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Recognition and
Management of
Pesticide Poisonings
Fifth Edition
-------
RECOGNITION AND
MANAGEMENT OF
PESTICIDE POISONINGS
Fifth Edition, 1999
J. Routt Reigart, M.D.
Professor of Pediatrics, Medical University of South Carolina
James R. Roberts, M.D., M.P.H.
Assistant Professor of Pediatrics, Medical University of South Carolina
Support for this publication was provided by:
Certification and Worker Protection Branch
Field and External Affairs Division
Office of Pesticide Programs
U.S. Environmental Protection Agency
401 M Street SW (7506C)
Washington, DC 20460
For additional copies or more information:
Tel: 703-305-7666
Fax: 703-308-2962
The manual is available in electronic format on the Internet at:
http://www.epa.gov/pesticides/safety/healthcare
-------
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 ofWashington
Wayne R. Snodgrass, M.D, Ph.D.
Professor and Head
Clinical Pharmacology-Toxicology
Texas Poison Center
Sheldon L.Wagner, M.D.
Professor of Clinical Toxicology
Oregon State University
Many other individuals contributed their time and skill to this publication. We are very appreciative
of the tireless efforts of Patricia Clark, our administrative assistant, who spent endless hours in text
review, securing references, communicating with reviewers, and otherwise making the revision process
possible and easier than anticipated. Gilah Langner of Stretton Associates, Inc., provided editorial super-
vision. Will Packard and Sarah Carter of Free Hand Press, Inc. were responsible for the format and
layout of the manual.
Cover photographs by Steve Delaney, EPA.
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CONTENTS
Section I: General Information
1 Introduction 2
2 General Principles in the Management of Acute Pesticide Poisonings 10
3 Environmental and Occupational History 17
Section II: Insecticides
4 Organophosphate Insecticides 34
5 N-Methyl Carbamate Insecticides 48
6 Solid Organochlorine Insecticides 55
7 Biologicals and Insecticides of Biological Origin 63
8 Other Insecticides, Acaricides, and Repellents 74
Section III: Herbicides
9 Chlorophenoxy Herbicides 94
10 Pentachlorophenol 99
11 Nitrophenolic and Nitrocresolic Herbicides 104
12 Paraquat and Diquat 108
13 Other Herbicides 118
Section IV: Other Pesticides
14 Arsenical Pesticides 126
15 Fungicides 137
16 Fumigants 156
17 Rodenticides 169
18 Miscellaneous Pesticides, Solvents, and Adjuvants 183
19 Disinfectants 196
Section V
Index of Signs and Symptoms 210
Index of Pesticide Products 223
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List of Tables
Dosage Tables
Sorbitol 12
Activated Charcoal 13
Syrup of Ipecac 14
Diazepam 14
Lorazepam 15
Atropine 42
Pralidoxime 43
Atropine 51
Diazepam 58
Atropine Sulfate 68, 72
Calcium Gluconate 84
Lorazepam 102
Bentonite and Fuller's Earth 113
Morphine Sulfate 115
BAL (Dimercaprol) 130
D-penicillamine 131
DMSA (Succimer) 131
DMPS 131
Cyanide Antidotes 166
Supplemental Sodium Nitrite and Sodium Thiosulfate 167
Phytonadione 171
Aquamephytonฎ 172
Calcium Gluconate 178
Tables
Pesticides Most Often Implicated in Symptomatic Illnesses, 1996 5
California Occupational Illnesses Due to Pesticides, 1991-1995 6
Screening Questions for Occupational and Environmental Exposures 18
Adult Interview for Occupational and Environmental Exposures 26
Steps in Investigating a Disease Outbreak 26
Approximate Lower Limits of Normal Plasma and
Red Cell Cholinesterase Activities in Humans 39
Toxicity of Common Herbicides 119
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Section I
GENERAL INFORMATION
-------
CHAPTER 1
Introduction
This fifth edition of Recognition and Management of Pesticide Poisonings is an up-
date and expansion of the 1989 fourth edition. The Office of Pesticide Pro-
grams of the United States Environmental Protection Agency has sponsored
the series since 1973. The purpose of the manual is to provide health profes-
sionals with recently available information on the health hazards of pesticides
currently in use, and current consensus recommendations for management of
poisonings and injuries caused by them.
Pesticide poisoning is a commonly under-diagnosed illness in America to-
day. Despite recommendations by the Institute of Medicine and others urging
the integration of environmental medicine into medical education, health care
providers generally receive a very limited amount of training in occupational
and environmental health, and in pesticide-related illnesses, in particular.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, associa-
tions of health professionals, and related organizations to help health care
providers become better aware, educated, and trained in the area of pesticide-
related health concerns. This larger initiative, entitled Pesticides and National
Strategies for Health Care Providers, was launched in April 1998.
As with previous updates, this new edition incorporates new pesticide prod-
ucts that are not necessarily widely known among health professionals. The
accumulated "use experience" of formulators, applicators, and field workers
provides an expanding basis for judging safety and identifying the environmen-
tal and workplace hazards of old and new pesticides. Major episodes of adverse
health effects reported in medical and scientific periodicals have been taken
into account. This literature also contributes importantly to improved under-
standing of toxic mechanisms. Clinical toxicology is a dynamic field of medi-
cine; new treatment methods are developed regularly, and the effectiveness of
old as well as new modalities is subject to constant critical review.
There is general agreement that prevention of pesticide poisoning remains a
much surer path to safety and health than reliance on treatment. In addition to
the inherent toxicity of pesticides, none of the medical procedures or drugs
used in treating poisonings is risk-free. In fact, many antidotes are toxic in their
own right, and such apparently simple procedures as gastric intubation incur
substantial risk. The clinical toxicologist must often weigh the hazards of vari-
ous courses of actionsometimes including no treatment at allagainst the
risks of various interventions, such as gastric emptying, catharsis, administration
INTRODUCTION
-------
of intravenous fluids, or administration of an antidote, if available. Clinical man-
agement decisions have to be made promptly and, as often as not, on the basis
of limited scientific and medical information. The complex circumstances of
human poisonings rarely allow precise comparisons of alternative management.
In no sense, then, are the treatment recommendations in this book infallible
guides to successful outcomes. They are no more than consensus judgments of
the best available clinical management options.
This manual deals almost entirely with short-term (acute) harmful effects
of pesticides. Although obviously important, the subject of chronic effects is
too complex to deal with exhaustively in a manual designed as guidance for
emergency management. Nonetheless, appropriate treatment of serious expo-
sures to pesticides represents an important step in avoiding chronic as well as
acute disease.
The pesticides and commercial products mentioned in this manual do not
represent the universe of pesticide products in existence. They were selected
based on frequency of use and exposure, severity of toxicity, and prior experi-
ence with acute poisonings. Products are discussed in this manual that have
been discontinued or whose U.S. pesticide registration has been revoked but
are judged to still be of risk due to use elsewhere or where there is a probability
of residual stocks. Agents long out of use in the U.S. and elsewhere were not
included in the manual.
The amount of pesticide absorbed is a critical factor in making treatment
decisions, and estimation of dosage in many circumstances of pesticide expo-
sure remains difficult. The terms "small amount" and "large amount" used in
this book are obviously ambiguous, but the quality of exposure information
obtained rarely justifies more specific terminology.
Sometimes the circumstances of exposure are a rough guide to the amount
absorbed. Exposure to spray drift properly diluted for field application is not
likely to convey a large dose unless exposure has been prolonged. Spills of
concentrated technical material onto the skin or clothing may well represent a
large dose of pesticide unless the contamination is promptly removed. Brief
dermal exposure to foliage residues of cholinesterase-inhibiting pesticides is
not likely to lead to poisoning, but prolonged exposures may well do so. Sui-
cidal ingestions almost always involve "large amounts," requiring the most ag-
gressive management. Except in children, accidental pesticide ingestions are
likely to be spat out or vomited. Ingestions of pesticides by children are the
most difficult to evaluate. The therapist usually must base clinical management
decisions on "worst case" assumptions of dosage. Childhood poisonings are still
further complicated by the greater vulnerability of the very young, not only to
pesticides themselves, but also to drugs and treatment procedures. The nature
of neurological development in children entails an additional level of risk that
is not present in adults. Some adult groups such as farmwrokers with poor
nutrition and high exposure may also be at increased risk.
INTRODUCTION 3
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Key Principles
General methods of managing pesticide poisonings are presented in Chap-
ter 2 and reflect a broad base of clinical experience. The following key points
deserve emphasis. The need to protect the airway from aspiration of vomitus
cannot be overstated. Death has occasionally resulted from this complication,
even following ingestions of substances having relatively low toxic potential. In
poisonings by agents that depress central nervous system function or cause
convulsions, early placement of a cuffed endotracheal tube (even when this
requires light general anesthesia) may be life saving. Maintenance of adequate
pulmonary gas exchange is another essential element of poisoning manage-
ment that deserves constant reemphasis.
Gastric intubation, with aspiration and lavage, remains a useful method for
removing poisons from the stomach shortly after they have been swallowed,
but the time after ingestion during which lavage is likely to be beneficial is
shorter than many clinical toxicologists have thought. Rarely are significant
amounts of swallowed toxicants recovered more than 1-2 hours after ingestion,
and, in many instances, the bulk of swallowed material passes into the duode-
num and beyond in 15-30 minutes. In addition, the majority of controlled
studies evaluating the effectiveness of gastric emptying procedures are done for
ingestions of solid material (pills) rather than liquids.
Full advantage should be taken of new highly adsorbent charcoals that are
effective in binding some pesticides in the gut. Unfortunately, charcoal does
not adsorb all pesticides, and its efficiency against many of them is not known.
In poisonings caused by large intakes of pesticide, hemodialysis and
hemoperfusion over adsorbents continue to be tested as methods for reducing
body burdens. Against some toxicants, these procedures appear valuable. Over-
all effectiveness appears to depend not only on efficiency of clearance from the
blood, but also on the mobility of toxicant already distributed to tissues before
the extracorporeal blood-purification procedure is started. The volume of dis-
tribution and avidity of tissue binding are important considerations in making
such decisions. The critical determinant of success in using these systems may
well be the speed with which they can be put into operation before tissue-
damaging stores of toxicant have accumulated.
There remains a need for systematic reporting of pesticide poisonings to a
central agency so that accurate statistics describing the frequency and circum-
stances of poisoning can be compiled, and efforts to limit these occurrences can
be properly directed. In some countries there has been an increase in the use of
pesticides as instruments of suicide and even homicide. Producers are now
devoting considerable effort to modifying formulation and packaging to deter
these misuses. This work is important because suicidal ingestions are often the
most difficult pesticide poisonings to treat successfully.
4 INTRODUCTION
-------
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 Pyrethrinsand 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 (organo-
phosphates, 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
INTRODUCTION
-------
below). Denominator information on the population at risk (numbers exposed)
would be needed to better understand the relative risk of different pesticides.
However, the main purpose of these tables is to give physicians a sense of what
types of cases they are most likely to see in their practice.
Although suicide cases make up roughly 3% of pesticide-related calls to
Poison Control Centers, they may account for nearly 10% of the cases seen in
a health care facility. The leading types of products involved in suicidal cases
include anticoagulant rodenticides (20% of total suicide attempts), pine oil dis-
infectants (14%),organophosphates (ll%),pyrethrins/pyrethroids (6%),unknown
rodenticides (5%), carbamate insecticides (4%), and phenol disinfectants (3%).
CALIFORNIA OCCUPATIONAL ILLNESSES LIKELY DUE TO
PESTICIDES, 1991-1995
Rank Pesticide
1 Sodium hypochlorite
2 Quaternary ammonia
3 Chlorine
4 Glutaraldehyde
5 Chlorpyrifos
6 Sulfur
7 Glyphosate
8 Propargite
9 Metam sodium**
10 Cyanuricacid
All Other
Total all pesticides/disinfectants
* Topical includes skin, eye, and respiratory
** Train derailment led to a cluster of cases
Systemic
167
9
112
38
113
48
9
3
64
14
1149
1726
effects.
due to metam
Topical*
858
348
124
118
39
69
94
96
33
76
1089
2944
sodium in 1991.
Source: Louise Mehler, M.S., California Pesticide Illness Surveillance Program,
Environmental Protection Agency.
Total
1025
357
236
156
152
117
103
99
97
90
2238
4670
California
Poison Control Centers are best at capturing pesticide exposures which
occur in residential environments. However, occupational exposures are not as
well covered. California's Pesticide Illness Surveillance Program is generally
regarded as the best in the country. The table above presents the number of
occupationally-related cases in California reported from 1991 through 1995
where a pesticide was considered a probable or definite cause of the resulting
illness. Pesticide combinations, where the primary pesticide responsible for the
illness could not be identified, are not included in this table. Among persons
who encounter pesticides in the course of their occupational activities, dermal
and eye injuries, rather than systemic poisonings, are more common. Systemic
poisonings, however, are likely to be more severe.
INTRODUCTION
-------
Format of this Manual
An effort has been made to format this book for quick reference by thor-
ough indexing and minimal references to other pages or chapters. However,
many different agents commonly require similar procedures in treating poison-
ings and it is not practical to repeat these protocols in every chapter. General
principles for management of pesticide poisoning, including skin and eye de-
contamination, gastrointestinal decontamination, and control of convulsions
are considered in Chapter 2, General Principles. These principles are refer-
enced throughout.
Changes in this reformatted edition include: tabular listings of Commercial
Products in each chapter, the addition of a new chapter on Disinfectants (Chapter
19), and the addition of a chapter on Environmental and Occupational History
(Chapter 3), which places pesticide poisonings in the context of other environ-
mental and occupational exposures, provides questionnaires designed to elicit ex-
posure information, discusses resources available to the practitioner, and provides a
list of governmental and non-government contacts and Web sites for more infor-
mation. In addition, each chapter is referenced to key references in readily accessible
current literature. Most references were selected as primary references in peer
review journals, although some review papers are also included.
The contents of this book have been derived from many sources: published
texts, current medical, toxicological, and pesticide product literature, and direct
communications with experts in clinical toxicology and pesticide toxicology and
environmental and occupational health specialists. A list of the major text sources
follows this introduction.
Reference
1. Institute of Medicine. Role of the Primary Care Physician in Occupational and Environ-
mental Medicine, Washington, DC: Institute of Medicine, 1988.
Texts and Handbooks on Pesticides,
Pesticide Toxicology, and Clinical Toxicology
Agricultural Chemicals Books I, II, III, IV
W.T.Thomson
Thomson Publications, Fresno, CA, 1994-95
Agrochemicals Desk Reference: Environmental Data
John H. Montgomery
Lewis Publishers, Boca Raton, FL, 1995
The Agrochemicals Handbook, 3rd Edition
The Royal Society of Chemistry, Cambridge, England, 1994
INTRODUCTION 7
-------
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. Anidur
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 Wilkms, Baltimore, MD, 1984
Farm Chemicals Handbook
Charlotte Sine, Editorial Director
Meister Publishing Company,Willoughby, Ohio, 1998
Handbook of Pesticide Toxicology
Wayland J. Hayes,Jr. and Edward R. Laws,Jr., Editors
Academic Press, San Diego, CA 1991
Handbook of Poisoning: Prevention, Diagnosis and Treatment,
12th Edition
Robert H. Dreisbach and William O. Robertson
Appleton and Lange, East Norwalk, CT, 1987
Herbicide Handbook, 7th Edition
Weed Science Society of America, 1994
Medical Toxicology: Diagnosis and Treatment of Human Poisoning
Matthew J. Ellenhorn and Donald G. Barceloux
Elsevier, New York, NY, 1988
8 INTRODUCTION
-------
The Merck Index, llth Edition
Martha Windholz and Susan Budavari, Editors
Merck and Company, Inc., Rahway, NJ, 1989
Patty's Industrial Hygiene and Toxicology, 4th Revised Edition
George D. Clayton and Florence E. Clayton
Wiley Interscience, New York, NY, 1991-95
Pesticide Manual, llth Edition
CDS Tomlin
The British Crop Protection Council, Farnham, Surrey, United Kingdom, 1997
Pesticide Pro files :Toxi city, Environmental Impact, and Fate
Michael A. Kamrin (Editor)
Lewis Publishers, Boca Raton, FL, 1997
The Pharmacological Basis of Therapeutics, 8th Edition
Louis S. Goodman and Alfred Gilman
Pergamon Press, New York, NY, 1990
POISINDEXฎ System
Barry H. Rumack, NK. 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
INTRODUCTION 9
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CHAPTER 2
General Principles in
the Management of
Acute Pesticide Poisonings
This chapter describes basic management techniques applicable to most acute
pesticide poisonings. Where special considerations and treatments are required
for a particular pesticide, they are addressed separately in the appropriate chapter.
Skin Decontamination
Decontamination must proceed concurrently with whatever resuscitative
and antidotal measures are necessary to preserve life. Shower patient with soap
and water, and shampoo hair to remove chemicals from skin and hair. If there
are any indications of weakness, ataxia, or other neurologic impairment, cloth-
ing should be removed and a complete bath and shampoo given while the
victim is recumbent. The possibility of pesticide sequestered under fingernails
or in skin folds should not be overlooked.
Flush contaminating chemicals from eyes with copious amounts of clean
water for 10-15 minutes. If eye irritation is present after decontamination, oph-
thalmologic consultation is appropriate.
Persons attending the victim should avoid direct contact with heavily con-
taminated clothing and vomitus. Contaminated clothing should be promptly
removed, bagged, and laundered before returning. Shoes and other leather items
cannot usually be decontaminated and should be discarded. Note that pesti-
cides can contaminate the inside surfaces of gloves, boots, and headgear. De-
contamination should especially be considered for emergency personnel such
as ambulance drivers at the site of a spill or contamination. Wear rubber gloves
while washing pesticide from skin and hair of patient. Latex and other surgical
or precautionary gloves usually will not always adequately protect from pesti-
cide contamination, so only rubber gloves are appropriate for this purpose.
Airway Protection
Ensure that a clear airway exists. Suction any oral secretions using a large
bore suction device if necessary. Intubate the trachea if the patient has respira-
tory depression or if the patient appears obtunded or otherwise neurologically
10 GENERAL PRINCIPLES
-------
impaired. Administer oxygen as necessary to maintain adequate tissue oxygen-
ation. In severe poisonings, it may be necessary to mechanically support pul-
monary ventilation for several days.
Note on Specific Pesticides: There are several special considerations
with regard to certain pesticides. In organophosphate and carbamate poi-
soning, adequate tissue oxygenation is essential prior to administering atropine.
As important, in paraquat and diquat poisoning, oxygen is contraindicated
early in the poisoning because of progressive oxygen toxicity to the lung tissue.
See specific chapters for more details.
Gastrointestinal Decontamination
A joint position statement has recently been released by the American
Academy of Clinical Toxicology and the European Association of Poisons Centres
and Clinical Toxicologists on various methods of gastrointestinal decontamina-
tion. A summary of the position statement accompanies the description of
each procedure.
1. Gastric Lavage
If the patient presents within 60 minutes of ingestion, lavage may be con-
sidered. Insert an orogastric tube and follow with fluid, usually normal saline.
Aspirate back the fluid in an attempt to remove any toxicant. If the patient is
neurologically impaired, airway protection with a cuffed endotracheal tube is
indicated prior to gastric lavage.
Lavage performed more than 60 minutes after ingestion has not proven to
be beneficial and runs the risk of inducing bleeding, perforation, or scarring
due to additional trauma to already traumatized tissues. It is almost always nec-
essary first to control seizures before attempting gastric lavage or any other
method of GI decontamination.
Studies of poison recovery have been performed mainly with solid mate-
rial such as pills. There are no controlled studies of pesticide recovery by these
methods. Reported recovery of material at 60 minutes in several studies was
8%-32%.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 con-
firmed in controlled studies.4
GENERAL PRINCIPLES 11
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2. Catharsis
Sorbitol and magnesium citrate are commonly used cathartic agents. Be-
cause magnesium citrate has not been studied as much, its use is not described
here. Sorbitol is often included in charcoal formulations. It will increase gut
motility to improve excretion of the charcoal-poison complex. The dosage of
sorbitol is 1-2 g/kg as a one-time dose. Repeat doses of cathartics may result in
fluid and electrolyte imbalances, particularly in children, and are therefore not
recommended. Sorbitol is formulated in 70% and 35% solutions and usually
packaged in 100 mL bottles. The gram dosage of sorbitol in a 100 mL bottle
can be calculated by multiplying 100 (mL) x 0.7 (for 70% solution) x 1.285 g
sorbitol/mL. Therefore the dose in mL is as follows:
Dosage of Sorbitol:
Adults: 70% sorbitol, 1-2 mL/kg.
Children: 35% sorbitol, 1.5-2.3 mL/kg (maximum dosage: 50 g).
Note on Specific Pesticides: Significant poisoning with organophos-
phates, carbamates, and arsenicals generally results in a profuse diarrhea. Poi-
soning with diquat and to a lesser extent paraquat results in an ileus. The use of
sorbitol is not recommended in any of the above pesticide poisonings.
Position Statement: The administration of a cathartic alone has no role
in the management of the poisoned patient. There are no definite indications
for the use of cathartics in the management of the poisoned patient. Data are
conflicting with regard to use in combination with activated charcoal, and its
routine use is not endorsed. If a cathartic is used, it should be as a single dose in
order to minimize adverse effects. There are numerous contraindications,
including absent bowel sounds, abdominal trauma or surgery, or intestinal
perforation or obstruction. It is also contraindicated in volume depletion,
hypotension, electrolyte imbalance, or the ingestion of a corrosive substance.5
3. Activated Charcoal Adsorption
Activated charcoal is an effective absorbent for many poisonings.Volunteer
studies suggest that it will reduce the amount of poison absorbed if given within
60 minutes.6 There are insufficient data to support or exclude its use if time
from ingestion is prolonged, although some poisons that are less soluble may be
adsorbed beyond 60 minutes. Clinical trials with charcoal have been done with
poisons other than pesticides. There is some evidence that paraquat is well
adsorbed by activated charcoal.7'8 Charcoal has been anecdotally successful with
other pesticides.
12 GENERAL PRINCIPLES
-------
Dosage of Activated Charcoal:
Adults and children over 12 years: 25-100 g in 300-800 mL water.
Children under 12years: 25-50 g per dose.
Infants and toddlers under 20 kg. I g per kg body weight.
Many activated charcoal formulations come premixed with sorbitol. Avoid giv-
ing more than one dose of sorbitol as a cathartic in infants and children due to
the risk of rapid shifts of intravascular fluid.
Encourage the victim to swallow the adsorbent even though spontaneous vom-
iting continues. Antiemetic therapy may help control vomiting in adults or older
children. As an alternative, activated charcoal may be administered through an
orogastric tube or diluted with water and administered slowly through a nasogastric
tube. Repeated administration of charcoal or other absorbent every 2-4 hours may
be beneficial in both children and adults, but use of a cathartic such as sorbitol
should be avoided after the first dose. Repeated doses of activated charcoal should
not be administered if the gut is atonic. The use of charcoal without airway protec-
tion is contraindicated in the neurologically impaired patient.
Note on Specific Pesticides: The use of charcoal without airway pro-
tection should be used with caution in poisons such as organophosphates, car-
bamates, and organochlorines if they are prepared in a hydrocarbon solution.
Position Statement: Single-dose activated charcoal should not be used
routinely in the management of poisoned patients. Charcoal appears to be most
effective within 60 minutes of ingestion and may be considered for use for this
time period. Although it may be considered 60 minutes after ingestion, there is
insufficient evidence to support or deny its use for this time period. Despite
improved binding of poisons within 60 minutes, only one study exists9 to suggest
that there is improved clinical outcome. Activated charcoal is contraindicated in
an unprotected airway, a GI tract not anatomically intact, and when charcoal
therapy may increase the risk of aspiration of a hydrocarbon-based pesticide.6
4. Syrup of Ipecac
Ipecac has been used as an emetic since the 1950s. In a pediatric study,
administration of ipecac resulted in vomiting within 30 minutes in 88% of
children.10 However, in light of the recent review of the clinical effectiveness of
ipecac, it is no longer recommended for routine use in most poisonings.
Most clinical trials involve the use of pill form ingestants such as aspirin,2'11
acetaminophen,12 ampicillin,1 and multiple types of tablets.13 No clinical trials
have been done with pesticides. In 1996, more than 2 million human exposures
to a poisonous substances were reported to American poison centers. Ipecac
was recommended for decontamination in only 1.8% of all exposures.14
GENERAL PRINCIPLES 13
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Dosage of Syrup of Ipecac:
Adolescents and adults: 15-30 mL followed immediately with 240 mL
of water.
Children 1-12 years: 15 mL preceded or followed by 120 to 240
mL of water.
Infants 6 months to 12 months: 5-10 mL preceded or followed by 120
to 240 mL of water.
Dose may be repeated in all age groups if emesis does not occur within
20-30 minutes.
Position Statement: Ipecac syrup should not be administered routinely
in poisoned patients. If ipecac is used, it should be administered within 60
minutes of the ingestion. Even then, clinical studies have demonstrated no ben-
efit from its use. It should be considered only in an alert conscious patient who
has ingested a potentially toxic ingestion. Contraindications to its use include
the following: patients with diminished airway protective reflexes, the ingestion
of hydrocarbons with a high aspiration potential, the ingestion of a corrosive
substance, or the ingestion of a substance in which advanced life support may
be necessary within the next 60 minutes.15
5. Seizures
Lorazepam is increasingly being recognized as the drug of choice for status
epilepticus, although there are few reports of its use with certain pesticides.
One must be prepared to assist ventilation with lorazepam and any other medi-
cation used to control seizures. See dosage table on next page.
For organochlorine compounds, use of lorazepam has not been reported
in the literature. Diazepam is often used for this, and is still used in other pesti-
cide poisonings.
Dosage of Diazepam:
Adults: 5-10 mg IV and repeat every 5-10 minutes to maximum of
30 mg.
Children: 0.2-0.5 mg/kg IV every 5 minutes to maximum of 10 mg
in children over 5 years and 5 mg in children under 5 years.
14 GENERAL PRINCIPLES
-------
Dosage of Lorazepam:
Adults: 2-4 nig/dose given IV over 2-5 minutes. Repeat if necessary
to a maximum of 8 mg in a 12 hour period.
Adolescents: Same as adult dose, except maximum dose is 4 mg.
Children under 12years: 0.05-0.10 mg/kg IV over 2-5 minutes. Re-
peat if necessary .05 mg/kg 10-15 minutes after first dose, with a
maximum dose of 4 mg.
Caution: Be prepared to assist pulmonary ventilation mechanically if
respiration is depressed, to intubate the trachea iflaryngospasm occurs,
and to counteract hypotensive reactions.
Phenobarbital is an additional treatment option for seizure control. Dos-
age for infants, children, and adults is 15-20 mg/kg as an IV loading
dose. An additional 5 mg/kg IV may be given every 15-30 minutes to a
maximum of 30 mg/kg. The drug should be pushed no faster than 1 mg/
kg/minute.
For seizure management, most patients respond well to usual management
consisting of benzodiazepines, or phenytoin and phenobarbital.
References
1. Tenenbein M, Cohen S, and Sitar DS. Efficacy of ipecac-induced emesis, orogastric lavage,
and activated charcoal for acute drug overdose. Ann Emerg Med 1987;16:838- 41.
2. Danel V, Henry JA, and Glucksman E. Activated charcoal, emesis, and gastric lavage in aspi-
rin overdose. BrMed/1988;296:1507.
3. Saetta JP, March S, Gaunt ME, et al. Gastric emptying procedures in the self-poisoned pa-
tient: 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. JToxicol Clin Toxicol 1997;35:711-9.
5. American Academy of Clinical Toxicology, European Association of Poisons Centres and
ClinicalToxicologists. Position statement: Cathartics. JToxicol 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. JToxicol Clin Toxicol
1997;35:721-41.
7. Gaudreault P, Friedman PA, and Lovejoy FH Jr. Efficacy of activated charcoal and magne-
sium citrate in the treatment of oral paraquat intoxication. Ann Emerg Med 1985;14:123-5.
8. Terada H, Miyoshi T, Imaki M, et al. Studies on in vitro paraquat and diquat removal by
activated carbon. JExp Med 1994;41:31-40.
9. Merigian KS, Woodward M, Hedges JR, et al. Prospective evaluation of gastric emptying in
the self-poisoned patient. Am J Emerg Med 1990;8:479-83.
GENERAL PRINCIPLES 15
-------
10. Robertson W. Syrup of ipecac: A slow or fast emetic? AJDC 1962;103:136-9.
11. Curtis RA, Barone J, and Giacona N. Efficacy of ipecac and activated charcoal/cathartic.
Arch Intern Med 1984;144:48-52.
12. McNamara RM, Aaron CK, Gemborys M, et al. Efficacy of charcoal cathartic versus ipecac in
reducing serum acetaminophen in a simulated overdose. Ann Emerg Med 1989;18:934-8.
13. Neuvonen PJ, Vartiainen M, and Tokola O. Comparison of activated charcoal and ipecac
syrup in prevention of drug absorption. Eur J Clin Pharmacol 1983;24:557-62.
14. Litovitz RL, Smilkstein M, Felberg L, et al. 1996 Annual Report of the American
Association of Poison Control 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. JToxicol Clin Toxicol 1997;35:699-709.
16 GENERAL PRINCIPLES
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CHAPTER 3
Environmental and
Occupational History
Pesticide poisonings may go unrecognized because of the failure to take a proper
exposure history. This chapter is intended to remedy this often overlooked area
by providing basic tools for taking a complete exposure history In some situ-
ations where exposures are complex or multiple and/or symptoms atypical, it is
important to consider consultation with clinical toxicologists or specialists in
environmental and occupational medicine. Local Poison Control Centers should
also be considered when there are questions about diagnosis and treatment.
Although this manual deals primarily with pesticide-related diseases and
injury, the approach to identifying exposures is similar regardless of the specific
hazard involved. It is important to ascertain whether other non-pesticide ex-
posures are involved because of potential interactions between these hazards
and the pesticide of interest (e.g., pesticide intoxication and heat stress in agri-
cultural field workers).Thus, the following section on pesticide exposures should
be seen in the context of an overall exposure assessment.
Most pesticide-related diseases have clinical presentations that are similar
to common medical conditions and display nonspecific symptoms and physical
signs. Knowledge of a patient's exposure to occupational and environmental
factors is important for diagnostic, therapeutic, rehabilitative and public health
purposes. Thus, it is essential to obtain an adequate history of any environmen-
tal or occupational exposure which could cause disease or exacerbate an exist-
ing medical condition.
In addition to the appropriate patient history-taking, one must also con-
sider any other persons that may be similarly exposed in the home, work or
community environment. Each environmental or occupational disease identi-
fied should be considered a potential sentinel health event which may require
follow-up activities to identify the exposure source and any additional cases. By
identifying and eliminating the exposure source, one can prevent continued
exposure to the initial patient and any other individuals involved.
Patients with these types of diseases may be seen by health care providers
that are not familiar with these conditions. If an appropriate history is obtained
and there appears to be a suspect environmental or occupational exposure, the
health care provider can obtain consultation with specialists (e.g., industrial
hygienists, toxicologists, medical specialists, etc.) in the field of environmental
and occupational health. For the more severe sentinel health events and those
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 17
-------
that involve numerous exposed individuals, additional assistance can be ob-
tained by contacting the state health department, state regulatory agency (e.g.,
the agriculture department in the case of pesticide illness and injury), or other
related organizations (see list at end of chapter). Furthermore, some states re-
quire reporting of certain environmental and occupational conditions (e.g.,
pesticide case reporting in Arizona, California, Florida, Oregon, Texas, and
Washington).
This chapter reviews the types of questions to be asked in taking an occupa-
tional and environmental history (for both adult and pediatric patients), discusses
legal, ethical, and public health considerations, and lists information resources.
Taking an Exposure History
Given the time constraints of most health care providers, a few screening
questions are likely to be preferable to a lengthy questionnaire in identifying
occupational or environmental hazards. The screening questions below could
be incorporated into an existing general health questionnaire or routine
patient interview.
SCREENING QUESTIONS FOR OCCUPATIONAL
AND ENVIRONMENTAL EXPOSURES*
For an adult patient:
After establishing the chief complaint and history of the presenting illness:
What kind of work do you do?
(if unemployed) Do you think your health problems are related to your home
or other location?
(if employed) Do you think your health problems are related to your work? Are
your symptoms better or worse when you are at home or at work?
Are you now or have you previously been exposed to pesticides, solvents, or
other chemicals, dusts, fumes, radiation, or loud noise?
For a pediatric patient (questions asked of parent or guardian):
Do you think the patient's health problems are related to the home, daycare,
school, or other location?
Has there been any exposure to pesticides, solvents or other chemicals, dusts,
fumes, radiation, or loud noise?
What kind of work do the parents or other household members engage in?
If the clinical presentation or initial medical history suggests a potential occu-
pational or environmental exposure, a detailed exposure interview is needed.
An extensive exposure history provides a more complete picture of pertinent
exposure factors and can take up to an hour. The detailed interview includes
questions on occupational exposure, environmental exposure, symptoms and
medical conditions, and non-occupational exposure potentially related to ill-
ness or injury. Although the focus is on pesticide exposures and related health
18
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY
-------
effects, concurrent non-pesticide exposures need to be considered in the over-
all patient health assessment. Questions typical of a detailed interview are listed
on the next several pages, preceded by special concerns in addressing exposures
of children and agricultural workers. For further details on taking a history for
all types of occupational and environmental hazards, consult the ATSDR mono-
graph entitled "Taking an Exposure History"1 or a general occupational and
environmental medicine reference text.2
Special Patient Populations
Children
In comparison to adults, children may be at greater risk from pesticide
exposures due to growth and developmental factors. Consideration of fetal,
infant, toddler or child characteristics is helpful in an exposure evaluation: physical
location, breathing zones, oxygen consumption, food consumption, types of
foods consumed and normal behavioral development.3 Furthermore, transpla-
cental absorption and breast milk may pose additional routes of exposure. Al-
though environmental (and, at times, occupational) exposure to pesticides is
the focus of this chapter, the most significant hazard for children is uninten-
tional ingestion.4 Thus, it is very important to ask about pesticides used and
stored in the home, day care facility, school, and play areas.
Agricultural Workers
Data from California's mandatory pesticide poisoning reporting system would
imply an annual national estimate of 10,000-20,000 cases of farmworker poison-
ing.5 However, it is believed that these figures still represent serious underreporting
due to the lack of medical access for many farmworkers and misdiagnosis by
some clinicians. For these high-risk patients, the exposure history should include
specific questions about the agricultural work being done. For example:
Are pesticides being used at home or work?
Were the fields wet when you were picking?
Was any spraying going on while you were working in the fields?
Do you get sick during or after working in the fields?
The use of pesticides in the residence and taking home agricultural pesticides or
contaminated work clothes that are not properly separated from other clothes
may pose hazards for other household members as well.
Obtaining Additional Pesticide Information
In addition to the patient history, it is often helpful to obtain further infor-
mation on suspect pesticide products. Two documents are useful starting points
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 19
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DETAILED INTERVIEW FOR OCCUPATIONAL
AND ENVIRONMENTAL EXPOSURES
(Questions marked in bold type are especially important for a pesticide exposure history)
(1) Adult Patient
OCCUPATIONAL EXPOSURE
What is your occupation? (If unemployed, go to next section)
How long have you been doing this job?
Describe your work and what hazards you are exposed to (e.g., pesticides, solvents or other
chemicals, dust, fumes, metals, fibers, radiation, biologic agents, noise, heat, cold, vibration)
Under what circumstances do you use protective equipment? (e.g., work clothes, safety glasses,
respirator, gloves, and hearing protection)
Do you smoke or eat at the worksite?
List previous jobs in chronological order, include full and part-time, temporary, second jobs,
summer jobs, and military experience. (Because this question can take a long time to answer, one
option is to ask the patient to fill out a form with this question on it prior to the formal history taking by
the clinician. Another option is to take a shorter history by asking the patient to list only the prior jobs
that involved the agents of interest. For example, one could ask for all current and past jobs involving
pesticide exposure.)
ENVIRONMENTAL EXPOSURE HISTORY
Are pesticides (e.g., bug or weed killers, flea and tick sprays, collars, powders, or shampoos)
used in your home or garden or on your pet?
Do you or any household member have a hobby with exposure to any hazardous materials (e.g.,
pesticides, paints, ceramics, solvents, metals, glues)?
If pesticides are used:
Is a licensed pesticide applicator involved?
Are children allowed to play in areas recently treated with pesticides?
Where are the pesticides stored?
Is food handled properly (e.g., washing of raw fruits and vegetables)?
Did you ever live near a facility which could have contaminated the surrounding area (e.g., mine,
plant, smelter, dump site)?
Have you ever changed your residence because of a health problem?
Does your drinking water come from a private well, city water supply, and/or grocery store?
Do you work on your car?
Which of the following do you have in your home: air conditioner/purifier, central heating (gas or oil), gas stove,
electric stove, fireplace, wood stove, or humidifier?
Have you recently acquired new furniture or carpet, or remodeled your home?
Have you weatherized your home recently?
Approximately what year was your home built?
SYMPTOMS AND MEDICAL CONDITIONS
(If employed)
Does the timing of your symptoms have any relationship to your work hours?
Has anyone else at work suffered the same or similar problems?
Does the timing of yoursymptoms have any relationship to environmental activities listed above?
Has any other household member or nearby neighbor suffered similar health problems?
ENVIRONMENTAL AND
20 OCCUPATIONAL HISTORY
-------
NON-OCCUPATIONAL EXPOSURES POTENTIALLY RELATED TO ILLNESS OR INJURY
Do you use tobacco? If yes, in what forms (cigarettes, pipe, cigar, chewing tobacco)? About how many
do you smoke or how much tobacco do you use per day? At what age did you start using tobacco? Are
there other tobacco smokers in the home?
Do you drink alcohol? How much per day or week? At what age did you start?
What medications or drugs are you taking? (Include prescription and non-prescription uses)
Has anyone in the family worked with hazardous materials that they might have brought home
(e.g., pesticides, asbestos, lead)? (If yes, inquire about household members potentially exposed.)
(2) PedJatrJC Patient (questions asked of parent or guardian)
OCCUPATIONAL EXPOSURE
What is your occupation and that of other household members? (If no employed individuals, goto
next section)
Describe your work and what hazards you are exposed to (e.g., pesticides, solvents or other
chemicals, dust, fumes, metals, fibers, radiation, biologic agents, noise, heat, cold, vibration)
ENVIRONMENTAL EXPOSURE HISTORY
Are pesticides (e.g., bug or weed killers, flea and tick sprays, collars, powders, or shampoos)
used in your home or garden or on your pet?
Do you or any household member have a hobby with exposure to any hazardous materials (e.g.,
pesticides, paints, ceramics, solvents, metals, glues)?
If pesticides are used:
Is a licensed pesticide applicator involved?
Are children allowed to play in areas recently treated with pesticides?
Where are the pesticides stored?
Is food handled properly (e.g., washing of raw fruits and vegetables)?
Has the patient ever lived near a facility which could have contaminated the surrounding area
(e.g., mine, plant, smelter, dump site)?
Has the patient ever changed residence because of a health problem?
Does the patient's drinking water come from a private well, city water supply, and/or grocery
store?
Which of the following are in the patient's home: air conditioner/purifier, central heating (gas or oil), gas stove,
electric stove, fireplace, wood stove, or humidifier?
Is there recently acquired new furniture or carpet, or recent home remodeling in the patient's home?
Has the home been weatherized recently?
Approximately what year was the home built?
SYMPTOMS AND MEDICAL CONDITIONS
Does the timing of symptoms have any relationship to environmental activities listed above?
Has any other household member or nearby neighbor suffered similar health problems?
NON-OCCUPATIONAL EXPOSURES POTENTIALLY RELATED TO ILLNESS OR INJURY
Are there tobacco smokers in the home? If yes, in what forms (cigarettes, pipe, cigar, chewing tobacco)?
What medications or drugs is the patient taking? (Include prescription and non-prescription uses)
Has anyone in the family worked with hazardous materials that they might have brought home
(e.g., pesticides, asbestos, lead)? (If yes, inquire about household members potentially exposed.)
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY
21
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in the identification and evaluation of the pesticide exposure: the material safety
data sheet (MSDS) and the pesticide label.
Material Safety Data Sheet (MSDS). Under OSHA's Hazard
Communications Standard (29 CFR 1910.1200), all chemical manu-
facturers are required to provide an MSDS for each hazardous chemi-
cal they produce or import. Employers are required to keep copies
of MSDSs and make them available to the workers. The following
items are contained in an MSDS:
- Material identification
- Ingredients and occupational exposure limits
- Physical data
- Fire and explosion data
- Reactivity data
- Health hazard data
- Spill, leak, and disposal procedures
- Special protection data
- Special precautions and comments.
These documents tend to have very limited information on health
effects and some of the active ingredients may be omitted due to
trade secret considerations. One cannot rely solely on an MSDS in
making medical determinations.
Pesticide label. EPA requires that all pesticide products bear labels
that provide certain information. This information can help in evalu-
ating pesticide health effects and necessary precautions. The items
covered include the following:
- Product name
- Manufacturer
- EPA registration number
- Active ingredients
- Precautionary statements:
i. Human hazard signal words "Danger" (most hazardous),
"Warning," and "Caution" (least hazardous)
ii. Child hazard warning
iii. Statement of practical treatment (signs and symptoms of
poisoning, first aid, antidotes, and note to physicians in the
event of a poisoning)
iv. Hazards to humans and domestic animals
v. Environmental hazards
vi. Physical or chemical hazards
ENVIRONMENTAL AND
22 OCCUPATIONAL HISTORY
-------
- Directions for use
- Name and address of manufacturer
- Net contents
- EPA registration number
- EPA establishment number
- Worker Protection Standard (WPS) designation, including re-
stricted entry interval and personal protection equipment required
(see WPS description on page 25).
The EPA registration number is useful when contacting EPA for infor-
mation or when calling the National Pesticide Telecommunications
Network hotline (see page 29). Pesticide labels may differ from one
state to another based on area-specific considerations. Also, different
formulations of the same active ingredients may result in different label
information. The pesticide label lists information only for active ingre-
dients (not for inert components) and rarely contains information on
chronic health effects (e.g., cancer and neurologic, reproductive, and
respiratory diseases).6 Although further pesticide information is often
needed, these documents should be considered as the first step in iden-
tifying and understanding the health effects of a given pesticide.
For the agricultural worker patient, the health care provider has
two legal bases the EPA Worker Protection Standard and USDA
regulations under the 1990 Farm Bill for obtaining from the
employer the pesticide product name to which the patient was ex-
posed.When requesting this information, the clinician should keep
the patient's name confidential whenever possible.
Assessing the Relationship of
Work or Environment to Disease
Because pesticides and other chemical and physical hazards are often asso-
ciated with nonspecific medical complaints, it is very important to link the
review of systems with the timing of suspected exposure to the hazardous agent.
The Index of Signs and Symptoms in Section V provides a quick reference to
symptoms and medical conditions associated with specific pesticides. Further
details on the toxicology, confirmatory tests, and treatment of illnesses related
to pesticides are provided in each chapter of this manual.A general understand-
ing of pesticide classes and some of the more common agents is helpful in
making a pesticide related disease diagnoses.
In evaluating the association of a given pesticide exposure in the workplace
or environment and a clinical condition, key factors to consider are:
Symptoms and physical signs appropriate for the pesticide being
considered
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 23
-------
Co-workers or others in the environment who are ill
Timing of the problems
Confirmation of physical exposure to the pesticide
Environmental monitoring data
Biomonitoring results
Biological plausibility of the resulting health effect
Ruling out non-pesticide exposures or pre-existing illnesses.
A concurrent non-pesticide exposure can either have no health effect, ex-
acerbate an existing pesticide health effect, or solely cause the health effect in a
patient. In the more complicated exposure scenarios, assistance should be sought
from specialists in occupational and environmental health (see Information Re-
sources on page 27).
Legal, Ethical, and Public Health Considerations
Following are some considerations related to government regulation of
pesticides, ethical factors, and public health concerns that health care providers
should be aware of in assessing a possible pesticide exposure.
Reporting Requirements
When evaluating a patient with a pesticide-related medical condition, it
is important to understand the state-specific reporting requirements for the
workers' compensation system (if there has been an occupational exposure)
or surveillance system. Reporting a workers' compensation case can have
significant implications for the worker being evaluated. If the clinician is not
familiar with this system or is uncomfortable evaluating work-related health
events, it is important to seek an occupational medicine consultation or make
an appropriate referral.
At least six states have surveillance systems within their state health depart-
ments that cover both occupational and environmental pesticide poisonings: Cali-
fornia, Florida, New York, Oregon, Texas, and Washington. These surveillance
systems collect case reports on pesticide-related illness and injury from clinicians
and other sources; conduct selected interviews, field investigations, and research
projects; and function as a resource for pesticide information within their state. In
some states, as noted earlier, pesticide case reporting is legally mandated.
Regulatory Agencies
Since its formation in 1970, EPA has been the lead agency for the regula-
tion of pesticide use under the Federal Insecticide, Fungicide and Rodenticide
Act. EPA's mandates include the registration of all pesticides used in the United
States, setting restricted entry intervals, specification and approval of label in-
ENVIRONMENTALAND
24 OCCUPATIONAL HISTORY
-------
formation, and setting acceptable food and water tolerance levels. In addition,
EPA works in partnership with state and tribal agencies to implement two field
programs the certification and training program for pesticide applicators
and the agricultural worker protection standard to protect workers and
handlers from pesticide exposures. EPA sets national standards for certification
of over 1 million private and commercial pesticide applicators.
The authority to enforce EPA regulations is delegated to the states. For
example, calls concerning non-compliance with the worker protection stan-
dard can typically be made to the state agricultural department. In five states,
the department of the environment or other state agency has enforcement
authority. Anonymous calls can be made if workers anticipate possible retalia-
tory action by management. It should be noted that not all state departments of
agriculture have similar regulations. In California, for instance, employers are
required to obtain medical supervision and biological monitoring of agricul-
tural workers who apply pesticides containing cholinesterase-inhibiting com-
pounds. This requirement is not found in the federal regulations.
Outside the agricultural setting, the Occupational Safety and Health
Administration (OSHA) has jurisdiction over workplace exposures. All workers
involved in pesticide manufacturing would be covered by OSHA. OSHA sets
permissible exposure levels for selected pesticides. Approximately half the states
are covered by the federal OSHA; the rest have their own state-plan OSHA.
Individual state plans may choose to be more protective in setting their workplace
standards. Anonymous calls can also be made to either state-plan or federal
OSHA agencies.
For pesticide contamination in water, EPA sets enforceable maximum
containment levels. In food and drug-related outbreaks, EPA works jointly with
the Food and Drug Administration (FDA) and the U.S. Department of
Agriculture (USDA) to monitor and regulate pesticide residues and their
metabolites. Tolerance limits are established for many pesticides and their
metabolites in raw agricultural commodities.
In evaluating a patient with pesticide exposure, the clinician may need
to report a pesticide intoxication to the appropriate health and/or regulatory
agency.
Worker Protection Standard
EPA's Worker Protection Standard (WPS) became fully effective in 1995.
The intent of the regulation is to eliminate or reduce pesticide exposure, mitigate
exposures that occur, and inform agricultural workers about the hazards of
pesticides. The WPS applies to two types of workers in the farm, greenhouse,
nursery, and forest industries: (1) agricultural pesticide handlers (mixer, loader,
applicator, equipment cleaner or repair person, and flagger), and (2) field workers
(cultivator or harvester).
The WPS includes requirements that agricultural employers notify workers
about pesticide treatments in advance, offer basic pesticide safety training, provide
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 25
-------
personal protective equipment for direct work with pesticides, and observe
restricted entry interval (REI) times. (The REI is a required waiting period before
workers can return to areas treated with pesticides.) Of special interest to health
care providers, the WPS also requires agricultural employers to:
Post an emergency medical facility address and phone number in a
central location.
Arrange immediate transport from the agricultural establishment to
a medical facility for a pesticide-affected worker.
Supply the affected worker and medical personnel with product name,
EPA registration number, active ingredient, label medical information,
a description of how the pesticide was used, and exposure information.
Ethical Considerations
Attempts to investigate an occupational pesticide exposure may call for ob-
taining further information from the worksite manager or owner. Any contact
with the worksite should be taken in consultation with the patient because of the
potential for retaliatory actions (such as loss of job or pay cuts). Ideally, a request
for a workplace visit or more information about pesticide exposure at the work-
place will occur with the 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 out-
break investigation.
Similarly, the discovery of pesticide contamination in a residence, school,
daycare setting, food product, or other environmental site or product can have
public health, financial, and legal consequences for the patient and other indi-
viduals (e.g., building owner, school district, food producer). It is prudent to
discuss these situations and follow-up options with the patient as well as a knowl-
edgeable environmental health specialist and appropriate state or local agencies.
Public Health Considerations
Health care providers are often the first to identify a sentinel health event that
upon further investigation develops into a full-blown disease outbreak. A disease
outbreak is defined as a statistically elevated rate of disease among a well-defined
population as compared to a standard population. For example, complaints about
infertility problems among workers at a dibromochloropropane (DBCP) manufac-
turing plant in California led to diagnoses of azoospermia (lack of sperm) or oli-
gospermia (decreased sperm count) among a handful of otherwise healthy young
men working at the plant.7 An eventual disease outbreak investigation resulted in the
first published report of a male reproductive toxicant in the workplace.At the time,
DBCP was used as a nematocide; it has since been banned in the United States.
Disease outbreak investigations are conducted for all kinds of exposures
ENVIRONMENTAL AND
26 OCCUPATIONAL HISTORY
-------
and health events, not only those in the occupational and environmental area.
Usually, assistance from government or university experts is needed in the in-
vestigation, which may require access to information, expertise, and resources
beyond that available to the average clinician. The steps involved in such an
investigation and the types of information typically gathered in the preliminary
clinical stages are outlined below. The clinician must be aware that an outbreak
investigation may be needed when a severe and widespread exposure and dis-
ease scenario exists. For more information on disease outbreak investigations,
consult the literature.8'9
STEPS IN INVESTIGATING A DISEASE OUTBREAK
Confirm diagnosis of initial case reports (the "index" cases)
Identify other unrecognized cases
Establish a case definition
Characterize cases by person, place, and time characteristics (e.g., age, race, ethnicity, gen-
der, location within a company or a neighborhood, timeline of exposure and health events)
Create plot of case incidence by time (an epidemic curve)
Determine if a dose-response relationship exists (i.e., more severe clinical case presen-
tation for individuals with higher exposures)
Derive an attack rate and determine if statistical significance is achieved (divide num-
ber of incident cases by number of exposed individuals and multiply by 100 to obtain
attack rate percentage)
Information Resources
Government Agencies:
EPA Office of Pesticide Programs
Overall pesticide regulation with special programs on agricultural workers and
pesticide applicators. Specific programs include the promotion of the reduc-
tion of pesticide use, establishment of tolerance levels for food, and investiga-
tion of pesticide releases and exposure events.
Address: EPA - Office of Pesticide Programs
401 M Street SW (7501C)
Washington, DC 20460
Telephone: 703-305-7090
Web site: www.epa.gov/pesticides
EPA - Certification and Worker Protection Branch
Within the Office of Pesticide Programs, the Certification and Worker Protec-
tion Branch addresses worker-related pesticide issues and pesticide applicator
certification activities. Special emphasis is placed on the adequate training of
farm workers, pesticide applicators, and health care providers.Various training
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY
27
-------
materials in several languages are available.
Address: EPA - OPP
401 M Street SW (7506C)
Washington, DC 20460
Telephone: 703-305-7666
Web site: www.epa.gov/pesticides/safety
Occupational Safety and Health Administration (OSHA)
More than 100 million workers and 6.5 million employers are covered under
the Occupational Safety and Health Act, which covers workers in pesticide
manufacturing as well as other industries. OSHA and its state partners have
approximately 2100 inspectors, plus investigators, standards writers, educators,
physicians, and other staff in over 200 offices across the country. OSHA sets
protective workplace standards, enforces the standards, and offers employers
and employees technical assistance and consultation programs. Note that some
states have their own OSHA plan.
Address: OSHA - US 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 land-
grant system, to provide farmers and ranchers information to reduce and
prevent agricultural-related work incidents. The Pesticide Applicator Training
program trains applicators in the safe use of pesticides and coordinates
pesticide-related safety training programs.
Address: USDA
14th & Independence SW
Washington, DC 20250
Telephone: 202-720-2791
Web site: www.reeusda.gov
ENVIRONMENTAL AND
28 OCCUPATIONAL HISTORY
-------
National Center for Environmental Health (NCEH),
Centers for Disease Control (CDC)
NCEH provides expertise in environmental pesticide case surveillance and dis-
ease outbreak investigations.
Address: NCEH, CDC
Mailstop F29
4770 Buford Highway NE
Atlanta, GA 30341
Tel: 770-488-7030
Web site: www.cdc.gov/nceh/ncehhome.htm
National Institute for Occupational Safety and Health (NIOSH),
Centers for Disease Control (CDC)
NIOSH is the federal agency responsible for conducting research on occupational
disease and injury. NIOSH may investigate potentially hazardous working condi-
tions upon request, makes recommendations on preventing workplace disease and
injury, and provides training to occupational 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
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 29
-------
Northeast Center for Agricultural
and Occupational Health
One Atwell Road
Cooperstown, NY 13326
Tel: 607-547-6023
Southwest Center for Agricultural
Health, Injury and Education
University ofTexas
Health Center at Tyler
PO Box 2003
Tyler,TX 75710
Tel: 903-877-5896
Pacific Northwest Agricultural Safety
and Health Center
University ofWashington
Department of Environmental Health
Seattle, WA 98195
Tel: 206-543-0916
Midwest Center for Agricultural
Research, Education and Disease and
Injury Prevention
National Farm Medicine Center
Marshfield,WI 54449-5790
Tel: 715-389-3415
Non-Governmental Organizations:
National Pesticide Telecommunications Network
The National Pesticide Telecommunications Network (NPTN) is based at
Oregon State University and is cooperatively sponsored by the University and
EPA. NPTN serves as a source of objective, science-based pesticide informa-
tion on a wide range of pesticide-related topics, such as recognition and man-
agement of pesticide poisonings, safety information, health and environmental
effects, referrals for investigation of pesticide incidents and emergency treat-
ment for both humans and animals, and cleanup and disposal procedures.
A toll-free telephone service provides pesticide information to callers in
the continental United States, Puerto Rico, and the Virgin Islands. Additionally,
pesticide questions and comments can be sent to an e-mail address. The Web
site has links to other sites and databases for further information.
NPTN hotline:
Hours of operation:
Web site:
E-mail address:
l_800-858-7378
9:30 am - 7:30 pm E.S.T daily except holidays
http: //ace. orst. edu/info/nptn/
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
ENVIRONMENTAL AND
30 OCCUPATIONAL HISTORY
-------
American Farm Bureau Federation
The AFBF is the nation's largest general farm organization. Information on how
to contact individual state-based farm bureaus is available on their Web site.
Web site: www.fb.com
Association of Occupational and Environmental Clinics (AOEC)
This association is a network of 63 clinics representing more than 250 specialists.
Address: AOEC
1010 Vermont Ave, NW, Suite 513
Washington, DC 20005
Telephone: 202-347-4976
Web site: http://152.3.65.120/oem/aoec.htm
Poison Control Centers
For a list of state and regional poison control centers, or the nearest location,
consult the NPTNWeb site (http://ace.orst.edu/info/nptn).
Pesticide Information Databases:
Extension Toxicology Network (EXTOXNET)
http://ace.ace. orst. edu/info/extoxnet
The Extension Service's Toxicology Network, EXTOXNET, provides science-
based information about pesticides to health care providers treating pesticide-
related health concerns. Pesticide toxicological information is developed
cooperatively by the University of California-Davis, Oregon State University,
Michigan State University, Cornell University, and the University of Idaho.
IRIS
www. epa.go v/ngispgm 3/iris
The Integrated Risk Information System IRIS is an electronic database, main-
tained by EPA, on human health effects that may result from exposure to various
chemicals in the environment. IRIS is intended for those without extensive training
in toxicology, but with some knowledge of health sciences. It provides hazard iden-
tification and dose-response assessment information. Combined with specific expo-
sure information, the data in IRIS can be used for characterization of the public
health risks of a chemical in a particular situation that can lead to a risk management
decision designed to protect public health. Extensive supporting documentation
available online.
ENVIRONMENTAL AND
OCCUPATIONAL HISTORY 31
-------
Agency for Toxic Substances and Disease Registry
http://atsdTl.atsdT.cdc.goV.8080/toxfaq.html
ATSDR (part of the Department of Human Health and Services) publishes
fact sheets and other information on pesticides and other toxic substances.
California Pesticide Databases
http://www. cdpr. ca.gov/docs/database/database.htm
Includes Pesticidal Chemical Ingredients Queries, links to EPA's OfHceof Pesticide
Programs chemical dictionary, Product/Label Database Queries (updated nightly),
a current listing of California's Section 18 Emergency Exemptions, and more.
References
1. Frank A and Balk S. ATSDR Case Studies in Environmental Medicine #26, Taking an
Exposure History. Atlanta: Agency forToxic Substances and Disease Registry, Oct. 1992.
2. LaDou J. Approach to the diagnosis of occupational illness. In: LaDou J (ed). Occupational
and Environmental Medicine, 2nd ed. Stamford, CT: Appleton and Lange, 1997.
3. Bearer C. Chapter 10: Pediatric developmental toxicology. In: Brooks SM, Gochfield M, Herzstein
J, et al. Environmental Medicine. St. Louis, MO: Mosby Yearbook, 1995, pp. 115-28.
4. Jackson RJ. Chapter 31: Hazards of pesticides to children. Ibid, pp. 377-82.
5. Blondell JM. Epidemiology of pesticide poisonings in the United States, with special refer-
ence to occupational cases. In: Keifer MC (ed). Human Health Effects of Pesticides, Occu-
pational Medicine: State of the Art Reviews, Philadelphia: Hanley & Belfus, Inc., 1997.
6. Keifer MC (ed). Ibid.
7. Osorio, AM. Chapter 26: Male reproductive toxicology. In: LaDou J (ed), op. cit.
8. Brooks SM, Gochfield M, Herzstein J, et al. Environmental Medicine. St. Louis, MO: Mosby
Yearbook, 1995.
9. Steenland K. Case Studies in Occupational Epidemiology. New York: Oxford University
Press, 1993.
ENVIRONMENTAL AND
32 OCCUPATIONAL HISTORY
-------
Section II
INSECTICIDES
-------
CHAPTER 4
HIGHLIGHTS
Acts through
phosphorylation of the
acetylcholinesterase enzyme
at nerve endings
Absorbed by inhalation,
ingestion, and skin
penetration
Muscarinic, nicotinic & CMS
effects
Signs and Symptoms:
Headache, hypersecretion,
muscle twitching, nausea,
diarrhea
Respiratory depression,
seizures, loss of
consciousness
Miosis is often a helpful
diagnostic sign
Treatment:
Clear airway, improve tissue
oxygenation
Administer atropine sulfate
intravenously
Pralidoxime may be
indicated
Proceed concurrently with
decontamination
Contraindicated:
Morphine, succinylcholine,
theophylline,
phenothiazines, reserpine
Organophosphate Insecticides
Since the removal of organochlorine insecticides from use, organophosphate
insecticides have become the most widely used insecticides available today. More
than forty of them are currently registered for use and all run the risk of acute
and subacute toxicity Organophosphates are used in agriculture, in the home,
in gardens, and in veterinary practice. All apparently share a common mecha-
nism of cholinesterase inhibition and can cause similar symptoms. Because they
share this mechanism, exposure to the same organophosphate by multiple routes
or to multiple organophosphates by multiple routes can lead to serious additive
toxicity. It is important to understand, however, that there is a wide range of
toxicity in these agents and wide variation in cutaneous absorption, making
specific identification and management quite important.
Toxicology
Organophosphates poison insects and mammals primarily by phosphory-
lation of the acetylcholinesterase enzyme (AChE) at nerve endings. The result
is a loss of available AChE so that the effector organ becomes overstimulated by
the excess acetylcholine (ACh, the impulse-transmitting substance) in the nerve
ending. The enzyme is critical to normal control of nerve impulse transmission
from nerve fibers to smooth and skeletal muscle cells, glandular cells, and
autonomic ganglia, as well as within the central nervous system (CNS). Some
critical proportion of the tissue enzyme mass must be inactivated by phospho-
rylation before symptoms and signs of poisoning become manifest.
At sufficient dosage, loss of enzyme function allows accumulation of ACh
peripherally at cholinergic neuroeffector junctions (muscarinic effects), skeletal
nerve-muscle junctions, and autonomic ganglia (nicotinic effects), as well as
centrally. At cholinergic nerve junctions with smooth muscle and gland cells,
high ACh concentration causes muscle contraction and secretion, respectively.
At skeletal muscle junctions, excess ACh may be excitatory (cause muscle twitch-
ing), but may also weaken or paralyze the cell by depolarizing the end-plate. In
the CNS, high ACh concentrations cause sensory and behavioral disturbances,
incoordination, depressed motor function, and respiratory depression. Increased
pulmonary secretions coupled with respiratory failure are the usual causes of
death from organophosphate poisoning. Recovery depends ultimately on gen-
eration of new enzyme in all critical tissues.
34
ORGANOPHOSPHATES
-------
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
Pro ban
DEF
De-Green
E-Z-Off D
demeton*
systox
demeton-S-methyl
Duratox
M eta systox 1
dial if or
Torak
diazinon
dichlorofenthion
COMMERCIAL
VC-13 Nemacide
dichlorvos
DDVP
Vapona
dicrotophos*
Bidrin
dimefos*
Hanane
Pestox XIV
dimethoate
Cygon
DeFend
dioxathion*
Delnav
disulfoton*
Disyston
ditalimfos
edifenphos
endothion*
EPBP
S-Seven
EPN+
ethion
Ethanox
ethoprop
Mocap
ethyl parathion*
E605
Parathion
thiophos
etrimfos
Ekamet
famphur
Bash
Bo-Ana
Famfos
fenamiphos*
Nemacur
fenitrothion
Accothion
Agrothion
Sumithion
fenophosphon*
Agritox
trichloronate
fensulfothion*
Dasanit
fenthion
Baytex
Entex
Tiguvon
fonofos*
Dyfonate
N-2790
formothion
Anthio
fosthietan*
Nem-A-Tak
heptenophos
Hostaquick
hiometon
Ekatin
PRODUCTS
hosalone
Zolone
IBP
Kitazin
iodofenphos
Nuvanol-N
isazofos
Brace
Miral
Triumph
isofenphos*
Amaze
Oftanol
isoxathion
E-48
Karphos
leptophos
Phosvel
malathion
Cythion
mephosfolan*
Cytrolane
merphos
Easy off-D
Folex
methamidophos*
Monitor
methidathion*
Supracide
Ultracide
methyl parathion*
E601
Penncap-M
methyl trithion
mevinphos*
Duraphos
Phosdrin
mipafox*
Isopestox
Pestox XV
monocrotophos*
Azodrin
naled
Dibrom
oxydemeton-methyl
Metasystox-R
oxydeprofos
Metasystox-S
phencapton
G 28029
phenthoate
dimephenthoate
Phenthoate
phorate*
Rampart
Thimet
phosalone
Azofene
Zolone
phosfolan*
Cylan
Cyolane
phosmet
Imidan
Prolate
phosphamidon*
Dimecron
phostebupirim
Aztec
phoxim
Baythion
pirimiphos-ethyl
Primicid
pirimiphos-methyl
Actellic
profenofos
Curacron
propetamphos
Safrotin
propyl thiopyro-
phosphate*
Aspon
prothoate
Fac
pyrazophos
Afugan
Curamil
pyridaphenthion
Ofunack
quinalphos
Bayrusil
ronnel
Fenchlorphos
Korlan
schradan*
OMPA
sulfotep*
Bladafum
Dithione
Thiotepp
sulprofos
Bolstar
Helothion
temephos
Abate
Abathion
terbufos
Contraven
Counter
tetrachlorvinphos
Gardona
Rabon
tetraethyl pyrophos-
phate+
TEPP
triazophos
Hostathion
trichlorfon
Dipterex
Dylox
Neguvon
Proxol
+ Indicates high toxidty. Highly
toxic organophosphates have
listed oral LD50 values (rat) less
than or equal to 50 mg/kg body
weight. Most other organo-
phosphates included in this table
are considered moderately toxic,
with LD50 values in excess of 50
mg/kg and less than 500 mg/kg.
ORGANOPHOSPHATES 35
-------
Organophosphates are efficiently absorbed by inhalation, ingestion, and skin
penetration. There is considerable variation in the relative absorption by these
various routes. For instance, the oral LD50 of parathion in rats is between 3-8 nig/
kg, which is quite toxic,1'2 and essentially equivalent to dermal absorption with
an LD5Q of 8 nig/kg.2 On the other hand, the toxicity of phosalone is much
lower from the dermal route than the oral route, with rat LD5Qs of 1500 mg/kg
and 120 mg/kg, respectively2 In general, the highly toxic agents are more likely
to have high-order dermal toxicity than the moderately toxic agents.
Chemical Classes: To some degree, the occurrence of poisoning depends
on the rate at which the pesticide is absorbed. Breakdown occurs chiefly by
hydrolysis in the liver; rates of hydrolysis vary widely from one compound to
another. In the case of certain organophosphates whose breakdown is relatively
slow, significant temporary storage in body fat may occur. Some organophos-
phates such as diazinon and methyl parathion have significant lipid solubility,
allowing fat storage with delayed toxicity due to late release.3 Delayed toxicity
may also occur atypically with other organophosphates, specifically
dichlorofenthion and demeton-methyl.4 Many organothiophosphates readily
undergo conversion from thions (P=S) to oxons (P=O). Conversion occurs in
the environment under the influence of oxygen and light, and in the body,
chiefly by the action of liver microsomes. Oxons are much more toxic than
thions, but oxons break down more readily. Ultimately, both thions and oxons
are hydrolyzed at the ester linkage, yielding alkyl phosphates and leaving groups,
both of which are of relatively low toxicity. They are either excreted or further
transformed in the body before excretion.
The distinction between the different chemical classes becomes important
when the physician interprets tests from reference laboratories. This can be espe-
cially important when the lab analyzes for the parent compound (i.e., chlorpyrifos
in its thiophosphate form) instead of the metabolite form (chlorpyrifos will be
completely metabolized to the oxon after the first pass through the liver).
Within one or two days of initial organophosphate binding to AChE, some
phosphorylated acetylcholinesterase enzyme can be de-phosphorylated (reac-
tivated) by the oxime antidote pralidoxime. As time progresses, the enzyme -
phosphoryl bond is strengthened by loss of one alkyl group from the phosphoryl
adduct, a process called aging. Pralidoxime reactivation is therefore no longer
possible after a couple of days,5 although in some cases, improvement has still
been seen with pralidoxime administration days after exposure.6
OPIDN: Rarely, certain organophosphates have caused a different kind of
neurotoxicity consisting of damage to the afferent fibers of peripheral and cen-
tral nerves and associated with inhibition of "neuropathy target esterase" (NTE).
This delayed syndrome has been termed organophosphate-induced delayed
neuropathy (OPIDN), and is manifested chiefly by weakness or paralysis and
paresthesia of the extremities.7 OPIDN predominantly affects the legs and may
36 ORGANOPHOSPHATES
-------
persist for weeks to years.These rare occurrences have been found shortly after
an acute and often massive exposure, but in some cases, symptoms have per-
sisted for months to years. Only a few of the many organophosphates used as
pesticides have been implicated as causes of delayed neuropathy in humans.
EPA guidelines require that organophosphate and carbamate compounds which
are candidate pesticides be tested in susceptible animal species for this neuro-
toxic property.
Three epidemiologic studies with an exposed group and a control group
also suggest that a proportion of patients acutely poisoned from any organo-
phosphate can experience some long-term neuropsychiatric sequelae. The
findings show significantly worse performance on a battery of neurobehavioral
tests, including memory, concentration, and mood, and compound-specific
peripheral neuropathy in some cases. These findings are subtle and may some-
times be picked up only on neuropsychologic testing rather than on a neuro-
logic exam.8"10 Follow-ups of case series have occasionally found some
individuals reporting persistent headaches, blurred vision, muscle weakness,
depression, memory and concentration problems, irritability, and/or develop-
ment of intolerance to selected chemical odors.11"15
Intermediate Syndrome: In addition to acute poisoning episodes and
OPIDN, an intermediate syndrome has been described. This syndrome occurs
after resolution of the acute cholinergic crisis, generally 24-96 hours after ex-
posure. It is characterized by acute respiratory paresis and muscular weakness,
primarily in the facial, neck, and proximal limb muscles. In addition, it is often
accompanied by cranial nerve palsies and depressed tendon reflexes. Like OPIDN,
this syndrome lacks muscarinic symptomatology, and appears to result from a
combined pre- and post-synaptic dysfunction of neuromuscular transmission.
Symptoms do not respond well to atropine and oximes; therefore treatment is
mainly supportive.16'17 The most common compounds involved in this syn-
drome are methyl parathion, fenthion, and dimethoate, although one case with
ethyl parathion was also observed.17
Other specific properties of individual organophosphates may render them
more hazardous than basic toxicity data suggest. By-products can develop in long-
stored malathion which strongly inhibit the hepatic enzymes operative in malathion
degradation, thus enhancing its toxicity. Certain organophosphates are exception-
ally prone to storage in fat tissue, prolonging the need for antidote for several days
as stored pesticide is released back into the circulation. Animal studies have demon-
strated potentiation of effect when two or more organophosphates are absorbed
simultaneously; enzymes critical to the degradation of one are inhibited by the
other. Animal studies have also demonstrated a protective effect from phenobar-
bital which induces hepatic degradation of the pesticide.1 Degradation of some
compounds to a trimethyl phosphate can cause restrictive lung disease.18
ORGANOPHOSPHATES 37
-------
Signs and Symptoms of Poisoning
Symptoms of acute organophosphate poisoning develop during or after
exposure, within minutes to hours, depending on the method of contact. Ex-
posure by inhalation results in the fastest appearance of toxic symptoms, fol-
lowed by the gastrointestinal route and finally the dermal route. All signs and
symptoms are cholinergic in nature and affect muscarinic, nicotinic, and central
nervous system receptors.5The critical symptoms in management are the respi-
ratory symptoms. Sufficient muscular fasciculations and weakness are often
observed as to require respiratory support; respiratory arrest can occur sud-
denly. Likewise, bronchorrhea and bronchospasm may often impede efforts at
adequate oxygenation of the patient.
Bronchospasm and bronchorrhea can occur, producing tightness in the
chest, wheezing, productive cough, and pulmonary edema. A life threatening
severity of poisoning is signified by loss of consciousness, incontinence, con-
vulsions, and respiratory depression. The primary cause of death is respiratory
failure, and there usually is a secondary cardiovascular component. The classic
cardiovascular sign is bradycardia which can progress to sinus arrest. However,
this may be superseded by tachycardia and hypertension from nicotinic (sym-
pathetic ganglia) stimulation.19 Toxic myocardiopathy has been a prominent
feature of some severe organophosphate poisonings.
Some of the most commonly reported early symptoms include headache,
nausea, dizziness, and hypersecretion, the latter of which is manifested by sweat-
ing, salivation, lacrimation, and rhinorrhea. Muscle twitching, weakness, tremor,
incoordination, vomiting, abdominal cramps, and diarrhea all signal worsening of
the poisoned state. Miosis is often a helpful diagnostic sign and the patient may
report blurred and/or dark vision. Anxiety and restlessness are prominent, as are a
few reports of choreaform movements. Psychiatric symptoms including depres-
sion, memory loss, and confusion have been reported.Toxic psychosis, manifested
as confusion or bizarre behavior, has been misdiagnosed as alcohol intoxication.
Children will often present with a slightly different clinical picture than adults.
Some of the typical cholinergic signs of bradycardia, muscular fasciculations, lac-
rimation, and sweating were less common. Seizures (22%-25%) and mental status
changes including lethargy and coma (54%-96%) were common.20'21 In com-
parison, only 2-3% of adults present with seizures. Other common presenting
signs in children include flaccid muscle weakness, miosis, and excessive salivation.
In one study, 80% of cases were transferred with the wrong preliminary diagno-
sis.20 In a second study, 88% of the parents initially denied any exposure history.21
See the preceding Toxicology section for information regarding the fea-
tures of the intermediate syndrome and OPIDN.
38 ORGANOPHOSPHATES
-------
Confirmation of Poisoning
If poisoning is probable, treat the patient immediately. Do not wait
for laboratory confirmation.
Blood samples should be drawn to measure plasma pseudocholinesterase
and red blood cell AChE levels. Depressions of plasma pseudocholinesterase
and/or RBC acetylcholinersterase enzyme activities are generally available bio-
chemical indicators of excessive organophosphate absorption. Certain organo-
APPROXIMATE LOWER LIMITS OF NORMAL PLASMA
AND RED CELL CHOLINESTERASE ACTIVITIES IN HUMANS*
Methods Plasma RBC
pH (Michel) 0.45 0.55
pH Stat(Nabb-Whitfield) 2.3 8.0
BMC Reagent Set
(Ellman-Boehringer) 1,875
DupontACA <8
Garry-Routh (Micro)
Technicon 2.0 8.0
Blood
3,000
Male 7.8
Female 5.E
Whole units
ApH per ml per hr
|iM per ml per min
mil per ml per min
Units per ml
HM-SH per 3mL per min
|iM per ml per min
1 Because measurement technique varies among laboratories, more accurate estimates of
minimum normal values are usually provided by individual laboratories.
phosphates may selectively inhibit either plasma pseudocholinesterase or RBC
acetylcholinesterase.22 A minimum amount of organophosphate must be ab-
sorbed to depress blood cholinesterase activities, but enzyme activities, espe-
cially plasma pseudocholinesterase, may be lowered by dosages considerably
less than are required to cause symptomatic poisoning.The enzyme depression
is usually apparent within a few minutes or hours of significant absorption of
organophosphate. Depression of the plasma enzyme generally persists several
days to a few weeks.The RBC enzyme activity may not reach its minimum for
several days, and usually remains depressed longer, sometimes 1 -3 months, until
new enzyme replaces that inactivated by organophosphate. The above table
lists approximate lower limits of normal plasma and RBC cholinesterase activi-
ties of human blood, measured by several methods. Lower levels usually in-
dicate excessive absorption of a cholinesterase-inhibiting chemical.
ORGANOPHOSPHATES 39
-------
In certain conditions, the activities of plasma and RBC cholinesterase are
depressed in the absence of chemical inhibition. About 3% of individuals have
a genetically determined low level of plasma pseudocholinesterase. These
persons are particularly vulnerable to the action of the muscle-paralyzing drug
succinylcholine (often administered to surgical patients), but not to organo-
phosphates. Patients with hepatitis, cirrhosis, malnutrition, chronic alcoholism,
and dermatomyositis exhibit low plasma cholinesterase activities. A number of
toxicants, notably cocaine, carbon disulfide, benzalkonium salts, organic mer-
cury compounds, ciguatoxins, and solanines may reduce plasma pseudocho-
linesterase activity. Early pregnancy, birth control pills, and metoclopramide
may also cause some depression. The RBC acetylcholinesterase is less likely
than the plasma enzyme to be affected by factors other than organophosphates.
It is, however, reduced in certain rare conditions that damage the red cell mem-
brane, such as hemolytic anemia.
The alkyl phosphates and phenols to which organophosphates are hydro-
lyzed in the body can often be detected in the urine during pesticide absorp-
tion and up to about 48 hours thereafter.These analyses are sometimes useful in
identifying and quantifying the actual pesticide to which workers have been
exposed. Urinary alkyl phosphate and phenol analyses can demonstrate orga-
nophosphate absorption at lower dosages than those required to depress cho-
linesterase activities and at much lower dosages than those required to produce
symptoms and signs. Their presence may simply be a result of organophos-
phates in the food chain.
Detection of intact organophosphates in the blood is usually not possible
except during or soon after absorption of a substantial amount. In general,
organophosphates do not remain unhydrolyzed in the blood for more than a
few minutes or hours, unless the quantity absorbed is large or the hydrolyzing
liver enzymes are inhibited.
Treatment
Caution: Persons attending the victim should avoid direct contact with heavily contami-
nated clothing and vomitus. Wear rubber gloves while washing pesticide from skin and
hair. Vinyl gloves provide no protection.
1. Airway protection. Ensure that a clear airway exists. Intubate the patient
and aspirate the secretions with a large-bore suction device if necessary.
Administer oxygen by mechanically assisted pulmonary ventilation if respiration
is depressed. Improve tissue oxygenation as much as possible before
administering atropine, so as to minimize the risk of ventricular
fibrillation. In severe poisonings, it may be necessary to support pulmonary
ventilation mechanically for several days.
40 ORGANOPHOSPHATES
-------
2. Atropine sulfate. Administer atropine sulfate intravenously, or intramuscu-
larly if intravenous injection is not possible. Remember that atropine can be
administered through an endotracheal tube if initial IV access is difficult to
obtain. Depending on the severity of poisoning, doses of atropine ranging from
very low to as high as 300 mg per day may be required,23 or even continuous
infusion.24'25 (See dosage on next page.)
The objective of atropine antidotal therapy is to antagonize the effects of
excessive concentrations of acetylcholine at end-organs having muscarinic re-
ceptors. Atropine does not reactivate the cholinesterase enzyme or accelerate
disposition of organophosphate. Recrudescence of poisoning may occur if tis-
sue concentrations of organophosphate remain high when the effect of atro-
pine wears off. Atropine is effective against muscarinic manifestations, but it is
ineffective against nicotinic actions, specifically muscle weakness and twitch-
ing, and respiratory depression.
Despite these limitations, atropine is often a life-saving agent in organophos-
phate poisonings. Favorable response to a test dose of atropine (1 mg in adults,
0.01 mg/kg in children under 12 years) can help differentiate poisoning by anti-
cholinesterase agents from other conditions. However, lack of response, with no
evidence of atropinization (atropine refractoriness) is typical of more severe poi-
sonings. The adjunctive use of nebulized atropine has been reported to improve
respiratory distress, decrease bronchial secretions, and increase oxygenation.26
3. Glycopyrolate has been studied as an alternative to atropine and found to
have similar outcomes using continuous infusion. Ampules of 7.5 mg of
glycopyrolate were added to 200 mL of saline and this infusion was titrated to the
desired effects of dry mucous membranes and heart rate above 60 beats/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 cho-
linesterase reactivator, in cases of severe poisoning by organophosphate pesti-
cides in which respiratory depression, muscle weakness, and/or twitching are
severe. (See dosage table on page 43.) When administered early (usually less
than 48 hours after poisoning), pralidoxime relieves the nicotinic as well as the
muscarinic effects of poisoning. Pralidoxime works by reactivating the cho-
linesterase and also by slowing the "aging" process of phosphorylated cho-
linesterase to a non-reactivatable form.
Note: Pralidoxime is of limited value and may actually be hazardous in poi-
sonings by the cholinesterase-inhibiting carbamate compounds (see Chapter 5).
ORGANOPHOSPHATES 41
-------
Dosage of Atropine:
In moderately severe poisoning (hypersecretion and other end-organ
manifestations without central nervous system depression), the follow-
ing dosage schedules have been used:
Adults and children over 12years: 2.0-4.0 mg, repeated every 15 min-
utes until pulmonary secretions are controlled, which may be ac-
companied by other signs of atropinization, including flushing, dry
mouth, dilated pupils, and tachycardia (pulse of 140 per minute).
Warning: In cases of ingestion of liquid concentrates of organo-
phosphate pesticides, hydrocarbon aspiration may complicate these
poisonings. Pulmonary edema and poor oxygenation in these cases
will not respond to atropine and should be treated as a case of acute
respiratory distress syndrome.
Children under 12 years: 0.05-0.1 mg/kg body weight, repeated ev-
ery 15 minutes until atropinization is achieved. There is a minimum
dose of 0.1 mg in children. Maintain atropinization by repeated
doses based on recurrence of symptoms for 2-12 hours or longer
depending on severity of poisoning.
Maintain atropinization with repeated dosing as indicated by clinical
status. Crackles in the lung bases nearly always indicate inadequate
atropinization. Pulmonary improvement may not parallel other signs
of atropinization. Continuation of, or return of, cholinergic signs indi-
cates the need for more atropine. When symptoms are stable for as
much as six hours, the dosing may be decreased.
Severely poisoned individuals may exhibit remarkable tolerance to at-
ropine; two or more times the dosages suggested above may be needed.
The dose of atropine may be increased and the dosing interval de-
creased as needed to control symptoms. Continuous intravenous infu-
sion of atropine may be necessary when atropine requirements are
massive. The desired end-point is the reversal of muscarinic
symptoms and signs with improvement in pulmonary status
and oxygenation, without an arbitrary dose limit. Preservative-free
atropine products should be used whenever possible.
Note: Persons not poisoned or only slightly poisoned by organophos-
phates may develop signs of atropine toxicity from such large doses.
Fever, muscle fibrillations, and delirium are the main signs of atropine
toxicity. If these appear while the patient is fully atropinized, atropine
administration should be discontinued, at least temporarily, while the
severity of poisoning is reevaluated.
42 ORGANOPHOSPHATES
-------
Dosage of Pralidoxime:
Adults and children over 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 inter-
vals if needed. In very severe poisonings, dosage rates may be doubled. Repeated
doses of pralidoxime are usually required. In cases that involve continuing ab-
sorption of organophosphate (as after ingestion of large amount), or continuing
transfer of highly lipophilic organophosphate from fat into blood, it may be nec-
essary to continue administration of pralidoxime for several days beyond the 48
hour post-exposure interval usually cited as the limit of its effectiveness. Pralidoxime
may also be given as a continuous infusion of approximately 500 mg/hour based
on animal case studies and adult patient reports.28'29
Blood pressure should be monitored during administration because of the
occasional occurrence of hypertensive crisis. Administration should be slowed
or stopped if blood pressure rises to hazardous levels. Be prepared to assist
pulmonary ventilation mechanically if respiration is depressed during or after
pralidoxime administration. If intravenous injection is not possible, pralidoxime
may be given by deep intramuscular injection.
5. Skin decontamination. In patients who have been poisoned by organo-
phosphate contamination of skin, clothing, hair, and/or eyes, decontamination
must proceed concurrently with whatever resuscitative and antidotal measures
are necessary to preserve life. Flush the chemical from the eyes with copious
amounts of clean water. If no symptoms are evident in a patient who remains
alert and physically stable, a prompt shower and shampoo may be appropriate,
provided the patient is carefully observed to insure against any sudden appear-
ance of poisoning. If there are any indications of weakness, ataxia, or other
neurologic impairment, clothing should be removed and a complete bath and
shampoo given while the victim is recumbent, using copious amounts of soap
and water. Attendants should wear rubber gloves as vinyl provides no protec-
tion against skin absorption. Surgical green soap is excellent for this purpose,
but ordinary soap is about as good. Wash the chemical from skin folds and from
under fingernails.
ORGANOPHOSPHATES 43
-------
Contaminated clothing should be promptly removed, bagged, and laundered
before returning. Contaminated leather shoes should be discarded. Note that the
pesticide can contaminate the inside surfaces of gloves, boots, and headgear.
6. Gastrointestinal decontamination. If organophosphate has been ingested
in quantity probably sufficient to cause poisoning, consideration should be given
to gastrointestinal decontamination, as outlined in Chapter 2, General Prin-
ciples. If the patient has already vomited, which is most likely in serious expo-
sures, further efforts at GI decontamination may not be indicated. In significant
ingestions, diarrhea and/or vomiting are so constant that charcoal adsorption
and catharsis are not indicated.
7. Observation. Observe patient closely for at least 72 hours to ensure that
symptoms (sweating, visual disturbances, vomiting, diarrhea, chest and abdomi-
nal distress, and sometimes pulmonary edema) do not recur as atropinization is
withdrawn. In very severe poisonings by ingested organophosphates, particu-
larly the more lipophilic and slowly hydrolyzed compounds, metabolic dispo-
sition of toxicant may require as many as 5-14 days. In some cases, this slow
elimination may combine with profound cholinesterase inhibition to require
atropinization for several days or even weeks. As dosage is reduced, the lung
bases should be checked frequently for crackles. If crackles are heard, or if there
is a return of miosis, bradycardia, sweating, or other cholinergic signs, atropin-
ization must be re-established promptly.
8. Furosemide may be considered if pulmonary edema persists in the lungs
even after full atropinization. It should not be used until the maximum benefit of
atropine has been realized. Consult package insert for dosage and administration.
9. Pulmonary ventilation. Particularly in poisonings by large ingested doses
of organophosphate, monitor pulmonary ventilation carefully, even after recov-
ery from muscarinic symptomatology, to forestall respiratory failure. In some
cases, respiratory failure has developed several days following organophosphate
ingestion, and has persisted for days to weeks.
10. Hydrocarbon aspiration may complicate poisonings that involve inges-
tion of liquid concentrates of organophosphate pesticides. Pulmonary edema
and poor oxygenation in these cases will not respond to atropine and should be
treated as a case of acute respiratory distress syndrome.
11. Cardiopulmonary monitoring. In severely poisoned patients, monitor
cardiac status by continuous EGG recording. Some organophosphates have sig-
nificant cardiac toxicity
44 ORGANOPHOSPHATES
-------
12. Seizure control. Rarely, in severe organophosphate poisonings, convul-
sions occur despite therapy with atropine and pralidoxime. Insure that causes
unrelated to pesticide toxicity are not responsible: head trauma, cerebral anoxia,
or mixed poisoning. Drugs useful in controlling convulsions are discussed in
Chapter 2. The benzodiazepines (diazepam or lorazepam) are the agents of
choice as initial therapy.
13. Contraindications. The following drugs are contraindicated in nearly all
organophosphate poisoning cases: morphine, succinylcholine, theophylline,
phenothiazines, and reserpine. Adrenergic amines should be given only if there
is a specific indication, such as marked hypotension.
14. Re-exposures. Persons who have been clinically poisoned by organo-
phosphate pesticides should not be re-exposed to cholinesterase-inhibiting
chemicals until symptoms and signs have resolved completely and blood cho-
linesterase activities have returned to at least 80 percent of pre-poisoning levels.
If blood cholinesterase was not measured prior to poisoning, blood enzyme
activities should reach at least minimum normal levels (see table on page 39)
before the patient is returned to a pesticide-contaminated environment.
15. Do not administer atropine or pralidoxime prophylactically to workers
exposed to organophosphate pesticides. Prophylactic dosage with either atropine
or pralidoxime may mask early signs and symptoms of organophosphate poison-
ing and thus allow the worker to continue exposure and possibly progress to
more severe poisoning. Atropine itself may enhance the health hazards of the
agricultural work setting: impaired heat loss due to reduced sweating and im-
paired ability to operate mechanical equipment due to blurred vision. This can
be caused by mydriasis, one of the effects of atropine.
General Chemical Structure
R is usually either ethyl or methyl. The insecticides with a double bonded sulfur are
organothiophosphates, but are converted to organophosphates in the liver. Phosphonate
contains an alkyl (R-) in place of one alkoxy group (RO-). "X" is called the "leaving
group " and is the principal metabolite for a specific identification.
RO^ 4, S (or 0)
P
no' ^ o
[Leaving Group|
ORGANOPHOSPHATES 45
-------
References
1. DuBois KP. The toxicity of organophosphorous compounds to mammals. Bull World Health
Organ 1971;44:233-40.
2. Pasquet J, Mazuret A, Fournel J, et al. Acute oral and percutaneous toxicity of phosalone in the
rat, in comparison with azinphosmethyl and parathion. ToxicolAppl Pharmacol 1976;37:85-92.
3. Garcia-Repetto R, Martinez D, and Repetto M. Coefficient of distribution of some organo-
phosphorus pesticides in rat tissue. Vet Hum Toxicol 1995;37:226-9.
4. Gallo MA and Lawryk NJ. Organic phosphorus pesticides. In: Haves WJ and Laws ER (eds),
Handbook of Pesticide Toxicology, vol 2, Classes of Pesticides. San Diego, CA: Academic
Press Inc., 1991.
5. Taylor P. Anticholinesterase agents. In: Gilman AG and Goodman LS (eds), The Pharmaco-
logical Basis of Therapeutics. New York: Macmillan Publishing Co. Inc.; 1985, pp.110-28.
6. De KortWL, Kiestra SH, and Sangster B.The use of atropine and oximes in organophos-
phate intoxications: A modified approach. Clin Toxicol 1988;26:199-208.
7. Jamal JA. Neurological syndromes of organophosphorus compounds. Adverse Drug React
Toxicol Rev 1997;16(3):133-70.
8. Steenland K, Jenkins B, Ames RG, et al. Chronic neurological sequelae to organophosphate
poisoning. Am J Public Health 1994;84:731-6.
9. Savage E, KeefeT, Mounce L,et al. Chronic neurological sequelae of acute organophosphate
pesticide poisoning. Arch Environ Health 1988;43:38-45.
10. Rosenstock L, Keifer M, Daniell^ et al. Chronic central nervous system effects of acute
organophosphate pesticide intoxication. Lancet 1991;338:223-7.
11. Gershon S and Shaw FH. Psychiatric sequelae of chronic exposure to organophosphorus
insecticides. Lancet 1961; 1:1371-4.
12. Metcalf DR and Holmes JH. EEG, psychological, and neurological alterations in humans
with organophosphorus exposure. Ann NYAcad Sci 1969;!60:357-65.
13. Holmes JH and Gaon MD. Observations on acute and multiple exposure to anticholinest-
erase agents. Trans Am Clin Climatol Assoc 1957; 68:86-103.
14. Hirshberg A and LermanY. Clinical problems in organophosphate insecticide poisoning:The
use of a computerized information system. Fundam Appl Toxicol 1984; 4:5209-14.
15. Miller CS and Mitzel HC. Chemical sensitivity attributed to pesticide exposure versus re-
modeling. Arch Environ Health 1995; 50:119-29.
16. DeBleeker J, Willems J,Van Den Neucker K, et al. Prolonged toxicity with intermediate
syndrome after combined parathion and methyl parathion poisoning. Clin Toxicol
1992;30:333-45.
17. DeBleecker J, Van Den Neucker K, and Colardyn F. Intermediate syndrome in organo-
phosphorous poisoning: A prospective study. Crit Care Med 1993;21:1706-11.
18. Aldridge WN and Nemery B. Toxicology of trialkylphosphorothioates with particular
reference to lung toxicity. Fundam Appl Toxicol 1984; 4:5215-23.
19. Bardin PG, Van Eeden SF, Moolman JA, et al. Organophosphate and carbamate poisoning.
Arch Intern Med 1994;154:1433-41.
20. Zwiener RJ and Ginsburg CM. Organophosphate and carbamate poisoning in infants and
children. Pediatrics 1988;81:121-683.
21. Sofer S,Tal A, and Shahak E. Carbamate and organophosphate poisoning in early childhood.
PediatrEmerg Care 1989;5(4):222-5.
46 ORGANOPHOSPHATES
-------
22. Sullivan JB and Blose J. Organophosphate and carbamate insecticides. In: Sullivan JB and
Krieger GR (eds), Hazardous Materials Toxicology. Baltimore, MD: Williams and Wilkins,
1992, pp. 1015-26.
23. Goswamy R, Chaudhuri A, and Mahashur AA. Study of respiratory failure in organophos-
phate and carbamate poisoning. Heart Lung 1994;23:466-72.
24. LeBlanc FN, Benson BE, and Gilg AD. A severe Organophosphate poisoning requiring the
use of an atropine drip. Clin Toxicol 1986;24:69-76.
25. DuToit PW, Muller FO, Van Tender WM, et al. Experience with the intensive care manage-
ment of Organophosphate insecticide poisoning. S Afr Med J 1981;60:227-9.
26. Shockley LW. The use of inhaled nebulized atropine for the treatment of malathion poison-
ing. ClinToxicol 1989;27:183-92.
27. Bardin PG and van Eeden SF Organophosphate poisoning: Grading the severity and compar-
ing treatment between atropine and glycopyrrolate. Crit Care Med 1990;18:956-60.
28. Thompson DF, Thompson GD, Greenwood RB, et al. Therapeutic dosing of pralidoxime
chloride. Drug Intell Clin Pharm 1987;21:590-2.
29. Tush GM and Anstead MI. Pralidoxime continuous infusion in the treatment of Organo-
phosphate poisoning. Ann Pharmacotherl997;3l:44l-4.
ORGANOPHOSPHATES 47
-------
CHAPTER 5
HIGHLIGHTS
Cause reversible
carbamylation of AChE
Muscarinic, nicotinic, CMS
effects
Signs and Symptoms:
Malaise, muscle weakness,
dizziness, sweating
Headache, salivation,
nausea, vomiting,
abdominal pain, diarrhea
CMS depression, pulmonary
edema in serious cases
Treatment:
Clear airway, improve tissue
oxygenation
Administer atropine sulfate
intravenously
Proceed immediately with
decontamination
procedures
N-Methyl Carbamate
Insecticides
N-Methyl carbamate insecticides are widely used in homes, gardens, and agri-
culture. They share with organophosphates the capacity to inhibit cholinest-
erase enzymes and therefore share similar symptomatology during acute and
chronic exposures. Likewise, exposure can occur by several routes in the same
individual due to multiple uses, and there is likely to be additive toxicity with
simultaneous exposure to organophosphates. However, due to the somewhat
different affinity for cholinesterases, as compared to organophosphates, these
poisonings are often somewhat easier to treat, as discussed later in this chapter.
Toxicology
The N-methyl carbamate esters cause reversible carbamylation of the ace-
tylcholinesterase enzyme, allowing accumulation of acetylcholine, the
neuromediator substance, at parasympathetic neuroeffector junctions (muscar-
inic effects), at skeletal muscle myoneural junctions and autonomic ganglia (nico-
tinic effects), and in the brain (CNS effects).The carbamyl-acetylcholinesterase
combination dissociates more readily than the phosphoryl-acetylcholinesterase
complex produced by organophosphate compounds. This lability has several
important consequences: (1) it tends to limit the duration of N-methyl car-
bamate poisonings, (2) it accounts for the greater span between symptom-
producing and lethal doses than in most organophosphate compounds, and (3)
it frequently invalidates the measurement of blood cholinesterase activity as a
diagnostic index of poisoning (see below).
N-methyl carbamates are absorbed by inhalation and ingestion and some-
what by skin penetration, although the latter tends to be the less toxic route. For
example, carbofuran has a rat oral LD50 of 5 mg/kg, compared to a rat dermal
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, respec-
tively. At skeletal muscle junctions, excess acetylcholine may be excitatory (cause
muscle twitching), but may also weaken or paralyze the cell by depolarizing the
end-plate. In the brain, elevated acetylcholine concentrations may cause sen-
48
N-METHYL CARBAMATES
-------
sory and behavioral disturbances, incoordination, and depressed motor func-
tion (rarely seizures), even though the N-methyl carbamates do not penetrate
the central nervous system very efficiently Respiratory depression combined
with pulmonary edema is the usual cause of death from poisoning by N-me-
thyl carbamate compounds.
Signs and Symptoms of Poisoning
As with organophosphate poisoning, the signs and symptoms are based on
excessive cholinergic stimulation. Unlike organophosphate poisoning, carbamate
poisonings tend to be of shorter duration because the inhibition of nervous tissue
AchE is reversible, and carbamates are more rapidly metabolized.2 Bradycardia and
seizures are less common than in organophosphate poisonings. However, blood
cholinesterase levels may be misleading due to in vitro reactivation of a
carbamylated enzyme.3'4 A falsely "normal" level can make the diagnosis more
difficult in the acute presentation in the absence of an exposure history.
The primary manifestations of serious toxicity are central nervous system
depression, as manifested by coma, seizures, and hypotonicity, and nicotinic
effects including hypertension and cardiorespiratory depression. Dyspnea, bron-
chospasm, and bronchorrhea with eventual pulmonary edema are other seri-
ous signs. Recent information indicates that children and adults differ in their
clinical presentation. Children are more likely than adults to present with the
CNS symptoms above. While children can still develop the classic muscarinic
signs, the absence of them does not exclude the possibility of carbamate poi-
soning in the presence of CNS depression.5
Malaise, muscle weakness, dizziness, and sweating are commonly reported
early symptoms. Headache, salivation, nausea, vomiting, abdominal pain, and
diarrhea are often prominent. Miosis with blurred vision, incoordination, muscle
twitching, and slurred speech are reported.
Confirmation of Poisoning
If there are strong clinical indications of acute N-methyl carbam-
ate poisoning, and/or a history of carbamate exposure, treat the pa-
tient immediately. Do not wait for laboratory confirmation.
Blood for plasma pseudocholinesterase and RBC AChE should be ob-
tained. Be advised that unless a substantial amount of N-methyl carbamate has
been absorbed and a blood sample is taken within an hour or two, it is unlikely
that blood cholinesterase activities will be found depressed. Even under the
above circumstances, a rapid test for enzyme activity must be used to detect an
effect, because enzyme reactivation occurs in vitro as well as in vivo. See the table
on page 39 for methods of measurement of blood cholinesterase activities, if
circumstances appear to warrant performance of the test.
Commercial Products
aldicarb*
Temik
aminocarb*
Matacil
bendiocarb*
Dycarb
Ficam
Multamat
Niomil
Tattoo
Turcam
bufencarb
Bux
metalkamate
carbaryl
Dicarbam
Sevin
carbofuran*
Crisfuran
Curaterr
Furadan
doethocarb*
Lance
dimetan
Dimethan
dioxacarb
Elecron
Fa mid
fenoxycarb
Torus
formetanate hydrochloride*
Carzol
isolan+
Primin
isoprocarb
Etrofolan
MIPC
methiocarb*
Draza
Mesurol
methomyl*
Lannate
Lanox
Nudrin
mexacarbate
Zectran
oxamyl*
DPX1410
Vydate L
pirimicarb
Abo I
Aficida
Aphox
Fernos
Pirimor
Rapid
(Continued on the next page)
N-METHYL CARBAMATES 49
-------
Commercial Products
(Continued)
promecarb
Carbamult
propoxur
aprocarb
Baygon
thiodicarb
Larvin
trimethacarb
Broot
Landrin
+ Indicates high toxicity.
Highly toxic N-methyl
carbamates have listed oral
LD50 values (rat) less than or
equal to 50 mg/kg body
weight. Most other
carbamates included in this
table are considered
moderately toxic, with LD50
values in excess of 50 mg/
kg and less than 500 mg/kg.
Absorption of some N-methyl carbamates can be confirmed by analysis of
urine for unique metabolites: alpha-naphthol from carbaryl, isopropoxyphenol
from propoxur, carbofuran phenol from carbofuran, and aldicarb sulfone, sul-
foxide, and nitrile from aldicarb. These complex analyses, when available, can be
useful in identifying the responsible agent and following the course of carbarn-
ate disposition.
Treatment
Caution: Persons attending the victim should avoid direct contact with
heavily contaminated clothing and vomitus.Wear rubber gloves while washing
pesticide from skin and hair. Vinyl gloves provide no protection.
1. Airway protection. Ensure that a clear airway exists. Intubate the patient
and aspirate the secretions with a large-bore suction device if necessary. Ad-
minister oxygen by mechanically assisted pulmonary ventilation if respiration is
depressed. Improve tissue oxygenation as much as possible before ad-
ministering atropine, to minimize the risk of ventricular fibrillation.
In severe poisonings, it may be necessary to support pulmonary ventilation
mechanically for several days.
2. Atropine. Administer atropine sulfate intravenously, or intramuscularly if
intravenous injection is not possible. Remember that atropine can be adminis-
tered through an endotracheal tube if initial IV access is difficult to obtain.
Carbamates usually reverse with much smaller dosages of atropine than those
required to reverse organophosphates.6 (See dosage on next page.)
The objective of atropine antidotal therapy is to antagonize the effects of
excessive concentrations of acetylcholine at end-organs having muscarinic re-
ceptors. Atropine does not reactivate the cholinesterase enzyme or accelerate
excretion or breakdown of carbamate. Recrudescence of poisoning may occur
if tissue concentrations of toxicant remain high when the effect of atropine
wears off. Atropine is effective against muscarinic manifestations, but is ineffec-
tive against nicotinic actions, specifically, muscle weakness and twitching, and
respiratory depression.
Despite these limitations, atropine is often a life-saving agent in N-methyl
carbamate poisonings. Favorable response to a test dose of atropine (1 mg in
adults, 0.01 mg/kg in children under 12 years) given intravenously can help
differentiate poisoning by anticholinesterase agents from other conditions such
as cardiogenic pulmonary edema and hydrocarbon ingestion. However, lack of
response to the test dose, indicating no atropinization (atropine refractoriness),
is characteristic of moderately severe to severe poisoning and indicates a need
for further atropine. If the test dose does not result in mydriasis and drying of
secretions, the patient can be considered atropine refractory.
50
N-METHYL CARBAMATES
-------
Dosage of Atropine:
In moderately severe poisoning (hypersecretion and other end-organ
manifestations without central nervous system depression), the follow-
ing dosage schedules have proven effective:
Adults and children over 12years: 2.0-4.0 mg, repeated every 15 min-
utes until pulmonary secretions are controlled, which may be ac-
companied by other signs of atropinization, including flushing, dry
mouth, dilated pupils, and tachycardia (pulse of 140 per minute).
Warning: In cases of ingestion of liquid concentrates of carbamate
pesticides, hydrocarbon aspiration may complicate these poisonings.
Pulmonary edema and poor oxygenation in these cases will not
respond to atropine and should be treated as a case of acute respira-
tory distress syndrome.
Children under 12years: 0.05-0.1 mg/kg body weight, repeated every
15 minutes until pulmonary secretions are controlled, which may be
accompanied by other signs of atropinization as above (heart rates
vary depending on age of child with young toddlers having a rate
approaching 200).There is a minimum dose of 0.1 mg in children.
Maintain atropinization by repeated doses based on recurrence of symp-
toms for 2-12 hours or longer depending on severity of poisoning. Crack-
les in the lung bases nearly always indicate inadequate atropinization and
pulmonary improvement may not parallel other signs. Continuation or
return of cholinergic signs indicates the need for more atropine.
Severely poisoned individuals may exhibit remarkable tolerance to at-
ropine; two or more times the dosages suggested above may be needed.
Reversal of muscarinic manifestations, rather than a specific dosage, is
the object of atropine therapy. However, prolonged intensive intrave-
nous administration of atropine sometimes required in organophos-
phate poisonings is rarely needed in treating carbamate poisoning.
Note: Persons not poisoned or only slightly poisoned by N-methyl
carbamates may develop signs of atropine toxicity from such large doses.
Fever, muscle fibrillations, and delirium are the main signs of atropine
toxicity. If these signs appear while the patient is fully atropinized, atro-
pine administration should be discontinued, at least temporarily, while
the severity of poisoning is reevaluated.
N-METHYL CARBAMATES 51
-------
3. Skin decontamination. In patients with contaminated skin, clothing, hair,
and/or eyes, decontamination must proceed concurrently with what-
ever resuscitative and antidotal measures are needed to preserve life.
Flush the chemical from eyes with copious amounts of clean water. For asymp-
tomatic individuals who are alert and physically able, a prompt shower and
shampoo may be appropriate for thorough skin decontamination, provided the
patient is carefully observed to insure against sudden appearance of poisoning.
If there are any indications of weakness ataxia or other neurologic impairment,
clothing should be removed and a complete bath and shampoo given while the
victim is recumbent, using copious amounts of soap and water. Attendants should
wear rubber gloves as vinyl provides no protection against skin absorption.
Wash the chemical from skin folds and from under fingernails.
Contaminated clothing should be promptly removed, bagged, and laundered
before returning. Contaminated leather shoes should be discarded. Note that the
pesticide can contaminate the inside surfaces of gloves, boots, and headgear.
4. Gastrointestinal decontamination. If N-methyl carbamate has been ingested
in a quantity probably sufficient to cause poisoning, consideration should be given
to gastrointestinal decontamination as outlined in Chapter 2. If the patient has
presented with a recent ingestion and is still asymptomatic, adsorption of poison
with activated charcoal may be beneficial. In significant ingestions, diarrhea and/or
vomiting are so constant that charcoal adsorption and catharsis are not indicated.
Attention should be given to oxygen, airway management, and atropine.
5. Urine sample. Save a urine sample for metabolite analysis if there is need to
identify the agent responsible for the poisoning.
6. Pralidoxime is probably of little value in N-methyl carbamate poisonings,
because atropine alone is effective. Although not indicated in isolated carbam-
ate poisoning, pralidoxime appears to be useful in cases of mixed carbamate/
organophosphate poisonings, and cases of an unknown pesticide with muscar-
inic symptoms on presentation.7'8 See Chapter 4,Treatment section, p. 41.
7. Observation. Observe patient closely for at least 24 hours to ensure that symp-
toms (sweating, visual disturbances, vomiting, diarrhea, chest and abdominal distress,
and sometimes pulmonary edema) do not recur as atropinization is withdrawn.The
observation period should be longer in the case of a mixed pesticide ingestion,
because of the prolonged and delayed symptoms associated with organophosphate
poisoning. As the dosage of atropine is reduced over time, check the lung bases
frequently for crackles. Atropinization must be re-established promptly, if crackles
are heard, or if there is a return of miosis, sweating, or other signs of poisoning.
8. Furosemide may be considered for relief of pulmonary edema if crackles
persist in the lungs even after full atropinization. It should not be considered
52 N-METHYL CARBAMATES
-------
until the maximum effect of atropine has been achieved. Consult package in-
sert for dosage and administration.
9. Pulmonary ventilation. Particularly in poisonings by large doses of N-
methyl carbamates, monitor pulmonary ventilation carefully, even after recov-
ery from muscarinic symptomatology, to forestall respiratory failure.
