

CI CI

CI-C-CI

CI

CH O

CI

CI

Methoxychlor

CI

H

C

C

3 OCH3

CI CI

CI CI

CI CI

CI CI

Dienochlor

CI

CI
SOLID ORGANOCHLORINES • 61

References

1. Friedman SJ. Lindane neurotoxic reaction in nonbullous congenital ichthyosiform erythroderma. Arch Dermatol 1987;123:1056-8.

2. Aks SE, Krantz A, Hryhorczuk DO, et al. Acute accidental lindane ingestion in toddlers. Ann

Emerg Med 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 HIVseropositive patient: An old medication’s new problem. J Fam Pract 1995;40(3):291-6.

5. Fischer TF. Lindane toxicity in a 24-year-old woman. Ann Emerg Med 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’s Toxicology: 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 and Appl Pharmacol 1974;28:126-32.

9. Ginsburg CM, Lowry W, and Reisch JS. Absorption of lindane (gamma benzene hexachloride) in infants and children. J Pediatr 1997;91(6):998-1000.

10. Rogan WJ. Pollutants in breast milk. Arch Pediatr Adolesc Med 1996;150:981-90.

11. Stevens MF, Ebell GF, and Psaila-Savona P. Organochlorine pesticides in Western Australian

nursing mothers. Med J Aust 1993;158(4):238-41.

12. Joy RM. The effects of neurotoxicants on kindling and kindled seizures. Fundam Appl Toxicol

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 AmVet Med Assoc 1975;166(6):591-5.

15. Rauch AE, Kowalsky SF, Lesar TS, et al. Lindane (Kwell)-induced aplastic anemia. Arch Intern

Med 1990;150:2393-5.

16. Furie B and Trubowitz S. Insecticides and blood dyscrasias. Chlordane exposure and selflimited refractory megaloblastic anemia. JAMA 1976;235(16):1720-2.

17. Vonier PM, Crain 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.

CI CI

CI

CI

CI

O

CI CI

CI

CI

CI

Chlordecone

CI CI

CI

CI

CI

CI CI

CI

CI

CI

CI

CI

Mirex
62 • SOLID ORGANOCHLORINES

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, Smout 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. Hosler J, Tschan C, Hignite CE, et al. Topical application of lindane cream (Kwell) and

antipyrine metabolism. J Invest Dermatol 1980;74:51-3.

21. Cohn WJ, Boylan JJ, Blanke RV, et al. Treatment of chlordecone (Kepone) toxicity with

cholestyramine. New Engl J Med 1978;298(5):243-8.
BIOLOGICALS • 63

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 primarily used and manufactured in India; little use or exposures are expected in the

United States.

Treatment

1. Skin decontamination. If skin exposure occurs, the skin should be thoroughly washed with soap and water.

2. Gastrointestinal decontamination. Due to the severe gastrointestinal irritation, gastric emptying and catharsis are not indicated. Consideration should

be given to administration of activated charcoal as outlined in Chapter 2.

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 GI

decontamination may be

indicated

• Nicotine, rotenone, and

sabadilla require aggressive

support
64 • BIOLOGICALS

BACILLUS THURINGIENSIS

Several strains of Bacillus thuringiensis are pathogenic to some insects. The

bacterial organisms are cultured, then harvested in spore form for use as insecticide. 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 concentrates, and granules for application to field crops and for control of mosquitoes and black flies.

Toxicology

The varieties of Bacillus thuringiensis used commercially survive when injected 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 commodities 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 suspension into the eye was successfully treated by subconjunctival injection of gentamicin (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 gastroenteritis: 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.

Commercial Products

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

Futura

Sok-Bt

Thuricide

Tribactur

Variety morrisoni

Variety tenebrionis:

Novodor

eugenol

gibberellic acid (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)
BIOLOGICALS • 65

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.

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 cultured fungus, formulated in tablets, granules, and liquid concentrates for application 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

Commercial Products

(Continued)

Rotacide

Rotenone Solution FK-11

Sypren-Fish

sabadilla

streptomycin

Agri-Mycin 17

Paushamycin, Tech.

Plantomycin

*Discontinued in the U.S.
66 • BIOLOGICALS

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. Extensive 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 neuromuscular 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 dosage 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 hypotension and bradycardia, with the latter two signs leading to shock.11,12 Seizures 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 absorption of nicotine.
BIOLOGICALS • 67

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 contaminated, 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 treatment, 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 supplemental oxygen if available, or mouth-to-mouth or mouth-to-nose methods if necessary. 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 activated charcoal as outlined in Chapter 2 is probably the best initial step in management. 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 administration. 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. Severe hypersecretion (especially salivation and diarrhea) or bradycardia may be

treated with intravenous atropine sulfate. See dosage on next page.
68 • BIOLOGICALS

Dosage of Atropine Sulfate:

• Adults and children over 12 years: 0.4-0.5 mg slowly IV, repeated every

5 minutes if necessary.

• Children under 12 years: 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 penetrate 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 enzymatic 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 reactions (rhinitis and asthma) have occurred following exposures.13,14 Single cases

exhibiting anaphylactic15 and pneumonitic manifestations16 have also been reported. 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
BIOLOGICALS • 69

poor bioavailability probably accounts in large part for their relatively low mammalian 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 piperonyl butoxide and n-octyl bicycloheptene dicarboximide have low toxic potential in humans, but organophosphates or carbamates included in the product

may have significant toxicity. Pyrethrins themselves do not inhibit cholinesterase 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 administration of inhaled B2

-agonists and/or systemic corticosteroids. Inhalation exposure 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 corticosteroid preparations. This should be done under the supervision of a physician. 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 according to their respective toxic actions, independent of pyrethrin-related effects.

6. Gastrointestinal decontamination. Even though most ingestions of pyrethrin 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.
70 • BIOLOGICALS

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 included in some commercial products. Rotenone degrades rapidly in the environment. 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 respiratory tract irritation have also been reported in occupationally exposed persons.

When rotenone has been injected into animals, tremors, vomiting, incoordination, 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 washing 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-containing 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.
BIOLOGICALS • 71

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 ectoparasites 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 veratrum alkaloid occur from the inadvertent ingestion of the plant.18

Toxicology

Sabadilla dust is very irritating to the upper respiratory tract, causing sneezing, 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 treatment 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 emptying. 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 charcoal 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, ECG monitoring of cardiac activity for

arrhythmia and conduction defects is appropriate. Bradycardia may be treated

with atropine.18,19 See dosage on next page.
72 • BIOLOGICALS

Dosage of Atropine Sulfate:

• Adults and children over 12 years: 0.4-0.5 mg slowly IV, repeated every 5 minutes if necessary.

• Children under 12 years: 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 nephrotoxicity and ototoxicity. Fortunately, it is poorly absorbed from the gastrointestinal 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, Hulbert TV, 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 Harris TM. Fatal nicotine ingestion. J Emerg Med 1991;9:133-6.

7. Svensson CK. Clinical pharmacokinetics of nicotine. Clin Pharm 1987;12:30-40.
BIOLOGICALS • 73

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. Br J Clin Pharmacol 1985;19:239-47.

10. Woolf A, Burkhart K, Caraccio T, et al. Self-poisoning among adults using multiple transdermal

nicotine patches. J Toxicol 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). J Toxicol Clin Toxicol 1996;34:475-6.

12. Malizia E, Andreucci G, Alfani F, et al. Acute intoxication with nicotine alkaloids and cannabinoids in children from ingestion of cigarettes. Hum Toxicol 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.

Med J Aust 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. J Forensic Sci 1986;31(4):1492-8.

18. Jaffe AM, Gephardt D, and Courtemanche L. Poisoning due to ingestion of veratrum viride

(false hellebore). J Emerg Med 1990;8:161-7.

19. Quatrehomme G, Bertrand F, Chauvet C, et al. Intoxication from veratrum album. Hum Exp

Toxicol 1993;12:111-5.
74 • OTHER INSECTICIDES

CHAPTER 8

Other Insecticides,

Acaricides, and Repellents

This chapter discusses insecticides, acaricides, and repellents that have toxicologic characteristics distinct from the insecticides discussed in previous chapters. 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

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 GI

decontamination

• Severe CNS symptoms may

require intensive care

management
OTHER INSECTICIDES • 75

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, incoordination, 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 contamination 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, gastrointestinal 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.1

 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)
76 • OTHER INSECTICIDES

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 absorbed 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 followed 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 Unconsciousness and respiratory depression signify life-threatening brain injury. Cyanosis, 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 serum 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.1

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.

2. Gastrointestinal decontamination. In acute poisonings, if a large amount

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)
OTHER INSECTICIDES • 77

has been ingested and the patient is seen within one hour of exposure, gastrointestinal 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 emesis 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 electrolyte solutions to sustain urinary excretion of borate. Monitor fluid balance and

serum electrolytes (including bicarbonate capacity) regularly. Monitor cardiac

status by ECG. 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 frequently than hemodialysis.1

6. Seizures should be controlled as recommended for other agents and outlined 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 generalCommercial Products

(Continued)

Demon

Flectron

Folcord

KafilSuper

NRDC 149

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)
78 • OTHER INSECTICIDES

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 products, 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 efficient.

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, specialized medical treatment should be obtained.

3. Gastrointestinal decontamination. If chlordimeform has been ingested

no more than an hour prior to treatment, consider gastrointestinal decontamination 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 hematuria 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.

Commercial Products

(Continued)

tetramethrin

Neopynamin

tralomethrin

SAGA

Tralex

SULFUR

many commercial products

nr = not registered or withdrawn
OTHER INSECTICIDES • 79

Toxicology

Chlorobenzilate is moderately irritating to the skin and eyes. Although structurally similar to DDT, chlorobenzilate is much more rapidly excreted following

absorption, chiefly in the urine as the benzophenone and benzoic acid derivatives. 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, specialized 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 administration 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 systemic 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 cancelled in the United States.
80 • OTHER INSECTICIDES

Treatment

1. Skin decontamination. Wash skin with soap and water. Remove contamination from the eyes by prolonged flushing with clean water or saline.

2. Gastrointestinal decontamination. Management of poisonings by ingestion should proceed on the assumption that cyhexatin is toxic, even though

rodent LD50 values are fairly high, and no human poisonings have been reported. Treatment should be as with other organotin compounds.

DIETHYLTOLUAMIDE (DEET)

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 toxicity.16 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 formulated 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-existing 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 concentrations 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, 23,24 The

more frequent cause of systemic toxicity has been ingestion: deliberate in adults

and accidental in young children.16,17
OTHER INSECTICIDES • 81

Manifestations of toxic encephalopathy have been behavioral disorders including 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 carbamoyl 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 repeated 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% DEET.25 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 metabolites 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 DEET.21

2. Gastrointestinal decontamination. If a substantial amount of DEET

has been ingested within an hour of treatment, gastrointestinal decontamination should be considered as outlined in Chapter 2. Induced emesis is
82 • OTHER INSECTICIDES

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 ingestion 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 ectoparasites on livestock, as well as crawling insects in homes and work buildings. 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 hazard to humans because of high inherent toxicity, and the possibility that children 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 toxicity.26, 27 Large loads of absorbed 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, children are still at great risk because of their smaller body mass compared to adults

in relation to the amount ingested.27
OTHER INSECTICIDES • 83

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 intracellular 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, specialized 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.
84 • OTHER INSECTICIDES

3. Calcium and magnesium. If the victim is fully alert, and if vomiting does

not totally prevent swallowing of a neutralizing agent, prompt oral administration 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. Magnesium-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 bicarbonate 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.

8. 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 12 years: 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.
OTHER INSECTICIDES • 85

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 continued 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 wettable 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 systemic toxicity is low. Methemoglobinemia is a theoretical risk from chloraniline

formed hydrolytically, but no reports of this form of toxicity have been reported 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.
86 • OTHER INSECTICIDES

METHOPRENE

Methoprene is a long chain hydrocarbon ester active as an insect growth

regulator. It is effective against several insect species. Formulations include slowrelease 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 poisonings 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 irritation 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.
OTHER INSECTICIDES • 87

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 pyrethrins, 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 combined with additional pesticides (sometimes highly toxic) in the technical product

or tank-mixed with other pesticides at the time of application. AASTAR (discontinued 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. However, systemic toxicity by inhalation and dermal absorption is low. Although limited 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 nervous system. Seizures have been reported in severe cases of pyrethroid intoxication. Of 573 cases reviewed in China, there were 51 cases with disturbed

consciousness and 34 cases with seizures. Of those, only 5 were from occupational 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 seizures in humans from exposure to permethrin.