10. Cardiopulmonary monitoring. In severely poisoned patients, monitor
cardiac status by continuous EGG recording.
11. Contraindications. The following drugs are probably contraindicated in
nearly all N-methyl carbamate poisoning cases: morphine, succinlycholine, theo-
phylline, phenothiazines, and reserpine. Adrenergic amines should be given
only if there is a specific indication, such as marked hypotension.
12. Hydrocarbon aspiration may complicate poisonings that involve inges-
tion of liquid concentrates of some carbamates that are formulated in a petro-
leum product base. Pulmonary edema and poor oxygenation in these cases will
not respond to atropine and should be treated as cases of acute respiratory
distress syndrome.
13. Do not administer atropine prophylactically to workers exposed to
N-methyl carbamate pesticides. Prophylactic dosage may mask early symptoms
and signs of carbamate poisoning and thus allow the worker to continue expo-
sure and possibly progress to more severe poisoning. Atropine itself may en-
hance the health hazards of the agricultural work setting: impaired heat loss
due to reduced sweating and impaired ability to operate mechanical equip-
ment due to blurred vision (mydriasis).
General Chemical Structure
References
1. Registry of Toxic Effects of Chemical Substances. National Institute for Occupational Safety
and Health, Cincinnati, OH. (CD-ROM Version, Micromedex, Inc. Englewood, CA 1991.)
2. Ecobichon DJ. Toxic effect of pesticides. In: Klaassen CD (ed), Casarett & Doull's Toxicol-
ogy: The Basic Science of Poisons, 5th ed. New York: McGraw-Hill, 1996, p. 659.
3. Rotenberg M and Almog S. Evaluation of the decarbamylation process of cholinesterase
during assay of enzyme activity. Clin ChimActa 1995;240:107-16.
N-METHYL CARBAMATES 53
-------
4. Jokanovic M and Maksimovic M. Abnormal cholinesterase activity: Understanding and in-
terpretation. BUT] Clin Chem Clin Biochem 1997;35:ll-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 chil-
dren: A clinical and laboratory study. Pediatrics 1994;93:652-5.
8. Kurtz PH. Pralidoxime in the treatment of carbamate intoxication. Am JEmerg Med 1990;8:68-70.
54 N-METHYLCARBAMATES
-------
CHAPTER 6
Solid Organochlorine Insecticides
EPA has sharply curtailed the availability of many organochlorines, particularly
DDT, aldrin, dieldrin, heptachlor, mirex, chlordecone, and chlordane. Others,
however, remain the active ingredients of various home and garden products
and some agricultural, structural, and environmental pest control products.
Hexachlorobenzene is a fungicide used as a seed protectant and is discussed
further in Chapter 15, Fungicides.
Technical hexachlorocyclohexane (misnamed benzene hexachloride, BHC)
includes multiple stereoisomers; only the gamma isomer (lindane) is insecticidal.
Lindane is the active ingredient of some pest control products used in the home
and garden, on the farm, and in forestry and animal husbandry. It is also the active
agent in the medicine Kwellฎ, used for human ectoparasitic disease. Lindane has
been reported on numerous occasions to be associated with acute neurological
toxicity either from ingestion or in persons treated for scabies or lice.1"6
Toxicology
In varying degrees, organochlorines are absorbed from the gut and also by
the lung and across the skin. The efficiency of dermal absorption is variable.
Hexachlorocyclohexane, including lindane, the cyclodienes (aldrin, dieldrin,
endrin, chlordane, heptachlor), and endosulfan are efficiently absorbed across
the skin, while dermal absorption efficiencies of DDT, dicofol, marlate, tox-
aphene, and mirex are substantially less.7 Lindane has a documented 9.3% der-
mal absorption rate,8 and is absorbed even more efficiently across abraded skin.1>9
This becomes especially important when taking into account its use on chil-
dren with severe dermatitis associated with scabies. Fat and fat solvents enhance
gastrointestinal, and probably dermal, absorption of organochlorines. While most
of the solid organochlorines are not highly volatile, pesticide-laden aerosol or
dust particles trapped in respiratory mucous and subsequently swallowed may
lead to significant gastrointestinal absorption.
Following exposure to some organochlorines (notably DDT), a significant
part of the absorbed dose is stored in fat tissue as the unchanged parent com-
pound. Most organochlorines are in some degree dechlorinated, oxidized, then
conjugated. The chief route of excretion is biliary, although nearly all orga-
nochlorines yield measurable urinary metabolites. Unfortunately, many of the
unmetabolized pesticides are efficiently reabsorbed by the intestine (enterohepatic
circulation), substantially retarding fecal excretion.
HIGHLIGHTS
Signs and Symptoms:
Absorbed dose is stored in
fat tissue
Sensory disturbances:
hyperesthesia and
paresthesia, headache,
dizziness, nausea,
hyperexcitable state
Convulsions
Treatment:
Anticonvulsants
(benzodiazepines)
Administer oxygen
Cardiopulmonary
monitoring
Contraindicated:
Epinephrine, other
adrenergic amines, atropine
Animal or vegetable oils or
fats taken orally
SOLID ORGANOCHLORINES 55
-------
Commercial Products
aldrin*
benzene hexachloride (BHC)*
HCH
hexachlor
hexachloran
chlordane*
(multiple trade names)
chlordecone*
Kepone
chlorobenzilate
DDT*
(multiple trade names)
dicofol
Kelthane
(multiple trade names)
dieldrin*
Dieldrite
dienochlor
Pentac
endosulfan
(multiple trade names)
endrin*
Hexadrin
heptachlor**
(multiple trade names)
hexacholorobenzene*
lindane
gamma BHC or HCH
Kwell
(multiple trade names)
methoxychlor
Marlate
mirex*
terpene polychlorinates*
Strobane
toxaphene*
* All U.S. registrations have
been cancelled.
** Registered in the United
States only for
underground use in
power lines for fire ants.
Metabolic dispositions of DDT and DDE (a DDT degradation product), the
beta isorner of hexachlorocyclohexane, dieldrin, heptachlor epoxide, and mirex
tend to be slow, leading to storage in body fat. Storable lipophilic compounds are
likely to be excreted in maternal milk.6'10'11 On the other hand, rapid metabolic
dispositions of lindane, methoxychlor, dienochlor, endrin, chlorobenzilate, dicofol,
toxaphene, perthane, and endosulfan reduce the likelihood that these organochlo-
rines will be detected as residues in body fat, blood, or milk.
The chief acute toxic action of organochlorine pesticides is on the nervous
system, where these compounds induce a hyperexcitable state in the brain.12
This effect is manifest mainly as convulsions, sometimes limited to myoclonic
jerking,but often expressed as violent seizures. Convulsions caused by cyclodienes
may recur over periods of several days. Other less severe signs of neurologic
toxicity such as paresthesias, tremor, ataxia, and hyperreflexia are also characteristic
of acute organochlorine poisoning. Agents such as DDT and methoxychlor
tend to cause the less severe effects, while the cyclodienes, mirex, and lindane
are associated with the more severe seizures and fatalities.7 Convulsions may
cause death by interfering with pulmonary gas exchange and by generating
severe metabolic acidosis.
High tissue concentrations of organochlorines increase myocardial irritability,
predisposing to cardiac arrhythmia.When tissue organochlorine concentrations
drop below threshold levels, recovery from the poisoning occurs.
Organochlorines are not cholinesterase inhibitors.
High tissue levels of some organochlorines (notably DDT, DDE, and cy-
clodienes) have been shown to induce hepatic microsomal drug-metabolizing
enzymes.13 This tends to accelerate excretion of the pesticides themselves, but
may also stimulate biotransformation of critical natural substances, such as ste-
roid hormones and therapeutic drugs, occasionally necessitating re-evaluation
of required dosages in persons intensively exposed to organochlorines. Human
absorption of organochlorine sufficient to cause enzyme induction is likely to
occur only as a result of prolonged intensive exposure.
Ingestion of hexachlorobenzene-treated wheat has been associated with
human dermal toxicity diagnosed as porphyria cutanea tarda.The skin blisters,
becomes very sensitive to sunlight, and heals poorly, resulting in scarring and
contracture formation.14 Unlike other organochlorine compounds, there have
been no reported cases of convulsions caused by the fungicide hexachloro-
benzene. Lindane and chlordane have rarely been associated anecdotally with
certain hematological disorders, including aplastic anemia and megaloblastic
anemia.15'16
There has been considerable interest recently in the interaction of orga-
nochlorines with endocrine receptors, particularly estrogen and androgen
receptors. In vitro studies and animal experimentation have supported the view
that the function of the endocrine system may be altered by these interac-
tions.17'18 This in turn may alter the reproductive development and success of
animals and humans. In addition, some organochlorines may inhibit lactation
and may also be developmental toxicants.10 Due to evidence of carcinogenic
56
SOLID ORGANOCHLORINES
-------
potential, some organochlorines have lost registration for use in the United
States or had their uses restricted. Although these effects are important, they are
beyond the scope of this manual.
Signs and Symptoms of Poisoning
Early manifestations of poisoning by some organochlorine pesticides, par-
ticularly DDT, are often sensory disturbances: hyperesthesia and paresthesia of
the face and extremities. Headache, dizziness, nausea, vomiting, incoordination,
tremor, and mental confusion are also reported. More severe poisoning causes
myoclonic jerking movements, then generalized tonic-clonic convulsions. Coma
and respiratory depression may follow the seizures.
Poisoning by the cyclodienes and toxaphene is more likely to begin with
the sudden onset of convulsions, and is often not preceded by the premonitory
manifestations mentioned above. Seizures caused by cyclodienes may appear as
long as 48 hours after exposure, and then may recur periodically over several
days following the initial episode. Because lindane and toxaphene are more
rapidly biotransformed in the body and excreted, they are less likely than diel-
drin, aldrin, and chlordane to cause delayed or recurrent seizures.
Confirmation of Poisoning
Organochlorine pesticides and/or their metabolites can sometimes be iden-
tified in blood by gas-liquid chromatographic examination of samples taken
within a few days of significant pesticide absorption. Such tests are performed
by a limited number of government, university, and private laboratories, which
can usually be contacted through poison control centers or health departments.
Some organochlorine pesticides or their products (notably DDT, dieldrin, mirex,
heptachlor, epoxide, chlordecone) persist in tissues and blood for weeks or
months after absorption, but others are likely to be excreted in a few days,
limiting the likelihood of detection. Blood levels tend to correlate more with
acute toxicity, while levels found in adipose tissue and breast milk usually re-
flect more long-term and historic exposure.19
Chromatographic methods make possible detection of most organochlo-
rines at concentrations much lower than those associated with symptoms of
toxicity. Therefore, a positive finding in a blood sample does not, of itself, justify
a diagnosis of acute poisoning. Lindane appears in the literature more frequently
than other compounds. The time of acquisition of the blood level in relation to
exposure time must be taken into account when interpreting blood levels. In
one study, lindane levels were measured at 10.3 ng/mL in healthy volunteers
three days after application to the skin.20
In a study with childhood dermal absorption using children with scabies
and a non-affected control group, lindane peaked at 28 ng/mL 6 hours after
application in the affected group, and at 24 ng/mL in the control group. At 48
SOLID ORGANOCHLORINES 57
-------
hours, levels were 6 ng/mL and 5 ng/mL respectively. Findings from this study
also provide evidence for increased absorption across abraded skin.9 A child
with severely abraded skin was treated for scabies and developed seizures.Three
days after exposure, his lindane level was 54 ng/mL.1 Most reports of acute
toxicity from lindane involve blood levels of 130 ng/mL or greater, with the
most severe and fatal cases involving levels exceeding 500 ng/mL.2
DDT, DDE, and a few other organochlorines are still found at very low
levels in blood samples from the general U.S. population, presumably due to
past and/or current low-level contamination of food by these environmentally
persistent pesticides.
In the absence of corresponding elevations of blood levels, the amount of
stored pesticides is not likely to be of clinical significance. Measurements of uri-
nary metabolites of some organochlorine pesticides can be useful in monitoring
occupational exposures; however, the analytical methods are complex, and are
not likely to detect amounts of metabolites generated by minimal exposures.
Treatment
1. Observation. Persons exposed to high levels of organochlorine pesticides
by any route should be observed for sensory disturbances, incoordination, speech
slurring, mental aberrations, and involuntary motor activity that would warn of
imminent convulsions.
2. Convulsions. If convulsions occur, place the victim in the left lateral decu-
bitus position with the head down. Move away furniture or other solid objects
that could be a source of injury. If jaw movements are violent, place padded
tongue blades between the teeth to protect the tongue. Whenever possible,
remove dentures and other removable dental work. Aspirate oral and pharyn-
geal secretion, and when possible, insert an oropharyngeal airway to maintain
an open passage unobstructed by the tongue. Minimize noise and any manipu-
lation of the patient that may trigger seizure activity.
Dosage of Diazepam:
Adults: 5-10 mg IV and repeat every 5-10 minutes to maximum of 30 mg.
Children: 0.2 to 0.5 mg/kg every 5 minutes to maximum of 10 mg in
children over 5 years, and maximum of 5 mg in children under 5 years.
Although lorazepam is widely accepted as a treatment of choice for
status epilepticus, there are no reports of its use for organochlorine
intoxication. Some cases have required aggressive seizure management
including the addition of phenobarbital and the induction of pento-
barbital coma.
58 SOLID ORGANOCHLORINES
-------
Seizures in patients caused by organochlorine toxicity are likely to be pro-
longed and difficult to control. Status epilepticus is common. For this reason,
patients with seizures that do not respond immediately to anticonvulsants should
be transferred as soon as possible to a trauma center and will generally require
intensive care admission until seizures are controlled and neurologic status is
improved. Initial therapy with benzodiazepines should be instituted.
3. Oxygen. Administer oxygen by mask. Maintain pulmonary gas exchange by
mechanically assisted ventilation whenever respiration is depressed.
4. Skin decontamination. Skin decontamination should be done thoroughly,
as outlined in Chapter 2.
5. Gastrointestinal decontamination. If organochlorine has been ingested
in a quantity sufficient to cause poisoning and the patient presents within an
hour, consideration should be given to gastric decontamination procedures, as
outlined in Chapter 2. If the patient presents more than an hour after ingestion,
activated charcoal may still be beneficial. If the victim is convulsing, it is almost
always necessary first to control seizures before attempting gastric decontami-
nation. Activated charcoal administration has been advocated in such poison-
ings, but there is little human or experimental evidence to support it.
6. Respiratory failure. Particularly in poisonings by large doses of
organochlorine, monitor pulmonary ventilation carefully to forestall
respiratory failure. Assist pulmonary ventilation mechanically with oxygen
whenever respiration is depressed. Since these compounds are often formulated
in a hydrocarbon vehicle, hydrocarbon aspiration may occur with ingestion of
these agents. The hydrocarbon aspiration should be managed in accordance
with accepted medical practice as a case of acute respiratory distress syndrome
which will usually require intensive care management.
7. Cardiac monitoring. In severely poisoned patients, monitor cardiac status
by continuous EGG recording to detect arrhythmia.
8. Contraindications. Do not give epinephrine, other adrenergic amines, or
atropine unless absolutely necessary because of the enhanced myocardial irrita-
bility induced by chlorinated hydrocarbons, which predisposes to ventricular
fibrillation. Do not give animal or vegetable oils or fats by mouth. They en-
hance gastrointestinal absorption of the lipophilic organochlorines.
9. Phenobarbital. To control seizures and myoclonic movements that some-
times persist for several days following acute poisoning by the more slowly
excreted organochlorines, phenobarbital given orally is likely to be effective.
SOLID ORGANOCHLORINES 59
-------
Dosage should be based on manifestations in the individual case and on infor-
mation contained in the package insert.
10. Cholestryamine resin accelerates the biliary-fecal excretion of the more
slowly eliminated organochlorine compounds.21 It is usually administered in 4
g doses, 4 times a day, before meals and at bedtime. The usual dose for children
is 240 mg/kg/24 hours, divided Q 8 hours. The dose may be mixed with a
pulpy fruit or liquid. It should never be given in its dry form and must always
be administered with water, other liquids or a pulpy fruit. Prolonged treatment
(several weeks or months) may be necessary.
11. Convalescence. During convalescence, enhance carbohydrate, protein, and
vitamin intake by diet or parenteral therapy.
General Chemical Structures
s=o
Cl Cl
Heptachlor
OCH,
Jc\-c-cr
Cl
Methoxychlor
Endosulfan
Cl Cl
Cl Cl
Cl Cl Cl Cl
Dienochlor
60
SOLID ORGANOCHLORINES
-------
Cl Cl
Cl
Cl
Mirex
Chlordecone
References
1. Friedman SJ. Lindane neurotoxic reaction in nonbullous congenital ichthyosiform erythro-
derma. Arch Dermatol 1987;123:1056-8.
2. Aks SE, Krantz A, Hryhorczuk DO, et al. Acute accidental lindane ingestion in toddlers. Ann
EmergMed 1995;25(5):647-51.
3. Tenenbein M. Seizures after lindane therapy. J Am Geriatr Soc 1991;39(4):394-5.
4. Solomon BA, Haut SR, Carr EM, and Shalita AR. Neurotoxic reaction to lindane in an HIV-
seropositive patient: An old medication s new problem. JFam Pract 1995;40(3):291-6.
5. FischerTF. Lindane toxicity in a 24-year-old woman. Ann EmergMed 1994;24(5):972-4.
6. Solomon LM, Fahrner L, and West DP. Gamma benzene hexachloride toxicity. Arch Dermatol
1977;113:353-7.
7. Echobichon DJ.Toxic effects of pesticides. In Klaassen CD (ed), Casarett & Doull's Toxicol-
ogy: The Basic Science of Poisons, 5th ed. New York: McGraw-Hill, 1996, pp. 649-55.
8. Feldmann RJ and Maibach HI. Percutaneous penetration of some pesticides and herbicides
in man. Toxicol andAppl Pharmacol 1974;28:126-32.
9. Ginsburg CM, Lowry W, and Reisch JS. Absorption of lindane (gamma benzene hexachlo-
ride) in infants and children. /Pediatr 1997;91(6):998-1000.
10. Rogan WJ. PoUutants 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. MedJAust 1993;158(4):238-41.
12. Joy RM.The effects of neurotoxicants on kindling and kindled seizures. Fundam ApplToxicol
1985;5:41-65.
13. Hunter J, Maxwell JD, Stewart DA, et al. Increased hepatic microsomal enzyme activity from
occupational exposure to certain organochlorine pesticides. Nature 1972;237:399-401.
14. Booth NH and McDowell JR. Toxicity of hexachlorobenzene and associated residues in
edible animal tissues. J Am Vet Med Assoc 1975;166(6):591-5.
15. Rauch AE, Kowalsky SF, LesarTS, et al. Lindane (Kwell)-induced aplastic anemia. Arch Intern
Medl990;150:2393-5.
16. Furie B and Trubowitz S. Insecticides and blood dyscrasias. Chlordane exposure and self-
limited refractory megaloblastic anemia. JAMA 1976;235(16):1720-2.
17. Vonier PM, Grain DA, McLachlanJA, et al. Interaction of environmental chemicals with the
estrogen and progesterone receptors from the oviduct of the American alligator. Environ
Health Perspect 1996;104(12):1318-22.
SOLID ORGANOCHLORINES 61
-------
18. Fry DM. Reproductive effects in birds exposed to pesticides and industrial chemicals. Environ
Health Perspect 1995;103(Suppl 7):165-71.
19. Frank R, Rasper J, Smout MS, and Braun HE. Organochlorine residues in adipose tissues,
blood and milk from Ontario residents, 1976-1985. Can ]Public Health 1988;79:150-8.
20. Hosier 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 JMed 1978;298(5):243-8.
62 SOLID ORGANOCHLORINES
-------
CHAPTER 7
Biologicals and Insecticides
of Biological Origin
This chapter covers several widely-used insecticidal products of natural origin, as
well as certain agents often identified as biological control agents. Of the many
living control agents, only the bacterial agent Bacillus thuringiensis will be discussed
in detail, since it is one of the most widely used. Many other agents, such as
parasitic wasps and insects, are so host-specific that they pose little or no risk to
human health. The agents are discussed in this chapter in alphabetic order.
AZADIRACHTIN
This biologically-obtained insecticide is derived from the Neem tree
(Azadirachta indica). It is an insect growth regulator that interferes with the
molting hormone ecdysone.
Toxicology
Azadirachtin causes severe dermal and gastrointestinal irritation. Central
nervous system stimulation and depression have been seen. This agent is prima-
rily used and manufactured in India; little use or exposures are expected in the
United States.
HIGHLIGHTS
Derived from living systems
Bacillus thuringensis is the
most important live agent
Generally of low order
toxicity
Signs and Symptoms:
Highly variable based on
specific agents
Several cause
gastrointestinal irritation
Nicotine and rotenone may
have serious CMS effects
Nicotine and sabadilla may
have cardiovascular effects
Treatment:
Specific to the agent
Skin, eye, and Gl
decontamination may be
indicated
Nicotine, rotenone, and
sabadilla require aggressive
support
Treatment
1. Skin decontamination. If skin exposure occurs, the skin should be thor-
oughly washed with soap and water.
2. Gastrointestinal decontamination. Due to the severe gastrointestinal ir-
ritation, gastric emptying and catharsis are not indicated. Consideration should
be given to administration of activated charcoal as outlined in Chapter 2.
BIOLOGICALS 63
-------
Commercial Products
BACILLUS THURINGIENSIS
azadirachtin
Align
Azatin
Bollwhip
Neemazad
Neemazal
Neemix
Turplex
Bacillus thuringiensis
Variety aizawai:
Agree
Design
Mattch
XenTari
Variety israelensis:
Aquabac
Bactimos
Gnatrol
Skeetal
Teknar
Vectobac
Vectocide
Variety kurstaki:
Bactospeine
Bactur
Dipel
Futura
Sok-Bt
Thuricide
Tribactur
Variety morrisoni
Variety tenebrionis:
Novodor
eugenol
gibberellicacid (GA3)
Active I
Berelex
Cekugib
Gibberellin
Gibrel
Grocel
Pro-Gibb
Pro-Gibb Plus
Regulex
nicotine
Black Leaf 40
Nico Soap
pyrethrins
rotenone
Chem-Fish
Noxfire
Noxfish
Nusyn-Foxfish
Prenfish
(Continued on the next page)
Several strains of Bacillus thuringiensis are pathogenic to some insects. The
bacterial organisms are cultured, then harvested in spore form for use as insec-
ticide. Production methods vary widely. Proteinaceous and nucleotide-like toxins
generated by the vegetative forms (which infect insects) are responsible for the
insecticidal effect.The spores are formulated as wettable powders, flowable con-
centrates, and granules for application to field crops and for control of mosqui-
toes and black flies.
Toxicology
The varieties of Bacillus thuringiensis used commercially survive when in-
jected into mice, and at least one of the purified insecticidal toxins is toxic to
mice. Infections of humans have been extremely rare. A single case report of
ingestion by volunteers of Bacillus thuringiensis var. galleriae resulted in fever and
gastrointestinal symptoms. However, this agent is not registered as a pesticide.
B. thuringiensis products are exempt from tolerance on raw agricultural com-
modities in the United States. Neither irritative nor sensitizing effects have
been reported in workers preparing and applying commercial products.
Treatment
1. Skin decontamination. Skin contamination should be removed with soap
and water. Eye contamination should be flushed from the eyes with clean water
or saline. If irritation persists, or if there is any indication of infection, treatment
by a physician should be obtained.
A single case of cornea! ulcer caused by a splash of B. thuringiensis suspen-
sion into the eye was successfully treated by subconjunctival injection of gen-
tamicin (20 mg) and cefazolin (25 mg).1
2. Gastrointestinal decontamination. If a B. thuringiensis product has been
ingested, the patient should be observed for manifestations of bacterial gastro-
enteritis: abdominal cramps, vomiting, and diarrhea. The illness is likely to be
self-limited if it occurs at all. The patient should be treated symptomatically and
fluid support provided as appropriate.
EUGENOL
This compound is derived from clove oil. It is used as an insect attractant.
64 BIOLOGICALS
-------
Toxicology
Eugenol is similar in its clinical effects to phenol. Although it works as an
anesthetic, in large doses it can cause burns to epithelial surfaces.2 Sloughing of
mucous membranes has occurred as an allergic reaction to a small dose applied
topically in the mouth.3 Gastric mucosal lesions have been reported in animals,
but no lesions were seen on endoscopy after clove oil ingestion.4 Large doses
may result in coma and liver dysfunction.5
Treatment
Treatment is primarily supportive as there is no antidote. If mucosal burns
are present, consider endoscopy to look for other ulcerations.
Commercial Products
(Continued)
Rotacide
Rotenone Solution FK-11
Sypren-Fish
sabadilla
streptomycin
Agri-Mycin 17
Paushamycin, Tech.
Plantomycin
*Discontinued in the U.S.
GIBBERELLIC ACID (Gibberellin, GA3)
Gibberellic acid is not a pesticide, but it is commonly used in agricultural
production as a growth-promoting agent. It is a metabolic product of a cul-
tured fungus, formulated in tablets, granules, and liquid concentrates for appli-
cation to soil beneath growing plants and trees.
Toxicology
Experimental animals tolerate large oral doses without apparent adverse
effect. No human poisonings have been reported. Sensitization has not been
reported, and irritant effects are not remarkable.
Treatment
1. Skin decontamination. Wash contamination from skin with soap and
water. Flush contamination from eyes with clean water or saline. If irritation
occurs, obtain medical treatment.
2. Gastrointestinal decontamination. If gibberellic acid has been swallowed,
there is no reason to expect adverse effects.
NICOTINE
Nicotine is an alkaloid contained in the leaves of many species of plants,
but is usually obtained commercially from tobacco. A 14% preparation of the
free alkaloid is marketed as a greenhouse fumigant. Significant volatilization of
nicotine occurs. Commercial nicotine insecticides have long been known as
Black Leaf 40. This formulation was discontinued in 1992. Other currently
BIOLOGICALS 65
-------
available formulations include dusts formulated with naphthalene and dried
blood used to repel dogs and rabbits. Be aware of Green Tobacco Syndrome
from dermal absorption.Very little nicotine insecticide is currently used in the
United States, although old preparations of nicotine insecticides may still be
found on occasion.6 Today, most nicotine poisonings are the result of ingestion
of tobacco products and incorrect use of nicotine skin patches.
Toxicology
Nicotine alkaloid is efficiently absorbed by the gut, lung, and skin. Exten-
sive biotransformation occurs in the liver with 70-75% occurring as a first pass
effect.7 Both the liver and kidney participate in the formation and excretion of
multiple end-products, which are excreted within a few hours. Estimates of the
half-life of nicotine range from about one hour in smokers to as much as two
hours in non-smokers.8'9
Toxic action is complex. At low doses, autonomic ganglia are stimulated.
Higher doses result in blockade of autonomic ganglia and skeletal muscle neuro-
muscular junctions, and direct effects on the central nervous system. Paralysis and
vascular collapse are prominent features of acute poisoning, but death is often due
to respiratory paralysis, which may ensue promptly after the first symptoms of
poisoning. Nicotine is not an inhibitor of the cholinesterase enzyme.
Signs and Symptoms of Poisoning
Early and prominent symptoms of poisoning include salivation, sweating,
dizziness, nausea, vomiting, and diarrhea. Burning sensations in the mouth and
throat, agitation, confusion, headache, and abdominal pain are reported. If dos-
age has been high, vascular collapse with hypotension, bradycardia or other
arrythmias, dyspnea then respiratory failure, and unconsciousness may ensue
promptly6'10'11'12 In some cases, hypertension and tachycardia may precede hy-
potension and bradycardia, with the latter two signs leading to shock.11'12 Sei-
zures may also occur.6'11 In one case of ingestion of a large dose of nicotine
alkaloid pesticide, the patient developed asystole within two minutes. He later
developed seizures and refractory hypotension.6
Confirmation of Poisoning
Urine content of the metabolite cotinine can be used to confirm absorp-
tion of nicotine.
66 BIOLOGICALS
-------
Treatment
1. Skin decontamination. If liquid or aerosol spray has come in contact with
skin, wash the area thoroughly with soap and water. If eyes have been contami-
nated, flush them thoroughly with clean water or saline. If irritation persists,
obtain specialized medical treatment.
If symptoms of poisoning appear during exposure to an airborne nicotine
insecticide, remove the person from the contaminated environment immediately,
wash any skin areas that may be contaminated, then transport the victim to the
nearest treatment facility. Although mild poisoning may resolve without treat-
ment, it is often difficult to predict the ultimate severity of poisoning at the onset.
2. Pulmonary ventilation. If there is any indication of loss of respiratory
drive, maintain pulmonary ventilation by mechanical means, using supplemen-
tal oxygen if available, or mouth-to-mouth or mouth-to-nose methods if nec-
essary. Toxic effects of nicotine other than respiratory depression are usually
survivable. The importance of maintaining adequate gas exchange is therefore
paramount.
3. Gastrointestinal decontamination. If a nicotine-containing product has
been ingested recently, immediate steps must be taken to limit gastrointestinal
absorption. If the patient is fully alert, immediate oral administration of acti-
vated charcoal as outlined in Chapter 2 is probably the best initial step in man-
agement. Repeated administration of activated charcoal at half or more the
initial dosage every 2-4 hours may be beneficial. Since diarrhea is often a part
of this poisoning, it is usually not necessary or appropriate to administer a
cathartic. Do not administer syrup of ipecac.
4. Cardiac monitoring. Monitor cardiac status by electrocardiography and
measure blood pressure frequently. Cardiopulmonary resuscitation may
be necessary. Vascular collapse may require administration of norepinephrine
and/or dopamine. Consult package inserts for dosages and routes of adminis-
tration. Infusions of electrolyte solutions, plasma, and/or blood may also be
required to combat shock.
5. Atropine sulfate. There is no specific antidote for nicotine poisoning. Se-
vere hypersecretion (especially salivation and diarrhea) or bradycardia may be
treated with intravenous atropine sulfate. See dosage on next page.
BIOLOGICALS 67
-------
Dosage of Atropine Sulfate:
Adults and children over 12years: 0.4-0.5 nig slowly IV, repeated every
5 minutes if necessary
Children under 12years:0.01 mg/kgbody weight, slowly IV, repeated
every 5 minutes if necessary There is a minimum dose of 0.1 mg.
6. Convulsions should be controlled as outlined in Chapter 2. If the patient
survives for four hours, complete recovery is likely
PYRETHRUM AND PYRETHRINS
Pyrethrum is the oleoresin extract of dried chrysanthemum flowers. The
extract contains about 50% active insecticidal ingredients known as pyrethrins.
The ketoalcoholic esters of chrysanthemic and pyrethroic acids are known as
pyrethrins, cinerins, and jasmolins. These strongly lipophilic esters rapidly pen-
etrate many insects and paralyze their nervous systems. Both crude pyrethrum
extract and purified pyrethrins are contained in various commercial products,
commonly dissolved in petroleum distillates. Some are packaged in pressurized
containers ("bug-bombs"), usually in combination with the synergists piperonyl
butoxide and n-octyl bicycloheptene dicarboximide.The synergists retard enzy-
matic degradation of pyrethrins. Some commercial products also contain
organophosphate or carbamate insecticides.These are included because the rapid
paralytic effect of pyrethrins on insects ("quick knockdown") is not always lethal.
Pyrethrum and pyrethrin products are used mainly for indoor pest control.
They are not sufficiently stable in light and heat to remain as active residues on
crops. The synthetic insecticides known as pyrethroids (chemically similar to
pyrethrins) do have the stability needed for agricultural applications. Pyrethroids
are discussed separately in Chapter 8.
Toxicology
Crude pyrethrum is a dermal and respiratory allergen, probably due mainly
to non-insecticidal ingredients. Contact dermatitis and allergic respiratory re-
actions (rhinitis and asthma) have occurred following exposures.13'14 Single cases
exhibiting anaphylactic15 and pneumonitic manifestations16 have also been re-
ported. The refined pyrethrins are probably less allergenic, but appear to retain
some irritant and/or sensitizing properties.
Pyrethrins are absorbed across the gut and pulmonary membrane, but only
slightly across intact skin.They are very effectively hydrolyzed to inert products
by mammalian liver enzymes. This rapid degradation combined with relatively
68 BIOLOGICALS
-------
poor bioavailability probably accounts in large part for their relatively low mam-
malian toxicity Dogs fed extraordinary doses exhibit tremor, ataxia, labored
breathing, and salivation. Similar neurotoxicity rarely, if ever, has been observed
in humans, even in individuals who have used pyrethrins for body lice control
(extensive contact) or pyrethrum as an anthelmintic (ingestion).
In cases of human exposure to commercial products, the possible role of
other toxicants in the products should be kept in mind. The synergists pipero-
nyl butoxide and n-octyl bicycloheptene dicarboximide have low toxic poten-
tial in humans, but organophosphates or carbamates included in the product
may have significant toxicity. Pyrethrins themselves do not inhibit cholinest-
erase enzyme.
Confirmation of Poisoning
There are at present no practical tests for pyrethrin metabolites or pyrethrin
effects on human enzymes or tissues that can be used to confirm absorption.
Treatment
1. Antihistamines are effective in controlling most allergic reactions. Severe
asthmatic reactions, particularly in predisposed persons, may require adminis-
tration of inhaled B2-agonists and/or systemic corticosteroids. Inhalation ex-
posure should be carefully avoided in the future.
2. Anaphylaxis-type reactions may require sub-cutaneous epinephrine,
epinepherine, and respiratory support.1
15
3. Contact dermatitis may require extended administration of topical corti-
costeroid preparations. This should be done under the supervision of a physi-
cian. Future contact with the allergen must be avoided.
4. Eye contamination should be removed by flushing the eye with large
amounts of clean water or saline. Specialized ophthalmologic care should be
obtained if irritation persists.
5. Other toxic manifestations caused by other ingredients must be treated ac-
cording to their respective toxic actions, independent of pyrethrin-related effects.
6. Gastrointestinal decontamination. Even though most ingestions of pyre-
thrin products present little risk, if a large amount of pyrethrin-containing
material has been ingested and the patient is seen within one hour, consider
gastric emptying. If the patient is seen later, or if gastric emptying is performed,
consider administration of activated charcoal as described in Chapter 2.
BIOLOGICALS 69
-------
ROTENONE
Although this natural substance is present in a number of plants, the source
of most rotenone used in the United States is the dried derris root imported
from Central and South America. It is formulated as dusts, powders, and sprays
(less than 5% active ingredient) for use in gardens and on food crops. Many
products contain piperonyl butoxide as synergist, and other pesticides are in-
cluded in some commercial products. Rotenone degrades rapidly in the envi-
ronment. Emulsions of rotenone are applied to lakes and ponds to kill fish.
Toxicology
Although rotenone is toxic to the nervous systems of insects, fish, and birds,
commercial rotenone products have presented little hazard to humans over
many decades. Neither fatalities nor systemic poisonings have been reported in
relation to ordinary use. However, there is one report of a fatality in a child
who ingested a product called Gallocide, which contains rotenone and etheral
oils, including clove oil. She developed a gradual loss of consciousness over two
hours and died of respiratory arrest.17
Numbness of oral mucous membranes has been reported in workers who
got dust from the powdered derris root in their mouths. Dermatitis and respira-
tory tract irritation have also been reported in occupationally exposed persons.
When rotenone has been injected into animals, tremors, vomiting, incoor-
dination, convulsions, and respiratory arrest have been observed. These effects
have not been reported in occupationally exposed humans.
Treatment
1. Skin decontamination. Skin contamination should be removed by wash-
ing with soap and water. Eye contamination should be removed by flushing the
eye thoroughly with clean water or saline. Dust in the mouth should be washed
out. If irritation persists, medical treatment should be obtained.
2. Gastrointestinal decontamination. If a large amount of a rotenone-con-
taining product has been swallowed and retained and the patient is seen within
an hour of exposure, consideration should be given to gastric emptying. Whether
or not gastric emptying is performed, consider use of activated charcoal as
outlined in Chapter 2.
3. Respiratory support should be used as necessary if mental status changes
and/or respiratory depression occurs.
70 BIOLOGICALS
-------
SABADILLA (Veratrum alkaloid)
Sabadilla consists of the powdered ripe seeds of a South American lily. It is
used as dust, with lime or sulfur, or dissolved in kerosene, mainly to kill ecto-
parasites on domestic animals and humans. Insecticidal alkaloids are those of
the veratrum type. The concentration of alkaloids in commercial sabadilla is
usually less than 0.5%. Little or no sabadilla is used in the United States today,
but some is probably used in other countries. Most toxic encounters with ver-
atrum alkaloid occur from the inadvertent ingestion of the plant.18
Toxicology
Sabadilla dust is very irritating to the upper respiratory tract, causing sneez-
ing, and is also irritating to the skin.Veratrin alkaloids are apparently absorbed
across the skin and gut, and probably by the lung as well. Veratrin alkaloids have a
digitalis-like action on the heart muscles (impaired conduction and arrhythmia).
Although poisoning by medicinal veratrum preparations may have occurred
in the past, systemic poisoning by sabadilla preparations used as insecticides has
been very rare. The prominent symptoms of veratrum alkaloid poisoning are
severe nausea and vomiting, followed by hypotension and bradycardia. Other
arrythmias or A-V block may occur.18'19
Treatment
1. Skin decontamination. Contaminated skin should be washed thoroughly
with soap and water. If eyes are affected, they should be flushed with copious
amounts of clean water or saline. If skin or eye irritation persists, medical treat-
ment should be obtained.
2. Gastrointestinal decontamination. If a large amount of sabadilla pesticide
product has been ingested in the past hour and retained, consider gastric empty-
ing. This may be followed by administration of charcoal. If only a small amount of
sabadilla pesticide has been ingested and retained, or if treatment is delayed, and if
the patient remains fully alert, immediate oral administration of activated char-
coal probably represents reasonable management, as outlined in Chapter 2.
3. Cardiac monitoring. If there is a suspicion that significant amounts of
sabadilla alkaloids have been absorbed, EGG monitoring of cardiac activity for
arrhythmia and conduction defects is appropriate. Bradycardia may be treated
with atropine.18'19 See dosage on next page.
BIOLOGICALS 71
-------
Dosage of Atropine Sulfate:
Adults and children over 12 years: 0.4-0.5 nig slowly IV, repeated ev-
ery 5 minutes if necessary.
Children under 12years:0.01 mg/kgbody weight, slowly IV, repeated
every 5 minutes if necessary. (There is a minimum dose of 0.1 mg).
STREPTOMYCIN
Streptomycin sulfate and nitrate are used as pesticides for the control of a
variety of commercially important bacterial plant pathogens. Streptomycin is
an antibiotic derived from the growth of Streptomyces griseus.
Toxicology
This antibiotic shares a toxic profile with the aminoglycoside antibiotics
commonly used to treat human diseases. Its major modes of toxicity are neph-
rotoxicity and ototoxicity Fortunately, it is poorly absorbed from the gastrointes-
tinal tract, so systemic toxicity is unlikely with ingestion.
Treatment
If a large amount of streptomycin has been ingested within one hour of the
patient's receiving care, gastric emptying should be considered. Administration
of activated charcoal, as outlined in Chapter 2, should be considered.
References
1. Samples JR and Buettner H. Cornea! ulcer caused by a biological insecticide (Bacillus
thuringiensis). Am ] Ophthalmol 1983;95:258.
2. Isaacs G. Permanent local anesthesia and anhydrosis after clove oil spillage. Lancet 1983;! :882.
3. Barkin ME, BoydJP, and Cohen S. Acute allergic reaction to eugenol. Oral Surg Oral Med Oral
Pathol 1984;57:441-2.
4. Lane BW, Ellenhorn MJ, HulbertTV, et al. Clove oil ingestion in an infant. Hum Exp Toxicol
1991;10:291-4.
5. Hartnoll G, Moore D, and Douek D. Near fatal ingestion of oil of cloves. Arch Dis Child
1993;69:392-3.
6. Lavoie FW and Harris TM. Fatal nicotine ingestion. /Emerg Med 1991 ;9:133-6.
7. Svensson CK. Clinical pharmacokinetics of nicotine. Clin Pharm 1987;12:30-40.
72 BIOLOGICALS
-------
8. Kyerematen MS, Damiano MD, Dvorchik BH, et al. Smoking-induced changes in nicotine
disposition: Application of a new HPLC assay for nicotine and its metabolites. Clin Pharmacol
Ther 1982;32:769-80.
9. Feyerabend C, Ings RMJ, and Russell MAH. Nicotine pharmacokinetics and its application
to intake from smoking. BrJ Clin Pharmacol 1985;19:239-47.
10. Woolf A, Burkhart K, Caraccio T, et al. Self-poisoning among adults using multiple transdermal
nicotine patches. JToxicol Clin Toxicol 1996;34:691-8.
11. Sanchez P, Ducasse JL, Lapeyre-Mestre M, et al. Nicotine poisoning as a cause of cardiac
arrest? (letter). JToxicol Clin Toxicol 1996;34:475-6.
12. Malizia E, Andreucci G, Alfani F, et al. Acute intoxication with nicotine alkaloids and can-
nabinoids in children from ingestion of cigarettes. 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.
MedJAust 1983; 1:378-80.
15. Culver CA, Malina JJ, and Talbert RL. Probable anaphylactoid reaction to a pyrethrin
pediculocide shampoo. Clin Pharm 1988;7:846-9.
16. Carlson JE and Villaveces JW. Hypersensitivity pneumonitis due to pyrethrum. JAMA
1977;237:1718-9.
17. DeWilde AR.A case of fatal rotenone poisoning in a child. / Forensic Sci 1986;31(4):1492-8.
18. Jaffe AM, Gephardt D, and Courtemanche L. Poisoning due to ingestion of veratrum viride
(false heUebore). JEmerg Med 1990;8:161-7.
19. Quatrehomme G, Bertrand F, Chauvet C, et al. Intoxication from veratrum album. Hum Exp
TaxfcoM993;12:lll-5.
BIOLOGICALS 73
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CHAPTERS
HIGHLIGHTS
Multiple agents, with
widely varying toxicity
Careful history will usually
reveal exposure history
Agents of particular
concern due to wide use
are pyrethroids,
diethyltoluamide, and
borates
Signs and Symptoms:
Variable and highly related
to the specific agent
Boric acid causes severe
erythematous and
exfoliative rash (boiled
lobster appearance)
Agents such as boric acid,
diethyltoluamide, and
pyrethroids should be
suspected in cases of
unusual nervous system
symptoms
Treatment:
Specific to the agents
Skin and Gl
decontamination
Severe CMS symptoms may
require intensive care
management
Other Insecticides,
Acaricides, and Repellents
This chapter discusses insecticides, acaricides, and repellents that have toxico-
logic characteristics distinct from the insecticides discussed in previous chap-
ters. Pesticides reviewed include: alkyl phthalates, benzyl benzoate, borates,
chlordimeform, chlorobenzilate, cyhexatin, diethyltoluamide, fluorides,
haloaromatic urea compounds, methoprene, propargite, pyrethroids, and sulfur.
ALKYL PHTHALATES
Dimethyl phthalate has been widely used as an insect repellent applied
directly to the skin. Dibutylphthalate is impregnated into fabric for the same
purpose. It is more resistant to laundering than dimethyl phthalate.
Toxicology
Dimethyl phthalate is strongly irritating to the eyes and mucous membranes.
It has caused little or no irritation when applied to skin, and dermal absorption is
apparently minimal. It has not caused sensitization.Tests in rodents have indicated
low systemic toxicity, but large ingested doses cause gastrointestinal irritation,
central nervous system depression, coma, and hypotension.
Treatment
No antidote is available. Supportive measures (hydration, oxygen if needed)
are probably adequate to manage all but the most severe poisonings.
BENZYL BENZOATE
Toxicology
Incorporated into lotions and ointments, this agent has been used for many
years in veterinary and human medicine against mites and lice. Apart from
occasional cases of skin irritation, adverse effects have been few. The efficiency
74 OTHER INSECTICIDES
-------
of skin absorption is not known. Absorbed benzyl benzoate is rapidly
biotransformed to hippuric acid which is excreted in the urine.When given in
large doses to laboratory animals, benzyl benzoate causes excitement, incoordi-
nation, paralysis of the limbs, convulsions, respiratory paralysis, and death. No
human poisonings have been reported.
Treatment
1. Skin decontamination. If significant irritant effect appears, medications
should be discontinued and the skin cleansed with soap and water. Eye con-
tamination should be treated by prolonged flushing with clean water or saline.
2. Gastrointestinal decontamination. If a potentially toxic amount has been
swallowed and retained and the patient is seen soon after exposure, gastrointes-
tinal decontamination should be considered as outlined in Chapter 2.
3. Seizures. If seizures occur, control may require anticonvulsant medication
as outlined in Chapter 2.
BORIC ACID AND BORATES
Boric acid is formulated as tablets and powder to kill larvae in livestock
confinement areas and cockroaches, ants, and other insects in residences. Rarely,
solutions are sprayed as a nonselective herbicide.
Toxicology
Boric acid powders and pellets scattered on the floors of homes do present
a hazard to children. Their frequent use for roach control increases access for
ingestion. A series of 784 patients has been described with no fatalities and
minimum toxicity Only 12% of these patients had symptoms of toxicity, mostly
to the gastrointestinal tract.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
deca hydrate
Borax
CHLORDIMEFORM (nr)
CHLOROBENZILATE (nr)
Acaraben
Akar
Benzilan
Folbex
CYHEXATIN (nr)
Acarstin
Metaran
Oxotin
Pennstyl
Plictran
DIETHYLTOLUAMIDE (DEET)
Auton
Detamide
Metadelphene
MGK
Muskol
Off!
Skeeter Beater
Skeeter Cheater
Skintastic for Kids
FLUORIDES
sodium fluoride (wood
protection only)
sodium fluosilicate (sodium
silico fluoride) (nr)
Prodan
Safsan
sodium fluoaluminate
Cryolite
Kryocide
Prokil
(Continued on the next page)
OTHER INSECTICIDES 75
-------
Commercial Products
(Continued)
HALOAROMATIC
SUBSTITUTED UREAS
diflubenzuron
Dimilin
Micromite
Vigilante
teflubenzuron
Dart
Diaract
Nomolt
METHOPRENE
Altosid
Apex
Diacon
Dianex
Kabat
Minex
Pharorid
Precor
PROPARGITE
Comite
Fenpropar
Omite
Ornamite
Mightikill
PYRETHROIDS
allethrin
Pynamin
barthrin (nr)
bioallethrin
D-trans
biopermethrin (nr)
bioresmethrin (nr)
cismethrin (nr)
cyfluthrin
Baythroid
cypermethrin
Ammo
Barricade
CCN52
Cymbush
Cymperator
Cynoff
Cyperkill
Cyrux
(Continued on the next page)
When determining toxicity to boric acid from ingestion, it is important to
distinguish between acute and chronic exposure. Chronic ingestion is more
likely to cause significant toxicity than acute exposure.1'2 Borates are well ab-
sorbed by the gut and by abraded or burned skin, but not by intact skin.6 The
kidney efficiently excretes them. The residence half-life in humans averages 13
hours, in a range of 4-28 hours.1
The gastrointestinal tract, skin, vascular system, and brain are the principal
organs and tissues effected. Nausea, persistent vomiting, abdominal pain, and
diarrhea reflect a toxic gastroenteritis.1'2'7 Lethargy and headache may occur,
but are more infrequent.1 In severe poisonings, a beefy red skin rash, most often
affecting palms, soles, buttocks, and scrotum, has been described. It has been
characterized as a "boiled lobster appearance." The intense erythema is fol-
lowed by extensive exfoliation.2'5'10 This may be difficult to distinguish from
staphylcoccal scalded skin syndrome.10
Headache, weakness, lethargy, restlessness, and tremors may occur, but are
less frequent than gastrointestinal effects.1 Seven infants who were exposed to a
mixture of borax and honey on their pacifiers developed seizures.11 Uncon-
sciousness and respiratory depression signify life-threatening brain injury. Cy-
anosis, weak pulse, hypotension, and cold clammy skin indicate shock, which is
sometimes the cause of death in borate poisoning.2'3'7
Acute renal failure (oliguria or anuria) may be a consequence of shock, of
direct toxic action on renal tubule cells, or both. It occurs in severe borate
poisoning.2'3'5'10 Metabolic acidosis may be a consequence of the acid itself, of
seizure activity, or of metabolic derangements.2 Fever is sometimes present in
the absence of infection.
Confirmation of Poisoning
Borate can be measured in serum by colorimetric methods, as well by
high-temperature atomic spectrometric methods. Urine borate concentrations
in non-exposed individuals are in the range of 0.004-.66 mg/dL. Normal se-
rum levels range up to 0.2 mg/dL in adults, and in children to 0.125 mg/dL.7
Levels reported in toxic incidents have varied widely, and it is felt that serum
levels are of little use in guiding therapy1
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
2. Gastrointestinal decontamination. In acute poisonings, if a large amount
76
OTHER INSECTICIDES
-------
has been ingested and the patient is seen within one hour of exposure, gas-
trointestinal decontamination should be considered as outlined in Chapter 2. It
is important to keep in mind that vomiting and diarrhea are common, and
severe poisoning may be associated with seizures. Therefore induction of erne-
sis by syrup of ipecac is probably contraindicated in these exposures. Catharsis
is not indicated if diarrhea is present.
3. Intravenous fluids. If ingestion of borate has been massive (several grams),
or has extended over several days, administer intravenous glucose and electro-
lyte solutions to sustain urinary excretion of borate. Monitor fluid balance and
serum electrolytes (including bicarbonate capacity) regularly. Monitor cardiac
status by EGG. Test the urine for protein and cells to detect renal injury, and
monitor serum concentration of borate. Metabolic acidosis may be treated with
sodium bicarbonate. If shock develops, it may be necessary to infuse plasma or
whole blood. Administer oxygen continuously. If oliguria (less than 25-30 mL
urine formed per hour) occurs, intravenous fluids must be slowed or stopped to
avoid overloading the circulation. Such patients should usually be referred to a
center capable of providing intensive care for critically ill patients.
4. Hemodialysis. If renal failure occurs, hemodialysis may be necessary to
sustain fluid balance and normal extracellular fluid composition. Hemodialysis
has had limited success in enhancing clearance of borates.1
5. Peritoneal dialysis has been performed in borate poisoning5'12 and is felt to
be as effective as, and safer than, exchange transfusion in removing borate. No
large study of efficacy has been done, but it is still used somewhat less fre-
quently than hemodialysis.1
6. Seizures should be controlled as recommended for other agents and out-
lined Chapter 2.
CHLORDIMEFORM
Chlordimeform is an ovicide and acaricide. Formulations are emulsifiable
concentrates and water-soluble powders.
Toxicology
In a reported episode of occupational exposure to chlordimeform, several
workers developed hematuria. Hemorrhagic cystitis, probably due to chloraniline
biodegradation products, was the source of the blood in the urine. Symptoms
reported by the affected workers included gross hematuria, dysuria, urinary
frequency and urgency, penile discharge, abdominal and back pain, a general-
Commercial Products
(Continued)
Demon
Flectron
Folcord
KafilSuper
NRDC149
Polytrin
Ripcord
Siperin
Ustadd
others
deltamethrin
Decis
DeltaDust
DeltaGard
Deltex
Suspend
dimethrin
fenothrin (nr)
fenpropanate (nr)
fenpropathrin
Danitol
Herald
Meothrin
Rody
fenvalerate
Belmark
Fenkill
Sumicidin
flucythrinate
Cybolt
Fluent
Payoff
fluvalinate
furethrin (nr)
permethrin
Ambush
Dragnet
Eksmin
Elimite
Kafil
Nix
Outflank
Permasect
Perthrine
Pounce
Pramex
Talcord
others
phthalthrin (nr)
resmethrin
Benzofuroline
Chrysron
Pynosect
(Continued on the next page)
OTHER INSECTICIDES 77
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Commercial Products
(Continued)
tetramethrin
Neopynamin
tralomethrin
SAGA
Tralex
SULFUR
many commercial products
nr= not registered or withdrawn
ized "hot" sensation, sleepiness, skin rash and desquamation, a sweet taste, and
anorexia. Symptoms persisted for 2-8 weeks after exposure was terminated.13
In a single case, methemoglobinemia was reported.14 Chlordimeform is not a
cholinesterase inhibitor. Chlordimeform has been voluntarily cancelled in the
U.S. due to concerns regarding increased bladder cancer incidence seen in
manufacturing workers.
Confirmation of Poisoning
Although methods do exist for measurement of urinary excretion prod-
ucts, these tests are not generally available.
Treatment
1. Precautions. Strenuous efforts should be made to protect against inhalation
and dermal contact with chlordimeform because absorption is evidently effi-
cient.
2. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
3. Gastrointestinal decontamination. If chlordimeform has been ingested
no more than an hour prior to treatment, consider gastrointestinal decontami-
nation as outlined in Chapter 2. Repeated doses of charcoal every 2-4 hours
may be beneficial.
4. Hydration. Because catharsis may cause serious dehydration and electrolyte
disturbances in young children, fluid balance and serum electrolytes should be
monitored. An adequate state of hydration should be maintained by oral and/
or intravenous fluids to support chlordimeform excretion.
5. Urinary analysis. Repeated analyses of urine for protein and red cells
should be done to detect injury to the urinary tract. Disappearance of hema-
turia can ordinarily be expected in 2-8 weeks. Relief from other symptoms can
usually be expected earlier.
CHLOROBENZILATE
Chlorobenzilate is a chlorinated hydrocarbon acaricide, usually formulated
as an emulsion or wettable powder for application in orchards. Use in the
United States has been discontinued.
78
OTHER INSECTICIDES
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Toxicology
Chlorobenzilate is moderately irritating to the skin and eyes. Although struc-
turally similar to DDT, chlorobenzilate is much more rapidly excreted following
absorption, chiefly in the urine as the benzophenone and benzoic acid deriva-
tives. Based on observation of dosed animals, extreme absorbed doses may cause
tremors, ataxia, and muscle weakness.There has been one case in humans of toxic
encephalopathy following spraying in a field for 14 days at 10 hours per day. The
patient did not wear a mask while spraying. His symptoms included muscle pain,
weakness, fever, and mental status changes progressing to a tonic-clonic seizure.
He recovered without sequelae within 6 days. Treatment included respiratory
support and seizure control with phenobarbital and phenytoin.15
Chlorobenzilate is not a cholinesterase inhibitor.
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
2. Gastrointestinal decontamination. If a large amount of chlorobenzilate
was ingested within a few hours prior to treatment, consider gastrointestinal
decontamination as outlined in Chapter 2. If the absorbed dose of chlorobenzilate
was small, if treatment is delayed, and if the patient is asymptomatic, oral ad-
ministration of activated charcoal and sorbitol may be indicated. Do not give
fats or oils.
3. Seizures. Any seizures should be treated as outlined in Chapter 2.
CYHEXATIN
Toxicology
Tricyclohexyl tin hydroxide is formulated as a 50% wettable powder for
control of mites on ornamentals, hops, nut trees, and some fruit trees. It is
moderately irritating, particularly to the eyes. While information on the sys-
temic toxicity of this specific tin compound is lacking, it should probably be
assumed that cyhexatin can be absorbed to some extent across the skin, and that
substantial absorbed doses would cause nervous system injury (see organotin
compounds in Chapter 15, Fungicides). Cyhexatin has been voluntarily can-
celled in the United States.
OTHER INSECTICIDES 79
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Treatment
1. Skin decontamination. Wash skin with soap and water. Remove contami-
nation from the eyes by prolonged flushing with clean water or saline.
2. Gastrointestinal decontamination. Management of poisonings by inges-
tion should proceed on the assumption that cyhexatin is toxic, even though
rodent LD50 values are fairly high, and no human poisonings have been re-
ported. Treatment should be as with other organotin compounds.
DIETHYLTOLUAMIDE (DEBT)
This chemical is a widely-used liquid insect repellent, suitable for application
to skin or to fabrics. It comes in a wide range of concentrations from 5% (Off!,
Skintastic for KidsR) to 100% (MuskoF). Compared to the widespread use of the
product, there are relatively few cases of toxicity16 However, if used improperly,
ingested, or a very high concentration is used on children, especially repeatedly
over large skin surfaces, the potential for severe toxicity exists.17 DEBT is formu-
lated with ethyl or isopropyl alcohol.
Toxicology
For many years, diethyltoluamide has been effective and generally well
tolerated as an insect repellent applied to human skin, although tingling, mild
irritation, and sometimes desquamation have followed repeated application. In
some cases, DEBT has caused contact dermatitis and excerbation of pre-exist-
ing skin disease.18'19 It is very irritating to the eyes, but not corrosive.
Serious adverse effects have occurred when used under tropical condition,
when it was applied to areas of skin that were occluded during sleep (mainly
the antecubital and popliteal fossae). Under these conditions, the skin became
red and tender, then exhibited blistering and erosion, leaving painful weeping
denuded areas that were slow to heal. Severe scarring occasionally resulted
from some of these severe reactions.20
DEET is efficiently absorbed across the skin and by the gut. Blood concen-
trations of about 0.3 mg/dL have been reported several hours after dermal
application in the prescribed fashion.17 The amount absorbed increases as the
concentration of DEET rises. In addition, many commercial formulations are
prepared with ethanol as a solvent, which further increases absorption.21 Toxic
encephalopathic reactions have apparently occurred in rare instances following
dermal application, mainly in children who were intensively treated.22'23'24The
more frequent cause of systemic toxicity has been ingestion: deliberate in adults
and accidental in young children.16'17
80 OTHER INSECTICIDES
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Manifestations of toxic encephalopathy have been behavioral disorders in-
cluding headache, restlessness, irritability, ataxia, rapid loss of consciousness,
hypotension, and seizures. Some cases have shown flaccid paralysis and areflexia.
Deaths have occurred following very large doses.16'17'22 Blood levels of DEBT
found in fatal systemic poisonings have ranged from 168 to 240 mg per liter.17
Interpretation of DEBT toxicity in some fatal cases has been complicated by
effects of simultaneously ingested ethanol, tranquilizers, and other drugs. One
well-documented case of anaphylactic reaction to DEET has been reported.
One fatal case of encephalopathy in a child heterozygous for ornithine car-
bamoyl transferase deficiency resembled Reyes syndrome, but the postmortem
appearance of the liver was not characteristic of the syndrome.
Discretion should be exercised in recommending DEET for persons who have
acne, psoriasis, an atopic predisposition, or other chronic skin condition. It should
not be applied to any skin area that is likely to be opposed to another skin surface
for a significant period of time (antecubital and popliteal fossae, inguinal areas).22
Great caution should be exercised in using DEET on children. Avoid re-
peated application day after day. Applications should be limited to exposed
areas of skin, using as little repellent as possible and washing off after use. Do
not apply to eyes and mouth and, with young children, do not apply to their
hands. Low concentrations (10% or below) are effective and may be preferred
in most situations. There are formulations labeled for children that have
concentrations of 5 to 6.5% DEET25 If continuous repellent protection is
necessary, DEET should be alternated with a repellent having another active
ingredient. If headache or any kind of emotional or behavioral change occurs,
use of DEET should be discontinued immediately.
Confirmation of Poisoning
Methods exist for measurement of DEET in blood and tissues and of me-
tabolites in urine, but these are not widely available.
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of
the eye with copious amounts of clean water or saline. If irritation persists,
specialized medical treatment should be obtained. Topical steroids and oral
antihistamines have been used for severe skin reactions that occasionally
follow application of DEET21
2. Gastrointestinal decontamination. If a substantial amount of DEET
has been ingested within an hour of treatment, gastrointestinal decontami-
nation should be considered as outlined in Chapter 2. Induced emesis is
OTHER INSECTICIDES 81
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usually considered contraindicated in these poisonings due to the rapid
onset of seizures.
3. Seizures. Treatment is primarily supportive, with control of seizures by
anticonvulsants, as outlined in Chapter 2. Persons surviving poisoning by in-
gestion of DEBT have usually recovered within 36 hours or less.16'17
FLUORIDES
Sodium fluoride is a crystalline mineral once widely used in the United
States for control of larvae and crawling insects in homes, barns, warehouses,
and other storage areas. It is highly toxic to all plant and animal life. The only
remaining use permitted is for wood treatement
Sodium fluosilicate (sodium silico fluoride) has been used to control ec-
toparasites on livestock, as well as crawling insects in homes and work build-
ings. It is approximately as toxic as sodium fluoride. All uses in the U.S. have
been cancelled.
Sodium fluoaluminate (Cryolite) is a stable mineral containing fluoride. It
is used as an insecticide on some vegetables and fruits. Cryolite has very low
water solubility, does not yield fluoride ion on decomposition, and presents
very little toxic hazard to mammals, including humans.
Hydrofluoric acid is an important industrial toxicant, but is not used as a
pesticide. Sulfuryl fluoride is discussed in Chapter 16, Fumigants.
Toxicology
Sodium fluoride and fluosilicate used as insecticides present a serious haz-
ard to humans because of high inherent toxicity, and the possibility that chil-
dren crawling on floors of treated dwellings will ingest the material.
Absorption across the skin is probably slight, and methods of pesticide use
rarely include a hazard of inhalation, but uptake of ingested fluoride by the gut
is efficient and potentially lethal. Excretion is chiefly in the urine. Within the
first 24 hours of intoxication, renal clearance of fluoride from the blood is
rapid. However, patients go on to continue to excrete large amounts of fluoride
for several days. This is thought to be due to a rapid binding of fluoride to a
body store, probably bone. The subsequent release of fluoride from bone is
gradual enough not to cause a recurrence of toxicity26'27 Large loads of ab-
sorbed fluoride may potentially poison renal tubule cells, resulting in acute
renal failure. Children will have greater skeletal uptake of fluoride than adults,
therefore limiting the amount the kidney needs to handle. Despite this, chil-
dren are still at great risk because of their smaller body mass compared to adults
in relation to the amount ingested.27
82 OTHER INSECTICIDES
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The toxic effects of fluoride in mammals are multiple, and all may threaten
life. The primary effects from fluoride result from an inhibition of critical intra-
cellular enzymes and the direct effect on ionized calcium in extra-cellular fluid.
Hypocalcemia commonly occurs.26'28'29'30
Ingested fluoride is transformed in the stomach to hydrofluoric acid, which
has a corrosive effect on the epithelial lining of the gastrointestinal tract.Thirst,
abdominal pain, vomiting, and diarrhea are usual symptoms. Hemorrhage in
the gastric mucosa, ulceration, erosions, and edema are common signs.31
Absorbed fluoride ion reduces extracellular fluid concentrations of
calcium and magnesium. Hypocalcemia sometimes results in tetany30 Cardiac
arrhythmia and shock are often prominent features of severe poisoning.
Hypotension and severe arrhythmia, sometimes progressing to ventricular
fibrillation, may also occur.26'32 These probably result from combinations of
effects of fluid and electrolyte disturbances including hyperkalemia32 and direct
actions of fluoride on heart and vascular tissues. Fluoride may directly affect the
central nervous system, resulting in headache, muscle weakness, stupor,
convulsions, and coma.26'27'28 Respiratory failure and ventricular arrythmias are
common causes of death.26'27
Confirmation of Poisoning
A population drinking water with a concentration of 1 mg per liter will
have a plasma inorganic fluoride concentration between 0.01 and 0.03 mg per
liter28 and rarely above 0.10 mg per liter. In fatal cases of poisoning, plasma
levels of 3.5 mg per liter and higher have been recorded, although survival has
been reported in patients with levels as high as 14 mg per liter.26'28
Treatment: Fluoride Toxicosis
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
2. Gastrointestinal decontamination. If sodium fluoride or sodium
fluosilicate has been ingested, consider gastric decontamination as outlined in
Chapter 2.
If the victim is obtunded or if vomiting precludes oral administration, the
airway should be protected by endotracheal intubation, then the stomach should
be gently intubated and lavaged with several ounces of one of the liquids named
below. Activated charcoal is not likely to be of use because it does not bind the
fluoride ion well.
OTHER INSECTICIDES 83
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3. Calcium and magnesium. If the victim is fully alert, and if vomiting does
not totally prevent swallowing of a neutralizing agent, prompt oral administra-
tion of milk, calcium gluconate, or magnesium citrate will precipitate
fluoride ion in the gut and therefore may be life-saving. The milk provides the
calcium ions that will bind to fluoride, thereby reducing absorption. Magne-
sium-based antacids have also been used to neutralize the acid and facilitate the
production of poorly absorbed salts.26 There are no data on the optimum
amounts to be administered.
4. Blood analysis. A blood specimen should be drawn for serum electrolyte
analysis for sodium, potassium, calcium, magnesium, fluoride, and bicarbon-
ate capacity. Blood should also be drawn to type and cross match for blood
transfusion.
5. Intravenous fluids (initially 5% dextrose in 0.9% saline) should be started
to combat dehydration, shock, and metabolic acidosis. Fluid balance should be
monitored closely to forestall fluid overload if renal failure occurs. If metabolic
acidosis is detected, sodium bicarbonate should be administered to keep the
urine alkaline as this may hasten excretion.27 Intravenous fluids must be stopped
if anuria or oliguria (less than 25-30 mL per hour) develops.
6. Hemodialysis should be reserved for compromised renal function.26
7. Monitor cardiac status by continuous electrocardiography Ventricular
arrhythmia may necessitate DC cardioversion.
S.Tetany. If overt or latent tetany occurs, or if hypocalcemia is demonstrated,
or if it appears likely that a significant amount of fluoride has been absorbed,
administer 10 mL of 10% calcium gluconate intravenously, at no more than
1 mL per minute.
Dosage of Calcium Gluconate:
Supplied as 100 mg/mL (10% solution)
Adults and children over 12years/10 mL of 10% solution, given slowly,
intravenously. Repeat as necessary.
Children under 12 years: 200-500 mg/kg/24 hr divided Q6 hr. For
cardiac arrest, 100 mg/kg/dose. Repeat dosage as needed.
9. Oxygen by mask should be administered for hypotension, shock, cardiac
arrhythmia, or cyanosis. Shock may require administration of plasma or blood.
84 OTHER INSECTICIDES
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10. Acid Burns. Since these compounds can cause severe acid burns to the
esophagus and stomach, patients should be referred for surgical evaluation and
endoscopy. If burns are documented, treatment for acid burns should be con-
tinued by a surgeon or gastroenterologist.
Treatment: Sodium Fluoaluminate (Cryolite)
Cryolite is much less toxic than other fluorides. If a very large amount has
been ingested, it may be appropriate to measure serum calcium to insure that
hypocalcemia has not occurred. If so, intravenous 10% calcium gluconate would
be indicated (see 8 above). It is unlikely that treatment for fluoride toxicity
would be necessary following ingestion of sodium fluoaluminate.
HALOAROMATIC SUBSTITUTED UREAS
Diflubenzuron is a haloaromatic substituted urea which controls insects by
impairing chitin deposition in the larval exoskeleton. It is formulated in wet-
table powders, oil dispersible concentrate, and granules for use in agriculture
and forestry, for aerial application against gypsy moth, and in settings where fly
populations tend to be large, such as feedlots. Teflubenzuron is another
haloaromatic substituted urea insecticide with similar toxicologic properties.
Toxicology
There is limited absorption of diflubenzuron across the skin and intestinal
lining of mammals, after which enzymatic hydrolysis and excretion rapidly
eliminate the pesticide from tissues. Irritant effects are not reported and sys-
temic toxicity is low. Methemoglobinemia is a theoretical risk from chloraniline
formed hydrolytically, but no reports of this form of toxicity have been re-
ported in humans or animals from diflubenzuron exposure. Teflubenzuron also
shows low systemic toxicity.
Treatment
1. Skin decontamination. Wash skin with soap and water as outlined in
Chapter 2. Eye contamination should be removed by prolonged flushing of the
eye with copious amounts of clean water or saline. If irritation persists, obtain
specialized medical treatment. Sensitization reactions may require steroid therapy.
2. Gastrointestinal decontamination. If large amounts of propargite have
been ingested and the patient is seen within an hour, consider gastrointestinal
decontamination. For small ingestions, consider oral administration of activated
charcoal and sorbitol.
OTHER INSECTICIDES 85
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METHOPRENE
Methoprene is a long chain hydrocarbon ester active as an insect growth
regulator. It is effective against several insect species. Formulations include slow-
release briquets, sprays, foggers, and baits.
Toxicology
Methoprene is neither an irritant nor a sensitizer in humans or laboratory
animals. Systemic toxicity in laboratory animals is very low. No human poi-
sonings or adverse reactions in exposed workers have been reported.
Treatment
1. Skin decontamination. Wash contaminated skin with soap and water.
Flush contamination from eyes with copious amounts of clean water or saline.
If irritation persists, medical attention must be obtained.
2. Gastrointestinal decontamination. If a very large amount ofmethoprene
has been ingested, oral administration of charcoal may be considered.
PROPARGITE
Propargite is an acaricide with residual action. Formulations are wettable
powders and emulsifiable concentrates.
Toxicology
Propargite exhibits very little systemic toxicity in animals. No systemic
poisonings have been reported in humans. However, many workers having
dermal contact with this acaricide, especially during the summer months, have
experienced skin irritation and possibly sensitization in some cases.33 Eye irri-
tation has also occurred. For this reason, stringent measures should be taken to
prevent inhalation or any skin or eye contamination by propargite.
Confirmation of Poisoning
There is no readily available method for detecting absorption of propargite.
86 OTHER INSECTICIDES
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Treatment
Treatment of contamination and ingestions should proceed essentially as
outlined for haloaromatic substituted urea.
PYRETHROIDS
These modern synthetic insecticides are similar chemically to natural pyre-
thrins, but modified to increase stability in the natural environment. They are
now widely used in agriculture, in homes and gardens, and for treatment of
ectoparasitic disease.
Pyrethroids are formulated as emulsifiable concentrates, wettable powders,
granules, and concentrates for ultra low volume application.They may be com-
bined with additional pesticides (sometimes highly toxic) in the technical product
or tank-mixed with other pesticides at the time of application. AASTAR (dis-
continued 1992), for instance, was a combination of fluey thrinate and phorate.
Phorate is a highly toxic organophosphate. Nix and Elimite are permethrin
creams applied to control human ectoparasites.
Toxicology
Certain pyrethroids exhibit striking neurotoxicity in laboratory animals when
administered by intravenous injection, and some are toxic by the oral route. How-
ever, systemic toxicity by inhalation and dermal absorption is low. Although lim-
ited absorption may account for the low toxicity of some pyrethroids, rapid
biodegradation by mammalian liver enzymes (ester hydrolysis and oxidation) is
probably the major factor responsible for this phenomenon.34 Most pyrethroid
metabolites are promptly excreted, at least in part, by the kidney.
The most severe, although more uncommon, toxicity is to the central ner-
vous system. Seizures have been reported in severe cases of pyrethroid intoxica-
tion. Of 573 cases reviewed in China, there were 51 cases with disturbed
consciousness and 34 cases with seizures. Of those, only 5 were from occupa-
tional exposure.35 Seizures are more common with exposure to the more toxic
cyano-pyrethroids, which include fenvalerate, flucythrinate, cypermethrin,
deltapermethrin, and fluvalinate.34 There are no reports in the literature of sei-
zures in humans from exposure to permethrin.
Apart from central nervous system toxicity, some pyrethroids do cause dis-
tressing paresthesias when liquid or volatilized materials contact human skin.
Again, these symptoms are more common with exposure to the pyrethroids
whose structures include cyano-groups.34 Sensations are described as stinging,
burning, itching, and tingling, progressing to numbness.35'36'37 The skin of the
face seems to be most commonly affected, but the face, hands, forearms, and
neck are sometimes involved. Sweating, exposure to sun or heat, and applica-
OTHER INSECTICIDES 87
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tion of water enhance the disagreeable sensations. Sometimes the effect is noted
within minutes of exposure, but a 1-2 hour delay in appearance of symptoms is
more common.36'37 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 ex-
perience itching and burning at the site of application, but this is chiefly an
exacerbation of sensations caused by the parasites themselves, and is not typical
of the paresthetic reaction described above.
Other signs and symptoms of toxicity include abnormal facial sensation, diz-
ziness, salivation, headache, fatigue, vomiting, diarrhea, and irritability to sound
and touch. In more severe cases, pulmonary edema and muscle fasciculations can
develop.35 Due to the inclusion of unique solvent ingredients, certain formula-
tions of fluvalinate are corrosive to the eyes. Pyrethroids are not cholinesterase
inhibitors. However, there have been some cases in which pyrethroid poisoning
has been misdiagnosed as organophosphate poisoning, due to some of the similar
presenting signs, and some patients have died from atropine toxicity35
Treatment
1. Skin decontamination. Wash skin promptly with soap and water as out-
lined in Chapter 2. If irritant or paresthetic effects occur, obtain treatment by a
physician. Because volatilization of pyrethroids apparently accounts for pares-
thesia affecting the face, strenuous measures should be taken (ventilation, pro-
tective face mask and hood) to avoid vapor contact with the face and eyes.
Vitamin E oil preparations (dL-alpha tocopheryl acetate) are uniquely effective
in preventing and stopping the paresthetic reaction.37'38 They are safe for appli-
cation to the skin under field conditions. Corn oil is somewhat effective, but
possible side effects with continuing use make it less suitable. Vaseline is less
effective than corn oil. Zinc oxide actually worsens the reaction.
2. Eye contamination. Some pyrethroid compounds can be very corrosive
to the eyes. Extraordinary measures should be taken to avoid eye contamina-
tion. The eye should be treated immediately by prolonged flushing of the eye
with copious amounts of clean water or saline. If irritation persists, obtain pro-
fessional ophthalmologic care.
3. Gastrointestinal decontamination. If large amounts of pyrethroids, espe-
cially the cyano-pyrethroids, have been ingested and the patient is seen soon
OTHER INSECTICIDES
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after exposure, consider gastrointestinal decontamination as outlined in Chap-
ter 2. Based on observations in laboratory animals34 and humans,35 large ingestions
of allethrin, cismethrin, fluvalinate, fenvalerate, or deltamethrin would be the
most likely to generate neurotoxic manifestations.
If only small amounts of pyrethroid have been ingested, or if treatment
has been delayed, oral administration of activated charcoal and cathartic prob-
ably represents optimal management. Do not give cathartic if patient has
diarrhea or an ileus.
4. Other treatments. Several drugs are effective in relieving the pyrethroid
neurotoxic manifestations observed in deliberately poisoned laboratory animals,
but none has been tested in human poisonings. Therefore, neither efficacy nor
safety under these circumstances is known. Furthermore, moderate neurotoxic
symptoms and signs are likely to resolve spontaneously if they do occur.
5. Seizures. Any seizures should be treated as outlined in Chapter 2.
SULFUR
Elemental sulfur is an acaricide and fungicide widely used on orchard,
ornamental, vegetable, grain, and other crops. It is prepared as dust in various
particle sizes and applied as such, or it may be formulated with various minerals
to improve flowability, or applied as an aqueous emulsion or wettable powder.
Toxicology
Elemental sulfur is moderately irritating to the skin and is associated with
occupationally related irritant dermatitis.39 Airborne dust is irritating to the
eyes and the respiratory tract. In hot sunny environments, there may be some
oxidation of foliage-deposited sulfur to gaseous sulfur oxides, which are very
irritating to the eyes and respiratory tract.
Ingested sulfur powder induces catharsis, and has been used medicinally
(usually with molasses) for that purpose. Some hydrogen sulfide is formed in
the large intestine and this may present a degree of toxic hazard.The character-
istic smell of rotten eggs may aid in the diagnosis. An adult has survived inges-
tion of 200 grams.40
Ingested colloidal sulfur is efficiently absorbed by the gut and is promptly
excreted in the urine as inorganic sulfate.
OTHER INSECTICIDES 89
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Treatment
1. Skin decontamination. Wash skin with soap and water. Contamination of
the eyes should be removed by prolonged flushing with clean saline or water. If
eye irritation persists, obtain ophthamologic care.
2. Gastrointestinal decontamination. Unless an extraordinary amount of
sulfur (several grams) has been ingested shortly prior to treatment, there is
probably no need for gastrointestinal decontamination. Adsorbability of sulfur
on activated charcoal has not been tested.
The most serious consequence of sulfur ingestion is likely to be that of
catharsis, resulting in dehydration and electrolyte depletion, particularly in chil-
dren. If diarrhea is severe, oral or intravenous administration of glucose and/or
electrolyte solutions may be appropriate.
References
1. Litovitz TL, Klein-Schwartz W, Oderda GM, and Schmitz BE Clinical manifestations of
toxicity in a series of 784 boric acid ingestions. Am JEmerg Med 1988;6(3):209- 13.
2. Restuccio A, Mortensen ME, and Kelley MT. Fatal ingestion of boric acid in an adult. Am J
Emerg Med 1992;10(6):545-7.
3. IshiiY, 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.]Pediati 1953; 43(6):631- 43.
5. Wong EC, Heimbach MD.Truscott DR, and Duncan BD. Boric acid poisoning. Can Med
Assoc/1964;90:1018-23.
6. DuceyJ andWilliams 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. BrJInd Med 1992;49:706-13.
9. Garabrant DH, Bernstein L, Peters JM, et al. Respiratory effects of borax dust. BrJInd 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(ll):1052-5.
14. ArimaT, Morooka H.TanigawaT, et al. Methemoglobinemia induced by chlorphenamidine.
Acta Med Okayama 1976;30:57-60.
90 OTHER INSECTICIDES
-------
15. Ravindran M.Toxic encephalopathy from chlorobenzilate poisoning: Report of a case. Clin
Electroencephalogrl97S;9(4):nO-2.
16. Veltri JC, OsimitzTG, Bradford DC, et al. Retrospective analysis of calls to poison control
centers resulting from exposure to the insect repellent N, N-diethyltoluamide (DEBT) from
1985-1989. ClinToxicol 1994;32:1.
17. Tenebein M. Severe toxic reactions and death following ingestion of diethyltoluamide-con-
taining insect repeUents. JAMA 1987;258:1509.
18. Maibach HI and Johnson HL. Contact urticaria syndrome. Arch Dermatol 1975;111:726.
19. Wantke F, Focke M, HemmerW, et al. Generalized urticaria induced by a diethyltoluamide-
containing insect repellent in a child. Contact Dermatitis 1996;35(3):186.
20. Reuveni H.andYagupsky P. Diethyltoluamide-containing insect repellent: Adverse effects in
worldwide use. Arch Dermatol 1982;! 18:582.
21. Stinecipher J and Shaw J. Percutaneous permeation of N,N-diethyl-m-toluamide (DEBT)
from commercial mosquito repellents and the effect of solvent. / Toxicol Environ Health
1997;52:119.
22. Lipscomb ]W, Kramer JE, and Leikin JB. Seizure following brief exposure to the insect
repeUent N,N-diethyl-m-toluamide. Ann Emerg Med 1992;21(3):315-17.
23. Zadikoff CM. Toxic encephalopathy associated with use of insect repellent. / Pediatr
1979;95:140-2.
24. Pronczuk de Garbino J and Laborda A.Toxicity of an insect repellent: N,N- diethyltoluamide.
Vet Hum Toxto/1983;25:422-3.
25. Hebert AA and Carlton S. Getting bugs to bug off: A review of insect repellents. Contemp
Ped/afrl998;15:85-95.
26. YolkenR.Konecny P, and McCarthy P. Acute fluoride poisoning. Pediatrics 1976;58(l):90-3.
27. Heifetz SB and Horowitz HS. Amounts of fluoride in self-administered dental products:
Safety considerations for children. Pediatrics 1986;77(6):876-82.
28. Gessner BD, Beler M, Middaugh JP, andWhitford GM. Acute fluoride poisoning from a
public water system. New Engl]Med 1994;330(2):95-9.
29. Swanson L, Filandrinos DT, Shevlin JM, andWillett 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, Sjostedt 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 hyper-
kalemia. Chest 1980;78:660.
33. Saunders LD, Ames RG, Knaak JB, et al. Outbreak of omite-cr-induced dermatitis among
orange pickers inTulare County, California. / Occup Med 1987;29:409-13.
34. Dorman DC and BeasleyVR. Neurotoxicology of pyrethrin and the pyrethroid insecticides.
VetHumToxto/1991;33(3):238-43.
35. He F.Wang S, Lui L, et al. Clinical manifestations and diagnosis of acute pyrethroid poison-
ing. 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: Adermatological
evaluation. Br J Ind Med 1985;42:363-72.
OTHER INSECTICIDES 91
-------
38. Tucker SB, Flannigan SA, and Ross CE. Inhibitions of cutaneous paresthesia resulting from
synthetic pyrethroid exposure. Int ]Dermatol 1984;10:686-9.
39. O'MaUey MA. Skin reactions to pesticides. Occup Med 1997;12:327-45.
40. Schwartz SM, Carroll HM, and Scharschmidt LA. Sublimed (inorganic) sulfur ingestion - A
cause of life-threatening metabolic acidosis with a high anion gap. Arch Intern Med
1986;146:1437-8.
92 OTHER INSECTICIDES
-------
Section III
HERBICIDES
-------
CHAPTER 9
HIGHLIGHTS
Signs and Symptoms:
Irritating to skin and
mucous membranes
Vomiting, diarrhea,
headache, confusion,
bizarre or aggressive
behavior, peculiar odor on
breath
Metabolic acidosis, renal
failure, tachycardia
Treatment:
Washing, Gl
decontamination
Administer IV
Forced alkaline diuresis
Chlorophenoxy Herbicides
Chlorophenoxy compounds are sometimes mixed into commercial fertilizers
to control growth of broadleaf weeds. Several hundred commercial products
contain chlorophenoxy herbicides in various forms, concentrations, and com-
binations. In some cases, the same name is used for products with different
ingredients. The exact composition must therefore be determined from the
product label. Sodium, potassium, and alkylamine salts are commonly formu-
lated as aqueous solutions, while the less water-soluble esters are applied as
emulsions. Low molecular weight esters are more volatile than the acids, salts,
or long-chain esters.
Toxicology
Some of the chlorophenoxy acids, salts, and esters are moderately irritating
to skin, eyes, and respiratory and gastrointestinal linings. In a few individuals,
local depigmentation has apparently resulted from protracted dermal contact
with chlorophenoxy compounds.
Chlorophenoxy compounds are well absorbed from the gastrointestinal
tract.1 They are less well absorbed from the lung. Cutaneous absorption appears
to be minimal.2 The compounds are not significantly stored in fat. Excretion
occurs almost entirely by way of urine. Apart from some conjugation of the
acids, there is limited biotransformation in the body.1'2 The compounds are
highly protein bound.2 The average residence half-life of 2,4-D in humans is
between 13 and 39 hours,1'3'4'5 while that of 2,4,5-T is about 24 hours. Excre-
tion is greatly enhanced in alkaline urine,4'5'6 and with a half-life as prolonged
as 70-90 hours with acidic urine.6 Half-life is also longer with large doses and
prolonged exposure.
Given in large doses to experimental animals, 2,4-D causes vomiting, diar-
rhea, anorexia, weight loss, ulcers of the mouth and pharynx, and toxic injury
to the liver, kidneys, and central nervous system. Myotonia (stiffness and inco-
ordination of hind extremities) develops in some species and is apparently due
to CNS damage: demyelination has been observed in the dorsal columns of the
cord, and 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 electrocar-
CHLOROPHENOXY
94 HERBICIDES
-------
diographic changes, myotonia, muscle weakness, myoglobinuria, and elevated
serum creatine phosphokinase, all reflecting injury to striated muscle.
Chlorophenoxy acids are weak uncouplers of oxidative phosphorylation; there-
fore, extraordinary doses may produce hyperthermia from increased produc-
tion of body heat.5
In the manufacture of some of these herbicides, other more toxic sub-
stances can be formed at excessive temperatures. These include chlorinated
dibenzo dioxin (CDD) and chlorinated dibenzo furan (CDF). The 2,3,7,8-
tetra CDD form is extraordinarily toxic to multiple mammalian tissues; it is
formed only in the synthesis of 2,4,5-T Hexa-, hepta-, and octa-compounds
exhibit less systemic toxicity, but are the likely cause of chloracne (a chronic,
disfiguring skin condition) seen in workers engaged in the manufacture of
2,4,5-T and certain other chlorinated organic compounds.7 Although toxic
effects, notably chloracne, have been observed in manufacturing plant workers,
these effects have not been observed in formulators or applicators regularly
exposed to 2,4,5-T or other chlorophenoxy compounds. All uses of 2,4,5-T in
the U.S. have been cancelled.
The medical literature contains reports of peripheral neuropathy following
what seemed to be minor dermal exposures to 2,4-D8 It is not certain that
exposures to other neurotoxicants were entirely excluded in these cases. Single
doses of 5 mg/kg body weight of 2,4-D and 2,4,5-T have been administered to
human subjects without any adverse effects. One subject consumed 500 mg of
2,4-D per day for 3 weeks without experiencing symptoms or signs of illness.
Commercial Products
2,4-dichlorophenoxyacetic acid
(2,4-D)
2,4-dichlorophenoxypropionic
acid (2,4-DP)
dichlorprop
2,4-dichlorophenoxybutyric
acid (2,4-DB)
2,4,5-trichlorophenoxy acetic
acid (2,4,5-T)
MCPA
MCPB
mecoprop (MCPP)
2-methyl-3, 6 dichlorobenzoic
acid
Banvel
Dicamba
Signs and Symptoms of Poisoning
Chlorophenoxy compounds are moderately irritating to skin and mucous
membranes. Inhalation of sprays may cause burning sensations in the nasophar-
ynx and chest, and coughing may result. Prolonged inhalation sometimes causes
dizziness. Adjuvant chemicals added to enhance foliage penetration might ac-
count for the irritant effects of some formulations.
Manifestations of systemic toxicity of chlorophenoxy compounds are known
mainly from clinical experience with cases of deliberate suicidal ingestion of
large quantities. Most reports of fatal outcomes involve renal failure, acidosis,
electrolyte imbalance, and a resultant multiple organ failure.3'6'9 The agents most
often involved in these incidents have been 2,4-D and mecoprop. The toxic
effects of other chlorophenoxy compounds are probably similar but not identical.
Patients will present within a few hours of ingestion with vomiting, diar-
rhea, headache, confusion, and bizarre or aggressive behavior. Mental status
changes occur with progression to coma in severe cases.4'5'6 A peculiar odor is
often noticed on the breath. Body temperature may be moderately elevated,
but this is rarely a life-threatening feature of the poisoning. The respiratory
drive is not depressed. Conversely, hyperventilation is sometimes evident, prob-
CHLOROPHENOXY
HERBICIDES
95
-------
ably secondary to the metabolic acidosis that occurs. Muscle weakness and
peripheral neuropathy have been reported after occupational exposure.6 Con-
vulsions occur very rarely. With effective urinary excretion of the toxicant,
consciousness usually returns in 48-96 hours.4'5'6
As mentioned above, chlorophenoxy compounds cause significant meta-
bolic changes. Metabolic acidosis is manifest as a low arterial pH and bicarbon-
ate content. The urine is usually acidic. Skeletal muscle injury, if it occurs, is
reflected in elevated creatine phosphokinase, and sometimes myoglobinuria.
Moderate elevations of blood urea nitrogen and serum creatinine are com-
monly found as the toxicant is excreted. Cases of renal failure are reported,
often with an accompanying hyperkalemia or hypocalcemia that was thought
to result in the cardiovascular instability that led to death.3>9 Tachycardia is com-
monly observed, and hypotension has also been reported.3>4>6T-wave flattening
has also been observed.5 Mild leukocytosis and biochemical changes indicative
of liver cell injury have been reported.
Myotonia and muscle weakness may persist for months after acute poison-
ing.5 Electromyographic and nerve conduction studies in some recovering pa-
tients have demonstrated a mild proximal neuropathy and myopathy
Confirmation of Poisoning
Gas-liquid chromatographic methods are available for detecting
chlorophenoxy compounds in blood and urine. These analyses are useful in
confirming and assessing the magnitude of chlorophenoxy absorption. Poison-
ing characterized by unconsciousness has shown initial blood chlorophenoxy
concentrations ranging from 80 to more than 1000 mg per liter.4 Urine samples
should be collected as soon as possible after exposure because the herbicides
may be almost completely excreted in 24-72 hours under normal conditions.
Urine samples can also confirm overexposure. In a study of asymptomatic her-
bicide applicators, their urinary excretion of chlorophenoxy compounds rarely
exceeded 1-2 mg/L.10The half-life may be much longer in cases of intoxica-
tion depending on the extent of absorption and urine pH.
Analyses can be performed at special laboratories usually known to local poi-
son control centers. If the clinical scenario indicates that excessive exposure to
chlorophenoxy compounds has occurred, initiate appropriate treatment measures
immediately. Do not wait for chemical confirmation of toxicant absorption.
Treatment
1. Precautions. Individuals with chronic skin disease or known sensitivity to
these herbicides should either avoid using them or take strict precautions to
avoid contact (respirator, gloves, etc.).
CHLOROPHENOXY
96 HERBICIDES
-------
2. Respiratory protection. If any symptoms of illness occur during or fol-
lowing inhalation of spray, remove victim from contact with the material for at
least 2-3 days. Allow subsequent contact with chlorophenoxy compounds only
if effective respiratory protection is practiced.
3. Skin decontamination. Flush contaminating chemicals from eyes with
copious amounts of clean water for 10-15 minutes. If irritation persists, an
ophthalmologic examination should be performed.
4. Gastrointestinal decontamination. If substantial amounts of chlorophenoxy
compounds have been ingested, spontaneous emesis may occur. Gastric decon-
tamination procedures may be considered, as outlined in Chapter 2.
5. Intravenous fluids. Administer intravenous fluids to accelerate excretion of
the chlorophenoxy compound, and to limit concentration of the toxicant in
the kidney. A urine flow of 4-6 mL/minute is desirable. Intravenous saline/
dextrose has sufficed to rescue comatose patients who drank 2,4-D and mecoprop
several hours before hospital admission.
Caution: Monitor urine protein and cells, BUN, serum creatinine, serum
electrolytes, and fluid intake/output carefully to insure that renal function re-
mains unimpaired and that fluid overload does not occur.
6. Diuresis. Forced alkaline diuresis has been used successfully in management
of suicidal ingestions of chlorophenoxy compounds, especially when initiated
early4'5'6 Alkalinizing the urine by including sodium bicarbonate (44-88 mEq
per liter) in the intravenous solution accelerates excretion of 2,4-D dramati-
cally and mecoprop excretion substantially. Urine pH should be maintained
between 7.6 and 8.8. Include potassium chloride as needed to offset increased
potassium losses: add 20-40 mEq of potassium chloride to each liter of intrave-
nous solution. It is crucial to monitor serum electrolytes carefully, especially
potassium and calcium.
There may possibly be some hazard to the kidneys when urine concentra-
tions of toxicant are very high, so the integrity of renal function and fluid
balance should be monitored carefully as the chlorophenoxy compound is ex-
creted. Renal failure has occurred in patients with severe intoxication during
alkaline diuresis. In one case, the diuresis was begun 26 hours after ingestion,6
and the other two were initiated a couple days after poisoning.3'9
7. Hemodialysis is not likely to be of significant benefit in poisonings by
chlorophenoxy compounds. It has been used in four patients who survived
intoxication.11 However, given the highly protein-bound nature of these herbi-
cides and lack of any other evidence, hemodialysis is not recommended.2
CHLOROPHENOXY
HERBICIDES 97
-------
8. Follow-up clinical examination should include electromyographic and
nerve conduction studies to detect any neuropathic changes and neuromuscu-
lar junction defects.
General Chemical Structure
Cl (orCH3)
References
1. Kohli JD, Khanna RN, Gupta BN, et al. Absorption and excretion of 2,4-dichlorophenoxy-
acetic. Xenobiotica 1974;4(2):97-100.
2. Arnold EK, Beasley MS, and Beasley VR.The pharmacokinetics of chlorinated phenoxy
acid Herbicides:A literature review. Vet Hum Toxicol 1989;31(2):121-5.
3. KellerT, Skopp G,Wu M, et al. Fatal overdose of 2,4-dichlorophenoxyacetic acid (2,4-D).
Forensic Sci Int 1994;65:13-8.
4. Friesen EG, Jones GR, andVaughan D. Clinical presentation and management of acute 2,4-
D oral mgestion. Drug Sa/1990;5(2): 155-90.
5. Prescott LF, Park J, and Darrien I. Treatment of severe 2,4-D and mecoprop intoxication
with alkaline diuresis. En journal of Clinical Pharmacology 1979;7:111-116.
6. Flanagan RJ, Meredith TJ, Ruprah M, et al. Alkaline diuresis for acute poisoning with
chlorophenoxy herbicides and ioxynil. Lancet 1990;335:454-8.
7. Poskitt LB, Duffill MB, and Rademaker M. Chloracne, palmoplantar keratoderma and local-
ized scleroderma in a weed sprayer. Clin and Exp Dermatol 1994; 19:264-7.
8. O'Reilly 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.
CHLOROPHENOXY
98 HERBICIDES
-------
CHAPTER 10
Pentachlorophenol
Pentachlorophenol (PCP) is currently registered in the United States only as
a restricted use pesticide for use as a wood preservative. PCP has been used as
an herbicide, algacide, defoliant, wood preservative, germicide, fungicide, and
molluscicide.1 As a wood preservative, it is commonly applied as a 0.1% solu-
tion in mineral spirits, No. 2 fuel oil, or kerosene. It is used in pressure treat-
ment of lumber at 5% concentration. Weed killers have contained higher
concentrations.
Pentachlorophenol volatilizes from treated wood and fabric. It has a signifi-
cant phenolic odor, which becomes quite strong when the material is heated.
Excessively treated interior surfaces may be a source of exposure sufficient to
cause irritation of eyes, nose, and throat.
Technical PCP contains lower chlorinated phenols (4-12%) plus traces of
chlorobenzodioxins, chlorobenzofurans, and chlorobenzenes. Incomplete com-
bustion of PCP-treated wood may lead to the formation of these compounds.
Toxicology
PCP is readily absorbed across the skin, the lungs, and the gastrointestinal
lining. In animals, the dermal LD50 is of the same order of magnitude as the
oral. With acute exposure it is rapidly excreted, mainly in the urine, as un-
changed PCP and as PCP glucuronide. In chronic exposures, the elimination
half-life has been reported to be very long, up to 20 days.2 In another study,
three volunteers took consecutive oral doses of PCP, and a half-life of 20 days
was also found. The long half-life was attributed to the low urinary clearance
because of high protein binding.3 In the blood, a large fraction of absorbed
PCP is protein-bound. It is widely distributed to other tissues in the body,
including kidney, heart, and adrenal glands.
At certain concentrations, PCP is irritating to mucous membranes and
skin. Contact dermatitis is common among workers having contact with PCP.
In a study of employees involved in the manufacture of PCP, chloracne was
found in 7% of the workers, and the risk was significantly higher among em-
ployees with documented skin contact compared to employees without skin
contact.4 Urticaria has also been reported as an uncommon response in ex-
posed persons.
HIGHLIGHTS
Absorbed by skin, lung, Gl
lining
Fatalities reported,
associated with intensive
exposure in hot
environments
Signs and Symptoms:
Irritation of the nose,
throat, and eyes
Hyperthermia, muscle
spasm, tremor, labored
breathing, and chest
tightness indicate serious
poisoning
Treatment:
No specific antidote
Control fever, replace fluids,
oxygen
Decontaminate eyes, skin,
hair, clothing
Monitor cardiac status,
control agitation
Contraindicated:
Salicylates for fever control
PENTACHLOROPHENOL 99
-------
Commercial Products
Chlorophen
PCP
Penchlorol
Penta
Pentacon
Penwar
Sinituho
The sodium salt is sodium
pentachlorophenate.
The primary toxicological mechanism is increased cellular oxidative me-
tabolism resulting from the uncoupling of oxidative phosphorylation. Heat pro-
duction is increased and leads to clinical hyperthermia. This clinical state may
mimic the signs and symptoms found in hyperthyroidism. Internally, large doses
are toxic to the liver, kidneys, and nervous system.
Based on laboratory experimentation on animals, PCP has been reported
to have fetotoxic and embrotoxic properties and to bind to various hormone
receptors.5'6 Epidemiological evidence suggests exposed persons may be at risk
for miscarriages, reduced birth weight, and other malformations.7'8
Albuminuria, glycosuria, aminoaciduria, and elevated BUN reflect renal
injury. Liver enlargement, anemia, and leukopenia have been reported in some
intensively exposed workers. Elevated serum alkaline phosphatase, AST, and
LDH enzymes indicate significant insult to the liver, including both cellular
damage and some degree of biliary obstruction.
Signs and Symptoms of Poisoning
The most common effects of airborne PCP include local irritation of the
nose, throat, and eyes, producing a stuffy nose, scratchy throat, and tearing.
Dermal exposure is also common and may lead to irritation, contact dermatitis,
or more rarely, diffuse urticaria or chloracne. Individual cases of exfoliative
dermatitis of the hands and diffuse urticaria and angioedema of the hands have
been reported in intensively exposed workers. Several infant deaths occurred in
a nursery where a PCP-containing diaper rinse had been used.
Severe poisoning and death have occurred as a result of intensive PCP
exposure. Acute poisoning occurs with systemic absorption which can occur
by any route of sufficient dosage. Most occupational poisonings occur through
dermal contact. Hyperthermia, muscle spasm, tremor, labored breathing, and
chest tightness indicate serious poisoning. The patient may also complain of
abdominal pain, and exhibit vomiting, restlessness, and mental confusion. Ta-
chycardia and increased respiratory rate are usually apparent. Other commonly
reported signs and symptoms of systemic poisoning include profuse sweating,
weakness, dizziness, anorexia, and intense thirst. Workers exposed over long
periods may experience weight loss.
Most adult fatalities have occurred in persons working in hot environ-
ments where hyperthermia is poorly tolerated. Cases of aplastic anemia and
leukemia have been reported which were associated temporally with PCP ex-
posure. Causal relationships in these cases were not established.9 Peripheral neu-
ropathies have also been reported in some cases of long-term occupational
exposure; however, a causal relationship has not been supported by longitudi-
nal studies.10
100
PENTACHLOROPHENOL
-------
Confirmation of Poisoning
If poisoning is strongly suspected on the basis of exposure, symptoms, and
signs, do not postpone treatment until diagnosis is confirmed.
PCP can be measured in blood, urine, and adipose tissue by gas-liquid
chromatography Plasma levels can be much greater than urine levels (ratio of
blood to urine is 1.0 to 2.5) so care must be taken in interpreting results.10'11
There is no clear-cut determination of what constitutes an abnormally high
level of PCP, and there is great variability among different references. Most
information on the extent of serum levels in relation to toxicity is based on
individual cases or small series of patients. Reports exist of asymptomatic in-
fants with serum levels as high as 26 parts per million (ppm).11>12 However, most
reports of non-occupational exposure in the general public involve levels in the
parts per billion range.1'13"15 Food is probably the main source of this nano-
gram-level dosage.1 Serum levels among occupationally exposed persons often
exceed 1 ppm.1 A report of a lethal case describes a plasma level of 16 ppm,16
but most cases generally involve serum levels in the range of 100 ppm or
higher.11'17 It is reasonable to assume that levels greater than 1 ppm are consis-
tent with an unusual exposure and that levels approaching 100 ppm are cause
for great concern.
Treatment
1. Supportive treatment and hyperthermia control. There is no specific
antidote to the poisoning; therefore treatment is supportive in nature including
oxygen, fluid replacement, and most importantly, fever control.
Reduce elevated body temperature by physical means. Administer sponge
baths and use fans to increase evaporation.18 In fully conscious patients, admin-
ister cold, sugar-containing liquids by mouth as tolerated. Cooling blankets and
ice packs to body surfaces may also be used.
Antipyretic therapy with salicylates is strongly contraindicated as salicy-
lates also uncouple oxidative phosphorylation. Other antipyretics are thought
to be of no use because of the peripherally mediated mechanism of hyperther-
mia in poisoning of this nature. Neither the safety nor the effectiveness of the
other antipyretics has been tested.
Administer oxygen continuously by mask to minimize tissue anoxia. Un-
less there are manifestations of cerebral or pulmonary edema or of inadequate
renal function, administer intravenous fluids to restore hydration and support
physiologic mechanisms for heat loss and toxicant disposition. Monitor serum
electrolytes, adjusting IV infusions to stabilize electrolyte concentrations. Fol-
low urine contents of albumin and cells, and keep an accurate hourly record of
intake/output to forestall fluid overload if renal function declines.
Caution: In the presence of cerebral edema and/or impaired renal func-
tion, intravenous fluids must be administered very cautiously to avoid increased
PENTACHLOROPHENOL 101
-------
intracranial pressure and pulmonary edema. Central monitoring of venous and
pulmonary wedge pressures may be indicated. Such critically ill patients should
be treated in an intensive care unit.
2. Skin decontamination. Flush the chemical from eyes with copious amounts
of clean water. Perform skin decontamination as described in Chapter 2.
3. Cardiopulmonary monitoring. In severe poisonings, monitor pulmo-
nary status carefully to insure adequate gas exchange, and monitor cardiac sta-
tus by EGG to detect arrhythmias. The toxicant itself and severe electrolyte
disturbances may predispose to arrhythmias and myocardial weakness.
4. Neurological. To reduce production of heat in the body, control agitation and
involuntary motor activity with sedation. Lorazepam or other benzodiazepines
should be effective, although use of these drugs in these poisonings has not been
reported. If lorazepam is chosen, administer slowly, intravenously.
Dosage of Lorazepam:
Adults: 2-4 mg/dose IV given over 2-5 minutes. Repeat if necessary
to a maximum of 8 mg in a 12-hour period.
Adolescents: Same as adult dose, except maximum dose is 4 mg.
Children under 12years: 0.05-0.10 mg/kg IV over 2-5 minutes. Re-
peat if necessary 0.05 mg/kg 10-15 minutes after first dose, with a
maximum dose of 4 mg.
Caution: Be prepared to assist pulmonary ventilation mechanically if
respiration is depressed, to intubate the trachea iflaryngospasm occurs,
and to counteract hypotensive reactions.
5. Gastrointestinal decontamination. If PGP has been ingested in a quan-
tity sufficient to cause poisoning and the patient presents within one hour,
consider gastric decontamination as outlined in Chapter 2.
6. Nutrition. During convalescence, administer a high-calorie, high-vitamin
diet to restore body fat and carbohydrates. Discourage subsequent contact with
the toxicant for 4-8 weeks (depending on severity of poisoning) to allow full
restoration of normal metabolic processes.
102
PENTACHLOROPHENOL
-------
Chemical Structure
Cl
References
1. Jorens PG and Schepens PJC. Human pentachlorophenol poisoning. Hum Exp Toxicol
1993;479-95.
2. Kalman DA and Horstman SW. Persistence of tetrachlorophenol and pentachlorophenol in
exposed woodworkers. JToxicol Clin Toxicol 1983;20:343.
3. Uhl S, Schmid P, and Schlatter C. Pharmacokinetics of pentachlorophenol in man. Arch
7oxfcoM986;58:182-6.
4. O'Malley MA, Carpenter AV, Sweeney MH, et al. Chloracne associated with employment in
the production of pentachlorophenol. Am ] Ind Med 1990; 17:411 -21.
5. Danzo BJ. Environmental xenobiotics may disrupt normal endocrine function by interfer-
ing with the binding of physiological ligands to steroid receptors and binding proteins.
Environ Health Perspect 1997;105:294-301.
6. Tran DQ, 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, andVerstaete R. Exposure to pentachlorophenol as a
possible cause of miscarriages. BrJ Obstet Gynaecol 1995;102:1010-1.
9. Roberts HJ.Aplastic anemia due to pentachlorophenol. NewEngl]Med 1981;305:1650-1.
10. Casarett LJ, Bevenue A.Yauger WL, and Whalen SA. Observations on pentachlorophenol in
human blood and urine. Am Ind HygAssoc J 1969;30:360-6.
11. Clayton GD and Clayton FE (eds). Patty's Industrial Hygiene and Toxic ologyvol 2B, 4th ed.
New York: John Wiley & Sons, 1994, pp. 1605-13.
12. Robson AM, Kissane JM, Elvick WH, et al. Pentachclorophenol poisoning in a nursery for
newborn infants: Clinical features and treatment. /Pediatr 1969;75:309-16.
13. Gomez-Catalan J,To-Figueras J, Planas J, et al. Pentachlorophenol and hexachlorobenzene in
serum and urine of the population of Barcelona. HumToxicol 1987;6:397-400.
14. Wylie JA, Gabica J, Benson WW, andYoder J. Exposure and contamination of the air and
employees of a pentachlorophenol plant, Idaho-1972. Pest Mom't/1975;9:150-3.
15. Wagner SL. Pentachlorophenol. In: Clinical Toxicology of Agricultural Chemicals. Corvallis,
OR: Oregon State University Press, 1981, pp. 131-7.
16. Wood S, Rom WN, White GL, and Logan DC. Pentachlorophenol poisoning. / Occup Med
1983;25:527-30.
17. Gray RE, Gilliland RD, Smith EE, et al. Pentachlorophenol intoxication: Report of a fatal
case, with comments on the clinical course and pathologic anatomy. Arch Environ Health
1985;40:161-4.
18. Graham BS, Lichtenstein MJ, Hinson JM, et al. Nonexertional heatstroke: Physiologic man-
agement and cooling in 14 patients. Arch Intern Med 1986;146:87-90.