Apart from central nervous system toxicity, some pyrethroids do cause distressing 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-
88 • OTHER INSECTICIDES

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, 37 Sensations 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 experience 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, dizziness, 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 formulations 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 toxicity.35

Treatment

1. Skin decontamination. Wash skin promptly with soap and water as outlined in Chapter 2. If irritant or paresthetic effects occur, obtain treatment by a

physician. Because volatilization of pyrethroids apparently accounts for paresthesia affecting the face, strenuous measures should be taken (ventilation, protective 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, 38 They are safe for application 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 contamination. The eye should be treated immediately by prolonged flushing of the eye

with copious amounts of clean water or saline. If irritation persists, obtain professional ophthalmologic care.

3. Gastrointestinal decontamination. If large amounts of pyrethroids, especially the cyano-pyrethroids, have been ingested and the patient is seen soon
OTHER INSECTICIDES • 89

after exposure, consider gastrointestinal decontamination as outlined in Chapter 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 probably 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 characteristic smell of rotten eggs may aid in the diagnosis. An adult has survived ingestion of 200 grams.40

Ingested colloidal sulfur is efficiently absorbed by the gut and is promptly

excreted in the urine as inorganic sulfate.
90 • OTHER INSECTICIDES

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 children. If diarrhea is severe, oral or intravenous administration of glucose and/or

electrolyte solutions may be appropriate.

References

1. Litovitz TL, Klein-Schwartz W, Oderda GM, and Schmitz BF. Clinical manifestations of

toxicity in a series of 784 boric acid ingestions. Am J Emerg Med 1988;6(3):209- 13.

2. Restuccio A, Mortensen ME, and Kelley MT. Fatal ingestion of boric acid in an adult. Am J

Emerg Med 1992;10(6):545-7.

3. Ishii Y, Fujizuka N, Takahashi T, et al. A fatal case of acute boric acid poisoning. Clin Toxicol

1993;31(2):345- 52.

4. Goldbloom RB and Goldbloom A. Boric acid poisoning. J Pediatr 1953; 43(6):631- 43.

5. Wong LC, Heimbach MD, Truscott DR, and Duncan BD. Boric acid poisoning. Can Med

Assoc J 1964;90:1018-23.

6. Ducey J and Williams DB. Transcutaneous absorption of boric acid. J Pediatr 1953;43(6):644-

51.

7. Linden CH, Hall AH, Kulig KW, and Rumack BH. Acute ingestions of boric acid. Clin

Toxicol 1986;24(4):269-79.

8. Hu X, Wegman DG, Eisen EA, et al. Dose related acute irritant symptom responses to

occupational exposure to sodium borate dusts. Br J Ind Med 1992;49:706-13.

9. Garabrant DH, Bernstein L, Peters JM, et al. Respiratory effects of borax dust. Br J Ind Med

1985;42:831-7.

10. Schillinger BM, Berstein M, Goldbert LA, and Shalita AR. Boric acid poisoning. J Am Acad

Dermatol 1982;7(5):667-73.

11. O’Sullivan K and Taylor M. Chronic boric acid poisoning in infants. Arch Dis Child

1983;58:737-49.

12. Segar WE. Peritoneal dialysis in the treatment of boric acid poisoning. New Engl J Med,

1960;262(16):798-800.

13. Folland DS, Kimbrough RD, Cline RE, et al. Acute hemorrhagic cystitis. JAMA

1978;239(11):1052-5.

14. Arima T, Morooka H, Tanigawa T, et al. Methemoglobinemia induced by chlorphenamidine.

Acta Med Okayama 1976;30:57-60.
OTHER INSECTICIDES • 91

15. Ravindran M. Toxic encephalopathy from chlorobenzilate poisoning: Report of a case. Clin

Electroencephalogr 1978;9(4):170-2.

16. Veltri JC, Osimitz TG, Bradford DC, et al. Retrospective analysis of calls to poison control

centers resulting from exposure to the insect repellent N, N-diethyltoluamide (DEET) from

1985-1989. Clin Toxicol 1994;32:1.

17. Tenebein M. Severe toxic reactions and death following ingestion of diethyltoluamide-containing insect repellents. JAMA 1987;258:1509.

18. Maibach HI and Johnson HL. Contact urticaria syndrome. Arch Dermatol 1975;111:726.

19. Wantke F, Focke M, Hemmer W, et al. Generalized urticaria induced by a diethyltoluamidecontaining insect repellent in a child. Contact Dermatitis 1996;35(3):186.

20. Reuveni H.and Yagupsky P. Diethyltoluamide-containing insect repellent: Adverse effects in

worldwide use. Arch Dermatol 1982;118:582.

21. Stinecipher J and Shaw J. Percutaneous permeation of N,N-diethyl-m-toluamide (DEET)

from commercial mosquito repellents and the effect of solvent. J Toxicol Environ Health

1997;52:119.

22. Lipscomb JW, Kramer JE, and Leikin 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. J Pediatr

1979;95:140-2.

24. Pronczuk de Garbino J and Laborda 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. Yolken R, Konecny P, and McCarthy P. Acute fluoride poisoning. Pediatrics 1976;58(1):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 JP, and Whitford GM. Acute fluoride poisoning from a

public water system. New Engl J Med 1994;330(2):95-9.

29. Swanson L, Filandrinos 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 F and Goetz C. Systemic fluoride intoxication with leukocytosis and pyrexia.

Vet Hum Toxicol 1993;35(4):351.

31. Spak CJ, Sjöstedt S, Eleborg L, 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 hyperkalemia. Chest 1980;78:660.

33. Saunders LD, Ames RG, Knaak JB, et al. Outbreak of omite-cr-induced dermatitis among

orange pickers in Tulare County, California. J Occup Med 1987;29:409-13.

34. Dorman DC and Beasley VR. Neurotoxicology of pyrethrin and the pyrethroid insecticides.

Vet Hum Toxicol 1991;33(3):238-43.

35. He F, Wang S, Lui L, et al. Clinical manifestations and diagnosis of acute pyrethroid poisoning. Arch Toxicol 1989;63:54-8.

36. Tucker SB and Flannigan SA. Cutaneous effects from occupational exposure to fenvalerate.

Arch Toxicol 1983;54:195-202.

37. Flannigan SA, Tucker SB, Key MM, et al. Synthetic pyrethroid insecticides: A dermatological

evaluation. Br J Ind Med 1985;42:363-72.
92 • OTHER INSECTICIDES

38. Tucker SB, Flannigan SA, and Ross CE. Inhibitions of cutaneous paresthesia resulting from

synthetic pyrethroid exposure. Int J Dermatol 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.
Section III

HERBICIDES
94 •

CHLOROPHENOXY

HERBICIDES

CHAPTER 9

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 combinations. 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 formulated 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. Excretion 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, diarrhea, anorexia, weight loss, ulcers of the mouth and pharynx, and toxic injury

to the liver, kidneys, and central nervous system. Myotonia (stiffness and incoordination 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 EEG 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 electrocarHIGHLIGHTS

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, GI

decontamination

• Administer IV

• Forced alkaline diuresis
 • 95

CHLOROPHENOXY

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; therefore, extraordinary doses may produce hyperthermia from increased production of body heat.5

In the manufacture of some of these herbicides, other more toxic substances 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-D.8

 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.

Signs and Symptoms of Poisoning

Chlorophenoxy compounds are moderately irritating to skin and mucous

membranes. Inhalation of sprays may cause burning sensations in the nasopharynx and chest, and coughing may result. Prolonged inhalation sometimes causes

dizziness. Adjuvant chemicals added to enhance foliage penetration might account 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, diarrhea, 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, probCommercial 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
96 •

CHLOROPHENOXY

HERBICIDES

ably secondary to the metabolic acidosis that occurs. Muscle weakness and

peripheral neuropathy have been reported after occupational exposure.6

 Convulsions 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 metabolic changes. Metabolic acidosis is manifest as a low arterial pH and bicarbonate 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 commonly 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.3,9 Tachycardia is commonly observed, and hypotension has also been reported.3,4,6 T-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 poisoning.5

 Electromyographic and nerve conduction studies in some recovering patients 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. Poisoning 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 herbicide applicators, their urinary excretion of chlorophenoxy compounds rarely

exceeded 1-2 mg/L.10 The half-life may be much longer in cases of intoxication depending on the extent of absorption and urine pH.

Analyses can be performed at special laboratories usually known to local poison 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.).
 • 97

CHLOROPHENOXY

HERBICIDES

2. Respiratory protection. If any symptoms of illness occur during or following 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 decontamination 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 remains 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 dramatically 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 intravenous solution. It is crucial to monitor serum electrolytes carefully, especially

potassium and calcium.

There may possibly be some hazard to the kidneys when urine concentrations of toxicant are very high, so the integrity of renal function and fluid

balance should be monitored carefully as the chlorophenoxy compound is excreted. 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 herbicides and lack of any other evidence, hemodialysis is not recommended.2
98 •

CHLOROPHENOXY

HERBICIDES

8. Follow-up clinical examination should include electromyographic and

nerve conduction studies to detect any neuropathic changes and neuromuscular junction defects.

General Chemical Structure

References

1. Kohli JD, Khanna RN, Gupta BN, et al. Absorption and excretion of 2,4-dichlorophenoxyacetic. 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. Keller T, 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, and Vaughan 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. Bri 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 localized scleroderma in a weed sprayer. Clin and Exp Dermatol 1994; 19:264-7.

8. O’Reilly JF. 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. Arch Toxicol 1983;54:257-65.

11. Durakovic Z, Durakovic A, Durakovic S, et al. Poisoning with 2,4- dichlorophenoxyacetic

acid treated by hemodialysis. Arch Toxicol 1992;66:518-21.

CI

CI (or CH )

— O — C — O — H 

Ester

Group

Alkyl

Amine

Sodium

H

H

or

3 
PENTACHLOROPHENOL • 99

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% solution in mineral spirits, No. 2 fuel oil, or kerosene. It is used in pressure treatment of lumber at 5% concentration. Weed killers have contained higher

concentrations.

Pentachlorophenol volatilizes from treated wood and fabric. It has a significant 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 combustion 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 unchanged 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 employees with documented skin contact compared to employees without skin

contact.4

 Urticaria has also been reported as an uncommon response in exposed persons.

HIGHLIGHTS

• Absorbed by skin, lung, GI

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
100 • PENTACHLOROPHENOL

The primary toxicological mechanism is increased cellular oxidative metabolism resulting from the uncoupling of oxidative phosphorylation. Heat production 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. Tachycardia 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 environments where hyperthermia is poorly tolerated. Cases of aplastic anemia and

leukemia have been reported which were associated temporally with PCP exposure. Causal relationships in these cases were not established.9

 Peripheral neuropathies have also been reported in some cases of long-term occupational

exposure; however, a causal relationship has not been supported by longitudinal studies.10

Commercial Products

Chlorophen

PCP

Penchlorol

Penta

Pentacon

Penwar

Sinituho

The sodium salt is sodium

pentachlorophenate.
PENTACHLOROPHENOL • 101

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 infants 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 nanogram-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 consistent 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, administer 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 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 the

other antipyretics has been tested.

Administer oxygen continuously by mask to minimize tissue anoxia. Unless 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. Follow 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 function, intravenous fluids must be administered very cautiously to avoid increased
102 • PENTACHLOROPHENOL

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 pulmonary status carefully to insure adequate gas exchange, and monitor cardiac status by ECG 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 12 years: 0.05-0.10 mg/kg IV over 2-5 minutes. Repeat 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 PCP has been ingested in a quantity 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.
PENTACHLOROPHENOL • 103

Chemical Structure

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. J Toxicol Clin Toxicol 1983;20:343.