PENTACHLOROPHENOL 103
-------
CHAPTER 11
HIGHLIGHTS
Highly toxic herbicides
Affect hepatic, renal, and
nervous systems
Signs and Symptoms:
Sweating, thirst, fever,
headache, confusion,
malaise, and restlessness
Hyperthermia, tachycardia,
tachypnea in serious cases
Characteristic bright yellow
staining of skin and hair
often present with topical
exposure
Treatment:
No specific antidote
Replace oxygen and fluids,
control temperature
Decontaminate skin, hair,
clothing
Contraindicated:
Antipyretic therapy with
salicylates
Atropine
Nitrophenolic and
Nitrocresolic Herbicides
These highly toxic chemicals have many uses in agriculture worldwide, as her-
bicides (weed-killing and defoliation), acaricides, nematocides, ovicides, and
fungicides. Relatively insoluble in water, most technical products are dissolved
in organic solvents and formulated for spray application as emulsions. There are
some wettable powder formulations. Only dinocap continues to have active
registrations in the United States.
Toxicology
Nitroaromatic compounds are highly toxic to humans and animals with
LD5Qs in the range of 25 to 50 mg/kg.1 Most nitrophenols and nitrocresols are
well absorbed by the skin, gastrointestinal tract, or lung when fine droplets are
inhaled.2 Fatal poisonings have occurred as a result of dermal contamination;
more common is a moderate irritation of the skin and mucous membranes.
Nitrophenols and nitrocresols undergo some biotransformation in humans,
chiefly reduction (one nitro group to an amino group) and conjugation at the
phenolic site. Although nitrophenols and metabolites appear consistently in
the urine of poisoned individuals, hepatic excretion is probably the main route
of disposition. Elimination is slow with a documented half-life in humans be-
tween 5 and 14 days.1 Blood and tissue concentrations tend to increase pro-
gressively if an individual is substantially exposed on successive days.
The basic mechanism of toxicity is stimulation of oxidative metabolism in
cell mitochondria, by the uncoupling of oxidative phosphorylation. This leads
to hyperthermia, tachycardia, headache, malaise, and dehydration, and in time,
depletes carbohydrate and fat stores. The major systems prone to toxicity are
the hepatic, renal, and nervous systems. The nitrophenols are more active as
uncouplers than chlorophenols such as pentachlorophenol (described in chap-
ter 10). Hyperthermia and direct toxicity on the brain cause restlessness and
headache, and in severe cases, seizures, coma, and cerebral edema. The higher
the ambient temperature, such as in an outdoor agricultural environment, the
more difficult it is to dissipate the heat.1'2 Liver parenchyma and renal tubules
show degenerative changes. Albuminuria, pyuria, hematuria, and azotemia are
signs of renal injury.
NITROPHENOLS &
104 NITROCRESOLS
-------
Cataracts occur in laboratory animals given nitrophenols, and have oc-
curred in humans, both as a result of ill-advised medicinal use and as a conse-
quence of chronic, occupational exposure.3 Cataract formation is sometimes
accompanied by glaucoma.
Signs and Symptoms of Poisoning
Most patients present within a few hours of exposure with generalized
non-specific signs and symptoms including profuse sweating, thirst, fever, head-
ache, confusion, malaise, and restlessness.The skin may appear warm and flushed
as hyperthermia develops, along with tachycardia, and tachypnea, all of which
indicate a serious degree of poisoning. Apprehension, anxiety, manic behavior,
seizures, and coma reflect cerebral injury; seizures and coma signify an immedi-
ately life-threatening intoxication. Labored breathing and cyanosis are conse-
quences of the stimulated metabolism and tissue anoxia. Renal failure may
occur early in cases of severe exposure. Liver damage is first manifested by
jaundice, and cell death can occur within 48 hours and is dose-dependent.4
Death may occur within 24 to 48 hours after exposure in cases of severe poi-
soning.2 In cases of survival of severe poisoning, complete resolution of symp-
toms may be slow due to the toxicant's long half-life.1'5
A characteristic bright yellow staining of skin and hair is often present with
topical exposure and can be an important diagnostic clue to the clinician.1'2'5
Yellow staining of the sclerae and urine indicates absorption of potentially
toxic amounts. Weight loss occurs in persons continually exposed to relatively
low doses of nitrophenols or nitrocresols.1'3
Confirmation of Poisoning
If poisoning is probable, do not await confirmation before beginning treatment.
Save urine and blood specimens on ice at temperature below 20ฐ C in the event
confirmation is necessary later on. Unmetabolized nitrophenols and nitrocresols
can be identified spectrophotometrically, or by gas-liquid chromatography, in the
serum at concentrations well below those that have been associated with acute
poisonings.The data on exposure and systemic levels of compounds in this group
are limited, and most reports specify the compound dinitro-ortho-cresol. In general,
blood levels of 10 mcg/dL or greater are usually seen when systemic toxicity is
evident.1'6 One fatal case occured with a level of 75 mcg/dL.6 Blood analysis is
useful in confirming the cause of poisoning. Monitoring of levels should be done
routinely during acute intoxication in order to establish a decay curve to determine
when therapy can be safely discontinued.
Commercial Products
dinitrocresol*
Chemsect DNOC
DNC
DNOC
Elgetol 30
Nitrador
Selinon
Sinox
Trifocide
dinitrophenol*
Chermox PE
dinobuton*
Ac rex
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
Am box
binapacryl
(Continued on the next page)
NITROPHENOLS &
NITROCRESOLS
105
-------
Commercial Products
(Continued)
Dapacryl
Endosan
FMC 9044
Hoe 002784
Morrodd
NIA 9044
dinosulfon*
dinoterb acetate*
dinoterb salts*
dinoterbon*
* All U.S. registrations have
been cancelled
Treatment
1. Supportive treatment and hyperthermia control. There is no specific
antidote to poisoning with nitrophenolic or nitrocresolic herbicides.Treatment
is supportive in nature and includes oxygen, fluid replacement, and tempera-
ture control.
Reduce elevated body temperature by physical means. Administer
sponge baths and ice packs, and use a fan to promote air flow and evaporation.7
In fully conscious patients, administer cold, sugar-containing liquids by mouth
as tolerated.
2. Contraindications. Antipyretic therapy with salicylates is strongly
contraindicated as salicylates also uncouple oxidative phosphorylation. Other
antipyretics are thought to be of no use because of the peripherally mediated
mechanism of hyperthermia in poisoning of this nature. Neither the safety nor
the effectiveness of other antipyretics has been tested.
Atropine is also absolutely contraindicated! It is essential not to con-
fuse the clinical signs for dinitrophenol with manifestations for cholinesterase
inhibition poisoning.2
3. Skin decontamination. If poisoning has been caused by contamination of
body surfaces, bathe and shampoo contaminated skin and hair promptly and
thoroughly with soap and water, or water alone if soap is not available. Wash the
chemical from skin folds and from under fingernails. Care should be taken to
prevent dermal contamination of hospital staff. See Chapter 2.
4. Other Treatment. Other aspects of treatment are identical to management
of pentachlorophenol poisoning, detailed in Chapter 10.
General Chemical Structure
02N{' \)0-H or
(ALKYL) (ALKYL)
References
1. Leftwich RB, Floro JF, Neal RA, et al. Dinitrophenol poisoning: A diagnosis to consider in
undiagnosed fever. South Med/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. VetHumToxicoIl9S6;2S:574-5.
NITROPHENOLS &
106 NITROCRESOLS
-------
4. Paktieira 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 herbi-
cide. Practitioner 1981;225:923-6.
6. NIOSH. Criteria document: Occupational exposure to dinitro-orthocresol. Cincinnati: NIOSH,
1978.
7. Graham BS, Lichtenstein MJ, Hinson JM, et al. Nonexertional heatstroke: Physiologic man-
agement and cooling in 14 patients. Arch Intern Med 1986;146:87-90.
NITROPHENOLS &
NITROCRESOLS 107
-------
CHAPTER 12
HIGHLIGHTS
Life-threatening effects on
Gl tract, kidney, liver, heart,
other organs
Pulmonary fibrosis is the
usual cause of death in
paraquat poisoning (but not
diquat)
Signs and Symptoms:
Paraquat and diquat
(ingestion): burning pain in
the mouth, throat, chest,
upper abdomen; pulmonary
edema, pancreatitis, other
renal, CMS effects
Paraquat (dermal): dry and
fissured hands, horizontal
ridging or loss of fingernails,
ulceration and abrasion
Diquat: neurologic toxicity
Treatment:
Immediate Gl
decontamination with
Bentonite, Fuller's Earth, or
activated charcoal
Maintain urinary output by
administering IV, but
monitor fluids in case of
renal failure
Decontaminate eyes and
skin
Contraindicated:
No supplemental oxygen
unless patient develops
severe hypoxemia
Paraquat and Diquat
The dipyridyl compounds paraquat and diquat are non-selective contact
herbicides that are relatively widely-used, primarily in agriculture and by
government agencies and industries for control of weeds. While paraquat is a
restricted-use pesticide in most forms for most uses in the United States, its
wide usage leads to significant potential for misuse and accidental and inten-
tional poisonings. In the past few decades, paraquat has been a popular agent
for suicide, but recent experience indicates a decline in such intentional
poisonings. Paraquat and diquat are highly toxic compounds and management
of poisonings requires a great deal of skill and knowledge of proper manage-
ment procedures.
PARAQUAT
Toxicology
When ingested in adequate dosage (see below), paraquat has life-threaten-
ing effects on the gastrointestinal tract, kidney, liver, heart, and other organs.
The 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 genera-
tion of free radicals with oxidative damage to lung tissue.1'2 While acute pul-
monary edema and early lung damage may occur within a few hours of severe
acute exposures,3'4 the delayed toxic damage of pulmonary fibrosis, the usual
cause of death, most commonly occurs 7-14 days after the ingestion.5 In pa-
tients who ingested a very large amount of concentrated solution (20%), some
have died more rapidly (within 48 hours) from circulatory failure.5
Both types I and II pneumatocytes appear to selectively accumulate paraquat.
Biotransformation of paraquat in these cells results in free-radical production
with resulting lipid peroxidation and cell injury1'2'4 Hemorrhage proteinaceous
edema fluid and leukocytes infiltrate the alveolar spaces, after which there is rapid
proliferation of fibroblasts.There is a progressive decline in arterial oxygen tension
and CO2 diffusion capacity. Such a severe impairment of gas exchange causes
progressive proliferation of fibrous connective tissue in the alveoli and eventual
death from asphyxia and tissue anoxia.6 One prospective study of survivors suggests
108 PARAQUAT & DIQUAT
-------
that some of the fibrous toxic damage may be reversible as evidence exists of
markedly improved pulmonary function three months after survival.7
Local skin damage includes contact dermatitis. Prolonged contact will pro-
duce erythema, blistering, abrasion and ulceration, and fingernail changes.8'9
Although absorption across intact skin is slow, abraded or eroded skin allows
efficient absorption.
The gastrointestinal (GI) tract is the site of initial or phase I toxicity to the
mucosal surfaces following ingestion of the substance. This toxicity is manifested
by swelling, edema, and painful ulceration of the mouth, pharynx, esophagus,
stomach, and intestine. With higher levels, other GI toxicity includes centrizonal
hepatocellular injury which can cause elevated bilirubin, and hepatocellular en-
zymes such as AST, ALT, and LDH.
Damage to the proximal renal tubule is often more reversible than the
destruction to lung tissue. However, impaired renal function may play a critical
role in determining the outcome of paraquat poisoning. Normal tubule cells
actively secrete paraquat into the urine, efficiently clearing it from the blood.
However, high blood concentrations poison the secretory mechanism and may
destroy the cells. Diquat poisoning typically results in greater renal injury com-
pared to paraquat.
Focal necrosis of the myocardium and skeletal muscle are the main features
of toxicity to any type of muscle tissue, and typically occur as a second phase.
Ingestion has also been reported to cause cerebral edema and brain damage.10
Although much concern has been expressed about the effects of smoking
paraquat-contaminated marijuana, toxic effects caused by this mechanism have
been either very rare or nonexistent. Most paraquat that contaminates marijuana
is pyrolyzed during smoking to dipyridyl, which is a product of combustion of
the leaf material itself (including marijuana) and presents little toxic hazard.
Signs and Symptoms of Poisoning
Initial clinical signs depend upon the route of exposure. Early symptoms
and signs of poisoning by ingestion are burning pain in the mouth, throat,
chest, and upper abdomen, due to the corrosive effect of paraquat on the mu-
cosal lining. Diarrhea, which is sometimes bloody, can also occur. Giddiness,
headache, fever, myalgia, lethargy, and coma are other examples of CNS and
systemic findings. Pancreatitis may cause severe abdominal pain. Proteinuria,
hematuria, pyuria, and azotemia reflect renal injury. Oliguria/anuria indicate
acute tubular necrosis.
Because the kidney is almost the exclusive route of paraquat elimination
from body tissues, renal failure fosters a build-up of tissue concentrations, in-
cluding those in the lung. Unfortunately, this pathogenic sequence may occur
in the first several hours following paraquat ingestion, generating lethal con-
centrations of paraquat in lung tissue before therapeutic measures to limit ab-
sorption and enhance disposition have taken effect. It is probably for this reason
Commercial Products
Paraquat
Liquid Concentrates:
Cekuquat
Crisquat
Dextrone
Esgram
Goldquat
Gramocil
Gramonol
Gramoxone
In combination with other
herbicides:
With diquat:
Actor
Preeglone
Preglone
Weedol(a 2.5% soluble
granule formulation)
With diuron:
Dexuron
Gramuron
Para-col
Tota-col
With monolinuron:
Gramonol
With simazine:
Pathclear
Terra klene
Diquat
Aquacide
Dextrone
Ortho Diquat
Reg lone
PARAQUAT & DIQUAT 109
-------
that methods for enhancing paraquat disposition several hours following inges-
tion have had little effect on mortality.
Cough, dyspnea, and tachypnea usually appear 2-4 days following paraquat
ingestion, but may be delayed as long as 14 days. Progressive cyanosis and dys-
pnea reflect deteriorating gas exchange in the damaged lung. In some cases, the
coughing up of frothy sputum (pulmonary edema) is the early and principal
manifestation of paraquat lung injury.
Clinical experience has offered a rough dose-effect scale on which to base
prognosis in cases of paraquat ingestion:9
Less than 20 rng paraquat ion per kg body weight (less than 7.5
mL of 20% [w/v] paraquat concentrate): No symptoms or only
gastrointestinal symptoms occur. Recovery is likely.
Twenty to 40 mg paraquat ion per kg body weight (7.5-15.0 mL
of 20% [w/v] paraquat concentrate): Pulmonary fibroplasia ensues.
Death occurs in most cases, but may be delayed 2-3 weeks.
More than 40 mg paraquat ion per kg body weight (more than
15.0 mL of 20% [w/v] paraquat concentrate): Multiple organ
damage occurs as in class II, but is more rapidly progressive. Often
characterized by marked ulceration of the oropharynx. Mortality is
essentially 100% in 1-7 days.
Dermal signs are common among agriculture workers with acute paraquat
toxicity Particularly in concentrated form, paraquat causes localized injury to
tissues with which it comes into contact. Fatal poisonings are reported to
have occurred as a result of protracted dermal contamination by paraquat, but
this is likely to occur only when the skin is abraded, eroded, or diseased,
when more efficient systemic absorption can occur. With an intact dermal
barrier, paraquat leaves the skin of the hands dry and fissured, can cause hori-
zontal ridging of the fingernails, and may even result in the loss of fingernails.
Prolonged contact with skin will create ulceration and abrasion, sufficient to
allow systemic absorption.
In addition, some agriculture workers can be exposed through prolonged
inhalation of spray droplets, and develop nosebleeds due to local damage.
However, inhalation has not resulted in systemic toxicity, due to the low
vapor pressure and lower concentration of paraquat field formulations. Eye
contamination with diquat concentrate or stronger solutions results in severe
conjunctivitis and sometimes protracted corneal opacification.
The hepatic injury from paraquat may be severe enough to cause jaun-
dice, which signifies severe injury. However, hepatotoxicity is rarely a major
determinant to clinical outcome. No other hepatic signs or symptoms are
present other than the abnormal laboratory values mentioned in the Toxicol-
ogy section.
110 PARAQUAT & DIQUAT
-------
DIQUAT
Toxicology
Diquat poisoning is much less common than paraquat poisoning, so that
human reports and animal experimental data for diquat poisoning are less ex-
tensive than for paraquat. Systemically absorbed diquat is not selectively con-
centrated in lung tissue, as is paraquat, and pulmonary injury by diquat is less
prominent. In animal studies, diquat causes mild, reversible injury to type I
pneumatocytes, but does not injure the type II cells. No progressive pulmonary
fibrosis has been noted in diquat poisoning. n~13
However, diquat has severe toxic effects on the central nervous system that
are not typical of paraquat poisoning.12'13 While laboratory experimentation has
suggested that diquat is not directly neurotoxic, there have been relatively con-
sistent pathologic brain changes noted in reported fatal cases of diquat poison-
ing. These consist of brain stem infarction, particularly involving the pons.12 It
is not clear whether these post-mortem changes represent direct toxicity or
secondary effects related to the systemic illness and therapy. (See Signs and
Symptoms section for CNS clinical effects.)
There is probably significant absorption of diquat across abraded or ulcer-
ated skin.
Signs and Symptoms of Poisoning
In many human diquat poisoning cases, clinical signs of neurologic toxicity
are the most important. These include nervousness, irritability, restlessness, com-
bativeness, disorientation, nonsensical statements, inability to recognize friends
or family members, and diminished reflexes. Neurologic effects may progress to
coma, accompanied by tonic-clonic seizures, and result in the death of the
patient.12'13 Parkinsonism has also been reported following dermal exposure to
diquat.14
Except for the CNS signs listed in the preceding paragraph, early symp-
toms of poisoning by ingested diquat are similar to those from paraquat, reflect-
ing its corrosive effect on tissues. They include burning pain in the mouth,
throat, chest, and abdomen, intense nausea and vomiting, and diarrhea. If the
dosage was small, these symptoms may be delayed 1-2 days. Blood may appear
in the vomitus and feces. Intestinal ileus, with pooling of fluid in the gut, has
characterized several human poisonings by diquat.
The kidney is the principal excretory pathway for diquat absorbed into the
body. Renal damage is therefore an important feature of poisonings. Proteinuria,
hematuria, and pyuria may progress to renal failure and azotemia. Elevations of
serum alkaline phosphatase, AST, ALT, and LDH reflect liver injury. Jaundice
may develop.
PARAQUAT & DIQUAT -111
-------
If the patient survives several hours or days, circulatory function may fail
due to dehydration. Hypotension and tachycardia can occur, with shock result-
ing in death. Other cardiorespiratory problems may develop, such as toxic car-
diomyopathy or a secondary infection such as bronchopneumonia.
Diquat is somewhat less damaging to the skin than paraquat, but irritant
effects may appear following dermal contamination with the concentrate. There
is probably significant absorption of diquat across abraded or ulcerated skin.
The great majority of poisonings by paraquat and diquat (discussed below)
have been caused by ingestion with suicidal intent in most cases, particularly in
Japan11 and many developing countries. Since 1987, there has been a decline in
most countries in the total numbers of suicidal deaths attributed to paraquat
and diquat. Nearly all of the few poisonings caused by occupational exposure
have been survived, but the mortality rate among persons who have swallowed
paraquat or diquat remains high.1'5 Avoidance of this mortality will probably
have to rely on preventive strategies or on stopping gastrointestinal absorption
very soon after the toxicant has been ingested.
Even though intestinal absorption of dipyridyls is relatively slow, lethal
uptake by critical organs and tissues apparently occurs within 18 hours, and
possibly within 6 hours, following ingestion of toxic quantities of paraquat or
diquat. Bipyridyls have large volumes of distribution. Once distribution to tis-
sues has occurred, measures to remove bipyridyls from the blood are very inef-
ficient in reducing the total body burden.
Several strategies are being tested to reduce the frequency of these occur-
rences. These include the addition of emetics, stenching agents, gelling sub-
stances, and bittering agents such as sodim denatonium.
Confirmation of Poisoning: Paraquat and Diquat
At some treatment facilities, a simple colorimetric test is used to identify
paraquat and diquat in the urine, and to give a rough indication of the magni-
tude of absorbed dose. To one volume of urine, add 0.5 volume of freshly
prepared 1% sodium dithionite (sodium hydrosulfite) in one normal sodium
hydroxide (1.0 N NaOH). Observe color at the end of one minute. A blue
color indicates the presence of paraquat in excess of 0.5 mg per liter. Both
positive and negative controls should be run to ensure that the dithionite has
not undergone oxidation in storage.
When urine collected within 24 hours of paraquat ingestion is tested, the
dithionite test appears to have some prognostic value: concentrations less than
one milligram per liter (no color to light blue) generally predict survival, while
concentrations in excess of one milligram per liter (navy blue to dark blue)
often foretell a fatal outcome.
Diquat in urine yields a green color with the dithionite test. Although
there is less experience with this test in diquat poisonings, the association of
bad prognosis with intense color is probably similar.
112 PARAQUAT & DIQUAT
-------
Paraquat and diquat can be measured in blood and urine by spectrophoto-
metric, gas chromatographic, liquid chromatographic, and radioimmunoassay
methods. These tests are available in numerous clinical reference laboratories
and sometimes by the manufacturing company Survival is likely if plasma con-
centrations do not exceed 2.0, 0.6, 0.3, 0.16, and 0.1 mg per liter at 4, 6,10,16,
and 24 hours, respectively, after ingestion.15
Treatment
1. Skin and eye decontamination. Flush skin immediately with copious
amounts of water. Material splashed in the eyes must be removed by pro-
longed irrigation with clean water. Eye contamination should thereafter be
treated by an ophthalmologist. Mild skin reactions usually respond if there is no
further contact with the pesticide, but the irritation may take several weeks to
resolve. Severe injuries with inflammation, cracking, secondary infection, or
nail injury should be treated by a dermatologist.
2. Gastrointestinal decontamination. If paraquat or diquat have been in-
gested, immediate administration of adsorbent is the one therapeutic
measure most likely to have a favorable effect. Bentonite (7.5% suspension)
and Fuller's Earth (15% suspension) are highly effective, but sometimes not
available.
Dosage of Bentonite and Fuller's Earth:
Adults and children over 12 years: 100-150 g.
Children under 12 years: 2 gm/kg body weight.
Caution: Hypercalcemia and fecaliths have sometimes occurred fol-
lowing administration of Fuller's Earth.
Activated charcoal is nearly as effective, and is widely available. See Chapter
2 for dosage of charcoal and further information on gastric decontamination.
Lavage has not been shown to be effective and should not be performed
unless the patient is seen within an hour of ingestion. Later lavage runs the risk
of inducing bleeding, perforation, or scarring due to additional trauma to al-
ready traumatized tissues. Repeated administration of charcoal or other absor-
bent every 2-4 hours may be beneficial in both children and adults, but use of
a cathartic such as sorbitol should be avoided after the first dose. Cathartics and
repeat doses of activated charcoal should not be administered if the gut is atonic.
Check frequently for bowel sounds. Ileus occurs commonly in diquat
poisoning, less often in paraquat poisoning.
PARAQUAT & DIQUAT 113
-------
3. Samples. Secure a blood sample as soon as possible for paraquat analysis, and
urine samples for either paraquat and/or diquat. Serial samples of urine for either
agent and plasma for paraquat may be followed for prognostic information.
4. Respiration. Do not administer supplemental oxygen until the pa-
tient develops severe hypoxemia. High concentrations of oxygen in the lung
increase the injury induced by paraquat, and possibly by diquat as well. There
may be some advantage in placing the patient in a moderately hypoxic envi-
ronment, i.e., 15%-16% oxygen, although the benefit of this treatment measure
has not been established empirically in human poisonings. Inhalation of nitric
oxide has been suggested as a method to maintain tissue oxygenation at low
inspired oxygen concentrations, but its efficacy is unproven. When the lung
injury is so far advanced that there is no expectation of recovery, oxygen may
be given to relieve air hunger.
5. Intensive care. In serious poisonings, care should be provided in an inten-
sive care setting, to allow proper monitoring of body functions and skilled
performance of necessary invasive monitoring and procedures.
6. Fluids. It is essential to maintain adequate urinary output.4 Administer in-
travenous fluids: isotonic saline, Ringer's solution, or 5% glucose in water. This
is highly advantageous early in poisonings as a means of correcting dehydra-
tion, accelerating toxicant excretion, reducing tubular fluid concentrations of
paraquat, and correcting any metabolic acidosis. However, fluid balance must
be monitored carefully to forestall fluid overload if renal failure develops. Monitor
the urine regularly for protein and cells, to warn of impending tubular necrosis.
Intravenous infusions must be stopped if renal failure occurs, and extracorpo-
real hemodialysis is indicated. Hemodialysis is not effective in clearing paraquat
or diquat from the blood and tissues.
7. Hemoperfusion over cellophane-coated activated charcoal may be consid-
ered. The procedure has been used in many paraquat poisonings because the
adsorbent does efficiently remove paraquat from the perfused blood. However,
recent reviews of effectiveness have failed to show any reduction in mortality as
a result of hemoperfusion.1'4 The apparent reason for this is the very small
proportion of paraquat body burden carried in the circulating blood even when
only a few hours have elapsed after ingestion. Theoretically, a patient who can
be hemoperfused within 10 hours of paraquat ingestion may derive some mar-
ginal benefit, but this has not been demonstrated.
If hemoperfusion is attempted, blood calcium and platelet concentrations
must be monitored. Calcium and platelets must be replenished if these con-
stituents are depleted by the procedure.
114 PARAQUAT & DIQUAT
-------
8. Seizure control. Convulsions and psychotic behavior sometimes encoun-
tered in diquat poisoning may be best controlled by lorazepam, given slowly
intravenously, as outlined in Chapter 2. Control convulsions as outlined in
Chapter 2.
9. Other drugs. Many drugs have been tested in animals or given in human
bipyridyl poisonings without clear evidence of benefit or harm: corticoster-
oids, superoxide dismutase, propranolol, cyclophosphamide, vitamin E, ribofla-
vin, niacin, ascorbic acid, clofibrate, desferrioxamine, acetylcysteine, and terpin
hydrate. However, recent evidence regarding the use of cyclophosphamide
and methylprednisolone may be effective in reducing the mortality associ-
ated with moderate to severe paraquat poisoning. Two studies found a reduced
mortality associated with the treatment, while one study found no difference.16
The dosages used for cyclophosphamide and methylprednisolone were 1 gram
daily for two days and 1 gram daily for three days respectively, and were given
after hemoperfusion. Each drug was administered as a two hour infusion, and
white cell counts, serum creatinine levels, chest radiography, and liver function
tests were monitored.16
10. Pain management. Morphine sulfate is usually required to control the
pain associated with deep mucosal erosions of the mouth, pharynx, and esophagus,
as well as abdominal pain from pancreatitis and enteritis. Mouthwashes, cold
fluids, ice cream, or anesthetic lozenges may also help to relieve pain in the
mouth and throat.
Dosage of Morphine Sulfate:
Adults and children over 12 years: 10-15 mg subcutaneously every 4
hours.
Children under 12years: 0.1 - 0.2 mg /kg body weight every 4 hours.
11. Transplantation. With severe pulmonary toxicity, recovery of the patient
may only be accomplished by lung transplantation. However, the transplanted
lung is susceptible to subsequent damage due to redistribution of paraquat.17
PARAQUAT & DIQUAT 115
-------
General Chemical Structures
ci
CH,
CH2CH2 2Br"
Diquat
References
1. Pond SM. Manifestations and management of paraquat poisoning. MedJAust 1990;! 52:256-9.
2. Giulivi C, Lavagno CC, Lucesoli F, et al. Lung damage in paraquat poisoning and hyper-
baric oxyen exposure: superoxide-mediated inhibition of phospholipase A2. Free Radic
BiolMedl995;18:203-13.
3. Nordquist RE, Nguyen H, Poyer JL, et al. The role of free radicals in paraquat-induced
cornea! lesions. Free Radic Res 1995;23:61-71.
4. Honore P, Hantson P, FauviHe JP, et al. Paraquat poisoning: State of the art. Acta Clin Belg
1994;49:220-8.
5. Bismuth C, Gamier R, Dally S, et al. Prognosis and treatment of paraquat poisoning: A
review of 28 cases. J Toxicol Clin Toxicol 1982;19:461-74.
6. Harsanyi L, Nemeth A, and Lang A. Paraquat (gramoxone) poisoning in south-west Hun-
gary, 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 EmergMed 1995;26:721-2.
8. Tungsanga K, Chusilp S, Israsena S, et al. Paraquat poisoning: Evidence of systemic toxicity
after dermal exposure. Postgrad Med] 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. Neurotoxicologyl988;9:243-8.
11. Lam HF, Azawa J, Gupta BN, et al. A comparison of the effects of paraquat and diquat on
lung compliance, lung volume, and single-breath diffusing capacity in the rat. Toxicology
1980;18:lll-23.
12. Vanholder R, Colardyn F, DeReuck J, et al. Diquat intoxication: Report of two cases and
review of the literature. Am ] Med 1981;70:1267-71.
13. Olson KR. Paraquat and diquat. In: Olson KR et al. (eds), Poisoning and Drug Overdose, 2nd
ed. Norwalk CT: Appelton and Lange, 1994, pp. 245-6.
14. Sechi GP, AgnettiV, Piredda M, et al. Acute and persistent Parkinsonism after use of diquat.
Neurology 1992;42:261-3.
15. Proudfoot AT, Stewart MS, Levitt T, et al. Paraquat poisoning: Significance of plasma-paraquat
concentrations. Lancet 1979;2:330-2.
116 PARAQUAT & DIQUAT
-------
16. Lin JL,Wei MC, and LiuYC. Pulse therapy with cyclophosphamide and methyprednislone
in patients with moderate to severe paraquat poisoning: A preliminary report. Thorax
1996;51:661-3.
17. Toronto Lung Transplant Group. Sequential bilateral lung transplantation for paraquat poi-
soning. A case report. JThoracic Cardiovas Surg 1985;89:734-42.
PARAQUAT & DIQUAT 117
-------
CHAPTER 13
Other Herbicides
Many herbicides are now available for use in agriculture and for lawn and
garden weed control. This chapter discusses herbicides other than the
chlorophenoxys, nitrophenols and chlorophenols, arsenicals, and dipyridyls, which
are the subjects of separate chapters. Many modern herbicides kill weeds selec-
tively by impairing metabolic processes that are unique to plant life. For this
reason, their systemic toxicities in mammals are generally low. Nonetheless,
some herbicides pose a significant risk of poisoning if handled carelessly, and
many are irritating to eyes, skin, and mucous membranes.
For several good reasons, all of the herbicides mentioned in this chapter
should be handled and applied only with full attention to safety measures that
minimize personal contact. Many formulations contain adjuvants (stabilizers,
penetrants, surfactants) that may have significant irritating and toxic effects. A
number of premixed formulations contain two or more active ingredients; the
companion pesticides may be more toxic than the principal herbicide. Good
hygienic practice should not be disregarded just because a pesticide is reported
to have a high LD5Q 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 histo-
ries, and some unpublished reports.The listing cannot be considered inclusive,
either of herbicide products or of effects.
118 OTHER HERBICIDES
-------
TOXICITY OF COMMON HERBICIDES
Chemical Class
Acetamides
Aliphatic acids
Anilides
Benzamide
Benzoic,
anisic acid
derivatives
Benzonitriles
Benzothiadiazinone
dioxide
Carbamates and
Thiocarbamates
(herbicidal)
Generic Name
metolachlor
trichloroacetic
acid
dichloropropionic
acid (dalapon)
alachlor
propachlor
propanil
pronamide
trichlorobenzoic
acid
dicamba
dichlobenil
bentazone
asulam
terbucarb
butylate
cycloate
pebulate
vernolate
EPIC
diallate
triallate
thiobencarb
Proprietary
Names
Dual, Pennant,
others
TCA
Dalapon,
Revenge
Lasso, Alanox
Ramrod, Bexton,
Prolex
DPA, Chem
Rice, Propanex,
Riselect, Stam,
Stampede
Kerb, Rapier
TCBA.Tribac,
2,3,6-TBA
Banvel
Casoron,
Dyclomec, Barrier
Basagran
Asulox
Azac, Azar
Sutan
Ro-Neet
Tillam, PEBC
Vernam
Eptam, Eradicane
Di-allate
Far-go
Bolero, Saturn
Acute Oral LD50
mg/kg
2,780
5,000
970
1,800
710
>2,500
8,350
1,500
2,700
>4,460
>1,000
>5,000
>34,000
3,500
2,000
921
1,800
1,630
395
1,675
1,300
Known or
Suspected
Adverse Effects
Irritating
to eyes
and skin.
Irritating to
skin, eyes,
and respiratory
tract.
Mild irritant.
Dermal irritant
and sensitizer.
Irritating to skin,
eyes, and
respiratory tract.
Moderately
irritating to eyes
Moderately
irritating to skin
and respiratory
tract.
Minimal toxic,
irritant effects
Irritating to eyes
and respiratory
tract.
Some are
irritating to
eyes, skin, and
respiratory tract,
particularly in
concentrated
form.
Some may be
weak inhibitors
of cholinesterase.
OTHER HERBICIDES 119
-------
TOXICITY OF COMMON HERBICIDES
Chemical Class
Carbanilates
Chloropyridinyl
Cyclohexenone
derivative
Dinitroamino-
benzene
derivative
Fluorodinitro-
toluidine
compounds
Isoxazolidinone
Nicotinic acid
isopropylamine
derivative
Oxadiazolinone
Phosphonates
Generic Name
chlorpropham
triclopyr
sethoxydim
butralin
pendimethalin
oryzalin
benfluralin
dinitramine
ethalfluralin
fluchloralin
profluralin
trifluralin
clomazone
imazapyr
oxadiazon
glyphosate
fosamine
ammonium
Proprietary
Names
Sprout-Nip
Chloro-IPC
Garlon, Turflon
Poast
Am ex
Tarn ex
Prowl, Stomp,
Accotab,
Herbodox,
Go-Go-San,
Wax Up
Surflan, Dirimal
Benefin, Balan,
Balfin, Quilan
Cobex
Sonalan
Basalin
Tolban
Treflan
Command
Arsenal
Ron star
Roundup,
Glyfonox
Krenite
Acute Oral LD50
mg/kg
3,800
630
3,125
12,600
>5,000
2,250
>1 0,000
>1 0,000
3,000
>1 0,000
1,550
1,808
>1 0,000
1,369
>5,000
>3,500
4,300
>5,000
Known or
Suspected
Adverse Effects
Skin irritants.
May generate
methemoglobin
at high dosage.
Irritating to skin
and eyes.
Irritating to skin
and eyes.
May be
moderately
irritating.
These herbicides
do not uncouple
oxidative
phosphorylation
or generate
methemoglobin.
May be mildly
irritating. These
herbicides do not
uncouple
oxidative
phosphorylation
or generate
methemoglobin.
May be
moderately
irritating.
Irritating to eyes
and skin. Does
not contain
arsenic.
Minimal toxic
and irritant
effects.
Irritating to eyes,
skin, and upper
respiratory tract.
Irritating to eyes,
skin, and upper
respiratory tract.
120 OTHER HERBICIDES
-------
TOXICITY OF COMMON HERBICIDES
Chemical Class
Phthalates
Picolinic acid
compound
Triazines
Triazole
Generic Name
chlorthaldimethyl
endothall
picloram
ametryn
atrazine
cyanazine
desmetryn
metribuzin
prometryn
propazine
simazine
terbuthylazine
tertutryn
prometon
amitrole,
aminotriazole
Proprietary
Names
Dachthal, DCPA
Aquathol
Tordon, Pinene
Ametrex, Evik,
Gesapax
Aatrex, Atranex,
Crisazina
Bladex, Fortrol
Semeron
Sencor, Lexone,
Sencoral, Sencorex
Caparol, Gesagard,
Prometrex
Milo-Pro,
Primatol, Prozinex
Gesatop, Princep,
Caliber 90
Gardoprim,
Primatol M
Ternit, Prebane,
Terbutrex
Gesafram 50
Pramitol 25E
Amerol, Azolan,
Azole, Weedazol
Acute Oral LD50
mg/kg
>1 0,000
51
8,200
1,750
1,780
288
1,390
1,100
5.235
>7,000
>5,000
2,000
2,500
2,980
>1 0,000
Known or
Suspected
Adverse Effects
Moderately
irritating to eyes.
Free acid is highly
toxic. Irritating to
skin, eyes and
respiratory tract.
See Chapter 18.
Irritating to skin,
eyes, and
respiratory tract.
Low systemic
toxicity.
Systemic
toxicity
is unlikely
unless large
amounts
have been
ingested.
Some
triazines
are moderately
irritating to
the eyes,
skin, and
respiratory
tract.
This particular
formulation of
prometon is
strongly irritating
to eyes, skin, and
respiratory tract.
Minimal systemic
toxicity. Slight
irritant effect.
OTHER HERBICIDES 121
-------
TOXICITY OF COMMON HERBICIDES
Known or
Chemical Class
Uracils
Urea
derivatives
Generic Name
bromacil
lenacil
terabacil
chlorimuron
ethyl
chlorotoluron
diuron
flumeturon
isoproturon
linuron
methabenz-
thiazuron
metobromuron
metoxuron
monolinuron
monuron
neburon
siduron
sulfemeturon-
methyl
Proprietary
Names
Hyvar
Venzar
Sinbar
Classic
Dicuran, Tolurex
Cekiuron,
Crisuron, Dailon,
Direx, Diurex,
Diuron,
Karmex, Unidron,
Vonduron
Cotoran,
cottonex
Alon, Arelon,
IP50, Tolkan
Afalon, Linex,
Linorox, Linurex,
Lorox, Sarclex
Tribunil
Pattonex
Deftor, Dosaflo,
Purivel, Sulerex
Aresin
Monuron
Granurex,
Neburex
Tupersan
Oust
Acute Oral LD50
mg/kg
5,200
>1 1,000
>5,000
>4,000
>1 0,000
>5,000
8,900
1,826
1,500
5,000
2,000
3,200
2,100
3,600
>1 1,000
>7,500
>5,000
Suspected
Adverse Effects
Irritant to skin,
eyes, and
respiratory tract.
Moderately
irritating.
Systemic
toxicity is
unlikely unless
large amounts
have been
ingested.
Many
substituted
ureas are
irritating to
eyes, skin, and
mucous
membranes.
tebuthiuron
Spike, Tebusan
644
122 OTHER HERBICIDES
-------
Confirmation of Poisoning
Although there are analytical methods for residues of many of the herbi-
cides mentioned in this chapter and for some of the mammalian metabolites
generated from them, these procedures are not generally available to confirm
human absorption of the chemicals. Exposure must be determined from a re-
cent history of occupational contact or accidental or deliberate ingestion.
Treatment
1. Skin decontamination. Skin contamination should be treated promptly
by washing with soap and water. Contamination of the eyes should be treated
immediately by prolonged flushing of the eyes with large amounts of clean
water. If dermal or ocular irritation persists, medical attention should be ob-
tained without delay. See Chapter 2.
2. Gastrointestinal decontamination. Ingestions of these herbicides are likely
to be followed by vomiting and diarrhea due to their irritant properties. Man-
agement depends on: (1) the best estimate of the quantity ingested, (2) time
elapsed since ingestion, and (3) the clinical status of the subject.
Activated charcoal is probably effective in limiting irritant effects and
reducing absorption of most or all of these herbicides. Aluminum hydroxide
antacids may be useful in neutralizing the irritant actions of more acidic agents.
Sorbitol should be given to induce catharsis if bowel sounds are present and if
spontaneous diarrhea has not already commenced. Dehydration and electrolyte
disturbances may be severe enough to require oral or intravenous fluids.
There are no specific antidotes for poisoning by these herbicides. In the
case of suicidal ingestions, particularly, the possibility must always be kept in
mind that multiple toxic substances may have been swallowed.
If large amounts of herbicide have been ingested and the patient is seen
within an hour of the ingestion, gastrointestinal decontamination should be
considered, as outlined in Chapter 2.
If the amount of ingested herbicides was small, if effective emesis has al-
ready occurred, or if treatment is delayed, administer activated charcoal and
sorbitol by mouth.
3. Intravenous fluids. If serious dehydration and electrolyte depletion have
occurred as a result of vomiting and diarrhea, monitor blood electrolytes and
fluid balance and administer intravenous infusions of glucose, normal saline, 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.
OTHER HERBICIDES 123
-------
4. Supportive measures are ordinarily sufficient for successful management
of excessive exposures to these herbicides (endothall is an exceptionsee Chap-
ter 18, p. 187). If the patient's condition deteriorates in spite of good supportive
care, the operation of an alternative or additional toxicant should be suspected.
124 OTHER HERBICIDES
-------
Section IV
OTHER PESTICIDES
-------
CHAPTER 14
HIGHLIGHTS
Life-threatening effects
on CMS, blood vessels,
kidney, liver
Signs and Symptoms:
In acute cases, garlic odor
of the breath and feces,
metallic taste in mouth,
adverse Gl symptoms
In chronic cases, muscle
weakness, fatigue,
weight loss,
hyperpigmentation,
hyperkeratosis, Mees
lines
Treatment:
Gl decontamination
Chelation therapy
Dimercaprol (BAL) or
DMPS to accelerate
arsenic excretion
Arsenical Pesticides
Many arsenic compounds have been discontinued in the United States as a
result of government regulations. However, arsenical pesticides are still widely
available in some countries, and many homes and farms have leftover supplies
that continue to represent some residual risk.
Arsine gas is discussed separately on page 132.
Toxicology
Arsenic is a natural element that has both metal and nonmetal physical/
chemical properties. In some respects, it resembles nitrogen, phosphorus, anti-
mony, and bismuth in its chemical behavior. In nature, it exists in elemental,
trivalent (-3 or +3), and pentavalent (+5) states. It binds covalently with most
nonmetals (notably oxygen and sulfur) and with metals (for example, calcium
and lead). It forms stable trivalent and pentavalent organic compounds. In bio-
chemical behavior, it resembles phosphorus, competing with phosphorus ana-
logs for chemical binding sites.
Toxicity of the various arsenic compounds in mammals extends over a
wide range, determined in part by the unique biochemical actions of each
compound, but also by absorbability and efficiency of biotransformation and
disposition. Overall, arsines present the greatest toxic hazard, followed closely
by arsenites (inorganic trivalent compounds). Inorganic pentavalent compounds
(arsenates) are somewhat less toxic than arsenites, while the organic (methy-
lated) pentavalent compounds represent the least hazard of the arsenicals that
are used as pesticides.1
The pentavalent arsenicals are relatively water soluble and absorbable across
mucous membranes.Trivalent arsenicals, having greater lipid solubility, are more
readily absorbed across the skin.2 However, poisonings by dermal absorption of
either form have been extremely rare. Ingestion has been the usual basis of
poisoning; gut absorption efficiency depends on the physical form of the com-
pound, its solubility characteristics, the gastric pH, gastrointestinal motility, and
gut microbial transformation. Arsine exposure occurs primarily through inha-
lation, and toxic effects may also occur with other arsenicals through inhalation
of aerosols.
Once absorbed, many arsenicals cause toxic injury to cells of the nervous
system, blood vessels, liver, kidney, and other tissues. Two biochemical mecha-
126 ARSENICALS
-------
nisms of toxicity are recognized: (1) reversible combination with thiol groups
contained in tissue proteins and enzymes, and (2) substitution of arsenic anions
for phosphate in many reactions, including those critical to oxidative phosphory-
lation. Arsenic is readily metabolized in the kidney to a methylated form, which
is much less toxic and easily excreted. However, it is generally safest to manage
cases of arsenical pesticide ingestion as though all forms are highly toxic.
The unique toxicology of arsine gas is described later in this chapter.
Signs and Symptoms of Poisoning
Manifestations of acute poisoning are distinguishable from those of chronic
poisoning.
Acute arsenic poisoning: Symptoms and signs usually appear within
one hour after ingestion, but may be delayed several hours. Garlic odor of the
breath and feces may help to identify the toxicant in a severely poisoned pa-
tient. There is often a metallic taste in the mouth. Adverse gastrointestinal (GI)
effects predominate, with vomiting, abdominal pain, and rice-water or bloody
diarrhea being the most common. Other GI effects include inflammation, vesicle
formation and eventual sloughing of the mucosa in the mouth, pharynx, and
esophagus.3 These effects result from the action of an arsenical metabolite on
blood vessels generally, and the splanchnic vasculature in particular, causing
dilation and increased capillary permeability.
The central nervous system is also commonly affected during acute expo-
sure. Symptoms may begin with headache, dizziness, drowsiness, and confusion.
Symptoms may progress to include muscle weakness and spasms, hypothermia,
lethargy, delirium, coma, and convulsions.1 Renal injury is manifest as pro-
teinuria, hematuria, glycosuria, oliguria, casts in the urine, and, in severe poi-
soning, acute tubular necrosis. Cardiovascular manifestations include shock,
cyanosis, and cardiac arrhythmia,4'5 which are due to direct toxic action and
electrolyte disturbances. Liver damage may be manifested by elevated liver en-
zymes and jaundice. Injury to blood-forming tissues may cause anemia, leuko-
penia, and thrombocytopenia.
Death usually occurs one to three days following onset of symptoms and is
often the result of circulatory failure, although renal failure also may contrib-
ute.1 If the patient survives, painful paresthesias, tingling, and numbness in the
hands and feet may be experienced as a delayed sequela of acute exposure. This
sensorimotor peripheral neuropathy, which may include muscle weakness and
spasms, typically begins 1-3 weeks after exposure.6 The muscle weakness may
be confused with Guillain-Barre syndrome.7
Chronic arsenic poisoning from repeated absorption of toxic amounts
generally has an insidious onset of clinical effects and may be difficult to diag-
nose. Neurologic, dermal, and nonspecific manifestations are usually more promi-
nent than the gastrointestinal effects that characterize acute poisoning. Muscle
Commercial Products
(Many have been discontinued)
arsenic acid
Hi-Yield 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
Methar30
Sodar
Weed-E-Rad 360
lead arsenate
Gypsine
Sop ra be I
methane arsonic acid (MAA)
monoammonium methane
arsonate (MAMA)
monosodium methane arsonate
(MSMA)
Ansar 170
(Continued on the next page)
ARSENICALS 127
-------
Commercial Products
(Continued)
Arsonate Liquid
Bueno 6
Daconate 6
Dal-E-Rad
Drexar 530
Herbi-AII
Merge 823
Mesamate
Target MSMA
Trans-Vert
Weed-E-Rad
Weed-Hoe
sodium arsenate
disodium arsenate
Jones Ant Killer
sodium arsenite
Prodalumnol Double
Sodanit
zinc arsenate
weakness and fatigue can occur, as can anorexia and weight loss. Hyperpig-
mentation is a common sign, and tends to be accentuated in areas that are
already more pigmented, such as the groin and areola. Hyperkeratosis is an-
other very common sign, especially on the palms and soles.8'9 Subcutaneous
edema of the face, eyelids, and ankles, stomatitis, white striations across the nails
(Mees lines), and sometimes loss of nails or hair are other signs of chronic,
continuous exposure.1'9 On occasion, these hyperkeratotic papules have under-
gone malignant transformation.8 Years after exposure, dermatologic findings
include squamous cell and basal cell carcinoma, often in sun-protected areas.
Neurologic symptoms are also common with chronic exposure. Peripheral
neuropathy, manifested by paresthesia, pain, anesthesia, paresis, and ataxia, may
be a prominent feature. It may often begin with sensory symptoms in the lower
extremities and progress to muscular weakness and eventually paralysis and
muscle wasting. Although less common, encephalopathy can develop with speech
and mental disturbances very much like those seen in thiamine deficiency
(Wernicke's syndrome).
Other organ systems are affected with arsenic toxicity Liver injury reflected
in hepatomegaly and jaundice may progress to cirrhosis, portal hypertension,
and ascites. Arsenic has direct glomerular and tubular toxicity resulting in oliguria,
proteinuria, and hematuria. Electrocardiographic abnormalities (prolongation
of the Q-T interval) and peripheral vascular disease have been reported. The
latter includes acrocyanosis, Raynaud's phenomenon, and frank gangrene.1'10
Hematologic abnormalities include anemia, leukopenia, and thrombocytopenia.1
Late sequelae of protracted high intakes of arsenic include skin cancer as described
above and an increased risk of lung cancer.1'8
Confirmation of Poisoning
Measurement of 24-hour urinary excretion of arsenic (micrograms per
day) is the most common way to confirm excessive absorption and is the
preferred method to follow serial levels and evaluate chronic exposure.1'11
Spot urine arsenic analysis expressed as a ratio with urinary creatinine is the
recommended method to evaluate occupational exposures.12 Methods to de-
termine blood arsenic concentration are available; however blood levels tend
to poorly correlate with exposure except in the initial acute phase.11'13 Spe-
cial metal-free acid-washed containers should be used for sample collection.
Arsenic excretion above 100 meg per day should be viewed with suspicion
and the test should be repeated.
Excretions above 200 meg per day reflect a toxic intake, unless seafood was
ingested.11'13'14'15 Diets rich in seafood, primarily shellfish in the previous 48
hours, may generate 24-hour urine excretion levels as high as 200 meg per day
and sometimes more.3'14 The majority of marine arsenic that is excreted is in
the methylated form (arsenobetaine) and is not considered acutely toxic. How-
128 ARSENICALS
-------
ever, a recent study supports that some of the arsenic released from mussels may
contain higher amounts of arsenic trioxide than previously thought.14 Urinary
arsenic may be speciated into inorganic and organic fractions to help deter-
mine the source of the exposure and to help guide treatment.
Concentrations of arsenic in blood, urine, or other biologic materials can be
measured by either wet or dry ashing, followed by colorimetric or atomic ab-
sorption spectrometric analysis. The latter method is preferred. Blood concentra-
tions in excess of about 100 meg per liter probably indicate excessive intake or
occupational exposure, provided that seafood was not ingested before the sample
was taken.3'11'13'15 Blood samples tend to correlate with urine samples during the
early stages of acute ingestion,11 but because arsenic is rapidly cleared from the
blood, the 24-hour urine sample remains the preferred method for detection and
for ongoing monitoring.1'11'13 Hair has been used for evaluation of chronic expo-
sure. Levels in unexposed people are usually less than 1 mg/kg; levels in individu-
als with chronic poisoning range between 1 and 5 mg/kg.15 Hair samples should
be viewed with caution because external environmental contamination such as
air pollution may artificially elevate arsenic levels.
Special tests for arsine toxicosis are described on page 132 under "Arsine
Gas."
Treatment
The following discussion applies principally to poisonings by arsenicals in
solid or dissolved form. Treatment of poisoning by arsine gas requires special
measures described below on page 132.
1. Skin decontamination. Wash arsenical pesticide from skin and hair with
copious amounts of soap and water. Flush contaminant from eyes with clean
water. If irritation persists, specialized medical treatment should be obtained.
See Chapter 2.
2. Gastrointestinal decontamination. If arsenical pesticide has been in-
gested within the first hour of treatment, consideration should be given to GI
decontamination, as outlined in Chapter 2. Because poisoning by ingested ar-
senic almost always results in profuse diarrhea, it is generally not appropriate to
administer a cathartic.
3. Intravenous fluids. Administer intravenous fluids to restore adequate hy-
dration, support urine flow, and correct electrolyte imbalances. Monitor in-
take/output continuously to guard against fluid overload. If acute renal failure
occurs, monitor blood electrolytes regularly. Blood transfusions and oxygen by
mask may be needed to combat shock.
ARSENICALS 129
-------
4. Cardiopulmonary monitoring. Monitor cardiac status by EGG to detect
ventricular arrhythmias including prolonged Q-T interval and ventricular ta-
chycardia, and toxic myocardiopathy (T wave inversion, long S-T interval).
5. Chelation therapy. Administration of Dimercaprol (BAL) is usually indi-
cated in symptomatic arsenic poisonings, although DMPS, where available, may
prove to be a better antidote. The following dosage schedule has proven to be
effective in accelerating arsenic excretion.
Monitor urinary arsenic excretion while any chelating agent is being ad-
ministered. When 24-hour excretion falls below 50 meg per day, it usually is
advisable to discontinue the chelation therapy.
RECOMMENDED INTRAMUSCULAR DOSAGE OF BAL
(DIMERCAPROL) IN ARSENIC POISONING
1st day
2nd day
3rd day
Each of the following
days for 10 days, or
until recovery
Severe Poisoning
3.0 mg/kg q4h
(6 injections)
3.0 mg/kg q4h
(6 injections)
3.0 mg/kg q6h
(4 injections)
3.0 mg/kg q12 hr
(2 injections)
Mild Poisoning
2.5 mg/kg q6h
(4 injections)
2.5 mg/kg q6h
(4 injections)
2.5 mg/kg q12h
(2 injections)
2.5 mg/kg qd
(1 injection)
BAL is provided as a 100 mg/mL solution in oil. Dosages in the table are in terms of BAL
itself, not of the solution. Dosages for children are consistent with the "Mild Poisoning"
schedule and can be between 2.5 and 3.0 mg/kg per dose.16
Caution: Disagreeable side effects often accompany the use of BAL: nausea,
headache, burning and tingling sensations, sweating, pain in the back and abdo-
men, tremor, restlessness, tachycardia, hypertension, and fever. Coma and con-
vulsions occur at very high dosage. Sterile abscesses may form at injection sites.
Acute symptoms usually subside in 30-90 minutes. Antihistamine drugs or an
oral dose of 25-50 mg ephedrine sulfate or pseudoephedrine provide relief.
These are more effective if given a few minutes before the injection of BAL.
BAL may potentially have other adverse effects. In rabbits, treatment of arsenite
exposure with BAL increased brain arsenic levels.17
6. Oral treatments. After the gastrointestinal tract is reasonably free of arsenic,
oral administration of d-penicillamine, Succimer (DMSA), or DMPS should
probably replace BAL therapy. However, d-penicillamine has demonstrated lim-
ited effectiveness for arsenic exposure in experimental models.18
130 ARSENICALS
-------
Dosage of d-penicillamine:
Adults and children over 12 years: 0.5 g every 6 hours, given 30-60
minutes before meals and at bedtime for about 5 days.
Children under 12years:O.I g/kg body weight, every 6 hours, given
30-60 minutes before meals and at bedtime for about 5 days. Not to
exceed 1.0 g per day.
Caution: Adverse reactions to short-term therapy are rare. However,
persons allergic to penicillin should not receive d-penicillamine
as they may suffer allergic reactions to it.
Succimer (DMSA) has been shown to be an effective chelator of arsenic,
though it is not labeled for this indication.19 In Europe, DMPS has been used
successfully in treatment of arsenic poisoning. In light of the lack of effective-
ness of d-penicillamine, coupled with the low toxicity and high therapeutic
index of DMPS and DMSA, it appears that the latter two agents may be the
preferred method for chronic toxicity or when oral chelation is acceptable.18'19
Dosage of DMSA (Succimer):
Adults and Children: 10 mg/kg every 8 hours for 5 days, followed by
10 mg/kg every 12 hours for an additional 14 days. (Maximum 500
mg per dose). Should be given with food.
Dosage of DMPS:
Adults: 100 mg every 8 hours for 3 weeks to 9 months.
7. Hemodialysis. Extracorporeal hemodialysis, used in combination with
BAL therapy, has limited effectiveness in removing arsenic from the blood.
Hemodialysis is clearly indicated to enhance arsenic elimination and main-
tain extracellular fluid composition if acute renal failure occurs.
8. Renal function. In patients with intact renal function, alkalinization of
the urine by sodium bicarbonate to maintain urine pH >7.5 may help pro-
tect renal function in the face of hemolysis occurring as part of the acute
poisoning.
ARSENICALS 131
-------
HIGHLIGHTS
Powerful hemolysin
Signs and Symptoms:
Malaise, dizziness, nausea,
abdominal pain
Hemoglobinuria and
jaundice.
Treatment:
Supportive
Exchange transfusion may
be considered
132 ARSENICALS
ARSINE GAS
Arsine is not used as a pesticide. However, some poisonings by arsine
have occurred in pesticide manufacturing plants and metal refining op-
erations when arsenicals came into contact with mineral acids or strong
reducing agents.
Toxicology
Arsine is a powerful hemolysin, a toxic action not exhibited by other
arsenicals. In some individuals, very little inhalation exposure is required to
cause a serious hemolytic reaction. Exposure times of 30 minutes at 25-50
parts per million are considered lethal.20 Symptoms of poisoning usually
appear 1-24 hours after exposure: headache, malaise, weakness, dizziness,
dyspnea, nausea, abdominal pain, and vomiting. Dark red urine (hemoglo-
binuria) is often passed 4-6 hours after exposure. Usually 1-2 days after
hemoglobinuria appears, jaundice is evident. Hemolytic anemia, sometimes
profound, usually provides diagnostic confirmation and can cause severe
weakness. Abdominal tenderness and liver enlargement are often apparent.
Basophilic stippling of red cells, red cell fragments, and ghosts are seen in
the blood smear. Methemoglobinemia and methemoglobinuria are evi-
dent. Elevated concentrations of arsenic are found in the urine, but these
are not nearly as high as are found in poisonings by solid arsenicals. Plasma
content of unconjugated bilirubin is elevated.
Renal failure due to direct toxic action of arsine and to products of
hemolysis represents the chief threat to life in arsine poisoning.21
Polyneuropathy and a mild psycho-organic syndrome are reported to
have followed arsine intoxication after a latency of 1 -6 months.
Treatment
1. Remove the victim to fresh air.
2. Administer intravenous fluids to keep the urine as dilute as possible and to
support excretion of arsenic and products of hemolysis. Include sufficient
sodium bicarbonate to keep the urine alkaline (pH greater than 7.5).
Caution: Monitor fluid balance carefully to avoid fluid overload if
renal failure supervenes. Monitor plasma electrolytes to detect disturbances
(particularly hyperkalemia) as early as possible.
3. Monitor urinary arsenic excretion to assess severity of poisoning. The
amount of arsine that must be absorbed to cause poisoning is small, and
therefore high levels of urinary arsenic excretion may not always occur,
even in the face of significant poisoning.21'22
4. If poisoning is severe, exchange blood transfusion may be considered.
It was successful in rescuing one adult victim of arsine poisoning.
5. Extracorporeal hemodialysis may be necessary to maintain normal extra-
cellular fluid composition and to enhance arsenic elimination if renal failure
occurs, but it is not very effective in removing arsine carried in the blood.
-------
General Chemical Structures
INORGANIC TRIVALENT
Arsenic trioxide
O
/ \
As-O-As
"White arsenic." Arsenous oxide. Has been
discontinued but still may be available
from prior registrations.
Sodium arsenite
Na-0-As = 0
Sodanit, Prodalumnol Double. All uses
discontinued in the U.S.
Calcium arsenite
O As=O
I
Ca (approx.)
I
OAs=0
Mono-calcium arsenite, London purple.
Flowable powder for insecticidal use on
fruit. All uses discontinued in the U.S.
Copper arsenite
(Acid copper arsenite)
HO-Cu-O-As = O
Wettable powder, for use as insecticide,
wood preservative. All uses discontinued
in the U.S.
Copper acetoarsenite
O
Cu-(O-C-CH3)2
3Cu-(O-As=O)2
Insecticide. Paris green, Schweinfurt green,
Emerald green, French green, Mitis green.
No longer used in the U.S.; still used
outside U.S.
Arsine
H
H
Not a pesticide. Occasionally generated
during manufacture of arsenicals.
\
As
I
H
INORGANIC PENTAVALENT
Arsenic acid
OH
HO
\ I
As=O
Hi-Yield Dessicant H-10, Zotox. Water
solutions used as defoliants, herbicides, and
wood preservatives.
HO
Sodium arsenate
NaO OH
Disodium arsenate. Jones Ant Killer. All
uses discontinued, but may still be
encountered from old registration.
As=0
NaO
ARSENICALS 133
-------
Tricalcium arsenate, Spra-cal, Turf-Cal.
Flo\vable po\vder formulations used
/ \ /, -x / \ against weeds, grubs. No longer used in
Ca As O Ca O As Ca the U S
\ / \ /
O O
Calcium arsenate
Lead arsenate
OH
O
Pb
\
\
Gypsine, Soprabel. Limited use in the
U.S.; wettable powder used as insecticide
outside the U.S.
As = O
O
O
Zinc arsenate
O O
O
Po\vder once used in U.S. as insecticide
on potatoes and tomatoes.
Zn
As O Zn O As Zn
O
\
O
ORGANIC (PENTAVALENT)
Cacodylic acid (sodium cacodylate) Non-selective herbicide, defoliant,
silvicide. Bolate, Bolls-Eye, Bophy Dilic,
OH OH
on3 ^ ^ on3 Kack^ phytar 56Q^ Rad_E_Cate 25, Salvo.
As
# \
O OH
(or Na)
Methane arsonic acid
CH3 OH
\ /
As
t \
O OH
MAA. Non-selective herbicide.
Monosodium methane arsonate
CH3 OH
\ /
As
-^ \
O OH
MSMA. Non-selective herbicide,
defoliant, silvicide. Ansar 170, Arsonate
Liquid, Bueno 6, Daconate 6, Dal-E-Rad,
Drexar 530, Herbi-All, Merge 823,
Mesamate, Target MSMA, Trans-Vert,
Weed-E-Rad, Weed-Hoe.
Disodium methane arsonate
CH3 ONa
\ /
As
^ \
O ONa
DSMA. Selective post-emergence
herbicide, silvicide. Ansar 8100,Arrhenal,
Arsmyl, Crab-E-Rad, Di-Tac, DMA,
Methar 30, Sodar, Weed-E-Rad 360.
Monoammonium methane arsonate MAMA. Selective post-emergence
CH3 ONH4
\ /
As
t \
O OH
herbicide. No longer used in the U.S.
134 ARSENICALS
-------
Calcium acid methane arsonate CAMA. Selective post-emergence
TH OH HO PH herbicide. Calar, Super Crab-E-Rad-
3\ X \ / 3 Calar, Super Dal-E-Rad.
As As
// \ / ^
O O - Ca - O O
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 in-
toxication. A study of 41 cases with observations on the effects of BAL (2,3-dimercapto-
propanol). N Engl J Med 1956;254:401-9.
7. Donofrio PD,WilbournAJ,AlbersJW, etal. Acute arsenic intoxication presenting as Guillain-
Barre-like syndrome. Muscle Nerve 1987; 10:114-20.
8. Maloney ME. Arsenic in dermatology. Dermatol Surg 1996;22:301-4.
9. Navarro B, Sayas MJ, Atienza A, and Leon 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. JToxicol Environ Health 1998;53A:85-93.
11. Fesmire FM, Schauben JL, and Roberge RJ. Survival following massive arsenic ingestion.
AmJEmergMed, 1998;6(6):602-6.
12. ACGIH. 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 follow-
ing ingestion of marine organisms by volunteers. Environ Res 1994;66:44-51.
15. Baselt RA and Cravey RH. Arsenic. In: Disposition ofToxic Drugs and Chemicals in Men,
3rd ed. Chicago, IL: Year Book Medical Publishers, 1990, pp. 65-9.
16. Barone MA. Drug doses; Dimercaprol. In:The Harriet Lane Handbook, 14th ed. Baltimore:
Mosby 1996, p. 525.
17. HooverTD and Aposhian HV. BAL increased the arsenic-74 content of rabbit brain. Toxicol
Appl Pharmacol 1983; 70:160-2.
ARSENICALS 135
-------
18. Kreppel H, Reichl FX, Forth W, and Fichtl B. Lack of effectiveness of d-peniciHamine in
experimental arsenic poisoning. Vet Hum Toxicol 1989;31:1 -5.
19. Muckter H, Liebl B, Beichl FX, et al. Are \ve ready to replace dimercaprol (BAL) as an
arsenic antidote? Hum Exp Toxicol 1997;16:460-5.
20. BlackweU M and Robbins A. NIOSH Current Intelligence BuUetin #32,Arsine (arsenic
hydride) poisoning in the workplace. Am Ind HygAssoc/1979;40:A56-61.
21. Fowler BA andWeissbergJB.Arsine poisoning. New Engl J Med 1974;291:1171-4.
22. Rathus E, Stingon RG, and PutmanJL.Arsine poisoning, country style. Med JAust 1979;! :163-6.
136 ARSENICALS
-------
CHAPTER 15
Fungicides
Fungicides are extensively used in industry, agriculture, and the home and gar-
den for a number of purposes, including: protection of seed grain during stor-
age, shipment, and germination; protection of mature crops, berries, seedlings,
flowers, and grasses in the field, in storage, and during shipment; suppression of
mildews that attack painted surfaces; control of slime in paper pulps; and pro-
tection of carpet and fabrics in the home.
Fungicides vary enormously in their potential for causing adverse effects in
humans. Historically, some of the most tragic epidemics of pesticide poisoning
occurred because of mistaken consumption of seed grain treated with organic
mercury or hexachlorobenzene. However, most fungicides currently in use are
unlikely to cause frequent or severe systemic poisonings for several reasons.
First, many have low inherent toxicity in mammals and are inefficiently ab-
sorbed. Second, many fungicides are formulated as suspensions ofwettable pow-
ders or granules, from which rapid, efficient absorption is unlikely. And third,
methods of application are such that relatively few individuals are intensively
exposed. Apart from systemic poisonings, fungicides as a class are probably re-
sponsible for a disproportionate number of irritant injuries to skin and mucous
membranes, as well as dermal sensitization.
The following discussion covers the recognized adverse effects of widely
used fungicides. For fungicides that have caused systemic poisoning, recom-
mendations for management of poisonings and injuries are set forth. For fungi-
cides not known to have caused systemic poisonings in the past, only general
guidelines can be offered.
The discussion of fungicide-related adverse effects proceeds in this order:
Substituted Benzenes
Thiocarbamates
Ethylene Bis Dithiocarbamates
Thiophthalimides
Copper Compounds
Organomercury Compounds
Organotin Compounds
Cadmium Compounds
Miscellaneous Organic Fungicides
HIGHLIGHTS
Numerous fungicides in use
with varying levels of
toxicity
Other than organomercury
compounds, most
fungicides are unlikely to be
absorbed enough to cause
systemic poisonings
Signs and Symptoms:
Variable
Treatment:
Dermal and eye
decontamination
Gl decontamination
Intravenous fluids
Contraindicated:
Atropine. Fungicides are
not cholinesterase
inhibitors
FUNGICIDES 137
-------
Commercial Products
SUBSTITUTED BENZENES
SUBSTITUTED BENZENES
chloroneb
Terraneb SP
chlorothalonil
Bravo
Clorto Caffaro
Clortosip
Daconil 2787
Exotherm Termil
Tuffcide
others
dicloran
Allisan
Clortran
DCNA
hexachlorobenzene*
Anticarie
Ceku C.B.
HCB
No Bunt
pentachloronitrobenzene
Avicol
Earthcide
Folosan
Kobu
Kobutol
PCNB
Pentagen
quintozene
Tri-PCNB
others
* Discontinued in the U.S.
Toxicology
Chloroneb is supplied as wettable powder for treatment of soil and seed.
This agent exhibits very low oral toxicity in mammals. It may be moderately
irritating to skin and mucous membranes. The metabolite dichloromethoxy-
phenol is excreted in the urine. No cases of systemic poisoning in humans have
been reported.
Chlorothalonil is available as wettable powder, water dispersible granules,
and flowable powders. Chlorothalonil has caused irritation of skin and mucous
membranes of the eye and respiratory tract on contact. Cases of allergic contact
dermatitis have been reported. There is one report of immediate anaphylactoid
reaction to skin contact.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 (en-
hances heat production). Extraordinary doses of dicloran given to laboratory
animals cause liver injury and corneal opacities.
Based on laboratory animal studies and effects of similar compounds, large
doses might be expected to cause liver injury, pyrexia, corneal opacities, and
possibly methemoglobinemia. None of these have been observed in humans
exposed to DCNA.
Hexachlorobenzene.Principal formulations are dusts and powders.
Hexachlorobenzene differs chemically and lexicologically from hexachlorocy-
clohexane, the gamma isomer of which (lindane) is still a widely-used insecticide.
Although this seed protectant fungicide has only slight irritant effects and
relatively low single-dose toxicity, long-term ingestion of HCB-treated grain
by Turkish farm dwellers in the late 1950s caused several thousand cases of
toxic porphyria resembling porphyria cutanea tarda.2This condition was due
to impaired hemoglobin synthesis, leading to toxic end-products (porphyrins)
in body tissues. The disease was characterized by excretion of red-tinged (por-
phyrin-containing) urine, bullous lesions of light-exposed skin, scarring and
atrophy of skin with overgrowth of hair, liver enlargement, loss of appetite,
arthritic disease, and wasting of skeletal muscle mass. Although most adults
ultimately recovered after they stopped consuming the HCB-treated grain, some
infants nursed by affected mothers died.
Hexachlorobenzene is effectively dechlorinated and oxidized in humans;
trichlorophenols are the major urinary excretion products. Disposition is suffi-
ciently prompt that occupationally exposed workers usually show only slight
138 FUNGICIDES
-------
elevation of blood HCB concentrations. HCB is sometimes present in blood
specimens from "non-occupationally exposed" persons in concentrations of up
to 5 meg per liter. Residues in food are the probable cause.
Pentachloronitrobenzene is used to dress seed and treat soil. Formula-
tions include emulsifiable concentrates, wettable powders, and granules.
Hexachlorobenzene is a minor contaminant to technical PCNB.
High concentrations in prolonged contact with skin have caused sensitiza-
tion in some tested volunteers, but neither irritation nor sensitization has been
reported in occupationally exposed workers. One case of conjunctivitis and keratitis
occurred following eye contamination. This resolved slowly but completely.
Systemic poisonings have not been reported. Clearance in laboratory ani-
mals is slow, probably due to enterohepatic recirculation. Excretion is chiefly
biliary, with some conversion to pentachloroaniline, pentachlorophenol, and
other metabolites in the liver. Although a methemoglobinemic effect might be
suspected (as from nitrobenzene), this has not been reported in humans or
animals, nor has toxic porphyria (as from hexachlorobenzene) been reported.
Confirmation of Poisoning
Hexachlorobenzene (HCB) can be measured in blood by gas chromatog-
raphy Chlorophenol metabolites can be measured in the urine. Although in-
herited disease and a number of exogenous agents may cause porphyrins to
appear in the urine, a test for porphyrins may be useful for toxicological diag-
nosis if there has been a known exposure to HCB or if a patient exhibits signs
suggestive of porphyria cutanea tarda.
Gas chromatography can be used to measure PCNB and metabolites,
chlorothalonil, and chloroneb, but the analysis is not widely available. Methods
have also been described for analysis of dicloran,but they are not widely available.
Treatment
1. Skin decontamination. Dermal contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water. If irritation persists, specialized medical care should be obtained. See
Chapter 2.
2. Gastrointestinal decontamination. If a large amount of the fungicide has
been ingested in the last few hours, and if copious vomiting has not already
occurred, it maybe reasonable to consider GI decontamination. Activated char-
coal can be used along with the addition of the cathartic sorbitol to the char-
coal slurry. If sorbitol is given separately, it should be diluted with an equal
volume of water before administration. No more than one dose of sorbitol is
recommended and it should be used with caution in children and the elderly.
See Chapter 2 for appropriate dosages.
FUNGICIDES 139
-------
Commercial Products
THIOCARBAMATES
ferbam
Carbamate WDG
Ferbam
Ferberk
Hexaferb
Knockmate
Trifungol
metam-sodium
A7 Vapam
Busan 1020
Karbation
Maposol
Metam-Fluid BASF
Nemasol
Solasan 500
Sometam
Trimaton
Vapam
VPM
thiram
Aules
Chipco Thiram 75
Fermide 850
Fernasan
Hexathir
Mercuram
Nomersam
Polyram-Ultra
Pomarsol forte
Spotrete-F
Spotrete WP75
Tetrapom
Thimer
Thioknock
Thiotex
Thiramad
Thirasan
Thiuramin
Tirampa
TMTD
Tram eta n
Tripomol
Tuads
ziram
Cuman
Hexazir
Mezene
Tricarbamix
Triscabol
Vancide MZ-96
Zincmate
Ziram F4
Ziram Technical
Zirberk
Zirex 90
Ziride
Zitox
If contact with the toxicant has been minimal (for example, oral contami-
nation only, promptly flushed out of the mouth), administration of charcoal
without a cathartic, followed by careful observation of the patient, probably
represents optimal management.
3. Porphyria. Persons affected by porphyria should avoid sunlight, which ex-
acerbates the dermal injury by porphyrins.
THIOCARBAMATES
Thiocarbamates are commonly formulated as dusts, wettable powders, or water
suspensions. They are used to protect seeds, seedlings, ornamentals, turf, veg-
etables, fruit, and apples. Unlike the N-methyl carbamates (Chapter 5),
thiocarbamates have very little insecticidal potency. A few exhibit weak anti-
cholinesterase activity, but most have no significant effect on this enzyme. Overall,
they are less of a threat to human health than the insecticidal carbamates. Fun-
gicidal thiocarbamates are discussed in this section, while those used as herbi-
cides are considered in Chapter 13.
METAM-SODIUM
Metam-sodium is formulated in aqueous solutions for application as a soil
biocide and fumigant to kill fungi, bacteria, weed seeds, nematodes, and insects.
All homeowner uses have been cancelled in the United States.
Toxicology
Metam-sodium can be very irritating to the skin. Poisonings by ingestion
of metam-sodium have not been reported. Although animal feeding studies do
not indicate extraordinary toxicity of metam-sodium by ingestion, its decom-
position in water yields methyl isothiocyanate, a gas that is extremely irritating
to respiratory mucous membranes, to the eyes, and to the lungs. Inhalation of
methyl isothiocyanate may cause pulmonary edema (severe respiratory distress,
coughing of bloody, frothy sputum). For this reason, metam-sodium is consid-
ered a fumigant. It must be used in outdoor settings only, and stringent precau-
tions must be taken to avoid inhalation of evolved gas.
Theoretically, exposure to metam-sodium may predispose the individual
to Antabuse reactions if alcohol is ingested after exposure. (See Thiram.) How-
ever, no such occurrences have been reported.
140 FUNGICIDES
-------
Confirmation of Poisoining
No tests for metam-sodium or its breakdown products in body fluids are
available.
Treatment
1. Skin decontamination. Skin contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water to avoid burns and cornea! injury. If dermal or eye irritation persists,
specialized medical treatment should be obtained. See Chapter 2.
2. Gastrointestinal decontamination. If a large amount has been ingested
recently, consider gastric emptying or charcoal and cathartic. See Chapter 2 for
appropriate dosages.
3. Pulmonary edema. If pulmonary irritation or edema occur as a result of
inhaling methyl isothiocyanate, transport the victim promptly to a medical fa-
cility. Treatment for pulmonary edema should proceed as outlined in Chapter
16, Fumigants.
4. Contraindicated: Metam-sodium is not a cholinesterase inhibitor. Atro-
pine is not an antidote.
THIRAM
Thiram is a common component of latex and possibly responsible for
some of the allergies attributed to latex.
Toxicology
Thiram dust is moderately irritating to human skin, eyes, and respiratory
mucous membranes. Contact dermatitis has occurred in occupationally ex-
posed workers. A few individuals have experienced sensitization to thiram.3
Systemic human poisonings by thiram itself have been very few, probably
due to limited absorption in most circumstances involving human exposure.
Those which have been reported have been similar clinically to toxic reactions
to disulfiram (Antabuse), the ethyl analogue of thiram which has been exten-
sively used in alcohol aversion therapy3 In laboratory animals, thiram at high
dosage has effects similar to those of disulfiram (hyperactivity, ataxia, loss of
muscle tone, dyspnea, and convulsions), but thiram appears to be about 10
times as toxic as disulfiram.
FUNGICIDES 141
-------
Neither thiram nor disulfiram are cholinesterase inhibitors. Both, however,
inhibit the enzyme acetaldehyde dehydrogenase, which is critical to the
conversion of acetaldehyde to acetic acid. This is the basis for the "Antabuse
reaction" that occurs when ethanol is consumed by a person on regular disulfiram
dosage. The reaction includes symptoms of nausea, vomiting, pounding headache,
dizziness, faintness, mental confusion, dyspnea, chest and abdominal pain, profuse
sweating, and skin rash. In rare instances, Antabuse reactions may have occurred
in workers who drank alcohol after previously being exposed to thiram.
Confirmation of Poisoning
Urinary xanthurenic acid excretion has been used to monitor workers
exposed to thiram. The test is not generally available.
Treatment: Thiram Toxicosis
1. Skin decontamination. Wash thiram from the skin with soap and water.
Flush contamination from the eyes with copious amounts of clean water. If irri-
tation of skin or eyes persists, specialized medical treatment should be obtained.
2. Gastrointestinal decontamination. If a large amount of thiram has been
swallowed within 60 minutes of presentation, and effective vomiting has not
already occurred, the stomach may be emptied by intubation, aspiration, and
lavage, taking all precautions to protect the airway from aspiration of vomitus.
Lavage should be followed by instillation of activated charcoal and cathartic. If
only a small amount of thiram has been ingested and/or treatment has been
delayed, oral administration of activated charcoal and cathartic probably repre-
sents optimal management.
3. Intravenous fluids. Appropriate IV fluids should be infused, especially if
vomiting and diarrhea are severe. Serum electrolytes and glucose should be
monitored and replaced as needed.
Treatment: Acetaldehyde Toxicosis (Antabuse Reaction)
1. Immediate management. Oxygen inhalation, Trendelenburg position-
ing, and intravenous fluids are usually effective in relieving manifestations of
Antabuse reactions.
2. Alochol avoidance. Persons who have absorbed any significant amount of
thiocarbamates must avoid alcoholic beverages for at least three weeks. Dispo-
sition of thiocarbamates is slow, and their inhibitory effects on enzymes are
slowly reversible.
142 FUNGICIDES
-------
ZIRAM AND FERBAM
These are formulated as flowable and wettable powders, used widely on
fruit and nut trees, apples, vegetables, and tobacco.
Toxicology
Dust from these fungicides is irritating to the skin, respiratory tract, and
eyes. Prolonged inhalation of ziram is said to have caused neural and visual
disturbances, and, in a single case of poisoning, a fatal hemolytic reaction.Theo-
retically, exposure to ziram or ferbam may predispose the individual to Antabuse
reactions if alcohol is ingested after exposure. (SeeThiram.) However, no such
occurrences have been reported.
Confirmation of Poisoning
No tests for these fungicides or their breakdown products in body fluids
are available.
Treatment
1. Skin decontamination. Skin contamination should be washed off with
soap and water. Flush contamination from the eyes with copious amounts of
water. If dermal or eye irritation persists, specialized medical treatment should
be obtained. See Chapter 2.
2. Gastrointestinal decontamination. If substantial amounts of ferbam or
ziram have been ingested recently, consideration should be given to gastric
emptying. If dosage was small and/or several hours have elapsed since inges-
tion, oral administration of charcoal and a cathartic probably represents optimal
management.
3. Hemolysis. If hemolysis occurs, intravenous fluids should be administered,
and induction of diuresis considered.
FUNGICIDES 143
-------
Commercial Products
ETHYLENE BIS
DITHIOCARBAMATES
(EBDC COMPOUNDS)
mancozeb
Dithane
Mancozin
manzeb
Manzin
Nemispor
Penncozeb
Ziman-Dithane
maneb
Kypman 80
Maneba
Manex
Manex 80
M-Diphar
Sopranebe
Trimangol
nabam
Chem Bam
DSE
Parzate
Spring Bak
zineb
Aspor
Dipher
Hexathane
Kypzin
Parzate C
Tritoftorol
Zebtox
ETHYLENE BIS DITHIOCARBAMATES
(EBDC COMPOUNDS)
MANEB, ZINEB, NABAM, AND MANCOZEB
Maneb and zineb are formulated as wettable and flowable powders. Nabarn
is provided as a soluble powder and in water solution. Mancozeb is a coordina-
tion product of zinc ion and maneb. It is formulated as a dust and as wettable
and liquid flowable powders.
Toxicology
These fungicides may cause irritation of the skin, respiratory tract, and eyes.
Both maneb and zineb have apparently been responsible for some cases of chronic
skin disease in occupationally exposed workers, possibly by sensitization.
Although marked adverse effects may follow injection of EBDC compounds
into animals, systemic toxicity by oral and dermal routes is generally low. Nabam
exhibits the greatest toxicity, probably due to its greater water solubility and
absorbability. Maneb is moderately soluble in water, but mancozeb and zineb
are essentially water insoluble. Absorption of the latter fungicides across skin
and mucous membranes is probably very limited. Systemic poisonings of humans
have been extremely rare. However, zineb apparently precipitated an episode of
hemolytic anemia in one worker predisposed by reason of multiple red cell
enzyme deficiencies.4 Maneb exposure has been reported in one person who
developed acute renal failure and was treated with hemodialysis.5 Another person
developed behavioral and neurological symptoms including tonic-clonic seizures
after handling maneb. He recovered uneventfully with supportive care.6
The EBDC compounds are not inhibitors of cholinesterase or of acetalde-
hyde dehydrogenase. They do not induce cholinergic illness or "Antabuse" re-
actions.
Confirmation of Poisoining
No tests for these fungicides or their breakdown products in body fluids
are available.
Treatment
See Treatment for Substituted Benzenes, p. 139.
144 FUNGICIDES
-------
THIOPHTHALIMIDES
Commercial Products
CAPTAN, CAPTAFOL, AND FOLPET
These agents are widely used to protect seed, field crops, and stored pro-
duce. They are formulated as dusts and wettable powders. Captafol is no longer
registered for use in the United States.
Toxicology
All of these fungicides are moderately irritating to the skin, eyes, and
respiratory tract. Dermal sensitization may occur; captafol appears to have been
responsible for several episodes of occupational contact dermatitis.7'8 No systemic
poisonings by thiophthalimides have been reported in humans, although captafol
has been reported to have exacerbated asthma after occupational exposure.9
Laboratory animals given very large doses of captan exhibit hypothermia,
irritability, listlessness, anorexia, hyporeflexia, and oliguria, the latter with
glycosuria and hematuria.
Confirmation of Poisoning
Captan fungicides are metabolized in the body to yield two metabolites
that can be measured in the urine.10
Treatment
See Treatment for Substituted Benzenes, p. 139.
COPPER COMPOUNDS
INORGANIC AND ORGANIC COMPOUNDS
Insoluble compounds are formulated as wettable powders and dusts. Soluble
salts are prepared as aqueous solutions. Some organometallic compounds are
soluble in mineral oils.
A great many commercial copper-containing fungicides are available. Some
are mixtures of copper compounds. Others include lime, other metals, and
other fungicides. Compositions of specific products can usually be provided by
manufacturers or by poison control centers.
Copper-arsenic compounds such as Paris green may still be used in agri-
culture outside the U.S. Toxicity of these compounds is chiefly due to arsenic
content (see Chapter 14, Arsenical Pesticides).
THIOPHTHALIMIDES
captafol*
Crisfolatan
Difolatan
Foltaf
Haipen
Merpafol
Mycodifol
Sanspor
captan
Captaf
Captanex
Merpan
Orthocide
Vondcaptan
folpet
Folpan
Fungitrol II
Phaltan
Thiophal
COPPER COMPOUNDS
Inorganic Copper Compounds
copper acetate
copper ammonium carbonate
copper carbonate, basic
copper hydroxide
copper lime dust
copper oxychloride
copper potassium sulfide
copper silicate
copper sulfate
cupric oxide
cuprous oxide
tribasic
Bordeaux Mixture
Organic Copper Compunds
copper linoleate
copper naphthenate
copper oleate
copper phenyl salicylate
copper quinolinolate
copper resinate
' Discontinued in the U.S.
FUNGICIDES 145
-------
Toxicology
The dust and powder preparations of copper compounds are irritating to the
skin, respiratory tract, and particularly to the eyes. Soluble copper salts (such as
the sulfate and acetate) are corrosive to mucous membranes and the cornea.
Limited solubility and absorption probably account for the generally low sys-
temic toxicity of most compounds. The more absorbable organic copper com-
pounds exhibit the greatest systemic toxicity in laboratory animals. Irritant effects
from occupational exposures to copper-containing fungicides have been fairly
frequent. Most of what is known about mammalian toxicity of copper com-
pounds has come from veterinary toxicology (livestock seem uniquely vulner-
able) and poisonings in humans due to deliberate ingestion of copper sulfate or to
consumption of water or food that had been contained in copper vessels.
Early signs and symptoms of copper poisoning include a metallic taste,
nausea, vomiting, and epigastric pain. In more severe poisonings, the gastrointes-
tinal irritation will worsen with hemetemesis and melanotic stools. Jaundice
and hepatomegaly are common. 11>12Hemolysis can occur, resulting in circula-
tory collapse and shock. Methemoglobinemia has been reported in these
cases.11'13'14 Acute renal failure with oliguria can also occur. Shock is a primary
cause of death early in the course, and renal failure and hepatic failure contrib-
ute to death more than 24 hours after poisoning.15
Treatment
Management of poisonings by ingestion of copper-containing fungicides
depends entirely on the chemical nature of the compound: the strongly ionized
salts present the greatest hazard; the oxides, hydroxides, oxychloride, and
oxysulfate are less likely to cause severe systemic poisoning.
1. Skin decontamination. Dust and powder should be washed from the skin
with soap and water. Flush the eyes free of irritating dust, powder, or solution,
using clean water or saline. If eye or dermal irritation persists, specialized medi-
cal treatment should be obtained. Eye irritation may be severe. See Chapter 2.
2. Anti-corrosive. Give water or milk as soon as possible to dilute the toxicant
and mitigate corrosive action on the mouth, esophagus, and gut.
3. Gastrointestinal decontamination. Vomiting is usually spontaneous in
acute copper ingestion. Further induction of emesis is contraindicated because
the corrosive nature of some copper salts can cause further damage to the
esophagus. Further GI decontamination should be determined on a case-by-
case basis, as outlined in Chapter 2. Gastric lavage may cause further damage.15
Charcoal has not been widely studied in metal poisonings as an effective
adsorbant.
146 FUNGICIDES
-------
Caution: Gastric intubation may pose a serious risk of esophageal perfo-
ration if corrosive action has been severe. In this event, it may be best to avoid
gastric intubation.
4. Intravenous fluids. If indications of systemic illness appear, administer in-
travenous fluids containing glucose and electrolytes. Monitor fluid balance, and
correct blood electrolyte concentrations as needed. If shock develops, give blood
transfusions and vasopressor amines, as required.
5. Hemolysis. Monitor plasma for evidence of hemolysis (free hemoglobin)
and the red cells for methemoglobin. If hemolysis occurs, alkalinize the urine
to about pH 7.5 by adding sodium bicarbonate to the intravenous infusion
fluid. Also, mannitol diuresis may be considered. If methemoglobinemia is se-
vere (> 30%), or the patient is cyanotic, administer methylene blue. The dosage
for adults/child is 1-2 mg/kg/dose, given as a slow IV push over a few minutes,
every 4 hours as needed.15
6. Pain management. Severe pain may require the administration of mor-
phine.
7. Chelating agents. The value of chelating agents in copper poisoning has
not been established.16 However, BAL appears to accelerate copper excretion
and may alleviate illness. D-penicillamine is the treatment for Wilson's disease
due to chronic copper toxicity; however, in the context of severe vomiting
and/or mental status changes from an acute ingestion, BAL would be a more
likely initial choice.13'15 For a recommended schedule of dosage for initial therapy
with BAL and subsequent penicillamine administration, see Chapter 14, Ar-
senical Pesticides.
Commercial Products
ORGANOMERCURY
COMPOUNDS
Methyl Mercury
Compounds
methyl mercury acetate
propionate
quinolinolate
Methoxyethyl Mercury
Compounds
methoxyethyl mercury acetate
MEMA
Panogen
Panogen M
methoxyethyl mercury chloride
Ceresan
Emisan 6
MEMC
Phenyl mercuric Acetate
Agrosan
Setrete
Gallotox
PMAA
Shimmer-ex
Tag HL331
Unisan
8. Hemodialysis. Although hemodialysis is indicated for patients with renal
failure, copper is not effectively removed in the dialysate.11
ORGANOMERCURY COMPOUNDS
METHYL MERCURY AND METHOXYETHYL
MERCURY COMPOUNDS, PHENYLMERCURIC ACETATE
These fungicides have been formulated as aqueous solutions and dusts.
They have been used chiefly as seed protectants. Use of alkyl mercury fungicides
in the United States has been virtually prohibited for several years. Phenyl-
mercuric acetate is no longer permitted to be used in the United States.
FUNGICIDES 147
-------
Toxicology
The mercurial fungicides are among the most toxic pesticides ever
developed, for both chronic and acute hazards. Epidemics of severe, often fatal,
neurologic disease have occurred when indigent residents of less developed
countries consumed methyl mercury-treated grain intended for planting of
crops.17'18 Poisoning has also occurred from eating meat from animals fed
mercury-treated seed.19 Most of what is known of poisoning by organic mercurial
fungicides has come from these occurrences.
Organic mercury compounds are efficiently absorbed across the gut and
possibly across the skin.Volatile organic mercury is readily taken up across the
pulmonary membrane. Methyl mercury is selectively concentrated in the tissue
of the nervous system, and also in red blood cells. Other alkyl mercury com-
pounds are probably distributed similarly. Excretion occurs almost entirely by
way of the bile into the bowel. The residence half-life of methyl mercury in
humans is about 65 days.20 There is significant conversion of organic mercury
to inorganic mercury in the red cell.
Early symptoms of poisoning are metallic taste in the mouth, numbness
and tingling of the digits and face, tremor, headache, fatigue, emotional lability,
and difficulty thinking. Manifestations of more severe poisoning are incoordi-
nation, slurred speech, loss of position sense, hearing loss, constriction of visual
fields, spasticity or rigidity of muscle movements, and deterioration of mental
capacity. Many poisonings caused by ingestion of organic mercurials have ter-
minated fatally, and a large percentage of survivors have suffered severe perma-
nent neurologic damage.17"19
Phenylmercuric acetate is not as extremely toxic as the alkyl mercury com-
pounds. It is not as efficiently absorbed from the gut as methyl mercury21 Phenyl-
mercuric acetate had been used to prevent fungal growth in latex paint. There
have been reports of acrodynia in persons exposed to mercury vapor from use of
interior latex paint. Symptoms include fever, erythema and desquamation of hands
and feet, muscular weakness, leg cramps, and personality changes.22 Phenyl-
mercuric compounds have since been banned from latex paint.20
Confirmation of Poisoning
Mercury content of blood and tissues can be measured by atomic absorp-
tion spectrometry Blood levels of 5 mcg/dL or greater are considered elevated
for acute exposure.21 Special procedures are needed for extraction and mea-
surement of organic mercury compounds specifically.
148 FUNGICIDES
-------
Treatment
Commercial Products
Every possible precaution should be taken to avoid exposure to organic
mercury compounds. Ingestion of an organic mercury compound, even at low
dosage, is life threatening, and management is difficult.Very little can be done
to mitigate neurologic damage caused by organic mercurials.
Persons experiencing symptoms (metallic taste in mouth) after inhalation of
volatile organic mercury compounds (methyl mercury is the most volatile) should
be removed promptly from the contaminated environment and observed closely
for indications of neurologic impairment. Following are the basic steps in man-
agement of poisoning:
1. Skin decontamination. Skin and hair contaminated by mercury-contain-
ing dust or solution should be cleansed with soap and water. Flush contamina-
tion from the eyes with clean water. If irritation persists, specialized medical
care should be obtained. See Chapter 2.
2. Gastrointestinal decontamination. Consider gastrointestinal decontami-
nation as outlined in Chapter 2.
3. Chelation is an essential part of the management of mercury poisoning. For
dosages of specific agents, see Chapter 14, Arsenical Pesticides. Succimer (DMSA)
appears to be the most effective agent available in the United States. Dimerca-
prol (BAL) is contraindicated in these poisonings due to its potential to in-
crease brain levels of mercury20 ED TA is apparently of little value in poisonings
by organic mercury. D-penicillamine is probably useful, is available in the United
States, and has proven effective in reducing the residence half-life of methyl
mercury in poisoned humans.20 2,3-dimercaptopropane-l-sulfonate acid
(DMPS) and N-acetyl-D,L-penicillamine (NAP) are probably also useful but
are not currently approved for use in the United States.
4. Hemodialysis. Extracorporeal hemodialysis and hemoperfusion may be
considered, although experience to date has not been encouraging.
ORGANOTIN
COMPOUNDS
fentin acetate*
Batasan
Brestan
Phenostat-A
Phentinoacetate
Suzu
TPTA
fentin chloride*
Tinmate
fentin hydroxide
Super Tin
Suzu-H
Tubotin
triphenyl tin
* Discontinued in the U.S.
ORGANOTIN COMPOUNDS
These compounds are formulated as wettable and flowable powders for use
mainly as fungicides to control blights on field crops and orchard trees. Fentin
chloride was also prepared as an emulsifiable concentrate for use as a mollusci-
cide (Aquatin 20 EC, discontinued 1995).Tributyltin salts are used as fungi-
cides and antifouling agents on ships. They are somewhat more toxic by the
oral route than triphenyltin, but toxic actions are otherwise probably similar.
FUNGICIDES 149
-------
Commercial Products
CADMIUM
COMPOUNDS
cadmium chloride*
Caddy
cadmium succinate*
Cadminate
cadmium sulfate*
Cad-Trete
Crag Turf Fungicide
Kromad
Miller 531
* Discontinued in the U.S.
Toxicology
These agents are irritating to the eyes, respiratory tract, and skin. They are
probably absorbed to a limited extent by the skin and gastrointestinal tract. Manifes-
tations of toxicity are due principally to effects on the central nervous system:
headache, nausea, vomiting, dizziness, and sometimes convulsions and loss of
consciousness. Photophobia and mental disturbances occur. Epigastric pain is
reported, even in poisoning caused by inhalation. Elevation of blood sugar, suffi-
cient to cause glycosuria, has occurred in some cases. The phenyltin fungicides
are less toxic than ethyltin compounds, which have caused cerebral edema,
neurologic damage, and death in severely poisoned individuals who were
exposed dermally to a medicinal compound of this type.23 No deaths and very
few poisonings have been reported as a result of occupational exposures to phenyltin
compounds.
Treatment
1. Skin decontamination. Skin contamination should be removed by wash-
ing with soap and water. Flush contaminants from the eyes with clean water or
saline. If irritation persists, specialized medical treatment should be obtained.
See Chapter 2.
2. Gastrointestinal decontamination. If large amounts of phenyltin com-
pound have been ingested in the past hour, measures may be taken to decon-
taminate the gastrointestinal tract, as outlined in Chapter 2.
3. Chelating agents. Neither BAL, penicillamine, nor other chelating agents
have been effective in lowering tissue stores of organotin compounds in ex-
perimental animals.
CADMIUM COMPOUNDS
Cadmium salts have been used to treat fungal diseases affecting turf and the
bark of orchard trees. They were formulated as solutions and emulsions. Miller
531 and Crag Turf Fungicide 531 were complexes of cadmium, calcium, cop-
per, chromium, and zinc oxides.They are now marketed as a generic fungicide.
Kromad is a mixture of cadmium sebacate, potassium chromate, and thiram.
Cad-Trete is a mixture of cadmium chloride and thiram. All cadmium fungi-
cides in the U.S. have been discontinued.
150 FUNGICIDES
-------
Toxicology
Cadmium salts and oxides are very irritating to the respiratory and gas-
trointestinal tracts. Inhaled cadmium dust or fumes can cause respiratory toxic-
ity after a latency period of several hours, including a mild, self-limited illness
of fever, cough, malaise, headaches, and abdominal pain, similar to metal fume
fever. A more severe form of toxicity includes chemical pneumonitis, and is
associated with labored breathing, chest pain, and a sometimes fatal hemor-
rhagic pulmonary edema.24'25 Symptoms may persist for weeks.
Ingested cadmium causes nausea, vomiting, diarrhea, abdominal pain, and
tenesmus. Relatively small inhaled and ingested doses produce serious symp-
toms. Protracted absorption of cadmium has led to renal damage (proteinuria
and azotemia), anemia, liver injury (jaundice), and defective bone structure
(pathologic fractures) in chronically exposed persons. Prolonged inhalation of
cadmium dust has contributed to chronic obstructive pulmonary disease.26
Confirmation of Poisoning
Cadmium can be measured in body fluids by appropriate extraction, fol-
lowed by flame absorption spectrometry It is reported that blood cadmium
concentrations tend to correlate with acute exposure and urine levels tend to
reflect total body burden. Blood levels exceeding 5 mcg/dL suggest excessive
exposure.25 Urinary excretion in excess of 100 meg per day suggests an unusu-
ally high body burden.
Treatment
1. Skin decontamination. Skin contamination should be removed by wash-
ing with soap and water. Flush contamination from the eyes with copious
amounts of clean water or saline. If irritation persists, specialized medical treat-
ment should be obtained. See Chapter 2.
2. Pulmonary edema. Respiratory irritation resulting from inhalation of
small amounts of cadmium dust may resolve spontaneously, requiring no
treatment. More severe reactions, including pulmonary edema and pneumonitis,
may require aggressive measures, including positive pressure mechanical
pulmonary ventilation, monitoring of blood gases, administration of diuretics,
steroid medications, and antibiotics.25 Codeine sulfate may be needed to control
cough and chest pain.
3. Gastrointestinal decontamination. The irritant action of ingested cadmium
products on the gastrointestinal tract is so strong that spontaneous vomiting
and diarrhea often eliminate nearly all unabsorbed cadmium from the gut. If
FUNGICIDES 151
-------
Commercial Products
MISCELLANEOUS
ORGANIC FUNGICIDES
anilazine*
Dyrene
benomyl
Benex
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.
retention of some cadmium in the lower GI tract is suspected, further
gastrointestinal decontamination may be considered, as outlined in Chapter 2.
4. Intravenous fluids may be required to overcome dehydration caused by
vomiting and diarrhea. Also, fluids limit cadmium toxicity affecting the kidneys
and liver. However, great care must be taken to monitor fluid balance and
blood electrolyte concentrations, so that failing renal function does not lead to
fluid overload.
5. Chelation therapy with calcium disodium EDTA may be considered for
acute poisoning, depending on measured cadmium in blood and urine, and the
status of renal function. Its therapeutic value in cadmium poisoning has not
been established, and use of the agent carries the risk that unduly rapid transfer
of cadmium to the kidney may precipitate renal failure. Urine protein and
blood urea nitrogen and creatinine should be carefully monitored during therapy.
The dosage should be 75 mg/kg/day in three to six divided doses for 5 days.
The total dose for the 5-day course should not exceed 500 mg/kg.27 Succimer
(DMSA) has also been used in this poisoning, but has not been demonstrated
to be efficacious.
6. Contraindications: Dimercaprol (BAL) is not recommended for treatment
of cadmium poisoning, chiefly because of the risk of renal injury by mobilized
cadmium.
7. Liver function. Monitor urine content of protein and cells regularly, and
perform liver function tests for indications of injury to these organs.
MISCELLANEOUS ORGANIC FUNGICIDES
Some modern organic fungicides are widely used. Reports of adverse ef-
fects on humans are few. Some of the known properties of these agents are
listed below.
Anilazine is supplied as wettable and flowable powders. Used on veg-
etables, cereals, coffee, ornamentals, and turf. This product has caused skin irri-
tation in exposed workers. Acute oral and dermal toxicity in laboratory animals
is low. Human systemic poisonings have not been reported.
Benomyl is a synthetic organic fungistat having little or no acute toxic
effect in mammals. No systemic poisonings have been reported in humans.
Although the molecule contains a carbamate grouping, benomyl is not a cho-
linesterase inhibitor. It is poorly absorbed across skin; whatever is absorbed is
promptly metabolized and excreted.
Skin injuries to exposed individuals have occurred, and dermal sensitiza-
tion has been found among agricultural workers exposed to foliage residues.
152 FUNGICIDES
-------
Cycloheximide is formulated as wettable powder, sometimes combined
with other fungicides. Cycloheximide is a product of fungal culture, effective
against fungal diseases of ornamentals and grasses. It is selectively toxic to rats,
much less toxic to dogs and monkeys. No human poisonings have been reported.
Animals given toxic doses exhibit salivation, bloody diarrhea, tremors, and
excitement, leading to coma and death due to cardiovascular collapse.
Hydrocortisone increases the rate of survival of deliberately poisoned rats.
Atropine, epinephrine, methoxyphenamine, and hexamethonium all relieved
the symptoms of poisoning, but did not improve survival.
Dodine is formulated as a wettable powder. It is commonly applied to
berries, nuts, peaches, apples, pears, and to trees afflicted with leaf blight. Dodine
is a cationic surfactant with antifungal activity. It is absorbed across the skin and
is irritating to skin, eyes, and gastrointestinal tract. Acute oral and dermal toxic-
ity in laboratory animals is moderate. Poisonings in humans have not been
reported. Based on animal studies, ingestion would probably cause nausea, vom-
iting, and diarrhea.
Iprodione is supplied as wettable powder and other formulations. It is
used on berries, grapes, fruit, vegetables, grasses, and ornamentals, and as a seed
dressing. Iprodione exhibits low acute oral and dermal toxicity in laboratory
animals. No human poisonings have been reported.
Metalaxyl is supplied as emulsifiable and flowable concentrates. It is used
to control soil-borne fungal diseases on fruit trees, cotton, hops, soybeans, pea-
nuts, ornamentals and grasses. Also used as seed dressing. Metalaxyl exhibits low
acute oral and dermal toxicity in laboratory animals. No human poisonings
have been reported.
Etridiazole is supplied as wettable powder and granules for application to
soil as a fungicide and nitrification inhibitor. Contact may result in irritation of
skin and eyes. Systemic toxicity is low. Human poisonings have not been re-
ported.
Thiabendazole is widely used as an agricultural fungicide, but most ex-
perience with its toxicology in humans has come from medicinal use against
intestinal parasites. Oral doses administered for this purpose are far greater than
those likely to be absorbed in the course of occupational exposure. Thiabenda-
zole is rapidly metabolized and excreted in the urine, mostly as a conjugated
hydroxy-metabolite. Symptoms and signs that sometimes follow ingestion are:
dizziness, nausea, vomiting, diarrhea, epigastric distress, lethargy, fever, flushing,
chills, rash and local edema, headache, tinnitus, paresthesia, and hypotension.
Blood enzyme tests may indicate liver injury. Persons with liver and kidney
disease may be unusually vulnerable to toxic effects. Adverse effects from use of
thiabendazole as a fungicide have not been reported.
Triadimefon is supplied as wettable powder, emulsifiable concentrate, sus-
pension concentrate, paste, and dry flowable powder. Used on fruit, cereals,
vegetables, coffee, ornamentals, sugarcane, pineapple, and turf, triadimefon ex-
hibits moderate acute oral toxicity in laboratory animals, but dermal toxicity is
FUNGICIDES 153
-------
low. It causes irritation if eyes are contaminated. Triadimefon is absorbed across
the skin. Overexposures of humans are said to have resulted in hyperactivity
followed by sedation.
Triforine is supplied as emulsifiable concentrate and wettable powder.
Used on berries, fruit, vegetables, and ornamentals, triforine exhibits low acute
oral and dermal toxicity in laboratory animals. Mammals rapidly excrete it
chiefly as a urinary metabolite. No human poisonings have been reported.
Confirmation of Poisoining
There are no generally available laboratory tests for these organic fungi-
cides or their metabolites in body fluids.
Treatment
See Treatment for Substituted Benzenes, p. 139.
References
1. Dannaker CJ, Maibach HI, and O'MaUey M. Contact urticaria and anaphylaxis to the fun-
gicide chlorothalonil. Cutis 1993;52:3120-5.
2. Peters HA, Gocmen A, Cripps DJ, et al. Epidemiology of hexachlorobenzene-induced por-
phyria in Turkey: Clinical and laboratory follow-up after 25 years. Arch Neural 1992;39:744-9.
3. Dalvi RR. Toxicology of 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, andTiberin P. Acute intoxication due to exposure to maneb and zineb:
A case with behavioral and central nervous system changes. Scand J Work Environ Health
1983;9:47-51.
7. Peluso AM.Tardio M, Adamo F, et al. Multiple sensitization due to bis-dithiocarbamate and
thiophthalimide pesticides. Contact Dermatitis 1991;25:327.
8. Vilaplana J and Romaguera C. Captan, a rare contact sensitizer in hairdressing. Contact Der-
matitis 1993;29:107.
9. Royce S, Wald P, Sheppard D, et al. Occupational asthma in a pesticides manufacturing
worker. Chest 1993;103:295-6.
10. Krieger RI and Thongsinthusak T Captan metabolism in humans yields two biomarkers,
tetrahydrophthalimide (THPI) and thiazolidine-2-thione-4-carboxylic acid (TTCA) in urine.
Drug Chem Toxicol 1993;16:207-25.
154 FUNGICIDES
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11. Agarwal SK.Tiwari SC, and Dash SC. Spectrum of poisoning requiring haemodialysis in a
tertiary care hospital in India. Int ]Artif Organs 1993;16:20-3.
12. Lament DL and Duflou JALC. Copper sulfate: Not a harmless chemical. Am JForensic Med
PatM1988;9:226-7.
13. Chugh KS, Singhal PC, and Sharma BK. Methemoglobinemia in acute copper sulfate poi-
soning. Ann Intern Med 1975;82:226-9.
14. Jantsch W, Kulig K, and Rumack BH. Massive copper sulfate ingestion resulting in hepato-
toxicity. ClinToxicol 1984-85;22:585-8.
15. POISINDEXฎ: Copper poisoning. Englewood, CO: Micromedex, 1998.
16. Hantson P, Lievens M, and Mahieu P. Accidental ingestion of a zinc and copper sulfate
preparation. Clin Toxicol 1996;34:725-30.
17. Bakir F, Rustam H.Tikritis S, et al. Clinical and epidemiological aspects of methylmercury
poisoning. Postgrad Med] 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]Med 1971;284:1014-5.