3. Uhl S, Schmid P, and Schlatter C. Pharmacokinetics of pentachlorophenol in man. Arch

Toxicol 1986;58:182-6.

4. O’Malley MA, Carpenter AV, Sweeney MH, et al. Chloracne associated with employment in

the production of pentachlorophenol. Am J Ind Med 1990;17:411-21.

5. Danzo BJ. Environmental xenobiotics may disrupt normal endocrine function by interfering with the binding of physiological ligands to steroid receptors and binding proteins.

Environ Health Perspect 1997;105:294-301.

 6. Tran DQ, Klotz DM, 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, and Verstaete R. Exposure to pentachlorophenol as a

possible cause of miscarriages. Br J Obstet Gynaecol 1995;102:1010-1.

9. Roberts HJ. Aplastic anemia due to pentachlorophenol. New Engl J 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 Hyg Assoc 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. J 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. J 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 management and cooling in 14 patients. Arch Intern Med 1986;146:87-90.
104 • NITROCRESOLS

NITROPHENOLS &

CHAPTER 11

Nitrophenolic and

Nitrocresolic Herbicides

These highly toxic chemicals have many uses in agriculture worldwide, as herbicides (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

LD50s 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 between 5 and 14 days.1

 Blood and tissue concentrations tend to increase progressively 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 chapter 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.

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
 • 105

NITROPHENOLS &

NITROCRESOLS

 Cataracts occur in laboratory animals given nitrophenols, and have occurred in humans, both as a result of ill-advised medicinal use and as a consequence 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, headache, 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 immediately life-threatening intoxication. Labored breathing and cyanosis are consequences 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 poisoning.2 In cases of survival of severe poisoning, complete resolution of symptoms 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 20° 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

Unicrop DNBP

Vertac

Vertac General Weed Killer

Vertac Selective Weed Killer

dinoseb acetate*

Aretit

dinoseb methacrylate*

Acricid

Ambox

binapacryl

(Continued on the next page)
106 • NITROCRESOLS

NITROPHENOLS &

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 temperature 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 confuse 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

References

1. Leftwich RB, Floro JF, 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 Industrial Toxicology, 4th ed.

Boston: John 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.

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
 • 107

NITROPHENOLS &

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. Toxicol Lett 1995;81:115-23.

5. Smith WD. An investigation of suspected dinoseb poisoning after agricultural use of a herbicide. 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 management and cooling in 14 patients. Arch Intern Med 1986;146:87-90.
108 • PARAQUAT & DIQUAT

CHAPTER 12

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 intentional 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 management procedures.

PARAQUAT

Toxicology

When ingested in adequate dosage (see below), paraquat has life-threatening effects on the gastrointestinal tract, kidney, liver, heart, and other organs.

The LD50 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 generation of free radicals with oxidative damage to lung tissue.1,2 While acute pulmonary 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 patients 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

HIGHLIGHTS

• Life-threatening effects on

GI 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 GI

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 & DIQUAT • 109

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 produce 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 enzymes 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 compared 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 mucosal 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, including those in the lung. Unfortunately, this pathogenic sequence may occur

in the first several hours following paraquat ingestion, generating lethal concentrations of paraquat in lung tissue before therapeutic measures to limit absorption 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
110 • PARAQUAT & DIQUAT

that methods for enhancing paraquat disposition several hours following ingestion 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 dyspnea 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 mg 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 horizontal 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 jaundice, 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 Toxicology section.
PARAQUAT & DIQUAT • 111

DIQUAT

Toxicology

Diquat poisoning is much less common than paraquat poisoning, so that

human reports and animal experimental data for diquat poisoning are less extensive than for paraquat. Systemically absorbed diquat is not selectively concentrated 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 consistent pathologic brain changes noted in reported fatal cases of diquat poisoning. 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 ulcerated 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, combativeness, 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 symptoms of poisoning by ingested diquat are similar to those from paraquat, reflecting 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.
112 • PARAQUAT & DIQUAT

If the patient survives several hours or days, circulatory function may fail

due to dehydration. Hypotension and tachycardia can occur, with shock resulting in death. Other cardiorespiratory problems may develop, such as toxic cardiomyopathy 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 tissues has occurred, measures to remove bipyridyls from the blood are very inefficient in reducing the total body burden.

 Several strategies are being tested to reduce the frequency of these occurrences. These include the addition of emetics, stenching agents, gelling substances, 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 magnitude 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.
PARAQUAT & DIQUAT • 113

Paraquat and diquat can be measured in blood and urine by spectrophotometric, 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 concentrations 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 prolonged 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 ingested, 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 12 years: 100-150 g.

• Children under 12 years: 2 gm/kg body weight.

Caution: Hypercalcemia and fecaliths have sometimes occurred following 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 already traumatized tissues. 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. 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.
114 • PARAQUAT & DIQUAT

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 patient 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 environment, 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 intensive 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 intravenous fluids: isotonic saline, Ringer’s solution, or 5% glucose in water. This

is highly advantageous early in poisonings as a means of correcting dehydration, 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 extracorporeal 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 considered. 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 marginal 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 constituents are depleted by the procedure.
PARAQUAT & DIQUAT • 115

8. Seizure control. Convulsions and psychotic behavior sometimes encountered 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: corticosteroids, superoxide dismutase, propranolol, cyclophosphamide, vitamin E, riboflavin, 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 associated 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 12 years: 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
116 • PARAQUAT & DIQUAT

General Chemical Structures

References

1. Pond SM. Manifestations and management of paraquat poisoning. Med J Aust 1990;152:256-9.

2. Giulivi C, Lavagno CC, Lucesoli F, et al. Lung damage in paraquat poisoning and hyperbaric oxyen exposure: superoxide-mediated inhibition of phospholipase A2. Free Radic

Biol Med 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, Garnier R, Dally S, et al. Prognosis and treatment of paraquat poisoning: A

review of 28 cases. J Toxicol Clin Toxicol 1982;19:461-74.

6. Harsanyi L, Nemeth A, and Lang A. Paraquat (gramoxone) poisoning in south-west Hungary, 1977-1984. Am J Forensic 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 Emerg Med 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, Meredith TJ, and Buckley BM. Paraquat poisoning: Clinical features and immediate

general management. Hum Toxicol 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;18:111-23.

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, Agnetti V, Piredda M, et al. Acute and persistent Parkinsonism after use of diquat.

Neurology 1992;42:261-3.

15. Proudfoot AT, Stewart MS, Levitt T, et al. Paraquat poisoning: Significance of plasma-paraquat

concentrations. Lancet 1979;2:330-2.

CI CI

CH N N

CI

+ +

–

3 CH

2 CI

3

Paraquat

N N

CH

+ +

–

2 CH 2 Br

2

Diquat
PARAQUAT & DIQUAT • 117

16. Lin JL, Wei MC, and Liu YC. 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 poisoning. A case report. J Thoracic Cardiovas Surg 1985;89:734-42.
118 • OTHER HERBICIDES

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 selectively 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 LD50 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 histories, and some unpublished reports. The listing cannot be considered inclusive,

either of herbicide products or of effects.
OTHER HERBICIDES • 119

Aliphatic acids trichloroacetic

acid

dichloropropionic

acid (dalapon)

TCA

Dalapon,

Revenge

5,000

970

Irritating to

skin, eyes,

and respiratory

tract.

Benzamide pronamide Kerb, Rapier 8,350 Moderately

irritating to eyes

Benzoic,

anisic acid

derivatives

trichlorobenzoic

acid

dicamba

TCBA, Tribac,

2,3,6-TBA

Banvel

1,500

 2,700

Moderately

irritating to skin

and respiratory

tract.

Benzonitriles dichlobenil Casoron,

Dyclomec, Barrier

>4,460 Minimal toxic,

irritant effects

Benzothiadiazinone

dioxide

bentazone Basagran >1,000 Irritating to eyes

and respiratory

tract.

Carbamates and

Thiocarbamates

(herbicidal)

asulam

terbucarb

butylate

cycloate

pebulate

vernolate

EPTC

diallate

triallate

thiobencarb

Asulox

Azac, Azar

Sutan

Ro-Neet

Tillam, PEBC

Vernam

Eptam, Eradicane

Di-allate

Far-go

Bolero, Saturn

>5,000

>34,000

3,500

2,000

921

1,800

1,630

395

1,675

1,300

Some are

irritating to

eyes, skin, and

respiratory tract,

particularly in

concentrated

form.

Some may be

weak inhibitors

of cholinesterase.

Chemical Class Generic Name

Proprietary

Names

Acute Oral LD50

mg/kg

Known or

Suspected

Adverse Effects

Acetamides metolachlor Dual, Pennant,

others

2,780 Irritating

to eyes

and skin.

Anilides alachlor

propachlor

propanil

Lasso, Alanox

Ramrod, Bexton,

Prolex

DPA, Chem

Rice, Propanex,

Riselect, Stam,

Stampede

1,800

710

>2,500

Mild irritant.

Dermal irritant

and sensitizer.

Irritating to skin,

eyes, and

respiratory tract.

TOXICITY OF COMMON HERBICIDES
120 • OTHER HERBICIDES

Chemical Class Generic Name

Proprietary

Names

Acute Oral LD50

mg/kg

Known or

Suspected

Adverse Effects

Fluorodinitrotoluidine

compounds

benfluralin

dinitramine

ethalfluralin

fluchloralin

profluralin

trifluralin

Benefin, Balan,

Balfin, Quilan

Cobex

Sonalan

Basalin

Tolban

Treflan

>10,000

3,000

>10,000

1,550

1,808

>10,000

May be mildly

irritating. These

herbicides do not

uncouple

oxidative

phosphorylation

or generate

methemoglobin.

Isoxazolidinone clomazone Command 1,369 May be

moderately

irritating.

Nicotinic acid

isopropylamine

derivative

imazapyr Arsenal >5,000 Irritating to eyes

and skin. Does

not contain

arsenic.

Oxadiazolinone oxadiazon Ronstar >3,500 Minimal toxic

and irritant

effects.

Phosphonates glyphosate

fosamine

ammonium

Roundup,

Glyfonox

Krenite

4,300

>5,000

Irritating to eyes,

skin, and upper

respiratory tract.

Irritating to eyes,

skin, and upper

respiratory tract.

TOXICITY OF COMMON HERBICIDES

Chloropyridinyl triclopyr Garlon, Turflon 630 Irritating to skin

and eyes.

Cyclohexenone

derivative

sethoxydim Poast 3,125 Irritating to skin

and eyes.

Dinitroaminobenzene

derivative

butralin

pendimethalin

oryzalin

Amex

Tamex

Prowl, Stomp,

Accotab,

Herbodox,

Go-Go-San,

Wax Up

Surflan, Dirimal

12,600

>5,000

2,250

>10,000

May be

moderately

irritating.

These herbicides

do not uncouple

oxidative

phosphorylation

or generate

methemoglobin.

Carbanilates chlorpropham Sprout-Nip

Chloro-IPC

3,800 Skin irritants.

May generate

methemoglobin

at high dosage.
OTHER HERBICIDES • 121

Triazines ametryn

atrazine

cyanazine

desmetryn

metribuzin

prometryn

propazine

simazine

terbuthylazine

tertutryn

prometon

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

1,750

1,780

288

1,390

1,100

5.235

>7,000

>5,000

2,000

2,500

2,980

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.

Triazole amitrole,

aminotriazole

Amerol, Azolan,

Azole, Weedazol

>10,000 Minimal systemic

toxicity. Slight

irritant effect.

TOXICITY OF COMMON HERBICIDES

Chemical Class Generic Name

Proprietary

Names

Acute Oral LD50

mg/kg

Known or

Suspected

Adverse Effects

Picolinic acid

compound

picloram Tordon, Pinene 8,200 Irritating to skin,

eyes, and

respiratory tract.

Low systemic

toxicity.

Phthalates chlorthaldimethyl

endothall

Dachthal, DCPA

Aquathol

>10,000

51

Moderately

irritating to eyes.