20. Clarkson TW. Mercury An element of mystery. New Engl ] 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. AndoY, Shibata E.Tsuchiyama F, et al. Elevated urinary cadmium concentrations in a patient
with acute cadmium pneumonitis. ScandJWork Environ Health 1996;22:150-3.
26. Hendrick DJ. Occupational and chronic obstructive pulmonary disease (COPD). Thorax
1996;51:947-55.
27. Klaassen CD. Heavy metals and heavy metal antagonists. In: Gilman AG, RallTW, Niew AS,
et al (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics, 3rd ed. New
York: Pergamon Press, 1990, pp. 1605-6.
FUNGICIDES 155
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CHAPTER 16
HIGHLIGHTS
Easily absorbed in lung, gut,
skin
Signs and Symptoms:
Highly variable based on
agent
Many are irritants
Carbon disulfide,
chloroform, hydrogen
cyanide, and naphthalene
may have serious CMS
effects
Methyl bromide and
aluminum phosphide
(phosphine gas) cause
pulmonary edema
Hydrogen cyanide causes
severe hypoxia without
cyanosis in early stages
Treatment:
Skin and eye
decontamination
Oxygen and diuresis for
pulmonary edema
Specific measures needed
for various agents
Contraindicated:
Ipecac should not be used
in cyanide poisoning
Fumigants
Fumigants have remarkable capacities for diffusion, a property essential to their
function. Some readily penetrate rubber and neoprene personal protective gear,
as well as human skin. They are rapidly absorbed across the pulmonary mem-
brane, gut, and skin. Special adsorbents are required in respirator canisters to
protect exposed workers from airborne fumigant gases. Even these may not
provide complete protection when air concentrations of fumigants are high.
The packaging and formulation of fumigants are complex. Fumigants which
are gases at room temperature (methyl bromide, ethylene oxide, sulfur dioxide,
hydrogen cyanide, sulfuryl fluoride) are provided in compressed gas cylinders. Liq-
uids are marketed in cans or drums. Solids which sublime, such as naphthalene,
must be packaged so as to prevent significant contact with air before they are used.
Mixtures of fumigants have several advantages. Carbon tetrachloride re-
duces the explosiveness of carbon disulfide and acrylonitrile. Chloropicrin, having
a strong odor and irritant effect, is often added as a "warning agent" to other
liquid fumigants.
Liquid halocarbons and carbon disulfide evaporate into the air while naph-
thalene sublimes. Paraformaldehyde slowly depolymerizes to formaldehyde.
Aluminum phosphide slowly reacts with water vapor in the air to liberate phos-
phine, an extremely toxic gas. Metam sodium, also a fumigant, is covered under
thiocarbamates in Chapter 15, Fungicides.
(in alphabetical order)
Acrolein (acrylaldehyde) is an extremely irritating gas used as a fumigant
and an aquatic herbicide. The vapor causes lacrimation and upper respiratory
tract irritation, which may lead to laryngeal edema, bronchospasm, and delayed
pulmonary edema. The consequences of ingestion are essentially the same as
those that follow ingestion of formaldehyde. Contact with the skin may cause
blistering.
Acrylonitrile is biotransformed in the body to hydrogen cyanide. Toxic-
ity and mechanisms of poisoning are essentially the same as for cyanide (see
under hydrogen cyanide below), except that acrylonitrile is irritating to the
eyes and to the upper respiratory tract.
Carbon disulfide vapor is only moderately irritating to upper respiratory
membranes, but it has an offensive "rotten cabbage" odor. Acute toxicity is due
156 FUMIGANTS
-------
chiefly to effects on the central nervous system. Inhalation of high concentra-
tions for short periods has caused headache, dizziness, nausea, hallucinations,
delirium, progressive paralysis, and death from respiratory failure. More pro-
longed exposure to lesser amounts has lead to blindness, deafness, paresthesia,
painful neuropathy, and paralysis. Carbon disulfide is a potent skin irritant,
often causing severe burns. Long-term occupational exposures have been shown to
accelerate atherosclerosis,leading to ischemic myocardiopathy, polyneuropathy,
and gastrointestinal dysfunction.1 Toxic damage to the liver and kidneys may
result in severe functional deficits of these organs. Reproductive failure has
been noted.
Carbon tetrachloride is less toxic than chloroform as a central nervous
system depressant, but is much more severely hepatotoxic, particularly follow-
ing ingestion. Liver cell damage is apparently due to free radicals generated in
the process of initial dechlorination.2 Cardiac arrhythmias, progressing to
fibrillation, may follow inhalation of high concentrations of carbon tetra-
chloride or ingestion of the liquid. Kidney injury also occurs sometimes with
minimal hepatic toxicity.The kidney injury may be manifested by acute tubular
necrosis or by azotemia and general renal failure. Even topical exposure has
resulted in acute renal toxicity.3
Chloroform has an agreeable sweet odor and is only slightly irritating to
the respiratory tract. It is well absorbed from the lungs and is also absorbed
from the skin and gastrointestinal tract. It is a powerful central nervous system
depressant (in fact, an anesthetic).4 Inhalation of toxic concentrations in air
leads to dizziness, loss of sensation and motor power, and then unconsciousness.
Inhalation of large amounts causes cardiac arrhythmias, sometimes progressing
to ventricular fibrillation. Large absorbed doses damage the functional cells of
the liver and kidney. Ingestion is more likely to cause serious liver and kidney
injury than is inhalation of the vapor.
Chloropicrin is severely irritating to the upper respiratory tract, eyes, and
skin. Inhalation of an irritant concentration sometimes leads to vomiting. In-
gestion could be expected to cause a corrosive gastroenteritis.
Dibromochloropropane is irritating to skin, eyes, and the respiratory
tract. Eye damage has resulted from repeated exposure to the vapors. When
absorbed, it causes headache, nausea, vomiting, ataxia, and slurred speech. Liver
and kidney damage are prominent features of acute poisoning. Chronic
exposure to relatively low concentrations has led to temporary or permanent
sterility of workers in a manufacturing plant, by causing diffuse necrosis of
seminiferous tubule cells. Because it is much less odiferous than ethylene
dibromide, exposure of workers to toxic concentrations ofDBCP is more likely.
Its use has been cancelled in the U.S.
Dichloropropene and dichloropropane are strongly irritating to the
skin, eyes, and respiratory tract. Bronchospasm may result from inhalation of
high concentrations. Liver, kidney, and cardiac toxicity are seen in animals, but
there are limited data in humans. It appears that risk of such toxicity is relatively
low for humans except via ingestion of large quantities.
Commercial Products
HALOCARBONS
carbon tetrachloride*
chloroform*
trichloromethane
chloropicrin
Aquinite
Dojyopicrin
Dolochlor
Larvacide
Pic-Clor
dibromochloropropane*
Nemafume
Nemanax
Nemaset
1,2-dichloropropane*
propylene dichloride
1,3-dichloropropene
D-D92
Telone II Soil Fumigant
ethylene dibromide*
Bromofume
Celmide
dibromoethane
E-D-Bee
EDB
Kopfume
Nephis
ethylene dichloride*
dichloroethane
EDC
methyl bromide
Celfume
Kayafume
Meth-0-Gas
MeBr
Sobrom 98
methylene chloride*
paradichlorobenzene
HYDROCARBONS
naphthalene
NITROGEN COMPOUNDS
acrylonitrile*
hydrogen cyanide*
hydrocyanic acid
prussic acid
(Continued on the next page)
FUMIGANTS 157
-------
Commercial Products
(Continued)
OXIDES AND ALDEHYDES
acrolein
Magnacide B
Magnacide H
1,2-epoxyethane
ethylene oxide
ETO
formaldehyde
oxirane
paraformaldehyde
PHOSPHORUS COMPOUNDS
phosphine (liberated from
aluminum phosphide or
magnesium phosphide)
Ag toxin
Alphos
Fumex
Fumitoxin
Phostoxin
Quickfos
Sanifume
Shaphos
others
SULFUR COMPOUNDS
carbon disulfide*
sulfur dioxide
sulfuryl fluoride
Vikane
* Discontinued in the U.S.
Ethylene dibromide is a severe irritant to skin, eyes, and respiratory tract.
The liquid causes blistering and erosion of skin, and is corrosive to the eyes.
Once absorbed, it may cause pulmonary edema and central nervous system
depression. Damage to testicular tissue has occurred in animals.5 Long-term
exposure may have some damaging effect on testicular tissue. Persons poisoned
by ingestion have suffered chemical gastroenteritis, liver necrosis, and renal tu-
bular damage. Death is usually due to respiratory or circulatory failure. A pow-
erful disagreeable odor is advantageous in warning occupationally exposed
workers of the presence of this gas.
Ethylene dichloride is moderately irritating to the eyes and respiratory
tract. Respiratory symptoms may have a delayed onset. It depresses the central
nervous system, induces cardiac arrhythmias, and damages the liver and kidney,
in much the same way as carbon tetrachloride. Symptoms and signs of poison-
ing include headache, nausea, vomiting, dizziness, diarrhea, hypotension, cy-
anosis, and unconsciousness.
Ethylene oxide and propylene oxide are irritants to all tissues they
contact.Aqueous solutions of ethylene oxide cause blistering and erosion of the
affected skin. The area of skin may thereafter be sensitized to the fumigant.
Inhalation of high concentrations is likely to cause pulmonary edema and car-
diac arrhythmias. Headache, nausea, vomiting, weakness, and a persistent cough
are common early manifestations of acute poisoning. Coughing of bloody, frothy
sputum is characteristic of pulmonary edema.
Airborne formaldehyde is irritating to the eyes and to membranes of the
upper respiratory tract. In some individuals, it is a potent sensitizer, causing aller-
gic dermatitis. In addition, it has been associated with asthma-like symptoms,
though there remains some controversy as to whether these represent true aller-
gic asthma caused by formaldehyde.6'7'8 High air concentrations may cause laryn-
geal edema, asthma, or tracheobronchitis, but apparently not pulmonary edema.
Aqueous solutions in contact with the skin cause hardening and roughness, due
to superficial coagulation of the keratin layer. Ingested formaldehyde attacks the
membrane lining of the stomach and intestine, causing necrosis and ulceration.
Absorbed formaldehyde is rapidly converted to formic acid. The latter is partly
responsible for the metabolic acidosis that is characteristic of formaldehyde poi-
soning. Circulatory collapse and renal failure may follow the devastating effects of
ingested formaldehyde on the gut, leading to death. Paraformaldehyde is a poly-
mer which slowly releases formaldehyde into the air. Toxicity is somewhat less
than that of formaldehyde, because of the slow evolution of gas.
Hydrogen cyanide gas causes poisoning by inactivating cytochrome oxi-
dase, the final enzyme essential to mammalian cellular respiration. The patient
will have signs of severe hypoxia, however, and in some cases may not appear
cyanotic. This is due to the failure of hemoglobin reduction in the face of loss
of cellular respiration. This will result in a pink or red color to the skin and
arteriolization of retinal veins. In addition to the suggestive physical findings,
158 FUMIGANTS
-------
one may also find an unusually high pO2 on a venous blood gas.9 Cyanosis is a
late sign and indicates circulatory collapse.
The cells of the brain appear to be the most vulnerable to cyanide action.
Presenting signs are nonspecific and can be found with many poisonings.
Unconsciousness and death may occur immediately following inhalation of a
high cyanide concentration, respiratory failure being the principal mechanism.
Metabolic acidosis is another common presenting sign. Lesser exposures cause
a constriction and numbness in the throat, stiffness of the jaw, salivation, nausea,
vomiting, lightheadedness, and apprehension. Worsening of the poisoning
is manifest as violent tonic or clonic convulsions. Fixed, dilated pupils,
bradycardia, and irregular gasping respiration (or apnea) are typical of profound
poisoning. The heart often continues to beat after breathing has stopped.9'10
A bitter almond odor to the breath or vomitus may be a clue to poisoning, but
not all individuals are able to detect this odor.9
Methyl bromide is colorless and nearly odorless, but is severely irritating
to the lower respiratory tract, sometimes inducing pulmonary edema, hemor-
rhage, or a confluent pneumonia. The onset of respiratory distress may be
delayed 4-12 hours after exposure. It is a central nervous system depressant, but
may also cause convulsions. Early symptoms of acute poisoning include
headache, dizziness, nausea, vomiting, tremor, slurred speech, and ataxia. The
more severe cases of poisoning exhibit myoclonic and generalized tonic clonic
seizures, which are sometimes refractory to initial therapy. Residual neurologi-
cal deficits including myoclonic seizures, ataxia, muscle weakness, tremors,
behavioral disturbances, and diminished reflexes may persist in more severely
poisoned patients.11'12 If liquid methyl bromide contacts the skin, severe
burning, itching, and blister formation occur. Skin necrosis may be deep and
extensive.
Methylene chloride is one of the less toxic halocarbons. It is absorbed by
inhalation and to a limited extent across the skin. Exposure to high concentra-
tions may cause central nervous system depression, manifested as fatigue,
weakness, and drowsiness. Some absorbed methylene chloride is degraded to
carbon monoxide in humans, yielding increased blood concentrations of
carboxyhemoglobin. However, concentrations are rarely high enough to cause
symptoms of carbon monoxide poisoning. Ingestion has caused death from
gastrointestinal hemorrhage, severe liver damage, coma, shock, metabolic
acidosis, and renal injury. In laboratory animals, extraordinary dosage has caused
irritability, tremor, and narcosis, leading to death. When heated to that point of
decomposition, one of the products is the highly toxic phosgene gas that has
caused a significant acute pneumonitis.13
Naphthalene is a solid white hydrocarbon long used in ball, flake, or cake
form as a moth repellent. It sublimes slowly. The vapor has a sharp, pungent odor
that is irritating to the eyes and upper respiratory tract. Inhalation of high con-
centrations causes headache, dizziness, nausea, and vomiting. Intensive prolonged
inhalation exposure, or ingestion or dermal exposure (from contact with heavily
FUMIGANTS 159
-------
treated fabric) may cause hemolysis, particularly in persons afflicted with glu-
cose -6-phosphate dehydrogenase deficiency14 The inheritance of glucose-6-
phosphate dehydrogenase (G-6-PD) deficiency is by a sex-linked gene with
intermediate dominance. For this reason it is most commonly expressed in
heterozygous males. However, homozygous females, who are far less common,
will have a similar expression. Heterozygous females have only a mild depres-
sion of this enzyme. This illness is most common in non-white African and
African-American ethnic groups. It is also seen in some Mediterranean ethnic
populations.
It is actually the metabolites of naphthalene that are responsible for the hemoly-
sis.15 Secondary renal tubular damage may ensue from the naphthol and from the
products of hemolysis. Convulsions and coma may occur, particularly in children.
In infants, high levels of hemoglobin, methemoglobin, and bilirubin in the plasma
may lead to encephalopathy Kernicterus has been specifically described as a com-
plication of exposure to naphthalene with severe hemolysis and resulting hyper-
bilirubinemia. Some individuals exhibit dermal sensitivity to naphthalene.
Paradichlorobenzene is solid at room temperature, and is now widely
used as a moth repellent, air freshener, and deodorizer in homes and in public
facilities. The vapor is only mildly irritating to the nose and eyes. Liver injury
and tremor may occur following ingestion of large amounts. Although acci-
dental ingestions, especially by children, have been fairly common, symptom-
atic human poisonings have been rare. Other stereoisomers of dichlorobenzene
are more toxic than the para-isomer.
Phosphine gas is extremely irritating to the respiratory tract. It also pro-
duces severe systemic toxicity It is used as a fumigant by placing solid aluminum
phosphide (phostoxin) near produce or in other storage spaces. Through hy-
drolysis, phosphine gas is slowly released. Most severe acute exposures have in-
volved ingestion of the solid aluminum phosphide, which is rapidly converted to
phosphine by acid hydrolysis in the stomach. Poisoning due to ingestion carries a
high mortality rate (50 to 90%).16>17 Mechanisms of toxicity are not well under-
stood. Extracellular magnesium levels have been found to be slightly elevated,
suggesting a depletion of intracellular magnesium from myocardial damage.18
Poisonings had become quite frequent during the late 1980s and early
1990s in some parts of India.16'17 The principal manifestations of poisoning are
fatigue, nausea, headache, dizziness, thirst, cough, shortness of breath, tachycar-
dia, chest tightness, paresthesia, and jaundice. Cardiogenic shock is present in
more severe cases. Pulmonary edema is a common cause of death. In other
fatalities, ventricular arrythmias, conduction disturbances, and asystole devel-
oped.16'19 Odor is said to resemble that of decaying fish.
Sulfur dioxide is a highly irritant gas, so disagreeable that persons inhal-
ing it are usually prompted to seek uncontaminated air as soon as possible.
However, laryngospasm and pulmonary edema have occurred, occasionally lead-
ing to severe respiratory distress and death. It is sometimes a cause of reactive
airways disease in occupationally exposed persons.
160 FUMIGANTS
-------
Sulfuryl fluoride has been used extensively for structural fumigation.
Although use experience has generally been good, some fatalities have oc-
curred when fumigated buildings have been prematurely reentered by unpro-
tected individuals.20 Since this material is heavier than air, fatal hypoxia may
follow early reentry. Manifestations of poisoning have been nose, eye, and throat
irritation, weakness, nausea, vomiting, dyspnea, cough, restlessness, muscle twitch-
ing, and seizures. Renal injury may induce proteinuria and azotemia.
Confirmation of Poisoning
There are no practical tests for absorbed alkyl oxides, aldehydes, or
phosphine that would be helpful in diagnosis of poisoning.
Carbon disulfide can be measured in urine by gas chromatography, but
the test is not generally available.
Cyanide ion from cyanide itself or acrylonitrile can be measured in
whole blood and urine by an ion-specific electrode or by colorimetry Symp-
toms of toxicity may appear at blood levels above 0.10 mg per liter.10 Urine
cyanide is usually less than 0.30 mg per liter in nonsmokers,but as much as 0.80
mg per liter in smokers. Thiocyanate, the metabolite of cyanide, can also be
measured in blood and urine. It is elevated at blood levels exceeding 12 mg per
liter.10 Urine thiocyanate is usually less than 4 mg per liter in nonsmokers, but
may be as high as 17 mg per liter in smokers.
Methyl bromide yields inorganic bromide in the body. Methyl bromide
itself has a short half-life and is usually not detectable after 24 hours.The bromide
anion is slowly excreted in the urine (half-life about 10 days), and is the preferred
method of serum measurement.11 The serum from persons having no excep-
tional exposure to bromide usually contains less than 1 mg bromide ion per 100
mL.The possible contributions of medicinal bromides to elevated blood content
and urinary excretion must be considered, but if methyl bromide is the exclusive
source, serum bromide exceeding 6 mg per 100 mL probably means some ab-
sorption, and 15 mg per 100 mL is consistent with symptoms of acute poisoning.
Inorganic bromide is considerably less toxic than methyl bromide; serum con-
centrations in excess of 150 mg per 100 mL occur commonly in persons taking
inorganic bromide medications. In some European countries, blood bromide
concentrations are monitored routinely in workers exposed to methyl bromide.
Blood levels over 3 mg per 100 mL are considered a warning that personal pro-
tective measures must be improved. A bromide concentration over 5 mg per 100
mL requires that the worker be removed from the fumigant-contaminated envi-
ronment until blood concentrations decline to less than 3 mg per 100 mL.
Methylene chloride is converted to carbon monoxide in the body, gener-
ating carboxyhemoglobinemia, which can be measured by clinical laboratories.
Naphthalene is converted mainly to alpha naphthol in the body and promptly
excreted in conjugated form in the urine. Alpha naphthol can be measured by gas
FUMIGANTS 161
-------
chromatography. Many halocarbons can be measured in blood by gas chromato-
graphic methods. Some can be measured in the expired air as well.
Paradichlorobenzene is metabolized mainly to 2,5-dichlorophenol, which
is conjugated and excreted in the urine. This product can be measured chro-
matographically
A serum fluoride concentration of 0.5 mg per liter was measured in one
fatality from sulfuryl fluoride fumigation. Serum fluoride in persons not
exceptionally exposed rarely exceeds 0.1 mg per liter.
Large industrial concerns sometimes monitor human absorption of
halocarbons by analysis of expired air. Similar technology is available in some
departments of anesthesiology. These analyses are rarely needed to identify the
offending toxicant, because this is known from the exposure history. In managing
difficult cases of poisoning, however, it may be helpful to monitor breath concen-
trations of toxic gas to evaluate disposition of the fumigant. Testing of the urine
for protein and red cells is needed to detect renal injury. Free hemoglobin in
urine most likely reflects hemolysis, as from naphthalene. Elevations of alkaline
phosphatase, lactate dehydrogenase (LDH), serum GGT,ALT, AST, and certain
other enzymes are sensitive indices of insult to liver cells. More severe damage
increases plasma concentrations of bilirubin. The chest x-ray may be used to
confirm the occurrence of pulmonary edema. Electromyography may be useful
in evaluating peripheral nerve injury. Sperm counts may be appropriate for workers
exposed to dibromochloropropane and ethylene dibromide.
Some occupational health agencies now urge periodic neurologic and
neuropsychologic testing of workers heavily exposed to fumigants and solvents
to detect injury to the nervous system as early as possible. This would be par-
ticularly desirable in the case of exposures to such agents as methyl bromide
and carbon disulfide which have well-documented chronic neurotoxic effects.
Treatment
1. Skin decontamination. Flush contaminating fumigants from the skin and
eyes with copious amounts of water or saline for at least 15 minutes. Some
fumigants are corrosive to the cornea and may cause blindness. Specialized
medical treatment should be obtained promptly following decontamination.
Skin contamination may cause blistering and deep chemical burns. Absorption
of some fumigants across the skin may be sufficient to cause systemic poisoning
in the absence of fumigant inhalation. For all these reasons, decontamination of
eyes and skin must be immediate and thorough. See Chapter 2.
2. Physical placement. Remove victims of fumigant inhalation to fresh air
immediately. Even though initial symptoms and signs are mild, keep the victim
quiet, in a semi-reclining position. Minimum physical activity limits the likeli-
hood of pulmonary edema.
162 FUMIGANTS
-------
3. Respiration. If victim is not breathing, clear the airway of secretions and
resuscitate with positive pressure oxygen apparatus. If this is not available, use
chest compression to sustain respiration. If victim is pulseless, employ cardiac
resuscitation.
4. Pulmonary edema. If pulmonary edema is evident, there are several mea-
sures available to sustain life. Medical judgment must be relied upon, however,
in the management of each case. The following procedures are generally
recommended:
Put the victim in a sitting position with a backrest.
Use intermittent and/or continuous positive pressure oxygen to
relieve hypoxemia. (Do not give oxygen at greater concentrations
or longer periods than necessary, because it may exaggerate the fu-
migant injury to lung tissue. Monitor arterial pO2.)
Slowly administer furosemide, 40 mg, intravenously (0.5-1 mg/kg
in children up to 20 mg), to reduce venous load by inducing diure-
sis. Consult package insert for additional directions and warnings.
Some patients may benefit from careful administration of anxiolytic drugs.
Whenever possible, such patients should be managed by intensivists in an in-
tensive care center. Limit victim's physical activity for at least 4 weeks. Severe
physical weakness usually indicates persistent pulmonary injury. Serial pulmo-
nary function testing may be useful in assessing recovery.
5. Shock. Combat shock by placing victim in the Trendelenburg position and
administering plasma, whole blood, and/or electrolyte and glucose solutions
intravenously, with great care, to avoid pulmonary edema. Central venous pres-
sure should be monitored continuously. Vasopressor amines must be given with
great caution, because of the irritability of the myocardium.
6. Control convulsions. Seizures are most likely to occur in poisonings by
methyl bromide, hydrogen cyanide, acrylonitrile, phosphine, and carbon disul-
fide. See Chapter 2 for seizure management. In some cases of methyl bromide,
seizures have been refractory to benzodiazepines and diphenylhydantoin, and
the authors resorted to anesthesia using thiopental.11
7. Gastrointestinal decontamination. If a fumigant liquid or solid has been
ingested less than an hour prior to treatment, consider gastric emptying, fol-
lowed by activated charcoal, as suggested in Chapter 2.
8. Fluid balance should be monitored, and urine sediment should be checked
regularly for indications of tubular injury. Measure serum alkaline phosphatase,
LDH, ALT, AST, and bilirubin to assess liver injury.
FUMIGANTS 163
-------
9. Extracorporeal hemodialysis may be needed to regulate extracellular
fluid composition if renal failure supervenes. It is probably not very effective in
removing lipophilic fumigant compounds from blood, but it is, of course, effec-
tive in controlling extracellular fluid composition if renal failure occurs.
10. Specific fumigants. Certain specific measures are recommended in poi-
sonings by particular fumigants (carbon disulfide, carbon tetrachloride, naph-
thalene, phosphine gas, and hydrogen cyanide and acrylonitrile):
Carbon Disulfide: Mild poisonings by carbon disulfide inhalation
may be managed best by no more than careful observation, even
though sensory hallucinations, delirium, and behavioral aberrations
can be alarming. Severe poisonings may require specific measures. If
manic behavior threatens the safety of the victim, diazepam (5-10
mg in adults, 0.2-0.4 mg/kg in children), administered slowly,intra-
venously, may be helpful as a tranquilizer. Give as much as is neces-
sary to achieve sedation. Do not give catecholamine-releasing agents
such as reserpine and amphetamines.
Carbon Tetrachloride: For carbon tetrachloride poisoning, sev-
eral treatment measures have been suggested to limit the severity of
hepatic necrosis. Hyperbaric oxygen has been used with some suc-
cess.2 Oral administration of N-acetyl cysteine (MucomystR) may
be worthwhile as a means of reducing free radical injury21 Dilute
the proprietary 20% product 1:4 in a carbonated beverage, and give
about 140 mg/kg body weight of the diluted solution as a loading
dose. Then give 70 mg/kg every 4 hours after the loading dose for a
total of 17 doses. (This dosage schedule is used for acetaminophen
poisonings.) Administration via duodenal tube may be necessary in
a few patients who cannot tolerate Mucomyst.22 Intravenous ad-
ministration of N-acetyl cysteine may be used; more information is
available through poison control centers.
Naphthalene: Naphthalene toxicosis caused by vapor inhalation
can usually be managed simply by removing the individual to fresh
air. Skin contamination should be removed promptly by washing
with soap and water. Eye contamination should be removed by flush-
ing with copious amounts of clean water. Eye irritation may be
severe, and if it persists, should receive ophthalmalogic attention.
Examine the plasma for evidence of hemolysis: a reddish-brown
tinge, especially in the blood smear for "ghosts" and Heinz bodies. If
present, monitor red blood cell count and hematocrit for anemia,
urine for protein and cells. Measure direct-and indirect-reacting bi-
164 FUMIGANTS
-------
lirubin in the plasma. Monitor fluid balance and blood electrolytes.
If possible, monitor urinary excretion of naphthol to assess severity
of poisoning and clinical progress.
If hemolysis is clinically significant, administer intravenous fluids
to accelerate urinary excretion of the naphthol metabolite and pro-
tect the kidney from products of hemolysis. Use Ringer's lactate or
sodium bicarbonate to keep urine pH above 7.5. Consider the use
of mannitol or furosemide to promote diuresis. If urine flow de-
clines, intravenous infusions must be stopped to prevent fluid over-
load and hemodialysis should be considered.15 If anemia is severe,
blood transfusions may be needed.
Phosphine Gas: Recent experience in India suggests that therapy
with magnesium sulfate may decrease the likelihood of a fatal out-
come.16'19'23 The mechanism is unclear, but may possibly be due to
the membrane stabilization properties of magnesium in protecting
the heart from fatal arrythmias. In one series of 90 patients, magne-
sium sulfate was found to decrease the mortality from 90% to 52%.16
Two controlled studies have been done, one of which showed a
reduction in mortality from 52% to 22%.23 The other study found
no effect on mortality24 The dosage for magnesium sulfate is: 3
grams during the first 3 hours as a continous infusion, followed by 6
grams per 24 hours for the next 3 to 5 days.16
Hydrogen Cyanide and Acrylonitrile: Poisonings by hydrogen
cyanide and acrylonitrile gases or liquids are treated essentially the
same as poisoning by cyanide salts. Because cyanide is so promptly
absorbed following ingestion, treatment should commence with
prompt administration of oxygen and antidotes. Gastrointestinal
decontamination should be considered if the patient presents within
a short interval after ingestion, and only after the above life-saving
treatment has commenced. Ipecac should be avoided due to the
potential for rapid onset of loss of consciousness.
The three antidotes amyl nitrite, sodium nitrite, and sodium thio-
sulfate are available as a kit called the Lilly Cyanide Antidote Kit,
available from Eli Lilly and Company, Indianapolis, IN. The dosages
vary between adults and children and are outlined below.
FUMIGANTS 165
-------
Dosage of Cyanide Antidotes
Adults:
Administer oxygen continuously. Hyperbaric oxygen has been evalu-
ated as effective in this condition.25 If respiration fails, maintain pul-
monary ventilation mechanically.
Administer amyl nitrite ampules by inhalation for 15-30 seconds
of every minute, while a fresh solution of 3% sodium nitrite is being
prepared. This solution is ready prepared in commercial cyanide
antidote kits.
As soon as solution is available, inject intravenously 10 mL of 3%
sodium nitrite solution over a 5-minute interval, keeping the needle
in place.
Caution: Monitor pulse and blood pressure during administration of amyl
nitrite and sodium nitrite. If systolic blood pressure falls below 80 mm Hg,
slow or stop nitrite administration until blood pressure recovers.
Follow sodium nitrite injection with an infusion of 50 mL of 25%
aqueous solution of sodium thiosulfate administered over a 10-
minute period. Initial adult dose should not exceed 12.5 g.
If symptoms persist or recur, treatment by sodium nitrite and so-
dium thiosulfate should be repeated at half the dosages listed above.
Measure hemoglobin and methemoglobin in blood. If more than
50% of total hemoglobin has been converted to methemoglobin,
blood transfusion or exchange transfusion should be considered, be-
cause conversion back to normal hemoglobin proceeds slowly.
Children:
Give amyl nitrite, oxygen, and mechanical respiratory support as
recommended for adults. The following dosages of antidotes have
been recommended for children.26
Children over 25 kg body weight should receive adult dosages of
sodium nitrite and sodium thiosulfate.
Children less than 25 kg body weight should first have two 3-4 mL
samples of blood drawn and then, through the same needle, receive
0.15-0.33 mL/kg up to 10 mL of the 3% solution of sodium nitrite
injected over a 5-minute interval. Following sodium nitrite, admin-
ister an infusion of 1.65 mL/kg of 25% sodium thiosulfate at a rate
of 3-5 mL per minute.
... continued
166 FUMIGANTS
-------
At this point, determine the hemoglobin content of the pretreat-
ment blood sample. If symptoms and signs of poisoning persist or
return, give supplemental infusions of sodium nitrite and sodium
thiosulfate based on hemoglobin level, as presented in the table.These
recommended quantities are calculated to avoid life-threatening
methemoglobinemia in anemic children. They are aimed at con-
verting approximately 40% of circulating hemoglobin to methemo-
globin. If possible, monitor blood methemoglobin concentrations as
treatment proceeds.
RECOMMENDED DOSAGES OF SUPPLEMENTAL SODIUM
NITRITE AND SODIUM THIOSULFATE
HEMOGLOBIN
Initial
Hemoglobin
Concentration
g/100mL
14.0
12.0
10.0
8.0
LEVEL
Volume of 3%
Sodium Nitrite
ml/kg
0.20
0.16
0.14
0.11
BASED ON
Dose
25% Sodium
Thiosulfate
ml/kg
1.00
0.83
0.68
0.55
Although various cobalt salts, chelates, and organic combinations have shown
some promise as antidotes to cyanide, they are not generally available in the
United States. None has been shown to surpass the nitrite-thiosulfate regimen
in effectiveness.
References
1. Wilcosky TC and Tyroler HA. Mortality from heart disease among workers exposed to
solvents. / Occup Med 1983;25:879-85.
2. Truss C and Killenberg 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;l: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.
FUMIGANTS 167
-------
6. Smedley J. Is formaldehyde an important cause of allergic respiratory disease? Clin Exp
Allergy 1996;26:247-9.
1. 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. ]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
Medl995;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. BrJInd Med 1993;50:155-9.
12. Deschamps FJ andTurpin 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-ll.
16. Katira R, Elhence GP, Mehrotra ML, et al. A study of aluminum phosphide poisoning with
special reference to electrocardiographic changes. JAssoc Physicians India 1990;38:471-3.
17. Singh S, Singh D,Wig N, et al. Aluminum phosphide ingestion:A clinico-pathologic study.
Clin Toxicol 1996;34:703-6.
18. Singh RB, Singh RG, and Singh U. Hypermagnesemia following aluminum phosphide
poisoning. Int J Clin PharmacolTher Toxicol 1991;29:82-5.
19. Gupta S and Ahlawat SK.Aluminum phosphide poisoning:A review. ClinToxicol 1995;33:19-24.
20. Scheuerman EH. Suicide by exposure to sulfuryl fluoride. J Forensic Sci 1986;31:1154-8.
21. Ruprah M, MantTGK, and Flanagan RJ. Acute carbon tetrachloride poisoning in 19 pa-
tients: Implications for diagnosis and treatment. Lancet 1985;l:1027-9.
22. Anker AL and Smilkenstein MJ. 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. JAssoc Physicians India 1994;42:107-10.
25. Myers RAM and Schnitzer BM. Hyperbaric oxygen use: Update 1984. Postgrad Med
1984;76:83-95.
26. Mofenson HC, Greensher J, Horowitz R, and Berlin CM. Treatment of cyanide poisoning.
Pediatrics 1970;46:793-6.
168 FUMIGANTS
-------
CHAPTER 17
Rodenticides
A wide variety of materials are used as rodenticides.They pose particular risks for
accidental poisonings for several reasons. First, as agents specifically designed to
kill mammals, often their toxicity is very similar for the target rodents and for
humans. (Warfarin and other anticoagulant rodenticides were initially developed
to overcome this problem by creating compounds that were highly toxic to ro-
dents, particularly after repeated exposures, but much less toxic to humans.) Sec-
ond, since rodents usually share environments with humans and other mammals,
the risk of accidental exposure is an integral part of the placement of baits for the
rodents. Finally, as rodents have developed resistance to existing rodenticides, there
is a continuous need to develop new and potentially more toxic rodenticides. As
rodents have become resistant to warfarin baits, for example, the development of
"superwarfarins" has increased the risk to humans.1'2 It is important to be familiar
with use patterns and development of more toxic compounds and to make every
effort to identify the actual agent used in order to institute the most appropriate
management for these poisonings.
COUMARINS AND INDANDIONES
Toxicology
Warfarin and related compounds (coumarins and indandiones) are the most
commonly ingested rodenticides in the United States, with 13,345 exposures
reported in 1996.3 Gastrointestinal absorption of these toxicants is efficient.
Warfarin can be absorbed across the skin, but this has occurred only under
extraordinary circumstances.
Coumarins and indandiones depress the hepatic synthesis of vitamin K
dependent blood-clotting factors (II (prothrombin),VII, IX, and X).The anti-
prothrombin effect is best known, and is the basis for detection and assessment
of clinical poisoning. The agents also increase permeability of capillaries through-
out the body, predisposing the animal to widespread internal hemorrhage. This
generally occurs in the rodent after several days of warfarin ingestion due to the
long half-lives of the vitamin K dependent clotting factors,1'2 although lethal
hemorrhage may follow smaller doses of the modern, more toxic compounds.1
The lengthened prothrombin time (PT) from a toxic dose of coumarins or
indandiones may be evident within 24 hours, but usually reaches a maximum
HIGHLIGHTS
Newer "superwarfarins"
are widely available and
toxic at much lower doses
than conventional warfarin
Signs and Symptoms:
Variable depending on
agent
Warfarin compounds cause
bleeding
Pulmonary edema results
from phosphine gas (from
zinc phosphide)
Cardiovascular, Gl, and CMS
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
Contraindicated:
Neither Vitamins K3 nor K4
may be used as a substitute
for Vitamin K,
Chelating agents are not
effective in thallium
poisoning
RODENTICIDES 169
-------
Commercial Products
COUMARINS
brodifacoum
Havoc
Klerat
Ratak Plus
Talon
Volid
bromadiolone
Bromone,
Contrac
Maki
coumachlor
Famarin
coumatetralyl
Racumin
difenacoum
Frunax-DS
Ratak
warfarin
Co-Rax
coumafene
Cov-R-Tox
Kypfarin
Liqua-Tox
RAX
Tox-Hid
zoocoumarin
INDANDIONES
chlorophacinone
Caid
Liphadione
Microzul
Ramucide
Ratomet
Raviac
Rozol
Topitox
diphacinone
diphacin
Ditrac
Ramik
Tomcat
pivalyn*
pindone
pival
pivaldione
*Discontinued in the U.S.
in 36-72 hours.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 toxicity1
Symptomatic poisoning, with prolonged symptoms due to the long half-
lives of superwarfarins, has been reported even with single exposures; however,
these are usually intentional and are large single dosages.2 Because of their
toxicity in relation to warfarin, patients may require higher dosages of vitamin
K and will require longer monitoring of their PT. One patient required vita-
min K for several months following discharge.6 Another patient was released
from the hospital with significant clinical improvement and only slightly el-
evated coagulation studies after brodifacoum ingestion. Two and a half weeks
later, he presented in a comatose state and was found to have massive intracra-
nial hemorrhage.7
Clinical effects of these agents usually begin several days after ingestion, due
to the long half-life of the factors. Primary manifestations include nosebleeds,
bleeding gums, hematuria, melena, and extensive ecchymoses.1'2'6'7'8 Patients may
also have symptoms of anemia, including fatigue and dyspnea on exertion.8 If the
poisoning is severe, the patient may progress to shock and death.
Unlike the coumarin compounds, some indandiones cause symptoms and
signs of neurologic and cardiopulmonary injury in laboratory rats leading to
death before hemorrhage occurs. These actions may account for the greater
toxicity of indandiones in rodents. Neither neurologic nor cardiopulmonary
manifestations have been reported in human poisonings.
Confirmation of Poisoning
Coumarin or indandione poisoning results in an increase in prothrombin
time, the result of reduced plasma prothrombin concentration. This is a reliable
test for absorption of physiologically significant doses. Detectable reduction in
prothrombin occurs within 24-48 hours of ingestion and persists for 1-3 weeks.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.
170 RODENTICIDES
-------
2. Vitamin Kr A patient presenting within 24 hours after ingestion will likely
have a normal PT. However, in a study of 1 1 0 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 (vita-
given orally protects against the anticoagulant effect of these rodenti-
mn
cides, with essentially no risk to the patient. In accidental ingestions with healthy
children involving only a taste or single swallow, no medical treatment is re-
quired, but children should be observed for bleeding and bruising. If a larger
amount may have been ingested, PT should be monitored at 24 and 48 hours,
with phytonadione therapy initiated for elevated PT or clinical signs of bleeding.
Caution: Phytonadione, specifically, is required. Neither vitamin K3 (me-
nadione, HykinoneR) nor vitamin K4 (menadiol) is an antidote for these anti-
coagulants.
Dosage of Phytonadione (oral):
Adults and children over 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, particu-
larly of the superwarfarin compounds, will likely have a very prolonged period
of decreased prothrombin activity. Patients may need to be treated for as long as
3 or 4 months.6'7
If the prothrombin time is significantly lengthened, give AquamephytonR
intramuscularly. See next page for dosage.
RODENTICIDES 171
-------
Dosage of AquamephytonR (intramuscular):
Adults and children over 12years: 5-10 nig.
Children under 12 years: 1-5 nig.
Decide dose within these ranges according to the degree of prothrom-
bin time lengthening and, in children, the age and weight of the child.
Substantially higher doses of phytonadione (50 to 125 nig) have been
required in some poisonings with brodifacoum when bleeding and PT
elevation persisted despite therapy6'7'9
Repeat prothrombin time in 24 hours. If it has not decreased from
the original value, repeat AquamephytonR dosage.
5. Bleeding. If victim is bleeding as a result of anticoagulant poisoning, ad-
minister AquamephytonR intravenously: up to 10 mg in adults and children
over 12 years, and up to 5 mg in children under 12 years. Initial dosage should
be decided chiefly on the basis of the severity of bleeding. Subsequent dosages
may need to be adjusted based on response, especially in the case of the
superwarfarins.6'7'9 Repeat intravenous AquamephytonR in 24 hours if bleeding
continues. Inject at rates not exceeding 5% of the total dose per minute. Intra-
venous infusion of the AquamephytonR diluted in saline or glucose solution is
recommended. Bleeding is usually controlled in 3-6 hours.
Caution: Adverse reactions, some fatal, have occurred from intravenous
phytonadione injections, even when recommended dosage limits and injection
rates were observed. For this reason, the intravenous route should be used only
in cases of severe poisoning. Flushing, dizziness, hypotension, dyspnea, and cy-
anosis have characterized adverse reactions.
Antidotal therapy in cases of severe bleeding should be supplemented with
transfusion of fresh blood or plasma. Use of fresh blood or plasma represents the
most rapidly effective method of stopping hemorrhage due to these anticoagu-
lants, but the effect may not endure. Therefore, the transfusions should be given
along with phytonadione therapy.
Determine PT and hemoglobin concentrations every 6-12 hours to assess
effectiveness of antihemorrhagic measures. When normal blood coagulation is
restored, it may be advisable to drain large hematomata.
Ferrous sulfate therapy may be appropriate in the recuperative period to
rebuild lost erythrocyte mass.
172 RODENTICIDES
-------
INORGANIC RODENTICIDES
Commercial Products
Toxicology
Thallium sulfate is well absorbed from the gut and across the skin. It
exhibits a very large volume of distribution (tissue uptake) and is distributed
chiefly to the kidney and liver, both of which participate in thallium excretion.
Most blood-borne thallium is in the red cells. Elimination half-life from blood
in the adult human is about 1.9 days. Most authors report the LD50 in humans
to be between 10 and 15 mg/kg.10
Unlike other inorganic rodenticides like yellow phosphorus and zinc phos-
phide, thallium poisoning tends to have a more insidious onset with a wide
variety of toxic manifestations. Alopecia is a fairly consistent feature of thallium
poisoning that is often helpful diagnostically; however, it occurs two weeks or
more after poisoning and is not helpful early in the presentation.10'11 In addi-
tion to hair loss, the gastrointestinal system, central nervous system, cardiovas-
cular system, renal system, and skin are prominently affected by toxic intakes.
Early symptoms include abdominal pain, nausea, vomiting, bloody diar-
rhea, stomatitis, and salivation. Ileus may appear later on. Elevated liver enzymes
may occur, indicating tissue damage. Other patients experience signs of central
nervous system toxicity including headache, lethargy, muscle weakness,
paresthesias, tremor, ptosis, and ataxia.These usually occur several days to more
than a week after exposure.10'12 Extremely painful paraesthesias, either in the
presence or absence of gastrointestinal signs, may be the primary presenting
complaint.11'13 Myoclonic movements, convulsions, delirium, and coma reflect
more severe neurologic involvement. Fever is a bad prognostic indication of
brain damage.
Cardiovascular effects include early hypotension, due at least in part to a
toxic myocardiopathy Ventricular arrythmias may occur. Hypertension occurs
later and is probably a result of vasoconstriction. The urine may show protein
and red cells. Patients may also develop alveolar edema and hyaline membrane
formation in the lungs, consistent with a diagnosis of Acute Respiratory Dis-
tress Syndrome.14 Death from thallium poisoning may be caused by respiratory
paralysis or cardiovascular collapse. Absorption of nonlethal doses of thallium
has caused protracted painful neuropathies and paresis, optic nerve atrophy,
persistent ataxia, dementia, seizures, and coma.11
Yellow phosphorus (also known as white phosphorus) is a corrosive agent
and damages all tissues it comes in contact with, including skin and the gut
lining. Initial symptoms usually reflect mucosal injury and occur a few minutes
to 24 hours following ingestion. The first symptoms include severe vomiting
and burning pain in the throat, chest, and abdomen.The emesis may be bloody
(either red, brown, or black)15 and on occasion may have a garlic smell.16'17 In
some cases, central nervous system signs such as lethargy, restlessness, and irrita-
INORGANICS
thallium sulfate
yellow phosphorus
zinc phosphide
Phosvin
Ridall-Zinc
Zinc-Tox
Yellow phosphorus is not sold
in the United States. Zinc
phosphide is still registered in
the United States, and can be
found in U.S. retail stores.
Thallium sulfate is no longer
registered for pesticidal use,
but is used by government
agencies only.
RODENTICIDES 173
-------
bility are the earliest symptoms, followed by symptoms of gastrointestinal in-
jury Shock and cardiopulmonary arrest leading to death may occur early in
severe ingestions.17
If the patient survives, a relatively symptom-free period of a few hours or
days may occur, although this is not always the case.15 The third stage of toxicity
then ensues with systemic signs indicating severe injury to the liver, myocar-
dium, and brain. This is due to phosphine gas (PH3) formed in and absorbed
from the gut. Nausea and vomiting recur. Hemorrhage occurs at various sites
reflecting a depression of clotting factor synthesis in the damaged liver. Also,
thrombocytopenia may contribute. Hepatomegaly and jaundice appear. Hypo-
volemic shock and toxic myocarditis may develop. Brain injury is manifested by
convulsions, delirium, and coma. Anuric renal failure commonly develops due
to shock and to the toxic effects of phosphorus products and accumulating
bilirubin on renal tubules.The mortality rate of phosphorus poisonings may be
as high as 50 percent.15
Zinc phosphide is much less corrosive to skin and mucous membranes
than yellow phosphorus, but inhalation of dust may induce pulmonary edema.
The emetic effect of zinc released in the gut may provide a measure of protection;
however, phosphine will be produced in the gut and absorbed along with the
zinc. Nausea and vomiting, excitement, chills, chest tightness, dyspnea, and cough
may progress to pulmonary edema. Patients face many of the same systemic tox-
icities as encountered with yellow phosphorus, including hepatic failure with
jaundice and hemorrhage, delirium, convulsions, and coma (from toxic encepha-
lopathy), tetany from hypocalcemia, and anuria from renal tubular damage.Ven-
tricular arrythmias from cardiomyopathy and shock also occur and are another
common cause of death.16'18 Inhalation of phosphine gas from improper use of
phosphide rodenticides has resulted in pulmonary edema, myocardial injury, and
multisystem involvement.19 For more information about the effects of phosphine
gas poisoning, see the section on phosphine in Chapter 16, Fumigants.
Confirmation of Poisoning
Phosphorus and phosphides sometimes impart a foul rotten fish odor
to vomitus, feces, and sometimes the breath. Luminescence of vomitus or feces
is an occasional feature of phosphorus ingestion. Hyperphosphatemia and hy-
pocalcemia occur in some cases, but are not consistent findings.
Thallium can be measured in the serum, urine, and hair. Hair analysis is
likely to be useful only in establishing protracted prior absorption. Serum con-
centration does not exceed 30 meg per liter in non-exposed persons.The most
reliable method for diagnosis is considered a 24-hour urine excretion. The
normal value is less than 10 meg/liter per 24 hours.10'13
174 RODENTICIDES
-------
Treatment: Thallium Sulfate
1. Gastrointestinal decontamination. If thallium sulfate was swallowed less
than an hour prior to treatment, consider gastrointestinal decontamination as
outlined in Chapter 2. Multiple doses of activated charcoal may be helpful in
increasing thallium elimination.13
2. Electrolyte and glucose solutions should be given by intravenous infu-
sion to support urinary excretion of thallium by diuresis. Monitor fluid balance
carefully to insure that fluid overload does not occur. If shock develops, give
whole blood, plasma, or plasma expanders. Pressor amines must be used very
carefully in light of myocardial injury. Monitor EGG for arrhythmias.
3. Convulsions. Control seizures and myoclonic jerking as outlined in Chap-
ter 2.
4. Combined hemodialysis and hemoperfusion has proven moderately
effective in reducing the body burden of thallium in victims of severe poison-
ing. In one case, peritoneal dialysis was not effective.
5. Chelation therapy. Several methods for chelating and/or accelerating dis-
position of thallium have been tested and found either relatively ineffective or
hazardous. Chelating agents are not recommended in thallium poisoning. Po-
tassium chloride has been recommended. However it has been reported to
increase toxicity to the brain,11'14 and has not shown to increase elimination in
6. Potassium ferric ferrocyanide (Prussian Blue) orally enhances fecal
excretion of thallium by exchange of potassium for thallium in the gut. It is not
available or approved for use in humans in the United States. Reports of its use
in humans are anecdotal and do not strongly support its use.
Treatment: Yellow Phosphorus and Zinc Phosphide
1. Skin decontamination. Brush or scrape non-adherent phosphorus from
the skin. Wash skin burns with copious amounts of water. Make sure all par-
ticles of phosphorus have been removed. If burned area is infected, cover with
an antimicrobial creme. See Chapter 2.
2. Supportive management. Poisonings by ingested yellow phosphorus or
zinc phosphide are extremely difficult to manage. Treatment is basically sup-
portive and symptomatic. Control of airway and convulsions must be estab-
lished prior to considering gastrointestinal decontamination as described in
Chapter 2.
RODENTICIDES 175
-------
Caution: Highly toxic phosphine gas may evolve from emesis, lavage fluid,
and feces of victims of these poisons. The patient's room should be well venti-
lated. Persons attending the patient must wear gloves to avoid contact with the
phosphorus.
3. Lavage with 1:5000 potassium permanganate solution has been used in the
management of ingested phosphorus compounds in the past; however, there is
not sufficient evidence for its efficacy and we do not recommend it.
4. Catharsis is probably not indicated, but there may be some benefit in ad-
ministering mineral oil. Dosage is 100 mL for adults and children over 12 years,
and 1.5 mL/kg body weight in children under 12 years. Do not give vegetable
oils or fats.
5. Transfusions. Combat shock and acidosis with transfusions of whole blood
and appropriate intravenous fluids. Monitor fluid balance and central venous
pressure to avoid fluid overload. Monitor blood electrolytes, glucose, and pH to
guide choice of intravenous solutions. Administer 100% oxygen by mask or
nasal tube.
6. Oxygen. Combat pulmonary edema with intermittent or continuous posi-
tive pressure oxygen.
7. Renal protection. Monitor urine albumin, glucose, and sediment to detect
early renal injury. Extracorporeal hemodialysis will be required if acute renal
failure occurs, but it does not enhance excretion of phosphorus. Monitor EGG
to detect myocardial impairment.
8. Liver damage. Monitor serum alkaline phosphatase, LDH, ALT, AST, pro-
thrombin time, and bilirubin to evaluate liver damage. Administer
AquamephytonR (vitamin Kj) if prothrombin level declines.
9. Pain management. Morphine sulphate may be necessary to control pain.
Adult dose: 2-15 mg IM/IV/SC Q 2-6 hours prn. Child's dose: 0.1-0.2 mg/
kg/dose Q 2-4 hours.
10. Phosphine gas. For specific therapy due to phosphine gas, refer to the
treatment of phosphine poisoning in Chapter 16, Fumigants.
176 RODENTICIDES
-------
CONVULSANTS
Commercial Products
Toxicology
Crimidine is a synthetic chlorinated pyrimidine compound that, in adequate
dosage, causes violent convulsions similar to those produced by strychnine.
Sodium fluoroacetate and fluoroacetamide are readily absorbed by
the gut, but only to a limited extent across skin.The toxic mechanism is distinct
from that of fluoride salts. Three molecules of fluoroacetate or fluoroacetamide
are combined in the liver to form a molecule of fluorocitrate, which poisons
critical enzymes of the tricarboxylic acid (Krebs) cycle, blocking cellular
respiration. The heart, brain, and kidneys are the organs most prominently a
ffected. The effect on the heart is to cause arrhythmias, progressing to ventri-
cular fibrillation, which is a common cause of death. Metabolic acidosis, shock,
electrolyte imbalance, and respiratory distress are all poor prognostic signs.
Neurotoxicity is expressed as violent tonic-clonic convulsions, spasms, and
rigor, sometimes not occurring for hours after ingestion.21
Strychnine is a natural toxin (nux vomica) which causes violent convul-
sions by direct excitatory action on the cells of the central nervous system,
chiefly the spinal cord. Death is caused by convulsive interference with pulmo-
nary function, by depression of respiratory center activity, or both. Strychnine
is detoxified in the liver. Residence half-life is about 10 hours in humans. On-
set of symptoms is usually within 15-20 minutes of ingestion. Lethal dose in
adults is reported to be between 50 and 100 mg, although as little as 15 mg can
kill a child.22
CONVULSANTS
crimidine
Castrix
fluoroacetamide*
Compound 1081
sodium fluoroacetate
Compound 1080
strychnine
* Discontinued in the U.S.
Only specially trained
personnel are allowed to use
strychnine. Crimidine and
sodium fluoroacetate are no
longer registered for use as
pesticides.
Confirmation of Poisoning
There are no generally available tests to confirm poisoning by the convul-
sant rodenticides.
Treatment: Sodium Fluoroacetate and Fluoroacetamide
Poisonings by these compounds have occurred almost entirely as a result of
accidental and suicidal ingestions. If the poison was ingested shortly before
treatment and convulsions have not yet occurred, the first step in treatment is
to remove the toxicant from the gut. If the victim is already convulsing, how-
ever, it is necessary first to control the seizures before gastric lavage and cathar-
sis are undertaken.
1. Control seizures as outlined in Chapter 2. Seizure activity from these
compounds may be so severe that doses necessary for seizure control may para-
lyze respiration. For this reason, it is best to intubate the trachea as early as
RODENTICIDES 177
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possible in the course of seizure control, and support pulmonary ventilation
mechanically. This has the added advantage of protecting the airway from aspi-
ration of regurgitated gastric contents.
2. Gastrointestinal decontamination. If the patient is seen within an hour
of exposure and is not convulsing, consider gastrointestinal decontamination as
outlined in Chapter 2.
3. Administer intravenous fluids cautiously to support excretion of ab-
sorbed toxicant. It is especially important to avoid fluid overload in the pres-
ence of a weak and irritable myocardium.
4. Monitor electocardiogram for arrhythmias and, if detected, treat with an
appropriate antiarrhythmic drug. Facilities for electroshock cardioversion should
be at hand. Some victims of fluoroacetate poisoning have been rescued after
repeated cardioversions.
5. Calcium gluconate (10% solution) given slowly intravenously should be
given to relieve hypocalcemia. Care must be taken to avoid extravasation.
Dosage of Calcium Gluconate:
Supplied as 100 mg/mL (10% solution)
Adults and children over 12years/10 mL of 10% solution, given slowly,
intravenously. Repeat as necessary.
Children under 12 years: 200-500 mg/kg/24 hr divided Q6 hr. For
cardiac arrest, 100 mg/kg/dose. Repeat dosage as needed.
6. Other therapies. Antidotal efficacy of glycerol monacetate and ethanol,
observed in animals, has not been substantiated in humans.These therapies are
not recommended in humans.
Treatment: Strychnine or Crimidine
Strychnine and crimidine cause violent convulsions shortly following in-
gestion of toxic doses. Both poisons are probably well adsorbed onto charcoal.
If the patient is seen fully conscious and not convulsing a few moments after
the ingestion, great benefit may derive from the immediate ingestion of acti-
vated charcoal. If the patient is already obtunded or convulsing, the involuntary
motor activity must be controlled before steps are taken to empty the gut and
limit toxicant absorption.
178 RODENTICIDES
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1. Control seizures as outlined in Chapter 2.
2. Gastrointestinal decontamination. Consider gastrointestinal decontami-
nation if patient is seen within an hour of ingestion.
3. Administer intravenous fluids to support excretion of absorbed toxi-
cants. Inclusion of sodium bicarbonate in the infusion fluid counteracts meta-
bolic acidosis generated by convulsions. Effectiveness of hemodialysis and
hemoperfusion has not been tested.
Commercial Products
MISCELLANEOUS
cholecalciferol
Muritan
Quintox
Rampage
red squill*
Dethdiet
Rodine
* Discontinued in the U.S.
MISCELLANEOUS RODENTICIDES:
RED SQUILL AND CHOLECALCIFEROL
Toxicology
Red squill is a little-used rodenticide, consisting of the inner portions of a
small cabbage plant grown in eastern Mediterranean countries. Its toxic prop-
erties have been known since ancient times and are probably due to cardiac
glycosides. For several reasons, mammals other than rodents are unlikely to be
poisoned: (1) red squill is intensely nauseant, so that animals which vomit (ro-
dents do not) are unlikely to retain the poison; (2) the glycoside is not effi-
ciently absorbed from the gut; and (3) absorbed glycoside is rapidly excreted.
Injection of the glycosides leads to effects typical of digitalis: alterations in
cardiac impulse conduction and arrhythmias.
Cholecalciferol is the activated form of vitamin D (vitamin Dj). Its toxic
effect is probably a combination of actions on liver, kidney, and possibly the
myocardium, the last two toxicities being the result of hypercalcemia. Early symp-
toms and signs of vitamin D-induced hypercalcemia in humans are fatigue, weak-
ness, headache, and nausea. Polyuria, polydipsia, proteinuria, and azotemia result
from acute renal tubular injury by hypercalcemia. This is commonly the cause of
death. Prolonged hypercalcemia results ultimately in nephrolithiasis and nephro-
calcinosis. Azotemia occurs as renal tubular damage progresses.
Confirmation of Poisoning
Cholecalciferol intoxication is indicated by an elevated concentration of
calcium (chiefly the unbound fraction) in the serum. There are no generally
available tests for the other rodenticides or their biotransformation products.
RODENTICIDES 179
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Treatment: Red Squill
Red squill is unlikely to cause poisoning unless ingested at substantial dos-
age. The problem is usually self-correcting due to its intense emetic effect. If,
for some reason, the squill is retained, syrup of ipecac, followed by 1 -2 glasses of
water, should be administered to initiate vomiting. Monitor cardiac status elec-
trocardiographically
Treatment: Cholecalciferol
Cholecalciferol at high dosage may cause severe poisoning and death.
Human poisonings from its use as a rodenticide have not been reported, but
vitamin D overdosage has occurred under clinical circumstances. Treatment is
directed at limiting gastrointestinal absorption, accelerating excretion, and
counteracting the hypercalcemic effect.
1. Gastrointestinal decontamination. If Cholecalciferol has been ingested
within an hour prior to treatment, consider gastric decontamination, as out-
lined in Chapter 2. Repeated administration of charcoal at half or more the
initial dosage every 2-4 hours may be beneficial.
2. Administer intravenous fluids (normal saline or 5% glucose) at moderate
rates to support excretory mechanisms and excretion. Monitor fluid balance to
avoid overload, and measure serum electrolytes periodically. Measure total and
ionized calcium levels in the blood 24 hours after Cholecalciferol ingestion to
determine severity of toxic effect. Monitor urine for protein, and red and white
cells to assess renal injury.
3. Furosemide (Lasix), 20-40 mg intravenously, or 40-120 mg daily by mouth
may be given to promote diuresis. Dosage for children under 12 is approximately
0.5-1.0 mg/kg body weight intravenously, 1.0-2.0 mg/kg body weight orally.
Monitor serum potassium after dosage; give potassium chloride if hypokalemia
occurs. Consult package insert for additional directions and warnings.
4. Predinisone and similar glucocorticoids reduce elevated blood calcium
levels in certain diseases. Although they have not been tested in Cholecalciferol
overdosage, it is possible that they would be beneficial. Dosage is approximately
1 mg per kilogram per day, to a maximum of 20 mg per day.
5. Calcitonin (salmon calcitonin, CalcimarR) is a logical antidote for cholecal-
ciferol actions, but has only very limited use in human poisoning.23 In other
conditions, the usual dosage is 4 International Units per kg body weight every
12 hours, by intramuscular or subcutaneous injection, continued for 2-5 days.
180 RODENTICIDES
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The dose may be doubled if calcium-lowering effect is not sufficient. Calcium
gluconate for intravenous injection should be immediately available if indica-
tions of hypocalcemia (carpopedal spasm, cardiac arrhythmias) appear. Consult
package insert for additional directions and warnings.
6. Cholestryamine appears effective in the treatment of vitamin D toxicity in
animals.24 It has seen very limited use in humans.25'26
References
1. Mack RB. Not all rats have four legs: Superwarfarin poisoning. N C Med] 1994;55:554-6.
2. Katona B andWason S. Superwarfarin poisoning. JEmerg Med 1989;7:627-31.
3. LitovitzTL, Smilkstein M, Felberg L, et al. 1996 Annual Report of the American Association of
Poison Control CentersToxic Exposure Surveillance System. Am J Emerg Med 1997;15:447-
500.
4. Burucoa C,Mura P, Robert R, et al. Chlorophacinone intoxication. ClinToxicol 1989;27:79-89.
5. Smolinske SC, Scherger DL, Kearns PS, et al. Superwarfarin poisoning in children: A pro-
spective study. Pediatrics 1989;84:490-4.
6. Lipton RA and Klass EM. Human ingestion of a 'superwarfarin' rodenticide resulting in a
prolonged anticoagulant effect. JAMA 1984;252:3004-5.
7. Helmuth RA, McCloskey DW, Doedens DJ, et al. Fatal ingestion of a brodifacoum-contain-
ing rodenticide. Lab Med 1989;20:25-7.
8. Norcross WA, GaniatsTG, Ralph LP, et al. Accidental poisoning by warfarin-contaminated
herbal tea. West J Med 1993;159:80-2.
9. Kruse JA and Carlson RW. Fatal rodenticide poisoning with brodifacoum. Ann Emerg Med
1992;21:331-6.
10. Mayfield SR, Morgan DP, and Roberts RJ. Acute thallium poisoning in a 3-year old child.
Clin Pediatr (Phila) 1983;23:461-2.
11. Bank WJ, Pleasure DE, Suzuki K, et al.Thallium poisoning. Arch Neurol 1972;26:456-64.
12. Fred HL and Accad ME Abdominal pain, leg weakness, and alopecia in a teenage boy. Hosp
Prnct 1997;32:69-70.
13. Meggs WJ, Hoffman RS, Shih RD, et al.Thallium poisoning from maliciously contaminated
food.JToxicol ClinToxicol 1994;32:723-30.
14. Roby DS, Fein AM, Bennett RH, et al. Cardiopulmonary effects of acute thallium poison-
ing. Chest 1984;85:236-40.
15. McMarron MM and Gaddis 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.
JAssoc Physicians India 1990;38:306-7.
19. Schoonbroodt D, Guffens P, Jousten P, et al. Acute phosphine poisoning? A case report and
review. Acta Clin Belg 1992;47:280-4.
RODENTICIDES 181
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20. Koshy KM and Lovejoy FH.Thallium ingestion with survival: Ineffectiveness of peritoneal
dialysis and potassium chloride diuresis. Clin Toxicol 1981;18:521-5.
21. Chi CH, Chen KW, Chan SH, et al. Clinical presentation and prognostic factors in sodium
monofluoroacetate intoxication. ClinToxicol 1996;34:707-12.
22. Benomran FA and Henry JD. Homicide by strychnine poisoning. Med Sci Law 1996;36:271-3.
23. Buckle RM, GamlenTR, and Pullen IM.Vitamin D intoxication treated with procine calci-
tonm. BrMed/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.
a-Med/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.
182 RODENTICIDES
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CHAPTER 18
Miscellaneous Pesticides,
Solvents, and Adjuvants
There are a variety of pesticides that do not fall into the broad categories
described in other chapters in this manual. Many of them are widely used and
are therefore associated with a high probability of human exposure. Some have
significant toxicity as well as a likelihood of human exposure, and are of real
concern. Many of the solvents and adjuvants used in the formulation of pesti-
cides also present a high likelihood of human exposure. Such exposures can
result in significant toxic effects that in many cases exceed the toxicity of the
active pesticide ingredient(s). Furthermore, it is sometimes more difficult to
obtain information about the solvents and adjuvants, complicating the issues of
diagnosis and management.
4-AMINOPYRIDINE
Toxicology
4-Aminopyridine is a highly toxic white powder used as a bird repellent. It
works by making one or two birds acutely ill, thus warning off the remaining
birds by cries of distress. It is toxic to all vertebrates.1 It is usually added to grain
baits in 0.5%-3.0% concentration, but 25% and 50% concentrates in powdered
sugar are available. Recent human exposure has come from its use as an inves-
tigational drug in the treatment of multiple sclerosis.2'3 It is rapidly absorbed by
the gut, less effectively across skin.The chief mechanism of toxicity is enhance-
ment of cholinergic transmission in the nervous system through the release of
acetylcholine both centrally and peripherally. Due to enhanced transmission at
neuromuscular junctions, severe muscle spasms may be a prominent manifesta-
tion of toxicity.2 4-Aminopyridine is rapidly metabolized and excreted.
No human poisonings have occurred as a result of ordinary use, but the
effects of ingestion of about 60 mg each by two adults have been reported.
Both experienced immediate abdominal discomfort, nausea and vomiting,
weakness, dizziness, and profuse diaphoresis, and one went on to develop a
tonic-clonic seizure and required ventilatory support. Acidosis was present in
both cases.1 Dizziness, giddiness, and gait disturbances are common, and sei-
zures may be severe, although recovery with supportive therapy and ventilatory
support has been the usual outcome.1'2'3
HIGHLIGHTS
Physicians may need to
actively seek information
from producers regarding
exact makeup of "inert
ingredients"
Signs and Symptoms:
Highly variable based on
agent
Many are irritants and
corrosives
Creosote (phenolic
compounds) give a smoky
color to urine
Methemoglobinemia may
occur with sodium
chlorate and creosote
poisoning
Sodium chlorate also
causes renal injury,
arrhythmia, shock, and
DIG
Pneumonitis occurs with
hydrocarbon aspiration
Treatment:
Skin, eye, and Gl
decontamination
Supportive care and
seizure control
Methylene blue for
methemoglobinemia
MISCELLANEOUS 183
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Commercial Products
Treatment
MISCELLANEOUS PESTICIDES
4-Aminopyridine
Avitrol
calcium cyanamide*
Cyanamide
nitrolime
creosote
endothall
Accelerate
Aquathol
Des-i-cate
Endothall Turf Herbicide
Herbicide 273
Hydrothol
metaldehyde
Antimilace
Cekumeta
Halizan
Metason
Namekil
others
sodium chlorate
Defol
De-Fol-Ate
Drop-Leaf
Fall
KM
Kusatol
Leafex
SYNERGISTS
piperonyl butoxide
SOLVENTS & ADJUVANTS
anticaking agents
dusts
emulsifiers
granular formations
penetrants
petroleum distillants
isopropanol
methanol
toluene
xylene
safeners
stickers and spreaders
*Discontinued in the U.S.
1. Skin decontamination. If skin or eye contamination has occurred, thor-
ough washing of the skin or eyes is indicated. See Chapter 2.
2. Gastrointestinal decontamination. If the patient is seen within an hour
of ingestion of a significant quantity of this compound, gastrointestinal decon-
tamination should be considered, as outlined in Chapter 2. If treatment is de-
layed, immediate oral administration of charcoal and sorbitol may represent
reasonable management.
3. Seizures may require anticonvulsant medication. See Chapter 2 for dosages.
4. Muscular spasms. Neuromuscular blockade with drugs such as d-
tubocuarine, metocurine and pancuronium bromide have been used sucessfully
to relieve the muscular spasms that occur with this agent. Such therapy must be
provided in an intensive care setting.1
5. Dehydration should be treated with intravenous fluids if oral fluids cannot
be retained.
CALCIUM CYANAMIDE
This synthetic compound is marketed as granules containing 44% calcium
cyanamide, yielding 19.5% nitrogen. It is incorporated into soil to serve as
fertilizer, fungicide, and herbicide. In contact with water, hydrogen cyanamide
is released. Acidic conditions accelerate this reaction. Hydrogen cyanamide is a
solid with considerable vapor pressure. It has toxic properties totally different
from those of cyanide, and it does not degrade to cyanide.
Toxicology
Calcium cyanamide is only moderately irritating to skin, but hydrogen
cyanamide is severely irritating and caustic to skin and the inhaled gas is strongly
irritating to mucous membranes.4 Dermal and mucosal lesions in the mouth,
tongue, and upper esophagus have occurred after exposure. No systemic symp-
toms from dermal exposure have been reported.5 Systemic poisonings have
followed inhalation of hydrogen cyanamide and ingestion of the salt. Manifes-
tations of poisoning include flushing, headache, vertigo, dyspnea, tachycardia,
and hypotension, sometimes progressing to shock.4 Because cyanamide is an
inhibitor of acetaldehyde dehydrogenase, ingestion of alcohol exaggerates the
symptoms. (A citrated form of cyanamide has been used in place ofAntabuse in
alcohol aversion therapy.)
184 MISCELLANEOUS
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Treatment
1. Skin decontamination. Skin contamination with either the calcium salt
or the free form should be removed by washing with soap and water. Flush eyes
with copious amounts of clean water. If skin or eye irritation persists, medical
attention should be obtained promptly. See Chapter 2.
2. Gastrointestinal decontamination. If large doses have been ingested within
an hour of exposure, gastrointestinal decontamination should be considered. If
dosage was small or treatment is delayed, oral administration of activated charcoal
and sorbitol probably represents reasonable management. See Chapter 2 for doses.
3. Hypotension or Antabuse-type reactions should be treated by placing
the patient in the Trendelenburg position, giving intravenous fluids, including
plasma or blood, if needed, and, if necessary, vasopressor drugs parenterally
4. Atropine is not antidotal.
CREOSOTE
Creosote is obtained by distillation of the tar formed by heating wood or
coal in the absence of oxygen. It is purified by extraction into oils. Creosote
from wood consists mainly of guaiacol (methoxy phenol) and cresol (methyl
phenol). Coal-derived creosote contains, in addition, some phenol, pyridine,
and pyridinol. Creosote is extensively used as a wood preservative, usually by
high-pressure impregnation of lumber. It has also been used as an animal dip
and disinfectant. Much of human exposure is in the form of various phenol
compounds.
Creosote is irritating to skin, eyes, and mucous membranes. Workers in
contact with technical creosote or with treated timbers sometimes develop
skin irritation, vesicular or papular eruptions, dermal pigmentation, and
occasionally gangrene and skin cancer.6 Photosensitization has been reported.
Eye contamination has resulted in conjunctivitis and keratitis, sometimes resulting
in corneal scarring. The constituents of creosote are efficiently absorbed across
the skin, but systemic poisonings following dermal absorption have occurred
very rarely. Absorption of ingested creosote from the gut occurs promptly, and
there may be significant absorption of vapor by the lung. Conjugates of absorbed
phenolic constituents are excreted mainly in the urine. Acute toxic effects are
similar to those oflysol, but the corrosive nature of creosote is somewhat less
because of greater dilution of phenol in the creosote.7 Irritation of the
gastrointestinal tract, toxic encephalopathy, and renal tubular injury are the
principal effects. A chronic toxicosis from continuing gastrointestinal absorption
(creosote used medicinally) has been described, consisting of gastroenteritis
and visual disturbances.
MISCELLANEOUS 185
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Manifestations of acute systemic poisoning are salivation, vomiting, dyspnea,
headache, dizziness, loss of pupillary reflexes, cyanosis, hypothermia, convulsions,
and coma. Death is due to multi-organ system failure as patients develop shock,
acidosis, respiratory depression, and anuric renal failure.
Confirmation of Poisoning
The presence of phenolic oxidation products imparts a dark, smoky color
to the urine.7 If there is suspicion of poisoning, addition of a few drops of ferric
chloride solution to the urine yields a violet or blue color, indicating the pres-
ence of phenolic compounds.
Treatment
1. Skin decontamination. Stringent measures should be taken to avoid con-
tamination of skin or eyes and inhalation of vapor. Skin contamination should
be promptly washed off with soap and water. Remove eye contamination by
washing with copious amounts of water, then obtain specialized medical atten-
tion promptly because cornea! injury may be severe. See Chapter 2.
2. Gastrointestinal decontamination. If a significant amount of creosote has
been ingested and the patient is alert and able to swallow, immediately administer
a slurry of activated charcoal by mouth. Further efforts to limit absorption will
depend on whether there has been corrosive injury to the esophagus. If pharyn-
geal redness and swelling are evident, neither induced emesis nor gastric lavage is
advisable due to potential re-exposure of the esophagus to the creosote, or perfo-
ration of the esophagus from a gastric tube. For further information on gastric
decontamination, including charcoal dosing, see Chapter 2.
3. Maintain pulmonary ventilation mechanically with oxygen, if necessary.
4. Blood and urine samples. Draw a blood sample to test for methemoglo-
binemia, to measure BUN and blood electrolytes, and to check for signs of liver
injury (bilirubin, GGT, LDH, ALT, AST, and alkaline phosphatase). Examine
the urine for protein and cells, and for "smoky" phenolic excretion products.
5. Intravenous fluids. Give fluids intravenously to correct dehydration and
electrolyte disturbances. Include glucose to protect the liver and bicarbonate to
relieve metabolic acidosis, as necessary. Monitor fluid balance carefully to signal
discontinuation of intravenous fluids if renal failure occurs. Plasma or blood
transfusion may be needed to overcome shock.
6. Monitor ECG to detect arrhythmias and/or conduction defects that may
appear as manifestations of a toxic myocardiopathy
186 MISCELLANEOUS
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7. Convulsions. Anticonvulsants may be needed to control seizures as out-
lined in Chapter 2.
8. Hemodialysis is not effective in accelerating disposition of phenol (or,
presumably, creosote), but hemoperfusion over charcoal probably is effective.8
This should be considered in severe creosote poisonings.
9. Methemoglobinemia is rarely severe, but intravenous administration of 1%
methylene blue may be considered if 25-30% of hemoglobin is converted. Dose
is 0.1 mL of 1% solution per kg body weight, given over no less than 10 minutes.
Nausea, dizziness, and a transient increase in blood pressure may occur.
ENDOTHALL
As the free acid or as sodium, potassium, or amine salts, endothall is used as
a contact herbicide, defoliant, aquatic herbicide, and algacide. It is formulated in
aqueous solutions and granules at various strengths.
Toxicology
Endothall is irritating to the skin, eyes, and mucous membranes. It is well
absorbed across abraded skin and from the gastrointestinal tract. Recognized
systemic toxic mechanisms in mammals are: corrosive effects on the gastrointes-
tinal tract (particularly from high concentrations of the free acid); cardiomy-
opathy and vascular injury leading to shock; and central nervous system injury,
causing convulsions and respiratory depression. A single case has been reported
of lethal poisoning in a previously healthy 21-year-old man who died after
ingestion of 7-8 grams of endothall. In this patient, hemorrhage and edema
were noted in the gastrointestinal tract and lungs.9 There are no standards for
levels, and they are not considered useful in management.
Treatment
1. Skin decontamination. Wash endothall from the skin with soap and water.
Flush contamination from the eyes with copious amounts of clean water. Ob-
tain medical attention if irritation of skin or eyes persists. See Chapter 2.
2. Gastrointestinal decontamination. If a large quantity has been ingested, the
patient is seen within an hour of exposure, and is fully alert and not convulsing,
gastrointestinal decontamination should be considered as outlined in Chapter 2.
Lavage is usually contraindicated due to the corrosive nature of this agent.
MISCELLANEOUS 187
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3. Intubation. If there are indications of corrosive effects in the pharynx,
gastric intubation should not be attempted because of the risk of esophageal
perforation.Treatment procedures appropriate for ingestions of corrosives (strong
acids and alkalis) may be necessary Referral should be made to a surgeon or
gastroenterologist for consideration of endoscopy
4. Oxygen should be given by mask. If respiratory drive is weak, pulmonary
ventilation may have to be supported mechanically
5. Monitor blood pressure closely Infusions of plasma, blood, other volume
expanders, and pressors may be needed to combat shock.
6. Administer intravenous fluids to correct dehydration, stabilize electro-
lytes, provide sugar, and support mechanisms for toxicant disposition. Give va-
soactive amines very carefully in light of possible myocardiopathy
7. Convulsions. Seizures may require administration of diazepam and/or other
anticonvulsants.
8. Hemodialysis. It is not known whether hemodialysis or hemoperfusion
would be effective in removing endothall from the blood. This option should
be considered if the patient's condition deteriorates despite supportive care.
METALDEHYDE
Toxicology
Metaldehyde is a four-unit cyclic polymer of acetaldehyde which has long
been used to kill slugs and snails, which are attracted to it without the use of
bait. Occasional poisonings of animals and children have resulted from inges-
tion of pellets intended as molluscicide, but tablets designed as a combustible
fuel ("meta-fuel") have also been responsible for human poisonings.10 Another
form of exposure is "snow storm tablets," which the user places at the end of a
lighted cigarette to create snow. Toxicity occurs through inhalation of
metaldehyde fumes.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 metaldehyde-
poisoned dogs.12
Ingestion of a toxic dose is often followed shortly by nausea and vomiting.
The other primary features of toxicity are pyrexia, generalized seizures, and
mental status changes, sometimes leading to coma.10'13 Other signs and symp-
toms that may occur include hypersalivation, facial flushing, dizziness, tachyp-
nea, and acidosis.10'11 Pneumonitis has followed inhalational exposure to
188 MISCELLANEOUS
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metaldehyde.11 While most cases are dramatic with significant seizures and coma,
fatal events are infrequent.10'13 Poisoned animals show tremors, ataxia, hyperes-
thesia, salivation, ataxia, and seizures.12 Autopsy findings in fatal human poison-
ings indicate severe damage to liver cells and renal tubular epithelium.
Confirmation of Poisoning
Metaldehyde can be measured in the blood and urine, although there are
very few reports of levels among poisoned humans. One patient who had se-
vere tonic clonic seizures and was comatose had a metaldehyde level in the
serum of 125 nig/L with a half-life of 27 hours. This patient did not have
detectable acetaldehyde in the serum.13
Treatment
1. Gastrointestinal decontamination. If ingestion occurred within an hour
of treatment, consider gastrointestinal decontamination as outlined in Chapter 2.
Activated charcoal may well be useful against metaldehyde.
2. Convulsions. If seizures occur, sedative anticonvulsants must be adminis-
tered. See Chapter 2 for dosage.
3. Supportive treatment. Appropriate supportive treatment including intra-
venous fluids containing saline and glucose should be given. Sodium bicarbon-
ate may be considered in the event of severe metabolic acidosis. Fluid balance
and electrolytes must be monitored carefully to avoid fluid overload if renal
failure supervenes.
4. Renal failure. There is no specific antidote for metaldehyde poisoning.
Hemodialysis is probably not effective in removing metaldehyde, but must be
instituted if renal failure occurs. The effectiveness of hemoperfusion has not
been tested.
5. Liver function tests and urine sediment examination should be done to
assess liver and kidney injury in poisoned patients.
SODIUM CHLORATE
Sodium chlorate is used in agriculture as a defoliant, nonselective contact
herbicide, and semipermanent soil sterilant. Because of its explosive nature, it
must be formulated with water-soluble fire retardant material, such as sodium
metaborate, soda ash, magnesium chloride, or urea. It is usually applied in water
solution.
MISCELLANEOUS 189
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Toxicology
Sodium chlorate is irritating to skin, eyes, and mucous membranes of the
upper respiratory tract.14 Dermal absorption is slight. Even though gastrointes-
tinal absorption is also inefficient, severe (sometimes fatal) poisoning follows
ingestion of a toxic dose, estimated at about 20 grams in the adult human.
Excretion is chiefly in the urine. The principal mechanisms of toxicity are
hemolysis, methemoglobin formation, cardiac arrhythmia (partly secondary to
hyperkalemia), and renal tubular injury14'15
The irritant action on the gut causes nausea, vomiting, and abdominal pain.
Once absorbed, hemoglobin is rapidly oxidized to methemoglobin, and intravas-
cular hemolysis occurs.14 Cyanosis is prominent if methemoglobinemia is severe
and may be the only presenting sign.15 Acute tubular necrosis and hemoglobin -
uria may result from the hemolysis or direct toxic injury. Plasma and urine are
dark brown from the presence of free hemoglobin and methemoglobin.14'15'16
Release of potassium from red cell destruction results in hyperkalemia which
may be severe enough to cause life-threatening arrythmias.16 The liver and spleen
are often enlarged due to uptake of hemolyzed erythrocytes.15 Hypoxemia may
lead to convulsions. Death may be the result of shock, tissue hypoxia, renal failure,
hyperkalemia, or disseminated intravascular coagulation (DIG).14'15'16
Confirmation of Poisoning
There are no widely available tests specifically for chlorate. Dark brown
staining of the plasma and urine indicates the action of a strong oxidizing agent
on hemoglobin. See Chapter 2.
Treatment
1. Skin decontamination. Skin contamination should be removed immedi-
ately by washing with soap and water. Medical attention should be sought if
irritation persists. Flush contamination from eyes with copious amounts of clean
water, then obtain specialized medical attention promptly, because irritant ac-
tion may be severe. See Chapter 2.
2. Gastrointestinal decontamination. If sodium chlorate has been ingested
within an hour prior to treatment, consider gastrointestinal decontamination as
outlined in Chapter 2.
3. Oxygen. If respiration is depressed, ventilatory support may be necessary.
4. Sodium thiosulfate has been recommended as an antidote against absorbed
sodium chlorate.Thiosulfate is thought to inactivate the chlorate ion to form the
190 MISCELLANEOUS
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less toxic chloride ion. It can be given orally or as an IV infusion over 60-90
minutes. The dose is 2-5 g dissolved in 200 mL of 5% sodium bicarbonate.14
5. Monitor blood pressure, fluid balance, blood electrolytes, BUN, methemo-
globin, and bilirubin, as well as urine protein, cells and free hemoglobin con-
tent, and EGG. Widening of the QRS complex and prolongation of the PR
interval indicate hyperkalemic cardiac toxicity
6. Milk may be helpful in relieving the pain of gastric irritation.
7. Administer intravenous fluids to sustain chlorate excretion. Maintain
urine pH in the alkaline range by adding sodium bicarbonate to the infusion
fluid. Monitor urine production closely, so that intravenous fluids can be slowed
or discontinued if renal failure occurs. Blood transfusion may be needed if
hemolysis and methemoglobinemia are severe. Exchange transfusion has been
recommended to enhance clearance and treat DIG.16
8. Hemodialysis may be life-saving in severe poisoning. It is effective in re-
moving chlorate from the blood, provides a means to control hyperkalemia,
and makes possible the control of extracellular fluid volume and composition
while renal function remains impaired.
9. Methemoglobinemia. Administration of methylene blue to reverse meth-
emoglobinemia may be considered if as much as 25-30% of hemoglobin is
converted. Give intravenously 0.1 mL/kg body weight of a 1% solution over a
period of at least 10 minutes. An increase in blood pressure, nausea, and dizzi-
ness may occur, but these effects are usually transient. As the use of this agent in
chlorate poisoning has not proven beneficial in the past, it is still advisable to
proceed to exchange transfusion as stated in #7.
SYNERGISTS:
PIPERONYL BUTOXIDE
Synergists are chemical agents included in pesticide products to enhance
the killing power of the active ingredients. The widely-used insecticide syner-
gist, piperonyl but oxide, acts by inhibiting the enzymatic degradation of pyre -
thrins, rotenone, N-methyl carbamates, and possibly some other insecticides.
There is limited dermal absorption on contact. Inherent toxicity in mammals is
low. Large absorbed doses may theoretically enhance the toxic hazard of the
rapidly metabolized insecticides used today, although inhibition of human drug-
metabolizing enzymes by these agents has not actually been demonstrated.Their
presence in pesticide products to which humans are exposed does not change
MISCELLANEOUS 191
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the basic approach to management of poisoning, except that some possibility of
enhanced toxicity of the active insecticidal ingredients should be kept in mind.
SOLVENTS AND ADJUVANTS
Liquid materials in which pesticides are dissolved and the solids on which
they are adsorbed (sometimes called carriers or vehicles) are selected by pro-
ducers to achieve stability of the active ingredient, convenience in handling
and application, and maximum killing power following application. Often, the
particular solvents and adjuvants selected by pesticide manufacturers are re-
sponsible for giving their commercial products a competitive edge. For this
reason, their inclusion in marketed products is usually proprietary information,
not available to the general public except in emergencies. If a poisoning emer-
gency exists, pesticide companies will usually cooperate in supplying physicians
with information needed to provide treatment. Some companies will put the
inert ingredients on the Material Safety Data Sheet (MSDS). The physician
should seek this information to assist in evaluating all possible exposures. A
direct request to the producer is the quickest way to secure this information.
Physicians may also contact EPA directly for this information (tel: 703-305-
7090) if needed for proper management of a case.
Petroleum distillates are the most commonly used solvents for lipo-
philic pesticides. Most insecticides are lipophilic. The distillates are mixtures of
aliphatic and aromatic hydrocarbons and have low boiling points.
Sometimes specific hydrocarbons, such as toluene or xylene (strongly
odiferous), are added to stabilize the solution of insecticide or make it more
emulsifiable. Hydrocarbon-dissolved pesticides are usually diluted for applica-
tion by adding measured amounts of water to form emulsions. Some chlori-
nated hydrocarbons may be present in particular technical mixtures. A strong
odor lingering after application of a structural pest control spray is often due to
the solvent rather than the active ingredient.
Less lipophilic active ingredients are sometimes dissolved in mixtures of
alcohols, glycols, ethers, or various chlorinated solvents. It is possible that these
enhance the dermal absorbability of some pesticides. Some solvents, such as
methanol and isopropanol, may represent a significant toxic hazard if swallowed
in sufficient dosage.
Granular formulations utilize various clay materials which adsorb pesti-
cide, retain it in more or less stable form until application, then desorb the
material slowly into treated soil. There is some significant desorption when
granules are in contact with human skin and very substantial desorption into
gastrointestinal secretions if granules are swallowed. The clay materials them-
selves are not a toxic hazard.
Dusts are infrequently used today. Various forms of talc (silicatecarbonate
particles) have been used in the past to adsorb pesticides for application to
192 MISCELLANEOUS
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foliage. Particle sizes are such that these dusts are usually trapped in the upper
respiratory mucous when inhaled.When the mucous is swallowed, the particles
desorb pesticide into gastrointestinal secretions. Dust formulations may, there-
fore, release enough of some pesticides to cause systemic poisonings.
Stickers and spreaders (film extenders) are organic substances added to
formulations to disperse pesticide over treated foliage surfaces and enhance
adhesion.The availability and persistence of residue on the leaf surfaces is thereby
increased. Substances used include proteinaceous materials (milk products, wheat
flour, blood albumin, gelatin), oils, gums, resins, clays, polyoxyethylene glycols,
terpenes, and other viscid organics. Some also include sulfated alcohols, fatty
acid esters, and alkyl and petroleum sulfonates. For persons exposed in the
course of formulation or application of pesticides, these adjuvants probably add
little or no toxic hazard to that inherent in the active pesticidal ingredients.
Emulsifiers serve to stabilize water-oil emulsions formed when water is
added to technical hydrocarbon concentrates. Chemically, they resemble deter-
gents (one part of the molecule lipophilic, the other hydrophilic). Long-chain
alkyl sulfonate ethers of polyethylene glycol and polyoxyethylene oleate are
exemplary emulsifiers. They have low inherent mammalian toxicity, and their
presence probably has little effect on the overall toxicity of formulated products
which include them.
Penetrants facilitate the transfer of herbicide from foliage surface to the
interior tissues. Some are lipids while others are detergent (surfactant) in na-
ture. Substances used include heavy petroleum oils and distillates, polyol fatty
acid esters, polyethoxylated fatty acid esters, aryl alkyl polyoxyethylene glycols,
alkyl amine acetate, alkyl aryl sulfonates, polyhydric alcohols, and alkyl phos-
phates. Some of these are eye and skin irritants, and may account for the irritant
effects of particular herbicide formulations whose active ingredients do not
have this property.
Safeners are substances added to mixtures of fertilizers with pesticides (com-
monly herbicides) to limit the formation of undesirable reaction products. Some
substances used are alcohol sulfates, sodium alkyl butane diamate, polyesters of
sodium thiobutane dioate, and benzene acetonitrile derivatives. Some are mod-
erately irritating to the skin and eyes. Systemic toxicities are generally low.
Anticaking agents are added to granular and dust formulations to facili-
tate application by preventing cakes and clumps. Among several products used
are the sodium salt of mono- and di-methyl naphthalene sulfonate, and diato-
maceous earth. Diatomaceous earth has little adverse effect except a drying
action on the skin. Methyl naphthalenes are said to be skin irritants and photo-
sensitizers; whether their derivatives have this effect is not known.
MISCELLANEOUS 193
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Treatment
Petroleum distillates are mineral hydrocarbons which undergo limited ab-
sorption across the gut. In general, clinical toxicologists do not recommend in-
duced emesis or gastric lavage in treating ingestions of these materials, because of
the serious risk of hydrocarbon pneumonitis if even tiny amounts of the liquid
are aspirated into the lung. However, this injunction against emptying the stom-
ach may be set aside when the petroleum distillate is a vehicle for toxic pesticides
in significant concentration. In such cases, if the patient is seen within one hour
of exposure, gastrointestinal decontamination should be considered.
Rapid respiration, cyanosis, tachycardia, and low-grade fever are the usual
indications of frank hydrocarbon pneumonitis. Patients with presumed hydrocar-
bon pneumonitis, who are symptomatic, should usually be hospitalized, prefer-
ably in an intensive care setting. If the patient has pulmonary symptoms, a chest
x-ray should be taken to detect or confirm signs of pneumonitis. In addition, the
urine should be examined for protein, sugar, acetone, casts, and cells, and an EGG
should be examined for arrhythmias and conduction defects. Mechanically as-
sisted pulmonary ventilation with 100% oxygen may be required. Hydrocarbon
pneumonitis is sometimes fatal, and survivors may require several weeks for full
recovery. In milder cases, clinical improvement usually occurs within several days,
although radiographic findings will remain abnormal for longer periods.17
The presence of chlorinated solvents in some formulations may add sig-
nificantly to the toxic hazard, particularly if the product is ingested. Certain
adjuvants are irritants to skin, eyes, and mucous membranes, and may account
for the irritant properties of some products whose active ingredients do not
have this effect. With these exceptions, however, the presence of adjuvants in
most finished pesticide products probably does not enhance or reduce systemic
mammalian toxicity to any great extent.
References
1. Spyker DA, Lynch C, Shabanowitz J, et al. Poisoning with 4-aminopyridine: Report of three
cases. ClinToxicol 1980;16:487-97.
2. PickettTA and Enns R. Atypical presentation of 4-aminopyridine overdose. Ann Emerg Med
1996;27:382-5.
3. Stork CM and Hoffman RS. Characterization of 4-aminopyridine in overdose. Clin Toxicol
1994;32:583-7.
4. Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
NJ: Noyes Publications, 1991, pp. 316-7.
5. Torrelo A, Soria C, Rocamora A, et al. Lichen planus-like eruption with esophageal involve-
ment as a result of cyanamide. J Am Acad Dermatol 1990;23:1168-9.
6. Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
NJ: Noyes Publications, 1991, pp. 450-3.
7. Bowman CE, Muhleman MF, andWalters E. A fatal case of creosote poisoning. Postgrad Med
/1984;60:499-500.
194 MISCELLANEOUS
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8. Christiansen RG and Klaman JS. Successful treatment of phenol poisoning with charcoal
hemoperfusion. Vet Hum Toxicol 1996;38:27-8.
9. AUenderWJ. Suicidal poisoning by endothall. / Anal Toxicol 1983;7:79-82.
10. LongstrethWT and Pierson DJ. Metaldehyde poisoning from slug bait ingestion. WestJMed
1982;137:134-7.
11. Jay MS, Kearns GL, Stone V, et al.Toxic pneumonitis in an adolescent following exposure to
snow storm tablets. JAdoIesc Health 1988;9:431-3.
12. Booze TF and Oehme FW. An investigation of metaldehyde and acetaldehyde toxicities in
dogs. Fundam ApplToxicol 1986;6:440-6.
13. Moody JP and Inglis FG. Persistence of metaldehyde during acute molluscicide poisoning.
Hum Exp Toxicol 1992;ll:361-2.
14. HelliwellM and Nunn J. Mortality in sodium chlorate poisoning. Br Med] 1979;! :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, NamasonthiV, and Ginsburg CM. Criteria for hospitalizing children who have
ingested products containing hydrocarbons. JAMA 1981;246:840-3.
MISCELLANEOUS 195
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CHAPTER 19
HIGHLIGHTS
Compounds are registered
for medical or medicinal use
rather than as pesticides
Several are among the most
frequently reported human
poisonings in the U.S.
Iodine is well absorbed
through abraded or burned
skin
Disinfectants
A wide variety of disinfectant agents are used to destroy microorganisms and
they differ greatly in their toxic effects. Most disinfectants can conveniently be
grouped into a few categories, some of which are also represented in other
classes of pesticides. Many of these materials are not registered as pesticides, but
are registered for medical or medicinal use. This chapter reviews a few of the
more common or more severely toxic disinfectants.
Signs and Symptoms:
Highly variable based on
agent
Many are irritants and
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
ALCOHOLS
Alcohols have a long history of use as disinfectants. Often disinfectants are
mixtures, usually of ethanol and isopropyl alcohol (isopropanol).The alcohol
most commonly used in households as a disinfectant is isopropyl alcohol, com-
monly marketed as a 70% solution. It is a clear, colorless liquid with an odor
similar to ethanol.
Toxicology of Isopropyl Alcohol
Isopropyl alcohol is well and rapidly absorbed from the gastrointestinal tract.
It is also well absorbed by skin and by inhalation. It is considered to be more toxic
to the central nervous system than ethanol, with similar effects. Both ingestion
and inhalation at high concentrations can result in the rapid onset of CNS
depression with subsequent coma and death. Apnea commonly accompanies
this CNS depression.1'2 Similar neurological toxicity has been reported with
excessive topical exposure to the umbilicus of a neonate.3 Irritation of the
gastrointestinal tract results in gastritis and severe vomiting. Isopropyl alcohol may
also produce mild hepatic injury with acute exposures. Acute tubular necrosis has
been reported with this agent,1 but the renal toxicity is not as great as with
methanol poisonings. Ketosis without metabolic acidosis but prominent hypogly-
cemia is common.2'3 This ketosis is the result of direct metabolism of this
compound to acetone.1'3 Monitoring of isopropyl levels is useful, when available.
In addition, blood levels of acetone and glucose should be determined to aid
in management.
196 DISINFECTANTS
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Confirmation of Poisoning
Commercial Products
Isopropyl alcohol can be measured in the blood and urine. Serum acetone
can also be measured. Blood isopropyl alcohol levels of 128-200 mg/dL have
been associated with death.
Treatment: Isopropyl Alcohol
1. Gastrointestinal decontamination. Since the onset of coma is often rapid
with this poisoning, induced emesis is contraindicated, though spontaneous
vomiting often occurs. If the patient has ingested a large amount, has not vom-
ited, and is seen within one hour of exposure, consideration should be given to
gastric emptying by lavage as outlined in Chapter 2.
Isopropyl alcohol is well adsorbed to charcoal, so activated charcoal should
probably be administered, as outlined in Chapter 2.
2. Supportive care for hypotension and respiratory depression is critical to
survival and should be administered whenever possible in an intensive care
setting.
3. If hypoglycemia occurs, glucose administration is indicated in order to
maintain normoglycemia.
4. Hemodialysis has been reported to be beneficial in patients with severe
poisoning unresponsive to standard supportive therapy1'4
ALDEHYDES
The two aldehydes most commonly used as disinfectants are formaldehyde
and glutaraldehyde. Formaldehyde is discussed in Chapter 17, Fumigants. Glu-
taraldehyde is very similar to formaldehyde in its toxicity and treatment, al-
though it is probably slightly less toxic. Glutaraldehyde is commonly prepared
as an aqueous solution at a 2% concentration, and is slightly alkaline in this
solution. It has been reported to cause respiratory irritation, resulting in rhini-
tis5'6 and occupational asthma.6'7'8 It has also resulted rarely in palpitations and
tachycardia in human subjects. At high dosage, given orally, it results in gas-
trointestinal irritation with diarrhea, which may be hemorrhagic. Due to the
irritant effects of glutaraldehyde, the wearing of personal protective equipment
is required for the protection of skin (29 CFR 1910.132), and eyes (29 CFR
1910.133). OSHA standards require the use of appropriate respirators by em-
ployees that may be exposed to glutaraldehyde during routine or emergency
work procedures (29 CFR 1910.134).
ALCOHOLS
Isopropyl alcohol
ALDEHYDES
formaldehyde
glutaraldehyde
CATIONIC DETERGENTS
benzalkonium chloride
cetrimide
cetylpyridium chloride
CHLORHEXIDINE
Hibiclens
Hibistat
Peridex
HYPOCHLORITES
calcium hypochlorite
sodium hypochlorite
IODINES
povidone-iodine
Betadine
loprep
Pharmadine
MERCURIALS
mercurobutol
mercurochrome
merthiolate
nitromersol
phenylmercuric acetate
phenylmercuric nitrate
thimerosol
PHENOLS
2-benzyl-4-chlorophenol
cresol
Lysol
hexachlorophene
Bilevon
Dermaadex
Exofene
Gamophen
Phisohex
Surgi-Cen
Surofene
Texosan
o-phenylphenol
phenol
4-tert-amylphenol
thymol
triclosan
PINE OIL
DISINFECTANTS 197
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Treatment: Glutaraldehyde
1. Gastrointestinal decontamination. If a large amount has been ingested
and retained, and the patient is seen within one hour of exposure, consider
gastric emptying as described in Chapter 2. Administration of activated char-
coal should be considered, as described in Chapter 2.
2. Oxygen. If patient has been in an area with strong odor of glutaraldehyde
due to vaporization, remove to fresh air area and administer oxygen as needed.
3. Skin decontamination. If skin irritation is noted, vigorous skin decon-
tamination is indicated. However, systemic toxicity from skin exposure appears
unlikely.
CATIONIC DETERGENTS
Several cationic detergents are used as disinfectants. All share the capacity,
in sufficient concentration, to behave as caustic agents, capable of causing rather
severe, caustic burns. It appears that concentrations greater than approximately
7.5% are necessary to produce significant caustic injuries. However, experience
with human exposures to these compounds is very limited. The three agents
most commonly used as detergent disinfectants are benzalkonium chloride,
cetrimide, and cetylpyridium chloride.
Though there are no cetrimide preparations available in the U.S., several
are available in European Union countries. Concentrated solutions are usually
only available in industrial settings, such as production of consumer products,
or for use in hospitals for disinfectant purposes. Therefore, acute poisonings are
uncommon.
Toxicology
In low-concentration solutions, these agents have been reported to cause
eye discomfort as well as skin rashes and irritation. In stronger concentrations,
they can cause severe cornea! and skin burns. Likewise, strong concentrations
will result in caustic burns to lips, oral mucosa, esophagus, and stomach.9'10
Vomiting, diarrhea, and abdominal pain have been reported.11 Necrosis of the
gut, with peritonitis, has also been reported.12 In severe exposures, there are also
reports of CNS depression, liver injury, and pulmonary edema.9'11
Treatment
1. Skin decontamination. If a high-concentration solution has been applied
to skin, aggressive skin contamination and treatment of burns is appropriate. If
198 DISINFECTANTS
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a high concentration solution is in contact with the eyes, profuse washing of
the eyes is indicated followed by a careful exam of the corneas. If burns have
occurred, appropriate ophthalmologic care should be provided.
2. Gastrointestinal decontamination. Gastric emptying and other methods
of gastrointestinal decontamination are contraindicated in these poisonings.
Some experts recommend cautious dilution with small amounts of milk or
water.9'13 Acidic solutions such as juices should never be offered for dilution.
3. Endoscopy. If a highly concentrated solution was ingested or oral burns are
noted, the patient needs urgent endoscopy for grading of the caustic injury. The
endoscopy should be performed within 24 hours to minimize the risk of per-
foration from the procedure.12 A competent surgeon or gastroenterologist should
provide subsequent care.
4. Other agents. Although corticosteroids are commonly used to treat these
burns, their use remains controversial. Use of other agents, such as H2 antago-
nists and sulcralfate, has been reported but remains controversial at this time.
5. CNS, pulmonary and other systemic effects should be treated symptom-
atically, consistent with sound medical practice.
CHLORHEXIDINE
Chlorhexidine is a cationic biguanide, available in concentrations up to 4%
as a topical agent used as a skin cleanser and mouthwash. Skin preparations of
0.5%-4% are marketed under the trade names HibiclensR and HibistatR. It is
also marketed as a mouthwash in a 0.12% solution under the trade name PeridexR.
There is very little human experience with poisonings, as these concentrations
do not appear to be significantly toxic.
Toxicology
Chlorhexidine is poorly absorbed from skin or the gastrointestinal tract.
Therefore most effects noted have been primarily local. If a low concentration
solution is ingested or applied to the skin, mild local irritation can be seen.
Contact dermatitis, urticaria, and anaphylaxis have followed repeated skin ex-
posures to this agent.14'15 Cornea! injuries have been described in several cases
after inadvertent exposure of the eyes to the 4% concentration. These injuries
have resulted in permanent corneal scarring.16 Esophageal burns have been
reported in a single case after ingestion of a large quantity of a 20% solution of
this agent.17 Ulcerative colitis has been described after an enema of the 4%
DISINFECTANTS 199
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solution mixed with tap water (10 mL in 2 liters water).18 Liver toxicity can
occur with large exposures.17
Treatment
1. Gastrointestinal decontamination. If ingestion of a large quantity has
occurred within an hour and the patient has not vomited, gastrointestinal de-
contamination as described in Chapter 2 should be considered. If a highly
concentrated solution has been ingested, manage as a caustic ingestion as de-
scribed in the cationic detergents, without gastrointestinal decontamination.
2. Liver injury panel should be performed with large ingestions.
3. Eye decontamination. If eye exposure has occurred, the eyes should be
vigorously irrigated and a careful ophthalmologic exam should be performed
for corneal injury. If an injury has occurred, an ophthalmologic consultation
should be obtained.
HYPOCHLORITES
Hypochlorites are implicated in a large proportion of the disinfectant
poisonings reported to poison control centers in the United States. Most are
solutions of sodium or calcium hypochlorite solutions. Chloramine, a disin-
fectant used by many municipal water supplies, is an infrequent cause of acute
poisonings. Sodium and calcium hypochlorite solutions are of relatively low
toxicity.They are mildly corrosive to the eyes,19 and mucous membrane burns
have been reported.20 Significant poisonings are very infrequent with these
agents in solution.21
When hypochlorite solutions are mixed with acids or ammonia solutions,
chlorine or chloramine gas is produced, resulting in an irritant with pulmonary
toxicity. Many brief exposures have led to transient symptoms requiring lim-
ited emergency department management.22 However, in cases of prolonged
exposure or exposure to high concentrations, there is the potential for severe
toxic pneumonitis.23 While severe injury may be the exception to the rule,
great efforts should be made to discourage mixing of these materials with acid
or ammonia.
Treatment
1. Gastric decontamination. After oral exposures, gastric emptying is not
indicated. If a granular material is ingested, and the patient has symptomatic
mucosal burns, referral to a surgeon or gastroenterologist for consideration of
endoscopy and management may be appropriate.
200 DISINFECTANTS
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2. Dilution with water or milk not to exceed approximately 15 mL/kg in a
child or 120-240 mL in an adult is probably appropriate if vomiting has not
occurred. Administration of acids is contraindicated, due to the risk or increas-
ing generation of chlorine gas.
3. Eye decontamination. If eyes were exposed, they should be irrigated
profusely with water or saline. If cornea! burns are detected, referral to an
ophthalmologist is appropriate.
4. Skin decontamination. Skin exposure should also be managed by copi-
ous water dilutions. See Chapter 2.
5. Fresh air. If exposure to vapors or chlorine or chloramine gas has occurred,
patient should immediately be moved to fresh air. If symptoms occur or persist,
oxygenation should be assessed and oxygen should be administered as needed. If
persistent symptoms occur, a chest film should be obtained and hospital care
considered. Intensive care may need to be provided in severe inhalations.
IODINE
The most common iodine-containing disinfectant is povidone-iodine
(proviodine),in 7.5-10% solutions. Povidone-iodine is described as an iodophor,
which is a complex of iodine and polyvinylpyrrolidone, a solubilizing agent. It
is intended to liberate free iodine in solution for its effect. Although reported
concentrations of iodine in these solutions is only 80-120 ugm/dL, the total
available iodine is approximately 10% of the povidone-iodine. Therefore a 10%
solution will have in the range of 1% total available iodine.
Toxicology of Povidone-iodine
This compound is very poorly absorbed from the gastrointestinal tract, due
to the rapid conversion of free iodine to iodide in the stomach. Although
highly concentrated iodine solutions or iodine salts are corrosive to the gas-
trointestinal tract,24 solutions of povidone-iodine have little caustic potential.
Likewise, the compound is poorly absorbed from intact skin. All symptomatic
poisonings reported have occurred either after repeated exposure to burned
skin, or following irrigation of wounds, joints, or serosal surfaces such as the
mediastinum.25^28 The one exception was an infant who received an enema of
povidone-iodine in a polyethylene glycol solution, followed by whole bowel
irrigation with polyethylene glycol mixed with povidone-iodine. This child
died with severe hyperglycemia and very high iodine levels.24
In povidone-iodine exposures by these routes, the primary symptoms ini-
tially appear to be neurological, with headache, dizziness, delirium, hallucina-
DISINFECTANTS 201
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tions, and seizures.26 Hypotension, arrythmias, cyanosis, metabolic acidosis, shock,
and acute renal failure occur in severe cases.25'27'28 Hepatic injury, manifested by
elevated serum transaminase levels, has also been reported with very high level
exposures.27 Hyperkalemia has occurred, and the serum chloride may be falsely
elevated due to the presence of a second halide.25
Treatment: Povidone-lodine
1. Skin decontamination. Remove skin contamination by vigorous washing
with soap and water. See Chapter 2.
2. Gastrointestinal decontamination. If the patient is seen soon after a very
large ingestion, and vomiting has not occurred, consider gastrointestinal de-
contamination, as outlined in Chapter 2. Consider single dose charcoal.
3. Iodine clearance is apparently enhanced by procedures that enhance chlo-
ride excretion. Therefore, osmotic or choluretic diuresis is probably indicated
in these poisonings, if symptomatic.
4. Seizures. Treat seizures with anticonvulsants, as outlined in Chapter 2.
5. Monitor thyroid function following recovery to confirm euthyroid state.
MERCURIALS
A wide variety of organic mercurials have been used as disinfectants and as
preservatives. Nearly all uses have been banned in the United States. The tox-
icity and treatment of exposure to these compounds is described in detail in
Chapter 15, Fungicides, under organomercury compounds and will not be
repeated here.
PHENOLS
Several phenols are used as disinfectants. Cresol and thymol are alkyl de-
rivatives of phenol, while hexachlorophene and triclosan are chlorinated phenols.
Common commercial preparations are LysolR, a 50% solution of mixed cresols
in soap, and hexachlorophene, marketed under several trade names in soap bars
and some cosmetics. Cresols and hexachlorophene are discussed individually as
examples of these compounds that are familiar and for which there are some
human data.
202 DISINFECTANTS
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Toxicology of Cresols
Cresols, in common with phenol and other phenolic compounds, are highly
corrosive to all surfaces.With ingestion of concentrated forms they cause severe
corrosive injury to the mouth and upper gastrointestinal tract. Likewise, severe
eye and skin caustic injuries can occur with cresol exposure.29 Symptoms usu-
ally include nausea, vomiting, and diarrhea. Hypotension, myocardial failure,
pulmonary edema, and neurological changes may also occur.30 Liver and renal
toxicity, methemoglobinemia, and hemolysis have all been reported.30'31 After
long-term, repeated exposure, contact dermatitis may complicate these expo-
sures. These compounds are well absorbed from the gastrointestinal tract and
are also significantly absorbed from the skin and by inhalation.
Treatment: Cresols
1. Gastrointestinal decontamination. Due to the corrosive nature of these
compounds, gastrointestinal decontamination should not be attempted. Con-
sideration of dilution with milk or water is appropriate if vomiting has not
occurred.
2. Endoscopy. If a corrosive injury has occurred with burns to the mouth, or
if there is a clear history of gastrointestinal exposure, endoscopy should be
considered and a gastroenterologist or surgeon should be consulted for diagno-
sis and management.
3. Skin decontamination. If skin or eye contamination has occurred, copi-
ous irrigation should be performed. This should be followed by a careful eye
examination for cornea! burns. If corneal burns are noted, ophthalmologic
consultation should be obtained.
4. Respiratory and circulatory support should be provided in accordance
with sound medical management. If severe systemic symptoms persist, the pa-
tient should be treated in an intensive care unit, if possible.
Toxicology of Hexachlorophene
Hexachlorophene is well absorbed orally and dermally Dermal exposures
have led to severe toxicity and death in neonates, due to application to dam-
aged skin, or repeated or high-concentration skin exposures.32 Hexachlorophene
should never be used as a disinfectant on open wounds or abraded or inflamed
skin surfaces. In distinction to other phenolic compounds, this agent is not
significantly caustic and exposure does not result in the severe caustic injuries
seen with other phenolic chemicals.
DISINFECTANTS 203
-------
Hexachlorophene is a potent neurotoxicant. It causes brain edema and
spongy degeneration of white matter.33 This neurotoxicity can be seen after
acute or chronic exposures, either by skin absorption or ingestion.The nervous
system symptoms are complex. Lethargy is an early manifestation, followed by
muscular weakness, muscular fasciculation, irritability, cerebral edema, and pa-
ralysis, leading to coma and death. Seizures commonly occur in more severe
cases.32'34 Blindness and optic atrophy have been reported following exposure
to hexachlorophene.35
In addition to the neurological effects, common early symptoms of poison-
ing are vomiting, diarrhea, and anorexia.34 These findings have been accompa-
nied in animals by significant hepatotoxicity.36 With skin exposure, an erythema-
tous desquamative rash is often noted at the site of exposure.34 With chronic
exposure, contact dermatitis may be noted. In severe poisonings, cardiovascular
symptoms, including hypotension and bradycardia, have been noted.37 In a single
case, repeated exposure to this compound led to asthma in a pediatric nurse.38
Treatment: Hexachlorophene
1. Gastrointestinal decontamination. Since this agent is not generally caustic,
consideration should be given to aggressive gastrointestinal decontamination. If
the patient has ingested a significant amount and is seen within one hour of
exposure, gastric emptying is likely to be useful, as described in Chapter 2.
Since hexachlorophene is thought to have an enterohepatic recirculation, it
is possible that repeated dosing of activated charcoal, as outlined in Chapter 2,
will enhance clearance of this compound. However, hexachlorophene does not
bind well to charcoal and there are no clinical trials of this therapy for this agent.
2. Other therapies. Though this compound is quite toxic systemically and
enhanced clearance methods would appear beneficial, there is no evidence to
support the efficacy of hemodialysis, peritoneal dialysis, hemoperfusion, or ex-
change transfusion.37
3. Skin decontamination. If exposure has occurred through the skin, aggres-
sive washing of skin with soap or detergent and water is probably beneficial, to
remove any residues still on the skin. Since hexachlorophene is not soluble in
water, water washing alone will provide no significant benefit. See Chapter 2.
4. Neurological support and control of seizures is critical to survival and
should be performed, when possible, in an intensive care setting. Seizure con-
trol should be in accordance with recommendations in Chapter 2.
5. Cardiovascular and respiratory support are also very important to suc-
cess in treating severe poisonings with this agent and should be provided in an
intensive care unit in accordance with accepted medical practice.
204 DISINFECTANTS
-------
PINE OIL
Pine oil detergent and disinfectant solutions are among the most common
poisonings reported to poison control centers in the U.S. A relatively high
number of these are reported as serious or fatal. Pine oil is found in a variety of
household and commercial cleaners and disinfectants. It is a mixture of mono-
terpenes derived from the distillation of wood from various pine species, with
approximately 57% being alpha-pinene.39 Its most common side effects in smaller
dosage are irritation of mucous membranes, gastrointestinal irritation, mild res-
piratory and CNS depression, and renal toxicity Larger ingestions can result in
severe respiratory distress, cardiovascular collapse, and severe CNS effects. Re-
nal failure and myoglobinuria have also been reported in severe poisonings.40
Since even small ingestions can result in severe aspiration pneumonia, all
ingestions should be considered potentially hazardous.
While many of the reported effects of poisoning with this agent are related
to direct irritant effect on mucous membranes, gastrointestinal tract, and lung
(by aspiration), some reports suggest significant absorption from oral and rectal
exposures. Other reports suggest a lesser rate of absorption.39 While alpha-
terpineol can be measured in blood, there are no data relating levels to degree
of toxicity. Consequently, this measure is not considered useful in guiding
diagnosis and management.
Treatment
1. Gastrointestinal decontamination. Since there is a high risk of aspira-
tion pneumonia, induced emesis is usually considered contraindicated in these
poisonings. However, spontaneous emesis may occur due to direct irritation of
the gastric mucosa.
If the patient is seen within an hour of ingestion and a large amount has
been ingested, gastric emptying by intubation and lavage may be considered, as
described in Chapter 2. However, some studies have suggested greater rates of
complications with lavage than with ipecac-induced emesis.40
There is no evidence that activated charcoal is helpful in these poisonings.
Likewise, though a variety of enhanced elimination methods have been pro-
posed and tried, there is no evidence to support their efficacy
2. Eye decontamination. If eye exposure has occurred, copious irrigation
of the eyes is appropriate.
3. Pulmonary symptoms. The patient should be observed for at least six
hours with any significant ingestion in order to observe the onset of any symp-
toms, particularly pulmonary symptoms. If any pulmonary symptoms are ob-
served, the patient should have a chest film and measurement of oxygenation,
DISINFECTANTS 205
-------
and hospitalization is appropriate. With severe pulmonary symptoms, transfer
to an intensive care unit is usually appropriate. With severe aspiration, manage-
ment should be handled as in any severe aspiration pneumonia, in accordance
with accepted medical practice. Other severe systemic effects should be treated
in accordance with accepted medical practice.
References
1. Lacouture PG.Wason S, Abrams A, et al. Acute isopropyl alcohol intoxication: Diagnosis and
management. Am ]Med 1983;75:680-6.
2. Rich], Scheife RT, Katz N, et al. Isopropyl alcohol intoxication. Arch Afeuro/1990;47:322-4.
3. Vivier PM, Lewander WJ, Martin HF, et al. Isopropyl alcohol intoxication in a neonate
through chronic dermal exposure: A complication of a culturally-based umbilical care prac-
tice. Pediatr Emerg Care 1994;10:91-3.
4. Manring E, Meggs W, Pape G, et al.Toxicity of an intravenous infusion of isopropyl alcohol.
JToxicol Clin Toxicol 1997;35:503.
5. Norback D. Skin and respiratory symptoms from exposure to alkaline glutaraldehyde in
medical services. ScandJWork Environ Health 1988;!4:366-71.
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 technolo-
gist 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. HumToxicol 1988;7:567-9.
10. Wilson JT and Burr IM. Benzaldonium chloride poisoning in infant twins. AJDC
1975;129:1208-9.
11. ChanTY. Poisoning due to savlon (cetrimide) liquid. Hum 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 Spe-
cialty Board. Englewood, CO: Micromedex, 1988.
14. WongWK, Goh CL, and Chan KW. Contact urticaria from chlorhexidine. Contact Dermatitis
1990;22:52.
15. Okano M, Nomura M, Hata S, et al. Anaphylactic symptoms due to chlorhexidine glucon-
ate. Arch Dermatol 1989;125:50-2.
16. Tabor E, Bostwick DC, and Evans CC. Cornea! 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;! :289.
18. Hardin RD andTedesco FJ. Colitis after hibiclens enema. / Clin Gastroenterol 1986;8:572-5.
19. Ingram TA. Response of the human eye to accidental exposure to sodium hypochlorite. /
Emfodl990;16:235-8.
206 DISINFECTANTS
-------
20. French RJ.Tabb HJ, and Rutledge LJ. Esophogeal stenosis produced by ingestion of bleach.
South Med/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/1993;86:654-7.
23. Reisz GR and Gammon RS. Toxic penumonitis from mixing household cleaners. Chest
1986:89:49-52.
24. KurtTL, HnilicaV, Bost R, et al. Fatal iatrogenic iodine toxicity in a 9-week old infant. Vet
Hum Toxto/1992;34:333.
25. Means LJ, Rescorla FJ, and Grosfield JL. Iodine toxicity: An unusual cause of cardiovascu-
lar collapse during anesthesia in an infant with Hirschsprung's Disease. / Pediatr Surg
1990;25:1278-9.
26. Ponn RB. Continuous povidone-iodine irrigation (letter). 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, Nogue S, and Bertran A. Acute renal failure in a patient treated by
continuous povidone-iodine mediastinum irrigation. /Pediatr Surg 1988;29:410-2.
29. Pegg SP and Campbell DC. Children's burning due to cresol. Burns 1985;ll:294-6.
30. Arthus GJ.Wise CC, and Coles GA. Poisoning by cresol. Anaesthesia 1977;32:642-3.
31. Chan TK, Mak LW, and Ng RP. Methemoglobinemia, heme bodies, and acute massive intra-
vascular hemolysis in lysol poisoning. Blood 1971;38:739-44.
32. Mullick FG. Hexachlorophene toxicity Human experience at the Armed Forces Institute
of Pathology. Pediatrics 1973;51 (2)11:395-9.
33. Anderson JM, Cockburn F, Forfar J, et al. Neonatal spongioform myelinopathy after re-
stricted application of hexachlorophane skin disinfectant./ Clin Pathol 1981;34:25-9.
34. Martin-Bouyer G, Lebreton R.Toga M, et al. Outbreak of accidental hexachlorophene poi-
soning in France. Lancet 1982;l:91-5.
35. SlamovitzTL, Burde RM, and KlingeleTG. Bilateral optic atrophy caused by chronic oral
ingestion and topical application of hexachlorophene. Am J Ophthalmol 1980;89:676-9.
36. Prasad GV, Rajendra W, and Indira K. Brain ammonia metabolism in hexachlorophene-
induced encephalopathy. Bull Environ Contam Toxicol 1987;38:561-4.
37. Boehm RM and Czajka PA. Hexachlorophene poisoning and the ineffectiveness of perito-
neal dialysis. JToxicol Clin Toxicol 1979;14(3);257-62.
38. Nagy 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. LitovitzTL, SchmidzBF, Matyunas N, et al. 1987 Annual Report of the American Association of
Poison Control Centers National Data Collection System. Am]EmergMed 1988;6:479-515.
DISINFECTANTS 207
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Index of Signs and Symptoms
Presented in this chapter are lists of pesticides reported to have caused particu-
lar symptoms and signs, or combinations thereof, in poisoned individuals. The
lists may help direct the attention of health professionals to possible toxic causes
of the various disease manifestations, prompting inquiry into likelihood of ex-
posure to the listed chemicals. If certain agents appear suspect, inquiry can then
be made into the presence of additional manifestations typical of poisoning by
those substances.
The limitations of this approach to diagnosis must be understood. First, all
manifestations of illness have multiple causes, pesticidal and nonpesticidal.
Second, there are no specific symptoms or signs that are invariably present in
poisonings by particular pesticides.Third, many poisonings are characterized by
unexpected manifestations.
Finally, neither route of exposure nor dosage of pesticide is taken into
account in this listing. For example, effects of high-dose ingestion are not
distinguished from effects of relatively low-dose dermal absorption, nor are
topical effects distinguished from systemic dermal manifestations. The lists of
pesticides can only be regarded as clues to prompt further inquiry by the inter-
viewing professional.
The term manifestation means either symptom or sign. The word "poison-
ing" is used loosely in these headings to include topical as well as systemic effects.
Pesticides which are relatively consistent in causing particular manifestations are
listed in the middle column, headed "Characteristic of These Agents." Pesticides
that have caused various conditions with less consistency, or are less prominent
features of poisoning, are listed in the right-hand column, headed "Occurs
withThese Agents." Obviously, the distinction is not clear-cut.
Some symptoms (malaise, fatigue, dizziness) occur so commonly in poi-
soned individuals that they have little or no value in differential diagnosis, and
are therefore not included in these tables.
210 SIGNS AND SYMPTOMS
-------
General
MANIFESTATION
Rotten egg odor
Hypothermia
Hyperthermia
(fever, pyrexia)
Chills
Hot sensations
Myalgia
Thirst
Anorexia
Alcohol intolerance
Sweet taste
in the mouth
Metallic taste in the
mouth
Salty, soapy taste
In the mouth
CHARACTERISTIC OF
THESE AGENTS
Sulfur
Creosote
Norbormide
Nitrophenols
Pentachlorophenol
Phosphine
Arsine
Nitrophenols
Chlordimeform
Paraquat
Chlorophenoxy compounds
Pentachlorophenol
Nitrophenois
Inorganic arsenicals
Phosphorus
Phosphides
Sodium fluoride
Cholecalciferol
Aminopyridine
Organophosphates
Carbamate insecticides
Nicotine
Pentachlorophenol
Hexachlorobenzene
Chlordimeform
Cholecalciferol
Thiram
Calcium cyanamide
Chlordimeform
Inorganic arsenicals
Organic mercury
Sodium fluoride
OCCURS WITH
THESE AGENTS
Bo rate
Thallium
Metaldehyde
Inorganic arsenicals
Chlorophenoxy compounds
Cadmium dusts
Naphthalene
Pentachlorophenol
Bo rate
Endothall
Halocarbon fumigants
Nitrophenols
Inorganic arsenicals
Aminopyridine
SIGNS AND SYMPTOMS 211
-------
Skin
MANIFESTATION
Irritation,
Rash,
Blistering, or
Erosion (without
sensitization)
Contact dermatitis
Flushing
Dermal sensitization
Beefy red palms, soles
Urticaria
Bullae
CHARACTERISTIC OF
THESE POISONINGS
Copper, organotin, cadmium
compounds
Metam sodium
Paraquat
Diquat
Sodium chlorate
Phosphorus
Sulfur
Glyphosate
Propargite
Sodium hypochlorite
Quaternary ammonia
Thiram
Chlordimeform
Cationic detergents
Hexachlorphene
Ethylene oxide
Formaldehyde
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
Bo rate
Chlorhexidine
PCP
DEET
Liquid fumigants
OCCURS WITH
THESE AGENTS
Pentachlorophenol
Picloram
Chlorophenoxy compounds
Captan
Rotenone
Diethyltoluamide
Creosote
Fungicides
Herbicides with
irritant properties
Petroleum distillate
Thiram plus alcohol
Anflazine
Chlorothalonil
Barban
Captafol
Formaldehyde
Fluoride
Pentachlorophenol
Hexachlorobenzene
212 SIGNS AND SYMPTOMS
-------
Skin (continued)
MANIFESTATION
Pallor
Cyanosis
Yellow stain
Keratoses, brown
discoloration
Ecchymoses
Jaundice
Excessive hair growth
Loss of hair
Loss of fingernails
Brittle nails, white striations
Sweating, diaphoresis
CHARACTERISTIC OF
THESE POISONINGS
Organochlorines
Fumigants
Sodium fluoride
Creosote
Sodium chlorate
Paraquat
Cadmium dusts
Sodium fluoroacetate
Strychnine
Crimidine
Nicotine
Organochlorines
Nitrophenols
Inorganic arsenicals
Coumarins
Indandiones
Carbon tetrachloride
Chloroform
Phosphorus
Phosphides
Phosphine
Paraquat
Sodium chlorate
Thallium
Organophosphates
Carbamate insecticides
Nicotine
Pentachlorophenol
Naphthalene
Aminopyridine
OCCURS WITH
THESE AGENTS
Coumarins
Indandiones
Organophosphates
Carbamate insecticides
Agents that cause shock,
myocardiopathy, severe
arrhythmias or convulsions
Phosphorus
Phosphides
Inorganic arsenicals
Diquat
Copper compounds
Hexachlorobenzene
Inorganic arsenicals
Paraquat
Inorganic arsenicals
Inorganic arsenicals
Thallium
Copper compounds
SIGNS AND SYMPTOMS 213
-------
Eye
MANIFESTATION
Conjunctivitis
(irritation of mucous
membranes, tearing)
Tearing
Yellow schlerae
Keratitis
Ptosis
Diplopia
Photophobia
Constricted visual fields
Optic atrophy
Miosis
Dilated pupils
Unreactive pupils
CHARACTERISTIC OF
THESE POISONINGS
Copper compounds
Organotin compounds
Cadmium compounds
Metam sodium
Paraquat
Diquat
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
OCCURS WITH
THESE AGENTS
Thiophthalimides
Thiram
Thiocarbamates
Pentachlorophenol
Chlorophenoxy compounds
Chlorothalonil
Picloram
Creosote
Aliphatic acids
Pentachlorophenol
Pyrethrins
Agents that cause jaundice
(see above under Skin)
Organotin compounds
Thallium
Nicotine (early)
214 SIGNS AND SYMPTOMS
-------
Nervous System
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Paresthesia
(chiefly facial,
transitory)
Organophosphates
Cyanopyrethroids
Phosphides
Organochlorines
Thiabendazole
Nicotine (late)
Paresthesia of extremities
Inorganic arsenicals
Organic mercury
Sodium fluoroacetate
Carbon disulfide
Thallium
Pyrethroids (transitory)
Headache
Organophosphates
Carbamate insecticides
Nicotine
Inorganic arsenicals
Organic mercury
Cadmium compounds
Organotin compounds
Copper compounds
Thallium
Fluoride
Borates
Naphthalene
Phosphine
Halocarbon fumigants
Creosote
Diquat
Cholecalciferol
Cyanamide
Organochlorines
Nitrophenols
Thiram
Pentachlorophenol
Paraquat
Diethyltoluamide
Behavioral - mood
Disturbances
(confusion, excitement,
mania, disorientation,
emotional lability)
Organic mercury
Inorganic arsenicals
Organotin compounds
Thallium
Nicotine
Sodium fluoroacetate
Diquat
Cyanide
Nitrophenols
Aminopyridine
Carbon disulfide
Methyl bromide
Organophosphates
Carbamate insecticides
Pentachlorophenol
Sodium fluoride
Diethyltoluamide
Organochlorines
Depression, stupor, coma,
respiratory failure, often
without convulsions
Organophosphates
Carbamate insecticides
Sodium fluoride
Bo rate
Diquat
Inorganic arsenicals
Metaldehyde
Sulfuryl fluoride
Halocarbon fumigants
Phosphorus
Phosphine
Paraquat
Chlorophenoxy compounds
Diethyltoluamide
Alkyl phthalates
SIGNS AND SYMPTOMS 215
-------
Nervous System (continued)
MANIFESTATION
Seizures/Convulsions
(clonic-tonic) sometimes
leading to coma
Muscle twitching
Myotonia
Tetany, carpopedal spasms
Tremor
Incoordination
(including ataxia)
Paralysis
Paresis, muscle weakness
Hearing loss
CHARACTERISTIC OF
THESE POISONINGS
Organochlorines
Strychnine
Crimidine
Sodium fluoroacetate
Nicotine
Cyanide
Acrylonitrile
Metaldehyde
Thallium
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
OCCURS WITH
THESE AGENTS
Nitrophenols
Pentachlorophenol
Inorganic arsenicals
Organotin compounds
Diquat
Bo rate
Sulfuryl fluoride
Methyl bromide
Chlorophenoxy compounds
Organophosphates
Carbamate insecticides
Aminopyridine
Organic mercury
Chlorophenoxy compounds
Chlorophenoxy compounds
Pentachlorophenol
Nitrophenole
Thiram
Organic mercury
Organochlorines
Organic mercury
Diethyltoluamide
216 SIGNS AND SYMPTOMS
-------
Nervous System (continued)
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Hypotension shock
Phosphorus
Phosphides
Phosphine
Sodium fluoride
Sodium chlorate
Bo rate
Thallium
Copper compounds
Endothall
Cyanamide
Inorganic arsenicals
Nicotine (late)
Creosote
Alkyl phthalate
Cycloheximide
Formaldehyde
Norbormide
Hypertension
Thallium (early)
Nicotine (early)
Organophosphates
Cardiovascular System
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Cardiac arrhythmias
Sodium fluoroacetate
Halocarbon fumigants
Nicotine
Sodium fluoride
Ethylene oxide
Sodium chlorate
Thallium-ventricular
Povidone-iodine
Veratrum alkaloid (sabadilla)
Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Organochlorines
Cyanide
Acrylonitrile
Fluoride
Bradycardia (sometimes to
asystole)
Cyanide
Organophosphates
Carbamate insecticides
Nicotine
Tachycardia
Nitrophenols
Pentachlorophenol
Cyanamide
Metaldehyde
Organophosphates
SIGNS AND SYMPTOMS 217
-------
Respiratory System
MANIFESTATION
Upper respiratory tract
irritation, rhinitis, scratchy
throat, cough
Sneezing
Runny nose
Pulmonary edema
(many chemicals come
packaged in a
hydrocarbon vehicle, well
known to cause
pulmonary edema)
Pulmonary consolidation
Dyspnea
CHARACTERISTIC OF
THESE POISONINGS
Naphthalene
Paraquat
Chloropicrin
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
Methyl isothiocyanate
Cadmium
Paraquat
Cadmium dusts
Methyl bromide
Organophosphates
Carbamate insecticides
Nicotine
Paraquat
ANTU
Cadmium dusts
Cyanamide
Sulfuryl fluoride
Pentachlorophenol
Methyl bromide
Sulfur dioxide
Chloropicrin
OCCURS WITH
THESE AGENTS
Dry formulation of copper, tin,
zinc compounds
Dusts of thiocarbamate and
other organic pesticides
Chlorophenoxy compounds
Aliphatic acides
Rotenone
Dry formulation of copper, tin,
zinc compounds
Dusts of thiocarbamate and
other organic pesticides
Chlorophenoxy compounds
Aliphatic acides
Rotenone
Organophosphates
Carbamate insecticides
Paraquat
Phosphides
Diquat
Nitrophenols
Cyanide
Creosote
Pyrethins
218 SIGNS AND SYMPTOMS
-------
Gastrointestinal Tract and Liver
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Nausea, vomiting,
commonly followed by
diarrhea
Organophosphates
Carbamate insecticides
Nicotine
Arsenicals
Fluoride
Cadmium compounds
Organotin compounds
Copper compounds
Sodium chlorate
Bo rate
Cyanide
Chlorophenoxy compounds
Phosphorus
Phosphides
Phosphine
Carbon disulfide
Chloropicrin
Halocarbon fumigants
Endothall
Metaldehyde
Thallium
Red quill
Diquat
Naphthalene
Methyl bromide
Dibromochloropropane
Veratrum alkaloid
Thiram
Pentachlorophenol
B. thuringiensis
Cholecalciferol
Thiram
Ethylene dichloride
Propane
Ethylene oxide
Cresol
Many pesticides have some
irritant property
Diarrhea (first)
Organophosphates
Carba mates
Pyrethoids
Borates
Sulfur
Nicotine
B. thuringiensis
Thiram
Cadmium
Cationic detergents
Cresol
Hexachlorophene
Chlorophenoxy compounds
Diarrhea (bloody)
Fluoride
Paraquat
Diquat
Thallium
Coumarins
Indandiones
Endothall
Arsenicals
Phosphorus
Phosphides
Cycloheximide
SIGNS AND SYMPTOMS 219
-------
Gastrointestinal Tract and Liver (continued)
MANIFESTATION
Abdominal pain
Stomatitis
Salivation
Ileus
CHARACTERISTIC OF
THESE POISONINGS
Organophosphates
Carbamate insecticides
Paraquat
Diquat
Nicotine
Methaldehyde
Fluoride
Bo rate
Phosphorous
Phosphides
Inorganic arsenicals
Cadmium compounds
Copper compounds
Thallium
Organotin compounds
Inorganic arsenicals
Paraquat
Diquat
Copper compounds
Organophosphates
Carbamate insecticides
Nicotine
Aminopyridine
Sodium fluoride
Cyanide
Cadmium compounds
Thallium
Diquat
OCCURS WITH
THESE AGENTS
Chlorophenoxy compounds
Aliphatic acids
Sodium chlorate
Creosote
Endothall
Aminopyridine
Coumarins
Indandiones
Fumigants (ingested)
Cycloheximide
Thallium
Liver
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Enlargement
Copper compounds
Sodium chlorate
Phosphine
Carbon tetrachloride
Cholorform
Inorganic arsenicals
Hexachlorobenzene
Jaundice -
see section on Skin
220 SIGNS AND SYMPTOMS
-------
Kidney
MANIFESTATION
Proteinuria
Hematuria
Sometimes leading
to oliguria
Acute renal failure with
azotemia
Dysuria, hematuria, pyuria
Polyuria
Hemoglobinuria
Wine-red urine
(porphyrinuria
Smoky urine
Glycosuria
Ketonuria
CHARACTERISTIC OF
THESE POISONINGS
Inorganic arsenicals
Copper compounds
Sodium fluoride
Naphthalene
Bo rate
Nitrophenols
Pentacholorphenol
Sodium chlorate
Sulfuryl fluoride
Paraquat
Diquat
Arsine
Ethylene dibromide
Chlordimeform
Cholecalciferol
Naphthalene
Sodium chlorate
Arsine
Hexachlorobenzene
Creosote
OCCURS WITH
THESE AGENTS
Cadmium compounds
Phosphorus
Phosphides
Phosphine
Chlorophenoxy compounds
Creosote
Organotin compounds
Fluoride
Organotin compounds
Bo rate
Reproductive System
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS WITH
THESE AGENTS
Low sperm count
Dibromochloropropane
Kepone
SIGNS AND SYMPTOMS 221
-------
Blood
MANIFESTATION
Hemolysis
Methemoglobinemia
Hypoprothrombinemia
Hyperkalemia
Hypocalcemia
Hypercalcemia
Carboxyhemoglobinemia
Anemia
Leukopenia,
Thrombocytopenia
Elevated LDH
GOT, GPT,
alkaline phosphatase,
ALT, AST enzymes
Depressed RBC
Acetylcholinesterase and
plasma
pseudocholinesterase
CHARACTERISTIC OF
THESE POISONINGS
Naphthalene
Sodium chlorate
Arsine
Sodium chlorate
Creosote
Coumarins
Indandiones
Sodium chlorate
Naphthalene
Arsine
Fluoride
Cholecalciferol
Naphthalene
Sodium chlorate
Arsine
Inorganic arsenicals
Inorganic arsenicals
Carbon tetrachloride
Chloroform
Phosphine
Organosphosphates
OCCURS WITH
THESE AGENTS
Copper compounds
Cresol
Chlordimeform
Cyanide
Cresol
Copper
Arsine
Phosphorus
Phosphides
Carbon tetrachloride
Sodium fluoride
Thallium
Phosphorus
Phosphides
Organotin compounds
Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Sodium chlorate
Nitrophenols
Pentachlorophenol
Thallium
Organochlorines
Chlorophenoxy compounds
Carbamate insecticides
222 SIGNS AND SYMPTOMS
-------
Index of Pesticide Products
Symbols
1,2-dichloropropane 157
1,2-epoxyethane 158
1,3-dichloropropene 157
2-benzyl-4-chlorophenol 197
2-methyl-3, 6 dichlorobenzoic acid. 95
2,3,6-TBA 119
2,4-D 94-95, 97-98
2,4-DB 95
2,4-dichlorophenoxyacetic acid . 95, 98
2,4-dichlorophenoxybutyric acid.... 95
2,4-dichlorophenoxypropionic acid 95
2,4-DP 95
2,4,5-T 94-95
2,4,5-trichlorophenoxy acetic acid.. 95
4-Ammopyridme 183-184, 194
4-tert-amylphenol 197
1080 177
1081 177
A7Vapam 140
Aaterra 152
Aatrex 121
Abate 35
Abathion 35
Abol 49
Acaraben 75
acaricides 74, 104
Acarstin 75
Accelerate 184
Accotab 120
Accothion 35
acephate 35
acetamides 119
Acrex 105
Acricid 105
acrolem 156, 158
acrylomtrile 156-157, 161, 163-165
Actellic 35
Activol 64
Actor 109
Afalon 122
Aficida 49
Afugan 35
Agree 64
Agri-Mycin 17 65
Agritox 35
Agrosan 147
Agrothion 35
Agtoxin 158
Akar 75
alachlor 119
Alanox 119
alcohols 192-193, 196-197
aldehydes 158, 161, 197
aldicarb 49, 50
aldrm 55-57
Align 64
alkyl phthalates 74-75
allethrm 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-Ammopyridme 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
Aresm 122
Aretit 105
Arrhenal 127, 134
Arsenal 120
INDEX OF PESTICIDES 223
-------
arsenic acid 127, 133
arsenic trioxide 127, 129, 133
arsenical pesticides.. 126, 145, 147, 149
arsme gas 126-127, 129, 132
Arsmyl 127,134
Arsonate Liquid 128, 134
Aspon 35
Aspor 144
asularn 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
Basalm 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
Betadme 197
Betasan 35
Bexton 119
Bidrm 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
bornyl 35
Bophy 127, 134
borates 74-77
Borax 75-76, 90
Bordeaux Mixture 145
boric acid 74-76,90
Brace 35
Bravo 138
Brestan 149
Brodan 35
brodifacoum 170-172, 181
bromacil 122
bromadiolone 170
Bromofume 157
Bromone 170
bromophos 35
bromophos-ethyl 35
Broot 50
Bueno6 128,134
bufencarb 49
Busan 1020 140
butralm 120
224 INDEX OF PESTICIDES
-------
butylate .
Bux
.119
.. 49
cacodylic acid 127, 134
Cad-Trete 150
Caddy 150
Cadminate 150
cadmium chloride 150
cadmium compounds 137, 150
cadmium succinate 150
cadmium sulfate 150
cadusafos 35
Caid 170
Calar 127,135
calcium acid methane arsonate. 127, 135
calcium arsenate 127, 134
calcium arsenite 127, 133
calcium cyanamide 184
calcium hypochlorite 197, 200
Caldon 105
Caliber 90 121
CAMA 127,135
Caparol 121
Captaf 145
captafol 145
captan 145, 154
Captanex 145
CarbamateWDG 140
carbamates 5, 12-13, 49-50,
53,69,119,140
Carbamult 50
Carbanilates 120
carbaryl 49-50
carbofuran 48-50
carbon disulfide 40,156-158,
161-164
carbon tetrachloride 157-158, 164,
167-168
carbophenothion 35
Carpene 152
Carzol 49
Casoron 119
Castrix 177
catiomc detergents 197-198, 200
CCN52 76
Cekiuron 122
CekuC.B 138
Cekugib 64
Cekumeta 184
Cekuquat 109
Celathion 35
Celfume 157
Celmide 157
Ceresan 147
cetrimide 197-198, 206
cetylpyridium chloride 197-198
Chem Bam 144
Chem-Fish 64
Chemox General 105
ChemoxPE 105
ChemsectDNBP 105
ChemsectDNOC 105
Chermox PE 105
ChipcoThiram 75 140
chlordane 55-57, 61
chlordecone 55-57, 62
chlordimeform 74-75, 77-78
chlorethoxyfos 35
chlorfenvinphos 35
chlorhexidme 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
chlorothaloml 138-139, 154
chlorotoluron 122
chlorphoxim 35
chlorpropham 120
chlorpyrifos 6, 35-36
chlorthaldimethyl 121
chlorthiophos 35
cholecalciferol 179-180
Chrysron 77
Ciodrin 35
cismethrin 76, 89
Classic 122
cloethocarb 49
clomazone 120
Clorto Caffaro 138
Clortosip 138
Clortran 138
Co-Ral 35
Co-Rax 170
Cobex 120
Comite 76
Command 120
Compound 1080 177
Compound 1081 177
Contrac 170
Contraven 35
convulsants 177
copper acetate 145
copper acetoarsenite 127, 133
INDEX OF PESTICIDES 225
-------
copper ammonium carbonate 145
copper arsenite
(acid copper arsenite) 127
copper carbonate, basic 145
copper compounds 137, 145-146
copper hydroxide 145
copper lime dust 145
copper linoleate 145
copper oxychloride 145
copper potassium sulfide 145
copper silicate 145
copper sulfate 145-146, 155
Cotoran 122
cottonex 122
coumachlor 170
coumafene 170
coumaphos 35
coumarins 169-171
coumatetralyl 170
Counter 35
Cov-R-Tox 170
Crab-E-Rad 127, 134
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
cyhexatm 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
2,4-D 94-95, 97-98
D-D92 157
D-trans 76
Dachthal 121
Daconate 6 128, 134
Dacoml 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
DEBT 80-82,91
DBF 35
Depend 35
Defol 184
Deftor 122
Delnav 35
DeltaDust 77
DeltaGard 77
deltamethrin 77, 89
Deltex 77
demeton 35
demeton-S-methyl 35
Demon 77
Denarin 152
Dermaadex 197
Des-i-cate 184
Design 64
desmetryn 121
Dessin 105
Detamide 75
226
INDEX OF PESTICIDES
-------
Dethdiet 179
Dextrone 109
Dexuron 109
Di-allate 119
Di-Tac 127,134
Diacon 76
dialifor 35
diallate 119
Dianex 76
Diaract 76
diatomaceous earth 193
diazinon 35-36
Dibrorn 35
dibromochloropropane 26, 157, 162
dibromoethane 157
dibutylphthalate 74-75
dicamba 95, 119
Dicarbam 49
dichlobeml 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
dieldrm 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
Dimtro 105, 107
Dinitro General Dynamyte 105
Dimtro Weed Killer 5 105
Dimtro-3 105
dinitrocresol 105
dinitrophenol 105-106
dinobuton 105
dmocap 104-105
Dmofen 105
dinopenton 105
dinoprop 105
dinosam 105
dmoseb 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
Dmrex 122
Diuron 122
dmron 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
DPX1410 49
Dragnet 77
Drawinol 105
Draza 49
Drexar 530 128, 134
INDEX OF PESTICIDES 227
-------
Drop-Leaf 184
DSE 144
DSMA 127,134
Dual 119
Duraphos 35
Duratox 35
Dursban 35
dusts 18, 66, 70, 90, 138,
140,145, 147,184,192-193
Dycarb 49
Dyclomec 119
Dyfonate 35
Dylox 35
Dyrene 152
E
E601 35
E-48 35
E-D-Bee 157
E-Z-OfFD 35
E605 35
Earthcide 138
Easy off-D 35
EBDC compounds 144
Ebufos 35
EDB 157
EDC 157
edifenphos 35
Ekarnet 35
Ekatm 35
Eksinin 77
Elecron 49
Elimite 77
Elgetol30 105
Elgetol318 105
Emerald green 127, 133
Emisan 6 147
emulsifiers 184, 193
Endosan 106
endosulfan 55, 56
endothall.. 121, 124, 184, 187-188, 195
Endothall Turf Herbicide 184
endothion 35
endrin 55-56
Entex 35
EPBP 35
EPN 35
1,2-epoxyethane 158
EPTC 119
Eradicane 119
Esgram 109
ethalfluralm 120
Ethanox 35
Ethazol 152
ethion 35
ethoprop 35
ethyl parathion 35, 37
ethylene dibromide .... 157-158,162, 167
ethylene dichlonde 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
Fac 35
Fall 184
Famarin 170
Famfos 35
Famid 49
famphur 35
Far-go 119
fenamiphos 35
Fenchlorphos 35
fenitrothion 35
Fenkill 77
fenophosphon 35
fenothrin 77
fenoxycarb 49
fenpropanate 77
Fenpropar 76
fenpropathrin 77
fensulfothion 35
fenthion 35, 37
fentin acetate 149
fentin chloride 149
fentin hydroxide 149
fenvalerate 77, 87, 89, 91
ferbam 140,143
Ferberk 140
FermideSSO 140
Fernasan 140
Fernos 49
Ficam 49
Electron 77
fluchloralm 120
flucythrinate 77, 87
Fluent 77
flumeturon 122
fluorides 74, 82, 85
fluoroacetamide 169, 177
fluvalmate 77,87-89
FMC9044 106
Folbex 75
Folcord 77
228
INDEX OF PESTICIDES
-------
Folex 35
Folosan 138
Folpan 145
folpet 145
Foltaf 145
fonofos 35
formaldehyde 156, 158, 168, 197
formetanate hydrochloride 49
formothion 35
Fortress 35
Fortrol 121
fosamine 120
fosthietan 35
French green 127, 133
Frunax-DS 170
Fumex 158
fumigants 82, 141, 156,162,
164,174,176,197
Fumitoxin 158
fungicides 55, 79,104, 137,
143-150,152-154,156
Funginex 152
Fungitrol II 145
Furadan 49
furethrin 77
Futura 64
G 28029 35
GA3 64-65
Gallotox 147
gamma BHC or HCH 56
Gamophen 197
Gardona 35
Gardoprim 121
Garlon 120
Gebutox 105
Gesafram 50 121
Gesagard 121
Gesapax 121
Gesatop 121
gibberellic Acid 64-65
Gibberellm 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
Gypsme 127,134
H
Haipen 145
Halizan 184
haloaromatic substituted ureas 85
halocarbon fumigants 156-157,
159, 162
Hanane 35
Havoc 170
HCB 138-139
HCH 56
Hel-Fire 105
Helothion 35
heptachlor 55-57
heptenophos 35
Herald 77
Herbi-All 128, 134
Herbicide 273 184
Herbodox 120
hexachlor 56
hexachloran 56
hexachlorobenzene 55-56, 61, 103,
137-139, 154
hexachlorophene 197, 202-204, 207
Hexadrin 56
Hexaferb 140
Hexathane 144
Hexathir 140
Hexazir 140
Hi-Yield Dessicant H-10 127, 133
Hibiclens 197,206
Hibistat 197
hiometon 35
Hoe 002784 106
hosalone 35
Hostaquick 35
Hostathion 35
hydrocyanic acid 157
hydrogen cyanide .... 156-158, 163-165
Hydrothol 184
hypochlorites 197,200
Hyvar 122
I
IBP 35
imazapyr 120
Imidan 35
INDEX OF PESTICIDES 229
-------
indandiones 169-171
inorganic copper compounds 145
Iodines 197
iodofenphos 35
loprep 197
IP50 122
iprodione 152-153
isazofos 35
isofenphos 35
isolan 49
Isopestox 35
isoprocarb 49
isopropanol 184, 192, 196
isopropyl alcohol 80, 196-197, 206
isoproturon 122
isoxathion 35
isoxazolidinone 120
Jones Ant Killer 128,133
K
Kabat 76
Kack 127,134
Kafil 77
KafilSuper 77
Karathane 105
Karbation 140
Karrnex 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
Kremte 120
Kromad 150
Kryocide 75
Kusatol 184
Kwell 55-56, 61-62
Kypfarm 170
Kypman 80 144
Kypzin 144
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
Imdane 55-58, 61-62, 138
Linex 122
Linorox 122
Linurex 122
linuron 122
Liphadione 170
Liqua-Tox 170
London purple 127, 133
Lorox 122
Lorsban 35
Lysol 185,197,207
M
M-Diphar 144
MAA 127,134
Magnacide B 158
Magnacide H 158
Maki 170
malathion 35, 37, 47
MAMA 127,134
mancozeb 144
Mancozin 144
maneb 144, 154
Maneba 144
Manex 144
ManexSO 144
manzeb 144
Manzin 144
Maposol 140
Marlate 55-56
Matacil 49
Mattch 64
MCPA 95,98
MCPB 95
MCPP 95
MeBr 157
mecoprop 95,97-98
Melprex 152
MEMA 147
MEMC 147
Meothrin 77
mephosfolan 35
Mercuram 140
230
INDEX OF PESTICIDES
-------
mercurials 148-149, 197, 202
mercurobutol 197
mercurochrome 197
Merge 823 128,134
Merpafol 145
Merpan 145
merphos 35
Mertect 152
merthiolate 197
Mesamate 128, 134
Mesurol 49
Metadelphene 75
metalaxyl 152-153
metaldehyde 184, 188-189, 195
metalkamate 49
Metam-Fluid BASF 140
metam-sodium 140-141
Metaran 75
Metason 184
Metasystox-R 35
Metasystox-S 35
Metasystoxl 35
Meth-O-Gas 157
methabenzthiazuron 122
methamidophos 35
methane arsonic acid 127, 134
methanol 184, 192, 196
Methar30 127, 134
methidathion 35
methomyl 49
methoprene 74, 76, 86
methoxychlor 56
methoxyethyl mercury acetate 147
methoxyethyl mercury chloride 147
methoxyethyl mercury compounds .. 147
methyl bromide 156-157,159,
161-163,168
2-methyl-3, 6 dichlorobenzoic acid ... 95
methyl mercury acetate 147
methyl mercury compounds 147
methyl naphthalenes 193
methyl parathion 35-37, 46
methyl trithion 35
methylene chloride. 157, 159, 161, 168
metobromuron 122
metolachlor 119
metoxuron 122
metribuzin 121
mevinphos 35
mexacarbate 49
Mezene 140
MGK 75
Micromite 76
Microzul 170
Mightikill 76
Miller 531 150
Milo-Pro 121
Minex 76
mipafox 35
MIPC 49
Miral 35
mirex 55-57
Mitis green 127,133
Mocap 35
Monitor 35
mono-calcium arsenite 127, 133
monoammonium methane
arsonate 127, 134
monocrotophos 35
monolinuron 109, 122
monosodium methane
arsonate 127, 134
monuron 122
Morrocid 106
MSMA 127,134
Multamat 49
Muritan 179
Muskol 75
Mycodifol 145
N
N-2790 35
n-methyl carbamates 48-51,
53, 140, 191
nabam 144
naled 35
Namekil 184
naphthalene 66, 156-157, 159-162,
164, 168, 193
naphthenate 145
naramycin 152
Neburex 122
neburon 122
Neemazad 64
Neemazal 64
Neemix 64
Neguvon 35
Nem-A-Tak 35
Nemacur 35
Nemafume 157
Nemanax 157
Nemaset 157
Nemasol 140
Nemispor 144
Neopynamin 78
Nephis 157
Nexagan 35
Nexion 35
NIA9044 106
Nico Soap 64
INDEX OF PESTICIDES 231
-------
nicotine 63-67,72-73
Niomil 49
Nitrador 105
nitrocresolic herbicides 104-105
nitrolime 184
nitromersol 197
nitrophenolic herbicides . 104-105, 118
Nitropone C 105
Nix 77
No Bunt 138
Nomersam 140
Nomolt 76
Novodor 64
Noxfire 64
Noxfish 64
NRDC 149 77
Nudrm 49
Nusyn-Foxfish 64
Nuvanol-N 35
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
OrthoDiquat 109
Orthocide 145
oryzalin 120
Oust 122
Outflank 77
Oxadiazolinone 120
oxadiazon 120
oxamyl 49
oxirane 158
Oxotin 75
oxydemeton-methyl 35
oxydeprofos 35
Panogen 147
Panogen M 147
Pansoil 152
Para-col 109
paradichlorobenzene 157, 160, 162
paraformaldehyde 156, 158
paraquat 11-12, 15, 107-117
Parathion 35, 46
Paris green 127, 133, 145
Parzate 144
Parzate C 144
Pathclear 109
Pattonex 122
Paushamytin, 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
permethrm 77,87-88
Perthrine 77
PestoxXIV 35
PestoxXV 35
petroleum distillates 68, 192, 194
Phaltan 145
Pharmadine 197
Pharorid 76
phencapton 35
phenol(s) 5-6, 40, 50, 65, 99, 185,
187,195,197,202-203
Phenostat-A 149
Phenthoate 35
phenthoate 35
Phentinoacetate 149
phenyl salicylate 145
phenylmercuric acetate 197
phenylmercuric nitrate 197
phenylphenol 197
Phisohex 197
Phorate 87
232
INDEX OF PESTICIDES
-------
phorate 35, 87
phosalone 35-36, 46
Phosdrin 35
phosfolan 35
phosmet 35
phosphamidon 35
phosphine 156, 158, 160-161,
163-165,169,174,176,181
phostebupirim 35
Phostoxin 158
phostoxin 160
Phosvel 35
Phosvin 173
phoxim 35
phthalthrin 77
Phytar560 127,134
Pic-Clor 157
picloram 121
pindone 170
pine oil 5-6, 196-197, 205, 207
Pmene 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
Polybor3 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
Premerge3 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
pyrethrms 5-6, 68-69, 87, 191
pyrethroids 5-6, 68, 74, 76, 87-88
pyrethrum 68-69, 73
pyridaphenthion 35
Quickfos 158
Quilan 120
quinalphos 35
quinolinolate 145, 147
Quintox 179
quintozene 138
Rabon 35
Racumin 170
Rad-E-Cate 25 127, 134
Ramik 170
Rampage 179
Rampart 35
Ramrod 119
Ramucide 170
Rapid 49,194
INDEX OF PESTICIDES 233
-------
Rapier
Ratak
Ratak Plus.
Ratomet....
Raviac
RAX
red squill ...
Reglone ....
119
170
170
170
170
170
179
109
Regulex 64
repellents 5, 74, 91
resinate 145
resmethrin 77
Revenge 119
Ridall-Zmc 173
Ridomil 152
Ripcord 77
Riselect 119
Ro-Neet 119
rodenticides 5-6, 169, 171,
173-174,177,179
Rodme 179
Rody 77
ronnel 35
Ronstar 120
Rotacide 65
rotenone 64, 70
Rotenone Solution FK-11 65
Roundup 120
Rovral 152
Rozol 170
Ruelene 35
Rugby 35
S-Seven 35
sabadilla 63,65,71
safeners 184,193
Safrotin 35
Safsan 75
SAGA 78
Salvo 127,134
Sanifume 158
Sanspor 145
Saprol 152
Sarclex 122
Saturn 119
schradan 35
Schweinfurt green 127, 133
Selinon 105
Semeron 121
Sencor 121
Sencoral 121
Sencorex 121
sethoxydim 120
Setrete 147
Sevm 49
Shaphos 158
Shimmer-ex 147
siduron 122
simazine 109, 121
Smbar 122
Smituho 100
Sinox 105
Siperin 77
Skeetal 64
Skeeter Beater 75
Skeeter Cheater 75
Skintastic for Kids 75
Snox General 105
Sobrom 98 157
Sodamt 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
SpotreteWP75 140
Spotrete-F 140
Spra-cal 127, 134
Spring Bak 144
Sprout-Nip 120
Stam 119
Stampede 119
stickers and spreaders 184, 193
Stomp 120
streptomycin 65, 72
Strobane 56
strychnine 169, 177-178, 182
Subdue 152
Subitex 105
substituted benzenes 137-138,
144-145,154
Sulerex 122
234
INDEX OF PESTICIDES
-------
sulfemeturon-methyl 122
sulfotep 35
sulfur 6, 71, 74, 78, 89, 90, 92
sulfur dioxide 156, 158, 160
sulfuryl fluoride 82, 156, 158,
161-162,168
sulprofos 35
Sumicidin 77
Sumithion 35
Super Crab-E-Rad-Calar 127, 135
Super Dal-E-Rad 127, 135
Super Tin 149
Supracide 35
Surecide 35
Surflan 120
Surgi-Cen 197
Surofene 197
Suspend 77
Sutan 119
Suzu 149
Suzu-H 149
Swat 35
synergists 68-69, 184, 191
Sypren-Fish 65
systox 35
2,4,5-T 94-95
Tag HL 331 147
Talan 105
Talcord 77
Talon 170
Tamex 120
Target MSMA 128, 134
Tattoo 49
2,3,6-TBA 119
TCA 119
TCBA 119
Tebusan 122
tebuthiuron 122
Tecto 152
teflubenzuron 76, 85
Teknar 64
Telone II Soil Fumigant 157
temephos 35
Temik 49
TEPP 35
terabacil 122
terbucarb 119
terbufos 35
terbuthylazine 121
Terbutrex 121
Termt 121
terpene poly chlorinates 56
Terraklene 109
Terraneb SP 138
Terrazole 152
Tersanl991 152
4-tert-amylphenol 197
tertutryn 121
tetrachlorvinphos 35
tetraethyl pyrophosphate 35
tetramethrin 78
Tetrapom 140
Texosan 197
thallium sulfate 173, 175
thiabendazole 152-153
Thibenzole 152
Thimer 140
thimerosol 197
Thimet 35
thiobencarb 119
thiocarbamate insecticides 137, 140,
142, 156
thiocarbamate herbicides 119
thiodicarb 50
Thioknock 140
Thiophal 145
thiophos 35
thiophthalimides 137, 145
Thiotepp 35
Thiotex 140
thiram 140-143, 150, 154
Thiramad 140
Thirasan 140
Thiuramin 140
Thuricide 64
thymol 197,202
Tiguvon 35
Tillam 119
Tinmate 149
Tirampa 140
TMTD 140
Tolban 120
Tolkan 122
toluene 184, 192
Tolurex 122
Tomcat 170
Topitox 170
Torak 35
Tordon 121
Torus 49
Tota-col 109
Tox-Hid 170
toxaphene 55-57
TPTA 149
Tralex 78
tralomethrin 78
Trametan 140
Trans-Vert 128, 134
INDEX OF PESTICIDES 235
-------
Treflan 120
Tri-PCNB 138
triadimefon 152-154
triallate 119
triazines 121
Triazole 121
triazophos 35
Tribac 119
Tribactur 64
Tribuml 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
trifluralm 120
Trifocide 105
Triforine 154
triforme 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
Tubotm 149
Tuffcide 138
Tupersan 122
Turcarn 49
Turf-Cal 127, 134
Turflon 120
Turplex 64
u
Ultracide 35
UmcropDNBP 105
Unidron 122
Unisan 147
uracils 122
Ustadd 77
V
VancideMZ-96 140
Vapam 140
Vapona 35
VC-13 Nemacide 35
Vectobac 64
Vectocide 64
Venturol 152
Venzar 122
veratrum alkaloid 71
Vernarn 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
VydateL 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
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
zmeb 144,154
ziram 140, 143
ZiramF4 140
Ziram Technical 140
Zirberk 140
Zirex90 140
Zmde 140
Zitox 140
Zolone 35
zoocoumarin 170
Zotox 127,133
236
INDEX OF PESTICIDES
-------
MM.I
ttwiran menial Protect Jon
vvEPA
Agency
Office of Prevent ion,
Pesticides, and Toxic
73&-H-98-OC4
iMteitiLier 1993
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Reconocimiento y Manejo
de los Envenenamientos
por Pesticidas
-------
RECONOCIMIENTO Y
MANEJO DE LOS
ENVENENAMIENTOS
FOR PESTICIDAS
Quinta Edition, 1999
J. Routt Reigart, M.D.
Profesor de Pediatria, Universidad Medica de Carolina del Sur
James R. Roberts, M.D., M.P.H.
Profesor Asistente de Pediatria, Universidad Medica de Carolina del Sur
El apoyo para esta publication fue provisto por:
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
Para copias adicionales o mayor information:
Tel: 703-505-7666
Fax:703-308-2962
El manual esta disponible en formato electronico en la Internet en:
http://www.epa.gov/pesticides/safety/healthcare
-------
Reconocimientos
Estamos sumamente agradecidos a la Oficina de Programas de Pesticidas (Office of Pesticide Programs) de
la Agencia para la Proteccion del Medio Ambience, por habernos provisto la oportunidad de colaborar en
esta nueva edicion. Le damos las gracias a Kevin Keaney, Director Interino, por su apoyo y vision, y por
haberle dado prioridad a esta publicacion.Tambien deseamos resaltar los esfuerzos de Jerome M. Bondell,
Ph.D.,M.P.H.,y Ameesha Mehta, M.P.H., cuya supervision y ayuda constante fueron de valor incalculable
para la finalizacion de este proyecto. Ana Maria Osorio, M.D., M.P.H., contribuyo el Capitulo 3, Historia
Ambiental y Ocupacional, de este manual. Le damos las gracias a Equity Research Corp. por la traduccion
al espanol y a DeltaValente, M.P.A., por su supervision y ayuda.
Expertos en la toxicologia clinica llevaron a cabo revisiones criticas del borrador. Estamos sumamente
agradecidos del tiempo y esfuerzo dedicado por los siguientes revisores:
Jeffery Lloyd Burgess, M.D, M.P.H.
Profesor Asistente
Unidad de Salud Ambiental y Ocupacional
Centro de Prevencion de la Universidad de Arizona
Matthew C. Keifer, M.D, M.P.H.
Profesor Asistente
Departamento de Medicina/Salud Ambiental
Universidad de Washington
Wayne R. Snodgrass, M.D, Ph.D.
Profesor y Director
Farmacologia-Toxicologia Clinica
Centro de Envenenamiento de Texas
Sheldon L.Wagner, M.D.
Profesor de Toxicologia Clinica
Universidad Estatal de Oregon
Muchas otras personas contribuyeron su tiempo y esfuerzo a esta publicacion. Estamos muy agrade-
cidos de los esfuerzos incansables de Patricia Clark, nuestra asistente administrativa, quien dedico inconta-
bles horas a la revision del texto, a la busqueda de referencias, a comunicarse con los revisores y a asegurarse
de que el proceso de revision fuera mucho mas facil de lo que se habia anticipado. Gilah Langner de
Stretton Associates, Inc., quien proveyo la supervision editorial.Will Packard y Sarah Carter de Free Hand
Press, Inc., quienes fueron responsables del formato del manual. Finalmente, queremos dar las gracias a
Terry Miller de la Universidad del Estado de Oregon/Servicio de Extension y a John Impson del Depar-
tamento de Agricultura de los Estados Unidos/Estado Cooperative para la Investigacion, Educacion, y
Servicio de Extension por facilitar la impresion de ambas versiones del Ingles y Espanol de este manual.
Lasfotograflas de la portado por Steve Delaney, Agenda de Proteccion del Medio Atnbiente de los Estados Unidos. El diseo de la
portado por Brian Adams, Big Fish Design. El diseo de el interior por la Campania Bluemont. Impreso por la imprenta United
Book Press, Baltimore, MD.
-------
CONTENIDO
Seccion I: Informacion General
1 Introduccion 2
2 Principios Generales en el Manejo de los
Envenenamientos Agudos Causados por Pesticidas 11
3 Historia Ambiental y Ocupacional 19
Seccion II: Insecticidas
4 Insecticidas Organofosfatados 40
5 Insecticidas Carbamatos de N-Metilo 55
6 Insecticidas de Cloruros Organicos Solidos 63
7 Insecticidas de Origen Biologico 72
8 Otros Insecticidas, Acaricidas y Repelentes 84
Seccion III: Herbicidas
9 Herbicidas Clorofenolicos 106
1C) Pentaclorofenol 112
11 Herbicidas Nitrofenolicos y Nitrocresolicos 118
12 Paraquat y Diquat 122
13 Otros Herbicidas 132
Seccion IV: Otros Pesticidas
14 Pesticidas Arsenicales 140
15 Fungicidas 152
16 Fumigantes 172
17 Rodenticidas 187
18 Pesticidas Diversos, Solventes y Adyuvantes 203
19 Desinfectantes 217
Seccion V
Indice de Senales y Sintomas 232
Indice de Productos Pesticidas 245
-------
Lista de Tablas
Tablas de Dosificacion
Sorbitol 13
Carbon Activado 14
Jarabe de Ipecacuana 15
Lorazepam 16,116
Diazepam 17, 67
Atropina 48,59
Pralidoxima 50
Sulfato de Atropina 77,81
Gluconato de Calcio 96, 197
Bentonita yTierra de Batan 128
Sulfato de Morfina 130
BAL (Dimercaprol) 144
D-Penicilamina 145
DMSA (Succimer) 146
DMPS 146
Antidotes de Cianuro 183
Suplemento de Nitrito de Sodio yTiosulfato de Sodio 184
Fitonadiona 190
AquamephytonR 190
Tablas
Pesticidas Mayormente Implicados en Enfermedades Sintomaticas, 1996 6
Enfermedades Ocupacionales de California Debido a Pesticidas, 1991-1995 7
Preguntas para el Examen para Exposiciones Ocupacionales y Ambientales 21
Entrevistas Detallada para Exposiciones Ocupacionales y Ambientales 22
Pasos en la Investigacion de un Brote de Enfermedad 31
Limites Bajos Aproximados de Actividad Colinesterasica Normal del Plasma y
los Eritrocitos de la Sangre Humana 46
Toxicidad de Herbicidas Comunes 133-136
-------
Seccion I
INFORMACION GENERAL
-------
CAPITULO
Introduccion
Esta quinta edicion de Reconodmiento y Manejo de los Envenenamientos por Pesti-
tidas es una revision y expansion de la cuarta edicion de 1989. La Oficina de
Programas de Pesticidas de la Agencia para la Proteccion del Medio Ambiente
de los Estados Unidos ha auspiciado la serie desde 1973. El proposito del ma-
nual es proveerle a los profesionales de la salud, informacion reciente acerca de
los peligros a la salud presentados por pesticidas utilizados al presente, y un
consenso de recomendaciones actualizadas para el rnanejo de envenenamientos
y lesiones causadas por los mismos.
En la actualidad, el envenenamiento por pesticidas es una enfermedad co-
munmente no diagnosticada o pasada por alto en los Estados Unidos. A pesar
de las recomendaciones efectuadas por el Institute de Medicina y otros, quienes
urgen la integracion de la medicina ambiental a la educacion medica, los pro-
veedores de salud generalmente reciben un entrenamiento muy limitado en lo
que a la salud ocupacional y ambiental se refiere, y en particular en lo que
respecta a las enfermedades relacionadas con pesticidas.1 La revision de este
manual forma parte de una iniciativa mayor de la Agencia para la Proteccion
del Medio Ambiente de los E.U., en conjuncion con numerosas agencias fede-
rates, asociaciones de profesionales de la salud y organizaciones relacionadas
para ayudar a los proveedores de salud a estar mas al tanto, educados y entrena-
dos en el area de la salud relacionada con los pesticidas. Esta directiva importan-
te, llamada Pesticidas y Estrategias a Nivel Nacional para los Proveedores de
Servicios de Salud fue lanzada en abril de 1998.
Como ha sido la costumbre con las revisiones anteriores, esta nueva edi-
cion incorpora nuevos productos de pesticidas que no necesariamente son alta-
mente reconocidos entre los profesionales de la salud. La "experiencia de uso"
acumulada de los formuladores, aplicadores y trabajadores del campo provee
una base extensa para pasar juicio sobre la seguridad e identificar los peligros
ambientales y del lugar de trabajo tanto de antiguos como de nuevos pesticidas.
Se han tornado en consideracion episodios importantes de efectos adversos a la
salud reportados en publicaciones medicas y cientificas. Esta literatura tambien
contribuye de manera importante a una mayor comprension de los mecanis-
mos toxicos. La toxicologia clinica es un campo dinamico dentro de la medici-
na; nuevos metodos de tratamiento son desarrollados regularmente y la efecti-
vidad, tanto de las antiguas como de las nuevas modalidades, esta sujeta a una
revision critica y constante.
PB INTRODUCCION
-------
Existe un consenso general de que la prevention de envenenamientos por
pesticidas continua siendo un camino mas seguro para la seguridad y salud, que
la dependencia en el tratamiento. En adicion a la toxicidad inherente de los
pesticidas, ninguno de los procedimientos medicos o drogas utilizadas en el
tratamiento de los envenenamientos esta libre de riesgos. De hecho, muchos
antidotes son toxicos de por si, y tales procedimientos aparentemente simples
como la intubacion gastrica conllevan riesgos considerables. El toxicologo cli-
nico debe a menudo pesar los peligros de diferentes cursos de accionlos
cuales en ocasiones no incluyen ningun tratamientocontra los riesgos de
diferentes intervenciones, tales como vaciado gastrico, catarsis, administracion
de fluidos por via intravenosa, o la administracion de un antidote, de haber uno
disponible. Las decisiones de tratamiento clinico tienen que ser efectuadas con
prontitud, y en la mayoria de los casos, con una informacion medica y cientifica
muy limitada. Las circunstancias complejas de los envenenamientos humanos
en raras ocasiones permiten comparaciones precisas de metodos alternos. Es
por ello, que las recomendaciones para tratamiento que aparecen en este ma-
nual no son en forma alguna guias infalibles para resultados exitosos. Las mis-
mas no son sino un consenso de juicios de las mejores opciones de tratamiento
clinico disponibles.
Este manual trata casi por completo con los efectos daiiinos de los pestici-
das a corto plazo (agudos). Aunque es obviamente importante, el tema de los
efectos cronicos es demasiado complejo para ser tratado exhaustivamente en
un manual designado como guia para el manejo de emergencias. Sin embargo,
el tratamiento adecuado de exposiciones serias a pesticidas representa un paso
importante para evitar enfermedades tanto cronicas como agudas.
Los pesticidas y productos comerciales mencionados en este manual no
representan la totalidad de los pesticidas en existencia. Los mismos fueron se-
leccionados debido a la frecuencia en su uso y exposicion, la severidad de la
toxicidad, y experiencia anterior con envenenamientos agudos. En este manual
se discuten productos que han sido descontinuados o cuyo registro como pes-
ticida en los E.U. ha sido revocado, los cuales sin embargo todavia representan
un peligro debido a su uso en otros lugares o alii donde todavia exista la proba-
bilidad de mercancia residual. Los agentes que no han sido utilizados durante
largo tiempo en los E.U. y en otros lugares no fueron incluidos en este manual.
La cantidad de pesticida absorbida es un factor critico en las decisiones de
tratamientos, y en muchos casos de exposicion a los pesticidas, la estimacion de
dosificacion continua siendo dificil. Los terminos "cantidad pequeiia" y "canti-
dad grande" utilizados en este manual son obviamente ambiguos, pero la cali-
dad de la informacion obtenida acerca de la exposicion raramente justifica una
terminologia mas especifica.
En ocasiones, las circunstancias de la exposicion son una guia aproximada
de la cantidad absorbida. La exposicion al desplazamiento de aerosol diluido
adecuadamente para la aplicacion en el campo probablemente no transmitira
una dosis grande a menos que la exposicion haya sido prolongada. Los derra-
INTRODUCCION 3
-------
mes de material tecnico concentrado en la piel o ropa pueden muy bien repre-
sentar una dosis grande de pesticida a menos que la contaminacion sea removi-
da de inmediato. Es poco probable que una corta exposicion dermica a los
residues de pesticidas de follaje que inhiben la colinesterasa cause envenena-
miento, sin embargo, las exposiciones prolongadas si podrian hacerlo. Las
ingestiones suicidas casi siempre envuelven "grandes cantidades", lo cual re-
quiere de un tratamiento agresivo. Excepto en el caso de los ninos, es probable
que la ingestion accidental de pesticidas sea escupida o vomitada. La ingestion
de pesticidas por ninos son mas dificiles de evaluar. El terapista generalmente
debe basar las decisiones de tratamiento clinico en conjeturas de una dosifica-
cion en el"peor de los casos". Los envenenamientos de ninos se complican aun
mas debido a la mayor vulnerabilidad de los pequenos, no solamente a los
pesticidas en si, sino tambien a los medicamentos y procedimientos de trata-
miento. La naturaleza del desarrollo neurologico en los ninos envuelve un nivel
adicional de riesgo, el cual no esta presente en los adultos. Algunos grupos de
adultos, tales como los trabaj adores agricolas con mala nutricion y alt a exposi-
cion tambien podrian estar mas a riesgo.
Principios Clave
Los metodos generales para el manejo de los envenenamientos por pestici-
das son presentados en el Capitulo 2 y los mismos reflejan una base extensa de
experiencias clinicas. Los puntos clave que siguen a continuacion merecen ser
enfatizados. La necesidad de proteger las vias respiratorias de la aspiracion del
vomito es sumamente importante. En ocasiones han ocurrido muertes como
resultado de esta complicacion, aun despues de que se hayan ingerido substan-
cias con un potencial toxico relativamente bajo. En los envenenamientos causa-
dos por agentes que deprimen las funciones del sistema nervioso central o que
causan convulsiones, la colocacion temprana de un tubo endotraqueal con ba-
16n iflable (aun cuando esto requiera una ligera anestesia general), podria salvar
la vida. El mantenimiento del intercambio de gases pulmonares adecuado es
otro elemento esencial en el manejo de envenenamientos, el cual merece ser
enfatizado constantemente.
La intubacion gastrica, con aspiracion y lavado, continua siendo un metodo
util para remover los venenos del estomago poco despues de que los mismos
hayan sido ingeridos, pero el tiempo, despues de la ingestion, durante el cual es
probable que el lavado sea beneficioso es mas corto de lo que muchos toxicologos
clinicos habian pensado. En muy raras ocasiones se recobran cantidades signifi-
cativas de toxicos ingeridos despues de 1-2 horas de ingestion, y en muchos
casos, la mayor cantidad del material ingerido pasa al duodeno y mas alia del
mismo en 15-30 minutos. En adicion, la mayoria de los estudios controlados
que evaluan la efectividad de los procedimientos de vaciado gastrico se efec-
tuan para ingestiones de materiales solidos (pildoras) en vez de liquidos.
PB INTRODUCCION
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Deberan aprovecharse al maximo los nuevos carbones altamente absorben-
tes, los cuales son efectivos en estipticar algunos pesticidas en los intestinos.
Desafortunadamente, el carbon no absorbe todos los pesticidas, y se desconoce
su eficiencia contra muchos de ellos. En los envenenamientos causados por
gran absorcion de pesticidas, la hemodialisis y hemoperfusion sobre los absor-
bentes continuan siendo probadas como metodos para la reduccion de cargas
corporeas. Estos procedimientos parecen ser de valor para el tratamiento de
algunos toxicos. La efectividad total parece depender no solamente de la efica-
cia con la cual se remueva de la sangre, sino tambien con la movilidad del
toxico ya distribuido en los tejidos antes de que se comience el procedimiento
extracorporeo de purificacion sanguinea. El volumen de distribucion y fuerza
del estiptica tisular son consideraciones importantes en la toma de decisiones
de esa indole. El determinante critico del exito en la utilizacion de estos siste-
nias niuy bien podria ser la rapidez con la cual scan puestos en operacion antes
de que se hayan acumulado cantidades de toxicos perjudiciales para los tejidos.
Continua habiendo la necesidad de que se informen sistematicamente los
envenenamientos por pesticidas a una agencia central, para que hayan estadisti-
cas acertadas que describan la frecuencia y circunstancias de los envenenamien-
tos y estas puedan ser recopiladas y asi dirigir apropiadamente los esfuerzos para
limitar estas ocurrencias. En algunos paises, ha habido un aumento en el uso de
pesticidas como instrumentos para el suicidio y aun para el homicidio. Los
productores estan dedicando ahora un esfuerzo considerable a la modificacion
de las formulaciones y empaque con el proposito de frenar estos usos
inapropiados. Este trabajo es importante debido a que las ingestiones suicidas
son a menudo los envenenamientos por pesticidas mas dificiles de tratar
exitosamente.
Envenenamientos Comunes por Pesticidas
De acuerdo a informacion recopilada en 1996 por el Centre para el Con-
trol de Envenenamientos de la Asociacion Americana, Sistema deVigilancia a la
Exposicion Toxica, los pesticidas mas comunmente implicados en envenena-
mientos, lesiones y enfermedades son enumerados a continuacion.
La lista esta basada en casos sintomaticos clasificados como de resultado
menor, moderado, mayor o fatal, los cuales fueron el resultado de casos
involuntarios que envolvieron un solo producto. El numero de casos informa-
dos comprende tanto a los niiios menores de seis anos como a los adultos y
ninos mayores. Los casos de suicidio/homicidio (intencional) han sido exclui-
dos. Los casos indicados como organofosfatos (y demas categorias) podrian in-
cluir tambien otros insecticidas tales como los carbamatos y los cloruros orga-
nicos en un mismo producto.
Aproximadamente el 90% de los casos sintomaticos envuelven solamente
sintomas menores de la clase que podria ser tratada tipicamente en el hogar con
INTRODUCCION
-------
PESTICIDAS MAYORMENTE IMPLICADOS EN ENFERMEDADES
SINTOMATICAS, 1996
Rango Pesticida o Clase de Pesticida Ninos
< 6 anos
1 Organofosfatos 700
2 Piretrinasy piretroides** 1.100
3 Desinfectantes a base de
con aceite de pino 1.336
4 Desinfectantes con hipoclorito 808
5 Repelentes contra insectos 1.81
6 Desinfectantes con fenol 630
7 Insecticides con carbamatos 202
8 Insecticides con organocloro 229
9 Herbicidas con fenoxido 63
10 Rodenticidasanticoagulantes 176
Todos los demas pesticidas 954
Total de todos los pesticidas/desinfectantes 7.279
Adultos
6-19 anos
3.274
2.850
1.
903
.291
997
405
817
454
387
33
3.604
15.015
Total*
4.002
3.950
2.246
2.109
2.086
1 .040
1.30
685
453
209
4.623
22.433
* Los totales incluyen una pequena cantidad de cases de edad desconocida.
** Estimado aproximado: incluye algunos productos veterinarios no clasificados por clase qufmica.
Fuente: Centra para el Control de Envenenamientos de la Asociacion Americana, Sistema
de Vigilancia a la Exposition Toxica, informacion recopilada en 1996.
dilucion o rnera observacion. Sin embargo, es mucho mas probable que siete de
las diez categorias principles enumeradas en la tabla que aparece arriba
(organofosfatos, piretrinas/piretroides, desinfectantes con hipoclorito, carbamatos,
cloruros organicos, herbicidas con fenoxido y los rodenticidas anticoagulantes)
requieran atencion medica.
La lista no puede ser considerada como representativa de todos los envene-
namientos sintomaticos debido a que la misma solo muestra los casos reporta-
dos a los Centres para el Control de Envenenamientos. Sin embargo, si provee
una idea de la frecuencia relativa y el riesgo por envenenamiento a traves de los
diferentes agentes o clases de agentes. La frecuencia relativa de los casos refleja
generalmente cuan extensamente es usado un producto en el ambiente. Por
ejemplo, un numero de desinfectantes aparecen en la lista de los diez principa-
les debido a que se encuentran mas comunmente en el hogar y en el ambiente
de trabajo que otros pesticidas (vease tambien la tabla de casos ocupacionales
que aparece a continuacion). La informacion denominadora de la poblacion a
riesgo (numero de personas expuestas) seria necesaria para comprender mejor
el riesgo relative de los diferentes pesticidas. Sin embargo, el proposito principal
de estas tablas es proveerle a los doctores una idea de los tipos de casos a los
cuales probablemente se enfrentaran en su practica.
Aunque los casos de suicidio comprenden aproximadamente el 3% de las
llamadas relacionadas con pesticidas efectuadas a los Centres para el Control de
Envenenamientos, podrian comprender el 10% de los casos vistos en una clini-
ca de salud. Los tipos de productos principles envueltos en los casos de suici-
PB
INTRODUCTION
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ENFERMEDADES OCUPACIONALES DE CALIFORNIA DEBIDO A
PESTICIDAS, 1991-1995
Rango Pesticida Sistemico Topico* Total
1 Hipoclorito de sodio 167 858 1.025
2 Amonia cuaternaria 9 348 357
3 Cloro 112 124 236
4 Glutarldehyde 38 118 156
5 Cloropirifos 113 39 152
6 Azufre 48 69 117
7 Glifosato 9 94 103
8 Propargita 3 96 99
9 Metam-sodio** 64 33 97
10 Acido danurico 14 76 90
Todos los demas 1.149 1.089 2.238
Total de todos los pesticidas/desinfectantes 1.726 2.944 4.670
* Topico incluye la piel, ojos y efectos respiratorios.
** Un descarrilamiento de tren causo un grupo de casos debido al metam-sodio en 1991.
Fuente: Louise Mehler, M.D., Programa de Vigilancia de Enfermedades causadas por
Pesticidas en California, Agenda para la Protection del Medio Ambiente de California.
dio incluye los rodenticidas anticoagulantes (20% del total de los intentos de
suicidio),los desinfectantes abase de aceite de pino (14%), los organofosfatos
(11%), las piretrinas/piretroides (6%), rodenticidas desconocidos (5%), insecti-
cidas con carbamato (4%) y desinfectantes con fenol (3%).
Los Centres para el Control de Envenenamientos estan en la niejor dispo-
sicion de hacer frente a las exposiciones que tienen lugar en ambientes residen-
ciales. Sin embargo, las exposiciones ocupacionales no son tan bien cubiertas. El
Programa de Vigilancia de Enfermedades causadas por Pesticidas en California
es visto generalmente como el mejor en el pais. La tabla que aparece arriba
presenta el numero de casos de indole ocupacional informados en California
de 1991 a 1995, en los cuales se consideraron los pesticidas como causa proba-
ble o defmitiva de la enfermedad resultante. Las combinaciones de pesticidas,
en las cuales el pesticida principal es responsable por la enfermedad no pudie-
ron ser identificadas y no son incluidas en esta tabla. Entre las personas que se
enfrentaron a pesticidas en el transcurso de sus actividades ocupacionales, fue-
ron mas comunes las lesiones dermicas y oculares en vez de los envenenamien-
tos sistemicos. Los envenenamientos sistemicos, sin embargo, tienen la tenden-
cia a ser mas severos.
Formato de este Manual
Se ha hecho el esfuerzo de estructurar este manual para una rapida referen-
da al crear un indice completo y minimizar las referencias a las otras paginas o
Capitulos del manual. Sin embargo, agentes diferentes requieren comunmente
INTRODUCTION 7
-------
procedimientos similares en el tratamiento de envenenamientos, por lo cual no
es practice repetir estos protocolos en cada Capitulo. Los principios generates
para el rnanejo de envenenamientos por pesticidas, incluyendo la descontami-
nacion dermica y ocular, descontaminacion gastrointestinal y el control de con-
vulsiones es considerado en el Capitulo 2, titulado Principios Generales. Se
hace referencia a estos principios en todo el manual.
Los cambios en la estructura de esta edicion incluyen: inclusiones tabulares
de Productos Comerciales en cada Capitulo, la adicion de un nuevo Capitulo
acerca de Desinfectantes (Capitulo 19), y la adicion de un Capitulo acerca del
Historial Ambiental y Ocupacional (Capitulo 3), el cual coloca los envenena-
mientos por pesticidas en el contexto de otras exposiciones ambientales y ocu-
pacionales,provee cuestionarios disenados para producir informacion acerca de
la exposicion, discute los recursos disponibles para el profesional de la salud y
provee una lista de contactos gubernamentales y civiles ademas de paginas Web
para mayor informacion. En adicion, cada Capitulo se ha hecho referencia a
referencias claves que aparecen en literatura actualizada facilmente accesible. La
mayor parte de las referencias principles fueron seleccionadas entre las referen-
cias en revistas de evaluacion por pares, aunque tambien se incluyen algunas
resenas criticas.
El contenido de este manual ha sido derivado de muchas fuentes: textos
publicados, literatura medica, toxicologica y literatura actualizada de productos
de pesticidas, ademas de la comunicacion directa con los expertos en la toxicologia
clinica, la toxicologia de pesticidas y especialistas de la salud ambiental y ocupa-
cional. Despues de esta introduccion se incluye una lista de los principles li-
bros de texto.
Referencia
1. Institute of Medicine. Role of the Primary Care Physician in Occupational and Environmental
Medicine, Washington, DC: Institute of Medicine, 1988.
Textos y Manuales sobre Pesticidas,
Toxicologia de los Pesticidas y Toxicologia Clinica
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
PB INTRODUCCION
-------
Casarett and DoulPs Toxicology, 5th Edition
John Doull, Curtis D. Klaassen, and Mary O. Arndur
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 Management of Poisoning and Drug Overdose, 3rd Edition
Lester M. Haddad, MichaelW Shannon,James FWinchester
W B. Saunders Company, Philadelphia, PA, 1998
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 Wilkms, Baltimore, MD, 1984
Disposition of Toxic Drugs and Chemicals in Man, 5th Edition
Randall C. Baselt
Chemical Toxicology Institute, Foster City, CA, 1999
Ellenhorn's Medical Toxicology: Diagnosis and Treatment
of Human Poisoning, 2nd Edition
Matthew J. Ellenhorn, Seth Schonwald, Gary Ordog, Jonathan Wasserberger
Williams and Wilkins, Baltimore, MD, 1997
Farm Chemicals Handbook
Richard T. Meister, Editor-in-Chief
Meister Publishing Company,Willoughby, Ohio, 1999
Goldfrank's Toxicologic Emergencies, 6th Edition
Lewis L. Goldfrank and others, Editors
Appleton & Lange, Stamford, CT, 1998
Goodman & Oilman's The Pharmacological Basis of Therapeutics,
9th Edition
Joel G. Hardman, Lee E. Limbird, et al., Editors
McGraw Hill, New York, NY, 1996
INTRODUCCION 9
-------
Handbook of Pesticide Toxicology
Wayland J. Hayes,Jr. and Edward R. Laws,Jr., Editors
Academic Press, San Diego, CA 1991
Herbicide Handbook, 7th Edition
Weed Science Society of America, 1994
The Merck Index, 12th Edition
Susan Budavari, Editor
Merck and Company, Inc.,Whitehouse Station, NJ, 1996
Patty's Industrial Hygiene and Toxicology, 4th Revised Edition
George D. Clayton and Florence E. Clayton
Wiley Interscience, New York, NY, 1991-95
Pesticide Manual, llth Edition
CDS Tomlin
The British Crop Protection Council, Farnham, Surrey, United Kingdom, 1997
Pesticide Pro files rToxicity, Environmental Impact, and Fate
Michael A. Kamrin, Editor
Lewis Publishers, Boca Raton, FL, 1997
POISINDEXR System
Barry H. Rumack, N.K. Sayre, and C.R. Gelman, Editors
Micromedex, Englewood, CO, 1974-98
Poisoning and Drug Overdose, 3rd Edition
Kent R. Olson, Editor
Appleton & Lange, Stamford, CT, 1999
PB INTRODUCCION
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CAPITULO 2
Principios Generales en el
Manejo de los Envenenamientos
Agudos Causados por Pesticidas
Este Capitulo describe el manejo de las tecnicas aplicables para el tratamiento
basico de los envenenamientos mas agudos causados por pesticidas. Alii donde se
hacen necesarias consideraciones y tratamientos especiales para algun pesticida en
particular, los mismos son tratados por separado en el Capitulo adecuado.
Descontaminacion Dermica
La descontaminacion debe llevarse a cabo a la vez que se efectue cualquier
rnedida necesaria de resucitacion y la administracion de un antidote para la
preservacion de la vida. El paciente debera ser duchado con agua y jabon. El
cabello debera ser lavado con champu para remover cualquier quimico de la
piel y el cabello. Si existiera alguna indicacion de debilidad, ataxia, u otro dete-
rioro 2neurol6gico, la ropa debera ser removida y debera administrarsele un
bano y lavado de cabello complete, mientras la victima se encuentra recumbente.
No debera pasarse por alto la posibilidad de que haya quedado pesticida debajo
de las uiias o en los pliegues de la piel.
Deberan lavarle los ojos con gran cantidad de agua limpia durante 10-15
minutos para erradicar cualquier contaminante quimico. Si hubiera irritacion
de los ojos despues de la descontaminacion, seria apropiado consultar a un
oftalmologo.
Las personas que asisten a la victima deberan evitar el contacto directo con
la ropa y el vomito altamente contaminado. La ropa contaminada debera ser
quitada, colocada en una funda y lavada prontamente antes de ser devuelta.
Generalmente ni los zapatos ni cualquier otro objeto de piel pueden ser
descontaminados, y por lo tanto deberan ser desechados. Tome en cuenta que
los pesticidas pueden contaminar el interior de las superficies de guantes, botas
y sombreros. Debera considerarse la descontaminacion, especialmente para el
personal de emergencia tal y como conductores de ambulancias que presten
servicios en un lugar en el que haya habido un derramamiento o donde haya
ocurrido contaminacion. Utilice guantes de goma mientras lava el pesticida
que haya en la piel o cabello del paciente. Los guantes de latex u otros guantes
PRINCIPIOS GENERALES 11
-------
quirurgicos o precautorios generalmente no ofrecen la proteccion adecuada
para la contaminacion por pesticidas, por lo cual, solamente los guantes de
goma son adecuados para este proposito.
Proteccion de las Vias Respiratorias
Asegurese de que las vias respiratorias esten libres de obstruccion. Succione
cualquier secrecion oral utilizando un tubo de succion de diametro grande, de
ser eso necesario. Intube la traquea si el paciente demuestra un cuadro de de-
presion respiratoria o de parecer obtundente o de otra forma neurologicamente
incapacitado. Administre oxigeno segun sea necesario para mantener la oxige-
nacion tisular adecuada. En casos de envenenamientos severos, tal vez sea nece-
sario mantener de forma mecanica la ventilacion pulmonar durante varies dias.
Nota Acerca de Pesticidas Especificos: Existen varias consideraciones
especiales con respecto a ciertos pesticidas. En el envenenamiento por
organofosfatos y carbamatos, la oxigenacion tisular adecuada es esencial
antes de la administracion de atropina. De igual importancia es el hecho de que
en el envenenamiento por paraquat y diquat, el oxigeno es contraindicado
temprano en el envenenamiento debido a la toxicidad progresiva del oxigeno
en el tejido pulmonar. Para mas detalles, consultense los Capitulos especificos.
Descontaminacion Gastrointestinal
Una declaracion conjunta fue recientemente hecha publica por la Acade-
mia Americana de Toxicologia Clinica (American Academy of Clinical
Toxicology) y la Asociacion Europea de Centres de Envenenamientos y
Toxicologos Clinicos (European Association of Poisons Centres and Clinical
Toxicologists) en referencia a diferentes metodos de descontaminacion
gastrointestinal. Un resumen de la declaracion, en cuanto a la posicion, acom-
pana la descripcion de cada procedimiento.
1. Lavado Gastrico
Si el paciente presenta sintomas dentro de los 60 minutos despues de la
ingestion, debera considerarse el lavado. Inserte un tubo orogastrico, el cual
debe ir seguido de liquidos, generalmente una solucion salina normal. Aspire el
fluido en un intento por remover cualquier agente toxico. Si el paciente esta
neurologicamente incapacitado, la proteccion de las vias respiratorias con un
tubo endotraqueal con balon inflable es indicada antes del lavado gastrico.
No se ha probado que el lavado efectuado mas de 60 minutos despues de la
ingestion sea beneficial y se corre el riesgo de inducir sangradura, perforacion o
cicatrices debido al trauma adicional a tejidos ya traumatizados. Casi siempre es
necesario controlar primeramente las convulsiones antes de intentar efectuar
PB PRINCIPIOSGENERALES
-------
un lavado gastrico o cualquier otro metodo de descontaminacion gastrointestinal.
Se han conducido estudios de recuperacion de envenenamientos princi-
palmente con materiales solidos tales como pastillas. No existen estudios con-
trolados acerca de recuperacion de pesticidas a traves de estos metodos. En
varies estudios, el informe de material recuperado 60 minutos despues fue de
8%-32%.1>2 Existe mayor evidencia de que el lavado podria impulsar el material
al intestine delgado, aumentado asi su absorcion.3
Nota Acerca de Pesticidas Especificos: El lavado es contraindicado en
la ingestion de hidrocarbono, un vehiculo comun en muchas formulaciones de
pesticidas.
Declaracion de la Posicion: El lavado gastrico no debera ser utilizado
rutinariamente en el manejo de envenenamientos. El lavado es indicado sola-
mente cuando el paciente haya ingerido una cantidad de veneno que poten-
cialmente ponga en peligro su vida y el procedimiento puede ser efectuado
dentro de los 60 minutos subsiguientes a la ingestion. Aun entonces, el benefi-
cio clinico no ha sido confirmado en estudios controlados.4
2. Catarsis
El sorbitol y citrato de magnesio son utilizados comunmente como agen-
tes catarticos. Debido a que el citrato de magnesio no ha sido estudiado detalla-
damente, su uso no es descrito aqui. El sorbitol es a menudo incluido en las
formulaciones de carbon. Este aumentara la movilidad intestinal para mejorar
la excrecion del producto del compuesto del carbono con el veneno. La dosifi-
cacion de sorbitol es de 1-2 g/kg en una sola dosis. Dosis repetidas de catarticos
podrian resultar en desbalances de fluido y electrolitos, particularmente en los
niiios, y por lo tanto, no se recomienda. El sorbitol es formulado en soluciones
de 70% y 35%, y generalmente es empacado en botellas de 100 ml. La dosifica-
cion en gramos de sorbitol en una botella de 100 ml puede ser calculada mul-
tiplicando 100 (ml) x 0,7 (para una solucion de 70%) x 1.285 g sorbitol/ml. Por
lo tanto, la dosis en ml es como sigue:
Dosis de Sorbitol:
Adultos: 70% sorbitol, 1-2 ml/kg.
Ninos: 35% sorbitol, 1,5-2,3 ml/kg (dosis maxima: 50 g).
Nota Acerca de Pesticidas Especificos: El envenenamiento significati-
ve con organofosfatos, carbamatos y arsenicos generalmente resulta en una
diarrea profusa. El envenenamiento con diquat y a menor grado con paraquat,
resulta en ileo. El uso de sorbitol no es recomendado en ninguno de los enve-
nenamientos por pesticidas arriba mencionados.
PRINCIPIOSGENERALES 13
-------
Declaracion de la Posicion: La administracion de un catartico solamen-
te no tiene lugar alguno en el nianejo de un paciente envenenado. No existen
indicaciones definitivas para el uso de catarticos en el manejo de un paciente
envenenado. La informacion acerca del uso en combinacion de carbon activa-
do es conflictiva, y su uso rutinario no es endosado. Si se utiliza un catartico,
debera hacerse en dosis sencilla con el proposito de minimizar los efectos ad-
versos. Existen numerosas contraindicaciones, incluyendo la falta de sonidos
intestinales, trauma abdominal o cirugia, o perforacion u obstruccion intestinal.
Tambien es contraindicado en la reduccion de volumen, hipotension, desbalance
de electrolitos o la ingestion de una substancia corrosiva.5
3. Absorcion de Carbon Activado
El carbon activado es un absorbente efectivo para muchos envenenamien-
tos. Estudios voluntaries sugieren que reduce la cantidad de veneno absorbido
si se administra dentro de los 60 minutos subsiguientes.6 No hay informacion
suficiente para apoyar o excluir su uso si se prolonga el tiempo de ingestion,
aunque algunos venenos menos solubles pueden ser absorbidos despues de 60
minutos. Existe evidencia de que el paraquat es bien absorbido por el carbon
activado.7'8 El carbon ha sido anecdoticamente exitoso con otros pesticidas.
Dosis de Carbon Activado:
Adultos y nines mayores de 12 anos: 25-100 g en 300-800 ml agua.
Ninos menores de 12 anos: 25-50 g por dosis.
Reden naddos e infantes con unpeso menor de 20kg: 1 g por kg de peso
corporeo.
Muchas formulaciones de carbon activado vienen premezcladas con sorbitol.
Evite darle mas de una dosis de sorbitol como catartico a infantes y niiios
debido al riesgo de cambios rapidos en el fluido intravascular.
Estimule a la victima a tomar el absorbente aunque continue el vomito
espontaneo. La terapia antiemetica podria ayudar a controlar los vomitos en los
adultos o niiios mayores. Como una alternativa, el carbon activado puede ser
administrado a traves de un tubo orogastrico o diluido con agua y administrado
lentamente a traves de un tubo nasogastrico. La administracion repetida de
carbon u otro absorbente cada 2-4 horas puede ser beneficial tanto para los
niiios como para los adultos, pero el uso de un catartico tal como el sorbitol
debera ser evitado despues de la primera dosis. Las dosis repetidas de carbon
activado no deberan ser administradas si el intestine esta atonico. El uso de
carbon sin la proteccion de las vias respiratorias es contraindicado para el pa-
ciente incapacitado neurologicamente.
PB PRINCIPIOSGENERALES
-------
Nota Acerca de Pesticidas Especificos: El uso de carbon sin la protec-
cion de las vias respiratorias debera ser utilizado con precaucion en lo que a
venenos tales como los organofosfatos, carbamatos y organoclorados se refiere,
si los mismos estan preparados en una solucion de hidrocarbono.
Declaracion de la Posicion: Una sola dosis de carbon activado no debe-
ra ser usada de forma rutinaria en el manejo de pacientes envenenados. El
carbon parece ser mas efectivo durante los 60 minutos subsiguientes a la inges-
tion y su utilizacion podria ser considerada durante este periodo de tiempo.
Aunque podria ser considerado 60 minutos despues de la ingestion, no existe
suficiente evidencia para apoyar o negar su uso durante este periodo de tiempo.
A pesar de la mejoria en el enlace de venenos dentro de los 60 minutos subsi-
guientes, solamente existe un estudio9 que sugiere que existe una mejoria en el
resultado clinico. El carbon activado es contraindicado en vias respiratorias sin
proteccion, en el sistema gastrointestinal que no esta anatomicamente intacto, y
cuando la terapia de carbon podria aumentar el riesgo de aspiracion de un
pesticida con base de hidrocarbono.6
4. Jarabe de Ipecacuana
La ipecacuana ha sido usada como un emetico desde la decada del 50. En un
estudio pediatrico, la administracion de ipecacuana resulto en vomito en los 30
minutos subsiguientes en el 88% de los ninos.10 Sin embargo, en vista de una
revision reciente de la efectividad clinica de la ipecacuana, ya no es recomenda-
ble para uso rutinario en la mayoria de los envenenamientos. La mayoria de las
pruebas clinicas envuelven el uso de ingestantes en forma de pildora, tales como
la aspirina,2'11, el acetaminofen,12, la ampicilina,1 y multiples tipos de tabletas.13
No se han efectuado pruebas clinicas con pesticidas. En 1996, mas de 2 millones
de exposiciones humanas a substancias venenosas fueron informadas a los centres
de envenenamiento norteamericanos. La ipecacuana fue recomendada para la
descontaminacion en solamente 1,8% de todas las exposiciones.14
Dosificacion de Jarabe de Ipecacuana:
Adokscentes y adultos: 15-30 ml seguido inmediatamente de 240 ml
de agua.
Ninos de 1-12 anos: 15 ml precedidos o seguidos por 120 a 240 ml
de agua.
Infantes de 6 a 12 meses: 5-10 ml precedidos o seguidos por 120 a
240 ml de agua.
La dosis puede ser repetida en todos los grupos de edad si la emesis no
ocurre en los 20-30 minutos subsiguientes.
PRINCIPIOSGENERALES 15
-------
Posicion de la Declaracion: El jarabe de ipecacuana no debe ser admi-
nistrado rutinariamente a pacientes de envenenamiento. Si la ipecacuana es
usada, debe ser administrada en los 60 minutos subsiguientes a la ingestion. Aun
entonces, estudios clinicos no han demostrado beneficio alguno. Este debe con-
siderarse solamente en un paciente alerta y conciente que haya ingerido una
cantidad potencialmente toxica. Las contraindicaciones para su uso incluyen las
siguientes: pacientes cuyos reflejos protectores de las vias respiratorias estan
disminuidos, la ingestion de hidrocarbonos con un alto potencial de aspiracion,
la ingestion de una substancia corrosiva, o la ingestion de una substancia para la
cual se haga necesario el sostenimiento de vida avanzado en los 60 minutos
subsiguientes.15
5. Convulsiones
El lorazepam esta siendo reconocido cada vez mas como el medicamento
de preferencia para status epilepticus, aunque existen algunos informes de su
uso con ciertos pesticidas. Se debe estar preparado para proveer ventilacion con
lorazepam y con cualquier otro medicamento utilizado para controlar las con-
vulsiones.Vease la tabla de dosis en la pagina siguiente.
En la literatura no se ha informado el uso de lorazepam para los compues-
tos organoclorados. El diazepam es a menudo usado para esto, y continua sien-
do usado en otros envenenamientos por pesticidas.
Dosificacion de Lorazepam:
Adultos: Dosis de 2-4 mg de aplicacion intravenosa durante un pe-
riodo de 2-5 minutos. Repetir de ser necesario hasta un maximo de
8 mg en un periodo de 12 horas.
Adokscentes: La misma dosis que los adultos, excepto que la dosis
maxima es de 4 mg.
Nines menores de 12 anos:0,05-0,10 mg/kg de aplicacion intravenosa
durante un periodo de 2-5 minutos. Repetir de ser necesario ,05
mg/kg 10-15 minutos despues de la primera dosis, con una dosis
maxima de 4 mg.
Precaucion: Este preparado para asistir la ventilacion pulmonar me-
canica si la respiracion se deprime, a intubar la traquea si ocurre un
laringospasmo, y a contrarrestar las reacciones de hipotension.
PB
PRINCIPIOSGENERALES
-------
Dosificacion de Diazepam:
Adultos: 5-10 nig de aplicacion intravenosa repetida cada 5-10 mi-
nutos hasta un maximo de 30 nig.
Nines: 0.2-0.5 nig/kg de aplicacion intravenosa cada 5 minutos has-
ta un maximo de 10 nig en ninos niayores de 5 anos y de 5 nig en
ninos nienores de 5 aiios.
El fenobarbital es una opcion adicional para el tratamiento en el control de
las convulsiones. La dosificacion para infantes, ninos y adultos es de 15-20
nig/kg conio una dosis intravenosa de recargo. Una cantidad adicional de 5
mg/kg de aplicacion intravenosa puede ser administrada cada 15-30 minutos
hasta un niaxinio de 30 mg/kg. El medicamento no debe ser administrado a no
mas de 1 mg/kg/minuto.
En lo que respecta al tratamiento de convulsiones, la mayoria de los pacien-
tes responden bien al tratamiento usual, el cual consiste de benzodiazepinas, o
fenitoina y fenobarbital.
Referencias
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 aspi-
rin overdose. Br Med] 1988;296:1507.
3. Saetta JP, March S, Gaunt ME, et al. Gastric emptying procedures in the self-poisoned pa-
tient: Are we forcing gastric content beyond the pylorus?J.R SocMed 1991;84:274-6.
4. American Academy of Clinical Toxicology, European Association of Poisons Centres and Clinical
Toxicologists. Position statement: Gastric lavage._/7oซVo/ Clin Toxicol 1997;35:711-9.
5. American Academy of Clinical Toxicology, European Association of Poisons Centres and
ClinicalToxicologists. Position statement: Cathartics.JToxicol 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 chaicoal.JToxicol Clin Toxicol
1997;35:721-41.
7. Gaudreault P, Friedman PA, and Lovejoy FH Jr. Efficacy of activated charcoal and magne-
sium citrate in the treatment of oral paraquat intoxication. Ann Emerg Med 1985;14:123-5.
8. Terada H, Miyoshi T, Imaki M, et al. Studies on in vitro paraquat and diquat removal by
activated caibon.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] Emerg Med 1990;8:479-83.
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.
PRINCIPIOSGENERALES 17
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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. EurJ 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.JIcraVo/ Clin Toxicol 1997;35:699-709.
PB PRINCIPIOSGENERALES
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CAPITULO 3
Historial Ambiental
y Ocupacional
El envenenamiento por pesticidas puede pasar desapercibido debido a la falla
en tomar el historial apropiado de la exposicion. Este Capitulo tiene como
meta remediar esta area, a menudo pasada por alto, proveyendo herramientas
basicas para tomar el historial complete de la exposicion. En algunas situacio-
nes, en las cuales las exposiciones scan complejas o multiples y/o cuyos sinto-
mas scan atipicos, es importante considerar la consulta con toxicologos clinicos
o especialistas en la medicina ambiental y ocupacional. Los Centres Locales
para el Control de Envenenamientos tambien deberian se considerados cuando
haya preguntas acerca del diagnostico y tratamiento.
Aunque este manual trata principalmente con las enfermedades y lesiones
relacionadas con los pesticidas, el metodo de acercamiento para la identifica-
cion de exposiciones es similar a pesar del riesgo especifico envuelto. Es impor-
tante cerciorarse de si han habido otras exposiciones no relacionadas con pesti-
cidas debido al potencial de interaccion entre estos riesgos y el pesticida de
interes (e.j., la intoxicacion por pesticidas y la fatiga causada por el calor en
trabajadores agricolas en el campo). Por lo tanto, la seccion que sigue a conti-
nuacion, la cual trata con exposiciones a pesticidas, debe ser vista dentro del
contexto de una evaluacion general a la exposicion.
La mayoria de las enfermedades relacionadas con los pesticidas tienen pre-
sentaciones clinicas similares a condiciones medicas comunes y muestran sinto-
mas y seiiales fisicas no especificas. El conocimiento de la exposicion del pa-
ciente a factores ocupacionales y ambientales es importante para propositos de
diagnosticos terapeuticos, de rehabilitacion y de salud publica. Por lo tanto, es
esencial obtener un historial adecuado de cualquier exposicion ambiental u
ocupacional que pudiera causar enfermedad o agravar una condicion medica
existente.
En adicion al registro apropiado del historial del paciente, tambien debera
considerarse cualquier otra persona que pueda haber estado similarmente ex-
puesta en el hogar, trabajo o comunidad. Cada enfermedad ambiental u ocupa-
cional identificada debera ser considerada como un evento de alerta potencial
de salud, que podria requerir actividades de seguimiento para identificar la
fuente de exposicion y cualquier otro caso adicional. Al identificar y eliminar la
fuente de exposicion se puede prevenir la exposicion continua al paciente ini-
cial y a cualesquiera otras personas envueltas.
HISTORIAL AMBIENTAL
Y OCUPACIONAL 19
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Los pacientes con esta clase de enfermedades pueden ser vistos por pro-
veedores de servicios de salud que no esten familiarizados con estas condi-
ciones. Si un historial apropiado es obtenido y al parecer existe una exposi-
cion ambiental u ocupacional sospechosa, el proveedor de servicios de salud
puede consultar con especialistas (e.j., higienistas industriales, toxicologos,
especialistas medicos, etc.) en el campo de la salud ambiental y ocupacional.
Para los eventos de alerta de salud mas severos y aquellos que envuelven a
numerosas personas, puede obtenerse ayuda adicional contactando al depar-
tamento de salud estatal,la agencia reguladora estatal (e.j., el departamento de
agricultura en el caso de enfermedades y lesiones causadas por pesticidas), u
otras organizaciones relacionadas (vease la lista al final del Capitulo).Ademas,
algunos estados requieren se informen ciertas condiciones ambientales y ocu-
pacionales (e.j., informe de casos que envuelven pesticidas en Arizona,
California, Florida, Oregon, Texas y Washington).
Este Capitulo revisa el tipo de preguntas a ser efectuadas al tomar el histo-
rial ocupacional y ambiental (tanto para pacientes adultos como pediatricos),
discute consideraciones legales, eticas y de salud publica y enumera recursos de
informacion.
Tomando el Historial de la Exposicion
Teniendo en cuenta el apremio de tiempo al que se enfrentan la mayoria de
los proveedores de servicios de salud, unas cuantas preguntas para el examen
seran preferibles a un largo cuestionario en cuanto a la identificacion de peli-
gros ocupacionales o ambientales se refiere. Las preguntas que siguen a conti-
nuacion podrian ser incorporadas a un cuestionario general de salud en exis-
tencia o a entrevistas rutinarias a pacientes.
Si la presentacion clinica o el historial medico inicial sugiere una exposi-
cion ocupacional o ambiental potencial, debera efectuarse una entrevista de
exposicion detallada. Un extenso historial de exposicion provee un cuadro mas
completo de factores de exposicion pertinentes y podria tomar hasta una hora.
La entrevista detallada incluye preguntas acerca de exposicion ocupacional, ex-
posicion ambiental, sintomas y condiciones medicas, y exposicion no ocupa-
cional potencialmente relacionada a las enfermedades o lesiones. Aunque el
enfoque es colocado en las exposiciones a los pesticidas y a los efectos de salud
relacionados, exposiciones concurrentes a otras cosas que no scan pesticidas
deben ser consideradas en la evaluacion general de la salud del paciente. Pre-
guntas tipicas de una entrevista detallada aparecen en las paginas que siguen a
continuacion, las cuales estan precedidas por preocupaciones especiales al tratar
con la exposicion de niiios y trabajadores agricolas. Para mas detalles acerca de
como tomar un historial para todas las clases de peligros ocupacionales y am-
bientales, consulte la monografia del ATSDR titulada "Taking an Exposure
History"1 o un texto de referencia medica ocupacional y ambiental general.2
HISTORIAL AMBIENTAL
PB Y OCUPACIONAL
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PREGUNTAS PARA EL EXAMEN PARA EXPOSICIONES
OCUPACIONALES Y AMBIENTALES*
Para un paciente adulto:
Despues de que se establezca cual es la queja principal y el historial de la enfermedad
presentada:
iQue tipo de trabajo Neva a cabo?
(De estar desempleado) ^Cree que sus problemas de salud estan relacionados
con su hogar u otra localization?
(De estar empleado) ^Cree usted que sus problemas de salud estan relaciona-
dos con su trabajo? ^Mejoran o empeoran sus sintomas cuando esta en el
hogar o en el trabajo?
^Esta siendo expuesto ahora o se ha visto expuesto anteriormente a pesticidas,
solventes u otros quimicos, polvos, emanaciones, radiadon o ruidos altos?
Para un paciente pediatrico (las preguntas son efectuadas al padre o guardian):
^Piensa que los problemas de salud del paciente estan relacionados al hogar,
guarderia, escuela u otra localizacion?
^Ha habido alguna exposicion a pesticidas, solventes u otros quimicos, polvos,
emanaciones, radiacion o ruido fuerte?
iQue tipo de trabajo llevan a cabo los padres u otros miembros del hogar?
Poblaciones de Pacientes Especiales
Ninos
En comparacion con los adultos, los ninos corren un mayor riesgo de ex-
posiciones a pesticidas debido a los factores de crecimiento y desarrollo. La
consideracion de las caracteristicas fetales, infantiles, de ninos pequeiios o ninos
mas grandes es de ayuda en la evaluacion de la exposicion: localizacion fisica,
zonas de respiracion, consume de oxigeno, consume de alimentos, tipos de
comida consumida y desarrollo normal de la conducta.3 Ademas, la absorcion
transplacentaria y la leche materna podrian crear rutas adicionales de exposi-
cion. Aunque la exposicion ambiental (y en ocasiones, ocupacional) a los pesti-
cidas es el punto central de este capitulo, el peligro mas significative para los
ninos lo es la ingestion no intencional.4 For lo tanto, es muy importante pre-
guntar acerca de los pesticidas usados y almacenados en el hogar, guarderia
infantil, escuelas y areas de juego.
Tmbojadores Agvicolas,
La informacion del sistema de informe obligatorio de envenenamientos
por pesticidas de California podria implicar un estimado nacional anual de
10.000-20.000 casos de envenenamiento de trabajadores agricolas.5 Sin embar-
go, se cree que estos numeros todavia no representan la seria realidad de no
informar debido a la falta de acceso medico a la cual se enfrentan muchos
HISTORIAL AMBIENTAL
Y OCUPACIONAL
21
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ENTREVISTA DETALLADA PARA EXPOSICIONES
OCUPACIONALES Y AMBIENTALES
(Las preguntas marcadas en negritas son especialmente importantes para un historial de exposicion a pesticidas)
(1) Paciente Adulto
EXPOSICION OCUPACIONAL
ฃCual es su ocupacion? (De estar desempleado, pase a la proxima seccion)
iDurante cuanto tiempo ha estado efectuando este trabajo?
Describa su trabajo y los peligros a los cuales esta expuesto (e.j., pesticidas, solventes u otros
quimicos, polvo, emanaciones, metales, fibras, radiadon, agentes biologicos, ruido, calor, f no, vibradones)
iBajo que circunstancias utiliza usted el equipo de protection? (E.j., ropa de trabajo, anteojos de
seguridad, respirador, guantes, y protection auditiva)
ฃFuma o come en el lugar de trabajo?