Free acid is highly

toxic. Irritating to

skin, eyes and

respiratory tract.

See Chapter 18.
122 • OTHER HERBICIDES

Chemical Class Generic Name

Proprietary

Names

Acute Oral LD50

mg/kg

Known or

Suspected

Adverse Effects

Urea

derivatives

chlorimuron

ethyl

chlorotoluron

diuron

flumeturon

isoproturon

linuron

methabenzthiazuron

metobromuron

metoxuron

monolinuron

monuron

neburon

siduron

sulfemeturonmethyl

tebuthiuron

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

Aresin

Monuron

Granurex,

Neburex

Tupersan

Oust

Spike, Tebusan

>4,000

>10,000

>5,000

8,900

1,826

1,500

5,000

2,000

3,200

2,100

3,600

>11,000

>7,500

>5,000

644

Systemic

toxicity is

unlikely unless

large amounts

have been

ingested.

Many

substituted

ureas are

irritating to

eyes, skin, and

mucous

membranes.

TOXICITY OF COMMON HERBICIDES

Uracils bromacil

lenacil

terabacil

Hyvar

Venzar

Sinbar

5,200

>11,000

>5,000

Irritant to skin,

eyes, and

respiratory tract.

Moderately

irritating.
OTHER HERBICIDES • 123

Confirmation of Poisoning

Although there are analytical methods for residues of many of the herbicides 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 recent 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 obtained 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. Management 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 already 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, Ringer’s

solution, or Ringer’s lactate to restore extracellular fluid volume and electrolytes.

Follow this with oral nutrients as soon as fluids can be retained.
124 • OTHER HERBICIDES

4. Supportive measures are ordinarily sufficient for successful management

of excessive exposures to these herbicides (endothall is an exception—see Chapter 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.
Section IV

OTHER PESTICIDES
126 • ARSENICALS

CHAPTER 14

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, antimony, 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 biochemical behavior, it resembles phosphorus, competing with phosphorus analogs 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 (methylated) 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 compound, its solubility characteristics, the gastric pH, gastrointestinal motility, and

gut microbial transformation. Arsine exposure occurs primarily through inhalation, 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 mechaHIGHLIGHTS

• 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 GI symptoms

• In chronic cases, muscle

weakness, fatigue,

weight loss,

hyperpigmentation,

hyperkeratosis, Mees

lines

Treatment:

• GI decontamination

• Chelation therapy

Dimercaprol (BAL) or

DMPS to accelerate

arsenic excretion
ARSENICALS • 127

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 phosphorylation. 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 patient. 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 exposure. 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 proteinuria, hematuria, glycosuria, oliguria, casts in the urine, and, in severe poisoning, 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 enzymes and jaundice. Injury to blood-forming tissues may cause anemia, leukopenia, 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 contribute.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 diagnose. Neurologic, dermal, and nonspecific manifestations are usually more prominent than the gastrointestinal effects that characterize acute poisoning. Muscle

Commercial Products

(Many have been discontinued)

arsenic acid

Hi-Yield Dessicant H-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)
128 • ARSENICALS

weakness and fatigue can occur, as can anorexia and weight loss. Hyperpigmentation is a common sign, and tends to be accentuated in areas that are

already more pigmented, such as the groin and areola. Hyperkeratosis is another 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 undergone 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 determine blood arsenic concentration are available; however blood levels tend

to poorly correlate with exposure except in the initial acute phase.11,13 Special metal-free acid-washed containers should be used for sample collection.

Arsenic excretion above 100 mcg per day should be viewed with suspicion

and the test should be repeated.

Excretions above 200 mcg 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 mcg 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. HowCommercial Products

(Continued)

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

sodium arsenate

disodium arsenate

Jones Ant Killer

sodium arsenite

Prodalumnol Double

Sodanit

zinc arsenate
ARSENICALS • 129

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 determine 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 absorption spectrometric analysis. The latter method is preferred. Blood concentrations in excess of about 100 mcg 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 exposure. Levels in unexposed people are usually less than 1 mg/kg; levels in individuals 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 ingested within the first hour of treatment, consideration should be given to GI

decontamination, as outlined in Chapter 2. Because poisoning by ingested arsenic almost always results in profuse diarrhea, it is generally not appropriate to

administer a cathartic.

3. Intravenous fluids. Administer intravenous fluids to restore adequate hydration, support urine flow, and correct electrolyte imbalances. Monitor intake/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.
130 • ARSENICALS

4. Cardiopulmonary monitoring. Monitor cardiac status by ECG to detect

ventricular arrhythmias including prolonged Q-T interval and ventricular tachycardia, and toxic myocardiopathy (T wave inversion, long S-T interval).

5. Chelation therapy. Administration of Dimercaprol (BAL) is usually indicated 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 administered. When 24-hour excretion falls below 50 mcg per day, it usually is

advisable to discontinue the chelation therapy.

RECOMMENDED INTRAMUSCULAR DOSAGE OF BAL

(DIMERCAPROL) IN ARSENIC POISONING

Severe Poisoning Mild Poisoning

1st day 3.0 mg/kg q4h 2.5 mg/kg q6h

(6 injections) (4 injections)

2nd day 3.0 mg/kg q4h 2.5 mg/kg q6h

(6 injections) (4 injections)

3rd day 3.0 mg/kg q6h 2.5 mg/kg q12h

(4 injections) (2 injections)

Each of the following 3.0 mg/kg q12 hr 2.5 mg/kg qd

days for 10 days, or (2 injections) (1 injection)

until recovery

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 abdomen, tremor, restlessness, tachycardia, hypertension, and fever. Coma and convulsions 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 limited effectiveness for arsenic exposure in experimental models.18
ARSENICALS • 131

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 12 years: 0.1 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 effectiveness 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 maintain 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 protect renal function in the face of hemolysis occurring as part of the acute

poisoning.
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 operations 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 (hemoglobinuria) 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 evident. 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 extracellular fluid composition and to enhance arsenic elimination if renal failure

occurs, but it is not very effective in removing arsine carried in the blood.

HIGHLIGHTS

• Powerful hemolysin

Signs and Symptoms:

• Malaise, dizziness, nausea,

abdominal pain

• Hemoglobinuria and

jaundice.

Treatment:

• Supportive

• Exchange transfusion may

be considered
ARSENICALS • 133

INORGANIC TRIVALENT

Arsenic trioxide

Sodium arsenite

Calcium arsenite

Copper arsenite

(Acid copper arsenite)

Copper acetoarsenite

Arsine

“White arsenic.” Arsenous oxide. Has been

discontinued but still may be available

from prior registrations.

Mono-calcium arsenite, London purple.

Flowable powder for insecticidal use on

fruit. All uses discontinued in the U.S.

Wettable powder, for use as insecticide,

wood preservative. All uses discontinued

in the U.S.

Insecticide. Paris green, Schweinfurt green,

Emerald green, French green, Mitis green.

No longer used in the U.S.; still used

outside U.S.

Sodanit, Prodalumnol Double. All uses

discontinued in the U.S.

INORGANIC PENTAVALENT

Arsenic acid

Sodium arsenate

Hi-Yield Dessicant H-10, Zotox. Water

solutions used as defoliants, herbicides, and

wood preservatives.

Disodium arsenate. Jones Ant Killer. All

uses discontinued, but may still be

encountered from old registration.

Not a pesticide. Occasionally generated

during manufacture of arsenicals.

O

O

As As O

Na O O As

O 

Ca 

O As O

As O

(approx.)

HO Cu O O As

O 

Cu (O C

3Cu

CH ) 3 2 

(O As O) 2 

H H 

As

H

HO 

HO 

As O

OH

NaO 

NaO 

As O

OH

General Chemical Structures
134 • ARSENICALS

Calcium arsenate

Lead arsenate

Zinc arsenate

Gypsine, Soprabel. Limited use in the

U.S.; wettable powder used as insecticide

outside the U.S.

Non-selective herbicide, defoliant,

silvicide. Bolate, Bolls-Eye, Bophy, Dilic,

Kack, Phytar 560, Rad-E-Cate 25, Salvo.

ORGANIC (PENTAVALENT)

Cacodylic acid (sodium cacodylate)

Methane arsonic acid

Monosodium methane arsonate

Disodium methane arsonate

Monoammonium methane arsonate

MAA. Non-selective herbicide.

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.

DSMA. Selective post-emergence

herbicide, silvicide. Ansar 8100, Arrhenal,

Arsinyl, Crab-E-Rad, Di-Tac, DMA,

Methar 30, Sodar, Weed-E-Rad 360.

MAMA. Selective post-emergence

herbicide. No longer used in the U.S.

Powder once used in U.S. as insecticide

on potatoes and tomatoes.

O 

O

Pb As O

OH

O 

O

Zn As O O

O O O

Zn

O

As Zn

CH 

O OH

(or Na)

As

3 CH 3 

CH 

O OH

As

3 OH 

CH 

O OH

As

3 OH 

CH 

O ONa

As

3 ONa 

CH 

O OH

As

3 4 ONH

Tricalcium arsenate, Spra-cal, Turf-Cal.

Flowable powder formulations used

against weeds, grubs. No longer used in

the U.S.

O 

O

Ca As O O

O O O

Ca

O

As Ca
ARSENICALS • 135

References

1. Malachowski ME. An update on arsenic. Clin 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 intoxication. A study of 41 cases with observations on the effects of BAL (2,3-dimercaptopropanol). N Engl J Med 1956;254:401-9.

7. Donofrio PD, Wilbourn AJ, Albers JW, et al. Acute arsenic intoxication presenting as GuillainBarre-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 León P. An unhappily married man with thick soles.

Lancet 1996;347:1596.

10. Lin TH, Huang YL, and Wang MY. Arsenic species in drinking water, hair, fingernails, and

urine of patients with blackfoot disease. J Toxicol Environ Health 1998;53A:85-93.

11. Fesmire FM, Schauben JL, and Roberge RJ. Survival following massive arsenic ingestion.

Am J Emerg Med, 1998;6(6):602-6.

12. ACGIH. 1997 TLVs 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 following ingestion of marine organisms by volunteers. Environ Res 1994;66:44-51.

15. Baselt RA and Cravey RH. Arsenic. In: Disposition of Toxic 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.

Calcium acid methane arsonate CAMA. Selective post-emergence

herbicide. Calar, Super Crab-E-RadCalar, Super Dal-E-Rad. CH 

O O Ca

As

3 CH OH HO 3 

O O

As
136 • ARSENICALS

18. Kreppel H, Reichl FX, Forth W, and Fichtl B. Lack of effectiveness of d-penicillamine in

experimental arsenic poisoning. Vet Hum Toxicol 1989;31:1-5.

19. Mückter 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 Hyg Assoc J 1979;40:A56-61.

21. Fowler BA and Weissberg JB. Arsine poisoning. New Engl J Med 1974;291:1171-4.

22. Rathus E, Stingon RG, and Putman JL. Arsine poisoning, country style. Med J Aust 1979;1:163-6.
FUNGICIDES • 137

CHAPTER 15

Fungicides

Fungicides are extensively used in industry, agriculture, and the home and garden for a number of purposes, including: protection of seed grain during storage, 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 protection 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 absorbed. Second, many fungicides are formulated as suspensions of wettable powders 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 responsible 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, recommendations for management of poisonings and injuries are set forth. For fungicides 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

• GI decontamination

• Intravenous fluids

Contraindicated:

• Atropine. Fungicides are

not cholinesterase

inhibitors
138 • FUNGICIDES

Commercial Products

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.

SUBSTITUTED BENZENES

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 dichloromethoxyphenol 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.1 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 (enhances 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 hexachlorocyclohexane, 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.2

 This 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 (porphyrin-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 sufficiently prompt that occupationally exposed workers usually show only slight
FUNGICIDES • 139

elevation of blood HCB concentrations. HCB is sometimes present in blood

specimens from “non-occupationally exposed” persons in concentrations of up

to 5 mcg per liter. Residues in food are the probable cause.

Pentachloronitrobenzene is used to dress seed and treat soil. Formulations include emulsifiable concentrates, wettable powders, and granules.

Hexachlorobenzene is a minor contaminant to technical PCNB.

High concentrations in prolonged contact with skin have caused sensitization 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 animals 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 chromatography. Chlorophenol metabolites can be measured in the urine. Although inherited disease and a number of exogenous agents may cause porphyrins to

appear in the urine, a test for porphyrins may be useful for toxicological diagnosis 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 charcoal can be used along with the addition of the cathartic sorbitol to the charcoal 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.
140 • FUNGICIDES

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

Trametan

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 contamination 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 exacerbates 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, vegetables, fruit, and apples. Unlike the N-methyl carbamates (Chapter 5),

thiocarbamates have very little insecticidal potency. A few exhibit weak anticholinesterase activity, but most have no significant effect on this enzyme. Overall,

they are less of a threat to human health than the insecticidal carbamates. Fungicidal thiocarbamates are discussed in this section, while those used as herbicides 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 decomposition 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 considered a fumigant. It must be used in outdoor settings only, and stringent precautions 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.) However, no such occurrences have been reported.
FUNGICIDES • 141

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 facility. Treatment for pulmonary edema should proceed as outlined in Chapter

16, Fumigants.

4. Contraindicated: Metam-sodium is not a cholinesterase inhibitor. Atropine 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 exposed 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 extensively 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.
142 • FUNGICIDES

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 irritation 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 represents 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 positioning, 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. Disposition of thiocarbamates is slow, and their inhibitory effects on enzymes are

slowly reversible.
FUNGICIDES • 143

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. Theoretically, exposure to ziram or ferbam may predispose the individual to Antabuse

reactions if alcohol is ingested after exposure. (See Thiram.) 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 ingestion, 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.
144 • FUNGICIDES

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 coordination 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 acetaldehyde dehydrogenase. They do not induce cholinergic illness or “Antabuse” reactions.

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.

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
FUNGICIDES • 145

THIOPHTHALIMIDES

CAPTAN, CAPTAFOL, AND FOLPET

These agents are widely used to protect seed, field crops, and stored produce. 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 agriculture outside the U.S. Toxicity of these compounds is chiefly due to arsenic

content (see Chapter 14, Arsenical Pesticides).

Commercial Products

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.
146 • FUNGICIDES

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 systemic toxicity of most compounds. The more absorbable organic copper compounds 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 compounds has come from veterinary toxicology (livestock seem uniquely vulnerable) 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 gastrointestinal irritation will worsen with hemetemesis and melanotic stools. Jaundice

and hepatomegaly are common.11,12 Hemolysis can occur, resulting in circulatory 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 contribute 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 medical 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-bycase 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.
FUNGICIDES • 147

Caution: Gastric intubation may pose a serious risk of esophageal perforation 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 intravenous 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 severe (> 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 morphine.

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, Arsenical Pesticides.

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. Phenylmercuric acetate is no longer permitted to be used in the United States.

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

Phenylmercuric Acetate

Agrosan

Setrete

Gallotox

PMAA

Shimmer-ex

Tag HL 331

Unisan
148 • FUNGICIDES

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 compounds 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 incoordination, 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 terminated fatally, and a large percentage of survivors have suffered severe permanent neurologic damage.17-19

Phenylmercuric acetate is not as extremely toxic as the alkyl mercury compounds. It is not as efficiently absorbed from the gut as methyl mercury.21 Phenylmercuric 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 Phenylmercuric compounds have since been banned from latex paint.20

Confirmation of Poisoning

Mercury content of blood and tissues can be measured by atomic absorption spectrometry. Blood levels of 5 mcg/dL or greater are considered elevated

for acute exposure.21 Special procedures are needed for extraction and measurement of organic mercury compounds specifically.
FUNGICIDES • 149

Treatment

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 management of poisoning:

1. Skin decontamination. Skin and hair contaminated by mercury-containing dust or solution should be cleansed with soap and water. Flush contamination from the eyes with clean water. If irritation persists, specialized medical

care should be obtained. See Chapter 2.

2. Gastrointestinal decontamination. Consider gastrointestinal decontamination 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. Dimercaprol (BAL) is contraindicated in these poisonings due to its potential to increase 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-1-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

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 molluscicide (Aquatin 20 EC, discontinued 1995). Tributyltin salts are used as fungicides and antifouling agents on ships. They are somewhat more toxic by the

oral route than triphenyltin, but toxic actions are otherwise probably similar.

Commercial Products

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.
150 • FUNGICIDES

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. Manifestations 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, sufficient 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 washing 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 compound have been ingested in the past hour, measures may be taken to decontaminate 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 experimental 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, copper, 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 fungicides in the U.S. have been discontinued.

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.
FUNGICIDES • 151

Toxicology

Cadmium salts and oxides are very irritating to the respiratory and gastrointestinal tracts. Inhaled cadmium dust or fumes can cause respiratory toxicity 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 hemorrhagic 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 symptoms. 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, followed 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 mcg per day suggests an unusually high body burden.

Treatment

1. Skin decontamination. Skin contamination should be removed by washing with soap and water. Flush contamination from the eyes with copious

amounts of clean water or saline. If irritation persists, specialized medical treatment 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
152 • FUNGICIDES

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 effects 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 vegetables, cereals, coffee, ornamentals, and turf. This product has caused skin irritation 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 cholinesterase inhibitor. It is poorly absorbed across skin; whatever is absorbed is

promptly metabolized and excreted.

Skin injuries to exposed individuals have occurred, and dermal sensitization has been found among agricultural workers exposed to foliage residues.

Commercial Products

MISCELLANEOUS

ORGANIC FUNGICIDES

anilazine*

Dyrene

benomyl

Benex

Benlate

Tersan 1991

cycloheximide*

naramycin

dodine

Carpene

Curitan

Melprex

Venturol

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.
FUNGICIDES • 153

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 toxicity in laboratory animals is moderate. Poisonings in humans have not been

reported. Based on animal studies, ingestion would probably cause nausea, vomiting, 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, peanuts, 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 reported.

Thiabendazole is widely used as an agricultural fungicide, but most experience 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. Thiabendazole 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, suspension concentrate, paste, and dry flowable powder. Used on fruit, cereals,

vegetables, coffee, ornamentals, sugarcane, pineapple, and turf, triadimefon exhibits moderate acute oral toxicity in laboratory animals, but dermal toxicity is
154 • FUNGICIDES

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 fungicides 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 fungicide chlorothalonil. Cutis 1993;52:3120-5.

2. Peters HA, Gocmen A, Cripps DJ, et al. Epidemiology of hexachlorobenzene-induced porphyria in Turkey: Clinical and laboratory follow-up after 25 years. Arch Neurol 1992;39:744-9.

3. Dalvi RR. Toxicology of thiram (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, and Tiberin 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 Dermatitis 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 Chem Toxicol 1993;16:207-25.
FUNGICIDES • 155

11. Agarwal SK, Tiwari SC, and Dash SC. Spectrum of poisoning requiring haemodialysis in a

tertiary care hospital in India. Int J Artif Organs 1993;16:20-3.

12. Lamont 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 poisoning. Ann Intern Med 1975;82:226-9.

14. Jantsch W, Kulig K, and Rumack BH. Massive copper sulfate ingestion resulting in hepatotoxicity. Clin Toxicol 1984-85;22:585-8.

15. POISINDEX®: Copper poisoning. Englewood, CO: Micromedex, 1998.

16. Hantson P, Lievens M, and Mahieu P. Accidental ingestion of a zinc and copper sulfate

preparation. Clin Toxicol 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. New Engl J Med 1971;284:1014-5.

20. Clarkson TW. 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 J Ind 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 J Work 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, Rall TW, Niew AS,

et al (eds). Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 3rd ed. New

York: Pergamon Press, 1990, pp. 1605-6.
156 • FUMIGANTS

CHAPTER 16

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 membrane, 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. Liquids 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 reduces 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 naphthalene sublimes. Paraformaldehyde slowly depolymerizes to formaldehyde.

Aluminum phosphide slowly reacts with water vapor in the air to liberate phosphine, an extremely toxic gas. Metam sodium, also a fumigant, is covered under

thiocarbamates in Chapter 15, Fungicides.

Toxicology (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. Toxicity 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

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 • 157

chiefly to effects on the central nervous system. Inhalation of high concentrations for short periods has caused headache, dizziness, nausea, hallucinations,

delirium, progressive paralysis, and death from respiratory failure. More prolonged 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 following 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 tetrachloride 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. Ingestion 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-O-Gas

MeBr

Sobrom 98

methylene chloride*

paradichlorobenzene

HYDROCARBONS

naphthalene

NITROGEN COMPOUNDS

acrylonitrile*

hydrogen cyanide*

hydrocyanic acid

prussic acid

(Continued on the next page)
158 • FUMIGANTS

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 tubular damage. Death is usually due to respiratory or circulatory failure. A powerful 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 poisoning include headache, nausea, vomiting, dizziness, diarrhea, hypotension, cyanosis, 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 cardiac 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 allergic dermatitis. In addition, it has been associated with asthma-like symptoms,

though there remains some controversy as to whether these represent true allergic asthma caused by formaldehyde.6,7,8 High air concentrations may cause laryngeal 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 poisoning. Circulatory collapse and renal failure may follow the devastating effects of

ingested formaldehyde on the gut, leading to death. Paraformaldehyde is a polymer 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 oxidase, 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,

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)

Agtoxin

Alphos

Fumex

Fumitoxin

Phostoxin

Quickfos

Sanifume

Shaphos

others

SULFUR COMPOUNDS

carbon disulfide*

sulfur dioxide

sulfuryl fluoride

Vikane

* Discontinued in the U.S.
FUMIGANTS • 159

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, hemorrhage, 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 neurological 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 concentrations 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 concentrations causes headache, dizziness, nausea, and vomiting. Intensive prolonged

inhalation exposure, or ingestion or dermal exposure (from contact with heavily
160 • FUMIGANTS

treated fabric) may cause hemolysis, particularly in persons afflicted with glucose-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 depression 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 hemolysis.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 complication of exposure to naphthalene with severe hemolysis and resulting hyperbilirubinemia. 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 accidental ingestions, especially by children, have been fairly common, symptomatic 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 produces severe systemic toxicity. It is used as a fumigant by placing solid aluminum

phosphide (phostoxin) near produce or in other storage spaces. Through hydrolysis, phosphine gas is slowly released. Most severe acute exposures have involved 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 understood. 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, tachycardia, 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 developed.16,19 Odor is said to resemble that of decaying fish.

Sulfur dioxide is a highly irritant gas, so disagreeable that persons inhaling it are usually prompted to seek uncontaminated air as soon as possible.

However, laryngospasm and pulmonary edema have occurred, occasionally leading to severe respiratory distress and death. It is sometimes a cause of reactive

airways disease in occupationally exposed persons.
FUMIGANTS • 161

Sulfuryl fluoride has been used extensively for structural fumigation.

Although use experience has generally been good, some fatalities have occurred when fumigated buildings have been prematurely reentered by unprotected 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 twitching, 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. Symptoms 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 exceptional 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 absorption, and 15 mg per 100 mL is consistent with symptoms of acute poisoning.

Inorganic bromide is considerably less toxic than methyl bromide; serum concentrations 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 protective measures must be improved. A bromide concentration over 5 mg per 100

mL requires that the worker be removed from the fumigant-contaminated environment until blood concentrations decline to less than 3 mg per 100 mL.

Methylene chloride is converted to carbon monoxide in the body, generating 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
162 • FUMIGANTS

chromatography. Many halocarbons can be measured in blood by gas chromatographic 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 chromatographically.

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 concentrations 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 particularly 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 likelihood of pulmonary edema.
FUMIGANTS • 163

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 measures 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 fumigant 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 diuresis. 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 intensive care center. Limit victim’s physical activity for at least 4 weeks. Severe

physical weakness usually indicates persistent pulmonary injury. Serial pulmonary 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 pressure 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 disulfide. 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, followed 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.
164 • FUMIGANTS

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, effective in controlling extracellular fluid composition if renal failure occurs.