Enumere sus trabajos previos en orden cronologico, incluyendo trabajos de Jornada completa y
parcial, temporeros, segundos trabajos, trabajos de verano, y experiencia militar. (Debido a que
esta pregunta podria tomar largo tiempo en ser contestada, una opcion es pedirle al paciente que llene un
formulario con esta pregunta antes de que el medico le tome el historial formal. Otra opcion es hacerle un
historial mas corto, pidiendole al paciente que enumere solamente los trabajos anteriores que envolvieron
los agentes de interes. Porejemplo, podrfan pedfrsele todos los trabajos actualesy pasadosque envuelvan
o hayan envuelto la exposicion a pesticidas.)
HISTORIAL DE EXPOSICION AMBIENTAL
iSe utilizan pesticidas (e.j., venenos contra insectos o hierbas, aerosoles contra pulgas y
garrapatas, collares, polvos o champus) en su hogar o jardin o en su mascota?
iParticipa usted, o algun miembro de su familia, de un pasatiempo que lo exponga a cualquier
material peligroso (e.j., pesticidas, pinturas, ceramica, solventes, metales, pegamento)?
Si se utilizan pesticidas:
iEsta envuelto un aplicador licenciado de pesticidas?
iSe permite que nirios jueguen en areas recientemente tratadas con los pesticidas?
ฃD6nde se guardan los pesticidas?
iSe manejan los alimentos apropiadamente (e.j., se lavan las frutas crudas y los vegetales)?
iHa vivido usted alguna vez cerca de una facilidad que pudiera haber contaminado el area
circunvecina (e.j., mina, planta, fabrica de fundicion, vertedero de basura)?
iSe ha mudado usted de residencia debido a problemas de salud?
^Proviene su agua potable de un pozo privado, agua de la ciudad, y/o la compra en un
supermercado?
^Trabaja usted en su automovil?
^Cual de lossiguientesarticulostiene usted en su hogar: aireacondicionado/purificador, calefacdon central
(gas o aceite), estufa de gas, estufa electrica, chimenea, estufa de madera, o humidificador?
^Ha adquirido recientemente alfombra o muebles nuevos, o ha remodelado su hogar?
^Ha aclimatado su hogar recientemente?
^Aproximadamente en que aho fue construida su casa?
SfNTOMAS Y CONDICIONES MEDICAS
(De estar empleado)
iExiste alguna relation entre el momento que dan inicio sus sintomas y sus horas de trabajo?
iHa sufrido alguien mas en el trabajo del mismo problema o de problemas similares?
iExiste alguna relation entre el momento en que aparecen sus sintomas con las actividades
ambientales arriba mencionadas?
iHa sufrido algun otro miembro del hogar o vecino cercano de problemas de salud similares?
HISTORIAL AMBIENTAL
PB Y OCUPACIONAL
-------
EXPOSICIONES NO OCUPACIONALES POTENCIALMENTE RELACIONADAS A ENFERMEDADES 0 LESIONES
iDsa usted tabaco? De ser afirmativa la respuesta, ^en que forma (cigarrillos, pipa, cigarros, tabaco de
masticar)? ^Mas o menos cuantos se fuma o cuanto tabaco usa al dia? ^A que edad comenzo a usar
tabaco? ^Hay otros fumadores de tabaco en el hogar?
ฃToma usted alcohol? ^Cuanto al dia o a la semana? ^A que edad comenzo?
iQue medicamentos odrogas esta tomando?(lnduya los medicamentosprescritosy los no prescritos)
iHa trabajado alguien en la familia con materiales peligrosos que pudieran haber llevado a la
casa (e.j., pesticidas, asbestos, plomo)? (De ser afirmativa la respuesta, pregunteacerca de los miembros
de la familia que hayan estado potencialmente expuestos.)
(2) PacientG PediatriCO (las preguntas le son efectuadas al padre o guardian)
EXPOSICION OCUPACIONAL
iCual es su ocupacion y la de los demas miembros del hogar? (De no haber personas empleadas,
pase a la siguiente seccion)
Describa su trabajo y los peligros a los cuales esta expuesto (e.j., pesticidas, solventes u otros
quimicos, polvo, emanaciones, metales, fibras, radiacion, agentes biologicos, ruido, calor, fno, vibradones)
HISTORIAL DE EXPOSICION AMBIENTAL
iSe utilizan pesticidas (e.j., venenos contra insectos o hierbas, aerosoles contra pulgas y
garrapatas, collares, polvos o champus) en su hogar o jardin, o en su mascota?
iParticipa usted, o algun miembro de su familia de un pasatiempo que lo exponga a cualquier
material peligroso (e.j., pesticidas, pinturas, ceramica, solventes, metales, pegamento)?
Si se utilizan pesticidas:
iEsta envuelto un aplicador licenciado de pesticidas?
iSe permite que nirios jueguen en areas recientemente tratadas con los pesticidas?
iDonde se guardan los pesticidas?
iSe manejan los alimentos apropiadamente (e.j., se lavan las frutas crudas y los vegetales)?
iHa vivido el paciente alguna vez cerca de una facilidad que pudiera haber contaminado el area
circunvecina (e.j., mina, planta, fabrica de fundicion, vertedero de basura)?
iSe ha mudado el paciente de residencia debido a problemas de salud?
iProviene el agua potable del paciente de un pozo privado, agua de la ciudad, y/o la compra en
un supermercado?
i_Cua\ de los siguientes articulos esta presente en el hogar del paciente: aire acondicionado/purificador,
calefaccion central (gas o aceite), estufa de gas, estufa electrica, chimenea, estufa de madera, o
humidificador?
(_Se ha adquirido recientemente alfombra o muebles nuevos, o se ha remodelado el hogar del paciente?
^Ha aclimatado su hogar recientemente?
^Aproximadamente en que aho se construyo la casa?
SfNTOMAS Y CONDICIONES MEDICAS
^Existe alguna relation entre el momento en que dan inicio los sintomas y las actividades
ambientales enumeradas arriba?
iHa sufrido algun otro miembro del hogar o vecino cercano problemas de salud similares?
EXPOSICIONES NO OCUPACIONALES POTENCIALMENTE RELACIONADAS A ENFERMEDADES 0 LESIONES
iHay personas en el hogar que fumen tabaco? De ser afirmativa la respuesta, ^en que forma (cigarrillos,
pipa, cigarros, tabaco de masticar)?
iQue medicamentos o drogas esta tomando el paciente? (Incluya los medicamentos prescritos y los
no prescritos)
iHa trabajado alguien en la familia con materiales peligrosos que pudieran haber llevado a la
casa (e.j., pesticidas, asbestos, plomo)? (De ser afirmativa la respuesta, pregunteacerca de los miembros
de la familia que hayan estado potencialmente expuestos.)
HISTORIAL AMBIENTAL
Y OCUPACIONAL
23
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trabajadores agricolas y el diagnostico erroneo efectuado por ciertos profesio-
nales de la salud. Para estos pacientes de alto riesgo, el historial de exposicion
deberia incluir preguntas especificas acerca del trabajo agricola que llevan a
cabo. Por ejemplo:
(Se estan usando pesticidas en el hogar o trabajo?
iEstaban mojados los campos cuando estaba recogiendo?
iSe estaba asperjando mientras usted estaba trabajando en el campo?
iSe enferma durante el tiempo en que esta trabajando en el campo
o despues?
El uso de pesticidas en la residencia y el llevar al hogar pesticidas agricolas o
ropa de trabajo contaminada que no es adecuadamente separada de la dernas
ropa, podria representar un peligro tambien para los otros miembros de la
familia.
Obteniendo Informacion Adicional Sobre Pesticidas
En adicion al historial del paciente, a menudo es de ayuda obtener infor-
macion adicional acerca de productos pesticidas sospechosos. Existen dos do-
cumentos muy utiles con los cuales comenzar la identificacion y evaluacion de
la exposicion a pesticidas: la hoja de informacion sobre seguridad de materiales
(MSDS) y la etiqueta del pesticida.
Hoja de informacion sobre seguridad de materiales (MSDS).
Bajo la Norrna de Comunicaciones de Alto Pviesgo de la OSHA
(29 CFR 1910.1200), se requiere que todos los fabricantes de qui-
micos provean una MSDS para cada quimico peligroso que produz-
can o importen. Se requiere que los patronos guarden copias de los
MSDS y esten disponibles para todos los trabajadores. A continua-
cion los articulos contenidos en una MSDS:
- Identificacion del material
- Ingredientes y limites de exposicion ocupacional
- Informacion fisica
- Informacion acerca de fuego y explosion
- Informacion acerca de la reactividad
- Informacion acerca de los peligros a la salud
- Derrames, filtraciones y procedimientos de eliminacion
- Informacion especial para la proteccion
- Precauciones especiales y comentarios
Estos documentos tienden a contener una informacion bastante li-
mitada acerca de los efectos en la salud y algunos de los ingredientes
activos podrian ser omitidos debido a consideraciones de los secre-
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tos de marca. No se puede depender solamente de la MSDS al efec-
tuar las determinaciones medicas.
Etiqueta del pesticida. La EPA requiere que todos los productos
pesticidas lleven etiquetas que provean cierta informacion. Esta in-
formacion puede ayudar en la evaluacion de los efectos del pesticida
en la salud y las precauciones necesarias. Los articulos cubiertos in-
cluyen los siguientes:
Nonibre del producto
Fabricante
Numero de registro de la EPA
Ingredientes activos
Declaraciones precautorias:
i. Rotulacion escrita exponiendo el peligro "Peligro" (lo mas pe-
ligroso), "Advertencia," y "Precaucion" (menos peligroso)
ii. Advertencia sobre peligro para los niiios
iii. Declaracion acerca de tratamientos practices (senales y sinto-
mas de envenenamiento, primeros auxilios, antidotes y nota a
los doctores en caso de un envenenamiento)
iv. Peligro a los humanos y a los animates domesticos
v. Peligros ambientales
vi. Peligros fisicos o quimicos
Direcciones para el uso
Nombre y direccion del fabricante
Contenido neto
Numero de registro de la EPA
Numero de establecimiento de la EPA
Designacion de la Norma de Proteccion para el Trabajador
(WPS), incluyendo el intervalo de entrada restringida y el
equipo de proteccion personal requerido (vease la descrip-
cion de la WPS en la pagina 29).
El numero de registro de la EPA es util al contactar la EPA para
informacion o cuando se llama a la linea de emergencia de la Red
Nacional de Telecomunicaciones de Pesticidas (vease la pagina 34).
Las etiquetas de los pesticidas podrian diferir de un estado a otro
dependiendo de las consideraciones de areas especificas. Ademas,
diferentes formulaciones de los mismos ingredientes activos podrian
resultar en una informacion diferente en la etiqueta. La etiqueta del
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pesticida solo enumera la informacion de los ingredientes activos
(no de los componentes inertes) y en raras ocasiones contiene in-
formacion acerca de los efectos cronicos a la salud (e.j., cancer y
enfermedades neurologicas, reproductivas y respiratorias).6 Aunque
a menudo hace falta mayor informacion sobre los pesticidas, estos
documentos deberian ser considerados como el primer paso en la
identificacion y comprension de los efectos a la salud de un pestici-
da dado.
En lo que respecta al paciente que es un trabajador agricola, el pro-
veedor de servicios de salud tiene dos bases legales La Norma de
Proteccion para el Trabajador de la EPA y las regulaciones de la
USDA (Departamento de Agricultura de los Estados Unidos) bajo
la Declaracion Agricola de 1990 para obtener del patrono el
nombre del pesticida al cual el paciente estuvo expuesto. Cuando el
medico solicite esta informacion, debera mantener en
confidencialidad el nombre del paciente, siempre que le sea posible.
Determinando la Relacion entre el Trabajo
o las Enfermedades Ambientales
Debido a que los pesticidas y otros objetos quimicos y fisicos son peligro-
sos y a menudo estan asociados con quejas medicas no especificas, es muy
importante enlazar el nuevo sistema de revision con el plazo en el cual tuvo
lugar la exposicion sospechosa al agente peligroso. El Indice de Senales y Sinto-
mas que aparece en la SeccionV provee una pronta referencia a los sintomas y
condiciones medicas asociadas con pesticidas especificos. Informacion mas de-
tallada acerca de la toxicologia, pruebas confirmatorias, y tratamiento de enfer-
medades relacionadas a los pesticidas son provistas en cada Capitulo de este
manual. Una comprension general de las clases de pesticidas y de algunos de los
agentes mas comunes es de ayuda para efectuar diagnosticos relacionados a
enfermedades causadas por pesticidas.
Al evaluarse la asociacion de la exposicion a un pesticida dado en el am-
biente de trabajo o una condicion ambiental y clinica, los factores claves a
considerarse son:
Sintomas y senales fisicas apropiadas para los pesticidas que estan
siendo considerados.
Companeros de trabajo u otros en el ambiente que estan enfermos
Plazos en los cuales han ocurrido los problemas
Confirmacion de la exposicion fisica al pesticida
Informacion sobre la vigilancia ambiental
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Resultados de la vigilancia biologica
Credibilidad biologica aparente de los efectos sobre la salud resul-
tantes
Descartar las exposiciones a agentes quimicos que no son pesticidas
o a enfermedades pre-existentes.
Una exposicion concurrente a un quimico que no sea un pesticida podria
o no tener efecto sobre la salud, agravar un efecto en existencia causado por un
pesticida, o meramente causar un efecto en la salud del paciente. En los escena-
rios de exposicion mis complicada, debera buscarse la asistencia de especialistas
en la salud ocupacional y ambiental (vease Recursos de Informacion en la
pagina 31).
Consideraciones Legales, Eticas y de Salud Publica
A continuacion algunas consideraciones relacionadas a la regulacion gu-
bernamental de pesticidas, factores eticos y preocupaciones de salud publica
que los proveedores de servicios de salud deberian conocer al evaluar posibles
exposiciones a pesticidas.
Reportando los Requisites
Cuando se evalue un paciente con una condicion niedica relacionada a un
pesticida, es importante comprender los requisites de informe especificos del
estado para el sistema de compensacion al trabajador (si ha habido exposicion
ocupacional) o sistema de vigilancia. Informar acerca de un caso de compensa-
cion al trabajador podria tener serias implicaciones para el trabajador que esta
siendo evaluado. Si el medico no esta familiarizado con este sistema o se siente
incomodo evaluando los eventos de salud relacionados con el trabajo, es impor-
tante que consulte a un medico ocupacional o que haga el referido adecuado.
Por lo menos seis estados tienen sistemas de vigilancia dentro de sus depar-
tamentos de salud estatales, los cuales cubren tanto los envenenamientos por
pesticidas a nivel ocupacional como ambiental: California, Florida, NuevaYork,
Oregon, Texas y Washington. Estos sistemas de vigilancia recopilan informes
efectuados por medicos y otras fuentes, de casos de enfermedades y lesiones
relacionadas con pesticidas; conducen entrevistas exclusivas, investigaciones de
campo y proyectos de investigacion; ademas funcionan como un recurso para la
informacion sobre pesticidas dentro del estado. En algunos estados, como se
dijera anteriormente, el informe de casos de pesticidas es un mandate de ley.
Agendas Reguladoras
Desde su formacion en 1970, la EPA ha sido la agencia principal para la
regulacion sobre uso de pesticidas bajo el Decreto Federal sobre Insecticidas,
HISTORIAL AMBIENTAL
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Fungicidas y Rodenticidas. El mandate de la EPA incluye el registro de todos
los pesticidas usados en los Estados Unidos,la aplicacion de intervalos de entra-
da restringida, la especificacion y aprobacion de informacion en las etiquetas, y
la fijacion de niveles de tolerancia aceptables para los alimentos y el agua. En
adicion, la EPA trabaja en conjunto con las agendas estatales y tribales para
implementar dos programas de campo el programa de certificacion y entre-
namiento para los aplicadores de pesticidas y la norrna de proteccion para el
trabajador agricola. La EPA fija las norrnas nacionales para la certificacion de
mas de 1 millon de aplicadores de pesticidas privados y comerciales.
La autoridad para hacer valer las regulaciones de la EPA es delegada a los
estados. Por ejemplo,llamadas concernientes a la falta de acatamiento a la nor-
ma de proteccion para el trabajador pueden ser efectuadas al departamento de
agricultura estatal. En cinco estados, el departamento ambiental u otra agencia
estatal tiene autoridad para hacer cumplir los reglamentos. Llamadas anonimas
pueden ser efectuadas si los trabajadores anticipan posibles acciones de represa-
lia por parte de la administracion. Debera tenerse en cuenta que no todos los
departamentos de agricultura estatal tienen las mismas regulaciones. En California,
por ejemplo, se requiere que los patronos obtengan supervision medica y ob-
servacion biologica para los trabajadores agricolas que aplican pesticidas que
contengan compuestos inhibidores de colinesterasa. Este requisite no se en-
cuentra en las regulaciones federales.
Fuera del ambiente de la agricultura, la Administracion de Seguridad y
Salud Ocupacional (Occupational Safety and Health Administration) (OSHA)
tiene jurisdiccion sobre las exposiciones en el lugar de trabajo.Todos los traba-
jadores envueltos en la fabricacion de pesticidas estan cubiertos por la OSHA.
La OSHA fija los niveles permisibles de exposicion para ciertos pesticidas. Aproxi-
madamente la mitad de los estados estan cubiertos por la OSHA federal; el
resto tienen sus propios planes estatales de OSHA. Podria darse el caso de que
los planes individuales de los estados ofrezcan mas proteccion en las normas
para el lugar de trabajo. Tambien pueden efectuarse llamadas anonimas a las
agencias estatales o a la OSHA federal.
En lo que respecta a la contaminacion del agua por pesticidas, la EPA fija
un nivel de contaminacion maximo ejecutable. En brotes relacionados con ali-
mentos y drogas,la EPA trabaja en conjunto con la Administracion de Alimen-
tos y Drogas (Food and Drug Administration) (FDA) y el Departamento de
Agricultura de los Estados Unidos (U.S. Department of Agriculture) (USDA)
para vigilar y regular los residues de pesticidas y sus metabolitos. Los limites de
tolerancia para muchos pesticidas y sus metabolitos son establecidos en produc-
tos agricolas brutos.
Al evaluar un paciente que haya estado expuesto a pesticidas, el medico
necesitara reportar la intoxicacion por pesticida a la agencia de salud y/o
reguladora apropiada.
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Norma de Protection para el Trabajador
La Norrna de Proteccion para el Trabajador (Worker Protection
Standard)(WPS) de la EPA entro en vigor en 1995. La intencion de la regula-
cion es eliminar o reducir las exposiciones a pesticidas, mitigar aquellas exposi-
ciones que ocurran, e informarle a los trabaj adores agricolas acerca de los peli-
gros de los pesticidas. La WPS se aplica a dos clases de trabajadores en fincas,
invernaderos, viveros y la industria de la silvicultura: (1) los manejadores de
pesticidas agricolas (mezcladores, cargadores, aplicadores, personas que limpian
o reparan el equipo y los marcadores de campo), (2) los trabajadores agricolas
(cultivadores o segadores).
La WPS incluye el requisite de que los patronos agricolas notifiquen a los
trabajadores por adelantado acerca de la utilizacion de pesticidas, ofrezcan un
entrenamiento basico acerca del rnanejo seguro de pesticidas, provean equipo
de proteccion personal para aquellos que trabajan directamente con pesticidas,
y observen el horario de intervalo de entrada restringida (restricted entry
interval) (REI). (El PvEI es un periodo de espera requerido antes de que los
trabajadores puedan regresar a areas tratadas con pesticidas.) De interes especial
para los proveedores de servicios de salud, la WPS tambien requiere que los
patronos agricolas:
Coloquen la direccion y el numero telefonico de una facilidad de
emergencia medica en una localizacion centralizada.
Hagan arreglos inmediatos para la transportacion, desde el estableci-
miento agricola hasta una facilidad medica, de un trabajador que se
haya visto afectado por un pesticida.
Le suplan al trabajador afectado y al personal medico el nombre del
producto, el numero de registracion de la EPA, los ingredientes acti-
vos, la informacion de la etiqueta medica, una descripcion de como
fue usado el pesticida, y la informacion acerca de la exposicion.
Considemdones Eticas
Tratar de investigar una exposicion ocupacional a pesticidas podria re-
querir la obtencion de informacion adicional de parte del administrador del
lugar de trabajo o dueno. Cualquier contacto con el lugar de trabajo debera
ser efectuado en consulta con el paciente, debido al potencial para represalias
(tales como la perdida del empleo o recortes salariales). Lo ideal seria que la
peticion para una visita al lugar de trabajo o para mayor informacion acerca
de una exposicion a pesticidas en el lugar de trabajo ocurra con el consenti-
miento del paciente. En situaciones en las cuales el potencial para el peligro a
la salud es substancial y muchas personas podrian verse afectadas, una llamada
al sistema de vigilancia de pesticidas (de haber uno disponible), al centre de
salud y seguridad agricola (de haber uno cerca), podria proveerle al Institute
Nacional para la Salud y Seguridad Ocupacional (National Institute for
HISTORIALAMBIENTAL
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Occupational Safety and Health) (NIOSH) o una agencia agricola estatal, la
asistencia necesaria para la investigacion de un brote.
De forma similar, el descubrimiento de contaminacion por pesticidas en
una residencia, escuela, guarderia, productos alimenticios, u otro lugar o pro-
ducto ambiental, podria tener consecuencias para la salud publica, fmancieras
y legales para el paciente y otras personas (e.j. dueno del edificio, distrito
escolar, productor de alimentos). Es prudente discutir estas situaciones y las
opciones para el seguimiento con el paciente asi tambien como con un espe-
cialista de salud ambiental bien informado y con las agencias estatales o loca-
les apropiadas.
Considevadones de Salud Publica
Los proveedores de servicios de salud son a menudo los primeros en iden-
tificar los eventos de alerta de salud que luego de mayor investigacion se con-
vierten en un brote a gran escala. Un brote es defmido como una tasa de
enfermedad estadisticamente elevada dentro de una poblacion bien defmida en
comparacion con una poblacion normal. Por ejemplo, quejas acerca de proble-
mas de infertilidad entre trabajadores en una planta fabricadora de
dibromocloropropano (DBCP) en California condujo a un diagnostico de
azoospermia (falta de esperma) u oligospermia (merma en el contaje de esper-
ma) entre un punado de hombres jovenes saludables quienes trabajaban en la
planta.7 Una investigacion subsiguiente acerca del brote resulto en el primer
informe publicado sobre un toxico al sistema reproductive masculine en el
lugar de trabajo. En aquel momento, el DBCP era utilizado como un nematocida;
a partir de ese momento fue prohibido en los Estados Unidos.
Las investigaciones de brotes son conducidas para toda clase de exposi-
ciones y eventos de salud, no solo aquellos en un area ocupacional y ambien-
tal. Generalmente, la asistencia de expertos gubernamentales o universitarios
es necesaria en la investigacion, la cual podria requerir acceso a informacion,
pericia, y recursos fuera del alcance del medico promedio. Los pasos envuel-
tos en una investigacion de esa indole y el tipo de informacion tipicamente
recopilada en la etapa clinica preliminar aparecen delineados abajo. El medico
debe estar al tanto de que la investigacion de un brote podria ser necesaria
cuando exista un escenario de enfermedad y una exposicion severa y difun-
dida. Para mas informacion acerca de investigaciones de brotes de enferme-
dad, consulte la literatura.8'9
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PASOS EN LA INVESTIGACION DE UN BROTE DE ENFERMEDAD
Confirmar el diagnostico de los informes del caso inicial (los casos "indice")
Identificar otros casos no reconocidos
Establecer una definition del caso
Caracterizar los casos por persona, lugar y caracteristicas de tiempo (e.j., edad, raza,
etnicidad, sexo, totalization dentro de una tompama o vecindario, periodo de tiempo
de la exposicion y eventos de salud)
Delinear la incidencia de los casos de acuerdo al tiempo (una curva epidemica)
Determinarsi existe una relation de dosis-respuesta (e.j. la presentation de casos clini-
cos mas severos para personas con una mayor exposicion)
Derivar una tasa de ataque y determinar si el significado estadistico es logrado (dividir
el numero de los casos por el numero de personas expuestas y multiplicarlo por 100
para obtener el por ciento de la tasa de ataque)
Recursos de Informacion
Agendas Gubernamentales:
Oficina de Programas de Pesticidas de la EPA
Regulacion general de pesticidas con programas especiales para trabaj adores
agricolas y aplicadores de pesticidas. Los programas especificos incluyen la pro-
mocion del uso reducido de pesticidas, el establecimiento de niveles de toleran-
cia para alimentos y la investigacion de escapes de pesticidas y eventos de expo-
sicion.
Direccion: EPA - Office of Pesticide Programs
401 M Street SW (7501C)
Washington, DC 20460
Telefono: 703-305-7090
Direccion web: www.epa.gov/pesticides
EPA - Rama de Certificacion y Proteccion para el Trabajador
Dentro de la Oficina de Programas de Pesticidas (Office of Pesticide Programs),
se encuentra la Rama de Certificacion y Proteccion para el Trabajador, la cual
trata asuntos relacionados con los trabaj adores y pesticidas, y las actividades de
Certificacion para los aplicadores de pesticidas. Se hace un enfasis especial en el
entrenamiento adecuado de los trabajadores agricolas, aplicadores de pesticidas
y proveedores de servicios de salud. Hay materiales de entrenamiento disponi-
bles en varies idiomas.
Direccion: EPA - OPP
401 M Street SW (7506C)
Washington, DC 20460
Telefono: 703-305-7666
Direccion web: www.epa.gov/pesticides/safety
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Administracion de Seguridad y Salud Ocupacional (OSHA)
(Occupational Safety and Health Administration)
Mas de 100 millones de trabajadores y 6,5 millones de patronos estan cubiertos
bajo la Norma de Salud y Seguridad Ocupacional, la cual cubre a obreros en la
fabricacion de pesticidas, asi tambien como en otras industrias. La OSHA y sus
contrapartes estatales, tienen aproximadamente 2.100 inspectores, ademas de
investigadores, escritores de norrnas, educadores, doctores y otro personal en
mas de 200 oficinas a traves de todo el pais. La OSHA establece norrnas protec-
toras para el lugar de trabajo, hace valer las norrnas y le ofrece a los empleados
y patronos asistencia tecnica y programas de consultoria. Note que algunos de
los estados tienen su propio plan de OSHA.
Direccion: OSHA - US DOL
Room N3647
Constitution Ave. NW
Washington, DC 20210
Telefono: 202-219-8021
Direccion web: www.osha.gov
Administracion de Alimentos y Drogas (FDA)
(Food and Drug Administration)
Asuntos relacionados con drogas y pesticidas en los alimentos:
Direccion: FDA
National Center for lexicological Research
5600 Fishers Lane
Rockville, MD 20857
Telefono: 301-443-3170
Internet: gopher.nctr.fda.gov
Servicio de Extension de la USDA
El Servicio de Extension de la USDA trabaja con sus companeros universitarios
y con el sistema de concesion de tierras estatal para proveerle informacion a los
agricultores y rancheros con el proposito de reducir y prevenir incidentes de
trabajo relacionados con la agricultura. El programa de Entrenamiento para el
Aplicador de Pesticidas (Pesticide Applicator Training) entrena a los aplicadores
en el uso seguro de pesticidas y coordina los programas de entrenamiento rela-
cionados con el manejo seguro de pesticidas.
Direccion: USDA
14th & Independence SW
Washington, DC 20250
Telefono: 202-720-2791
Direccion web: www.reeusda.gov
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Centre Nacional para la Salud Ambiental (NCEH),
Centres para el Control de Enfermedades (CDC)
(National Center for Environmental Health [NCEH],
Centers for Disease Control [CDC])
La NCEH provee asesoramiento en casos de control de pesticidas ambientales
e investigaciones en caso de un brote.
Direccion: NCEH, CDC
Mailstop F29
4770 Buford Highway NE
Atlanta, GA 30341
Telefono: 770-488-7030
Direccion web: www.cdc.gov/nceh/ncehhonie.htm
Instituto Nacional para la Seguridad y Salud Ocupacional (NIOSH),
Centros para el Control de Enfermedades (CDC)
(National Institute for Occupational Safety and Health [NIOSH],
Centers for Disease Control [CDC])
NIOSH es la agencia federal responsable de llevar a cabo la investigacion de
enfermedades y accidentes ocupacionales. Si se le pide, NIOSH puede investi-
gar condiciones de trabajo potencialmente peligrosas, efectuar recomendacio-
nes acerca de corno prevenir enfermedades y accidentes en el lugar de trabajo y
proveer entrenamiento a profesionales de seguridad y salud ocupacional.
Direccion: NIOSH
Humphrey Building, Room 715H
200 Independence Ave. SW
Washington, DC 20201
Linea de auxilio: 1-800-356-4674
Direccion web: www.cdc.gov/niosh/homepage.html
Centros de Salud y Seguridad Agricola NIOSH
(NIOSH Agricultural Health and Safety Centers)
NIOSH le ha provisto fondos a ocho Centros de Salud y Seguridad Agricola a
traves del pais, los cuales envuelven medicos y otros especialistas de la salud en
el area de enfermedades y accidentes relacionados con pesticidas. Los centres
apoyados por NIOSH se encuentran en:
University of California Agricultural High Plains Intermountain Center
Health and Safety Center for Agricultural Health and Safety
Old Davis Road Colorado State University
University of California Fort Collins, CO 80523
Davis, CA 95616 Tel: 970-491-6152
Tel: 916-752-4050
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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
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
P.O. Box 2003
Tyler,TX 75710
Tel: 903-877-5896
Pacific Northwest Agricultural Safety
and Health Center
University ofWashington
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
Ovganizadones No Gubernamentales:
Red de Telecomunicaciones Nacional sobre Pesticidas
La Red de Telecomunicaciones Nacional sobre Pesticidas (NPTN) tiene su
base en la Universidad Estatal de Oregon y es auspiciada de forma cooperativa
por la Universidad y la EPA. La NPTN sirve como una fuente de informacion
objetiva y cientifica sobre pesticidas en un sinnumero de topicos relacionados
con pesticidas, tales como reconocimiento y manejo de envenenamientos por
pesticidas, informacion sobre seguridad, efectos en la salud y ambientales, refe-
ridos para investigacion de incidentes que envuelven pesticidas, tratamientos de
emergencia tanto para humanos como animates y procedimientos de limpieza
y eliminacion.
Un servicio telefonico de acceso gratuito provee informacion sobre pesti-
cidas a personas que llamen dentro de los Estados Unidos continentales, Puerto
Rico y las IslasVirgenes. En adicion, preguntas y comentarios sobre pesticidas
pueden ser enviadas a la direccion de correo electronico. La pagina Web tiene
enlaces a otras direcciones y bases de datos para mayor informacion.
Linea de emergencia de la NPTN: 1-800-858-7378
Horas de operacion:
Direccion web:
Correo electronico:
9:30 a.m. - 7:30 p.m. E.S.T (Hora del
este), excepto en dias feriados
http://ace.orst.edu/info/nptn/
nptn@ace.orst.edu
PB
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Fondo de Justicia para el Trabajador Agricola
(Farmworkers Justice Fund)
El Fondo de Justicia para el Trabajador Agricola puede proveer el referido apro-
piado a una red de servicios legales y a grupos sin fines de lucro, los cuales
representan a los trabajadores agricolas gratuitamente.
Direccion: Farmworker Justice Fund
1111 19th Street, NW Suite 1000
Washington, DC 20036
Telefono: 202-776-1757
Correo electronico: fjf@nclr.org
Federacion Americana del Negociado de Fincas (American Farm
Bureau Federation)
La AFBF es la organizacion general de fmcas mas grandes de la nacion. Infor-
macion acerca de como contactar negociados de fmcas individuales en los esta-
dos esta disponible en su pagina de Web.
Direccion Web: www.fb.com
Asociacion de Clmicas Ocupacionales y Ambientales (AOEC)
(Association of Occupational and Environmental Clinics)
Esta asociacion es una red de 63 clinicas, las cuales representan a mas de 250
especialistas.
Direccion: AOEC
1010 Vermont Ave., NW, Suite 513
Washington, DC 20005
Telefono: 202-347-4976
Direccion web: http://152.3.65.120/oem/aoec.htm
Centres para el Control de Envenenamientos (Poison Control Centers)
Para una lista de los centres para el control de envenenamientos estatales y
regionales, o la localizacion mas cercana, consulte la pagina Web de la NPTN
(http://ace.orst.edu/info/nptn).
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Base de Datos sobre Information de Pestiddas:
Red de la Extension de Toxicologia (EXTOXNET)
(Extension Toxicology Network)
http: //ace. ace. orst. edu /info /extoxnet
La Red de la Extension de Servicios de Toxicologia (EXTOXNET) (Extension
Service's Toxicology Network), le provee informacion con base cientifica acer-
ca de los pesticidas a los proveedores de servicios de salud que estan tratando
casos de salud relacionados con pesticidas. La informacion toxicologica sobre
pesticidas es desarrollada en cooperacion con la Universidad de California-
Davis, la Universidad Estatal de Oregon, la Universidad Estatal de Michigan,
Cornell University y la Universidad de Idaho.
IRIS
www. epa .gov/ngispgm3/iris
El Sistema Integrado de Informacion sobre Riesgos (Integrated Risk Information
System) - IRIS - es una base de datos electronica, mantenida por la EPA, acerca
de los efectos en la salud humana que pueden surgir como consecuencia de la
exposicion a diferentes quimicos en el ambiente. IRIS esta dirigida a personas
sin un extenso entrenamiento en la toxicologia, pero con cierto conocimiento
de las ciencias de la salud. La misma provee identificacion de peligros e infor-
macion sobre la evaluacion de respuestas a dosis. En combinacion con informa-
cion especifica acerca de las exposiciones, la informacion encontrada en IRIS
puede ser usada para la caracterizacion de riesgos a la salud publica causados
por un quimico en una situacion particular, lo cual puede conducir a una deci-
sion sobre el manejo de riesgos disenada para proteger la salud publica. Existe
extensa documentacion de apoyo en la Internet.
Agencia para Substancias Toxicas y Registro de Enfermedades
(Agency for Toxic Substances and Disease Registry)
http://atsdrl.atsdr.cdc.gov.8080/toxfaq.html
LaATSDR (parte del Departamento de Salud y Servicios Humanos [Department
of Health and Human Services]) publica hojas de datos y otra informacion
sobre pesticidas y otras substancias toxicas.
Bases de Datos sobre Pesticidas de California (California Pesticide
Databases)
http: I Iwww. cdpr. ca.gov/docs/database/database.htm
Incluye Pesticidal Chemical Ingredients Queries (preguntas sobre ingredientes
quimicos de pesticidas), enlaces al diccionario quimico de la Oficina de Pro-
gramas de Pesticidas de la EPA, Product/Label Database Queries (base de datos
sobre preguntas acerca de los productos/etiquetas) (puesto al dia todas las no-
ches), un listado al dia de la Seccion 18 de las Exenciones de Emergencia de
California y mucho mas.
HISTORIALAMBIENTAL
PB YOCUPACIONAL
-------
Referencias
1. Frank A and Balk S. ATSDR Case Studies in Environmental Medicine #26, Taking an
Exposure History. Atlanta: Agency forToxic Substances and Disease Registry, Oct. 1992.
2. LaDouJ. Approach to the diagnosis of occupational illness. In: LaDou J (ed). Occupational
and Environmental Medicine, 2nd ed. Stamford, CT: Appleton and Lange, 1997.
3. Bearer C. Chapter 10: Pediatric developmental toxicology. In: Brooks SM, Gochfield M, Herzstein
J, et al. Environmental Medicine. St. Louis, MO: Mosby Yearbook, 1995, pp. 115-28.
4. Jackson RJ. Chapter 31: Hazards of pesticides to children. Ibid, pp. 377-82.
5. Blondell JM. Epidemiology of pesticide poisonings in the United States, with special refer-
ence to occupational cases. In: Keifer MC (ed). Human Health Effects of Pesticides, Occu-
pational Medicine: State of the Art Reviews, Philadelphia: Hanley & Belfus, Inc., 1997.
6. Keifer MC (ed). Ibid.
7. Osorio, AM. Chapter 26: Male reproductive toxicology. In: LaDouJ (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.
HISTORIALAMBIENTAL
YOCUPACIONAL 37
-------
Seccion II
INSECTICIDAS
-------
CAPITULO 4
PUNTOS
IMPORTANTES
Actua a traves de la
fosforilacion de la enzima
acetilcolinesterasa en las
terminaciones nerviosas.
Absorbido por inhalation,
ingestion y penetration
dermica
Efectos muscarinicos,
nicotfnicos y del sistema
nervioso central
Senales y Smtomas:
Dolor de cabeza,
hipersecredon, contraction
muscular, nausea, diarrea
Depresion respiratoria,
convulsiones, perdida de
conciencia
La miosis es a menudo
serial util para el
diagnostico
Tratamiento:
Despeje las vfas aereas,
mejore la oxigenacion
tisular
Administre el sulfato de
atropina por via intravenosa
La pralidoxima puede ser
indicada
Proceda concurrentemente
con la descontaminadon
Contraindicaciones:
Morfina, succinilcolina,
teofilina, fenotiacina,
reserpina
Insecticidas Organofosfatados
Desde la remocion de los insecticidas de cloruros organicos, los insecticidas
organofosfatados se han convertido en los insecticidas de mayor uso en la ac-
tualidad. Actualmente, mas de cuarenta de ellos estan registrados para uso, y
todos corren el riesgo de toxicidad aguda y subaguda. Los organofosfatos son
utilizados en la agricultura, en el hogar, en los jardines y en la practica veterina-
ria.Aparentemente todos comparten un mecanismo comun de inhibicion de la
colinesterasa y pueden causar sintomas similares. Debido a que comparten este
mecanismo, la exposicion a los mismos organofosfatados por rutas multiples o a
multiples organofosfatados por rutas multiples podria conducir a una toxicidad
aditiva seria. Es importante comprender, sin embargo, que existe una gran va-
riedad de toxicidad en estos agentes y una gran variacion en la absorcion cuta-
nea, lo cual hace que la identificacion y el manejo especifico sea sumamente
importante.
Toxicologia
Los organofosfatos envenenan a insectos y mamiferos principalmente por
la fosforilacion de la enzima acetilcolinesterasa (ACE) en las terminaciones
nerviosas. El resultado es la perdida de la acetilcolinesterasa por lo cual el orga-
no efector es sobreestimulado por la acetilcolinesterasa excesiva (ACE, la subs-
tancia que transmite el impulso) en las terminaciones nerviosas. La enzima es
imprescindible para el control normal de la transmision de los impulses nervio-
sos que van desde las fibras nerviosas hasta las celulas musculares y glandulares y,
tambien hacia otras celulas nerviosas en los ganglios autonomos, como tambien
al sistema nervioso central (SNC). Antes de que se manifiesten senales y sinto-
mas de envenenamiento, debe inactivarse una proporcion importante de la en-
zima tisular a causa de la fosforilacion.
Cuando la dosificacion es suficiente, la perdida de la funcion enzimatica
permite la acumulacion de acetilcolina (AC) en las uniones colinergicas
neuroefectoras (efectos muscarinicos), en las uniones mioneurales del esqueleto
y los ganglios autonomos (efectos nicotinicos) asi tambien como a nivel central.
Una concentracion alta de acetilcolina en las uniones colinergicas nerviosas
con el musculo liso y las celulas glandulares puede causar contraccion del mus-
culo y secrecion, respectivamente. En las uniones musculo-esqueleticas, el ex-
ceso de acetilcolina puede ser excitatorio (causa espasmos musculares), pero
PB
ORGANOFOSFATADOS
-------
acefato
Orthene
bensulida
Betasan
Lescosan
bomil+
Swat
bromofos
Nexion
bromofostato etilico
Nexagan
cadusafosfatos
Apache
Ebufos
Rugby
carbofenotion*
Trithion
danofenfos*
Surecide
danofos
Cyanox
citioato
Cyflee
Proban
dorfenvinfos
Apachlor
Birlane
clorfoxim
Baythion-C
dormef6s+
Dotan
doropirifos
Brodan
Dursban
Lorsban
dortiofos*
Celathion
crotoxifos
Ciodrin
Cypona
crufomato
Ruelene
cumafos
Asuntol
Co-Ral
DEF
De-Green
E-Z-Off D
demetoir
Systox
dial if or
Torak
diazinon
diclofention
VC-13 Nemacide
didorvos
DDVP
Vapona
dicrotofos+
Bidrin
dimefox*
Hanane
PRODUCTOS
Pestox XIV
dimetoato
Cygon
DeFend
dioxation*
Delnav
disulfoton*
Disyston
ditalimfos
edifenfos
endotion*
EPBP
S-Seven
EPN+
etilopa ration*
E605
Parathion
Thiophos
etion
Ethanox
etoprop
Mocap
etrimfos
Ekamet
famfur
Bash
Bo-Ana
Famfos
fenamifos*
Nemacur
fencapton
G 28029
fenitrotion
Accothion
Agrothion
Sumithion
fenofosfon*
Agritox
tricloronato
fensulfotion*
Dasanit
fention
Baytex
Entex
Tiguvon
fentoato
dimefentoato
Fentoato
fonofos*
Dyfonate
N-2790
forato+
Rampart
Thimet
formotion
Anthio
fosalona
Azofene
Zolone
fosfamidon*
Dimecron
fosfato de cloroetoxi
COMERCIALES
Fortress
fosfolan*
Cylan
Cyolane
fosmet
Imidan
Prolate
fostebupirina
Aztec
fostietan*
Nem-A-Tak
foxim
Baythion
heptenofos
Hostaquick
hiometon
Ekatin
hosalona
Zolone
IBP
Kitazin
iodofenfos
Nuvanol-N
isazofosfatos
Brace
Miral
Triumph
isofenfos*
Amaze
Oftanol
isoxation
E-48
Karphos
leptofos
Phosvel
malation
Cythion
mefosfolan*
Cytrolane
merfos
Easy off-D
Folex
metamidofos*
Monitor
metidation*
Supracide
Ultracide
metilo-azinfos*
Gusathion
Guthion
metilo-demeton-S
Duratox
Metasystox
metilo-oxidemeton
Metasystox-R
metilo-pa ration*
E601
Penncap-M
metiltrition
mevinfos*
Duraphos
Phosdrin
mipafox*
Isopestox
Pestox XV
monocrotofos*
Azodrin
naled
Dibrom
oxideprofos
Metasystox-S
pirazofos
Afugan
Curamil
piridafention
Ofunack
pirimifos etilo
Primicid
pirimifos metilo
Actellic
pirofosfato de
tetraetilo*
TEPP
profenofos
Curacron
propetanfos
Safrotin
propiltiopirofosfato*
Aspon
protoato
Fac
quinalfos
Bayrusil
ronnel
Fenchlorphos
Korlan
scradan*
OMPA
sulfotep*
Bladafum
Dithione
Thiotepp
sulprofos
Bolstar
Helothion
temefos
Abate
Abathion
terbufos
Contraven
Counter
tetraclorovinfos
Gardona
Rabon
triazofos
Hostathion
triclorfon
Dipterex
Dylox
Neguvon
Proxol
+ Indica alta toxiddad. Los
organofosfatos de alta toxiddad
tienen valores (rata) de DL50 oral
menores que o iguales a 50 mg/
kg por peso corporeo. La mayoria
de los demas organofosfatos
inclufdos en esta tabla son
considerados moderadamente
toxicos, con valores de DL50 mayor
exceso de 50 mg/kg y menor de
500 mg/kg.
ORGANOFOSFATADOS 41
-------
tambien puede debilitar o paralizar la celula, despolarizando la placa terminal.
Altas concentraciones de acetilcolina en el sistema nervioso central causan alte-
raciones sensoriales y de comportamiento, incoordinacion, depresion de la fun-
don motora y depresion respiratoria. Un aumento en las secreciones pulmonares
y la depresion respiratoria son las causas usuales de muerte en el envenena-
miento por organofosfatos. La recuperacion depende, en ultima instancia, de la
generacion de nuevas enzimas en todos los tejidos criticos.
Los organofosfatos se absorben con facilidad por inhalacion, ingestion y
penetracion dermica. Existe una variacion considerable en la absorcion relativa
a traves de estas vias diferentes. Por ejemplo, la DL50 oral de la parationa en ratas
es de entre 3-8 mg/kg, lo cual es bastante toxico,1'2 y esencialmente equivale a
la absorcion dermica de una DL50 de 8 mg/kg.2 Por otra parte, la toxicidad de
la fosalona es mucho mas baja por la ruta dermal que por la oral, con una DL50
en ratas de 1500 mg/kg y 120 mg/kg, respectivamente.2 En general, es mas
probable que los altos agentes toxicos tengan una alta toxicidad dermica que los
agentes de toxicidad moderada.
Clases de Quimicos: Hasta cierto punto,la aparicion del envenenamien-
to depende de la proporcion en que se absorbe el pesticida. La degradacion del
pesticida ocurre principalmente por hidrolisis hepatica; el grado de hidrolisis
varia de un compuesto a otro. En el caso de ciertos organofosfatos cuya degra-
dacion es relativamente lenta, puede ocurrir un almacenamiento temporal sig-
nificative en el tejido graso. Algunos organofosfatados tales como el diazinon y
la metilparationa poseen una solubilidad lipida significativa, lo cual permite el
almacenamiento de grasa con una toxidad retrasada debido a la liberacion tar-
dia.3 La toxicidad retrasada puede ocurrir atipicamente con otros organofosfatos,
especificamente con la dicolorofentiona y con la demetona metilo.4 Muchos
organofosfatos se convierten con facilidad de tiones (P=S) a oxones (P=O). La
conversion ocurre en el ambiente bajo la influencia de oxigeno y luz, y en el
cuerpo, principalmente por la accion de los microsomas hepaticos. Los oxones
son mucho mas toxicos que los tiones, pero se inactivan con mas facilidad que
estos. Por ultimo, tanto los tiones como los oxones se hidrolizan en la union
ester para producir fosfatos de alquilo y grupos salientes, los cuales son de rela-
tiva baja toxicidad. Estos se excretan o sufren una transformacion posterior
antes de que el cuerpo los elimine.
La distincion entre las diferentes clases quimicas se torna importante cuan-
do el medico interpreta los examenes provenientes de laboratories de referen-
da. Esto podria ser especialmente importante cuando el laboratorio hace un
analisis del compuesto madre (e.j. cloropirifos en su forma tiofosfato) en vez de
en su forma metabolito (el clorpirifos sera completamente metabolisado a oxon
despues de la primera fase por el higado).
En los primeros dos dias a partir del enlace inicial del organofosfato con la
acetilcolinesterasa, parte de la enzima acetilcolinesterasa fosforilada puede ser
defosforilada (reactivada) por la oxima con propiedades de antidote llamada
PB ORGANOFOSFATADOS
-------
pralidoxima. Conforme pasa el tiempo, la union enzima-fosforilo se ve reforza-
da por la perdida de un grupo alquilo del aducto fosforilo, un proceso llamado
envejecimiento. Por lo tanto, la reactivacion de la pralidoxima es imposible
despues de unos cuantos dias,5 aunque en algunos casos, se ha visto cierta me-
joria en la administracion de la pralidoxima dias despues de la exposicion.6
Neuropatia Retardada Inducida Por Organofosfatados: Ocasionalmente,
ciertos organofosfatados han causado una forma diferente de neurotoxicidad
que consiste en el dano a los axones de los nervios perifericos y centrales,y que
se asocia con la inhibicion de la"enterasa neurotoxica" (ENT). Este sindrome
retardado ha sido llamado neuropatia retardada inducida por organofosfatos y
las manifestaciones han sido, principalmente, debilidad o paralisis y parestesia de
las extremidades.7 La neuropatia retardada inducida por organofosfatos afecta
predominantemente las piernas y puede persistir durante semanas o anos. Estos
casos raros han sido vistos poco despues de una exposicion aguda y en ocasiones
masiva, pero en algunos casos, los sintomas han persistido meses y hasta aiios.
Solamente unos cuantos de los muchos organofosfatos usados como pesticidas
han sido implicados como causas para la neuropatia retardada en los humanos.
Las normas de la Agencia para la Proteccion del Medio Ambiente requieren
que los compuestos organofosfatados y carbamicos que se evaluan para usarse
como pesticidas, scan probados en especies de animales susceptibles a esta
propiedad neurotoxica.
Tres estudios epidemiologicos con un grupo expuesto y un grupo de control
tambien sugieren que una proporcion de pacientes agudamente envenenados
con organofosfatos pueden experimentar una secuela neurosiquiatrica a largo
plazo. Los hallazgos demuestran una funcion significativamente peor en una bateria
de examenes de comportamiento neurologico, incluyendo memoria,
concentracion y disposicion,y en algunos casos neuropatia periferal de compuesto
especifico. Estos hallazgos son sutiles y en ocasiones solo pueden ser detectados
en examenes neurosicologicos en lugar de examenes neurologicos.8'9'10 El
seguimiento de casos ha encontrado ocasionalmente personas que informan
persistentes dolores de cabeza, vision nublada, debilidad muscular, depresion,
problemas de memoria y concentracion, irritabilidad,y/o desarrollo de intolerancia
a olores quimicos selectos.1"5
Sindrome Intermedio: En adicion a los episodios de envenenamiento
agudo y de neuropatia retardada inducida por organofosfatos, se ha descrito
un sindrome intermedio. Este sindrome ocurre despues de la resolucion de la
crisis colinergica aguda, generalmente entre 24-96 horas despues de la expo-
sicion. La misma esta caracterizada por la paresis respiratoria aguda y la debi-
lidad muscular, principalmente facial, del cuello y de los musculos proximales
de las extremidades. En adicion, a menudo se ve acompanada por paralisis de
los nervios craniales y depresion de los reflejos del tendon. Al igual que la
neuropatia retardada inducida por organofosfatos, este sindrome carece de
ORGANOFOSFATADOS 43
-------
sintomatologia muscarinica, y parece ser el resultado de una disfuncion pre y
pos-sinaptica combinada de transmision neuromuscular. Los sintomas no res-
ponden bien a la atropina y oximas; por lo tanto, el tratamiento es principal-
mente sustentador.16'17 Los compuestos mas comunes envueltos en este sin-
drome, lo son la metilparationa, fentiona y dimetoato, aunque tambien se
observe un caso con etil parationa.17
Otras propiedades especificas de los organofosfatos individuates podrian
hacerlos mas peligrosos de lo que la informacion toxica basica sugiere. Produc-
tos secundarios pueden desarrollarse en el malation almacenado por largo tiempo,
los cuales inhiben grandemente las enzimas hepaticas activas en la degradacion
del malation, intensificando su toxicidad. Ciertos organofosfatos son excepcio-
nalmente propensos a depositarse en tejido graso, prolongando la necesidad de
administrar antidotes durante varies dias mientras el pesticida se libera de nue-
vo al torrente circulatorio. Estudios llevados a cabo en animates han demostra-
do la potentacion del efecto cuando dos o mas organofosfatos se absorben a la
vez; las enzimas esenciales para la degradacion de uno son inhibidas por el otro.
Estudios llevados a cabo en animales, tambien han demostrado un efecto pro-
tector del fenobarbital, el cual induce la degradacion hepatica del pesticida.1 La
degradacion de algunos compuestos a fosfato de trimelito puede causar enfer-
medad pulmonar restrictiva.18
Sehales y Sintomas de Envenenamiento
Los sintomas del envenenamiento agudo por organofosfatados aparecen
durante la exposicion a ellos, en pocos minutos u horas, dependiendo del me-
todo de contacto. La exposicion por inhalacion resulta en la aparicion mas
rapida de sintomas toxicos, seguida por la ruta gastrointestinal y fmalmente por
la ruta dermica. Todos los sintomas y seiiales son colinergicos en naturaleza y
afectan los receptores muscarinicos, nicotinicos y del sistema nervioso central.5
Los sintomas criticos en el tratamiento son los sintomas respiratorios. Suficien-
tes fasciculaciones musculares y debilidad son a menudo observadas como para
requerir apoyo respiratorio; el paro respiratorio puede ocurrir repentinamente.
De igual manera, la broncorrea y broncoespasmos pueden a menudo impedir
esfuerzos para la oxigenacion adecuada del paciente.
Los broncoespasmos y broncorrea pueden ocurrir, produciendo opresion
en el pecho, sibilancias, tos productiva y edema pulmonar. La inconsciencia,
incontinencia, convulsiones y depresion respiratoria son caracteristicas de un
envenenamiento grave que pone en peligro la vida. La causa principal de muer-
te lo es el fallo respiratorio, y a menudo tambien existe un segundo componen-
te cardiovascular. El sintoma cardiovascular clasico lo es la bradicardia, la cual
puede conducir a un arresto sinosoidal. Sin embargo, esta puede ser substituida
por taquicardia e hipertension por estimulacion nicotinica (ganglio simpati-
PB ORGANOFOSFATADOS
-------
co).19La miocardiopatia toxica ha sido una caracteristica sobresaliente de algu-
nos envenenamientos graves por organofosfatos.
Algunos de los sintornas iniciales mis comunmente informados incluyen
dolor de cabeza, nausea, mareos e hipersecrecion, la cual se manifiesta a traves de
la transpiracion, salivacion, lagrimeo y rinorrea. Espasmos musculares, debilidad,
temblor, incoordinacion, vomito, calambres abdominales y diarrea son sintomas
que senalan el empeoramiento del estado de envenenamiento. La miosis es a
menudo un signo util para el diagnostico y el paciente puede informar vision
borrosa y/o perdida de vision. La ansiedad y desasosiego son prominentes, como
lo son tambien unos cuantos informes de movimientos coreatiformes. Se han
informado sintomas siquiatricos incluyendo la depresion, perdida de memoria y
confusion. La psicosis toxica, manifestada como confusion o comportamiento
extrano, ha sido diagnosticada erroneamente como intoxicacion de alcohol.
Los ninos a menudo presentaran un cuadro clinico un poco diferente al de
los adultos. Algunas senales colinergicas tipicas de bradicardia, fasciculaciones
musculares, lagrimeo y transpiracion son menos comunes. Convulsiones (22%-
25%), y cambios mentales, incluyendo el letargo y la coma (54%-96%) fueron
comunes.20'21 En comparacion, solo 2-3% de los adultos presentaron convulsio-
nes. Otras senales comunes en los niiios incluyen debilidad debido a flacidez
muscular, miosis y salivacion excesiva. En un estudio, 80% de los casos fueron
transferidos con un diagnostico preliminar erroneo.20 En un segundo estudio,
88% de los padres negaron inicialmente cualquier historial de exposicion.21
Vease la seccion de Toxicologia precedente para informacion acerca de las
peculiaridades del sindrome intermedio y de la neuropatia retardada inducida
por organofosfatos.
Confirmacion de Envenenamiento
Si se presentan indicaciones de envenenamiento, trate al paciente inme-
diatamente. No espere a la confirmacion del laboratorio.
Deberan tomarse muestras sanguineas para medir la actividad colinesterasica
plasmatica y los niveles de ACE en los globules rojos. La depresion de la pseudo
colinesterasa plasmatica y/o actividad eritrocitaria, generalmente son indicadores
bioquimicos disponibles de absorcion excesiva de organofosfatos. Algunos
organofosfatos pueden inhibir, de forma selectiva, la colinesterasa plasmatica o
la eritrocitaria.22 Una cantidad minima de organofosfatos debe ser absorbida
para deprimir la actividad colinesterasica de la sangre,pero la actividad enzimatica,
especialmente la colinesterasica plasmatica puede ser disminuida a traves de
dosificaciones considerablemente menores que las requeridas para causar un
envenenamiento sintomatico. Generalmente, la depresion enzimatica se torna
aparente despues de unos cuantos minutos u horas de una absorcion significa-
tiva de organofosfatos. La depresion de la enzima plasmatica persiste general-
mente durante varies dias a pocas semanas. La actividad de la enzima eritrocitaria
ORGANOFOSFATADOS 45
-------
LIMITES BAJOS APROXIMADOS DE ACTIVIDAD
COLINESTERASICA NORMAL DEL PLASMA Y LOS
ERITROCITOS DE LA SANGRE HUMANA*
Metodo Plasma
pH (Michel) 0.45
pH Stat(Nabb-Whitfield) 2.3
BMC Reagent Set
(Ellman-Boehringer) 1,875
DupontACA <8
Garry-Routh (Micro)
RBC
0.55
8.0
Eritrocitos
3,000
Male 7.8
Female 5.!
Technicon
2.0
8.0
Sangre Unidades
ApH per ml per hr
|iM per ml per min
mil per ml per min
Units per ml
HM-SH per 3mL per min
|iM per ml per min
* Por lo general, los mismos laboratories son los que propordonan la estimation mas segura
de losvalores minimos normales, en virtud de que la tecnica de medicion varia de un
laboratorio a otro.
puede no alcanzar su minimo durante varies dias, y generalmente permanece
deprimida durante mas tiempo, en ocasiones de uno a tres rneses, hasta que la
enzima nueva reemplaza aquella inactivada por el organofosfato. La tabla que
aparece arriba enumera los limites bajos aproximados de actividad colinesterasica
normal del plasma y los eritrocitos de la sangre humana, medidos en diferentes
metodos. Los niveles mas bajos generalmente indican una absorcion
excesiva de un quimico inhibidor de la colinesterasa.
En ciertas condiciones, las actividades colinesterasicas del plasma y de los
eritrocitos se reducen aunque no existe inhibicion quimica. Alrededor del 3%
de los individuos tiene un nivel de pseudocolinesterasa plasmatica bajo, el cual
esta determinado geneticamente. Estas personas son particularmente vulnera-
bles a la accion del medicamento succinilcolina que paraliza los musculos, (que
con frecuencia se administra a pacientes quirurgicos), pero no a los
organofosfatados. Pacientes con hepatitis, cirrosis, desnutricion, alcoholismo
cronico y dermatomiositis muestran actividades bajas de colinesterasa plasmatica.
Varies toxicos, en especial, cocaina, disulfuro de carbono, sales de benzalconio,
compuestos de mercuric organico, ciguatoxinas y solaninas, pueden reducir la
actividad de la pseudocolinestersa plasmatica. El embarazo temprano, los
anticonceptivos y la metoclopramida tambien pueden causar alguna depresion.
La acetilcolinesterasa eritrocitaria es menos afectada por factores diferentes a los
organofosfatos que la enzima plasmatica; sin embargo, se encuentra reducida en
algunas condiciones poco comunes que danan la membrana celular de los
eritrocitos, como la anemia hemolitica.
PB
ORGANOFOSFATADOS
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Los organofosfatos que se hidrolizan en el organismo para dar fosfatos de
alquilo y fenoles, con frecuencia pueden detectarse en la orina durante la ab-
sorcion del pesticida y hasta 48 horas despues. En ocasiones, estos analisis resul-
tan utiles para identificar con certeza el pesticida al cual han estado expuestos
los trabajadores. Los analisis de fosfatos de alquilo y fenoles en la orina pueden
demostrar la absorcion de organofosfatos en dosificaciones menores a las re-
queridas para disminuir las actividades de la colinesterasa y mucho mis bajas
que las necesarias para causar senales y sintomas. Su presencia podria sirnple-
niente ser el resultado de organofosfatos en la cadena alimenticia.
La deteccion de organofosfatos intactos en la sangre es generalmente im-
posible, excepto durante o poco despues de la absorcion de una cantidad subs-
tancial. En general, los organofosfatos no permanecen en la sangre sin hidrolizarse
por mas de unos cuantos minutos u horas, a rnenos que la cantidad absorbida
sea grande o que las enzimas hepaticas hidrolizantes esten inhibidas.
Tratamiento
Advertenda: Las personas que atienden a la victima deben evitar el contacto directo con
ropas altamente contaminadas, asi como con el vomito. Deben usarguantes degomapara
el lavado del pesticida de la piel y del cabello. Los guantes de vinilo no ofrecen proteccion
alguna.
1. Proteccion de las vias aereas. Asegurese de que las vias aereas esten
despejadas. Intube al paciente y aspire las secreciones con un tubo de succion
de diametro grande, de ser necesario. Si la respiracion se deprime, administrele
oxigeno a traves de la ventilacion pulmonar mecanicamente. Mejore la oxi-
genacion del tejido lo mas posible antes de administrar la atropina,
para minimizar asi el riesgo de fibrilacion ventricular. En casos de
envenenamiento grave, podria ser necesario apoyar la ventilacion pulmonar
mecanicamente durante varies dias.
2. Sulfato de atropina. Administre el sulfato de atropina por via intravenosa,
o por inyeccion intramuscular si no es posible la primera via. Recuerde que la
atropina puede ser administrada a traves de un tubo endotraqueal, si el acceso
intravenoso inicial es dificil de obtener. Dependiendo de la severidad del enve-
nenamiento, podrian requerirse dosis variables de atropina que van de bajas a
muy elevadas, de hasta de 300 mg por dia,23 o hasta una infusion continua.24'25
(Vease la dosificacion en la pagina siguiente.)
El objetivo de la terapia con atropina antidotal es antagonizar los efectos de
la concentracion excesiva de acetilcolina en los organos bianco que tienen
receptores muscarinicos. La atropina no reactiva la enzima colinesterasa ni ace-
lera la eliminacion de los organofosfatos. Si las concentraciones tisulares del
organofosfato se mantienen elevadas, cuando el efecto de la atropina desapare-
ORGANOFOSFATADOS 47
-------
Dosificacion de Atropina:
En casos de envenenamiento moderadamente seven (hipersecrecion y otras
manifestaciones de organos bianco sin depresion del sistenia nervioso
central), se han utilizado las siguientes dosis:
Adultos y ninos mayores de 12 anos: 2,0-4,0 nig repetidos cada 15
minutos hasta que las secreciones pulmonares scan controladas, las
cuales podrian ir acompanadas de otras senales de atropinizacion,
incluyendo, piel hiperemica, boca seca, pupilas dilatadas y
taquicardia (pulso de 140 por minuto). Advertencia: En casos de
ingestion de liquidos concentrados de pesticidas organofosfatados,
la aspiracion de hidrocarburo podria complicar los envenenamien-
tos. El edema pulmonar y oxigenacion pobre en estos casos no
responderan a la atropina y deberan tratadrse corno un caso de
sindrome de depresion respiratoria aguda.
Ninos menores de 12 afios: 0,05-0,1 nig/kg de peso corporeo, repeti-
dos cada 15 minutos hasta que se logre la atropinizacion. La dosis
maxima para ninos es de 0,1 mg. Mantenga la atropinizacion me-
diante dosis repetidas en base a los sintomas recurrentes durante un
periodo de 2-12 horas o mayor, dependiendo de la severidad del
envenenamiento.
Mantenga la atropinizacion con dosis recurrentes como es indicado
por el estado clinico. Estertores en la base de los pulmones casi siempre
indican atropinizacion inadecuada. La mejoria pulmonar puede no ser
paralela a otras senales de atropinizacion. La continuacion o retorno de
senales colinergicas indican la necesidad de mas atropina. La dosis po-
dra ser disminuida cuando los sintomas se mantengan estables durante
por lo menos seis horas.
Envenenamiento severo. Las personas que sufren de envenenamiento
severe podrian exhibir una tolerancia marcada a la atropina, por lo que
podria ser necesario administrar de dos a tres veces mas la dosificacion
sugerida. La dosis de atropina podria ser incrementada y el intervalo
disminuido de la forma necesaria para controlar los sintomas. Podria
requerirse una infusion intravenosa continua de atropina cuando se
requieran cantidades masivas de la misma. El punto final deseado lo
es la reversion de las senales y sintomas muscarinicos y senales
de mejoria en el estado pulmonar y oxigenacion, sin un limite
arbitrario de dosis. Siempre que sea posible, deben usarse productos de
atropina libres de preservatives.
PB
ORGANOFOSFATADOS
-------
Nota: Personas no envenenadas o envenenadas ligeramente por
organofosfatos podrian desarrollar senates de toxicidad por atropina a
causa de estas dosis tan alt as. La fiebre, fibrilacion muscular y delirio
son las senales mas importantes de intoxicacion por atropina. Si estas
aparecen mientras el paciente esta totalmente atropinizado, es necesa-
rio descontinuar la administracion de atropina, al menos temporal-
mente, hasta reevaluar la severidad del envenenamiento.
ce, puede surgir un recrudecimiento del envenenamiento. La atropina es eficaz
para controlar las manifestaciones muscarinicas, pero no lo es para las nicotinicas,
en especial, la debilidad y el temblor muscular y la depresion respiratoria.
A pesar de estas limitaciones, la atropina es un agente que, con frecuencia,
salva la vida en los envenenamientos por organofosfatos. La respuesta favorable
a una dosis de prueba de atropina (1 mg en adultos, 0,01 mg/kg en ninos
menores de 12 anos) puede ayudar a diferenciar el envenenamiento por agentes
anticolinesterasicos de otras condiciones. Sin embargo, la fait a respuesta, sin
evidencia alguna de atropinacion (resistencia a la estimulacion por atropina), es
tipica de los envenenamientos mas graves. Se ha informado que el uso subordi-
nado de atropina en atomizador ha mejorado la insuficiencia respiratoria, ha
disminuido las secreciones de los bronquios y aumentado la oxigenacion.26
3. El Glicopirolato ha sido estudiado como una alternativa para la atropina; se
ha encontrado un resultado similar en la utilizacion de infusion continua. Am-
pollas de glicopirolato de 7.5 mg fueron anadidas a 200 ml de solucion salina y
esta infusion fue titulada a los efectos deseados de las membranas mucosas secas
y a un ritmo promedio del corazon de 60 palpitaciones/minuto. Durante este
estudio, la atropina fue usada como un bolo para un ritmo promedio del cora-
zon de menos de 60 palpitaciones/minuto. La otra ventaja aparente de este
regimen fue una cantidad menor de infecciones respiratorias. Esto podria re-
presentar una alternativa cuando existe la preocupacion de infecciones respira-
torias debido a secreciones excesivas y dificiles de controlar, y ante la presencia
de un nivel alterado de conciencia, donde la distincion entre la toxicidad por
atropina o una recaida al envenenamiento por organofosfatados sea incierta.27
4. Pralidoxima. Antes de administrar la pralidoxima, tome una muestra de
sangre (hiparinizada) para hacer el analisis de colinesterasa (debido a que la
pralidoxima tiende a revertir la depresion de la colinesterasa). Administre la
pralidoxima (Protopam, 2-PAM),un reactivador de la colinesterasa, en casos de
envenenamiento grave por pesticidas organofosfatados en los que la depresion
respiratoria, la debilidad y los espasmos musculares scan severos. (Vease la tabla
de dosificacion en la pagina 50. Cuando se administra al inicio (en general antes
de 48 horas despues del envenenamiento), la pralidoxima disminuye tanto los
ORGANOFOSFATADOS 49
-------
efectos nicotinicos del envenenamiento, corno los muscarinicos. La pralidoxima
funciona al reactivar la colinestersa y tambien al disminuir el proceso de "enve-
jecimiento" de la fosforilacion de la colinesterasa para convertirse en una forma
no reactivable.
Nota: La pralidoxima tiene valor limitado en las intoxicaciones de com-
puestos con carbamatos inhibidores de la colinesterasa, e inclusive puede ser
peligrosa (vease el Capitulo 5).
Dosis de Pralidoxima:
Adultos y ninos mayores de 12 afios: 1,0-2,0 g por via intravenosa en
dosis no mayores de 0,2 g por minuto. La administracion lenta de
pralidoxima es muy recomendable, suministrando la dosis total en
solucion salina normal de 100 ml en 30 minutos o mas.
Nines menores de 12 anos: 20-50 mg/kg de peso corporal (segun la
gravedad del envenenamiento) por via intravenosa, suministrando
la dosis en solucion salina normal de 100 ml en 30 minutos.
La dosificacion de pralidoxima puede ser repetida despues de 1 a 2 horas y
luego, a intervales de 10 a 12 horas, de ser necesario. En casos de envenena-
mientos muy graves, esta dosificacion puede duplicarse. Es comun que se re-
quieran dosis repetidas de pralidoxima.Tal vez sea necesario continuar adminis-
trando pralidoxima por varies dias, despues de las 48 horas de intervalo post-
exposicion, que se mencionan comunmente como limite de su eficacia, en
casos en los que hay una absorcion continua de organofosfatos (e.j. despues de
la ingestion de una gran cantidad) o una transferencia continua de organofosfatos
altamente lipofilicos de la grasa a la sangre. Basado en estudios con animates y
en reportes de pacientes adultos, la pralidoxima tambien puede ser administrada
como infusion continua de aproximadamente 500 mg/hora.28'29
La presion sanguinea debera medirse durante la administracion debido a la
posibilidad de que ocurra una crisis hipertensiva. La administracion debe ha-
cerse mas lenta, o interrumpirse, si la presion sanguinea sube hasta un nivel
peligroso. Se debe estar preparado para apoyar mecanicamente la ventilacion
pulmonar, si se deprime la respiracion durante la administracion de la pralidoxima
o despues de la misma. Si la administracion de la pralidoxima por inyeccion
intravenosa no es posible, se debe inyectar por via intramuscular profunda.
5. Descontaminacion dermica. En pacientes envenenados con organofosfatos
por contaminacion dermica, de ropa, cabello y/u ojos, la descontaminacion
debera proceder simultaneamente con cualquier medida de resucitacion o con
la administracion del antidote necesario para preservar la vida. Elimine la con-
taminacion ocular enjuagando con cantidades abundantes de agua limpia. Si no
PB ORGANOFOSFATADOS
-------
hay sintomas evidentes en un paciente que se mantiene alerta y fisicamente
capaz, puede ser apropiado realizar una ducha rapida y un lavado de cabeza con
champu, al mismo tiempo que se mantiene la observacion cuidadosa del pa-
ciente para asegurarse de reconocer sintomas de envenenamiento que aparez-
can de forma abrupta. Si se presenta cualquier indicio de debilidad, ataxia u
otros deterioros neurologicos, desvista al paciente dele un bano completo y
lavele la cabeza, usando cantidades abundantes de agua y champu, mientras la
victima esta recostada. Los asistentes deben usar guantes de goma, ya que los de
vinilo no proveen proteccion alguna contra la absorcion dermica. El jabon
quirurgico verde es excelente para este proposito, pero tambien puede utilizar-
se jabon comun. Lave los residues del pesticida que puedan haber quedado en
los pliegues de la piel o debajo de las unas.
La ropa contaminada debe ser prontamente removida, empacada y lavada
antes de ser devuelta. Los zapatos de cuero contaminados deberan ser descarta-
dos. Recuerde que el pesticida puede contaminar la parte interior de guantes,
botas y sombreros.
6. Descontaminacion gastrointestinal. Si se ha ingerido el organofosfato
en cantidad suficiente como para causar envenenamiento, debera considerarse
la descontaminacion gastrointestinal, como fuera delineada en el Capitulo 2,
bajo Principios Generales. Si el paciente ya ha vomitado, lo cual es lo mas
probable en exposiciones serias, es contraindicado efectuar mayores esfuerzos
para la descontaminacion gastrointestinal. En ingestiones significativas, la dia-
rrea y/o vomito son tan constantes, que la absorcion de carbon y la catarsis son
contraindicadas.
7. Observacion. Observe al paciente cuidadosamente durante por lo menos
72 horas para asegurarse de que los sintomas (transpiracion, alteraciones visua-
les, vomito, diarrea, molestias en el pecho y abdomen, y a veces edema pulmonar)
no reaparezcan cuando se retire la atropinizacion. En casos de envenenamiento
muy severos por ingestion de organofosfatos, en particular los compuestos mas
lipofilicos de hidrolisis lenta, la eliminacion metabolica del toxico puede re-
querir de 5-14 dias. En algunos casos, puede combinarse la eliminacion lenta
con una inhibicion intensa de la colinesterasa, que requiera la atropinizacion
por varies dias e incluso semanas. Al reducir la dosificacion, la base de los pul-
mones debe revisarse con frecuencia para buscar estertores. Si se escuchan
estertores o reaparecen la miosis, bradicardia, transpiracion y otras senales
colinergicas, la atropinizacion debera restablecerse de inmediato.
8. La furosemida puede considerarse para aliviar el edema pulmonar, aun
despues de la completa atropinizacion. No debera utilizar este producto antes
de obtener el beneficio maximo de la atropina. Consulte las indicaciones del
paquete para la dosificacion y administracion.
ORGANOFOSFATADOS 51
-------
9.Ventilacion pulmonar. En envenenamientos por ingestion de grandes do-
sis de organofosfatos, en particular, monitoree cuidadosamente la ventilacion
pulmonar, aun despues de la recuperacion de los sintomas muscarinicos, para
evitar un paro respiratorio. En algunos casos, varies dias despues de la ingestion
del organofosfato, ha surgido una falla respiratoria que ha persistido por dias y
hasta semanas.
10. La Aspiracion de hidrocarburo puede complicar los envenenamientos
que envuelvan la ingestion de liquidos concentrados de pesticidas
organofosfatados. En estos casos, el edema pulmonar y oxigenacion pobre no
respondera a la atropina y debera ser tratada como un caso de depresion respi-
ratoria grave.
11. Monitoree la condicion cardiopulmonar. En pacientes con envenena-
miento grave, monitoree la condicion cardiaca a traves del registro continuo
del electrocardiograma. Algunos organofosfatos tienen una toxicidad cardiaca
significativa.
12. Control de convulsiones. En raras ocasiones se presentan convulsiones
en envenenamientos graves por organofosfatos, que no respondan a la terapia
con atropina y pralidoxima. Se debe investigar si hay causas no relacionadas con
la toxicidad del pesticida que scan responsables de este hecho: trauma craneal,
anoxia cerebral o envenenamiento mixto. Los medicamentos que son utiles
para controlar las convulsiones se presentan en el Capitulo 2. Las benzodiazepinas
(diazepam o lorazepam) son los agentes de eleccion para la terapia inicial.
13. Contraindicaciones. Los medicamentos que se mencionan a continua-
cion probablemente estan contraindicados en casi todos los casos de envenena-
mientos por organofosfatos: morfina, succinilcolina, teofilina, fenotiazinas y
reserpina. Las aminas adrenergicas deben administrarse solo si existe indicacion
especifica, por ejemplo, una hipotension marcada.
14. Nueva exposicion. Las personas que hayan tenido manifestaciones clini-
cas de envenenamiento por pesticidas organofosfatados no deben exponerse de
nuevo a agentes quimicos inhibidores de la colinesterasa hasta que, tanto los
sintomas como las seiiales, hayan desaparecido de forma total y la actividad de la
colinesterasa en la sangre haya regresado, por lo menos, al 80% de los niveles
previos al envenenamiento. Si no se midio el nivel de la colinesterasa en la
sangre antes del envenenamiento, la actividad enzimatica sanguinea debera al-
canzar por lo menos los niveles minimos normales (vease la tabla en la pagina
46), antes de que el paciente regrese al ambiente contaminado con pesticidas.
15. No administre atropina o pralidoxima con fines profilacticos a
trabajadores expuestos a pesticidas organofosfatados. La administracion
PB ORGANOFOSFATADOS
-------
profilactica, ya sea de atropina o pralidoxima, puede enmascarar las primeras
senates y sintomas del envenenamiento por organofosfatados, y por lo tanto,
permitir que el trabajador continue expuesto y evolucione progresivamente a
un envenenamiento mas grave. La atropina por si misma puede aumentar los
peligros del medio laboral agricola para la salud: menoscabo en el control ter-
mico por la reduccion de la transpiracion y perdida de la habilidad para operar
equipo mecanico a causa de la vision borrosa. Esto podria ser causado por la
midriasis, uno de los efectos de la atropina.
Estructura Quimica General
La R es, por lo general, un grupo etilo o metilo. Los insectiddas con un enlace doble de
azufre son organotiofosfatos,pero se convierten en organofosfatos en el higado. Losfosfonatos
condemn ungmpo alquilo (R-) en lugar de ungmpo alkoxi (RO-). La "X" es llamada
"gmpo saliente y es el metabolite principal para una identification especifica.
/ S (u O)
>
RQX ^ O
Grupo Saliente
Referencias
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. ToxicolAppl Pharmacol 1976;37:85-92.
3. Garcia-Repetto R, Martinez D, and Repetto M. Coefficient of distribution of some organo-
phosphorus pesticides in rat tissue. Vet Hum Toxicol 1995;37:226-9.
4. Gallo MA and Lawryk NJ. Organic phosphorus pesticides. In: Haves WJ and Laws ER (eds),
Handbook of Pesticide Toxicology, vol 2, Classes of Pesticides. San Diego, CA: Academic
Press Inc., 1991.
5. Taylor P. Anticholinesterase agents. In: Gilman AG and Goodman LS (eds), The Pharmaco-
logical Basis of Therapeutics. New York: Macmillan Publishing Co. Inc.; 1985, pp.110-28.
6. De KortWL, Kiestra SH, and Sangster B.The use of atropine and oximes in organophos-
phate intoxications: A modified approach. Clin Toxicol 1988;26:199-208.
7. Jamal JA. Neurological syndromes of organophosphorus compounds. Adverse Drug React
Toxicol Rev 1997;16(3):133-70.
8. Steenland K, Jenkins B, Ames RG, et al. Chronic neurological sequelae to organophosphate
poisoning. Am J Public Health 1994;84:731-6.
9. Savage E, KeefeT, Mounce L, et al. Chronic neurological sequelae of acute organophosphate
pesticide poisoning. Arch Environ Health 1988;43:38-45.
ORGANOFOSFATADOS 53
-------
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 NYAcad Sci 1969;160:357-65.
13. Holmes JH and Gaon MD. Observations on acute and multiple exposure to anticholinest-
erase agents. Trans Am Clin Climatol Assoc 1957; 68:86-103.
14. Hirshberg A and LermanY. Clinical problems in organophosphate insecticide poisoning:The
use of a computerized information system. Fundam Appl Toxicol 1984; 4:5209-14.
15. Miller CS and Mitzel HC. Chemical sensitivity attributed to pesticide exposure versus re-
modeling. Arch Environ Health 1995; 50:119-29.
16. DeBleeker J, Willems J.Van Den Neucker K, et al. Prolonged toxicity with intermediate
syndrome after combined parathion and methyl parathion poisoning. Clin Toxicol
1992;30:333-45.
17. DeBleecker J, Van Den Neucker K, and Colardyn F. Intermediate syndrome in organo-
phosphorous poisoning: A prospective study. Crit Care Med 1993;21:1706-11.
18. Aldridge WN and Nemery B. Toxicology of trialkylphosphorothioates with particular
reference to lung toxicity. Fundam Appl Toxicol 1984; 4:5215-23.
19. Bardin PG, Van Eeden SF, Moolman JA, et al. Organophosphate and carbamate poisoning.
Arch Intern Med 1994;154:1433-41.
20. Zwiener RJ and Ginsburg CM. Organophosphate and carbamate poisoning in infants and
children. Pediatrics 1988;81:121-683.
21. Sofer S,Tal A, and Shahak E. Carbamate and organophosphate poisoning in early childhood.
Pediatr Emerg Care 1989;5(4):222-5.
22. Sullivan JB and Blose J. Organophosphate and carbamate insecticides. In: Sullivan JB and
Krieger GR (eds), Hazardous Materials Toxicology. Baltimore, MD: Williams and Wilkins,
1992, pp. 1015-26.
23. Goswamy R, Chaudhuri A, and Mahashur AA. Study of respiratory failure in organophos-
phate and carbamate poisoning. Heart Lung 1994;23:466-72.
24. LeBlanc FN, Benson BE, and Gilg AD. A severe organophosphate poisoning requiring the
use of an atropine drip. ClinToxicol 1986;24:69-76.
25. DuToit PW, Muller FO, Van Tender WM, et al. Experience with the intensive care manage-
ment of organophosphate insecticide poisoning. SAfr Med] 1981;60:227-9.
26. Shockley LW. The use of inhaled nebulized atropine for the treatment of malathion poison-
ing. ClinToxicol 1989;27:183-92.
27. Bardin PG and van Eeden SF. Organophosphate poisoning: Grading the severity and compar-
ing treatment between atropine and glycopyrrolate. Crit Care Med 1990;18:956-60.
28. Thompson DF, Thompson GD, Greenwood RB, et al. Therapeutic dosing of pralidoxime
chloride. Drug Intell Clin Pharm 1987;21:590-2.
29. Tush GM and Anstead MI. Pralidoxime continuous infusion in the treatment of organo-
phosphate poisoning. Ann Pharmacother 1997;31:441-4.
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CAPITULO 5
Insecticidas Carbamatos
de N-Metilo
Los insecticidas de carbamato de N-metilo son muy utilizados en el hogar, jardi-
nes y agricultura. Estos comparten con los organofosfatos, la capacidad de inhibir
las enzimas colinesterasicas y por lo tanto comparten una sintomatologia similar
durante las exposiciones agudas y cronicas. Igualmente, la exposicion puede ocu-
rrir por diferentes rutas en la misma persona debido a usos multiples, y es proba-
ble que haya toxicidad adicional con la exposicion simultanea a los organofosfatos.
Sin embargo, debido a la afinidad un tanto diferente a las colinesterasas, en com-
paracion con los organofosfatos, estos envenenamientos son un poco mas faciles
de tratar, como se discutira mas adelante en este capitulo.
Toxicologia
Los esteres de carbamato de N-metilo causan carbamilacion reversible de
la enzima acetilcolinesterasa, lo que permite la acumulacion de acetilcolina, la
substancia neuromediadora en las uniones nueroefectoras parasimpaticas (efec-
tos muscarinicos), en las uniones mioneurales del musculo esqueletico y en los
ganglios autonomos (efectos nicotinicos), asi como en el cerebro (efectos en el
SNC). La combinacion carbamilo-acetilcolinesterasa se disocia mas rapidamente
que el complejo fosforilo-acetilcolinesterasa producido por los compuestos
organofosfatados. Esta labilidad tiene varias consecuencias importantes: (1) tiende
a limitar la duracion del envenenamiento con insecticida carbamato N-metilo;
(2) es responsable de que el intervalo que existe entre la dosis que genera los
sintomas y la dosis letal sea mayor que el que existe en el caso de la mayoria de
los compuestos organofosfatados; y, (3) con frecuencia invalida la medicion de
la actividad de la colinesterasa en la sangre como indicador diagnostico del
envenenamiento (vea a continuacion).
Los carbamatos de N-metilo se absorben por inhalacion, ingestion y algu-
nos penetran por la piel, aunque esta ultima tiende a ser la ruta menos toxica.
Por ejemplo, el carbofuran tiene una DL50 por via oral de 5 mg/kg en ratas,
comparado con una DL50 dermal de 120 mg/kg, lo cual hace la ruta oral aproxi-
madamente 24 veces mas toxica cuando ingerido.1 Los carbamatos N-metilo
son hidrolizados enzimaticamente por el higado y los productos de degrada-
cion se excretan por los rinones y el higado.
PUNTOS
IMPORTANTES:
Causa reversible
carbamilacion de ACE
Efectos muscarinicos,
nicotinicos, SNC
Senales y Sintomas:
Malestar, debilidad
muscular, mareo,
transpiracion
Dolor de cabeza, salivadon,
nausea, vomito, dolor
abdominal, diarrea
Depresion del SNC, edema
pulmonar en casos series
Tratamiento:
Despejar via aerea, mejorar
oxigenacion tisular
Administradon intravenosa
de sulfato de atropina
Proceder inmediatamente
con procedimientos de
descontaminadon
CARBAMATOS DE N-METILO 55
-------
Productos Comerdales
aldicarb*
Temik
aminocarb*
Matacil
bendiocarb
Dycarb
Ficam
Multamat
Niomil
Tattoo
Turcam
bufencarb
Bux
metalkamate
carbarilo
Dicarbam
Sevin
carbofurano*
Crisfuran
Curaterr
Furadan
doetocarb*
Lance
dimetan
Dimethan
dioxacarb
Elecron
Famid
fenoxicarb
Torus
hidrocloruro de formetanato*
Carzol
isolan+
Primin
isoprocarb
Etrofolan
MIPC
metiocarb*
Draza
Mesurol
metomilo*
Lannate
Lanox
Nudrin
mexacarbato
Zectran
oxamilo*
DPX1410
Vydate L
pirimicarb
Abol
Aficida
Aphox
Fernos
Pirimor
Rapid
(Continue en la
proxima pagina)
En las uniones nerviosas colinergicas con musculo liso y celulas glandula-
res, la alta concentracion de acetilcolina causa contracciones musculares y se-
crecion respectivamente. En las uniones musculares esqueleticas, el exceso de
acetilcolina puede producir excitacion (espasmos musculares), pero tambien
puede debilitar o paralizar la celula al despolarizar la placa terminal. Las con-
centraciones elevadas de acetilcolina pueden causar alteraciones sensoriales y
conductuales, incoordinacion y depresion en la funcion motora en el cerebro
(aunque raras veces causan convulsiones), a pesar de que los insecticidas de
carbamato de N-metilo no penetran eficazmente al sistema nervioso central.
La depresion respiratoria, combinada con edema pulmonar, es la causa comun
de muerte en el envenenamiento con estos compuestos.
Sehales y Sintomas de Envenenamiento
Como ocurre con el envenenamiento con organofosfatos, los sintomas y
seiiales estan basados en la estimulacion colinergica excesiva. A diferencia del
envenenamiento por organofosfatos, los envenenamientos carbamaticos tienden
a ser mas corta de duracion debido a que la inhibicion del tejido nervioso ACE es
reversible, y los carbamatos son metabolizados mas rapidamente.2 La bradicardia y
convulsiones son menos comunes que en los envenenamientos por organofosfatos.
Sin embargo, los niveles de la colinesterasa en la sangre podrian ser enga-
nosos debido a la reactivacion in vitro de la enzima carbamilada.3'4 Un
nivel "normal" falso puede hacer mas dificil el diagnostico en la presentacion
aguda ante la ausencia de un historial de exposicion.
Los sintomas iniciales de toxicidad seria son la depresion del sistema ner-
vioso central, manifestado a traves de coma, convulsiones, hipotonia y efectos
nicotinicos, incluyendo la hipertension y la depresion cardiorespiratoria. La
disnea, broncoespasmos y broncorrea con una eventual edema pulmonar son
otras seiiales serias. Informacion reciente indica que los ninos y adultos difieren
en la presentacion clinica. Los ninos estan mas propensos que los adultos a
presentar los sintomas del sistema nervioso central arriba mencionados. Aun-
que los ninos pueden desarrollar las seiiales muscarinicas clasicas, la ausencia de
las mismas no excluye la posibilidad de envenenamiento carbamatico ante la
presencia de depresion del SNC.5
El malestar, debilidad muscular, mareo y transpiracion son sintomas inicia-
les de envenenamiento informados con frecuencia. El dolor de cabeza, saliva-
cion, nausea, vomito, dolor abdominal y diarrea son a menudo notorios. La
miosis con vision borrosa, incoordinacion, espasmos musculares y lenguaje len-
to tambien son informados.
PB CARBAMATOS DE N-METILO
-------
Confirmacion de Envenenamiento
Si existen indicaciones clinicas de envenenamiento agudo por
carbamato de N- metilo, y/o un historial de exposicion carbamica,
trate al paciente inmediatamente. No espere a la confirmacion del
laboratorio.
Debera obtenerse sangre para medir la pseudocolinesterasa plasmatica y
deberan obtenerse los eritrocitos ACE. Es importante recordar que a menos
que se haya absorbido una cantidad substancial del insecticida de carbamato de
N-metilo, y se tome una muestra sanguinea una 6 dos horas despues, es poco
probable que la actividad de la colinesterasa sanguinea se encuentre deprimida.
Incluso en estas condiciones, se debe utilizar una prueba rapida de la actividad
enzimatica para detectar un efecto, ya que la reactivacion enzimatica ocurre
tanto in vivo como in vitro. Consulte el cuadro en la pagina 46. Para los metodos
de medicion de la actividad de la colinesterasa sanguinea, si las circunstancias
parecen garantizar la realizacion de la prueba.
La absorcion de algunos insecticidas de carbamatos de N-metilo puede
confirmarse a traves del analisis de la orina para buscar metabolitos especificos:
alfa-naftol para el carbarilo, isopropoxifenol para el propoxur, carbofuran-fenol
para el carbofuran, aldicarb sulfona y aldicarb nitrilo para el aldicarb. Estos
analisis complejos, cuando estan disponibles, pueden ser utiles en la identifica-
cion del agente responsable y pueden ser utilizados para seguir el curso de la
excrecion de carbamatos.
Productos Comerdales
(Continuation)
promecarb
Carbamult
propoxur
aprocarb
Baygon
* thiodicarb
Larvin
trimetacarb
Broot
Landrin
+ Indica alta toxicidad. Los
carbamatos N-metilo
altamente toxicos tienen una
DL50 por via oral, en ratas,
menores que o iguales a 50
mg/kg de peso corporeo. La
mayoria de los demas
carbamatos incluidos en esta
tabla son considerados
moderadamente toxicos, con
un valor DL50 mayor de 50 mg/
kg y menor de 500 mg/kg.
Tratamiento
Advertencia: Las personas que atiendan a la victima deben evitar el con-
tacto directo con ropas altamente contaminadas, asi como con el vomito. Use
guantes de goma al lavar el pesticida de la piel y el cabello. Los guantes de vinilo
no proveen proteccion.
1. Proteccion de la via aerea. Asegurese de que la via aerea este despejada.
Intube al paciente y aspire las secreciones con un tubo de succion de diametro
grande de ser necesario. Administrele oxigeno mediante ventilacion pulmonar
mecanicamente, si la respiracion se deprime. Mejore la oxigenacion tisular al
maximo antes de administrarle atropina, para minimizar el riesgo de
fibrilacion ventricular. En casos de envenenamiento grave, tal vez sea necesa-
rio mantener la ventilacion pulmonar mecanicamente durante varies dias.
2. Atropina. Administre sulfato de atropina por via intravenosa o, si esto no es
posible, por via intramuscular. Recuerde que la atropina puede ser administrada
a traves de un tubo endotraqueal si el acceso intravenoso inicial es dificil de
obtener. Los carbamatos generalmente se revierten con dosificaciones mucho
CARBAMATOS DE N-METILO 57
-------
menores de atropina que las requeridas para revertir los organofosfatos.6 (Vease
la dosificacion en la proxima pagina.)
El objetivo de usar atropina como antidoto es antagonizar los efectos de las
concentraciones excesivas de acetilcolina en los organos bianco con receptores
muscarinicos. La atropina no reactiva la enzima colinesterasa, no acelera la excre-
cion, ni descompone el carbamato. Puede ocurrir un recrudecimiento del enve-
nenamiento si las concentraciones del toxico en el tejido permanecen elevadas
cuando desaparece el efecto de la atropina. La atropina es eficaz para controlar las
manifestaciones muscarinicas, pero es ineficaz en las acciones nicotinicas, en espe-
cial, debilidad y espasmos musculares y depresion respiratoria.
A pesar de estas limitaciones, la atropina con frecuencia es un agente que
puede salvar la vida en envenenamientos por insecticidas carbamato N-metilo.
Una respuesta favorable a una dosis de prueba de atropina (1 nig en adultos,
0,01 nig/kg en ninos menores de 12 anos) administrada por via intravenosa
puede ayudar a diferenciar el envenenamiento por agentes anticolinesterasicos
de otras condiciones tales como edema pulmonar cardiogenico e ingestion de
hidrocarburo. Sin embargo, la fait a de respuesta a la dosis de prueba, indicando
que no ha habido atropinizacion (resistencia a la atropina), es caracteristica del
envenenamiento moderadamente severe y severe, e indica la necesidad de mas
atropina. Si la dosis de prueba no resulta en midriasis y sequedad de las secreciones,
el paciente podria ser considerado como intratable con atropina.
3. Descontaminacion dermica. En pacientes con contaminacion dermica,
de la ropa, cabello y/u ojos, proceda a la descontaminacion simultanea-
mente con cualquier medida de resucitacion o administracion de
antidotes que sea necesaria para preservar la vida. Elimine la contami-
nacion ocular enjuagando con cantidades abundantes de agua limpia. En indi-
viduos asintomaticos, alertas y fisicamente capaces, puede ser util administrar
una ducha rapida y un lavado de cabeza con champu, mientras se mantiene la
vigilancia estrecha del paciente en caso de aparicion abrupta de sintomas de
envenenamiento. Si se presenta cualquier indicacion de debilidad, ataxia u otra
alteracion neurologica, desvista al paciente y recuestelo para darle un bafio
complete y lavarle la cabeza con abundante agua y champu. Los asistentes de-
beran usar guantes de goma ya que los de vinilo no proveen proteccion alguna
contra la absorcion dermica. Remueva el pesticida que pueda haber en los
pliegues de la piel y debajo de las unas.
La ropa contaminada debe serle quitada al paciente con prontitud, guarda-
da en una funda y lavada antes de ser devuelta. Los zapatos de cuero contami-
nados deberan ser descartados. Considere la probabilidad de que el pesticida
pueda haber contaminado la parte interior de guantes, botas o sombreros.
4. Descontaminacion gastrointestinal. Si el carbamato de N-metilo ha
sido ingerido en una cantidad suficiente como para causar envenenamiento,
debera considerarse la descontaminacion gastrointestinal como es delineada en
PB CARBAMATOS DE N-METILO
-------
Dosificacion de Atropina:
En envenenamientos modemdamente graves (hipersecrecion y otras mani-
festaciones de organos bianco, sin depresion del sistema nervioso central),
la dosificacion que se nienciona a continuacion ha probado su eficacia:
Adultos y nines mayores de 12 anos: 2,0-4,0 mg., repetida cada 15
minutos hasta que las secreciones pulmonares scan controladas, las
cuales podrian ir acompanadas de otras senales de atropinizacion,
incluyendo piel hiperemica,boca seca, pupilas dilatadas y taquicardia
(pulso de 140 por minuto). Precaucion: En casos de ingestion de
liquidos concentrados de carbamatos, la aspiracion de hidrocarbono
podria complicar los envenenamientos. El edema pulmonar y la
oxigenacion pobre en estos casos no responderan a la atropina y
deberan tratarse como un caso de sindrome de depresion respirato-
ria aguda.
Ninos menores de 12 anos: 0,05-0,1 mg/kg de peso corporeo, repetida
cada 15 minutos hasta que las secreciones pulmonares scan controla-
das, las cuales podrian ir acompanadas de otras senales de atropinizacion,
como se indicara arriba (el ritmo del corazon varia dependiendo de la
edad del nino. Los ninos pequenos tienen un ritmo de casi 200). La
dosis minima para ninos es de 0,1 mg.
Mantenga la atropinizacion mediante dosis repetidas durante 2 a 12
horas en base a los sintomas recurrentes, o durante mas tiempo depen-
diendo de la severidad del envenenamiento. Los estertores en las bases
pulmonares casi siempre indican una atropinizacion inadecuada. La me-
joria pulmonar podria no ser paralela a otras senales. La continuacion o
regreso de manifestaciones colinergicas indican la necesidad de mas
atropina.
Los individuos sevemmente envenenados podrian desarrollar una tole-
rancia marcada a la atropina, por lo que podria ser necesario adminis-
trar dos o mas veces la dosificacion sugerida. El objetivo de la terapia
con atropina es revertir las manifestaciones muscarinicas mas que ad-
ministrar una dosificacion especifica. No obstante, la administracion
prolongada e intensiva de atropina por via intravenosa, que algunas
veces se requiere en el envenenamiento por organofosfatos, rara vez es
necesaria para tratar el envenenamiento por carbamatos.
CARBAMATOS DE N-METILO 59
-------
Nota: Las personas no envenenadas o con un envenenamiento leve
por insecticidas carbamatos N-metilo podrian desarrollar senales de
toxicidad por atropina a causa de estas dosis altas. Las principles sena-
les de la intoxicacion con atropina son fiebre, fibrilacion muscular y
delirio. Si estas senales aparecen mientras el paciente esta completa-
mente atropinizado, es necesario descontinuar la administracion de
atropina, al menos temporalniente, hasta reevaluar la severidad del en-
venenamiento.
el Capitulo 2. Si el paciente ha ingerido el quimico recientemente y permane-
ce asintomatico, la absorcion del veneno con carbon activado podria ser bene-
ficiosa. En ingestiones significativas, la diarrea y/o vomito son tan constantes
que la absorcion de carbon y la catarsis son contraindicadas. Debera prestarse
atencion al oxigeno, tratamiento de las vias aereas y atropina.
5. Muestra de orina. Guarde una muestra de orina para el analisis de metabolitos
si existe la necesidad de identificar el agente responsable del envenenamiento.
6. La pralidoxima es probable que sea de poco valor en los envenenamientos
por insecticidas de carbamatos de N-metilo, debido a que solo la atropina es
efectiva.Aunque no ha sido indicado en envenenamientos aislados por carbamato,
la pralidoxima parece ser util en casos de envenenamientos mixtos en los que
participan carbamatos/organofosfatados, y en casos de pesticidas desconocidos
con sintomas de presentacion muscarinica.7>8Vease el Capitulo 4, seccion de
Tratamiento, pag 49.
7. Observacion. Observe al paciente cuidadosamente, por lo menos durante
24 horas, para asegurarse que no reaparezcan los sintomas (transpiracion, altera-
ciones visuales, vomito, diarrea, molestias en el pecho y el abdomen, y algunas
veces edema pulmonar) cuando se retire la atropinizacion. El periodo de obser-
vacion debera ser mayor en caso de ingestion mixta de pesticidas, debido a los
sintomas prolongados y retrasados asociados con los envenenamientos por
organofosfatos. Segun se reduzca la dosificacion de atropina con el correr del
tiempo, revise con frecuencia la base de los pulmones para buscar estertores. En
caso de que estos aparezcan o que regrese la miosis, transpiracion u otras senales
de envenenamiento, restablezca rapidamente la atropinizacion.
8. La furosemida podria ser considerada para aliviar el edema pulmonar si
persisten los estertores, aun despues de una atropinizacion completa. No se
debe utilizar antes de que la atropina alcance el efecto maximo. Consulte las
indicaciones del paquete para la dosificacion y administracion.
PB CARBAMATOS DE N-METILO
-------
9.Ventilacion pulmonar. En los envenenamientos con grandes dosis de in-
secticidas de carbaniatos de N-nietilo, monitoree la ventilacion pulmonar cui-
dadosamente, incluso despues de la recuperacion de la sintomatologia muscarinica
para prevenir un paro respiratorio.
10. Monitoree la condicion cardiopulmonar. En casos de pacientes con
envenenamiento severe, monitoree la condicion cardiaca mediante el registro
continue del electrocardiograma.
11. Contraindicaciones. Es probable que los siguientes medicamentos esten
contraindicados en casi todos los casos de envenenamientos por insecticidas de
carbamatos de N-metilo: morfina, succinilcolina, teofilina, fenotiazinas y reserpina.
Las aminas adrenergicas deben administrarse solo si existe una indicacion espe-
cifica, como por ejemplo, una hipotension marcada.
12. La aspiracion de hidrocarburo podria complicar los envenenamientos
que envuelvan la ingestion de concentrados liquidos de algunos carbamatos
formulados a base de petroleo. El edema pulmonar y la oxigenacion pobre en
estos casos no responderan a la atropina y deberan tratarse como un caso de
sindrome de depresion respiratoria aguda.
13. No administre atropina de manera profilactica a trabajadores ex-
puestos a pesticidas de carbamatos de N-metilo. La dosificacion profilactica
puede encubrir los primeros sintomas y seiiales del envenenamiento por
carbamatos y permitir que la exposicion del trabajador continue y pueda evo-
lucionar a un envenenamiento mas severe. La atropina por si misma puede
aumentar los peligros del medio laboral agricola para la salud: menoscabo en el
control termico por reduccion de la transpiracion y habilidad deteriorada para
operar equipo mecanico a causa de la vision borrosa (midriasis).
Estructura Quimica General
H3C
\
N- C - 0- GrupoSaliente
H
Referencias
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 Toxicol-
ogy: The Basic Science of Poisons, 5th ed. New York: McGraw-Hill, 1996, p. 659.
CARBAMATOS DE N-METILO 61
-------
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.
4. Jokanovic M and Maksimovic M. Abnormal cholinesterase activity: Understanding and in-
terpretation. EurJ Clin Chem Clin Biochem 1997;35:ll-6.
5. Lifshitz M, Shahak E, Bolotin A, et al. Carbamate poisoning in early childhood and in adults.
ClinToxicol 1997;35:25-7.
6. Gos\vamy R et al. Study of respiratory failure in organophosphate and carbamate poisoning.
Heart Lung 1994;23:466-72.
7. Lifshitz M.Totenberg M, Sofer S, et al. Carbamate poisoning and oxime treatment in chil-
dren: A clinical and laboratory study. Pediatrics 1994;93:652-5.
8. Kurtz PH. Pralidoxime in the treatment of carbamate intoxication. Am J Emerg Med 1990;8:68-70.
PB CARBAMATOS DE N-METILO
-------
CAPITULO 6
Insecticidas de Cloruros
Organicos Solidos
La Agencia para la Proteccion del Medio Ambiente de los Estados Unidos
(EPA) ha suspendido drasticamente la disponibilidad de un buen numero de
insecticidas de cloruros organicos en especial DDT, aldrin, dieldrin, heptacloro,
mirex, clordecona y clordano. Sin embargo, hay otros que son ingredientes
activos de varies productos que aun se utilizan en casas y jardines, y algunos
utilizados para controlar plagas ambientales, de materiales de construccion y
agricolas. El hexaclorobenceno se usa como fungicida para proteger semillas y
sera discutido mas detalladamente en el Capitulo 15, Fungicidas.
El hexaclorocicloexano tecnico (mal llamado hexacloruro de benceno,BHC,
por su nombre en ingles) incluye multiples estereoisomeros; solo el isomero
gamma (lindano) es insecticida. El lindano es el ingrediente active de algunos
productos para controlar plagas en casas y jardines, en granjas, silvicultura y en
la cria de animales. Tambien es el agente active en el medicamento KwellR,
usado en los humanos para enfermedades por extoparasitos. En numerosas oca-
siones se ha informado que el lindano ha estado asociado con toxicidad
neurologica aguda o debido a su ingestion o a que ha sido utilizado por indivi-
duos en el tratamiento de sarna o piojos.1"6
Toxicologia
Los cloruros organicos se absorben en varies grades en el intestine, pulmon
y piel. La eficiencia de la absorcion dermica es variable. El hexaclorociclohexano,
incluyendo el lindano, los ciclodienicos (aldrin, dieldrin, endrin, clordano,
heptacloro), y el endosulfan son absorbidos eficientemente a traves de la piel,
mientras que la eficiencia en la absorcion cutanea del DDT, dicofol, marlate,
toxafeno y mirex son considerablemente menor.7 El lindano tiene una tasa de
absorcion dermica documentada de 9,3%,8 y es absorbido con mayor eficiencia a
traves de la piel lacerada.1'9 Esto se torna especialmente importante cuando se
toma en consideracion su uso en niiios con dermatitis severa asociada con la
sarna. La grasa y los disolventes de grasa aumentan la absorcion gastrointestinal y
probablemente dermal de los cloruros organicos. Aunque la mayoria de los cloruros
organicos solidos no son altamente volatiles, los pesticidas en aerosol o las parti-
culas de polvo atrapadas en la mucosa respiratoria y posteriormente ingeridas,
pueden conducir a una absorcion gastrointestinal de importancia.
PUNTOS
IMPORTANTES
Senales y Sintomas:
La dosis absorbida es
almacenada en el tejido
graso
Alteraciones sensoriales:
hiperestesia y parestesia,
dolor de cabeza, mareo,
nausea, estado de sobre
excitation
Convulsiones
Tratamiento:
Anticonvulsivantes
(benzodiazepina)
Administrar oxfgeno
Monitoreo cardiopulmonar
Contraindicaciones:
Epinefrina, otras aminas
adrenergicas, atropina
Aceites de animales o
vegetales, o grasas
ingeridas por via oral
CLORUROS
ORGANICOS SOLIDOS 63
-------
Productos Comerdales
aldrin*
hexaclorodclohexano (hexacloruro
debenceno [BHC])*
HCH
hexacloro
hexadoran
clordano*
(multiples nombres de fabrica)
clordecona*
Kepone
clorobenzilato
DDT*
(multiples nombres de fabrica)
dicofol
Kelthane
(multiples nombres de fabrica)
dieldrin*
Dieldrite
dienoclor
Pentac
endosulfan
(multiples nombres de fabrica)
endrin*
Hexadrin
heptaclor"
(multiples nombres de fabrica)
hexaclorobenzina
lindano
gamma BHC o HCH
Kwell
(multiples nombres de fabrica)
metoxiclor
Marlate
mi rex*
terpeno policlorado*
Strobane
toxafeno*
* Todas las registraciones han
sido canceladas en los Estados
Unidos.
** Registrado en los Estados
Unidos solamente para uso
subterraneo en lineas electricas
contra las hormigas bravas
(rojas).
Despues de la exposicion a algunos cloruros organicos (en particular el
DDT), una parte importante de la dosis absorbida se almacena en el tejido
graso, como el compuesto principal inalterado. La mayoria de los cloruros orga-
nicos son, en cierto grado, desclorados, oxidados y, despues, conjugados. La ruta
principal de excrecion es la biliar, aunque casi todos los cloruros organicos
producen metabolitos urinarios medibles. Desafortunadamente, el intestino
reabsorbe con eficiencia muchos de los pesticidas sin metabolizar (circulacion
enterohepatica),lo cual retarda substancialmente la excrecion fecal.