10. Specific fumigants. Certain specific measures are recommended in poisonings by particular fumigants (carbon disulfide, carbon tetrachloride, naphthalene, 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, intravenously, may be helpful as a tranquilizer. Give as much as is necessary to achieve sedation. Do not give catecholamine-releasing agents

such as reserpine and amphetamines.

• Carbon Tetrachloride: For carbon tetrachloride poisoning, several treatment measures have been suggested to limit the severity of

hepatic necrosis. Hyperbaric oxygen has been used with some success.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 administration 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 flushing 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-
FUMIGANTS • 165

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 protect 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 declines, intravenous infusions must be stopped to prevent fluid overload 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 outcome.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, magnesium 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 thiosulfate — 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.
166 • FUMIGANTS

Dosage of Cyanide Antidotes

Adults:

• Administer oxygen continuously. Hyperbaric oxygen has been evaluated as effective in this condition.25 If respiration fails, maintain pulmonary 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 sodium 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, because 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, administer an infusion of 1.65 mL/kg of 25% sodium thiosulfate at a rate

of 3-5 mL per minute. ... continued
FUMIGANTS • 167

• At this point, determine the hemoglobin content of the pretreatment 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 converting approximately 40% of circulating hemoglobin to methemoglobin. If possible, monitor blood methemoglobin concentrations as

treatment proceeds.

RECOMMENDED DOSAGES OF SUPPLEMENTAL SODIUM

NITRITE AND SODIUM THIOSULFATE BASED ON

HEMOGLOBIN LEVEL

Initial Dose

Hemoglobin Volume of 3% 25% Sodium

Concentration Sodium Nitrite Thiosulfate

g/100 mL mL/kg mL/kg

14.0 0.20 1.00

12.0 0.16 0.83

10.0 0.14 0.68

8.0 0.11 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. J Occup Med 1983;25:879-85.

2. Truss C and Killenberg P. Treatment of carbon tetrachloride poisoning with hyperbaric

oxygen. Gastroenterology 1982;82:767-9.

3. Perez AJ, Courel M, Sobrado J, et al. Acute renal failure after topical application of carbon

tetrachloride. Lancet 1987;1:515-6.

4. Dykes MH. Halogenated hydrocarbon ingestion. Intern Anesthesiol Clin 1970;8:357-68.

5. Amir D. The spermicidal effect of ethylene dibromide in bulls and rams. Mol Reprod Dev

1991;28:99-109.
168 • FUMIGANTS

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. J Emerg Med 1988;6:401-4.

10. Yen D, Tsai J, 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. Br J Ind Med 1993;50:155-9.

12. Deschamps FJ and Turpin JC. Methyl bromide intoxication during grain store fumigation.

Occupat Med 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-307-11.

16. Katira R, Elhence GP, Mehrotra ML, et al. A study of aluminum phosphide poisoning with

special reference to electrocardiographic changes. J Assoc Physicians India 1990;38:471-3.

17. Singh S, Singh D, Wig N, et al. Aluminum phosphide ingestion: A clinico-pathologic study.

Clin Toxicol 1996;34:703-6.

18. Singh RB, Singh RG, and Singh U. Hypermagnesemia following aluminum phosphide

poisoning. Int J Clin Pharmacol Ther Toxicol 1991;29:82-5.

19. Gupta S and Ahlawat SK. Aluminum phosphide poisoning: A review. Clin Toxicol 1995;33:19-24.

20. Scheuerman EH. Suicide by exposure to sulfuryl fluoride. J Forensic Sci 1986;31:1154-8.

21. Ruprah M, Mant TGK, and Flanagan RJ. Acute carbon tetrachloride poisoning in 19 patients: Implications for diagnosis and treatment. Lancet 1985;1:1027-9.

22. Anker AL and Smilkenstein MJ. Acetominophen: 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. J 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.
RODENTICIDES • 169

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 rodents, particularly after repeated exposures, but much less toxic to humans.) Second, 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 antiprothrombin effect is best known, and is the basis for detection and assessment

of clinical poisoning. The agents also increase permeability of capillaries throughout 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, GI, 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
170 • RODENTICIDES

in 36-72 hours.1,4,5 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 halflives 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 vitamin K for several months following discharge.6

 Another patient was released

from the hospital with significant clinical improvement and only slightly elevated coagulation studies after brodifacoum ingestion. Two and a half weeks

later, he presented in a comatose state and was found to have massive intracranial 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.1,4,5

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.

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.
RODENTICIDES • 171

2. Vitamin K1. 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.5

 Therefore, 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 (vitamin Kl

) given orally protects against the anticoagulant effect of these rodenticides, with essentially no risk to the patient. In accidental ingestions with healthy

children involving only a taste or single swallow, no medical treatment is required, 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

 (menadione, HykinoneR) nor vitamin K4

 (menadiol) is an antidote for these anticoagulants.

Dosage of Phytonadione (oral):

• Adults and children over 12 years: 15-25 mg.

• Children under 12 years: 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, particularly 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.
172 • RODENTICIDES

Dosage of AquamephytonR (intramuscular):

• Adults and children over 12 years: 5-10 mg.

• Children under 12 years: 1-5 mg.

Decide dose within these ranges according to the degree of prothrombin 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, administer 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. Intravenous 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 cyanosis 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 anticoagulants, 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.
RODENTICIDES • 173

INORGANIC RODENTICIDES

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 LD50 in humans

to be between 10 and 15 mg/kg.10

Unlike other inorganic rodenticides like yellow phosphorus and zinc phosphide, 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 addition to hair loss, the gastrointestinal system, central nervous system, cardiovascular system, renal system, and skin are prominently affected by toxic intakes.

Early symptoms include abdominal pain, nausea, vomiting, bloody diarrhea, 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 Distress 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 irritaCommercial Products

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.
174 • RODENTICIDES

bility are the earliest symptoms, followed by symptoms of gastrointestinal injury. 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.15 The third stage of toxicity

then ensues with systemic signs indicating severe injury to the liver, myocardium, 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. Hypovolemic 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 toxicities as encountered with yellow phosphorus, including hepatic failure with

jaundice and hemorrhage, delirium, convulsions, and coma (from toxic encephalopathy), tetany from hypocalcemia, and anuria from renal tubular damage. Ventricular 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 hypocalcemia 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 concentration does not exceed 30 mcg 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 mcg/liter per 24 hours.10,13
RODENTICIDES • 175

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 infusion 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 ECG for arrhythmias.

3. Convulsions. Control seizures and myoclonic jerking as outlined in Chapter 2.

4. Combined hemodialysis and hemoperfusion has proven moderately

effective in reducing the body burden of thallium in victims of severe poisoning. In one case, peritoneal dialysis was not effective.

5. Chelation therapy. Several methods for chelating and/or accelerating disposition of thallium have been tested and found either relatively ineffective or

hazardous. Chelating agents are not recommended in thallium poisoning. Potassium 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

some cases.20

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 particles 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 supportive and symptomatic. Control of airway and convulsions must be established prior to considering gastrointestinal decontamination as described in

Chapter 2.
176 • RODENTICIDES

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 ventilated. 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 administering 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 positive 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 ECG

to detect myocardial impairment.

8. Liver damage. Monitor serum alkaline phosphatase, LDH, ALT, AST, prothrombin time, and bilirubin to evaluate liver damage. Administer

AquamephytonR (vitamin K1

) 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.
RODENTICIDES • 177

CONVULSANTS

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 ventricular 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 convulsions by direct excitatory action on the cells of the central nervous system,

chiefly the spinal cord. Death is caused by convulsive interference with pulmonary function, by depression of respiratory center activity, or both. Strychnine

is detoxified in the liver. Residence half-life is about 10 hours in humans. Onset 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

Confirmation of Poisoning

There are no generally available tests to confirm poisoning by the convulsant 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, however, it is necessary first to control the seizures before gastric lavage and catharsis 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 paralyze respiration. For this reason, it is best to intubate the trachea as early as

Commercial Products

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.
178 • RODENTICIDES

possible in the course of seizure control, and support pulmonary ventilation

mechanically. This has the added advantage of protecting the airway from aspiration 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 absorbed toxicant. It is especially important to avoid fluid overload in the presence 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 12 years: 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 ingestion 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 activated 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.
RODENTICIDES • 179

1. Control seizures as outlined in Chapter 2.

2. Gastrointestinal decontamination. Consider gastrointestinal decontamination if patient is seen within an hour of ingestion.

3. Administer intravenous fluids to support excretion of absorbed toxicants. Inclusion of sodium bicarbonate in the infusion fluid counteracts metabolic 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 properties 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 (rodents do not) are unlikely to retain the poison; (2) the glycoside is not efficiently 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 D3

). 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 symptoms and signs of vitamin D-induced hypercalcemia in humans are fatigue, weakness, 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 nephrocalcinosis. 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.
180 • RODENTICIDES

Treatment: Red Squill

Red squill is unlikely to cause poisoning unless ingested at substantial dosage. 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 electrocardiographically.

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 outlined 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 cholecalciferol 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.
RODENTICIDES • 181

The dose may be doubled if calcium-lowering effect is not sufficient. Calcium

gluconate for intravenous injection should be immediately available if indications 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 J 1994;55:554-6.

2. Katona B and Wason S. Superwarfarin poisoning. J Emerg Med 1989;7:627-31.

3. Litovitz TL, Smilkstein M, Felberg L, 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. Clin Toxicol 1989;27:79-89.

5. Smolinske SC, Scherger DL, Kearns PS, et al. Superwarfarin poisoning in children: A prospective 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-containing rodenticide. Lab Med 1989;20:25-7.

8. Norcross WA, Ganiats TG, 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 MF. Abdominal pain, leg weakness, and alopecia in a teenage boy. Hosp

Pract 1997;32:69-70.

13. Meggs WJ, Hoffman RS, Shih RD, et al. Thallium poisoning from maliciously contaminated

food. J Toxicol Clin Toxicol 1994;32:723-30.

14. Roby DS, Fein AM, Bennett RH, et al. Cardiopulmonary effects of acute thallium poisoning. Chest 1984;85:236-40.

15. McMarron MM and Gaddis GP. Acute yellow phosphorus poisoning from pesticide pastes.

Clin Toxicol 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.

J Assoc 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.
182 • RODENTICIDES

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. Clin Toxicol 1996;34:707-12.

22. Benomran FA and Henry JD. Homicide by strychnine poisoning. Med Sci Law 1996;36:271-3.

23. Buckle RM, Gamlen TR, and Pullen IM. Vitamin D intoxication treated with procine calcitonin. Br Med J 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 Med J 1985;290:748-9.

26. Thomson RB and Johnson JK. Another family with acute vitamin D intoxication: Another

cause of familial hypercalcaemia. Postgrad Med J 1986;62:1025-8.
MISCELLANEOUS • 183

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 pesticides 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 investigational 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 enhancement 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 manifestation 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 seizures 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

DIC

• Pneumonitis occurs with

hydrocarbon aspiration

Treatment:

• Skin, eye, and GI

decontamination

• Supportive care and

seizure control

• Methylene blue for

methemoglobinemia
184 • MISCELLANEOUS

Treatment

1. Skin decontamination. If skin or eye contamination has occurred, thorough 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 decontamination should be considered, as outlined in Chapter 2. If treatment is delayed, 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 dtubocuarine, 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 symptoms from dermal exposure have been reported.5 Systemic poisonings have

followed inhalation of hydrogen cyanamide and ingestion of the salt. Manifestations 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.)

Commercial Products

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.
MISCELLANEOUS • 185

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.
186 • MISCELLANEOUS

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 presence of phenolic compounds.

Treatment

1. Skin decontamination. Stringent measures should be taken to avoid contamination 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 attention 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 pharyngeal 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 perforation 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 methemoglobinemia, 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.
MISCELLANEOUS • 187

7. Convulsions. Anticonvulsants may be needed to control seizures as outlined 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 gastrointestinal tract (particularly from high concentrations of the free acid); cardiomyopathy 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. Obtain 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.
188 • MISCELLANEOUS

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 electrolytes, provide sugar, and support mechanisms for toxicant disposition. Give vasoactive 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 ingestion 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.11 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 metaldehydepoisoned 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 symptoms that may occur include hypersalivation, facial flushing, dizziness, tachypnea, and acidosis.10,11 Pneumonitis has followed inhalational exposure to
MISCELLANEOUS • 189

metaldehyde.11 While most cases are dramatic with significant seizures and coma,

fatal events are infrequent.10,13 Poisoned animals show tremors, ataxia, hyperesthesia, salivation, ataxia, and seizures.12 Autopsy findings in fatal human poisonings 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 severe 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 administered. See Chapter 2 for dosage.

3. Supportive treatment. Appropriate supportive treatment including intravenous fluids containing saline and glucose should be given. Sodium bicarbonate 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.
190 • MISCELLANEOUS

Toxicology

Sodium chlorate is irritating to skin, eyes, and mucous membranes of the

upper respiratory tract.14 Dermal absorption is slight. Even though gastrointestinal 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 intravascular hemolysis occurs.14 Cyanosis is prominent if methemoglobinemia is severe

and may be the only presenting sign.15 Acute tubular necrosis and hemoglobinuria 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 (DIC).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 immediately 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 action 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
MISCELLANEOUS • 191

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, methemoglobin, and bilirubin, as well as urine protein, cells and free hemoglobin content, and ECG. 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 DIC.16

8. Hemodialysis may be life-saving in severe poisoning. It is effective in removing 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 methemoglobinemia 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 dizziness 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 synergist, piperonyl butoxide, acts by inhibiting the enzymatic degradation of pyrethrins, 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 drugmetabolizing enzymes by these agents has not actually been demonstrated. Their

presence in pesticide products to which humans are exposed does not change
192 • MISCELLANEOUS

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 producers 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 responsible 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 emergency 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 lipophilic 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 application by adding measured amounts of water to form emulsions. Some chlorinated 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 pesticide, 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 themselves 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
MISCELLANEOUS • 193

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, therefore, 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 detergents (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 nature. 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 phosphates. 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 (commonly 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 moderately irritating to the skin and eyes. Systemic toxicities are generally low.

Anticaking agents are added to granular and dust formulations to facilitate application by preventing cakes and clumps. Among several products used

are the sodium salt of mono- and di-methyl naphthalene sulfonate, and diatomaceous earth. Diatomaceous earth has little adverse effect except a drying

action on the skin. Methyl naphthalenes are said to be skin irritants and photosensitizers; whether their derivatives have this effect is not known.
194 • MISCELLANEOUS

Treatment

Petroleum distillates are mineral hydrocarbons which undergo limited absorption across the gut. In general, clinical toxicologists do not recommend induced 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 stomach 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 hydrocarbon pneumonitis, who are symptomatic, should usually be hospitalized, preferably 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 ECG

should be examined for arrhythmias and conduction defects. Mechanically assisted 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 significantly 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. Clin Toxicol 1980;16:487-97.

2. Pickett TA 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 of Toxic 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 involvement as a result of cyanamide. J Am Acad Dermatol 1990;23:1168-9.

6. Sittig M. Handbook of Toxic 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

J 1984;60:499-500.
MISCELLANEOUS • 195

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. J Anal Toxicol 1983;7:79-82.

10. Longstreth WT and Pierson DJ. Metaldehyde poisoning from slug bait ingestion. West J Med

1982;137:134-7.

11. Jay MS, Kearns GL, Stone V, 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 Appl Toxicol 1986;6:440-6.

13. Moody JP and Inglis FG. Persistence of metaldehyde during acute molluscicide poisoning.

Hum Exp Toxicol 1992;11:361-2.

14. Helliwell M and Nunn J. Mortality in sodium chlorate poisoning. Br Med J 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 1991;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.
196 • DISINFECTANTS

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

Signs and Symptoms:

• Highly variable based on

agent

• Many are irritants and

corrosives

• 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

CHAPTER 19

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.

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, commonly 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 hypoglycemia 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.
DISINFECTANTS • 197

Confirmation of Poisoning

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 vomited, 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. Glutaraldehyde is very similar to formaldehyde in its toxicity and treatment, although 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 rhinitis5,6 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 gastrointestinal 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 employees that may be exposed to glutaraldehyde during routine or emergency

work procedures (29 CFR 1910.134).

Commercial Products

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

Ioprep

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
198 • DISINFECTANTS

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 charcoal 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 decontamination 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
DISINFECTANTS • 199

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 perforation 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 antagonists and sulcralfate, has been reported but remains controversial at this time.

5. CNS, pulmonary and other systemic effects should be treated symptomatically, 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 exposures 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%
200 • DISINFECTANTS

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 decontamination as described in Chapter 2 should be considered. If a highly

concentrated solution has been ingested, manage as a caustic ingestion as described 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 disinfectant 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 limited 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.
DISINFECTANTS • 201

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 increasing 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 copious 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 gastrointestinal 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 initially appear to be neurological, with headache, dizziness, delirium, hallucina-
202 • DISINFECTANTS

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-Iodine

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 decontamination, as outlined in Chapter 2. Consider single dose charcoal.

3. Iodine clearance is apparently enhanced by procedures that enhance chloride 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 toxicity 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 derivatives 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.
DISINFECTANTS • 203

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 usually 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 exposures. 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. Consideration 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 diagnosis and management.

3. Skin decontamination. If skin or eye contamination has occurred, copious 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 patient 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 damaged 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.
204 • DISINFECTANTS

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 paralysis, 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 poisoning are vomiting, diarrhea, and anorexia.34 These findings have been accompanied in animals by significant hepatotoxicity.36 With skin exposure, an erythematous 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 exchange transfusion.37

3. Skin decontamination. If exposure has occurred through the skin, aggressive 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 control should be in accordance with recommendations in Chapter 2.

5. Cardiovascular and respiratory support are also very important to success in treating severe poisonings with this agent and should be provided in an

intensive care unit in accordance with accepted medical practice.
DISINFECTANTS • 205

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 monoterpenes 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 respiratory and CNS depression, and renal toxicity. Larger ingestions can result in

severe respiratory distress, cardiovascular collapse, and severe CNS effects. Renal 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 alphaterpineol 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 aspiration 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 proposed 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 symptoms, particularly pulmonary symptoms. If any pulmonary symptoms are observed, the patient should have a chest film and measurement of oxygenation,
206 • DISINFECTANTS

and hospitalization is appropriate. With severe pulmonary symptoms, transfer

to an intensive care unit is usually appropriate. With severe aspiration, management 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 J Med 1983;75:680-6.

2. Rich J, Scheife RT, Katz N, et al. Isopropyl alcohol intoxication. Arch Neurol 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 practice. Pediatr Emerg Care 1994;10:91-3.

4. Manring E, Meggs W, Pape G, et al. Toxicity of an intravenous infusion of isopropyl alcohol.

J Toxicol Clin Toxicol 1997;35:503.

5. Norback D. Skin and respiratory symptoms from exposure to alkaline glutaraldehyde in

medical services. Scand J Work Environ Health 1988;14:366-71.

6. Corrado OJ, Osman J, and Davies RJ. Asthma and rhinitis after exposure to glutaraldehyde

in endoscopy units. Hum Toxicol 1986;5:325-8.

7. Chan-Yeung M, McMurren T, Catonio-Begley F, et al. Occupational asthma in a technologist exposed to glutaraldehyde. J Allergy Clin Immunol 1993; 91(5):974-8.

8. Stenton SC, Beach JR, Dennis JH, et al. Glutaraldehyde, asthma, and work – a cautionary

tale. Occup Med 1994;44(2):95-8.

9. Mucklow ES. Accidental feeding of a dilute antiseptic solution (chlorhexidine 0.05% with

cetrimide 1%) to five babies. Hum Toxicol 1988;7:567-9.

10. Wilson JT and Burr IM. Benzaldonium chloride poisoning in infant twins. AJDC

1975;129:1208-9.

11. Chan TY. Poisoning due to savlon (cetrimide) liquid. Hum Exp Toxicol 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 Specialty Board. Englewood, CO: Micromedex, 1988.

14. Wong WK, 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 gluconate. 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 and Tedesco FJ. Colitis after hibiclens enema. J Clin Gastroenterol 1986;8:572-5.

19. Ingram TA. Response of the human eye to accidental exposure to sodium hypochlorite. J

Endod 1990;16:235-8.
DISINFECTANTS • 207

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 Saunders WH. 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. Kurt TL, Hnilica V, Bost R, et al. Fatal iatrogenic iodine toxicity in a 9-week old infant. Vet

Hum Toxicol 1992;34:333.

25. Means LJ, Rescorla FJ, and Grosfield JL. Iodine toxicity: An unusual cause of cardiovascular collapse during anesthesia in an infant with Hirschsprung’s Disease. J Pediatr Surg

1990;25:1278-9.

26. Ponn RB. Continuous povidone-iodine irrigation (letter). Ann Thorac 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, Nogué S, and Bertrán 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;11:294-6.

30. Arthus GJ, Wise CC, and Coles GA. Poisoning by cresol. Anaesthesia 1977;32:642-3.

31. Chan TK, Mak LW, and Ng RP. Methemoglobinemia, heme bodies, and acute massive intravascular 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)II:395-9.

33. Anderson JM, Cockburn F, Forfar J, et al. Neonatal spongioform myelinopathy after restricted application of hexachlorophane skin disinfectant. J Clin Pathol 1981;34:25-9.

34. Martin-Bouyer G, Lebreton R, Toga M, et al. Outbreak of accidental hexachlorophene poisoning in France. Lancet 1982;1:91-5.

35. Slamovitz TL, Burde RM, and Klingele TG. 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 hexachloropheneinduced encephalopathy. Bull Environ Contam Toxicol 1987;38:561-4.

37. Boehm RM and Czajka PA. Hexachlorophene poisoning and the ineffectiveness of peritoneal dialysis. J Toxicol Clin Toxicol 1979;14(3);257-62.

38. Nagy L and 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. Arch Toxicol 1981;49:73-8.

40. Litovitz TL, Schmidz BF, Matyunas N, et al. 1987 Annual Report of the American Association of

Poison Control Centers National Data Collection System. Am J Emerg Med 1988;6:479-515.
210 • SIGNS AND SYMPTOMS

Index of Signs and Symptoms

Presented in this chapter are lists of pesticides reported to have caused particular 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 exposure 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 interviewing professional.