La distribucion metabolica del DDT y DDE (un producto de degradacion
del DDT), del isomero beta del hexaclorociclohexano, dieldrin, epoxido de
heptacloro y mirex, tiende a ser lenta, lo que conduce a que se almacenen en la
grasa corporea. Los compuestos lipofilicos almacenables pueden ser excretados
en la leche materna.6'10> n For otra parte, la rapida eliminacion metabolica del
lindano, metoxicloro, dienoclor, endrin, clorobencilato, dicofol, toxafeno, pertano
y endosulfan reduce la probabilidad de que estos cloruros organicos scan detec-
tados como residues en la grasa corporea, sangre o leche.
La accion toxica principal de los pesticidas de cloruros organicos se dirige
al sistema nervioso, en donde estos compuestos inducen a un estado de sobre
excitacion en el cerebro.12 Este efecto se manifiesta principalmente en convul-
siones, algunas veces limitadas a contracciones mioclonicas, pero con frecuen-
cia se expresa en ataques violentos. Las convulsiones causadas por los ciclodienos
que son metabolizados con mas lentitud, pueden repetirse en periodos de va-
rios dias. Otras senales menos severas de toxicidad neurologica tales como
parestesia, agitacion involuntaria, ataxia e hiperreflexia tambien son caracteris-
ticas del envenenamiento por cloruros organicos. Agentes tales como el DDT y
el metoxicloro tienden a causar efectos menos severos, mientras que los
ciclodienos, el mirex y el lindano estan asociados con ataques mas violentos y
muertes.7 Es posible que las convulsiones causen la muerte porque interfieren
con el intercambio de gases pulmonares y generan acidosis metabolica severa.
Las concentraciones tisulares elevadas de cloruros organicos aumentan la
irritabilidad del miocardio, lo que predispone a arritmias cardiacas. Cuando las
concentraciones tisulares del organoclorado caen por debajo de los niveles de
umbral, se presenta la recuperacion del envenenamiento. Los cloruros organi-
cos no son inhibidores de la colinesterasa.
Los niveles elevados de algunos cloruros organicos (en especial DDT, DDE
y ciclodienos),han demostrado inducir las enzimas microsomales hepaticas que
metabolizan medicamentos.13 Esto tiende a acelerar la excrecion de los mismos
pesticidas, pero tambien puede estimular la biotransformacion de sustancias
naturales criticas, tales como hormonas esteroidales y medicamentos, lo que
ocasionalmente obliga a la reevaluacion de la dosificacion en personas expues-
tas intensivamente a cloruros organicos. La absorcion humana de cloruros or-
ganicos en cantidad suficiente para causar induccion enzimatica generalmente
ocurre como resultado de una exposicion intensa y prolongada.
PB
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ORGANICOS SOLIDOS
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La ingestion de trigo tratado con hexoclorobenzano ha sido asociada con
toxicidad dermica en los humanos, diagnosticada conio porfiria cutanea tardia.
Las ampollas son muy sensitivas a la luz solar y no sanan bien, lo cual resulta en
cicatrices y formacion de contractura.14 A diferencia de otros compuestos de
cloruros organicos, no se han informado casos de convulsiones causadas por el
fungicida hexoclorobenzano. El lindano y clordano se han asociado
anecdoticamente a ciertos trastornos hematologicos raros, entre los cuales se in-
cluyen las anemias aplastica y megaloblasta.15'16
Recientemente ha habido considerable interes en la interaccion de los
cloruros organicos con receptores endocrinos, en particular los receptores de
estrogeno y androgeno. Estudios in vitro y experimentos con animales han apo-
yado el punto que sostiene que la funcion del sistema endocrino podria verse
alterada por estas interacciones.17'18 Esto a su vez podria alterar el desarrollo y
exito reproductive tanto de los animales como de los humanos. Ademas, algu-
nos cloruros organicos podrian inhibir la secrecion de leche y podrian tambien
ser toxicos para el desarrollo.10 Debido a la evidencia de potencial carcinogeno,
algunos cloruros organicos han perdido la registracion para su uso en los Esta-
dos Unidos o su uso ha sido restringido.Aunque estos efectos son importantes,
estan mas alia del alcance de este manual.
Sehales y Smtomas de Envenenamiento
Los sintomas iniciales de envenenamiento por pesticidas de cloruros orga-
nicos, en particular el DDT, son a menudo alteraciones sensoriales: hiperestesia
y parestesia de la cara y extremidades. Tambien se han informado dolor de
cabeza, mareo, nausea, vomito, incoordinacion, temblor y confusion mental. El
envenenamiento mas severe causa movimientos espasmodicos mioclonicos se-
guidos de convulsiones clonico-tonicas generalizadas. Los ataques pueden ser
seguidos de coma y depresion respiratoria.
Es mas probable que el envenenamiento por ciclodienos y toxafeno origi-
ne convulsiones repentinas que, con frecuencia, no son precedidas por las ma-
nifestaciones premonitorias arriba mencionadas. Los ataques causados por
ciclodienos pueden aparecer hasta 48 horas despues de la exposicion y pueden
repetirse periodicamente durante varies dias despues del episodic inicial. Debi-
do a que el lindano y el toxafeno son biotransformados en el cuerpo con mas
rapidez y excretados, es menos probable que causen convulsiones tardias o re-
currentes como ocurre con el dieldrin, aldrin y clordano.
Confirmacion de Envenenamiento
Es posible identificar los pesticidas de cloruros organicos y/o sus metabolitos
en la sangre mediante el analisis por cromatografia gas-liquido, de muestras
tomadas pocos dias despues de una absorcion importante del pesticida. Las
CLORUROS
ORGANICOS SOLI DOS 65
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pruebas pueden realizarse en un numero reducido de laboratories guberna-
mentales, de universidades y de tipo privado, con los cuales se puede establecer
el contacto a traves de centres de control de envenenamientos o departamentos
de salud.Algunos pesticidas de cloruros organicos o sus productos (en particu-
lar el DDT, dieldrin, mirex, heptacloro, epoxido, clordecona) persisten en los
tejidos y en la sangre durante semanas y hasta meses despues de la absorcion,
pero otros pueden ser excretados en unos cuantos dias, lo que reduce la posibi-
lidad de su deteccion. Los niveles sanguineos tienden a correlacionarse mas con
la toxicidad aguda, mientras que los niveles encontrados en el tejido adiposo y
la leche materna generalmente reflejan una exposicion a largo plazo.19
Los metodos cromatograficos hacen posible la deteccion de la mayoria de
los cloruros organicos a concentraciones mucho mas bajas que las que se aso-
cian con un envenenamiento agudo; por consiguiente, un hallazgo positive en
una muestra de tejido no justifica, por si mismo, un diagnostico de envenena-
miento. El lindano aparece en la literatura con mayor frecuencia que los demas
compuestos. Cuando se interpreten los niveles sanguineos, debera tomarse en
consideracion el tiempo de adquisicion del mismo en relacion al tiempo de
exposicion. En un estudio, los niveles de lindano fueron medidos a 10,3 ng/ml
en voluntaries saludables tres dias despues de que fueran aplicados a la piel.20
En un estudio de absorcion dermica en ninos, en el cual se utilizaron ninos
con sarna y un grupo de control no afectado, el lindano alcanzo su nivel maxi-
mo de 28 ng/ml 6 horas despues de la aplicacion al grupo afectado, y de 24 ng/
ml en el grupo de control. A las 48 horas, los niveles eran de 6 ng/ml y 5 ng/ml
respectivamente. Hallazgos de este estudio tambien proveen evidencia de una
mayor absorcion a traves de la piel lacerada.9 La sarna en un niiio con piel
severamente lacerada fue tratada, y desarrollo convulsiones.Tres dias despues de
la exposicion, su nivel de lindano era 54 ng/ml.1 La mayoria de los informes de
envenenamiento agudo con lindano envuelven niveles sanguineos de 130 ng/
ml o mayores. Los casos de envenenamiento severe y fatalidades envuelven
niveles que sobrepasan 500 ng/ml.2
El DDT, DDE y unos cuantos cloruros organicos todavia se encuentran en
niveles de concentracion muy bajos en muestras sanguineas de la poblacion
general en los Estados Unidos, tal vez debido a un bajo nivel (actual y pasado)
de contaminacion de los alimentos por pesticidas que persisten en el ambiente.
Las cantidades de pesticidas almacenados que son insuficientes para identi-
ficarse en la sangre, posiblemente carezca de importancia clinica. Las determi-
naciones de metabolitos urinarios de algunos pesticidas de cloruros organicos
pueden ser utiles para medir exposiciones ocupacionales; sin embargo, los me-
todos analiticos son complejos y no es probable que detecten las cantidades de
metabolitos que se generan por exposiciones minimas.
CLORUROS
PB ORGANICOS SOLIDOS
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Tratamiento
1. Observacion. Las personas expuestas a cantidades importantes de pesticidas
de cloruros organicos por cualquier via deben observarse para identificar alte-
raciones sensoriales, incoordinacion, lenguaje lento, aberraciones mentales y
actividad motora involuntaria, los que alertarian sobre la posibilidad de convul-
siones inminentes.
2. Convulsiones. Si se presentan convulsiones, coloque a la victima en posi-
cion de decubito lateral izquierdo con la cabeza hacia abajo. Retire cualquier
mueble u otros objetos solidos que pueden causar lesiones. Si los movimientos
de la mandibula son violentos, coloque un abatelenguas acojinado entre los
dientes, con el fin de proteger la lengua. Siempre que sea posible, quite denta-
duras postizas o cualquier otro trabajo dental removible. Aspire las secreciones
orales y faringeas y cuando sea posible, inserte un tubo aereo orofaringeo para
mantener el conducto abierto y que no sea obstruido por la lengua. Reduzca el
ruido y cualquier manipulacion del paciente que pueda provocar alguna activi-
dad convulsiva.
Dosificacion de Diazepam:
Adultos: 5-10 nig por via intravenosa, repetida cada 10-15 rninu-
tos hasta un niaxinio de 30 nig.
Ninos: 0,2-0,5 nig/kg cada 5 minutos hasta un niaxinio de 10 nig
en niiios mayores de 5 anos, y un niaxinio de 5 nig en niiios
menores de 5 aiios.
Aunque la lorazepam ha sido generalmente aceptada como el trata-
miento mas probado para el status epilepticus, no existen reportes de
su uso para la intoxicacion por organoclorados. Algunos casos han re-
querido tratamiento agresivo para las convulsiones, incluyendo la adi-
cion de fenobarbital y la induccion de una coma por fenobarbital.
Las convulsiones causadas por envenenamiento de cloruros organicos tien-
den a ser prolongadas y dificiles de controlar. El status epilepticus es comun. Por
esta razon, los pacientes con convulsiones que no respondan inmediatamente a
anticonvulsivantes deberan ser transferidos lo mas pronto posible a un centre
de trauma. Generalmente, requeriran admision a la unidad de terapia intensiva
hasta que las convulsiones scan controladas y el estado neurologico mejore.
Debera instituirse terapia inicial con benzodiapecina.
CLORUROS
ORGANICOS SOLIDOS 67
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3. Oxigeno. Administre el oxigeno por mascarilla. Si la respiracion esta depri-
mida, es necesario mantener el intercambio de gases pulmonares mediante ven-
tilacion mecanica.
4. Descontaminacion dermica. Debera llevarse a cabo una completa des-
contaminacion dermica corno aparece delineado en el Capitulo 2.
5. Descontaminacion gastrointestinal. Si el organoclorado se ha ingerido
en cantidad suficiente para causar envenenamiento, y el paciente presenta sin-
tomas dentro de la primera hora, debera considerarse el procedimiento de des-
contaminacion gastrica, tal y corno aparece delineado en el Capitulo 2. Si el
paciente presenta sintomas despues de una hora de haber ingerido el pesticida,
el carbon activado todavia podria ser beneficial. Si la victima tiene convulsio-
nes, casi siempre sera necesario controlar las convulsiones antes de tratar de
llevar a cabo la descontaminacion gastrica. La administracion de carbon activa-
do ha sido apoyada en envenenamientos de esa indole, pero es poca la evidencia
experimental y humana disponible.
6. Insuficiencia respiratoria. En envenenamientos con grandes dosis de
cloruros organicos, monitoree la ventilacion pulmonar cuidadosamente
para impedir un paro respiratorio. Proveale ventilacion pulmonar y oxigeno
mecanicamente, si la respiracion esta deprimida. Debido a que estos compues-
tos a menudo son formulados en un vehiculo de hidrocarburo, la aspiracion de
hidrocarburo podria ocurrir con la ingestion de estos agentes. La aspiracion de
hidrocarburo debera ser manejada de acuerdo a la practica medica aceptada
como un caso de sindrome de depresion respiratoria aguda, lo cual general-
mente requerira tratamiento de terapia intensiva.
7. Monitoreo cardiaco. En pacientes severamente envenenados, monitoree la
condicion cardiaca a traves de un registro continuo del EGG para detectar
arritmias.
8. Contraindicaciones. No administre epinefrina, otras aminas adrenergicas
ni atropina debido a que pueden aumentar la irritabilidad del miocardio que es
inducida por hidrocarburos dorados, lo cual predispone a la fibrilacion ventricular.
No administre aceites o grasas vegetales o animales por la boca, pues incrementan
la absorcion intestinal de los cloruros organicos lipofilicos.
9. Fenobarbital. El fenobarbital por via oral podria ser efectivo para controlar las
convulsiones y los movimientos del mioclono que en ocasiones persisten durante
varies dias despues del envenenamiento agudo, debido a las excreciones mas len-
tas de los cloruros organicos. La dosificacion debera estar basada en las manifesta-
ciones en cada caso individual y en las indicaciones contenidas en el paquete.
CLORUROS
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10. La resina colestiramina acelera la excrecion biliar-fecal de los compues-
tos de cloruros organicos que se eliminan con mas lentitud.21 For lo general, se
administra en dosis de 4 g, 4 veces al dia, antes de las comidas yala hora de
dormir. La dosis usual para ninos es de 240 mg/kg/24 horas dividida Q 8 horas.
La dosis pude ser mezclada con fruta carnosa o liquidos. Nunca debe ser admi-
nistrada en su forma seca. Debe ser administrada siempre con agua, otros liqui-
dos o fruta carnosa. Puede ser necesario efectuar un tratamiento prolongado
(de varias semanas o meses).
11. Convalescencia. Durante la convalecencia, incremente la ingesta de
carbohidratos, proteinas y vitaminas, ya sea a traves de la dieta o por terapia
parenteral.
Estructuras Quimicas Generales
ci
s=o
o
CI CI
Heptacloro
OCH,
VCI-C-CIV
CI
Metoxicloro
Endosulfan
CI CI
CI CI
CI CI CI CI
Dienocloro
CLORUROS
ORGANICOS SOLI DOS 69
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Cl Cl
Cl
Cl
Clordecona
Referencias
1. Friedman SJ. Lindane neurotoxic reaction in nonbullous congenital ichthyosiform erythro-
dermz.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 therapyj/lm Geriatr Soc 1991;39(4):394-5.
4. Solomon BA, Haut SR, Carr EM, and Shalita AR. Neurotoxic reaction to lindane in an HIV-
seropositive patient: An old medication's new problem.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 Toxicol-
ogy: The Basic Science of Poisons, 5th ed. New York: McGraw-Hill, 1996, pp. 649-55.
8. Feldmann RJ and Maibach HI. Percutaneous penetration of some pesticides and herbicides
in man. Toxicol andAppl Phamiacol 1974;28:126-32.
9. Ginsburg CM, Lowry W, and Reisch JS. Absorption of lindane (gamma benzene hexachlo-
ride) 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. MedJAust 1993;158(4):238-41.
12. Joy RM.The effects of neurotoxicants on kindling and kindled seizures. Fundam ApplToxicol
1985;5:41-65.
13. Hunter J, Max\vellJD, Ste\vart DA, et al. Increased hepatic microsomal enzyme activity from
occupational exposure to certain organochlorine pesticides. Nature 1972;237:399-401.
14. Booth NH and McDo\vell JR. Toxicity of hexachlorobenzene and associated residues in
edible animal tissues J/lm Vet Med Assoc 1975;166(6):591-5.
15. Rauch AE, Kowalsky SF, LesarTS, et al. Lindane (K\vell)-induced aplastic anemia. Arch Intern
Med 1990;150:2393-5.
16. Furie B and Trubowitz S. Insecticides and blood dyscrasias. Chlordane exposure and self-
limited refractory megaloblastic anemia.JAMA 1976;235(16):1720-2.
17. Vonier PM, Grain DA, McLachlan JA, et al. Interaction of environmental chemicals with the
estrogen and progesterone receptors from the oviduct of the American alligator. Environ
Health Perspect 1996;104(12):1318-22.
PB
CLORUROS
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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] Public Health 1988;79:150-8.
20. Hosier 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
cholestyramme. New EnglJ Med 1978;298(5):243-8.
CLORUROS
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CAPITULO 7
PUNTOS
IMPORTANTES
Derivado de sistemas
vivientes
El agente vivo mas
importante lo es el Bacillus
thuringensis
Generalmente de baja
toxicidad
Senates y Smtomas:
Altamente variable basado
en los agentes especfficos
Varies causan irritation
gastrointestinal
La nicotina y rotenona
podrfan causar series
efectos al SNC
La nicotina y la cebadilla
pueden tener efectos
cardiovasculares
Tratamiento:
Especffico al agente
Podrfa indicarse la
descontaminadon dermica,
ocular y gastrointestinal
La nicotina, rotenona y
cebadilla requieren manejo
agresivo
Insecticidas de Origen Biologico
Este Capitulo trata sobre varies productos insecticidas de origen natural am-
pliamente utilizados, y tambien sobre ciertos agentes a rnenudo identificados
como agentes de control biologico. De los muchos agentes vivientes utilizados
para el control, solamente el agente bacterial Bacillus thuringiensis sera discutido
en detalle, debido a que es el mis ampliamente utilizado. Muchos otros agentes,
tales como las avispas e insectos parasiticos, son tan especificos en el huesped
que posan poco si algun riesgo a la salud humana. Los agentes son discutidos en
este capitulo en orden alfabetico.
AZADIRACHTIN
Este insecticida biologico se deriva del arbol de Neem (Azadirachta indica).
Regula el crecimiento de los insectos, interfiriendo con la hormona mudadora
ecdisona.
Toxicologia
La azadiractina causa severa irritacion dermica y gastrointestinal. Tambien
se ha visto estimulacion y depresion del sistema nervioso central. Este agente es
utilizado y fabricado primordialmente en la India; no se espera mucho uso ni
exposicion en los Estados Unidos.
Tratamiento
1. Descontaminacion dermica. Si ocurre exposicion dermica, la piel debera
ser completamente lavada con agua y jabon.
2. Descontaminacion gastrointestinal. Debido a la severa irritacion
gastrointestinal, el vaciado gastrico y la catarsis son contraindicadas. Debera
prestarse atencion a la administracion de carbon activado tal y como es delinea-
do en el Capitulo 2.
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BIOLOGICO
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BACILLUS THURINGIENSIS
Productos Comerdales
Varias cepas de Bacillus thuringiensis son patogenas para algunos insectos. Las
bacterias se cultivan y se cosechan en forma de esporas para ser usadas corno
insecticida. Los metodos de produccion son muy variados. Las toxinas de tipo
proteico y nucleotido generadas por las formas vegetativas (que infectan a los
insectos) son las responsables del efecto insecticida. Las esporas se formulan
como polvos humectables, concentrados suspendibles y granules para ser apli-
cados en cultivos de campo y para controlar mosquitos y moscas.
Toxicologia
Las variedades del Bacillus thuringiensis de uso comercial sobreviven cuando
se inyectan a ratones, y se ha comprobado que por lo rnenos una de las toxinas
insecticidas purificadas es toxica para el raton. Las infecciones en humanos son
extremadamente raras. Se ha informado solamente un caso de ingestion, y esta
fue una ingestion deliberada de Bacillus thuringiensis var.galleriae por voluntaries.
La ingestion resulto en fiebre y sintomas gastrointestinales. Sin embargo, este
agente no esta registrado como pesticida. En los Estados Unidos, los productos
de B. thuringiensis estan exentos de tolerancia en productos agricolas no
industrializados. No se han descrito efectos irritantes ni de sensibilizacion en
los trabaj adores que preparan y aplican los productos comerciales.
Tratamiento
1. Descontaminacion dermica. Elimine la contaminacion dermica con agua
y jabon.Trate la contaminacion ocular con enjuagues de agua limpia o solucion
salina. Si la irritacion persiste, o si existe cualquier indicacion de infeccion,
obtenga tratamiento medico.
Un caso unico de ulcera cornea! causada por la salpicadura de una suspen-
sion de B. thuringiensis fue tratado con exito, aplicando una inyeccion
subconjuntival de gentamicina (20 mg) y cefazolina (25 mg).1
2. Descontaminacion gastrointestinal. Si el paciente ha ingerido algun
producto de B. thuringiensis, vigilelo con el fin de detectar manifestaciones de
gastroenteritis: espasmos abdominales, vomito y diarrea. En caso de que aparez-
ca, la enfermedad se curara por si misma. El paciente debera ser tratado
sintomaticamente y debera proveersele liquidos, segun sea necesario.
EUGENOL
Este compuesto se deriva del clavo aromatico. Es usado como un atrayente
para los insectos.
acido giberelico (GA3)
Active I
Berelex
Cekugib
Gibberellin
Gibrel
Grocel
Pro-Gibb
Pro-Gibb Plus
Regulex
azadirachtin
Align
Azatin
Bollwhip
Neemazad
Neemazal
Neemix
Turplex
Bacillus thuringiensis
Variedad aizawai:
Agree
Design
Mattch
XenTari
Variedad israelensis:
Aquabac
Bactimos
Gnatrol
Skeetal
Teknar
Vectobac
Vectocide
Variedad kurstaki:
Bactospeine
Bactur
Dipel
Futura
Sok-Bt
Thuricide
Tribactur
Variedad morrisoni
Variedad tenebrionis:
Novodor
cebadilla
estreptomidna
Agri-Mycin 17
Paushamycin, Tech.
Plantomycin
eugenol
nicotina
Black Leaf 40
Nico Soap
piretrinas
(Continue en la pagina siguiente)
BIOLOGICO- 73
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Productos Comerdales
(Continuation)
rote no na
Chem-Fish
Noxfire
Noxfish
Nusyn-Foxfish
Prenfish
Rotacide
Rotenone Solution FK-11
Sypren-Fish
Toxicologia
El eugenol es similar en sus efectos clinicos al fenol.Aunque trabaja como
un anestesico, en grandes dosis puede causar quemaduras a la superficie epitelial.2
Las membranas mucosas han sido mudadas como reaccion alergica a una pe-
quena dosis aplicada localmente en la boca.3 Lesiones mucosas gastricas han
sido informadas en animales, pero ninguna lesion fue vista a traves de la
endoscopia despues de haberse ingerido clavo aromatico.4 Las grandes dosis
podrian resultar en coma y en la disfuncion hepatica.5
Descontinuado en los Estados
Unidos.
Tratamiento
El tratamiento es principalmente de apoyo, debido a que no existe antido-
to. Si existen quemaduras de las membranas mucosas, debera considerarse una
endoscopia para asegurarse que no hayan otras ulceraciones.
ACIDO GIBERELICO (Gibberelina, GA3)
El acido giberelico no es un pesticida, pero se usa comunmente en la pro-
duccion agricola como agente promotor del crecimiento. Es un producto
metabolico de hongos cultivados, formulado en tabletas, granules y concentra-
dos liquidos para aplicarse a la tierra para el crecimiento de plantas y arboles.
Toxicologia
Los animales experimentales toleran grandes dosis orales sin efectos adversos
aparentes. No se han informado envenenamientos en humanos, ni se ha identifi-
cado sensibilizacion, de modo que los efectos irritantes no son importantes.
Tratamiento
1. Descontaminacion dermica. Lave la contaminacion de la piel con agua y
jabon. Enjuague la contaminacion ocular con agua limpia o solucion salina. Si
se presenta irritacion, obtenga tratamiento medico.
2. Descontaminacion gastrointestinal. No existe razon para esperar efectos
adversos cuando se haya ingerido acido giberelico.
NICOTINA
La nicotina es un alcaloide que se encuentra en las hojas de una gran varie-
dad de plantas pero que, en general, se obtiene comercialmente del tabaco. Una
PB
BIOLOGICO
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preparacion de alcaloide libre al 14% es vendida corno fumigante para inverna-
deros. Ocurre una volatilizacion irnportante de la nicotina. Los insecticidas de
nicotina comercial se han conocido por largo tiempo como Black Leaf 40. Esta
formulacion fue descontinuada en 1992. Otras formulaciones disponibles al
presente incluyen polvos formulados con naftaleno y sangre seca usada para
repeler perros y conejos. Este consciente del Sindrome deTabaco Verde causa-
do por absorcion dermica. En la actualidad, ya casi no se utilizan insecticidas a
base de nicotina en los Estados Unidos, aunque pueden encontrarse ocasional-
niente antiguas preparaciones de insecticidas con nicotina.6 En la actualidad, la
mayoria de los envenenamientos por nicotina son el resultado de ingestion de
productos de tabaco y del uso incorrecto de los parchos cutaneos de nicotina.
Toxicologia
El intestino y pulmon, al igual que la piel, absorben con eficiencia el alca-
loide libre. Una extensa biotransformacion ocurre en el higado, ocurriendo el
70-75% como una primera depuracion.7 Tanto el higado como los rinones
participan en la formacion y excrecion de multiples productos terminales, los
cuales se excretan en unas pocas horas. Estimados de la vida media de la nico-
tina fluctuan entre aproximadamente una hora para los fumadores hasta dos
horas para los no fumadores.8'9
La accion toxica es compleja. En dosis bajas, estimula los ganglios autono-
mos. En dosis altas, resulta en un bloqueo de los ganglios autonomicos y de las
uniones neuromusculares musculo esqueleticas, como tambien en efectos di-
rectos en el sistema nervioso central. La paralisis y el colapso vascular son rasgos
caracteristicos del envenenamiento agudo. Sin embargo, en general, la muerte
se debe a paralisis respiratoria, la cual puede sobrevenir inmediatamente des-
pues de los primeros sintomas de envenenamiento. La nicotina no inhibe la
enzima colinesterasa.
Sehales y Sintomas de Envenenamiento
Los sintomas iniciales del envenenamiento son salivacion, nausea, vomito y
diarrea. Se han informado sensaciones de ardor en la boca y garganta, agitacion,
confusion, dolor de cabeza y dolor abdominal. Si la dosificacion es elevada,
pueden sobrevenir de inmediato el colapso vascular con hipotension, bradicardia
u otras arritmias, disnea y por consiguiente falla respiratoria, luego de lo cual
sobrevendria prontamente la inconciencia.6'10> n> 12 En algunos casos, la
hipertension y taquicardia pueden preceder la hipotension y bradicardia. Estos
dos sintomas conducen a un cheque subsecuente.11'12 Tambien pueden ocurrir
convulsiones.6'n En un caso de ingestion de una dosis grande de un pesticida
de nicotina alcaloide, el paciente desarrollo asistolia en dos minutos. Mas tarde,
desarrollo convulsiones e hipotension refractaria.6
BIOLOGICO- 75
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Confirmacion de Envenenamiento
El contenido del metabolito cotinina en la orina puede ser utilizado para
confirmar la absorcion de la nicotina.
Tratamiento
1. Descontaminacion dermica. Si el liquido o el aerosol ha entrado en
contacto con la piel, lave el area con abundante agua y jabon. Si la contamina-
cion llega a los ojos, enjuaguelos con abundante agua linipia o solucion salina.
Si la irritacion persiste, busque tratamiento medico especializado.
Si los sintomas de envenenamiento aparecen durante la exposicion a un
insecticida con nicotina presente en el aire, retire de inmediato a la persona del
ambiente contaminado, lave el area de la piel que pueda estar contaminada y
lleve a la victima al lugar mas cercano en el que pueda recibir tratamiento. Un
envenenamiento leve puede resolverse sin tratamiento, pero al inicio del enve-
nenamiento no siempre es posible predecir cual sera la gravedad final.
2. Ventilacion pulmonar. Si existe cualquier indicio de perdida del ritmo
respiratorio, mantenga la respiracion pulmonar mecanicamente, incluyendo el
oxigeno suplementario, si se dispone de este, por respiracion boca a boca, o de
boca a nariz, si es necesario. En general, se sobrevive a los efectos toxicos de la
nicotina distintos a la depresion respiratoria. Por consiguiente, es de vital im-
portancia mantener un intercambio de gases adecuado.
3. Descontaminacion gastrointestinal. Si se ha ingerido un producto con
nicotina, tome acciones inmediatas con el fin de reducir la absorcion
gastrointestinal. Si el paciente se encuentra totalmente alerta, probablemente la
administracion inmediata por via oral de carbon activado, como se delinean en
el Capitulo 2, sea el mejor inicio en el tratamiento. La administracion repetida
de carbon activado a la mitad o mas de la dosificacion inicial cada 2-4 horas
podria ser beneficiosa. Debido a que la diarrea, generalmente forma parte de
esta clase de envenenamiento, no es necesario o apropiado administrar un ca-
tartico. No administre jarabe de ipecacuana.
4. Monitoreo cardiaco. Monitoree el estado cardiaco por electrocardiografia y
mida la presion sanguinea con frecuencia. Tal vez sea necesaria la resucitacion
cardiopulmonar. El colapso vascular puede requerir de la administracion de
norepinefrina y/o dopamina. Consulte las indicaciones del paquete para las
dosificaciones y forma de administracion. Las infusiones de soluciones electroliticas,
plasma y/o sangre pueden ayudar a combatir el cheque.
PB BIOLOGICO
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Dosificacion de Sulfato de Atropina:
Adultos y ninos mayores de 12 afios: 0,4-0,5 nig por via intravenosa
lenta, repetida cada 5 minutos, de ser necesario.
Nines menores de 12 anos: 0,01 mg/kg de peso corporeo por via
intravenosa lenta, repetida cada 5 minutos, de ser necesario. Existe
una dosis minima de 0,1 mg.
5. Sulfato de atropina. No existe un antidote especifico para el envenena-
miento con nicotina. La hipersecrecion severa (en especial la salivacion y dia-
rrea) o bradicardia pueden controlarse con sulfato de atropina por via intravenosa.
6. Las convulsiones deberan ser controladas segun como fuera delineado en el
Capitulo 2. Si el paciente sobrevive durante cuatro horas, lo mas probable es
que ocurra una recuperacion completa.
PIRETRO Y PIRETRINAS
El piretro es el extracto de oleorresina de las flores secas de crisantemo. El
extracto contiene aproximadamente 50% de ingredientes insecticidas activos
conocidos como piretrinas. Los esteres ceto-alcoholicos de los acidos
crisantemico y piretroico se conocen como piretrinas, cinerinas y jasmolinas.
Estos esteres son fuertemente lipofilicos, penetran con suma rapidez en muchos
insectos y paralizan su sistema nervioso. El extracto crudo de piretro y las
piretrinas purificadas se encuentran en varies productos comerciales,
comunmente disueltos en destilados de petroleo. Algunos de ellos se empacan
en recipientes presurizados ("bombas para insectos"), casi siempre en
combinacion con sustancias sinergicas, como el butoxido de piperonilo y la n-
octil-biciclohepten-dicarboximida. Estas sustancias sinergicas retardan la
degradacion enzimatica de las piretrinas.Algunos productos comerciales tambien
contienen insecticidas organofosfatados o carbamicos. Estos se incluyen debido
a que el rapido efecto paralitico de las piretrinas en los insectos ("efecto de
derribo rapido") no siempre es letal.
Los productos a base de piretro y piretrinas se utilizan para controlar plagas
en interiores, pues no son lo suficientemente estables en presencia de luz y
calor para permanecer como residues activos en los cultivos. En cambio, los
insecticidas sinteticos conocidos como piretroides (quimicamente similares a
las piretrinas) si tienen la estabilidad necesaria para la aplicacion agricola. Los
piretroides se discuten en el Capitulo 8.
BIOLOGICO- 77
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Toxicologia
El piretro crudo es un alergeno respiratorio y dermico, probablemente a
causa de los ingredientes sin accion insecticida. Despues de las exposiciones,
han ocurrido dermatitis de contacto y reacciones respiratorias alergicas (rinitis
y asma).13'14 Se han descrito casos aislados de manifestaciones anfilacticas15 y
neumonicas.lf> Las piretrinas refinadas son probablemente menos alergenicas
pero, al parecer, conservan algunas propiedades irritantes y/o sensibilizantes.
Las piretrinas se absorben a traves del intestine y de la membrana pulmonar
y solo muy poco a traves de la piel intacta. Las enzimas hepaticas de los mami-
feros son capaces de hidrolizarlas con gran eficacia para dar productos inertes.
La degradacion acelerada, combinada con una biodisponibilidad hasta cierto
punto pobre, explica, en gran medida, que su toxicidad para los mamiferos sea
relativamente baja. Los perros alimentados con dosis extraordinarias de tales
compuestos presentan temblor, ataxia, respiracion dificil y salivacion. En los
humanos, incluidas las personas que han utilizado piretrinas para controlar pio-
jos en el cuerpo (contacto extenso), o el piretro como antihelmintico (inges-
tion), rara vez se ha observado una neurotoxicidad similar.
En los casos de exposicion humana a productos comerciales debe conside-
rarse el posible papel de otros toxicos que se encuentren en los productos. Las
sustancias sinergicas como el butoxido de piperonilo y la n-octil-biciclohepten
dicarboximida tienen un bajo potencial toxico en humanos, pero los
organofosfatos y los carbamatos incluidos en el producto pueden tener una
toxicidad de importancia. Las piretrinas, por si mismas, no inhiben la enzima
colinesterasa.
Confirmacion de Envenenamiento
Al presente, no existen pruebas practicas para los metabolitos de la piretrina
o los efectos de la piretrina en las enzimas o tejidos humanos que puedan ser
usadas para confirmar la absorcion.
Tratamiento
1. Los antihistammicos son eficaces para controlar la mayoria de las reaccio-
nes alergicas. Las personas predispuestas a reacciones asmaticas severas pueden
requerir la administracion inhalada de agonistas B2y/o corticosteroides sistemicos.
Deben evitarse a toda costa futuras exposiciones por inhalacion.
2. Las reacciones de tipo anafilaxis podrian requerir epinefrina subcutanea,
epinefrina y apoyo respiratorio.15
PB BIOLOGICO
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3. La dermatitis por contacto podria requerir la administracion extendida
de preparaciones corticosteroides topicas. Esto debera hacerse bajo la supervi-
sion de un medico. Debera evitarse el contacto future con el alergeno.
4. La contaminacion ocular debera eliminarse enjuagando los ojos con abun-
dante agua limpia o con solucion salina. En el caso de que la irritacion persista,
debe obtenerse atencion oftalmologica.
5. Otras manifestaciones toxicas causadas por otros ingredientes deben
tratarse de acuerdo con las acciones toxicas respectivas, independientemente de
los efectos relacionados con las piretrinas.
6. Descontaminacion gastrointestinal. Aunque la mayoria de las ingestiones
de productos a base de piretrinas presentan riesgos leves, en el caso de ingerir
una gran cantidad de material con piretrinas, y si el paciente es atendido en una
hora, debera considerarse el vaciado del estomago. Si el paciente es visto mas
tarde, o si se lleva a cabo el vaciado del estomago, considere la administracion de
carbon activado como fuera delineado en el Capitulo 2.
ROTENONA
Aunque esta sustancia natural esta presente en diversas plantas, la fuente
mas importante de la rotenona utilizada en los Estados Unidos es la raiz seca de
derris, que se importa de America Central y America del Sur. Se formula como
polvos y aerosoles (menos del 5% de ingrediente active), para su uso en jardines
y cultivos alimentarios.Varios productos contienen butoxido de piperonilo como
sustancia sinergica; en algunos productos comerciales, se incluyen otros pestici-
das. La rotenona se degrada con rapidez en el ambiente. Las emulsiones de
rotenona se aplican en lagos y lagunas para eliminar peces.
Toxicologia
Aunque la rotenona es toxica para el sistema nervioso de insectos, peces y
aves, a lo largo de varias decadas los productos comerciales a base de rotenona
no han representado un peligro significative para el hombre: no se han infor-
mado fallecimientos ni envenenamientos sistemicos en los humanos con rela-
cion a su uso comun. Sin embargo, si existe un informe de una fatalidad, envol-
viendo a una nina quien ingirio el producto llamado Gallocide, el cual contie-
ne rotenona y aceites etereos, incluyendo el clavo aromatico. Ella desarrollo una
perdida de conciencia gradual durante un periodo de dos horas y murio de
paro respiratorio.17
Se ha informado que los trabaj adores en cuyas bocas entro polvo de raiz de
derris, sufrieron entumecimiento de las membranas mucosas orales.Tambien se
BIOLOGICO- 79
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ha informado dermatitis e irritacion del tracto respiratorio en personas expues-
tas ocupacionalmente.
Cuando la rotenona ha sido inyectada a los animales se han observado
temblores, vomito, incoordinacion, convulsiones y paro respiratorio. Estos efectos
no se han informado en humanos expuestos ocupacionalmente.
Tratamiento
1. Descontaminacion dermica. Elimine la contaminacion dermica con agua
y jabon. Elimine la contaminacion ocular con enjuagues abundantes de agua
limpia o solucion salina. El polvo en la boca debe enjuagarse y escupirse. Si la
irritacion persiste debera obtenerse tratamiento medico.
2. Descontaminacion gastrointestinal. Si se ha ingerido y retenido un pro-
ducto que contenga rotenona, y el paciente es visto dentro de una hora despues
de la exposicion, debera considerarse el vaciado del estomago.Ya bien se realice
o no el vaciado del estomago, considere el uso de carbon activado como fuera
delineado en el Capitulo 2.
3. El apoyo respiratorio debera ser usado de ser necesario en caso de que
ocurra un cambio en el estado mental y/o depresion respiratoria.
CEBADILLA (alcaloide veratro)
La cebadilla se elabora a partir de las semillas maduras molidas de un lirio
sudamericano. Se usa como polvo, con cal o azufre, o se disuelve en queroseno,
en especial, para matar extoparasitos en animales domesticos y en humanos. Los
alcaloides insecticidas son del tipo de la veratrina. La concentracion de los
alcaloides en la cebadilla comercial es, en general, de menos de 0,5%. En la
actualidad, la cebadilla casi no se utiliza en los Estados Unidos, pero es posible
que se use en otros paises. Los encuentros mas toxicos con alcaloide veratro han
ocurrido debido a la ingestion accidental de la planta.18
Toxicologia
El polvo de cebadilla es muy irritante para el tracto respiratorio superior y
causa estornudos.Tambien es un irritante dermico. Aparentemente, los alcaloides
derivados de la veratrina son absorbidos a traves de la piel, intestino y, probable-
mente, por el pulmon. Estos compuestos tienen una accion parecida a la de la
digital en el musculo cardiaco (conduccion deteriorada y arritmias).
Aunque es probable que en el pasado ocurrieran envenenamientos por
ingestion de preparaciones medicinales con veratrina, no han ocurrido envene-
PB BIOLOGICO
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namientos sistemicos por preparaciones de cebadilla usadas corno insecticidas,
o los mismos han sido rnuy raros. Los sintomas prominentes de envenenamien-
to por alcaloide veratro son la nausea severa y vomito, seguido por hipotension
y bradicardia. Otras arritmias o bloqueos A-V pueden ocurrir.18'19
Tratamiento
1. Descontaminacion dermica. Lave cuidadosamente la piel contaminada
con agua y jabon. Si los ojos se contaminan, enjuaguelos con cantidades abun-
dantes de agua linipia o solucion salina. Si persiste la irritacion de los ojos o de
la piel obtenga tratamiento medico.
2. Descontaminacion gastrointestinal. Si se ha ingerido una gran cantidad
del producto pesticida con cebadilla en la ultima hora y este se ha retenido,
considere el vaciado del estomago. Esto podria ir seguido de la administracion
de carbon. Si solo se ha ingerido y retenido una pequeiia cantidad de pesticida
con cebadilla, o si el tratamiento se ha retrasado y el paciente permanece
completamene alerta, el manejo mas adecuado es administrar de inmediato
carbon activado por via oral, como fuera delineado en el Capitulo 2.
3. Monitoreo cardiaco. Si se sospecha que se han absorbido cantidades de
importancia de alcaloides de cebadilla, realice el monitoreo de la actividad cardia-
ca con EGG para evaluar arritmias y defectos en la conduccion. La bradicardia
puede ser tratada con atropina.18>19Vease la dosificacion que sigue a continuacion.
Dosificacion de Sulfato de Atropina:
Adultos y ninos mayores de 12 anos: 0,4-0,5 mg por via intravenosa
lenta, repetida cada 5 minutos, de ser necesario.
Ninos menores de 12 anos: 0,01 mg/kg de peso corporeo por via
intravenosa lenta, repetida cada 5 minutos, de ser necesario. (Existe
una dosis minima de 0,1 mg).
ESTREPTOMICINA
El sulfato y nitrato de estreptomicina son usados como pesticidas para el
control de una variedad de importantes patogenos bacteriales de plantas co-
merciales. La estreptomicina es un antibiotico derivado del cultivo de
Streptomyces griseus.
BIOLOGICO- 81
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Toxicologia
Este antibiotico comparte un perfil toxico con los antibioticos
aminoglicosidos utilizados comunmente para tratar enfermedades humanas. Su
mayor modo de toxicidad lo son la nefrotoxicidad y ototoxicidad. Afortunada-
mente, no es muy bien absorbido por el tracto gastrointestinal, por lo cual es
improbable la toxicidad sistemica debido a la ingestion.
Tratamiento
Si el paciente ingirio una gran cantidad de estreptomicina dentro de la
hora anterior de recibir cuidado medico, debera considerarse el vaciado del
estomago. Debera considerarse la administracion de carbon activado, como fuera
delineado en el Capitulo 2.
Referencias
1. Samples JR and Buettner H. Cornea! ulcer caused by a biological insecticide (Bacillus
thuringiensis)./lmj Ophthalmol 1983;95:258.
2. Isaacs G. Permanent local anesthesia and anhydrosis after clove oil spillage. Lancet 1983;! :882.
3. Barkin ME, Boyd JP, and Cohen S. Acute allergic reaction to eugenol. Oral Surg Oral Med Oral
Pathol 1984;57:441-2.
4. Lane BW, Ellenhorn MJ, HulbertTV, et al. Clove oil ingestion in an infant. Hum Exp Toxicol
1991;10:291-4.
5. Hartnoll G, Moore D, and Douek D. Near fatal ingestion of oil of cloves. Arch Dis Child
1993;69:392-3.
6. Lavoie FW and 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.
8. Kyerematen MS, Damiano MD, Dvorchik BH, et al. Smoking-induced changes in nicotine
disposition: Application of a new HPLC assay for nicotine and its metabolites. Clin Pharmacol
Ther 1982;32:769-80.
9. Feyerabend C, Ings RMJ, and Russell MAH. Nicotine pharmacokinetics and its application
to intake from smoking. BrJ Clin Pharmacol 1985;19:239-47.
10. Woolf A, Burkhart K, Caraccio T, et al. Self-poisoning among adults using multiple transdermal
nicotine patches.JToxicol Clin Toxicol 1996;34:691-8.
11. Sanchez P, Ducasse JL, Lapeyre-Mestre M, et al. Nicotine poisoning as a cause of cardiac
arrest? (letter).]Toxicol ClinToxicol 1996;34:475-6.
12. Malizia E, Andreucci G, Alfani F, et al. Acute intoxication with nicotine alkaloids and can-
nabinoids in children from ingestion of cigarettes. 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.
MedJAust 1983; 1:378-80.
15. Culver CA, Malina JJ, and Talbert RL. Probable anaphylactoid reaction to a pyrethrin
pediculocide shampoo. Clin Pharm 1988;7:846-9.
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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) JEmeig Med 1990;8:161-7.
19. Quatrehomme G, Bertrand F, Chauvet C, et al. Intoxication from veratrum album. Hum Exp
Toซซ>/1993;12:lll-5.
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CAPITULO 8
PUNTOS
IMPORTANTES
Agentes multiples, con una
gran variedad de toxicidad
Un historial cuidadoso
generalmente revelara un
historial de exposition
Los agentes de mayor
preocupadon, debido a su
amplio uso, son los
piretroides, dietiltoluamida
y boratos
Otros Insecticidas,
Acaricidas y Repelentes
Este Capitulo trata sobre insecticidas, acaricidas y repelentes con caracteristicas
toxicologicas distintas de las correspondientes a los insecticidas mencionados
en los Capitulos anteriores. Entre los pesticidas discutidos se encuentran: ftalatos
de alquilo, benzoato de bencilo, boratos clordimeformo, clorobenzilato, cihexatin
dietitoluamida, fluoruros, compuestos haloaromaticos de urea sustituida,
metropeno, propargita, piretroides y sulfuro.
Senates y Sintomas:
Variables y altamente
relacionados a los agentes
especfficos
El acido borico causa
eritema intensa y
exfoliation de salpullido
(apariencia de langosta
hervida)
Debe sospecharse de
agentes como el acido
borico, dietiltoluamida y
piretroides en casos de
sintomas inusuales del
sistema nervioso
Tratamiento:
Especffico a los agentes
Descontaminadon dermica
y del tracto gastrointestinal
Los sintomas severos del
sistema nervioso central
podrfan requerir
tratamiento de terapia
intensiva
FTALATOS DE ALQUILO
El ftalato de dimetilo se ha utilizado ampliamente como repelente de in-
sectos, aplicado de manera directa a la piel. El ftalato de dibutilo se impregna en
las telas con el mismo proposito, puesto que es mas resistente al lavado que el
ftalato de dimetilo.
Toxicologia
El ftalato de dimetilo es un fuerte irritante para los ojos y las membramas
mucosas. Casi no causa irritacion cuando se aplica a la piel y la absorcion dermica
es, en apariencia, minima. No origina sensibilizacion. Las pruebas efectuadas en
roedores indican una baja toxicidad sistemica,pero la ingestion de grandes dosis
causa irritacion gastrointestinal, depresion del sistema nervioso central, coma e
hipotension.
Tratamiento
No existen antidotes. En la mayoria de los casos de envenenamiento, ex-
cepto los mas graves, el manejo mas adecuado es utilizar medidas de apoyo
(hidratacion y oxigeno, de ser necesario).
PB
OTROS INSECTICIDAS
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BENZOATO DE BENCILO
Productos Comerdales
Toxicologia
Este agente, incorporado a lociones y ungiientos, se ha utilizado durante
muchos anos en medicina veterinaria y humana en contra de garrapatas y pio-
jos.Aparte de que se han presentado casos ocasionales de irritacion cutanea, los
efectos adversos no han sido importantes. Se desconoce la eficiencia de la ab-
sorcion a partir de la piel. El benzoato de bencilo que es absorbido se
biotransforma con rapidez para dar acido hipurico, el cual se excreta en la
orina. Cuando se administran grandes dosis a animales de laboratorio, el com-
puesto causa excitacion, incoordinacion, paralisis de las extremidades, convul-
siones, paralisis respiratoria y muerte. No se ha informado de envenenamientos
en seres humanos.
Tratamiento
1. Descontaminacion dermica. Descontinue el niedicaniento si aparece
irritacion y limpie la piel con agua y jabon.Trate la contaminacion ocular con
enjuagues prolongados utilizando agua limpia o solucion salina.
2. Descontaminacion gastrointestinal. Si se ha ingerido una cantidad po-
tencialmente toxica y esta se ha retenido, tome medidas para eliminar el com-
puesto del tracto gastrointestinal, como fuera delineado en el Capitulo 2.
3. Convulsiones. Si se presentan convulsiones, puede requerirse la administra-
cion de medicamentos anticonvulsivantes para controlarlas, como fuera deli-
neado en el Capitulo 2.
ACIDO BORICO Y BORATOS
El acido borico se formula como tabletas y polvos para matar larvas en las
areas de encierro de ganado y cucarachas en las casas. Ocasionalmente se rocian
en solucion como herbicidas no selectivos.
Toxicologia
El polvo y las tabletas de acido borico esparcidas en el piso de los hogares
representan un peligro para los ninos. Su uso frecuente como control para las
cucarachas aumenta las posibilidades de ser ingerido. Se han informado unos
784 pacientes sin que haya habido ninguna fatalidad y una toxicidad minima.
Solo el 12% de estos pacientes presentaron sintomas de toxicidad, en su mayoria
ACIDO BORICO Y BORATOS
acido borico
poliborato sodico
Polybor 3
tetraborato sodico
decahidrato
Borax
AZUFRE
muchos productos comerciales
BENZOATO DE BENCILO
CIHEXATlN (nr)
Acarstin
Metaran
Oxotin
Pennstyl
Plictran
CLORDIMEFORMO (nr)
CLOROBENCILATO (nr)
Acaraben
Akar
Benzilan
Folbex
COMPUESTOS
HALOAROMATICOS DE
UREASUSTITUIDA
diflubenzuron
Dimilin
Micromite
Vigilante
teflubenzuron
Dart
Diaract
Nomolt
DIETILTOLUAMIDA (DEET)
Auton
Detamide
Metadelphene
MGK
Muskol
Off!
Skeeter Beater
Skeeter Cheater
Skintastic for Kids
(Continue en la pagina siguiente)
OTROS INSECTICIDAS
85
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Productos Comerdales
(Continuacion)
FLUORUROS
fluoruro sodico (protection para
la madera solamente)
fluosilicato sodico (silicofluoruro
sodico) (nr)
Prodan
Safsan
(Continua en la pagina
siguiente)
Productos Comerdales
(Continuacion)
fluoaluminato sodico
(aluminofluoruro sodico)
Cryolite
Kryocide
Prokil
FTALATOS DE ALQUILO
ftalato de dibutilo
ftalato de dimetilo
DMP
METOPRENO
Altosid
Apex
Diacon
Dianex
Kabat
Minex
Pharorid
Precor
PIRETROIDES
aletrina
Pynamin
bartrina (nr)
bioaletrina
D-trans
biopermetrina (nr)
bioresmetrina (nr)
cismetrina (nr)
ciflutrina
Baythroid
cipermetrina
Ammo
Barricade
CCN52
Cymbush
Cymperator
Cynoff
Cyperkill
(Continua en la pagina siguiente)
del tracto gastrointestinal.1 Sin embargo, se han informado algunos casos recientes
de envenenamientos con fatalidades,2'3 y un gran numero de los envenenamientos
en recien nacidos ocurridos en las decadas de 1950 y 1960 a menudo terminaron
en muerte.4'5 Historicamente,la mayoria de los envenenamientos han sido por
usos imprudentes en la medicina humana para controlar el crecimiento
bacteriano, tales como colocar compresas en quemaduras, polvos para el salpullido
causado por panales y soluciones de irrigacion.6'7 Con el aumento en el uso del
acido borico para el control de las cucarachas, es probable que aumente la
ingestion en casos de suicidio y accidentales.3'7
El polvo de borax es un irritante moderado para la piel. El polvo inhalado
causo irritacion del tracto respiratorio entre los trabaj adores en una planta de
borax. Los sintomas incluyeron irritacion nasal, resequedad de las membranas
mucosas, tos, respiracion acortada y estrechez en el pecho.8'9
Cuando se determine la toxicidad del acido borico ingerido, es importante
hacer una distincion entre la exposicion aguda y cronica. Es mas comun que la
ingestion cronica cause una toxicidad significativa que la exposicion aguda.1'2
Los boratos son bien absorbidos por el intestino y por la piel lacerada o
quemada, pero no por la piel intacta.6 El rinon los excreta de manera eficiente.
La residencia de vida media en humanos es de 13 horas con un intervalo de
4a28horas.1
Los principales organos y tejidos afectados son el tracto gastrointestinal,
piel, sistema vascular y cerebro. La nausea, el vomito persistente, el dolor
abdominal y la diarrea indican gastroenteritis toxica.1'2'7 El letargo y dolor de
cabeza pueden ocurrir, pero con mucha menos frecuencia.1 En los
envenenamientos graves se ha descrito una erupcion roja y papulomatosa que,
con frecuencia, afecta las palmas, plantas de los pies, nalgas y escroto, la misma se
ha caracterizado como una"apariencia de langosta hervida".El eritema intense
es seguido por exfoliacion extensa.2'5'10 Seria dificil distinguir esto del sindrome
estafilococia de escaldadura de la piel.10
El dolor de cabeza, debilidad, letargo, inquietud y temblores pueden ocurrir
pero son menos frecuentes que los efectos gastrointestinales.1 Siete infantes
expuestos a una mezcla de borax y miel en sus chupetes desarrollaron
convulsiones.11 La inconsciencia y depresion respiratoria indican dano cerebral
que pone en riesgo la vida. La cianosis, pulso debil, hipotension, y piel humeda
y fria indican shock, el cual es algunas veces la causa de muerte en el
envenenamiento por boratos.2'3'7
La insuficiencia renal aguda (oliguria o anuria) puede ser consecuencia del
shock, de accion toxica directa sobre las celulas de los tubulos renales, o de ambas
situaciones, y solo ocurre en el envenenamiento severe por boratos.2'3> 5> 10 La
acidosis metabolica puede ser consecuencia del acido mismo, de la actividad
convulsiva o de trastornos metabolicos.2 Algunas veces hay fiebre en ausencia
de infeccion.
PB
OTROS INSECTICIDAS
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Confirmacion de Envenenamiento
El borato puede medirse en el suero mediante un procedimiento
colorimetrico, asi tambien como por metodos espectrometricos atomicos de
alta temperatura. Las concentraciones de borato en la orina de personas no
expuestas fluctuan entre 0,004-.66 nig/dl. El promedio normal del nivel del
suero en los adultos es de hasta 0,2 mg/dl y en los ninos de hasta 0,125 mg/
dl.7 Los niveles informados en incidentes toxicos varian bastante, y debido a
ello se entiende que los niveles de suero son de poco valor en la decision de
la terapia a seguir.1
Tratamiento
1. Descontaminacion dermica. Elimine la contaminacion de la piel lavando
la zona afectada con agua y jabon, como fuera delineado en el Capitulo 2.Trate
la contaminacion ocular con enjuagues prolongados utilizando cantidades abun-
dantes de agua o solucion salina. Si persiste la irritacion, obtenga tratamiento
medico especializado.
2. Descontaminacion gastrointestinal. La descontaminacion gastrointestinal,
tal y como fuera delineada en el Capitulo 2, deberia ser considerada en casos de
envenenamientos agudos, de haberse ingerido una gran cantidad y si el pacien-
te es visto dentro de la primera hora despues de la exposicion. Es importante
recordar que el vomito y la diarrea son comunes y que el envenenamiento
severe podria estar asociado con convulsiones. Por lo tanto, la induccion de
emesis utilizando jarabe de ipecacuana es probablemente contraindicado en
este tipo de exposicion. La catarsis no es indicada si hay diarrea.
3. Fluidos intravenosos. Si la ingestion de borato ha sido masiva (varies gra-
mos) o se ha prolongado por varies dias, administre glucosa intravenosa y solu-
ciones electroliticas para mantener la excrecion urinaria del borato. Monitoree
el balance de los fluidos y los electrolitos sanguineos (incluida la capacidad del
bicarbonate) de manera regular.Vigile la condicion cardiaca con EGG. Realice
pruebas de orina para buscar proteinas y celulas a fin de detectar dano renal, y
monitoree la concentracion serica de borato. Si se detecta acidosis metabolica,
la misma puede tratarse con bicarbonate de sodio. Si se presenta un shock, tal
vez sea necesario administrar plasma o sangre total. Administre oxigeno conti-
nuamente. Si ocurre oliguria (menos de 25 a 30 ml de orina formada por hora)
baje la velocidad de los liquidos intravenosos, o bien, suspendalos para evitar
una sobrecarga en la circulacion. Este tipo de paciente debera ser referido a un
centre capaz de proveer terapia intensiva para pacientes en estado critico.
Productos Comerdales
(Continuation)
Cyrux
Demon
Flectron
Folcord
KafilSuper
NRDC 149
Polytrin
Siperin
Ustadd
otros
deltametrina
Decis
DeltaDust
DeltaGard
Deltex
Suspend
dimetrina
fenotrina (nr)
fenopropanato (nr)
fenpropatrina
Danitol
Herald
Meothrin
Rody
fenvalerato
Belmark
Fenkill
Sumicidin
flucitrinato
Cybolt
Fluent
Payoff
fluvalinato
furetrina (nr)
permetrina
Ambush
Dragnet
Eksmin
Elimite
Kafil
Nix
Outflank
Permasect
Perthrine
Pounce
Pram ex
Tal cord
otros
ftaltrina (nr)
resmetrina
Benzofuroline
Chrysron
Pynosect
(Continue en la pagina siguiente)
OTROS INSECTICIDAS
87
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Productos Comerdales
(Continuation)
tetrametrina
Neopynamin
tralometrina
SAGA
Tralex
PROPARGITA
Comite
Fenpropar
Omite
Ornamite
Mightikill
nr = no esta registrado o fue
retirado
4. Hemodialisis. Si se presenta insuficiencia renal, puede ser necesario efec-
tuar hemodialisis para mantener el balance de los liquidos y la composicion
normal del liquido extracelular. La hemodialisis ha tenido un exito limitado en
la evacuacion de boratos.1
5. La dialisis peritoneal ha sido efectuada en casos de envenenamientos con
borato5'12 y se siente que es tan efectiva, y aun hasta mas segura, que la transfu-
sion para la eliminacion de borato. No se ha efectuado un gran estudio en
cuanto a la eficacia, pero todavia continua siendo usada, aunque con menos
frecuencia que la hemodialisis.
6. Las convulsiones deberan ser controladas como fuera recomendado para
otros agentes y delineado en el Capitulo 2.
CLORDIMEFORMO
El clordimeformo es un ovicida y acaricida. Las formulaciones son con-
centrados emulsificables y polvos solubles en agua.
Toxicologia
En un episodic de exposicion ocupacional al clordimeformo, varies traba-
jadores desarrollaron hematuria. El origen de la sangre en la orina fue la cistitis
hemorragica, debida probablemente a productos de biodegradacion de la
cloroanilina. Los sintomas informados por los trabajadores afectados fueron:
hematuria, disuria, frecuencia y urgencia urinaria, secreciones por el pene, do-
lor abdominal y de la espalda, sensacion generalizada de "calor", somnolencia,
salpullido y descamacion cutanea, sabor dulce y anorexia. Los sintomas persis-
tieron de 2 a 8 semanas despues de fmalizada la exposicion.13 En un caso se
informo la metahemoglobilenia.14 El clordimeformo no es un inhibidor de la
colinesterasa. El clordimeformo ha sido voluntariamente retirado en los Esta-
dos Unidos debido a preocupacion por el aumento en la incidencia de cancer
de la vejiga en trabajadores de fabrica.
Confirmacion de Envenenamiento
Aunque existen metodos para medir los productos de excrecion urinaria,
los mismos no estan generalmente disponibles.
Tratamiento
1. Precauciones. Deben realizarse esfuerzos continues para evitar la inhalacion y
el contacto dermico con el clordimeformo porque la absorcion es muy eficiente.
PB
OTROS INSECTICIDAS
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2. Descontaminacion dermica. Lave la piel contaminada con agua y jabon,
como fuera delineado en el Capitulo 2. Trate la contaminacion ocular con
enjuagues abundantes de agua limpia o solucion salina. Si la irritacion persiste,
obtenga tratamiento medico especializado.
3. Descontaminacion gastrointestinal. Si el clordimeformo se ingirio me-
nos de una hora antes del tratamiento, debera considerarse la descontaminacion
gastrointestinal como fuera delineado en el Capitulo 2. La administracion de
dosis repetidas de carbon cada 2 a 4 horas puede ser benefica.
4. Hidratacion. Debido a que el catartico puede causar deshidratacion grave y
alteraciones electroliticas en niiios pequeiios, debera vigilarse el balance de flui-
dos y electrolitos en el suero. Mantenga un estado adecuado de hidratacion
mediante la administracion de liquidos orales y/o intravenosos para facilitar la
excrecion de clordimeformo.
5. Uroanalisis. Realice uroanalisis repetidos para buscar proteinas y eritrocitos,
y detectar danos en el tracto urinario. La desaparicion de la hematuria puede
esperarse entre 2 a 8 semanas. Una mejoria de los otros sintomas puede esperar-
se antes.
CLOROBENCILATO
El clorobencilato es un hidrocarburo clorado acaricida que se formula por
lo general como emulsion o polvo humectable para aplicarse en huertos. Su
uso ha sido descontinuado en los Estados Unidos.
Toxicologia
El clorobencilato es moderadamente irritante para la piel y los ojos. Aunque
el clorobencilato, desde el punto de vista estructural es similar al DDT, despues de
la absorcion se excreta mas rapidamente que este, principalmente en la orina
como derivados de la benzofenona y del acido benzoico. Con base en las obser-
vaciones efectuadas en animates a los que se les administro el compuesto, se infor-
ma que la absorcion de dosis extremas puede causar temblores, ataxia y debilidad
muscular. Se ha informado un caso humano de encefalopatia toxica despues de la
aspercion de un campo durante 14 dias, 10 horas por dia. El paciente no utilize
mascarilla durante la aspercion. Sus sintomas incluyeron dolor muscular, debili-
dad, fiebre y cambios en el estado mental, culminando con una convulsion toni-
co-clonica. El paciente se recobro sin secuela en 6 dias. El tratamiento incluyo
apoyo respiratorio y control de las convulsiones con fenobarbital y fenitoina.15
El clorobencilato no es un inhibidor de la colinesterasa.
OTROS INSECTICIDAS 89
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Tratamiento
1. Descontaminacion dermica. Lave la piel con agua yjabon, como fuera
delineado en el Capitulo 2.Trate la contaminacion ocular con enjuagues pro-
longados utilizando agua linipia o solucion salina. Si la irritacion persiste, ob-
tenga tratamiento medico especializado.
2. Descontaminacion gastrointestinal. Si se ingirio una cantidad grande de
clorobencilato unas cuantas horas antes del tratamiento, considere la desconta-
minacion gastrointestinal como fuera delineado en el Capitulo 2. Si la dosis de
clorobencilato absorbida fue pequena, el tratamiento se retrasa o el paciente
esta asintomatico, el manejo mas adecuado es administrar carbon activado y
sorbitol por via oral. No administre aceites ni grasas.
3. Convulsiones. Cualquier convulsion debera ser tratada tal y como fuera
delineado en el Capitulo 2.
CIHEXATIN
Toxicologia
El hidroxido de triciclohexil estano se formula como un polvo humectable
al 50% para controlar acaros en plantas ornamentales, lupulo, arboles de nogal y
algunos arboles frutales. Es moderadamente irritante en particular para los ojos.
Si bien se carece de informacion sobre la toxicidad sistemica de este compuesto
especifico del estaiio, es probable que el cihexatin pueda absorberse en cierto
grado a traves de la piel y que la absorcion de dosis sustanciales cause una lesion
en el sistema nervioso (consulte la seccion sobre compuestos organoestanicos
en el Capitulo 15: Fungicidas). El cihexatin ha sido voluntariamente retirado
en los Estados Unidos.
Tratamiento
1. Descontaminacion dermica. Lave la piel con agua y jabon. Trate la con-
taminacion ocular con enjuagues prolongados utilizando agua limpia o solu-
cion salina.
2. Descontaminacion gastrointestinal. El manejo de envenenamientos por
ingestion debera proceder asumiendo que el cihexatin es toxico, a pesar de que
los valores de la DL5Q en roedores son claramente elevados y de que no se ha
informado de envenenamientos en humanos. El tratamiento debera ser el mis-
mo utilizado para otros compuestos de organoestano.
PB OTROS INSECTICIDAS
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DIETILTOLUAMIDA (DEBT)
Este compuesto quimico se utiliza comunmente corno repelente liquido
de insectos, adecuado para aplicarse en la piel humana o las telas. Se formula en
una gran gama de concentraciones desde 5% (Offl, Skintastic for KidsR) hasta
10% (MuskolR). En comparacion con el uso difundido del producto, son relati-
vamente pocos los casos de toxicidad.16 Sin embargo, si se usa inapropiadamente,
se ingiere, o se utiliza una concentracion demasiado alt a en niiios, especialmen-
te de forma repetida sobre grandes superficies de la piel, existe el potencial para
toxicidad severa.17 La DEET se formula con alcohol etilico o isopropilico.
Toxicologia
For muchos anos, la dietiltoluamida ha sido eficaz y generalmente tolerado
muy bien como repelente de insectos aplicado a la piel humana, aunque des-
pues de aplicaciones repetidas causa hormigueo, irritacion leve y algunas veces
descamacion. En algunos casos, la DEET ha causado dermatitis por contacto y
exacerbacion de enfermedades cutaneas preexistentes.18> 19 Es muy irritante para
los ojos, pero no corrosiva.
Se han presentado efectos adversos graves cuando se ha utilizado en condi-
ciones tropicales y se ha aplicado en areas de la piel que se obstruyen durante el
sueno (en especial, en las fosas antecubital y poplitea). En estas condiciones, la piel
se torna roja y sensible, despues presenta ampollas y erosiones, dejando areas lasti-
madas y dolorosas que exudan y se curan con lentitud. La en ciertas ocaciones de
las reacciones mas severas dan por resultado cicatrices permanentes.20
La DEET es absorbida eficientemente por la piel y el intestino. Se han
informado concentraciones en la sangre de alrededor 0,3 mg/dl varias horas
despues de la aplicacion dermica de la manera prescrita.17La cantidad absorbida
aumenta segun incrementa la concentracion de DEET En adicion, muchas
formulaciones comerciales son preparadas con etanol como solvente, lo que
aumenta aun mas su absorcion.21 Las manifestaciones de encefalopatia toxica
han ocurrido aparentemente en raras ocasiones despues de la aplicacion dermica,
principalmente en niiios que fueron tratados intensivamente.22'23'24 La causa
mas frecuente de toxicidad sistemica lo ha sido la ingestion: deliberada en adul-
tos y accidental en los niiios pequenos.16'17
Las manifestaciones de encefalopatia toxica han sido alteraciones
conductuales incluyendo dolor de cabeza, inquietud, irritabilidad, ataxia, pron-
ta perdida de consciencia, hipotension y convulsiones. Algunos casos han mos-
trado paralisis flacida y arreflexia. Despues de la exposicion a grandes dosis, se
han presentado muertes.16'17'22 Los niveles de DEET en la sangre que se han
informado en envenenamientos sistemicos fatales han oscilado entre 168 a 240
miligramos por litro.17 La interpretacion de la toxicidad de la DEET en algunos
casos fatales se ha complicado por los efectos de la ingestion simultanea de
OTROS INSECTICIDAS 91
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etanol, tranquilizantes u otros medicamentos. Existe el informe de un caso bien
documentado de reaccion anafilactica a la DEBT. Un caso fatal de encefalopatia
en un nino heterocigoto en la deficiencia de ornitina carbamilo transferasa fue
similar al sindrome de Reyes, pero la apariencia postmortem del higado no fue
la caracteristica del sindrome.
Es importante ser precavido cuando se recomiende el uso de DEET a
personas que padecen de acne, psoriasis, predisposicion atopica u otra condi-
cion cronica de la piel. Esta sustancia no debe aplicarse en ninguna zona que
tenga la posibilidad de estar en contacto con otra area de la piel por un periodo
significative (fosas antecubital y poplitea, zonas inguinales).22
Es importante tomar grandes precauciones cuando se aplica DEET en ni-
iios. Debe evitarse la aplicacion repetida dia tras dia. Las aplicaciones deberan
limitarse a las areas expuestas de la piel, usando la menor cantidad posible del
repelente, y lavando despues del uso. No debe aplicarse a los ojos y la boca, y en
el caso de niiios pequenos, no debera aplicarseles en las manos. Las concentra-
ciones bajas (10% o menos) son efectivas y podrian preferirse en la mayoria de
las situaciones. Existen formulaciones marcadas para el uso por ninos. Las mis-
mas tienen concentraciones de 5 a 6,5% de DEET.25 Si se requiere una protec-
cion continua con el repelente, la DEET debe alternarse con un repelente que
tenga otro ingrediente active. Si se presenta dolor de cabeza o cualquier cambio
conductual o emocional, el uso de DEET debera descontinuarse de inmediato.
Confirmacion de Envenenamiento
Aunque existen metodos para medir el DEET en la sangre y tejidos y sus
metabolitos en la orina, por lo general no estan disponibles.
Tratamiento
1. Descontaminacion dermica. Lave la piel con agua y jabon, como fuera
delineado en el Capitulo 2.Trate la contaminacion ocular con enjuagues pro-
longados utilizando agua limpia o solucion salina. Si la irritacion persiste, ob-
tenga tratamiento medico especializado. Los medicamentos topicos con esteroides
y antihistaminicos orales han sido usados en las reacciones severas de la piel que
se presentan ocasionalmente despues de aplicar DEET21
2. Descontaminacion gastrointestinal. Si se ha ingerido una cantidad sus-
tancial de DEET una hora antes del tratamiento, debera considerarse la descon-
taminacion gastrointestinal como fuera delineado en el Capitulo 2. La induc-
cion de vomito es contraindicada en estos envenenamientos debido al rapido
inicio de convulsiones.
PB OTROS INSECTICIDAS
-------
3. Convulsiones. El tratamiento es primordialmente de apoyo, controlandose
las convulsiones con anticonvulsivantes, conio fuera delineado en el Capitulo 2.
Las personas que sobreviven a la ingestion de DEBT se recuperan, por lo gene-
ral en 36 horas o nienos.16'll
FLUORUROS
El fluoruro sodico es un mineral cristalino que se uso ampliamente en los
Estados Unidos para controlar larvas e insectos trepadores en casas, graneros,
almacenes y otras areas de deposito. Es altamente toxico para todo tipo de vida
animal y vegetal. El unico uso restante, para el cual esta permitido es el trata-
miento de madera.
El fluosilicato sodico (silicofluoruro de sodio) se usa para controlar
extoparasitos en el ganado, asi como insectos trepadores en casas y edificios de
trabajo. Es casi tan toxico como el fluoruro sodico. Todo su uso ha sido cance-
lado en los Estados Unidos.
El fluoaluminato de sodio (aluminofluoruro de sodio, criolita) es un mine-
ral estable que contiene fluor. Se utiliza como insecticida en algunos vegetales y
frutas. La criolita tiene muy baja solubilidad en agua, no produce iones defluoruro
al descomponerse y es de baja toxicidad para mamiferos, incluido el hombre.
El acido fluorhidrico es un toxico industrial importante, pero no se usa
como pesticida. El fluoruro de sulfurilo es discutido en el Capitulo 16:
Fumigantes.
Toxicologia
Cuando el fluoruro y fluosilicato sodico se utilizan como insecticidas re-
presentan un peligro toxico serio para los humanos, debido a su alt a toxicidad
intrinseca yala posibilidad de que los ninos que gatean o se arrastran en los
pisos de casas tratadas los ingieran.
La absorcion a traves de la piel es probablemente escasa y los metodos
relacionados con el uso del pesticida rara vez representan un peligro por inha-
lacion; sin embargo, la absorcion en el intestine del fluoruro ingerido es rapida
y potencialmente letal. La excrecion se realiza principalmente por la orina.
Durante las primeras 24 horas de intoxicacion, la excrecion renal del fluoruro
presente en la sangre es rapida. Sin embargo, los pacientes continuan excretando
grandes cantidades de fluoruro durante varies dias. Se cree que esto se deba a la
rapida union del fluoruro al deposito del cuerpo, probablemente a los huesos.
La liberacion subsecuente de fluoruro de los huesos es lo suficientemente gra-
dual como para no causar una recurrencia de toxicidad.26'27 Grandes cargas de
fluoruro envenenan las celulas de los tubulos renales y pueden causar alteracio-
nes tubulares funcionales y, a veces, insuficiencia renal aguda. Los ninos tendran
OTROS INSECTICIDAS 93
-------
una mayor absorcion esqueletica de fluoruro que los adultos, limitando de esa
forma la cantidad que los rinones tendran que manejar. A pesar de ello, los
ninos todavia se enfrentan a un gran riesgo debido a su masa de cuerpo mas
pequena en comparacion a la de los adultos en relacion a la cantidad ingerida.27
Los efectos toxicos del fluoruro en mamiferos son multiples y pueden ame-
nazar la vida. Con excepcion del efecto directo sobre el calcio ionizado en el
liquido extracelular, las acciones del fluoruro provienen de la inhibicion de
enzimas intracelulares criticas. La hipocalcemia ocurre con regularidad.26'28'29'30
El fluoruro ingerido tiene un efecto corrosive sobre la capa epitelial del
tracto gastrointestinal debido, en parte, al acido fluorhidrico altamente corrosi-
vo que se forma en el estomago. Los sintomas usuales son sed, dolor abdominal,
vomito y diarrea. La hemorragia en la mucosa gastrica, ulceracion, erosiones y
edemas son senales comunes.31
El ion fluoruro absorbido reduce las concentraciones de calcio y magnesio
en los liquidos extracelulares. Algunas veces la hipocalcemia origina tetania.30
Con frecuencia, las arritmias cardiacas y el shock son caracteristicas importantes
del envenenamiento severe. La hipotension y arritmias severas, en ocasion lle-
gan a originar fibrilacion ventricular.26'32 Estas posiblemente son el resultado de
la combinaciones de efectos de las alteraciones de liquidos y electrolitos, inclu-
yendo la hipercaliemia32 y de la accion directa del fluoruro en el corazon y los
tejidos vasculares. El fluoruro podria afectar directamente el sistema nervioso
central, resultando en dolores de cabeza, debilidad muscular, estupor, convul-
siones y coma.26'27'28 La falla respiratoria y las arritmias ventriculares son causas
comunes de muerte.26'27
Confirmacion de Envenenamiento
Las concentraciones de fluoruro inorganico en el plasma de la poblacion
general que toma agua con una concentracion de Img por litro fluctuan entre
0,01 y 0,03 mg por litro28 y rara vez exceden a los 0,10 mg por litro. En casos
fatales de envenenamiento, se han registrado niveles plasmaticos de 3,5 mg por
litro y mas, aunque se ha informado acerca de la sobrevivencia de pacientes con
niveles de hasta 14 mg por litro.26'28
Tratamiento: Intoxicacion por Fluoruros
1. Descontaminacion dermica. Lave la piel con agua y jabon, como fuera
delineado en el Capitulo 2.Trate la contaminacion ocular, con enjuagues pro-
longados utilizando abundante agua limpia o solucion salina. Si la irritacion
persiste, obtenga tratamiento medico especializado.
PB OTROS INSECTICIDAS
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2. Descontaminacion gastrointestinal. Si se ha ingerido fluoruro sodico
o fluosilicato de sodio, debera considerarse la descontaminacion gastrica
como fuera delineado en el Capitulo 2.
Si la victima esta embotada, o si el vomito imposibilita la administracion
oral, proteja la via aerea por intubacion endotraqueal. Despues, intube el esto-
mago con cuidado y lavelo con varias onzas de los liquidos senalados abajo. El
carbon activado no capta el ion fluoruro y, por lo tanto, no tiene ningun valor
en envenenamiento con fluoruros.
3. Calcio y magnesio. Si la victima esta completamente alerta y el vomito no
impide totalmente la ingestion de un agente neutralizante, administre de inme-
diato por via oral,leche, gluconato calcico o citrato magnesico,los cuales
precipitaran la mayor parte del ion fluoruro que se encuentra en el intestine y,
por consiguiente, pueden salvar la vida. La leche provee el ion calcio que se
unira al fluoruro, reduciendo asi su absorcion. Los antiacidos a base de magnesio
tambien han sido utilizados para neutralizar el acido y facilitar la produccion de
sales pobremente absorbidas.26 No existe informacion disponible acerca de las
cantidades optimas a ser administradas.
4. Analisis de sangre. Obtenga una muestra de sangre para realizar el analisis
serico de electrolitos en sodio, potasio, calcio, magnesio, fluoruro y la capacidad
de bicarbonate. Obtenga otra muestra para llevar a cabo la tipificacion y clasifi-
cacion de la sangre en caso de que haya necesidad de efectuar una transfusion
san guinea.
5. Fluidos intravenosos. Inicie la administracion de fluidos intravenosos (ini-
cialmente dextrosa al 5% en solucion salina al 0,9%) para combatir la deshidra-
tacion, shock y acidosis metabolica. Monitoree muy de cerca el balance de los
fluidos para prevenir una sobrecarga, en caso de insuficiencia renal. Si llega a
detectar acidosis metabolica, administre bicarbonate de sodio para mantener la
orina alcalina, ya que esto puede acelerar la excrecion.27 Detenga la administra-
cion de fluidos intravenosos en caso de anuria u oliguria (menos de 25 a 30 ml
por hora).
6. La hemodialisis debera reservarse para casos en que se presenten problemas
en la funcion renal.26
7. Monitoree el estado cardiaco a traves de electrocardiografia continua. Las
arritmias ventriculares pueden necesitar cardiversion CD.
S.Tetania. En caso de que se presente tetania evidente o latente o se demuestre
hipocalcemia, o se haya absorbido una cantidad importante de fluoruro, admi-
nistre 10 ml de gluconato de calcio al 10% por via intravenosa, a no mas de
1 ml por minuto.
OTROS INSECTICIDAS 95
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Dosificacion de Gluconato de Calcio
Provista corno 100 mg/ml (solucion al 10%)
Adultos y ninos mayores de 12 anos: 10 ml de la solucion al 10%, admi-
nistrada lentamente por via intravenosa. Repetir de ser necesario.
Ninos menores de 12 afios: 200 a 500 mg/kg/24 horas dividido Q6
horas. Para detencion cardiaca, 100 mg/kg/dosis. Repetir la dosifi-
cacion de ser necesario.
9. Oxigeno debera ser administrado por mascarilla en caso de hipotension,
shock, arritmias cardiacas o cianosis. El shock puede requerir la administracion
de plasma o sangre.
10. Quemaduras por acido. Debido a que estos compuestos pueden causar
quemaduras severas al esofago y estomago, los pacientes deberan ser referidos
para evaluacion quirurgica y endoscopia. Si se documentan quemaduras, el tra-
tamiento para las quemaduras por acido debera ser efectuado por un cirujano o
gastroenterologo.
Tratamiento: Fluoaluminato Sodico (Criolita)
La criolita es mucho menos toxica que los demas fluoruros. Si se ha inge-
rido una cantidad considerable, seria apropiado medir el calcio en el suero para
asegurarse que no haya ocurrido hipocalcemia. De ser asi, seria indicado admi-
nistrar gluconato de calcio por via intravenosa al 10% (vease el inciso 8). Es
improbable que se requiera tratamiento para envenenamiento por fluoruro luego
de la ingestion de fluoaluminato de sodio.
COMPUESTOS HALOAROMATICOS
DE UREASUSTITUIDA
El diflubenzuron es una urea aromatica sustituida que controla los insectos
y evita el deposito de quitina en el exoesqueleto de la larva. Se formula en
polvos humectables o en concentrados oleosos capaces de dispersarse, asi como
en granules para uso en agricultura, silvicultura y lugares donde las poblaciones
de moscas tienden a ser grandes, como en corrales de engorde. El teflubenzuron
es otro insecticida haloaromatico de urea sustituida, con propiedades toxicologicas
similares.
PB OTROS INSECTICIDAS
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Toxicologia
Existe absorcion limitada del diflubenzuron a traves de la piel y la capa
intestinal de los mamiferos, despues de la cual la hidrolisis enzimatica y la ex-
crecion eliminan con rapidez el pesticida de los tejidos. No se informan efectos
irritantes y la toxicidad sistemica es baja. La metahemoglobinemia es un riesgo
teorico de la cloroanilina que se forma por hidrolisis, pero esta forma de toxi-
cidad no se ha informado en humanos o animales a causa de la exposicion a
diflubenzuron. El teflubenzuron tambien informa una toxicidad sistemica baja.
Tratamiento
1. Descontaminacion dermica. Lave la piel con agua yjabon, como fuera
delineado en el Capitulo 2. Trate la contaminacion ocular con enjuagues
prolongados utilizando abundante agua limpia o solucion salina. Si persiste la
irritacion, obtenga tratamiento medico especializado. Las reacciones de
sensibilizacion pueden requerir terapia con esteroides.
2. Descontaminacion gastrointestinal. Si se han ingerido grandes cantida-
des de propargita y el paciente es visto dentro de una hora, debera considerarse
la descontaminacion gastrointestinal. Si la cantidad ingerida fue poca, debera
considerarse la administracion oral de carbon activado y sorbitol.
METOPRENO
El metopreno es un ester de hidrocarburo de cadena larga active como
regulador del crecimiento de los insectos. Es efectivo contra diferentes especies
de insectos. Las formulaciones incluyen briquetas de accion retardada (escape
lento), aerosoles, rociadores y carnadas.
Toxicologia
El metopreno no es ni irritante ni sensibilizador en los humanos o anima-
les de laboratorio. La toxicidad sistemica en los animales de laboratorio es leve.
No se han informado envenenamientos humanos o reacciones adversas en tra-
baj adores expuestos al mismo.
Tratamiento
1. Descontaminacion dermica. Lave la piel contaminada con agua y jabon.
Trate la contaminacion ocular con enjuagues utilizando abundante agua limpia
o solucion salina. Si la irritacion persiste, obtenga tratamiento medico.
OTROS INSECTICIDAS 97
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2. Descontaminacion gastrointestinal. Si se ha ingerido una cantidad grande
de methoprene, puede considerarse la administracion oral de carbon.
PROPARGITA
La propargita es un acaricida con accion residual. Las formulaciones son
polvos humectables y concentrados emulsificables.
Toxicologia
La propargita tiene una toxicidad sistemica muy baja en animales. No se
han informado envenenamientos sistemicos en humanos. Sin embargo, muchos
trabajadores que han tenido contacto dermico con este acaricida han sufrido
irritacion cutanea y, en algunos casos, posiblemente sensibilizacion.33 Tambien
se ha presentado irritacion ocular. For esta razon se deben tomar medidas es-
trictas para evitar la inhalacion o cualquier contaminacion de la piel o de los
ojos por propargita.
Confirmacion de Envenenamiento
No existe ningun metodo facilmente disponible para detectar la absorcion
de propargita.
Tratamiento
El tratamiento para la contaminacion e ingestion debera proceder esencial-
mente de la manera delineada para los haloaromaticos de urea sustituida.
PIRETROIDES
Estos insecticidas sinteticos modernos son similares, quimicamente a las
piretrinas naturales, pero las estructuras basicas han sido modificadas para
incrementar su estabilidad en el ambiente natural. En la actualidad, se utilizan
ampliamente en la agricultura, en casas y jardines, y para el tratamiento de
enfermedades por extoparasitos.
Los piretroides se formulan como concentrados emulsificables, polvos
humectables, granules y concentrados para aplicacion en volumen ultra bajo.
En el producto tecnico pueden estar combinados con otros pesticidas (algunas
veces altamente toxicos), o bien, ser mezclados en el momento de la aplicacion
con otros pesticidas en el tanque. El AASTAR (descontinuado en 1992), por
ejemplo, es una combinacion de flucitrinato y forato, este ultimo, un
PB OTROS INSECTICIDAS
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organofosfatado altamente toxico. El Nix y Elimite son cremas de permetrina
aplicadas para el control de extoparasitos en humanos.
Toxicologia
Ciertos piretroides presentan una gran neurotoxicidad en animales de la-
boratorio cuando se administran por inyeccion intravenosa, y otros son toxicos
por via oral, pero la toxicidad sistemica por inhalacion y absorcion dermica es
baja. Aunque la absorcion limitada puede ser responsable de la baja toxicidad de
algunos piretroides, el factor principal de este fenomeno puede ser la rapida
biodegradacion por las enzimas hepaticas de los mamiferos (hidrolisis y oxida-
cion de esteres).34 La mayoria de los metabolites de los piretroides se excretan
con rapidez, al rnenos en parte, por el rinon.
La toxicidad mas severa, aunque menos comun, lo es al sistema nervioso
central. Se han informado convulsiones en casos de intoxicacion severa por
piretroides. De 573 casos revisados en China, 51 mostraron alteracion de la
consciencia y 34 mostraron convulsiones. De esos, solo 5 se debieron a la expo-
sicion ocupacional.35 Las convulsiones son mas comunes en la exposicion mas
toxicos, ciano-piretroides, entre los cuales se encuentran el fenvalerato,flucitrinato,
cipermetrina, deltapermetrina y fluvalinato.34 No existen informes de convul-
siones en humanos debido a la exposicion a la permetrina.
Ademas de la neurotoxicidad sistemica, algunos piretroides causan parestesia
en humanos, cuando los materiales liquidos o volatiles entran en contacto con
la piel. Nuevamente, estos sintomas son mas comunes en la exposicion a los
piretroides cuyas estructuras incluyen grupos ciano.34 Las sensaciones se han
descrito como picazon, ardor, comezon y hormigueo, que avanza hasta entu-
mecimiento.35'36> 37 La piel de la cara parece ser el lugar mas afectado, pero
algunas veces estas sensaciones aparecen en las manos, antebrazos y cuello. La
transpiracion, la exposicion al sol o al calor y la aplicacion de agua incrementan
las sensaciones desagradables. Algunas veces el efecto se nota minutos despues
de la exposicion, pero es mas comun que los sintomas aparezcan 162 horas
despues.36'37 Las sensaciones rara vez persisten mas de 24 horas. Cuando se
informa parestesia, no se presenta reaccion inflamatoria o esta es leve. Se supone
que el efecto es el resultado del contacto del piretroide con las terminaciones
nerviosas sensoriales de la piel. La reaccion parestesica no es de naturaleza alergica,
aunque se han informado respuestas alergicas como un fenomeno indepen-
diente de la exposicion a los piretroides. La raza, el tipo de piel o la predisposi-
cion a una enfermedad alergica no afecta la probabilidad de la reaccion o su
severidad.
Las personas tratadas con permetrina para controlar piojos o infestaciones de
moscas experimentan, a veces, comezon y ardor en el lugar de la aplicacion,
aunque esto es, fundamentalmente, una exacerbacion de las sensaciones causadas
por los parasites mismos y no es tipica de la reaccion parestesica antes descrita.
OTROS INSECTICIDAS 99
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Otras senales y sintomas de toxicidad incluyen sensacion facial anormal,
desequilibrio, salivacion, dolor de cabeza, fatiga, vomito, diarrea e irritabilidad
al tacto y al sonido. En casos mas severos puede desarrollarse la edema pulmonar
y las fasciculaciones musculares.35 Debido a la inclusion de ingredientes solven-
tes especiales, algunas formulaciones de fluvalinato son corrosivas para los ojos.
Los piretroides no son inhibidores de la colinesterasa. Sin embargo, han habido
casos en los cuales el envenenamiento por piretroides ha sido mal diagnosticado
como envenenamiento por organofosfatos, debido a los sintomas similares de
presentacion, y algunos pacientes han muerto de toxicidad atropinica.35
Tratamiento
1. Descontaminacion dermica. Lave la piel inmediatamente con agua y
jabon, como fuera delineado en el Capitulo 2. Si aparecen efectos parestesicos o
irritantes, obtenga tratamiento medico. Debido a que la volatilizacion del
piretroide explica, en apariencia, la parestesia que afecta la cara, tome medidas
energicas (ventilacion, mascarilla para proteger la cara y campana) a fin de evi-
tar el contacto del vapor con la cara y los ojos. Las preparaciones oleosas de
vitamina E (acetato de dl-alfa tocoferilo) son muy eficaces para prevenir la
reaccion parestesica y detenerla.37'38 Las mismas seguras y pueden aplicarse a la
piel en condiciones de campo. El aceite de maiz es mas o menos eficaz, pero
pueden surgir efectos colaterales debido a su uso continuo, lo que no lo hace
muy adecuado. La vaselina es menos eficaz que el aceite de maiz, y el oxido de
zinc de hecho empeora la reaccion.
2. Contaminacion ocular. Algunos piretroides pueden ser muy corrosives a
los ojos. Deberan tomarse medidas extraordinarias para evitar la contaminacion
ocular. Trate de inmediato la contaminacion ocular enjuague prolongado con
abundante agua limpia o solucion salina. Si la irritacion persiste, obtenga aten-
cion oftalmologica especializada.
3. Descontaminacion gastrointestinal. Si el paciente ha ingerido grandes
cantidades de piretroides, especialmente de aquellos cuyas estructuras incluyen
grupos ciano, y es visto poco tiempo despues de la exposicion, considere la
descontaminacion gastrointestinal como fuera delineado en el Capitulo 2. Ba-
sado en observaciones de animates de laboratorio34 y humanos35, las grandes
ingestiones de aletrina, cismetrina, fluvalinato, fenvalerato o deltametrina serian
las que con mayor probabilidad causaran manifestaciones neurotoxicas.
Si se han ingerido cantidades pequenas de piretroides, o si se ha retrasado el
tratamiento, el manejo mas adecuado es administrar de inmediato carbon acti-
vado por via oral y un catartico. No administre un catartico si el paciente tiene
diarrea o una obstruccion intestinal.
PB OTROS INSECTICIDAS
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4. Otros tratamientos.Varies medicamentos son eficaces para aliviar las mani-
festaciones neurotoxicas por piretroides que se observan en animales de laborato-
rio envenenados deliberadamente. Ninguno se ha probado en envenenamientos
en humanos. Por consiguiente, no se conoce su eficacia ni seguridad en estas
circunstancias. Ademas, es probable que los sintomas y senales neurotoxicos mo-
derados, si es que aparecen, desaparezcan de manera espontanea.
5. Convulsiones. Cualquier convulsion debera ser tratada como fuera deli-
neado en el Capitulo 2.
AZUFRE
El azufre elemental es un acaricida y fungicida utilizado ampliamente en
huertos, plantas ornamentales, vegetales, granos y otros cultivos. Se prepara como
polvo en varies tamanos de particulas y se aplica asi, o bien, se formula con
varies minerales para mejorar la fluidez o se aplica como una emulsion acuosa
o polvo humectable.
Toxicologia
El azufre elemental es moderadamente irritante para la piel y esta asociado
a la dermatitis irritante por exposicion ocupacional.39 Cuando se encuentra
como polvo en el aire, irrita los ojos y el tracto respiratorio. En ambientes
soleados y calurosos puede presentarse alguna oxidacion del azufre depositado
en el follaje para dar oxidos de azufre gaseosos, que pueden causar una fuerte
irritacion en los ojos y el tracto respiratorio.
El polvo de azufre ingerido funciona como catartico y se ha utilizado como
medicamento (en general con melazas) para este proposito. Se forma algo de
acido sofihidrico en el intestino grueso,lo que puede presentar un cierto grado
de peligro toxico. El olor caracteristico a huevos podridos puede ayudar en el
diagnostico. Un adulto sobrevivio a una ingestion de 200 gramos de azufre.40
El intestino absorbe con rapidez el azufre coloidal que se ha ingerido, el
cual se excreta con rapidez por la orina como sulfato inorganico.
Tratamiento
1. Descontaminacion dermica. Lave la piel con agua y jabon.Trate la con-
taminacion ocular con enjuagues prolongados utilizando agua limpia o solu-
cion salina. Si persiste la irritacion, obtenga cuidado oftalmologico.
2. Descontaminacion gastrointestinal. A menos que se haya ingerido una
cantidad extraordinaria de azufre (varies gramos) inmediatamente antes del
OTROS INSECTICIDAS 101
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tratamiento, es probable que no exista la necesidad de vaciar el estomago. No se
ha probado la capacidad de absorcion de carbon activado para el azufre.
Una de las consecuencias mas graves de la ingestion del azufre es su efecto
catartico que causa deshidratacion y baja en los electrolitos, en particular en los
ninos. Si la diarrea es severa, es conveniente administrar glucosa y/o soluciones
electroliticas, ya sea por via oral o intravenosa.
Referencias
1. Litovitz TL, Klein-Schwartz W, Oderda GM, and Schmitz BE Clinical manifestations of
toxicity in a series of 784 boric acid mgestions.AmJEmerg Med 1988;6(3):209- 13.
2. Restuccio A, Mortensen ME, and Kelley MT. Fatal ingestion of boric acid in an adult. Am]
Emerg Med 1992;10(6):545-7.
3. IshiiY, 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 EC, Heimbach MD,Truscott DR, and Duncan BD. Boric acid poisoning. Can Med
Assocjl964;90:1018-23.
6. Ducey J andWilliams 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. CHn
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. BrJInd Med 1992;49:706-13.
9. Garabrant DH, Bernstein L, Peters JM, et al. Respiratory effects of borax dust. BrJ Ind Med
1985;42:831-7.
10. Schillinger BM, Berstein M, Goldbert LA, and Shalita AR. Boric acid poisoning.J Am Acad
Demwto/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. SegarWE. 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(ll):1052-5.
14. ArimaT, Morooka H.TanigawaT, et al. Methemoglobinemia induced by chlorphenamidine.
Ada Med Okayama 1976;30:57-60.
15. Ravindran M.Toxic encephalopathy from chlorobenzilate poisoning: Report of a case. Clin
Electroencephalogrl91%;9(4):\10-2.
16. Veltri JC, OsimitzTG, Bradford DC, et al. Retrospective analysis of calls to poison control
centers resulting from exposure to the insect repellent N, N-diethyltoluamide (DEBT) from
1985-1989. ClinToxicol 1994;32:1.
17. Tenebein M. Severe toxic reactions and death following ingestion of diethyltoluamide-con-
taining insect repellents J>1M>1 1987;258:1509.
18. Maibach HI and Johnson HL. Contact urticaria syndrome. Arch Demiatol 1975;111:726.
19. Wantke F, Focke M, HemmerW, et al. Generalized urticaria induced by a diethyltoluamide-
containing insect repellent in a child. Contact Dermatitis 1996;35(3):186.
PB OTROS INSECTICIDAS
-------
20. Reuveni H.andYagupsky P. Diethyltoluamide-containing insect repellent: Adverse effects in
worldwide use. Arch Dermatol1982;! 18:582.
21. Stinecipher J and Shaw J. Percutaneous permeation of N,N-diethyl-m-toluamide (DEBT)
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
repeUent 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. YolkenR.Konecny P, and McCarthy P. Acute fluoride poisoning. Pediatrics 1976;58(l):90-3.
27. Heifetz SB and Horowitz HS. Amounts of fluoride in self-administered dental products:
Safety considerations for children. Pediatrics 1986;77(6):876-82.
28. Gessner BD, Beler M, Middaugh JP, andWhitford GM. Acute fluoride poisoning from a
public water system. New EnglJMed 1994;330(2):95-9.
29. Swanson L, Filandrinos DT, Shevlin JM, andWillett 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, Sjostedt S, Eleborg L, et al. Tissue response of gastric mucosa after ingestion of
fluoride. Br Med] 1989;298:1686-7.
32. Baltazar RD, Mower MM, Reider R, et al. Acute fluoride poisoning leading to fatal hyper-
kalemia. Chest 1980;78:660.
33. Saunders LD, Ames RG, Knaak JB, et al. Outbreak of omite-cr-induced dermatitis among
orange pickers inTulare County, California. J Occup Med 1987;29:409-13.
34. Dorman DC and BeasleyVR. 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 poison-
ing. Arch Toxicol 1989;63:54-8.
36. Tucker SB and Flannigan SA. Cutaneous effects from occupational exposure to fenvalerate.
ArchToxicol 1983;54:195-202.
37. Flannigan SA,Tucker SB, Key MM, et al. Synthetic pyrethroid insecticides: Adermatological
evaluation. BrJInd Med 1985;42:363-72.
38. Tucker SB, Flannigan SA, and Ross CE. Inhibitions of cutaneous paresthesia resulting from
synthetic pyrethroid exposure. IntJ 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.
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Seccion III
HERBICIDAS
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CAPITULO 9
PUNTOS
IMPORTANTES
Senales y Smtomas:
Irritante para la piel y las
membranas mucosas
Vomito, diarrea, dolor de
cabeza, confusion,
conducta extrana o
agresiva, olor peculiar en el
aliento
Acidosis metabolica, fallo
renal y taquicardia
Tratamiento:
Enjuague,
descontaminadon
gastrointestinal
Administradon de Ifquidos
por via intravenosa
Diuresis alcalina forzada
Herbicidas Clorofenolicos
Algunos compuestos clorofenolicos se rnezclan en ocasiones en fertilizantes
comerciales para controlar el crecimiento de hierbas de hoja ancha. Cientos de
productos comerciales contienen herbicidas clorofenolicos en varias formas,
concentraciones y combinaciones. En algunos casos, se usa el mismo nombre
para productos con diferentes ingredientes; por lo tanto, la composicion exacta
debe consultarse en la etiqueta del producto. Las sales de sodio, potasio y
alquilamina se formulan comunmente como soluciones acuosas, mientras que
los esteres menos solubles en agua se aplican como emulsiones. Los esteres de
bajo peso molecular son mas volatiles que los acidos, las sales o los esteres de
cadena larga.
Toxicologia
Algunos de los acidos clorofenolicos, sus sales y esteres son irritantes
moderados a la piel, ojos y mucosas respiratoria y gastrointestinal. En algunas
personas, ha ocurrido despigmentacion local aparentemente por contacto
dermico prolongado con compuestos clorofenolicos.
Los compuestos clorofenolicos se absorben a traves del tracto gastrointestinal.1
Se absorben menos a traves del pulmon. La absorcion cutanea parece ser mini-
ma.2 Los compuestos no se almacenan en la grasa de manera significativa. La
excrecion ocurre casi totalmente por la orina. Aparte de que se presenta alguna
conjugacion de los acidos, la biotransformacion en el cuerpo es limitada.1'2 Los
compuestos tienen una alta fijacion a las proteinas.2 La vida media del 2,4-D en el
humano es de unas 13 a 39 horas,1'3'4'5 mientras que el del 2,4,5-T es de unas 24
horas. La excrecion es incrementada en la orina alcalina,4'5> 6 y su vida media es
prolongada a 70 a 90 horas en la orina acidica.6 La vida media es tambien mayor
como resultado de grandes dosis y exposicion prolongada.
Cuando se administran grandes dosis a animates experimentales, el 2,4-D
causa vomito, diarrea, anorexia, perdida de peso, ulceras en la boca y laringe, y
dano toxico al higado, rinones y sistema nervioso central. Se desarrolla miotonia
(rigidez e incoordinacion de las extremidades posteriores) en algunas especies,
aparentemente por dano en el sistema nervioso central. Se ha observado
desmieliniacion en la parte dorsal de la medula espinal y los cambios en el EEG
indican alteraciones funcionales cerebrales en animates experimentales a los
que se administran dosis elevadas.
PB
HERBICIDAS
CLOROFENOLICOS
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La ingestion de grandes cantidades de acidos clorofenolicos por hurnanos
ha dado corno resultado acidosis metabolica severa. Tales casos se han asociado
con cambios electrocardiograficos, miotonia, debilidad muscular, mioglobinuria
y una elevacion de la creatina-fosfoquinasa en el suero;todo ello refleja dano en
los musculos estriados. Los acidos clorofenolicos son desacopladores debiles de
la fosforilacion oxidante, por lo que dosis muy elevadas pueden producir hiper-
termia por incremento de la produccion de calor corporal.5
En la produccion de algunos de estos herbicidas pueden formarse otras
substancias aun mas toxicas debido a temperaturas excesivas. Estos incluyen
cloro-dibenzo-dioxinas (CDD- por sus siglas en ingles) y cloro-dibenzo-furanos
(CDF- por sus siglas en ingles). El compuesto 2,3,7,8-tetra-CDD es extraordi-
nariamente toxico para multiples tejidos de mamiferos y se forma en la sintesis
del 2,4,5-T. Los compuestos hexa-,hepta- y octaclorados muestran menos toxi-
cidad sistemica, pero son la causa mas comun del cloracne (una condicion cro-
nica y desfigurante de la piel) que se observa en personas que trabajan en la
elaboracion del 2,4,5-T y otros compuestos organicos dorados.7 A pesar de
que los efectos toxicos, sobre todo el cloracne, se han observado en trabajadores
de las plantas de produccion, estos efectos no han aparecido en formuladores o
aplicadores expuestos con regularidad al 2,4,5-T u otros compuestos
clorofenolicos. En los Estados Unidos se cancelaron todos los usos del 2,4,5-T.
La literatura medica contiene algunos informes sobre la presencia de neuropatia
periferica despues de exposiciones cutaneas leves al 2,4-D.8 No es seguro que
estos individuos no hayan estado expuestos a otros neurotoxicos. Se administra-
ron dosis unicas de 5 mg/kg de peso corporal del 2,4-D y del 2,4,5-T a personas
sin que se observaran efectos adversos. Un individuo consumio 500 mg de 2,4-D
por dia durante 3 semanas sin experimentar sintomas o seiiales de enfermedad.
Productos Comerdales
acido 2,4-didorofenoxiacetico
(2,4-D)
acido 2,4-didorofenoxipropionico
(2,4-DP)
dicloroprop
acido 2,4-didorofenoxibutirico
(2,4-DB)
acido 2,4,5-tridorofenoxiacetico
(2,4,5-T)
MCPA
MCPB
mecorprop (MCPP)
acido 2-metilo-3, 6-
diclorobenzoico
Banvel
Dicamba
Sehales y Sintomas de Envenenamiento
Los compuestos clorofenolicos son moderadamente irritantes a la piel y las
membranas mucosas. La inhalacion de sus aerosoles puede causar sensaciones
de quemadura en el tracto nasofaringeo y en el pecho, ademas de provocar tos.
Algunas veces la inhalacion prolongada causa vertigo. Los adyuvantes quimicos
que se anaden para incrementar la penetracion del herbicida al follaje pueden
explicar los efectos irritantes de algunas formulaciones.
Las manifestaciones de la toxicidad sistemica de los compuestos clorofenolicos
se conocen principalmente por la experiencia medica en los casos de ingestion
deliberada suicida de grandes cantidades. La mayoria de los informes de muertes
envuelven fallo renal, acidosis, desbalance de electrolitos, y como resultado un
fallo de multiples organos.3'6'9 Los agentes que con mayor frecuencia han estado
envueltos en estos incidentes han sido el 2,4-D y el mecroprop. Los efectos toxi-
cos de otros compuestos clorofenolicos pueden ser similares, pero no identicos.
HERBICIDAS
CLOROFENOLICOS 107
-------
Pocas horas despues de la ingestion, los pacientes presentaran un cuadro de
vomito, diarrea, dolor de cabeza, confusion y conducta extrana o agresiva. En
los casos severos, ocurrira cambio en el estado mental, el cual progresara hasta
una coma.4'5'6 A menudo se nota un olor peculiar en el aliento. La temperatura
corporea puede subir un poco, pero rara vez se trata de una caracteristica del
envenenamiento que ponga en riesgo la vida. El ritmo respiratorio no se en-
cuentra deprimido. Sin embargo, en algunos casos la hiperventilacion es evi-
dente, probablemente como consecuencia de la acidosis metabolica que tiene
lugar. Se ha informado debilidad muscular y neuropatia periferal luego de la
exposicion ocupacional.6 Es muy raro que ocurran convulsiones. Si la excre-
cion urinaria del toxico es eficaz, por lo general se recupera la consciencia entre
48 y 96 horas despues.4'5'6
Como se mencionara anteriormente, los compuestos clorofenolicos cau-
san cambios metabolicos significativos. La acidosis metabolica se manifiesta en
un bajo contenido de pH arterial y bicarbonate. La orina es en general acidica.
Si se presenta la lesion en musculos esqueleticos, se refleja en una elevacion de
la creatina-fosfoquinasa y, algunas veces, en mioglobinuria. Cuando se elimina
el producto toxico, por lo general se encuentran elevaciones moderadas tem-
porales de nitrogeno ureico y de la creatinina serica. Se han informado casos de
fallo renal, los cuales a menudo han ido acompanados de hipercalemia o
hipocalcemia que se cree fue el resultado de la inestabilidad cardiovascular que
llevo a la muerte.3'9 Se ha observado taquicardia y bradicardia, y tambien se ha
informado hipotension.3'4'6 Tambien se ha observado el aplanamiento e inver-
sion de la onda T.5 Se ha informado leucocitosis leve y cambios bioquimicos
indicadores de dano celular hepatico.
La miotonia y la debilidad muscular pueden persistir durante meses des-
pues de un envenenamiento agudo. Los estudios electromiograficos y de con-
duccion nerviosa en algunos pacientes en convalecencia han demostrado una
neuropatia proximal leve y miopatia.
Confirmacion de Envenenamiento
Se cuenta con metodos de cromatografia gas-liquido para detectar y medir
los compuestos clorofenolicos en sangre y orina. Estos analisis son utiles para
confirmar y evaluar la magnitud de la absorcion de estas sustancias. Los envene-
namientos caracterizados por inconsciencia han mostrado concentraciones ini-
ciales de compuestos clorofenolicos en la sangre que van desde 80 a mas de
1.000 mg por litro.4 Las muestras de orina deben obtenerse tan pronto como
sea posible despues de la exposicion, debido a que bajo condiciones normales,
los herbicidas pueden excretarse totalmente entre las 24 y 72 horas. Los uroanalisis
tambien pueden confirmar una exposicion excesiva. En un estudio de aplicadores
de herbicidas asintomaticos, la excrecion de compuestos clorofenolicos rara-
mente excedio 1 a 2 mg/L.10 La vida media podria ser mucho mayor en casos
de intoxicacion, dependiendo del grado de absorcion y del pH urinario.
HERBICIDAS
PB CLOROFENOLICOS
-------
Los analisis pueden efectuarse en laboratories especiales que usualmente
son conocidos conio centres locales para el control de envenenamientos. Si las
circunstancias indican con bastante certeza que se ha presentado una exposi-
cion excesiva a compuestos clorofenolicos, inicie de inmediato las medidas de
tratamiento. No espere a que la absorcion del toxico se confirme por la via
quimica.