The term manifestation means either symptom or sign. The word “poisoning” 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 poisoned individuals that they have little or no value in differential diagnosis, and

are therefore not included in these tables.
SIGNS AND SYMPTOMS • 211

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

General
212 • SIGNS AND SYMPTOMS

Irritation,

Rash,

Blistering, or

Erosion (without

sensitization)

Contact dermatitis

Flushing

Dermal sensitization

Beefy red palms, soles

Urticaria

Bullae

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

Acrolein

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

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

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Skin
SIGNS AND SYMPTOMS • 213

Pallor

Cyanosis

Yellow stain

Keratoses, brown

discoloration

Ecchymoses

Jaundice

Excessive hair growth

Loss of hair

Loss of fingernails

Brittle nails, white striations

Sweating, diaphoresis

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

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

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Skin (continued)
214 • SIGNS AND SYMPTOMS

Copper compounds

Organotin compounds

Cadmium compounds

Metam sodium

Paraquat

Diquat

Acrolein

Chloropicrin

Sulfur dioxide

Naphthalene

Formaldehyde

Ethylene oxide

Methyl bromide

Endothall

Toluene

Xylene

Organophosphates

Carbamate insecticides

Chloropicrin

Acrolein

Nitrophenols

Paraquat

Thallium

Organophosphates

Carbamate insecticides

Nicotine

Organic mercury

Organophosphates

Carbamate insecticides

Cyanide

Fluoride

Cyanide

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)

Conjunctivitis

 (irritation of mucous

 membranes, tearing)

Tearing

Yellow schlerae

Keratitis

Ptosis

Diplopia

Photophobia

Constricted visual fields

Optic atrophy

Miosis

Dilated pupils

Unreactive pupils

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Eye
SIGNS AND SYMPTOMS • 215

Organophosphates

Cyanopyrethroids

Phosphides

Organochlorines

Thiabendazole

Inorganic arsenicals

Organic mercury

Sodium fluoroacetate

Carbon disulfide

Thallium

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

Organic mercury

Inorganic arsenicals

Organotin compounds

Thallium

Nicotine

Sodium fluoroacetate

Diquat

Cyanide

Nitrophenols

Aminopyridine

Carbon disulfide

Methyl bromide

Organophosphates

Carbamate insecticides

Sodium fluoride

Borate

Diquat

Nicotine (late)

Pyrethroids (transitory)

Organochlorines

Nitrophenols

Thiram

Pentachlorophenol

Paraquat

Diethyltoluamide

Organophosphates

Carbamate insecticides

Pentachlorophenol

Sodium fluoride

Diethyltoluamide

Organochlorines

Inorganic arsenicals

Metaldehyde

Sulfuryl fluoride

Halocarbon fumigants

Phosphorus

Phosphine

Paraquat

Chlorophenoxy compounds

Diethyltoluamide

Alkyl phthalates

Paresthesia

 (chiefly facial,

 transitory)

Paresthesia of extremities

Headache

Behavioral – mood

Disturbances

(confusion, excitement,

mania, disorientation,

emotional lability)

Depression, stupor, coma,

respiratory failure, often

without convulsions

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Nervous System
216 • SIGNS AND SYMPTOMS

Organochlorines

Strychnine

Crimidine

Sodium fluoroacetate

Nicotine

Cyanide

Acrylonitrile

Metaldehyde

Thallium

DEET

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

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

Seizures/Convulsions

(clonic-tonic) sometimes

leading to coma

Muscle twitching

Myotonia

Tetany, carpopedal spasms

Tremor

Incoordination

(including ataxia)

Paralysis

Paresis, muscle weakness

Hearing loss

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Nervous System (continued)
SIGNS AND SYMPTOMS • 217

Phosphorus

Phosphides

Phosphine

Sodium fluoride

Sodium chlorate

Borate

Thallium

Copper compounds

Endothall

Cyanamide

Thallium (early)

Nicotine (early)

Hypotension shock

Hypertension

Inorganic arsenicals

Nicotine (late)

Creosote

Alkyl phthalate

Cycloheximide

Formaldehyde

Norbormide

Organophosphates

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Nervous System (continued)

Cardiac arrhythmias

Bradycardia (sometimes to

asystole)

Tachycardia

Sodium fluoroacetate

Halocarbon fumigants

Nicotine

Sodium fluoride

Ethylene oxide

Sodium chlorate

Thallium-ventricular

Povidone-iodine

Veratrum alkaloid (sabadilla)

Cyanide

Organophosphates

Carbamate insecticides

Nitrophenols

Pentachlorophenol

Cyanamide

Inorganic arsenicals

Phosphorus

Phosphides

Phosphine

Organochlorines

Cyanide

Acrylonitrile

Fluoride

Nicotine

Metaldehyde

Organophosphates

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Cardiovascular System
218 • SIGNS AND SYMPTOMS

Naphthalene

Paraquat

Chloropicrin

Acrolein

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

Acrolein

Pyrethiods

Sulfur dioxide

Cationic detergents

Creosote

Methylisothiocyanate

Cadmium

Paraquat

Cadmium dusts

Methyl bromide

Organophosphates

Carbamate insecticides

Nicotine

Paraquat

ANTU

Cadmium dusts

Cyanamide

Sulfuryl fluoride

Pentachlorophenol

Methyl bromide

Sulfur dioxide

Chloropicrin

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

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

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Respiratory System
SIGNS AND SYMPTOMS • 219

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

Organophosphates

Carbamates

Pyrethoids

Borates

Sulfur

Nicotine

B.thuringiensis

Thiram

Cadmium

Fluoride

Paraquat

Diquat

Thallium

Coumarins

Indandiones

Endothall

Arsenicals

Pentachlorophenol

B.thuringiensis

Cholecalciferol

Thiram

Ethylene dichloride

Propane

Ethylene oxide

Cresol

Many pesticides have some

irritant property

Cationic detergents

Cresol

Hexachlorophene

Chlorophenoxy compounds

Phosphorus

Phosphides

Cycloheximide

Nausea, vomiting,

commonly followed by

diarrhea

Diarrhea (first)

Diarrhea (bloody)

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Gastrointestinal Tract and Liver
220 • SIGNS AND SYMPTOMS

Abdominal pain

Stomatitis

Salivation

Ileus

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Gastrointestinal Tract and Liver (continued)

Enlargement

Jaundice –

see section on Skin

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Liver

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

Copper compounds

Sodium chlorate

Phosphine

Carbon tetrachloride

Cholorform

Chlorophenoxy compounds

Aliphatic acids

Sodium chlorate

Creosote

Endothall

Aminopyridine

Coumarins

Indandiones

Fumigants (ingested)

Cycloheximide

Thallium

Inorganic arsenicals

Hexachlorobenzene
SIGNS AND SYMPTOMS • 221

Proteinuria

Hematuria

Sometimes leading

to oliguria

Acute renal failure with

azotemia

Dysuria, hematuria, pyuria

Polyuria

Hemoglobinuria

Wine-red urine

(porphyrinuria

Smoky urine

Glycosuria

Ketonuria

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Kidney

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

Cadmium compounds

Phosphorus

Phosphides

Phosphine

Chlorophenoxy compounds

Creosote

Organotin compounds

Fluoride

Organotin compounds

Borate

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Reproductive System

Low sperm count Dibromochloropropane Kepone
222 • SIGNS AND SYMPTOMS

Hypocalcemia

Hypercalcemia

Carboxyhemoglobinemia

Anemia

Leukopenia,

Thrombocytopenia

Elevated LDH

GOT, GPT,

alkaline phosphatase,

ALT, AST enzymes

Depressed RBC

Acetylcholinesterase and

plasma

pseudocholinesterase

Hemolysis

Methemoglobinemia

Hypoprothrombinemia

Hyperkalemia

MANIFESTATION CHARACTERISTIC OF

THESE POISONINGS

OCCURS WITH

THESE AGENTS

Blood

Naphthalene

Sodium chlorate

Arsine

Sodium chlorate

Creosote

Coumarins

Indandiones

Sodium chlorate

Naphthalene

Arsine

Copper compounds

Cresol

Chlordimeform

Cyanide

Cresol

Copper

Arsine

Phosphorus

Phosphides

Carbon tetrachloride

Sodium fluoride

Fluoride

Cholecalciferol

Naphthalene

Sodium chlorate

Arsine

Inorganic arsenicals

Inorganic arsenicals

Carbon tetrachloride

Chloroform

Phosphine

Organosphosphates

Thallium

Phosphorus

Phosphides

Organotin compounds

Inorganic arsenicals

Phosphorus

Phosphides

Phosphine

Sodium chlorate

Nitrophenols

Pentachlorophenol

Thallium

Organochlorines

Chlorophenoxy compounds

Carbamate insecticides
INDEX OF PESTICIDES • 223

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

A

A7 Vapam ......................................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

Index of Pesticide Products

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

Ansar 8100 ............................ 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
224 • INDEX OF PESTICIDES

arsenic acid............................ 127, 133

arsenic trioxide ............... 127, 129, 133

arsenical pesticides .. 126, 145, 147, 149

arsine gas .................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

Bueno 6 ................................ 128, 134

bufencarb ....................................... 49

Busan 1020 ...................................140

butralin .........................................120
INDEX OF PESTICIDES • 225

butylate .........................................119

Bux ................................................ 49

C

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

Carbamate WDG ..........................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

Ceku C.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

Chemox PE ..................................105

Chemsect DNBP ..........................105

Chemsect DNOC .........................105

Chermox PE .................................105

Chipco Thiram 75 .........................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
226 • INDEX OF PESTICIDES

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

Crag Turf 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 ....................................... 76

Cymperator.................................... 76

Cynoff ........................................... 76

Cyolane.......................................... 35

Cyperkill ........................................ 76

cypermethrin ............................ 76, 87

Cypona .......................................... 35

Cyrux ............................................ 76

cythioate ........................................ 35

Cythion ......................................... 35

Cytrolane ....................................... 35

D

2,4-D ............................. 94-95, 97-98

D-D92 ..........................................157

D-trans........................................... 76

Dachthal .......................................121

Daconate 6 ............................ 128, 134

Daconil 2787 ................................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
INDEX OF PESTICIDES • 227

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

Drexar 530 ............................ 128, 134
228 • INDEX OF PESTICIDES

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

E 601 ............................................. 35

E-48............................................... 35

E-D-Bee .......................................157

E-Z-Off D ..................................... 35

E605 .............................................. 35

Earthcide.......................................138

Easy off-D ...................................... 35

EBDC compounds ........................144

Ebufos ............................................ 35

EDB .............................................157

EDC .............................................157

edifenphos ...................................... 35

Ekamet........................................... 35

Ekatin ............................................ 35

Eksmin ........................................... 77

Elecron .......................................... 49

Elimite ........................................... 77

Elgetol 30......................................105

Elgetol 318 ....................................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

Exotherm Termil ...........................138

F

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

Fermide 850..................................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

FMC 9044 ....................................106

Folbex ............................................ 75

Folcord .......................................... 77
INDEX OF PESTICIDES • 229

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

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
230 • INDEX OF PESTICIDES

indandiones ........................... 169-171

inorganic copper compounds.........145

Iodines ..........................................197

iodofenphos ................................... 35

Ioprep ...........................................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

J

Jones Ant Killer ..................... 128, 133

K

Kabat ............................................. 76

Kack ..................................... 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

Kypman 80 ...................................144

Kypzin ..........................................144

L

Lance ............................................. 49

Landrin .......................................... 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

Manex 80......................................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
INDEX OF PESTICIDES • 231

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

MetasystoxI .................................... 35

Meth-O-Gas .................................157

methabenzthiazuron ......................122

methamidophos.............................. 35

methane arsonic acid ............. 127, 134

methanol ........................ 184, 192, 196

Methar 30 ............................. 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

NIA 9044 .....................................106

Nico Soap ...................................... 64
232 • INDEX OF PESTICIDES

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

o-phenylphenol .............................197

Off! ........................................... 75, 80

Oftanol .......................................... 35

Ofunack ......................................... 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

P

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

Paris green ..................... 127, 133, 145

Parzate ..........................................144

Parzate C ......................................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

Pestox XIV..................................... 35

Pestox XV ...................................... 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
INDEX OF PESTICIDES • 233

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

Phytar 560............................. 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

Polybor 3 ....................................... 75

Polyram-Ultra ...............................140

Polytrin .......................................... 77

Pomarsol forte ...............................140

Pounce ........................................... 77

povidone-iodine ......197, 201-202, 207

Pramex........................................... 77

Pramitol 25E .................................121

Prebane .........................................121

Precor ............................................ 76

Preeglone ......................................109

Preglone........................................109

Premerge 3....................................105

Prenfish .......................................... 64

Primatol ........................................121

Primatol M ...................................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

Q

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
234 • INDEX OF PESTICIDES

Rapier...........................................119

Ratak ............................................170

Ratak Plus.....................................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

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

Sobrom 98 ....................................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

Solasan 500 ...................................140

solvents and adjuvants ............ 183, 192

Sometam .......................................140

Sonalan .........................................120

Soprabel ................................ 127, 134

Sopranebe .....................................144

Spike .............................................122

Spotrete WP 75 .............................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
INDEX OF PESTICIDES • 235

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

T

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
236 • INDEX OF PESTICIDES

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 ........................................... 35

VC-13 Nemacide........................... 35

Vectobac ........................................ 64

Vectocide ....................................... 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

Y

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

Ziram F4 .......................................140

Ziram Technical.............................140

Zirberk .........................................140

Zirex 90 ........................................140

Ziride ...........................................140

Zitox.............................................140

Zolone ........................................... 35

zoocoumarin .................................170

Zotox .................................... 127, 133