Tratamiento
1. Precauciones. Personas con enfermedades cutaneas cronicas o sensibilidad
a estos herbicidas deberan evitar usarlos o tornar estrictas precauciones para
evitar el contacto (respirador, guantes, etc.).
2. Proteccion respiratoria. Si se presenta cualquier sintoma de enfermedad
durante o despues de la inhalacion de aerosol, aleje a la victima del contacto
con el material durante por lo rnenos 2 a 3 dias. Permita el contacto posterior
con compuestos clorofenolicos solamente si se practica la proteccion respirato-
ria adecuada.
3. Descontaminacion dermica. Enjuague los agentes contaminantes de los
ojos con cantidades abundantes de agua limpia durante 10 a 15 minutos. Si la
irritacion persiste, debera efectuarse un examen oftalmologico.
4. Descontaminacion gastrointestinal. Si se han ingerido cantidades
substanciales de compuestos clorofenolicos, puede presentarse vomito esponta-
neo. Los procedimientos para la descontaminacion gastrointestinal pueden ser
considerados, como fuera delineado en el Capitulo 2.
5. Liquidos intravenosos. Administre liquidos intravenosos para acelerar la
excrecion del compuesto clorofenolico y limitar la concentracion del toxico
en el rinon. Es deseable un flujo urinario de 4 a 6 ml/minuto. La administra-
cion de solucion salina/dextrosa por via intravenosa ha sido suficiente para
rescatar a pacientes comatosos que ingirieron 2,4-D y mecoprop varias horas
antes de entrar al hospital.
Advertencia: Monitoree cuidadosamente las proteinas y celulas urinarias,
nitrogeno ureico sanguineo, creatinina serica, electrolitos sericos e ingresos/
egresos de liquidos para asegurarse que la funcion renal no se ha danado y que
no se presenta una sobrecarga de liquidos.
6. Diuresis. La diuresis forzada alcalina se ha utilizado con exito para manejar
las ingestiones suicidas de compuestos clorofenolicos, especialmente cuando se
inicia temprano.4'5'6 Si se alcaliniza la orina incluyendo bicarbonate de sodio
(44 a 88 mEq por litro) en la solucion intravenosa, al parecer se acelera la
HERBICIDAS
CLOROFENOLICOS 109
-------
excrecion de 2,4-D de rnanera dramatica y la de rnecoprop de forma substan-
cial. El pH urinario debe mantenerse en el intervalo de 7,6-8,8. Incluya cloru-
ro de potasio de acuerdo con las necesidades para compensar el aumento de la
perdida de potasio: anada 20 a 40 mEq de cloruro de potasio por cada litro de
solucion intravenosa.Vigile con cuidado los electrolitos sericos, especialmente
el potasio y el calcio.
Puede haber cierto peligro para los rinones cuando las concentraciones
urinarias del toxico son muy elevadas, por lo que la integridad de la funcion
renal y del balance de liquidos deben monitorearse con sumo cuidado confor-
me va excretandose el compuesto clorofenolico. El fallo renal ha ocurrido en
pacientes con intoxicacion severa durante la diuresis alcalina. En un caso, la
diuresis fue comenzada 26 horas despues de la ingestion,6 y en otros dos, fue
iniciada unos cuantos dias despues del envenenamiento.3'9
7. Es poco probable que la hemodialisis represente un beneficio de importan-
cia en envenenamientos con compuestos clorofenolicos. La misma ha sido usa-
da en cuatro pacientes que sobrevivieron a la intoxicacion.11 Sin embargo, dado
a la naturaleza de alto enlace proteinico de estos herbicidas y a la falta de otra
evidencia, no se recomienda la hemodialisis.2
8. Seguimiento clinico. Durante el seguimiento clinico, los examenes deben
incluir estudios electromiograficos y de conduccion nerviosa para detectar cual-
quier cambio neuropatico y defectos en la conexion neuromuscular.
Estructura Quimica General
Cl (oCH3)
O
O H
Referencias
1. Kohli JD, Khanna RN, Gupta BN, et al. Absorption and excretion of 2,4-dichlorophenoxy-
acetic. Xenobiotica 1974;4(2):97-100.
2. Arnold EK, Beasley MS, and Beasley VR.The pharmacokinetics of chlorinated phenoxy
acid Herbicides:A literature review. Vet Hum Toxicol 1989;31(2):121-5.
3. KellerT, Skopp G,Wu M, et al. Fatal overdose of 2,4-dichlorophenoxyacetic acid (2,4-D).
Forensic Sci Int 1994;65:13-8.
4. Friesen EG, Jones GR, andVaughan D. Clinical presentation and management of acute 2,4-
D oral ingestion. Drug Sa/1990;5(2): 155-90.
PB
HERBICIDAS
CLOROFENOLICOS
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5. Prescott LF, Park J, and Darrien I. Treatment of severe 2,4-D and mecoprop intoxication
with alkaline diuresis. Brijournal of Clinical Pharmacology 1979;7:111-116.
6. Flanagan RJ, Meredith TJ, Ruprah M, et al. Alkaline diuresis for acute poisoning with
chlorophenoxy herbicides and ioxynil. Lancet 1990;335:454-8.
7. Poskitt LB, Duffill MB, and Rademaker M. Chloracne, palmoplantar keratoderma and local-
ized scleroderma in a weed sprayer. CHn and Exp Dennatol 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. CHn 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 hemodiaiysis. Arch Toxicol 1992;66:518-21.
HERBICIDAS
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CAPITULO 10
PUNTOS
IMPORTANTES
Se absorbe a traves de la
piel, el pulmon y el tracto
gastrointestinal
Las fatalidades informadas
han ocurrido entre personas
que trabajaban en
ambientes calurosos
Senales y Smtomas:
Irritation de la nariz,
garganta y ojos
La hipertermia, espasmos
musculares, temblores,
respiration diffcil y la
constriction del pecho
indican envenenamiento
serio
Tratamiento:
No existe un antidote
especffico
Control de la fiebre,
reemplazo de fluidos,
oxfgeno
Descontaminadon de los
ojos, piel, pelo y ropa
Monitorear el estado
cardfaco, controlar la
agitacion
Contraindicaciones:
Los salicilatos para el
control de la fiebre
Pentaclorofenol
Al presente, el pentaclorofenol (PCP) esta registrado en los Estados Unidos sola-
mente como pesticida de uso restringido para la conservacion de madera. El PCP
ha sido utilizado como herbicida, alguicida, defoliante, conservador de madera,
germicida, fungicida y molusquicida.1 Como conservador de madera, por lo ge-
neral se aplica en una solucion al 0,1% en esencias minerales, combustoleo Num.
2 o queroseno. Es usado para tratar la madera a presion en una concentracion al
5%. Los herbicidas han contenido concentraciones mayores.
El pentaclorofenol se volatiliza a partir de la madera y de los productos
textiles tratados. El mismo tiene un significative olor fenolico, que aumenta
cuando el material es calentado. Las superficies interiores tratadas en exceso
pueden ser una fuente de exposicion suficiente como para causar irritacion de
los ojos, nariz y garganta.
El PCP tecnico contiene cantidades bajas de fenoles dorados (4-12%) ade-
mas de trazas de clorobenzodioxinas, clorobenzofuranos y clorobencenos. La
combustion incompleta de madera tratada con PCP puede conducir a la for-
mulacion de estos compuestos.
Toxicologia
El PCP se absorbe bien a traves de la piel, el pulmon y el tracto
gastrointestinal. En animales la DL50 dermal es de la misma magnitud que la
oral. En exposiciones agudas, es rapidamente excretada, principalmente en la
orina, como PCP inalterado y como PCP glucuronido. En exposiciones croni-
cas, se ha informado que la eliminacion de la vida media ha sido muy prolon-
gada, de hasta 20 dias.2 En otro estudio, tres voluntaries ingirieron dosis orales
consecutivas de PCP,y tambien se encontro una vida media de 20 dias. La larga
vida media fue atribuida a la baja excrecion urinaria causada por el alto nivel de
union proteinica.3 Una gran fraccion del PCP absorbido esta fijado a proteinas
en la sangre. Este es ampliamente distribuido a otros tejidos del cuerpo, inclu-
yendo los rinones, corazon y las glandulas suprarrenales.
El PCP es irritante para las membramas mucosas y la piel en concentraciones
adecuadas. La dermatitis por contacto ocurre comunmente en trabajadores que
manipulan el compuesto. En un estudio de empleados envueltos en la fabricacion
de PCP, se encontro cloracne en 7% de los trabajadores, y el riesgo fue
significativamente mayor entre los empleados con contacto cutaneo documenta-
PB
PENTACLOROFENOL
-------
do en comparacion con empleados sin contacto cutaneo.4 La urticaria tambien
ha sido informada conio un sintoma poco coniun en personas expuestas.
El mecanismo principal de accion toxica es el incremento en el metabolis-
mo oxidante celular, como resultado del desacoplamiento de la fosforilacion
oxidante. La produccion de calor aumenta y conduce a la hipertermia. Este
estado clinico iniita las seiiales y sintomas encontrados en el hipertiroidismo.
Internamente, las grandes dosis son toxicas para el higado, rinones y el sistema
nervioso.
Como resultado de experimentos con animates de laboratorio, se ha infor-
mado que el PCP tiene propiedades fetotoxicas y embriotoxicas y que se une a
varies receptores hormonales.5'6 La evidencia epidemiologica sugiere que las
personas expuestas pueden sufrir el riesgo de abortos espontaneos, reduccion
en el peso de nacimiento y otras formaciones defectuosas.7'8
La albuminuria, glicosuria, aminoaciduria y una elevacion en el nitrogeno
ureico sanguineo reflejan danos renales. El agrandamiento del higado, anemia y
leucopenia se han informado en algunos trabaj adores con exposiciones masivas.
La elevacion de la fosfatasa alcalina en el suero,AST, y enzimas deshidrogenasas
(LDH - por sus siglas en ingles) indican una lesion de importancia en el higado,
en la que se incluyen dano celular y cierto grado de obstruccion biliar.
Productos Comerdales
Chlorophen
PCP
Penchlorol
Penta
Pentacon
Pen war
Sinituho
La sal de sodio es el
pentaclorofenato sodico.
Sehales y Sintomas de Envenenamiento
La irritacion de la nariz, garganta y ojos es el efecto mas comun del PCP
que se encuentra en el aire, el que causa congestionamiento de nariz y garganta
con sensacion de escozor y lagrimeo. La exposicion dermal conduce a derma-
titis por contacto, pero rara vez ocasiona urticaria difusa o cloracne. Casos indi-
viduales de dermatits con exfoliacion de las manos, urticaria difundida y
angioedema de las manos han sido informados en trabajadores con gran
exposicion.Varias muertes infantiles ocurrieron en una guarderia en la cual se
habia utilizado un enjuague de panales que contenia PCP.
Ha ocurrido envenenamiento severe y muerte como resultado de una
exposicion intensa al PCP. El envenenamiento agudo ocurre con la absorcion
sistemica, la cual puede ocurrir con una dosificacion suficiente a traves de
cualquier ruta. La mayoria de los envenenamientos ocupacionales ocurren por
contacto dermico. Los indicadores del envenenamiento agudo severe son la
hipertermia, espasmos musculares, temblor, respiracion dificil y constriccion
del pecho. El paciente tambien podria quejarse de dolor abdominal y exhibir
sintomas de vomito, inquietud y confusion mental. Otras senales y sintomas de
envenenamiento sistemico, informados con frecuencia, incluyen la transpiracion
excesiva, debilidad, mareo, anorexia y sed intensa. Los trabajadores expuestos
durante largos periodos de tiempo pueden experimentar perdida de peso.
La mayoria de las fatalidades entre adultos han ocurrido en personas que
trabajaban en ambientes calurosos, entre los cuales la hipertermia es poco tole-
PENTACLOROFENOL 113
-------
rada. Casos de anemia aplastica y de leucemia, asociados temporeramente a la
exposicion del PCP, tambien han sido informados. No se establecieron relacio-
nes casuales en estos casos.9 La neuropatia periferal tambien ha sido informada
en algunos casos de exposicion ocupacional; sin embargo, una relacion casual
no ha sido apoyada por estudios longitudinales.10
Confirmacion de Envenenamiento
Si se sospecha envenenamiento debido a exposicion, sintomas y senales, no
debera posponerse el tratamiento hasta que se confirme el diagnostico.
El PCP puede medirse en sangre, orina y tejido adiposo mediante
cromatografia gas-liquido. Los niveles plasmaticos pueden ser mucho mayores
que los urinarios (el radio de sangre a orina es de 1,0 a 2,5), por lo cual debe
tenerse sumo cuidado en la interpretacion de los resultados.10'11 No existe una
determinacion clara de lo que constituye un nivel anormalmente alto de PCP,
y existe una gran variacion entre las diferentes referencias. La mayoria de la
informacion, en lo que a las concentraciones sericas en relacion a la toxicidad se
refiere, esta basada en casos individuales o en pequenos estudios de pacientes.
Existen informes de infantes asintomaticos con concentraciones sericas de has-
ta 26 partes por millon (ppm).11'12 Sin embargo, la mayoria de los informes de
exposicion no ocupacional entre el publico en general envolvieron concentra-
ciones en el promedio de partes por billon.1'13"15 La comida es probablemente
la fuente principal de esta dosificacion de nivel de nanogramo.1 Las concentra-
ciones sericas entre personas expuestas ocupacionalmente a menudo exceden 1
ppm.1 Un informe de un caso letal describe el nivel plasmatico de 16 ppm,16
pero la mayoria de los casos envuelven concentraciones sericas de 100 ppm o
mayores.11'17 Es razonable asumir que concentraciones mayores de 1 ppm son
consistentes con una exposicion poco usual y que las concentraciones de aproxi-
madamente 100 ppm son causa de gran preocupacion.
Tratamiento
1.Tratamiento de apoyo y control de hipertermia. No existe un antidote
especifico para el envenenamiento; por lo tanto el tratamiento de apoyo incluye
oxigeno, substitucion de fluidos, y lo mas importante, control de la fiebre.
Reduzca la temperatura corporal elevada a traves de medios fisicos. Admi-
nistre bafios con esponja y utilice abanicos para aumentar la evaporacion.18 En
pacientes conscientes, administre por via oral, liquidos tan frios y azucarados
como puedan ser tolerados. Tambien pueden utilizarse cobijas frias y fundas de
hielo en el cuerpo.
La terapia antipiretica con salicilatos es energicamente contraindicada,
debido a que los salicilatos tambien desacoplan la fosforilacion oxidante. Se
cree que otros antipireticos no ofrecen resultado alguno debido a la naturaleza
PB PENTACLOROFENOL
-------
del mecanismo periferalmente indirecto de la hipertermia en este envenena-
miento. No se ha probado la seguridad ni la efectividad de otros antipireticos.
Para minimizar la anoxia tisular, administre oxigeno continuamente por
mascarilla. A menos que no haya manifestaciones de edema cerebral o pulmonar
o de funcion renal inadecuada, administre fluidos intravenosos para restaurar la
hidratacion y sostener los mecanismos fisiologicos para la perdida de calor y
disposicion toxica. Monitoree los electrolitos sericos, ajustando las infusiones
intravenosas para estabilizar las concentraciones de electrolitos. Observe el con-
tenido de albumina y celulas urinarias, y mantenga un registro exacto por hora
de la absorcion/excrecion para evitar la sobrecarga de fluidos si disminuye la
funcion renal.
Advertencia: Ante la presencia de edema cerebral y/o deterioro renal,
fluidos intravenosos deben ser administrados cuidadosamente para evitar un
aumento en la presion intracraneal y edema pulmonar. Podria indicarse la
monitorizacion de la presion venosas y pulmonar de curia. Pacientes en estado
critico deberan ser tratados en una unidad de terapia intensiva.
2. Descontaminacion dermica. Enjuague el quimico de los ojos utilizando
cantidades abundantes de agualimpia.Trate la descontaminacion dermica como
fuera delineado en el Capitulo 2.
3. Monitoreo cardiopulmonar. En casos de envenenamientos severos,
monitoree cuidadosamente el estado pulmonar para asegurar un intercambio
adecuado de gases. Monitoree el estado cardiaco por electrocardiograma para
detectar arritmias. El agente toxico en si, y las alteraciones severas de los
electrolitos podrian predisponer a la persona a arritmias y a debilidad miocardica.
4. Neurologico. Para reducir la produccion de calor en el cuerpo, controle la
agitacion y la actividad motora involuntaria con sedantes. El lorazepam y otras
benzodiazepinas deberian ser efectivos, aunque el uso de estos medicamentos
en este tipo de envenenamiento no ha sido informado. Si se escoge el lorazepam,
debera administrarse lentamente por via intravenosa.
5. Descontaminacion gastrointestinal. Si el PCP ha sido ingerido en can-
tidades suficientes como para causar envenenamiento y el paciente presenta
sintomas en una hora, debera considerarse la descontaminacion gastrica como
fuera delineada en el Capitulo 2.
6. Nutricion. Durante la convalecencia, debera administrarse una dieta alta en
calorias y vitaminas para restaurar el tejido graso y los carbohidratos. Disuada el
contacto subsecuente con el veneno durante 4 a 8 semanas (dependiendo de la
severidad del envenenamiento) para permitir una completa restauracion del
proceso metabolico normal.
PENTACLOROFENOL -115
-------
Dosificacion de Lorazepam
Adultos: 2 a 4 mg/dosis intravenosa durante 2 a 5 minutos. Repetir de
ser necesario hasta un maximo de 8 nig en un periodo de 12 horas.
Adolescentes: La misnia dosis que los adultos, con la excepcion de
que la dosis maxima es de 4 mg.
Nines menores de 12 anos: 0,05 a 0,10 mg/kg por via intravenosa du-
rante 2 a 5 minutos. Repetir de ser necesario 0,05 mg/kg 10 a 15
minutos despues de la primera dosis, hasta una dosis maxima de 4 mg.
Advertencia: Este preparado para asistir la ventilacion pulmonar me-
canicamente si se deprime la respiracion, a intubar la traquea si ocurre
un laringospasmo y a contrarrestar las reacciones que causen hipotension.
Estructura Quimica
Cl
Cl
0 H
(oNa)
Referencias
1. Jorens PG and Schepens PJC. Human pentachlorophenol poisoning. Hum Exp Toxicol
1993;479-95.
2. Kalman DA and Horstman SW. Persistence of tetrachlorophenol and pentachlorophenol in
exposed woodworkers.JToxicol ClinToxicol 1983;20:343.
3. Uhl S, Schmid P, and Schlatter C. Pharmacokinetics of pentachlorophenol in man. Arch
Toxicol 1986;58:182-6.
4. O'Malley MA, Carpenter AV, S\veeney MH, et al. Chloracne associated \vith 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 interfer-
ing 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.
PB
PENTACLOROFENOL
-------
8. DeMaeyer J, Schepens PJ.Jorens PG, andVerstaete R. Exposure to pentachlorophenol as a
possible cause of miscarriages. Br] Obstet Gynaecol 1995;102:1010-1.
9. Roberts HJ. Aplastic anemia due to pentachlorophenol. New EnglJ 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 HygAssocJ 1969;30:360-6.
11. Clayton GD and Clayton FE (eds). Patty's Industrial Hygiene and Toxic ologyvol 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-FiguerasJ, 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, andYoder J. Exposure and contamination of the air and
employees of a pentachlorophenol plant, Idaho-1972. Pest MonitJ 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, RomWN,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 man-
agement and cooling in 14 patients. Arch Intern Med 1986;146:87-90.
PENTACLOROFENOL 117
-------
CAPITULO 11
PUNTOS
IMPORTANTES
Herbicidas altamente
toxicos
Afectan el sistema hepatico,
renal y nervioso
Senales y Smtomas:
Transpiration profusa, sed,
fiebre, dolor de cabeza,
confusion, malestar y
lasitud
Hipertermia, taquicardia y
taquipnea en casos series
Manchas caracterfsticas
amarillas en la piel y el
cabello por lo general
indican contacto topico
Tratamiento:
No existe un antidote
especffico
Substitution de oxfgeno y
fluidos, y control de
temperatura
Descontaminadon de la
piel, cabello y ropa
Contraindicaciones:
Terapia antipiretica con
salicilato
Atropina
Herbicidas Nitrofenolicos y
Nitrocresolicos
Estos agentes altamente toxicos tienen muchos usos en la agricultura mundial,
como herbicidas (matamalezas y defoliantes), acaricidas, nematicidas, ovicidas y
fungicidas. La mayoria de los productos tecnicos son relativamente insolubles
en agua, se disuelven en disolventes organicos y se formulan como emulsiones
para aplicarse como rocios. Existen algunas formulaciones como polvos
humectables. Solamente el dinocap retiene su registracion activa en los Estados
Unidos.
Toxicologia
Los compuestos nitroaromaticos son altamente toxicos para humanos y
animales con una DL50 de aproximadamente 25 a 50 mg/kg.1 La mayoria de los
nitrofenoles y nitrocresoles son bien absorbidos por la piel, el tracto
gastrointestinal o los pulmones al inhalarse finas gotas.2 Han habido envenena-
mientos fatales como resultado de la contaminacion dermica. Lo mas comun es
una irritacion moderada de la piel y las membranas mucosas.
Los nitrofenoles y nitrocresoles sufren biotransformacion parcial en los se-
res humanos, en especial, reduccion (grupo nitro a grupo amino) y conjuga-
cion en el grupo fenolico. Aunque los nitrofenoles y sus metabolitos aparecen
siempre en la orina de los individuos envenenados, la excrecion hepatica tal vez
sea la principal ruta de eliminacion. La eliminacion es lenta y se ha documen-
tado una vida media en humanos de 5 a 14 dias.1 Si un individuo se expone de
manera substancial durante varies dias consecutivos,las concentraciones tisulares
y sanguineas aumentan progresivamente.
El mecanismo basico de toxicidad es la estimulacion del metabolismo
oxidativo en las mitocondrias celulares, por interferencia con el acoplamiento
normal de la oxidacion de los carbohidratos a la fosforilacion. Esto conduce a la
hipertermia, taquicardia, dolor de cabeza, malestar y deshidratacion y, despues
de un tiempo, reduce las reservas de carbohidratos y grasas. Los sistemas princi-
pales con mayor propensidad al envenenamiento son el hepatico, renal y ner-
vioso. Los nitrofenoles son mas activos como desacopladores que los clorofenoles,
como por ejemplo el pentaclorofenol (descrito en el Capitulo 10). La hiperter-
mia y la accion directa en el cerebro causan inquietud y dolor de cabeza y, en
PB
NITROFENOLICOS Y
NITROCRESOLICOS
-------
casos severos, convulsiones, coma y edema cerebral. Mientras mas alta sea la
temperatura del ambiente, tal y como el ambiente agricola a campo raso, mas
dificil sera disipar el calor.1'2 El parenquima hepatico y los tubulos renales mues-
tran cambios degenerativos. La albuminuria, piuria, hematuria y azotemia son
senales de dano renal.
La formacion de cataratas en animales de laboratorio a los cuales se les han
administrado nitrofenoles, han ocurrido en humanos, como resultado del uso
imprudente de medicamentos y como consecuencia cronica de la exposicion
ocupacional.3 La formacion de cataratas se acompana algunas veces de glaucoma.
Senales y Sintomas de Envenenamiento
La mayoria de los pacientes presentan pocas horas despues de la exposicion,
sintomas y senales generalizadas pero no especificas, entre los cuales se encuen-
tran la transpiracion profusa, sed, fiebre, dolor de cabeza, confusion, malestar y
lasitud. La piel puede lucir enrojecida y caliente segun se desarrolla la hipertermia,
junto con la taquicardia y la taquipnea, sintomas que indican la gravedad del
envenenamiento. La inquietud, recelo, ansiedad, conducta maniaca, convulsiones
y coma reflejan dano cerebral. La aparicion de convulsiones y la coma indican
una intoxicacion que amenaza la vida. La respiracion dificil y cianosis son conse-
cuencias de la estimulacion del metabolismo y de la anoxia tisular. El fallo renal
puede ocurrir temprano en los casos de exposicion severa. El dano al higado se
manifiesta primeramente por la ictericia, y la muerte de las celulas puede ocurrir
dentro de 48 horas y depende de la dosis.4 En casos de envenenamiento severe, la
muerte puede ocurrir en las 24 a 48 horas despues de la exposicion.2 En casos en
que se sobreviva al envenenamiento severe, la completa resolucion de los sinto-
mas puede ser lenta debido a la vida media del agente toxico.1'5
La aparicion de manchas amarillas en la piel y el cabello por lo general,
indica contacto topico con un compuesto y puede ser una serial diagnostica
para el medico.1'2'5 Las manchas en la esclerotica y orina constituyen senales de
absorcion de cantidades potencialmente toxicas. La perdida de peso ocurre en
personas expuestas continuamente a dosis relativamente bajas de nitrofenoles o
nitrocresoles.1'3
Confirmacion de Envenenamiento
Si existe la posibilidad de envenenamiento, no espere a recibir confirma-
cion antes de iniciar el tratamiento. Guarde especimenes de orina y sangre en
hielo a una temperatura menor de 20-C en caso de que se necesitara confirma-
cion mas tarde. Los nitrofenoles y nitrocresoles que no han sido metabolizados
pueden identificarse espectrofotometricamente o por cromatografia gas-liqui-
do en suero a concentraciones muy inferiores a las asociadas con envenena-
mientos agudos. La informacion acerca de niveles de exposicion y sistemicos de
Productos Comerdales
acetato de dinoseb*
Aretit
acetato de dinoterb*
dinitrocresol*
Chemsect DNOC
DNC
DNOC
Elgetol 30
Nitrador
Selinon
Sinox
Trifocide
dinitrofenol*
Chermox PE
dinobuton*
Ac rex
Dessin
Dinofen
Drawinol
Talan
dinocap
Crotothane
Karathane
dinopenton
dinoprop*
dinosam*
Chemox General
DNAP
dinoseb*
Basanite
Caldon
Chemax General
Chemax PE
Chemsect DNBP
Dinitro
Dinitro-3
Dinitro General Dynamyte
Dinitry 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
dinosulfon*
dinoterbon*
metacrilato de dinoseb*
Acricid
Am box
binapacrilo
(Continue en la proxima pagina)
NITROFENOLICOS Y
NITROCRESOLICOS 119
-------
Productos Comerdales
(Continuation)
Dapacryl
Endoscan
FMC 9044
Hoe 002784
Morrodd
NIA 9044
sales de dinoterb*
los compuestos en este grupo son limitados,y la mayoria de los informes espe-
cifican el compuesto dinitro-orto-cresol. En general, niveles sanguineos de 10
nicg/dl o mayores son vistos cuando existe toxicidad sistemica.1'6 Un caso fatal
ocurrio con un nivel de 75 nicg/dl.6 El analisis sanguineo es util para confirmar
la causa del envenenamiento. El monitoreo de los niveles debera ser rutinario
durante la intoxicacion aguda para ayudar en el establecimiento de una curva
de degeneracion, con el proposito de determinar cuando puede descontinuarse
sin peligro la terapia.
* Todas las registraciones en los
Estados Unidos han sido
canceladas
Tratamiento
l.Tratamiento de apoyo y control de hipertermia. No existe un antidote
especifico para el envenenamiento con herbicidas nitrofenolicos o nitrocresolicos.
El tratamiento es de apoyo, en su naturaleza e incluye oxigeno, substitucion de
fluidos y control de temperatura.
Reduzca la temperatura corporal elevada a traves de medios fisi-
cos. Administre banos con esponja y bolsas de hielo, y utilice un abanico para
promover el fluir del aire y la evaporacion.7 En pacientes totalmente conscien-
tes, administre liquidos tan frios y azucarados por via oral, como pueda tolerarlo
el paciente.
2. Contraindicaciones. La terapia antipiretica con salicilatos es alta-
mente contraindicada debido a que los salicilatos desacoplan la fosforilacion
oxidante. Se cree que otros antipireticos no scan de uso alguno debido a la
naturaleza del mecanismo periferalmente indirecto de la hipertermia en este
envenenamiento. No se ha probado la seguridad o efectividad de otros
antipireticos.
;La atropina es absolutamente contraindicada! Es esencial no con-
fundir las senales medicas del dinitrofenol con las manifestaciones de envene-
namiento que inhiben la colinesterasa.2
3. Descontaminacion dermica. Si el envenenamiento se ha producido por
contaminacion de la superficie corporal, rapidamente de un bano y lave el
cabello con agua y jabon, o agua sola, si no dispone de jabon. Lave el contami-
nante que se encuentra en los pliegues de la piel y debajo de las unas. Debera
ejercer cuidado para que el personal del hospital no se contamine dermicamente.
Vease el Capitulo 2.
4. Otro tratamiento. Otros aspectos del tratamiento son identicos al trata-
miento para envenenamiento por pentaclorofenol, detallado en el Capitulo 10.
PB
NITROFENOLICOS Y
NITROCRESOLICOS
-------
Estructura Quimica General
0 H or
(ALQUILO) (ALQUILO)
Referencias
1. Leftwich RB, Floro JF, Neal RA, et al. Dinitrophenol poisoning: A diagnosis to consider in
undiagnosed fever. South MedJ 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.
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 herbi-
cide. Practitioner 1981;225:923-6.
6. NIOSH. Criteria document: Occupational exposure to dinitro-orthocresol. Cincinnati: NIOSH,
1978.
7. Graham BS, Lichtenstein MJ, Hinson JM, et al. Nonexertional heatstroke: Physiologic man-
agement and cooling in 14 patients. Arch Intern Med 1986;146:87-90.
NITROFENOLICOS Y
NITROCRESOLICOS
121
-------
CAPITULO 12
PUNTOS
IMPORTANTES
Efectos en el tracto
gastrointestinal, rinon, higado,
corazon y otros organos que
ponen a riesgo la vida
La fibrosis pulmonar es la
causa usual de muerte en
envenenamiento por paraquat
(pero no por diquat)
Senales y Smtomas:
Ingestion de paraquat y diquat:
sensation de quemadura en la
boca, garganta, pecho y abdomen
superior; edema pulmonar,
pancreatitis, otros efectos renales y
del sistema nervioso central
Paraquat (dermal): manos
secas y agrietadas, ondas
horizontales o cafda de las
unas, ulceracion y abrasion
Diquat: toxicidad neurologica
Tratamiento:
Descontaminadon
gastrointestinal inmediata con
bentonita, Tierra de Batan, o
carbon activado
Mantener una excrecion
urinaria adecuada
administrando fluidos
intravenosos, pero monitorear
los fluidos en caso de
insuficiencia renal
Descontaminar los ojosy la piel
Contraindicaciones:
No administre oxfgeno suplemen-
tario hasta que el paciente
desarrolle hipoxemia severa
Paraquat y Diquat
El paraquat y el diquat son herbicidas bipiridilos no selectivos que se usan
bastante, principalmente en la agricultura y por las agendas de gobierno e
industrias para el control de malas hierbas. Aunque en los Estados Unidos, el
paraquat es un pesticida de uso restringido en la mayor parte de sus formas y
usos, su uso generalizado conlleva un gran potencial para el rnal uso y para los
envenenamientos accidentales e intencionales. Durante las ultimas decadas, el
paraquat ha sido un quimico popular utilizado en suicidios, pero la experiencia
reciente indica un declinar en envenenamientos intencionales de esa indole. El
paraquat y el diquat son compuestos altamente toxicos y el tratamiento de los
envenenamientos requiere gran destreza y conocimiento de los procedicimientos
apropiados de tratamiento.
PARAQUAT
Toxicologia
Cuando se ingiere en una dosificacion adecuada (vease abajo), el paraquat
afecta el tracto gastrointestinal, rinon, higado, corazon y otros organos, ponien-
do a riesgo la vida. La DL50 en humanos es aproximadamente 3 a 5 mg/kg, lo
cual se traduce a tan solo 10 a 15 ml en una solucion al 20%.1>2
Los pulmones son el primer bianco del paraquat, y los efectos pulmonares
representan la manifestacion mas letal y menos tratable de la toxicidad. Sin
embargo, la toxicidad por inhalacion es rara. El mecanismo principal lo es la
generacion de radicales libres que oxidan el tejido pulmonar.1'2 Aunque el ede-
ma pulmonar agudo y los danos al pulmon pueden ocurrir unas cuantas horas
despues de exposiciones agudas severas,3'4 la lesion toxica retrasada de la fibrosis
pulmonar, la causa usual de muerte, ocurre mas comunmente entre 7 a 14 dias
despues de la ingestion.5 En algunos pacientes que ingirieron una gran canti-
dad de forma concentrada (20%), murieron mas rapidamente debido a la insu-
ficiencia circulatoria (dentro de 48 horas).5
Tanto los neumatocitos tipo I y II parecen acumular el paraquat de forma
selectiva. La biotransformacion de paraquat en estas celulas genera radicales
libres, lo que trae como resultado la peroxidacion de lipidos y dano a las celu-
las.1'2'4 La hemorragia, los fluidos del edema y los leucocitos infiltran los espa-
cios alveolares, despues de lo cual aparece de inmediato la proliferacion de
PB PARAQUAT Y DIQUAT
-------
fibroblastos. Existe un decenso progresivo de la tension del oxigeno arterial y
en la capacidad de difusion del CO2. Un deterioro corno tal en el intercambio
de gases causa la proliferacion progresiva de tejido conectivo fibroso en los
alveoles causando finalmente la muerte por asfixia y anoxia tisular.6 Un presun-
to estudio de sobrevivientes sugiere que parte del dano toxico a las fibras podria
ser reversible debido a que existe evidencia de una marcada mejoria en la fun-
cion pulmonar tres rneses despues de la intoxicacion.7
El dano dermico local incluye dermatitis por contacto. El contacto prolon-
gado producira eritema, aparicion de ampollas, abrasion y ulceracion, ademas
de cambios en las unas de las manos.8'9 Aunque la absorcion a traves de la piel
intacta es lenta, cuando esta se encuentra lacerada o erosionada la absorcion es
muy eficiente.
El tracto gastrointestinal es donde ocurre la primera fase, o fase inicial de
toxicidad de las capas mucosas luego de la ingestion de la substancia. Esta toxi-
cidad es manifestada por hinchazon, edema y ulceracion dolorosa de la boca,
faringe, esofago, estomago e intestine. Con niveles mayores, otros sintomas de
toxidiad del tracto gastrointestinal incluyen dano centrozonal hepatocelular, lo
cual puede causar una bilirubina elevada y enzimas hepatocelulares tales como
AST, ALT y LDH (por sus siglas en ingles).
Es mas probable que el efecto a las celulas tubulares renales sea mas rever-
sible que la destruccion del tejido pulmonar. Sin embargo, el deterioro de la
funcion renal podria jugar un papel importante en la determinacion del resul-
tado del envenenamiento con paraquat. Las celulas tubulares normales secretan
paraquat en la orina con rapidez, eliminandolo de forma eficiente de la sangre.
Sin embargo, las altas concentraciones sanguineas intoxican el mecanismo secretor
y pueden destruir las celulas. El envenenamiento con diquat resulta tipicamente
en un mayor dano renal en comparacion con el paraquat.
La necrosis focal del miocardio y musculo esqueletico son los aspectos
principales de la toxicidad a cualquier clase de tejido muscular, y ocurren tipi-
camente durante la segunda fase. Tambien se ha informado que la ingestion
causa edema y lesion cerebral.10
Aunque se ha expresado gran preocupacion debido a los efectos de fumar
marihuana contaminada con paraquat, en este caso los efectos toxicos han sido
raros o no han existido. La mayor parte del paraquat que contamina la marihua-
na es pirolizado durante la combustion del cigarrillo convirtiendose en bipiridilo,
el cual es un producto de la combustion del material mismo de la hoja (incluida
la marihuana) y presenta muy poco peligro toxico.
Productos Comerdales
Paraquat
Concentrados liquidos:
Cekuquat
Crisquat
Dextrone
Esgram
Goldquat
Gramocil
Gramonol
Gramoxone
En combination con otros
herbicidas:
Con diquat:
Actor
Preeglone
Preglone
Weedol (al 2,5% soluble en
formuladon granulada)
Con diuron:
Dexuron
Gramuron
Para-col
Tota-col
Con monolinuron:
Gramonol
Con simazine:
Pathclear
Terra klene
Diquat
Aquacide
Dextrone
Ortho Diquat
Reg lone
Sehales y Sintomas de Envenenamiento
Las senales medicas iniciales del envenenamiento dependen de la ruta de
exposicion. Los sintomas y senales tempranas de envenenamiento por inges-
tion son sensacion de quemadura en la boca, garganta, pecho y abdomen supe-
PARAQUAT Y DIQUAT 123
-------
rior debido al efecto corrosive del compuesto en la capa mucosa. La diarrea, la
cual en ocasiones puede ser sanguinolenta, tambien puede ocurrir. El vertigo,
dolor de cabeza, fiebre, mialgia, letargo y coma son otros ejemplos de hallazgos
sistemicos y del sistema nervioso central. La pancreatitis puede causar dolor
abdominal severe. La proteinuria, hematuria, piuria y azotemia reflejan dano
renal. La oliguria/anuria indican necrosis tubular aguda.
Debido a que el rinon es casi exclusivamente la ruta para la eliminacion del
paraquat de los tejidos del cuerpo, la insuficiencia renal fomenta el aumento de
concentraciones tisulares, incluyendo las del pulmon. Lamentablemente, esta se-
cuencia patogenica puede ocurrir durante las primeras horas despues de la inges-
tion de paraquat, generando concentraciones letales de paraquat en el tejido
pulmonar antes de que hayan surtido efecto medidas terapeuticas para limitar la
absorcion y estimular la disposicion. Probablemente se deba a esta razon que los
metodos para la estimulacion de la disposicion del paraquat varias horas despues
de la ingestion no hayan surtido mucho efecto en cuanto a la mortalidad.
La tos, disnea y taquipnea aparecen generalmente entre 2 y 4 dias despues
de la ingestion de paraquat, pero podrian retrasarse hasta 14 dias. La cianosis
progresiva y la falta de aire reflejan un deterioro en el intercambio de gases en
el pulmon daiiado. En algunos casos, la primera manifestacion de la lesion
pulmonar por paraquat y la principal es la tos con esputo espumoso (edema
pulmonar).
La experiencia medica, ha elaborado una escala aproximada de la relacion
dosis-efecto con la cual puede hacerse el pronostico de los casos de ingestion
de paraquat:9
Menos de 20mg de paraquat ionico por kilogramo de peso cor-
poreo (menos de 7,5 ml al 20% p/v de concentrado de paraquat).
No existen sintomas o solo se presentan sintomas gastrointestinales.
La recuperacion es probable.
De 20 a 40 mg de paraquat ionico por kilogramo de peso corpo-
reo (7,5 a 15,0 ml al 20% [p/v] de concentrado de paraquat).Apare-
ce la fibroplasia pulmonar. En la mayoria de los casos sobreviene la
muerte, la que puede retrasarse de 2 a 3 semanas.
Mas de 40 mg de paraquat ionico por kilogramo de peso corpo-
reo (mas de 15,0 ml al 20% [p/v] de concentrado de paraquat).
Ocurre dano organico multiple como en la clase II, pero avanza con
mas rapidez. Con frecuencia se caracteriza por ulceracion marcada
en la orofaringe. La mortalidad es en general del 100%, en un tiem-
po de 1 a 7 dias.
Las senales dermicas son comunes entre los trabajadores agricolas con toxi-
cidad aguda de paraquat. El paraquat en forma concentrada, causa lesiones loca-
lizadas a los tejidos con los que entra en contacto. Se han informado envenena-
PB PARAQUAT Y DIQUAT
-------
mientos con fatalidad como resultado de contaminacion dermica extensa por
paraquat, pero lo mas probable es que una absorcion sistemica eficiente ocurra
cuando la piel esta lesionada, corroida, o enferma. Cuando el paraquat encuen-
tra una barrera dermica intacta, deja la piel de las manos seca y agrietada, y
puede causar ondas horizontales en las unas e incluso, algunas veces, provoca la
caida de las mismas. El contacto prolongado con la piel puede causar suficiente
ulceracion y abrasion como para permitir la absorcion sistemica.
En adicion, algunos trabajadores agricolas podrian exponerse a traves de la
inhalacion prolongada de gotitas de aerosol y desarrollar hemorragia nasal de-
bido al dano local. Sin embargo, la inhalacion no ha resultado en toxicidad
sistemica, debido a la baja presion del vapor y la baja concentracion de paraquat
en las formulaciones utilizadas en el campo. La contaminacion ocular con diquat
concentrado o soluciones mas fuertes puede resultar en conjuntivitis severa y
en ocasiones, en la opacidad cornea! prolongada o permanente.
El dano hepatico debido al paraquat puede ser tan severe que cause icteri-
cia, lo cual significa un dano severe. Sin embargo, la hepatotoxicidad es en raras
ocasiones un determinante importante del resultado medico. No se presenta
ninguna otra serial o sintoma que los valores anormales de laboratorio mencio-
nados en la seccion de Toxicologia.
DIQUAT
Toxicologia
El envenenamiento con diquat es mucho menos comun que el envenena-
miento con paraquat, por lo cual los informes humanos y la informacion de
experimentos con animales para el envenenamiento con diquat son menos
extensos que para el paraquat. El diquat absorbido sistemicamente no se con-
centra de manera selectiva en el tejido pulmonar, como lo hace el paraquat, por
lo cual la lesion pulmonar causada por el diquat es menos grave. En estudios
con animales, el diquat causa lesiones ligeras y reversibles a los neumatocitas
tipo I, pero no lesiona las celulas tipo II. No se ha advertido fibrosis pulmonar
progresiva en el envenenamiento con diquat.11"13
Sin embargo, el diquat tiene efectos toxicos severos en el sistema nervioso
central que no son tipicos del envenenamiento por paraquat.12'13 Aunque la expe-
rimentacion de laboratorio ha sugerido que el diquat no es directamente
neurotoxico, se han informado cambios patologicos del cerebro relativamente
consistentes en casos fatales de envenenamiento por paraquat. Estos consisten de
infartacion del tronco del cerebro, envolviendo en particular el puente.12 No es
claro si estos cambios post-mortem representan toxicidad directa o efectos secun-
darios relacionados con la enfermedad sistemica y terapia. (Vease la seccion de
Senales y Sintomas para los efectos medicos al sistema nervioso central.)
PARAQUAT Y DIQUAT 125
-------
Es probable que haya una absorcion significativa de diquat a traves de la
piel ulcerada o escoriada.
Sehales y Sintomas de Envenenamiento
En muchos casos de envenenamiento por diquat entre humanos, las senates
y sintomas medicos de toxicidad neurologica son los mas importantes. Estos
incluyen nerviosismo, irritabilidad, inquietud, combatividad, desorientacion,
declaraciones sin sentido, incapacidad de reconocer a amigos o miembros de la
familia y disminucion de los reflejos. Los efectos neurologicos pueden progre-
sar hasta la coma, ir acompaiiados de convulsiones tonico-clonicas y resultar en
la muerte del paciente.12>13Tambien se ha informado el Parkinsonismo despues
de una exposicion dermica al diquat.14
Con excepcion a las senales del sistema nervioso central enumeradas en el
parrafo precedente, los sintomas tempranos del envenenamiento por ingestion
por diquat son similares a los del paraquat, reflejando su efecto corrosive en los
tejidos. Estos incluyen, sensacion de quemadura en la boca, garganta, pecho y
abdomen, nausea intensa y vomito, y diarrea. Si la dosificacion fue pequeiia, los
sintomas pueden retrasarse hasta 162 dias. Puede presentarse sangre en el
vomito y en las heces. La presencia de ileo intestinal es una caracteristica del
envenenamiento severe por diquat en humanos, con atraccion de fluidos al
intestino.
El diquat absorbido en el cuerpo se excreta por el rinon como via princi-
pal. Por lo tanto, el dano renal es una caracteristica importante del envenena-
miento. La proteinuria, hematuria y piuria pueden conducir a una insuficiencia
renal y azotemia. La elevacion en fosfatasa alcalina serica, AST, ALT y LDH
reflejan dano hepatico; se puede desarrollar ictericia.
Si el paciente sobrevive varias horas o dias, la funcion circulatoria puede
fallar debido a la deshidratacion. La hipotension y taquicardia pueden ocurrir, y
el shock puede resultar en muerte. Otros problemas cardiorespiratorios, tales
como la cardiomiopatia toxica o una infeccion secundaria como la
bronconeumonia pueden desarrollarse.
El diquat es un poco menos danino para la piel que el paraquat, pero pue-
den aparecer efectos irritantes despues de la contaminacion dermica con el
concentrado. Es probable que la piel absorba el diquat de manera significativa si
se encuentra ulcerada o escoriada.
La gran mayoria de los envenenamientos por paraquat y diquat (discutidos
abajo) han sido causados por la ingestion, con intencion suicida en la mayoria
de los casos, particularmente en Japon11 asi como en muchos paises en vias de
desarrollo. Desde 1987, ha habido un decenso en la mayoria de paises en el
numero total de muertes suicidas atribuidas al paraquat y diquat. Casi todos los
pocos pacientes envenenados a traves de la exposicion ocupacional han sobre-
vivido, pero la tasa de mortalidad entre las personas que ingieren paraquat o
PB PARAQUAT Y DIQUAT
-------
diquat permanece siendo elevada.1'5 Para evitar la mortalidad, una vez ingerido
el toxico es importante desarrollar estrategias preventivas o detener precozmente
la absorcion gastrointestinal.
A pesar de que la absorcion intestinal de los bipiridilos es relativamente
lenta, el ingreso letal a organos y tejidos criticos ocurre dentro de 18 horas,y tal
vez dentro de las primeras 6 horas, siguientes a la ingestion de cantidades toxi-
cas de paraquat o diquat. Los bipiridilos tienen grandes volumenes de distribu-
cion. Una vez ha ocurrido la distribution en los tejidos, las medidas para rerno-
verlos de la sangre son ineficaces para reducir la carga corporea total.
Varias estrategias estan siendo probadas para reducir la frecuencia de estas
ocurrencias. Estas incluyen la adicion de formulaciones emeticas, agentes que
confieran un olor nauseabundo, substancias gelatinosas y agentes amargos como
el denatoniato de sodio.
Confirmacion de Envenenamiento: Paraquat y Diquat
En algunas facilidades de tratamiento, se usa una simple prueba colorimetrica
para identificar el paraquat y el diquat en la orina y dar una indicacion aproxi-
mada de la magnitud de la dosis absorbida. A un volumen de orina anada la
mitad de esa cantidad (0,5) de una solucion recien preparada de ditionito sodico
(hidrosulfito sodico) al 1% en una solucion normal de hidroxido sodico. (1,0 N
NaOH). Observe el color luego de un minuto. El color azul indica la presencia
de paraquat en exceso de 0,5 mg por litro. Es importante comparar los contro-
les positives y negatives para asegurarse que el ditionito no se ha oxidado du-
rante el almacenamiento.
Al parecer, la prueba de ditionito tiene un valor pronostico aproximado
cuando se realiza la prueba con orina recolectada en las primeras 24 horas
despues de ingerir paraquat: concentraciones menores a un miligramo por litro
(incoloro azul claro) generalmente predicen sobrevivencia, mientras que las
concentraciones superiores a un miligramo por litro (azul marino a azul oscu-
ro) con frecuencia vaticinan un resultado fatal.
En esta prueba, el diquat en la orina produce un color verde. Aunque existe
menos experiencia con la prueba de ditionito en envenenamientos por diquat,
es posible asociar un pronostico similar si aparece un color intenso.
El paraquat y el diquat pueden medirse en sangre y orina por metodos
espectrofotometricos, de cromatografia de gases, cromatografia de liquidos y
radioinmunoensayo. Estos metodos se encuentran disponibles en numerosos
laboratories de referencia clinica y en ocasiones, en companias fabricadoras. Es
probable que haya sobrevivencia si las concentraciones de plasma no exceden
2,0,0,6,0,3,0,16 y 0,1 mg por litro alas 4,6,10,16 y 24 horas,respectivamente,
despues de la ingestion.15
PARAQUAT Y DIQUAT 127
-------
Tratamiento
1. Descontaminacion dermica y ocular. Enjuague la piel de inmediato
con cantidades abundantes de agua. Si el material ha salpicado en los ojos,
eliminelo con irrigacion prolongada con agua limpia. Despues del lavado, la
contaminacion ocular debe ser tratada por un oftalmologo. Las reacciones
dermicas menores por lo general desaparecen cuando se suspende el contacto,
pero la irritacion puede tardar varias semanas en desaparecer. Los danos graves,
corno inflamacion, agrietamiento, infeccion secundaria o lesiones en unas de-
ben ser tratados por un dermatologo.
2. Descontaminacion gastrointestinal. Si se ha ingerido paraquat o diquat
en cualquier cantidad, administre de inmediato un absorbente. Esta es
probablemente la medida terapeutica mas favorable para obtener un efecto fa-
vorable. La bentonita (7,5% en suspension) y la Tierra de Batan (15% en
suspension) son altamente eficaces, pero algunas veces no estan disponibles.
Dosificacion de Bentonita y Tierra de Batan:
Adultos y ninos mayores de 12 anos: 100 a 150 g.
Nines menores de 12 anos: 2 gm/kg peso corporeo.
Advertencia: La hipercalcemia y fecalitos han ocurrido ocasional-
mente despues de la administracion de Tierra de Batan.
El carbon activado tambien es util, y ademas, por lo general esta disponible.
Vease el Capitulo 2 para la dosificacion de carbon y para mayor informacion
acerca de la descontaminacion gastrica.
No se ha probado que el lavado sea efectivo y este no debera llevarse a cabo
a menos que el paciente sea visto dentro de la primera hora despues de la
ingestion. Efectuar el lavado mas tarde, podria inducir una hemorragia, perfora-
cion o cicatriz debido al trauma adicional a los tejidos ya traumatizados. La
administracion repetida del carbon u otro absorbente cada 2 a 4 horas puede ser
benefica tanto para los ninos como para los adultos, pero el uso de un catartico
como el sorbitol debera ser evitado despues de la primera dosis. Los catarticos y
dosis repetidas de carbon activado no deberan administrarse si el intestine esta
atonico. Revise con frecuencia el intestino para detectar sonidos. El ileo
ocurre mas comunmente en el envenenamiento por diquat y con menos fre-
cuencia en el envenenamiento por paraquat.
3. Muestras. Asegurese de tomar una muestra de sangre tan pronto como sea
posible, para hacer el analisis de paraquat, y muestras de orina para el paraquat
PB PARAQUAT Y DIQUAT
-------
y/o diquat. Para la prognosis, deberan seguirse las muestras de orina en serie
tanto para el agente o plasma para el paraquat.
4. Respiracion. No administre oxigeno suplementario hasta que el pa-
ciente desarrolle hipoxemia severa. Las concentraciones elevadas de oxigeno en
los pulmones incrementan el dano inducido por el paraquat y, tal vez, tambien
el de diquat. Podrian existir algunas ventajas si se coloca el paciente en un
ambiente moderadamente hipoxico, es decir, 15%-16% de oxigeno, aunque no
se sabe si esta medida de tratamiento es benefica debido a que no se ha estable-
cido empiricamente en envenenamientos humanos. Se ha sugerido la inhala-
cion de oxido nitrico como un metodo para mantener la oxigenacion tisular
en bajas concentraciones de inspiracion de oxigeno, pero su eficacia no ha sido
probada. Cuando la lesion pulmonar se encuentra tan avanzada que no hay
expectativas de recuperacion, proporcione oxigeno para aliviar la falta de aire.
S.Terapia intensiva. En envenenamientos series, debera proveerse el cuidado
en una unidad de terapia intensiva, para permitir el monitoreo apropiado de las
funciones corporeas y el experto desempeiio del monitoreo y procedimientos
agresivos necesarios.
6. Fluidos. Es esencial mantener una excrecion urinaria adecuada.4 Administre
fluidos intravenosos: solucion salina isotonica, solucion de Pvinger o glucosa al 5%
en agua. Esto es altamente ventajoso en el inicio del envenenamiento para corregir
la deshidratacion, acelerar la excrecion del toxico, reducir las concentraciones del
paraquat de los fluidos tubulares y corregir la acidosis metabolica. Sin embargo,
monitoree cuidadosamente el balance de liquidos para evitar la sobrecarga de flui-
dos si aparece insuficiencia renal. Monitoree la orina regularmente para buscar
proteinas y celulas como alerta de necrosis tubular. Suspenda las infusiones intravenosas
si se presenta insuficiencia, e instituya la hemodialisis extracorporea. La hemodialisis
no es eficaz para eliminar el paraquat o diquat de la sangre y tejidos.
7. La hemoperfusion sobre carbon activado recubierto de celofan podria ser
considerada. El procedimiento ha sido utilizado en muchos envenenamientos
con paraquat debido a que el absorbente lo elimina con eficiencia de la sangre
perfundida. Sin embargo, las revisiones recientes sobre la eficacia de la
hemoperfusion no han demostrado que se reduzca la mortalidad como resulta-
do la misma.1'4 La razon aparente es la proporcion tan pequeiia de carga corpo-
rea de paraquat que lleva la sangre circulante, incluso pocas horas despues de la
ingestion. Teoricamente, un paciente que ha sido hemoperfundido dentro de
las primeras 10 horas a partir de la ingestion de paraquat, puede obtener algun
beneficio marginal, pero esto no ha sido demostrado.
Si intenta la hemoperfusion, vigile las concentraciones de calcio y plaquetas.
El calcio y las plaquetas deben ser reemplazados si sus niveles bajan como resul-
tado del procedimiento.
PARAQUAT Y DIQUAT 129
-------
8. Control de convulsiones. La mejor manera de controlar las convulsiones
y la conducta psicotica que en ocasiones ocurren en el envenenamiento por
diquat es administrando lentamente lorazepam por via intravenosa, conio fuera
delineado en el Capitulo 2. Controle las convulsiones como fuera delineado en
el Capitulo 2.
9. Otros medicamentos. Muchos farmacos han sido probados en animates o
se han suministrado a humanos en envenenamientos por bipiridilos sin una
clara evidencia de beneficio o dano: corticosteroides, superoxido dismutasa,
propanolol, ciclofosfamida, vitamina E, riboflavina, niacina, acido ascorbico,
colifibrato, desferrioxamina, acetilcisteina e hidrato de terpina. Sin embargo,
evidencia reciente con respecto al uso de ciclofosfamida y metilprednisolona
podria ser efectiva en la reduccion de la mortalidad asociada con el envenena-
miento moderado y severe por paraquat. Dos estudios encontraron una reduc-
cion de la mortalidad asociada con el tratamiento, mientras que otro estudio no
encontro diferencia alguna.16 Las dosificaciones usadas para la ciclofosfamida y
metilprednisolona fueron 1 gramo diario durante dos dias y 1 gramo diario
durante tres dias respectivamente, y fueron administradas despues de la
hemoperfusion. Cada medicamento fue administrado como una infusion de
dos horas, y el contaje de celulas blancas, los niveles de creatinina serica, la
radiografia toraxica y las pruebas de funcion hepatica fueron monitoreadas.16
10. Control del dolor. El sulfato de morfma se requiere usualmente para
controlar el dolor asociado con las erosiones profundas de la mucosa de la boca,
faringe y esofago, asi tambien como para el dolor abdominal debido a la
pancreatitis y enteritis. Los enjuagues bucales, fluidos frios, helados o compri-
midos anestesicos pueden ayudar a aliviar el dolor en la boca y garganta.
Dosificacion de Sulfato de Morfina:
Adultos y ninos mayores de 12 anos: 10 a 15 mg por via subcutanea
cada 4 horas.
Ninos menores de 12 afios: 0,1 a 0,2 mg/kg peso corporeo cada 4 horas.
11. Transplante. En los casos de toxicidad pulmonar severa, la recuperacion
del paciente tal vez pueda lograrse solamente a traves de un transplante de
pulmon. Sin embargo, el pulmon transplantado es susceptible a danos
subsecuentes debido a la redistribucion del paraquat.17
PB PARAQUAT Y DIQUAT
-------
Estructuras Quimicas Generales
ci
2Br"
Referencias
1. Pond SM. Manifestations and management of paraquat poisoning. MedJAust 1990;! 52:256-9.
2. Giulivi C, Lavagno CC, Lucesoli F, et al. Lung damage in paraquat poisoning and hyper-
baric oxyen exposure: superoxide-mediated inhibition of phospholipase A2. Free Radic
BiolMed 1995;18:203-13.
3. Nordquist RE, Nguyen H, Poyer JL, et al. The role of free radicals in paraquat-induced
cornea! lesions. Free Radic Res 1995;23:61-71.
4. Honore P, Hantson P, Fauville JP, et al. Paraquat poisoning: State of the art. Ada Clin Belg
1994;49:220-8.
5. Bismuth C, Gamier R, Dally S, et al. Prognosis and treatment of paraquat poisoning: A
review of 28 cases.JToxicol ClinToxicol 1982;19:461-74.
6.
Harsanyi L, Nemeth A, and Lang A. Paraquat (gramoxone) poisoning in south-west Hun-
gary, 1977-1984. Am 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 MedJ 1983;59:338-9.
9. Vale JA, MeredithTJ, 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, AzawaJ, Gupta BN, et al. A comparison of the effects of paraquat and diquat on
lung compliance, lung volume, and single-breath diffusing capacity in the rat. Toxicology
1980;18:lll-23.
12. Vanholder R, Colardyn F, DeReuck J, et al. Diquat intoxication: Report of two cases and
review of the literature. Am J Med 1981;70:1267-71.
13. Olson KR. Paraquat and diquat. In: Olson KR et al. (eds), Poisoning and Drug Overdose, 2nd
ed. Norwalk CT: Appelton and Lange, 1994, pp. 245-6.
14. Sechi GP, AgnettiV, Piredda M, et al. Acute and persistent Parkinsonism after use of diquat.
Neurology 1992;42:261-3.
15. Proudfoot AT, Stewart MS, Levitt T, et al. Paraquat poisoning: Significance of plasma-paraquat
concentrations. Lancet 1979;2:330-2.
16. Lin JL, Wei MC, and LiuYC. Pulse therapy with cyclophosphamide and methyprednislone
in patients with moderate to severe paraquat poisoning: A preliminary report. Thorax
1996;51:661-3.
17. Toronto Lung Transplant Group. Sequential bilateral lung transplantation for paraquat poi-
soning. A case report. JThoracic Cardiovas Surg 1985;89:734-42.
PARAQUAT Y DIQUAT 131
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CAPITULO 13
Otros Herbicidas
Actualmente, se encuentran disponibles muchos herbicidas para el uso agricola
y para controlar los yerbajos del cesped y el jardin. Este capitulo trata acerca de
otros herbicidas excluidos de los derivados de clorofenolicos, nitrofenoles y
clorofenoles, arsenicos y bipiridilos, los cuales pertenecen a temas en otros ca-
pitulos. Muchos herbicidas modernos destruyen los yerbajos de manera selec-
tiva impidiendo los procesos metabolicos, unices de la vida vegetal. For esta
razon, la toxicidad sistemica es generalmente baja hacia los mamiferos. No
obstante, hay algunos que posan un riesgo de envenenamiento significativo si
se manejan de manera poco cautelosa,y muchos causan irritacion en los ojos,la
piel y las membranas mucosas.
Existen buenas razones por las que todos los herbicidas mencionados en
este capitulo deban manej arse y aplicarse unicamente con suma atencion a las
medidas de seguridad para minimizar el contacto personal. Muchas formulas
contienen adjutores (estabilizadores, penetrantes, surfactantes) que pueden cau-
sar substanciales efectos toxicos e irritantes. Un numero de formulas ya prepa-
radas contienen dos o mas ingredientes activos; el insecticida acompaiiante puede
que sea mas toxico que el herbicida principal. No se deben ignorar las buenas
practicas de higiene solo porque se haya informado que en las ratas de labora-
torio el insecticida posee un alto DL5Q.
Los profesionales de la salud quienes necesitan evaluar las consecuencias
del contacto previo, deben entender la fatalidad de estos compuestos una vez
hayan sido ingeridos por humanos. Los herbicidas solubles en agua no son
retenidos por largos periodos en los tejidos del cuerpo, asi como lo eran los
viejos insecticidas organocloricos lipofilicos, como el DDT. La mayoria se
excretan, mayormente en la orina, de uno a cuatro dias.
Toxicologia
La tabla en las paginas a continuacion enumera los herbicidas de mayor uso
comun, los cuales no son discutidos en ninguna otra parte de este manual. El DL50
oral critico de las ratas es otorgado como un indice aproximado del potencial de
toxicidad letal. (Si se han informado una serie de valores mediante varias fuentes,
aqui se ha registrado el mas bajo.) La informacion de los efectos adversos se extrae
de distintas fuentes, que incluyen la etiqueta del producto, libros de texto, historias
de casos publicados,y algunos casos que no han sido publicados. Las listas no deben
ser consideradas globales tanto para los productos herbicidas o los efectos.
PB OTROS HERBICIDAS
-------
TOXICIDAD DE LOS HERBICIDAS COMUNES
Clase Quimica
Acetamidas
Acidos alfaticos
Anilidas
Benzamida
Derivados del
acido anisico y
benzoico
Benzonitrilos
Dioxido de
Benzotia-
Diazinona
Carmabatos y
Tio-carmabatos
(herbiddas)
Nombre Generico
metaclor
acido
tridoroacetico
acido didoropro-
pionico (dalapon)
alaclor
propaclor
propanilo
pronamida
acido
triclorobenzoico
dicamba
diclobenilo
bentason
ausulam
terbucarb
butilato
cicloato
pebulato
vernolato
EPIC
dialato
trialato
tiobencarb
Nombre de
Patente
Dual, Pennant,
otros
TCA
Dalapon,
Revenge
Lasso, Alanox
Ramrod, Bexton,
Prolex
DPA, Chem
Rice, Propanex,
Riselect, Stam,
Stampede
Kerb, Rapier
TCBA.Tribac,
2,3,6-TBA
Banvel
Casoron,
Dyclomec, Barrier
Basagran
Asulox
Azac, Azar
Sutan
Ro-Neet
Tillam, PEBC
Vernam
Eptam, Eradicane
Di-allate
Far-go
Bolero, Saturn
DL50 Oral
Critica mg/kg
2,780
5,000
970
1,800
710
>2,500
8,350
1,500
2,700
>4,460
>1,000
>5,000
>34,000
3,500
2,000
921
1,800
1,630
395
1,675
1,300
Posibles
Efectos
Adversos
Irritacion
de ojos y
piel.
Irritacion de
la piel, ojos y
tracto
respiratorio.
Irritacion leve.
Sensitividad e
irritation epidermal.
Irritacion de los
ojos, la piel y
tracto respiratorio.
Moderadamente
irritanteparabsojos.
Moderadamente
irritante para la
piel y el tracto
respiratorio.
Efectos toxicos e
irritantes minimos.
Irritante para los
ojos y el tracto
respiratorio.
Algunos irritan
los ojos, la piel,
y el tracto respi
ratorio, particular-
mente de foma
concentrada.
Algunos pueden
ser inhibidores
debiles de laof
colinesterasa.
OTROS HERBICIDAS 133
-------
TOXICIDAD DE LOS HERBICIDAS COMUNES
Clase Quimica
Carbanilatos
Cloropiridimilo
Derivados de
Ciclohexanona
Derivados de
dinitroamino-
benceno
Compuestos de
Fluorodinitrito-
Toluidina
Isoxazolidinona
Derivados de
Isopropilamina
del acido
nicotinico
Oxadiazolinona
Fosfonatos
Nombre Generico
clorprofan
triclopyr
sethoxydim
butralin
pendimentalina
Orizalina
benfluralina
dinitramina
etalfluralina
flucloralina
profluralina
trifluralina
clomazona
imazapyr
oxadiazon
glifosato
fosamina
de amonio
Nombre de
Patente
Sprout-Nip
Chloro-IPC
Garlon, Turflon
Poast
Am ex
Tarn ex
Prowl, Stamp,
Accotab,
Herbodox,
Go-Go-San,
Wax Up
Surflan, Dirimal
Benefin, Balan,
Balfin, Quilan
Cobex
Sonalan
Basalin
Tolban
Treflan
Command
Arsenal
Ron star
Roundup,
Glyfonox
Krenite
DL50 Oral
Critica mg/kg
3,800
630
3,125
12,600
>5,000
2,250
>1 0,000
>1 0,000
3,000
>1 0,000
1,550
1,808
>1 0,000
1,369
>5,000
>3,500
4,300
>5,000
Posibles
Efectos
Adversos
Irritantes cutaneos.
Pueden produdr
methemoglobina
en dosis altas.
Irritante para la
piel y los ojos.
Irritantes para la
piel y los ojos.
Moderadamente
irritantes. Estos
herbicidas no
desacoplan la
fosforilacion
oxidante ni
generan
methemoglobina.
Moderadamente
irritantes. Estos
herbicidas no
desacoplan la
fosforilacion o
generan
methemoglobina.
Moderadamente
irritante.
Irritante para los
ojos y la piel. No
contiene
arsenico.
Minimos efectos
toxicos e
irritantes.
Irritating to eyes,
skin, and upper
respiratory tract.
Irritante para los
ojos, la piel y el
tracto respiratorio
superior.
PB OTROS HERBICIDAS
-------
TOXICIDAD DE LOS HERBICIDAS COMUNES
Clase Quimica
Ptalatos
Compuestos de
acido picolfnico
Triazinas
Triazoles
Nombre Generico
clortaldimetilo
endotal
pidoran
ametrina
atrazina
crisazina
desmetrina
metribuzina
prometrina
propazina
simazina
terbutilazina
terbutrin
prometon
amitrol,
aminotriazol
Nombre de DL50 Oral
Patente Critica mg/kg
Dachthal, DCPA >1 0,000
Aquathol 51
Tordon, Pinene 8,200
Ametrex, Evik, 1,750
Gesapax
Aatrex, Atranex, 1,780
Crisazina
Bladex, Fortrol 288
Semeron 1,390
Sencor, Lexone, 1,100
Sencoral, Sencorex
Caparol, Gesagard, 5.235
Prometrex
Milo-Pro, >7,000
Primatol, Prozinex
Gesatop, Princep, >5,000
Caliber 90
Gardoprim, 2,000
Primatol M
Ternit, Prebane, 2,500
Terbutrex
Gesafram 50 2,980
Pramitol 25E
Amerol, Azolan, >1 0,000
Azole, Weedazol
Posibles
Efectos
Adversos
Moderadamente
Irritanteparabsojos.
Es un radical libre
altamente toxico
Irritante para los
ojos, la piel y el
tracto respiratorio.
Veaseel Capitulo2.
Irritante para los
ojos, la piel y el
tracto respiratorio.
Baja toxiddad
sistemica.
Improbable
toxicidad
sistematica a
menos que se
ingieran grandes
cantidades
Algunas triazinas
son
moderadamente
irrritantes para
los ojos, la piel y
el tracto
respiratorio.
Esta formula
particular de
prometon es
fuerte mente
irritante para los
ojos, la piel el
tracto respiratorio.
Toxicidad sistemica
minima. Leve
efecto irritante.
OTROS HERBICIDAS 135
-------
TOXICIDAD DE LOS HERBICIDAS COMUNES
Clase Quimica
Uracilos
Derivados
De Urea
Nombre Generico
bromacilo
lenacilo
terbacilo
dorimuron
etilico
dorotoluron
diuron
flumeturon
isoproturon
linuron
metabenzo-
tiazuron
metobromuron
metoxuron
monolinuron
monuron
neburon
siduron
sulfometuron-
metilo
Nombre de
Patente
Hyvar
Venzar
Sinbar
Classic
Dicuran, Tolurex
Cekiuron,
Crisuron, Dilon,
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
DL50 Oral
Critica mg/kg
5,200
>1 1,000
>5,000
>4,000
>1 0,000
>5,000
8,900
1,826
1,500
5,000
2,000
3,200
2,100
3,600
>1 1,000
>7,500
>5,000
Posibles
Efectos
Adversos
Irritante para los
ojos, la piel y el
tracto respipiratorio.
Moderadamente
irritante.
Improbable
toxicidad
sistemica a
menos que se
ingieran grandes
cantidades.
Muchos
derivados de
urea irritan los
ojos, la piel y las
membra nas
mucosas.
tebutiuron
Spike, Tebusan
644
PB OTROS HERBICIDAS
-------
Confirmacion de Envenenamiento
A pesar de que existen metodos analiticos para [estudiar] los residues de
muchos de los herbicidas mencionados en este capitulo y para algunos de los
metabolites generados de ellos, estos procedimientos no estan generalmente
disponibles para corroborar [que haya ocurrido] absorcion quimica humana.
El contacto tiene que ser determinado mediante el reciente historial ocupacio-
nal o mediante la ingestion deliberada o accidental.
Tratamiento
1. Descontaminacion dermica. La contaminacion dermica debe tratarse a
tiempo mediante el lavado con agua yjabon. La contaminacion ocular debe
tratarse inmediatamente a traves de un prolongado enjuague utilizando una
abundante cantidad de agua limpia. Si la irritacion ocular y dermica persiste,
obtenga cuidado medico lo mas pronto posible. Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Probablemente despues de la in-
gestion de estos herbicidas ocurran vomitos y diarrea debido a sus propiedades
irritantes. El manejo dependera de: (1) el mejor estimado de la cantidad inge-
rida, (2) el lapso de tiempo desde la ingestion, y (3) el estado clinico del sujeto.
El carbon activado es probablemente lo mas efectivo para eliminar los
efectos irritantes y la reduccion de la absorcion para la mayoria de todos estos
herbicidas. Los antiacidos de hidroxido de aluminio pueden ser utiles para la
neutralizacion de las acciones irritantes de los agentes mas acidosos. Administre
sorbitol para inducir catarsis si existen sonidos intestinales y de no haber comen-
zado la diarrea espontanea. La deshidratacion y disturbios electroliticos pueden
ser lo suficientemente severos como para requerir fluidos intravenosos u orales.
No existen antidotes especificos para el envenamiento de estos herbicidas.
En caso, particularmente de ingestion suicida, debe mantenerse siempre en
mente la posibilidad de que se hayan ingerido multiples sustancias toxicas.
Si se han ingerido grandes cantidades de herbicidas y el paciente es visto
dentro de una hora de la ingestion, debe considerarse la descontaminacion
gastrointestinal, como fuera explicado en el Capitulo 2.
Si la cantidad del herbicida ingerido fuese pequena, y si ha ocurrido una
emesis efectiva, o si el tratamiento ha sido demorado, administre carbon activa-
do y sorbitol por via bucal.
3. Fluidos intravenosos. Si ha ocurrido una deshidratacion seria o una baja
de electrolitos como resultado de vomitos y diarrea, examine los electrolitos
sanguineos y el balance de los fluidos y administre suero intravenoso de glucosa,
normal o salino, solucion Ringer o lactato de Ringer para restaurar el volumen
del fluido extracelular y de los electrolitos. Continue esto con nutrientes orales
tan pronto como se empiecen a retener los fluidos.
OTROS HERBICIDAS 137
-------
4. Medidas de apoyo son generalmente suficientes para el manejo exitoso del
contacto excesivo de los herbicidas (endotal es la excepcionvease el Capitulo
18, p. 207. Si la condicion del paciente se deteriorara a pesar de las medidas de
apoyo, es sospechado que este operando un toxico adicional o alternative.
PB OTROS HERBICIDAS
-------
Seccion IV
OTROS PESTICIDAS
-------
CAPITULO 14
PUNTOS
IMPORTANTES
Los efectos al SNC, vasos
sanguineos, rifion e
hfgado pueden causar la
muerte
Senales y Smtomas:
En casos agudos, fuerte
olor a ajo en el alientoy
las heces fecales y
sintomas Gl adversos
En casos cronicos,
debilidad muscular,
fatiga, perdida de peso,
hipercoloradon,
hiperqueratosisy Ifneas
de Mees
Tratamiento:
Descontaminadon
gastrointestinal
Terapia de quelacion
Dimercaprol (BAL) o
DMPS para acelerar la
excrecion de arsenicos
Pesticidas Arsenicales
Muchos compuestos arsenicales han sido descontinuados en los Estados Unidos
como resultado de normas gubernamentales. Sin embargo, los insecticidas arsenicales
aun pueden obtenerse con facilidad en algunos paises y en muchas fincas y hogares
existen cantidades sobrantes que continuan siendo un riesgo residual.
El gas arsina es tratado separadamente en la pagina 146.
Toxicologia
El arsenico es un elemento natural que tiene propiedades fisicas y quimicas
de metales y de no metales. En algunos aspectos, se asemeja al nitrogeno, fosfo-
ro, antimonio y bismuto en su comportamiento quimico. En la naturaleza, exis-
te en sus estados elemental, trivalente (-3 6 +3) y pentavalente (+5). Se liga
compartiendo su carga equivalente con la mayoria de los no metales (particu-
larmente con oxigeno y sulfuro) y con los metales (por ejemplo, calcio y plo-
mo). Forma compuestos trivalentes y pentavalentes organicos estables. En su
comportamiento bioquimico se asemeja al fosforo, compitiendo con los fosfo-
ros analogos por los puntos de aleacion quimica.
La toxicidad de varies compuestos arsenicos en los mamiferos cubre un am-
plio ambito, determinado en parte por las acciones excepcionales bioquimicas de
cada compuesto, pero tambien por la eficiencia y absorbencia de las transforma-
ciones biologicas y la disposicion. En general, los [gases] arsinas posan el mayor
riesgo toxico, seguido de cerca por los arsenitos (compuestos inorganicos
trivalentes). Los compuestos inorganicos pentavalentes (arseniatos) son apenas
menos toxicos que los arsenitos, mientras que los compuestos organicos (metilados)
pentavalentes representan a los insecticidas arsenicales de menor riesgo.1
Los arsenicales pentavalentes son relativamente solubles en agua y son absor-
bidos a traves de las membranas mucosas. Los arsenicales trivalentes que tienen
una mayor solubilidad lipida, son absorbidos mas rapidamente a traves de la piel.2
Sin embargo, los envenenamientos por absorcion cutanea de cualquiera de estas
formas han sido muy raros. La ingestion ha sido la forma usual de envenenamien-
to; pero la eficiencia de la absorcion depende de la forma fisica del compuesto, sus
caracteristicas de solubilidad, el pH gastrico, la movilidad gastrointestinal y las
tranformaciones microbianas del intestine. El contacto con arsina ocurre primor-
dialmente por medio de inhalacion y sus efectos toxicos pueden ocurrir tambien
con otros arsenicales mediante la inhalacion de aerosoles.
PB
ARSENICALES
-------
Una vez absorbidos, muchos arsenicales causan lesiones toxicas a las celulas
del sistema nervioso, los vasos sanguineos, el higado, los rinones,y otros tejidos.
Se reconocen dos mecanismos bioquimicos de toxicidad: (1) la combinacion
reversible con los grupos tioles contenidos en proteinas de los tejidos y las
enzimas, y (2) la sustitucion de aniones de arsenico en lugar de fosfatos en
muchas reacciones, incluyendo aquellos criticos para la fosforilacion oxidativa.
El arsenico se metaboliza rapidamente en el rinon a una forma de metilo, la
cual es mucho menos toxica y facilmente excretada. Sin embargo, es general-
mente mas seguro manejar los casos de insecticidas arsenicales como si todas las
formas fueran altamente toxicas.
La toxologia unica del gas arsina es descrita mas tarde en este capitulo.
Sehales y Sintomas de Envenenamiento
Las manifestaciones de un envenenamiento agudo son distintas a aquellas
de un envenenamiento cronico.
Envenenamiento agudo de arsenico: Las senales y sintomas aparecen
generalmente dentro de la hora despues de la ingestion, pero pueden retrasarse
por varias horas. Un olor a ajo en el aliento y en las heces fecales puede ayudar
a identificar el toxico en pacientes severamente envenenados. Hay un sabor
metalico presente en la boca la mayoria de las veces. Predominan efectos
gastrointestinales adversos, con vomitos, dolor estomacal, y diarrea sangrienta o
como de agua de arroz, estos son los sintomas mas comunes. Otros efectos
gastrointestinales incluyen, la formacion vesicular y eventualmente esfacelo de
la mucosa de la boca, faringe y esofago.3 Estos efectos son resultados de un
metabolito arsenical generalmente en los vasos sanguineos, causando dilatacion
y aumento de la permeabilidad capilar y particularmente en la vasculatura
esplecnica.
El sistema nervioso central tambien es comunmente afectado durante el
contacto agudo. Los sintomas pueden comenzar con dolor de cabeza, mareo,
letargo, y confusion. Los sintomas pueden progresar incluyendo espasmos y
debilidad muscular, hipotermia letargo, delirio, y convulsiones.1 El dano renal
se manifiesta por proteinuria, hematuria, glicosuria, oliguria, residues en la ori-
na, y, en casos de envenenamiento severe, necrosis tubular aguda. Las manifesta-
ciones cardiovasculares incluyen shock, cianosis y arritmia cardiaca,4'5 las cuales
se deben a la accion toxica directa y a los disturbios electroliticos. El dano
hepatico se puede manifestar por un incremento de las enzimas del higado e
ictericia. La lesion en los tejidos hematopoyeticos puede causar anemia,
leucopenia y trombocitopenia.
La muerte ocurre de uno a tres dias despues de iniciarse los sintomas y
generalmente el resultado es fallo circulatorio, aunque el fallo renal tambien
puede ser contribuyente.1 Si el paciente sobrevive, este puede sentir entumeci-
miento en las manos y en los pies como una secuela retardada de contacto
Productos Comerdales
(Muchos han sido suspendidos)
acido arsenico
Hi-Yield Dessicant H-10
Zotox
trioxido arsenico
acido cacodflico (cacodilato sodico)
Bolate
Bolls-Eye
Bophy
Dilie
Kack
Phytar 560
Rad-E-Cate25
Salvo
calcio acido metanoarsonico
(CAMA)
Calar
Super-Crab-E-Rad-Calar
Super Dal-E-Rad
arsenato de calcio
Spra-cal
arsenato tricalcico
Turf-Cal
arsenito de calcio
London purple
arsenito mono-calcico
acetoarsenito de cobre
Emerald green
French green
Mitis green
Paris green
Schweinfurt green
arsenito de cobre (acido arsenito
cuprico)
arsonato metano disodico
Ansar8100
Arrhenal
Arsinyl
Crab-E-Rad
Di-Tac
DMA
DSMA
Methar30
Sodar
Weed-E-Rad 360
arsenato de plomo
Gypsine
Soprabel
Acido metano arsonico (AMA)
arsonato metano monoamonio
(MAMA)
arsonato metano monosodico
(MSMA)
Ansar 170
(Continue en la proxima pagina)
ARSENICALES 141
-------
Productos Comerdales
(Continuation)
Arsonato liquido
Bueno 6
Daconate 6
Dal-E-Rad
Drexar 530
Herbi-AII
Merge 823
Mesamate
Target MSMA
Trans-Vert
Weed-E-Rad
Weed-Hoe
arsenato sodico
arsenato disodico
Jones Ant Killer
arsenito sodico
Prodalumnol Double
Sodanit
arsenato de zinc
agudo asi corno comezon y parestesia dolorosa. Esta neuropatia periferal del
sistema sensoriomotor que incluye debilidad muscular y espasmos, tipicamente
empieza de una a tres semanas despues del contacto.6 La debilidad muscular no
debe ser confundida con el sindrome Guillain-Barre.7
El envenenamiento cronico de arsenico debido a la absorcion repeti-
da de cantidades toxicas tiene una aparicion insidiosa de efectos clinicos que
pueden ser dificiles de diagnosticar. Las manifestaciones neurologicas cutaneas
y no especificas son usualmente mas prominentes que los efectos gastrointestinales
que caracterizan el envenenamiento agudo. Puede ocurrir fatiga y debilidad
muscular asi como anorexia y perdida de peso. Una senal comun es la
hiperpigmentacion y tiende de ser acentuada en areas que generalmente estan
mas pigmentadas asi como la ingle y la areola. Hiperqueratosis es otra senal
comun especialmente en la palma de las manos y en la planta de los pies.8'9
Edema subcutaneo de la cara, parpados y tobillos asi como estomatitis, estrias
blancas a lo largo de las unas (lineas de MEES),y algunas veces perdida de unas
y pelo son otros signos de contacto cronico y continue.1>9 En ocasiones estas
papulas hiperqueratosicas pueden resultar en transformaciones malignas.8 Des-
pues de anos de contacto dermatologico, se han encontrado celulas basales
carcinomas, celulas escamosas generalmente en areas protegidas del sol. Sinto-
mas neurologicos tambien son comunes con el contacto cronico. Una caracte-
ristica destacada puede ser la neuropatia periferal manifestada por parestesia,
dolor, anestesia, paresis o ataxia. Puede comenzar con sintomas sensoriales de
las extremidades bajas y progresar a debilidad muscular y eventualmente parali-
sis y desgaste muscular. Aunque poco comun, se puede desarrollar encefalopatia
con disturbio del habla y mentales muy parecidos a aquellos evidenciados en
deficiencia de tiamina (sindrome deWernickes).
Otros sistemas son afectados por la toxicidad arsenica. Los danos hepaticos
reflejados en la hepatomegalia e ictericia pueden progresar a cirrosis hipertension
portal y ascitis. El arsenico tiene una toxicidad glomerular y tubular directa que
resulta en oliguria, proteinuria y hematuria. Se han informado anormalidades
electrocardiograficas (prolongacion del intervalo Q-T) y enfermedad vascular
periferal. Esta ultima incluye acrosianosis, el fenomeno de Raynaud, y gangrena.1>10
Anormalidades hematologicas incluyen anemia, leucopenia, y trombositopenia.1
Esta ultima secuela de altas dosis de arsenico incluye cancer de la piel como
descrito anteriormente y un alto riesgo de cancer del pulmon.1'8
Confirmacion de Envenenamiento
El metodo mas comun para confirmar la absorcion excesiva de arsenico es
mediante la medicion de excrecion urinaria (microgramos por dia) durante un
periodo de 24 horas, siendo este el metodo preferido para observar niveles
consecutivos y para evaluar el contacto cronico.1'11 El metodo recomendado
para evaluar el contacto ocupacional es el analisis inmediato de arsenico en la
PB
ARSENICALES
-------
orina, expresado en una razon de creatinina urinaria.12 Hay metodos disponi-
bles para determinar la concentracion de arsenico en la sangre; sin embargo, los
niveles de sangre tienden a correlacionar pobremente con el contacto excepto
en la fase inicial aguda.11'13 Deben usarse envases especiales no-metalicos, lava-
dos en acido para la coleccion del especimen. Una excrecion de arsenico que
exceda sobre 100 meg al dia debe ser considerada sospechosa y la prueba debe
ser repetida.
Excreciones sobre 200 meg al dia reflejan una ingestion toxica, a no ser que
se hayan ingerido mariscos. n>13>14>15 Una dieta rica en mariscos, principalmente
durante las primeras 48 horas, pudiera generar un nivel de excrecion de orina de
24 horas tan alto como de 200 meg al dia y muchas veces hasta mas alto.3'14 La
mayoria del arsenico marino que es excretado es de forma metilada (arsenobetano)
y no es considerado extremadamente toxico. Sin embargo, un estudio reciente
confirma que parte del arsenico liberado por los mejillones puede contener ma-
yores cantidades de trioxido de arsenico que lo previamente pensado.14 El arseni-
co en la orina se puede separar en fracciones organicas e inorganicas para ayudar
a determinar la fuente de contacto y ayudar con la guia del tratamiento.
Las concentraciones de arsenico en la sangre, orina y otros materiales bio-
logicos se pueden medir por medio de incineracion seca o humeda, seguido de
una espectrometria de absorcion atomica. Este ultimo metodo es el preferido.
Las concentraciones en la sangre en exceso de 100 meg por litro probablemen-
te indica ingestion o contacto ocupacional, siempre y cuando no se hayan inge-
rido mariscos antes de que se haya tornado el especimen.3'11'13'15 Las muestras de
sangre tienden a estar correlacionadas con las muestras de orina durante las
primeras etapas critica de ingestion,n pero debido a que el arsenico desaparece
rapidamente de la sangre, la muestra de orina de 24 horas permanece como el
metodo preferido para la deteccion y continua observacion.1>11>13 Las muestras
de cabello tambien han sido usadas para evaluacion del contacto cronico. Los
niveles de personas no expuestas generalmente son lmg/kg;los niveles en indi-
viduos con envenenamiento cronico varian entre 1 y 5mg/kg.15 Las muestras
de cabello deben ser estudiadas con cautela debido a factores externos de con-
taminacion ambiental tales como la contaminacion del aire, la cual puede au-
mentar los niveles de arsenico.
Pruebas especiales para toxicosis de arsina estan descritas en la pagina 146
bajo el "Gas Arsina."
Tratamiento
La siguiente discusion se aplica principalmente a envenenamientos por
arsenicales solidos o de forma disuelta. El tratamiento del envenenamiento con el
gas arsina requiere medidas especiales descritas a continuacion en la pagina 146.
1. Descontaminacion dermica. Lave el insecticida arsenical de la piel y el
cabello con abundante cantidad de agua y jabon. Enjuague la contaminacion
ARSENICALES 143
-------
ocular con agua clara. Si la irritacion persiste, obtenga cuidado medico especia-
lizado.Vease el Capitulo 2.
2. Descontaminacion gastroinstestinal. Si el insecticida arsenical se ha in-
gerido dentro de la primera hora del tratamiento, se debera considerar la des-
contaminacion gastrointestinal, como fuera delineado en el Capitulo 2. Debido
a que el envenenamiento por ingestion casi siempre resulta en diarreas profusas,
no es apropiado generalmente administrar un catartico.
3. Fluidos intravenosos. Administre fluidos intravenosos para restaurar la
hidratacion adecuadamente, mantener el flujo urinario, y corregir el desbalance
de electrolitos. Observe continuamente el ingreso/egreso para evitar una so-
brecarga de fluidos. Si ocurre insuficiencia renal aguda, revise los electrolitos de
la sangre regularmente. Es posible que sea necesario administrar tratamientos
de oxigeno y transfusiones de sangre para combatir el shock.
4. Monitoreo cardiopulmonar. Monitoree el estado cardiaco por EGG para
detectar arritmias ventriculares incluyendo intervales Q-T alargados y taquicardia
ventricular, y miocardiopatia (inversion de la ondaT, intervalo S-T alargado).
S.Terapia de quelacion. En caso de envenenamiento sintomatico de arsenico
se indica generalmente la administracion de Dimercaprol (BAL), aunque DMPS,
cuando disponible, pruebe ser un mejor antidoto. El esquema de dosis a conti-
nuacion ha probado ser efectivo para la aceleracion de la excrecion de arsenico.
Monitoree la excrecion de arsenico en la orina mientras se este adminis-
trando cualquier agente quelante.Tan pronto la excrecion de 24 horas disminu-
ya bajo 50 meg por dia, es recomendable suspender la terapia de quelacion.
DOSIFICACION INSTRAMUSCULAR RECOMENDADA DE BAL
(DIMERCAPROL) EN ENVENENAMIENTO POR ARSENICO
Envenenamiento Grave Envenenamiento Leve
1erdfa
2* dia
3'd dia
Diario por 10 dias,
o hasta la
recuperadon
3.0 mg/kg c/4h
(6 inyecciones)
3.0 mg/kg c/4h
(6 inyecciones)
3.0 mg/kg c/6h
(4 inyecciones)
3.0 mg/kg c/12 hr
(2 inyecciones)
2.5 mg/kg c/6h
(4 inyecciones)
2.5 mg/kg c/6h
(4 inyecciones)
2.5 mg/kg q12h
(2 inyecciones)
2.5 mg/kg c/dia
(1 inyecciones)
El BAL es propordonado como una solution oleosa de 10Omg/ml. Las fracdones senaladas en la
tabla estan en terminos del BAL mismo, no de la solution. La dosis de ninos es consistente con el
esquema de la fraction de "Envenenamiento Leve" y puede ser entre 2,5 y 3,0 mg/kg per dosis.16
PB
ARSENICALES
-------
Advertencia: El uso de BAL va acompanado a menudo de efectos secunda-
rios desagradables: nauseas, dolor de cabeza, sensacion de comezon y ardor,
sudor, dolor de espalda y abdomen, temblor, inquietud, taquicardia, hipertension
y fiebre. En dosis altas, pueden ocurrir coma y convulsiones. Pueden formarse
absesos esteriles en los lugares donde se aplique la inyeccion. Los sintomas
criticos disminuyen despues de haber pasado 30 a 90 minutos. La administra-
cion de antiestaminicos o una dosis oral de 25-50 mg de sulfato de efedrina
proporcionan alivio. Estos son mas efectivos si se administran unos minutos
antes de inyectar el BAL. El BAL potencialmente puede tener otros efectos
adversos. Se ha encontrado que el tratamiento del contacto con arsenito con
BAL ha aumentado el nivel de arsenico en conejos.17
6.Tratamiento oral. Despues que el tracto gastrointestinal se encuentre razo-
nablemente libre de arsenico, debe de reemplazarse la terapia de BAL con
administracion de D-Penicilamina, succimer (DMSA) 6 DMPS. Sin embargo,
la D-Penicilamina ha demostrado efectividad limitada al contacto de arsenico
en modelos experimentales.18
Dosificacion de D-Penicilamina:
Para adultos y ninos mayores de 12 anos:0,5g cada 6 horas, administra-
da de 30 a 60 minutos antes de comidas y al momento de acostarse
por un periodo de unos 5 dias.
Para ninos menores de 12 anos: 0,lg/kg peso corporeo, cada 6 horas
administrada de 30 a 60 minutos antes de comidas y al momento de
acostarse por un periodo de unos 5 dias. No exceda l,0g por dia.
Advertencia: Las reacciones adversas a terapia de corto plazo son
raras. Sin embargo, las personas alergicas a la penicilina no deben de
recibir tratamiento de D-Penicilamina ya que pueden sufrir reacciones
alergicas a esta.
Succimer (DMSA) ha demostrado ser efectivo como terapia de quelacion de
arsenico, aunque no ha sido catalogado para esta indicacion.19 El DMPS ha sido
usado efectivamente en Europa en el tratamiento de envenenamiento con arse-
nico. Ante la falta de eficacia de la D-Penicilamina, parece ser que el aparea-
miento de la baja toxicidad y el alto indice terapeutico del DMPS y el DMSA
estos dos agentes pudieran ser el metodo preferido para toxicidad cronica o
cuando la terapia de quelacion oral es aceptable.18>19
ARSENICALES 145
-------
Dosificacion de DMSA (Succimer):
Adultos y ninos: lOrng/kg cada 8 horas por 5 dias, seguido por lOmg/
kg cada 12 horas por 14 dias adicionales. (Maximo de SOOmg per
dosis). Debe ser administrado con alimentos.
Dosificacion de DMPS:
Adultos: lOOmg cada 8 horas entre 3 semanas a 9 meses.
7. Hemodialisis: La hemodialisis extracorporea, usada en combinacion con la
terapia BAL, tiene una efectividad limitada en la eliminacion de arsenico de la
sangre. La hemodialisis es claramente indicada para mejorar la eliminacion del
arsenico y mantener la composicion del fluido extracelular en caso de que
ocurra un fallo renal agudo.
8. Funcion Renal: En pacientes con funcion renal intacta, la alcalinizacion de
la orina por el bicarbonate de sodio para mantener un pH de orina > 7,5
podria ayudar a proteger la funcion renal ante la ocurrencia de hemolisis como
parte del envenenamiento agudo.
PUNTOS
IMPORTANTES
Hemosflico potente
Senales y Smtomas:
Malestar, mareo, nausea y
dolor abdominal
Hemoglobinuria e ictericia
Tratamiento:
De apoyo
Puede considerarse una
exsanguineo-transfusion
GAS ARSINA
El gas arsina no se usa como insecticida. Sin embargo, han ocurrido
algunos envenenamientos por arsina en plantas manufactureras de insec-
ticidas y en operaciones de refinacion de metales cuando los arsenicales
entran en contacto con minerales acidos 6 fuertes agentes reductores.
Toxicologia
El gas arsina es una hemolicina poderosa, una accion toxica no ex-
hibida por otros arsenicales. En algunos individuos un contacto leve por
inhalacion puede desarrollar una reaccion hemolitica grave. Un contacto
de 25-50 partes por millon por 30 minutos es considerado letal.20 Los
sintomas de envenenamiento aparecen usualmente de 1 a 24 horas des-
pues del contacto: dolor de cabeza, malestar, debilidad, vertigo, nausea,
disnea, dolor estomacal y vomitos. De 4 a 6 horas despues del contacto
aparece un color rojo en la orina (hemoglobinuria). Generalmente de 1 a
2 dias despues que aparece la hemoglobinuria la ictericia es evidente.
Anemia hemolitica, muchas veces intensa, es confirmada generalmente y
PB
ARSENICALES
-------
puede causar debilidad severa. Se observan con frecuencia hipersensiblidad
abdominal y agrandamiento hepatico. En un frotis de sangre pueden
observarse un puntiado de los eritrocitos en forma de basofilos, fragmen-
tos de eritrocitos y eritrocitos despigmentados como evidencia de
metahemoglobinemia y metahemoglobinuria. Se encuentran en la orina
concentraciones elevadas de arsenico, pero estas no son tan altas como las
que se encuentran en los envenenamientos por arsenicales solidos. El
contenido plasmatico de la bilirrubina no conjugada es elevado. La insu-
ficiencia renal debido a la accion toxica directa de la arsina y a los pro-
ductos de la hemolisis representa la principal amenaza de vida en el enve-
nenamiento por arsina.21
Se ha informado un sindrome psicologico leve y polyneuropatia luego
de haber ocurrido una intoxicacion de arsina despues de un periodo
latente de 1 a 6 meses.
Tratamiento
1. Traslade a la victima a un lugar ventilado con aire fresco.
2. Administre fluidos intravenosos para mantener la orina lo mas diluida
posible y ayudar a la excrecion del arsenico y los productos de la hemolisis.
Incluya suficiente bicarbonate de sodio para mantener la orina alcalina
(con un pH mayor de 7,5).
Advertencia: Monitoree cuidadosamente el balance de los fluidos
para evitar una sobrecarga en caso de que ocurra una insuficiencia renal.
Vigile los electrolitos plasmaticos para detectar irregularidades (especial-
mente hiperkalemia) lo mas pronto posible.
3. Monitoree la excrecion urinaria de arsenico para evaluar la severidad
del envenenamiento. La cantidad de arsina necesaria para causar envene-
namiento es pequeiia, y por lo tanto, no se deben encontrar altos niveles
de arsenico en la excrecion de orina, aun ante un envenenamiento signi-
ficativo.21'22
4. Si ocurre un envenenamiento severe, debe considerarse la posibilidad
de una exanguinotransfusion sanguinea. Este fue un tratamiento positive
en el rescate de una victima de envenenamiento por arsina.
5. Es necesario que se administre hemodialisis extracorporea para mante-
ner la composicion normal de los liquidos extracelulares y ayudar a eli-
minar el arsenico si ocurriera un fallo renal, pero no es muy eficaz para la
eliminacion del [gas] arsina transportado en la sangre.
ARSENICALES 147
-------
Estructuras Quimicas Generales
TRIVALENTES INORGANICOS
Trioxido de Arsenico
O
/ \
As-O-As
"Arsenico bianco." Oxido Arsenuoso Ha
estado fuera de circulacion pero puede ser
obtenido a traves de registros viejos.
Arsenito de Sodio
Na-O-As = O
Sodanit, Prodalumnol doble. Todos sus
usos se encuentran fuera de circulacion.
Arsenito de Calcio
O As = O
I
C3 (aprox.)
I
O As = O
Arsenito monocalcico, Purpura de
Londres. Polvo liquido absorbente para uso
insecticida en frutas.Todos sus usos se
encuentran fuera de circulacion.
Arsenito de Cobre
(Arsenito acido de cobre)
HO-Cu-O-As = O
Polvo liquido absorbente que se usa corno
Insecticida, y preservador de rnadera. El uso
esta fuera de circulacion en los E.E.U.U.
Acetoarsenito de Cobre
O
Cu-(O-C-CH3)2
3Cu-(O-As=O)2
Insecticida.Verde de Paris, verde
Schweinfurt, verde esmeralda, verde
frances, verde mitis.Ya no se usa en los
E.E.U.U.; todavia se usa en otros paises.
H
Arsina
H
\
As
I
H
No es un insecticida. Generado
ocasionalmente durante la produccion
de arsenicales.
PENTAVALENTES INORGANICOS
Acido arsenico
OH
HO
\ I
As=O
Hi-Yield Dessicant H-10, Zotox. Solucio-
nes acuosas utilizadas corno defoliantes,
herbicidas y preservadores de rnadera.
HO
Arseniato de sodio
OH
NaO
As=O
Arseniato disodico Jones Ant Killer Todo su
uso se encuentra fuera de circulacion, pero
puede ser encontrado a traves de registros
viejos.
NaO
PB
ARSENICALES
-------
o
x \
Ca As O
\ x
O
Arseniato de Calcio
O O
Ca
o
^ x \
O As Ca
\ x
O
Arsenato tricalcico, Spra-cal,Turf-cal.
Formula en polvo liquido absorbente
usado en contra yerbajos y larvas. No se
usa en los Estados Unidos.
Arseniato de Plomo
O OH
x \
Pb As = O
\ x
O
Gypsine, Soprable,Talbot. De uso
limitado en los Estados Unidos; polvo
liquido absorbente que se usa corno
insecticida en otros paises.
O
x \
Zn As
\ x
O
Arseniato de Zinc
O O O
^. x \
O Zn O As Zn
\ x
O
Polvo que se uso en los Estados
Unidos conio insecticida para papas y
tomates.
(PENTAVALENTES) ORGANICOS
Acido cacodilico (cacodilato de sodio) Herbicida no selective, defoliante
silvicida. Bolate, Bolls-eye, Bophy, Dilc,
CH3 ^ ^ CH3 Kack^ phytar 56Q^ Rad_E_Cate 25, Salvo.
As
# \
O OH
(or Na)
Acido metanoarsonico
CH3 OH
\ x
As
t \
O OH
MAA. Herbicida no selective.
Metanoarsonato Monosodico
CH3 OH
\ x
As
* \
O OH
MSMA. Herbicida no slectivo, defoliante,
silvicida. Ansar 170,Arsonato Liquido,
Bueno 6, Dal-E-Rad, Drexar 530, Herbi-
All, Merge 823. Mesamate,Target MSMA,
Trans- Vert, Weed-E-Rad-Weed-Hoe.
Metanoarsonato disodico
CH3 ONa
\ x
As
S \
O ONa
MSMA. Herbicida no selective, defoliante,
silvicida. Anthar 8100, Arrhenal, Arsinyl,
Crab-E-Rad, Di-Tac, DMA, Methar 30,
Sodar,Weed-E-Rad 360.
Metanoarsonato monoamonico
CH3 ONH4
\ x
As
x \
O OH
MOMA. Herbicida post emergente
selectivo.
ARSENICALES 149
-------
Metanoarsonato acido de calcio CAMA. Herbicida post emergente
,-,, _,, u/-. _,, selective. Calar, Super Crab-E-Rad-Calar,
i-rlo \Jr\ n{J *-no
_
3\ / \ X 3 Super Dal-E-Rad.
As As
// \ / -^
O - Ca - O O
Referencias
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 EnglJ
Med 1980; 303(19).1096-8.
6. Heyman A, Pfeiffer JB Jr., Willett RW, et al. Peripheral neuropathy caused by arsenical in-
toxication. A study of 41 cases with observations on the effects of BAL (2,3-dimercapto-
propanol). NEnglJ Med 1956;254:401-9.
7. Donofrio PD.Wilbourn AJ, Albers JW, et al. Acute arsenic intoxication presenting as Guillain-
Barre-like syndrome. Muscle Nerve 1987; 10:114-20.
8. Maloney ME. Arsenic in dermatology. Dennatol Surg 1996;22:301-4.
9. Navarro B, Sayas MJ, Atienza A, and Leon P. An unhappily married man with thick soles.
Laซotf 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.
AmJEmergMed, 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 follow-
ing ingestion of marine organisms by volunteers. Environ Res 1994;66:44-51.
15. Baselt RA and Cravey RH. Arsenic. In: Disposition ofToxic Drugs and Chemicals in Men,
3rd ed. Chicago, IL: Year Book Medical Publishers, 1990, pp. 65-9.
16. Barone MA. Drug doses; Dimercaprol. In:The Harriet Lane Handbook, 14th ed. Baltimore:
Mosby 1996, p. 525.
17. Hoover TD and Aposhian HV. BAL increased the arsenic-74 content of rabbit brain. Toxicol
Appl Pharmacol 1983; 70:160-2.
18. Kreppel H, Reichl FX, Forth W, and Fichtl B. Lack of effectiveness of d-penicillamine in
experimental arsenic poisoning. Vet Hum Toxicol 1989;31:l-5.
19. Miickter 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.
PB ARSENICALES
-------
20. BlackweU M and Robbins A. NIOSH Current Intelligence BuUetin #32, Arsine (arsenic
hydride) poisoning in the -workplace. Am Ind HygAssoc] 1979;40:A56-61.
21. Fowler BA and WeissbergJB. Arsine poisoning. New Engl] Med 1974;291:1171-4.
22. Radius E, Stingon RG, and PutmanJL.Arsine poisoning, country style. MedJAust 1979;l:163-6.
ARSENICALES 151
-------
CAPITULO 15
PUNTOS
IMPORTANTES
El uso de una gran cantidad
de fungicidas con varies
niveles toxicos
Aparte de los compuestos
organomercuricos, la
mayoria de los fungicidas
una baja probabilidad de
aborcion para causar
envenenamientos
sistemicos
Senates y Smtomas:
Variados
Tratamiento:
Descontaminadon dermica
y ocular
Descontaminadon
gastrointestinal
Fluidos intravenosos
Contraindicaciones:
Atropina. Los fungicidas no
son inhibidores de la
colinesterasa.
FUNGICIDAS
Los fungicidas son usados extensamente en la industria, la agricultura, en el
hogar y el jardin para un numero de propositos que incluyen: para proteccion
de las semillas de granos durante su almacenamiento, transportacion y la
germinacion; para la proteccion de los cultivos maduros, de las fresas, los semi-
lleros,las flores e hierbas silvestres, durante su almacenamiento y transportacion;
para la eliminacion de mohos que atacan las superficies pintadas; para el control
del limo en la pasta del papel [de empapelar]; y para la proteccion de alfombras
y telas en el hogar.
El potencial que tienen los fungicidas para causar efectos adversos en los
humanos varia enormemente. Historicamente, algunas de las epidemias mas
tragicas de envenenamiento por fungicidas han ocurrido mediante el consumo
de semillas de granos que fueron tratadas con mercurio organico o
hexaclorobenceno. Sin embargo, es improbable que la mayoria de los fungicidas
que se utilizan en la actualidad causen severos envenenamientos frecuentes o
sistemicos debido a varias razones. Primeramente, muchos de ellos tienen una
toxicidad inherente baja para los mamiferos y son absorbidos ineficazmente. En
segundo lugar, muchos fungicidas se formulan en una suspencion de polvos y
granules absorbentes en agua, por lo cual una absorcion rapida y eficiente es
improbable. En tercer lugar, los metodos de aplicacion son tales que relativa-
mente son pocos los individuos que estan altamente expuestos. Aparte de los
envenenamientos sistemicos, los fungicidas, en su clase, son responsables proba-
blemente de un numero desproporcional de danos irritantes a la piel, las mem-
branas mucosas y sensibilizacion cutanea.
La siguiente discusion cubre los efectos adversos reconocidos de una gran
variedad de los fungicidas mas utilizados. Para aquellos fungicidas que han cau-
sado envenenamientos sistemicos, se han proporcionado a continuacion reco-
mendaciones de las direcciones a seguir en caso de envenenamiento y dano.
Para los fungicidas a los cuales se les desconoce causa de envenenamientos
sistemicos en el pasado, se han ofrecido solamente unas directrices generales.
La discusion de los efectos adversos relacionados a los fungicidas precede
en el siguiente orden:
Bencenos sustituidos
Tiocarbamatos
Etilen-bis-Ditiocarbamatos
PB
FUNGICIDAS
-------
Tioftalimidas
Compuestos de Cobre
Compuestos Organomercuricos
Compuestos Organoestanicos
Compuestos de Cadmio
Fungicidas Organicos Diversos
BENCENOS SUSTITUIDOS
Toxicologia
Cloroneb se suple en polvo liquido absorbente para el tratamiento del
terreno y semillas. Este agente exhibe una toxicidad oral baja en los mamiferos.
Puede ser moderadamente irritante a la piel y a las membranas mucosas. El
metabolito diclorometoxifenol es excretado en la orina. No se han informado
casos de envenenamiento sistemico en humanos.
Clorotalonil es disponible en polvo liquido absorbente, granules disolventes
en agua y en polvos irrigables. Clorotalonil ha causado irritacion a la piel y a las
membranas mucosas de los ojos y cuando entra en contacto con el tracto respi-
ratorio. Se han informado casos de dermatitis alergica debido al contacto.1 Apa-
rentemente es pobremente absorbido a traves de la piel y la capa gastroinstestinal.
No se han informado casos de envenenamiento sistemico en humanos.
Dicloran es un fungicida de amplio espectro utilizado liberalmente para la
proteccion de productos [alimenticios] perecederos. Esta formulado en polvo
liquido absorbente, suspension en polvo y en polvo irrigable. El dicloran es
absorbido por trabajadores expuestos ocupacionalmente, pero es eliminado ra-
pidamente en la orina. Entre los productos de transformacion biologica se in-
cluye el dicloroaminofenol, el cual es un desacoplador de fosforilacion oxidativa
(incrementa la produccion de calor). Dosis masivas de dicloran administradas a
animales de laboratorio causan dano hepatico y opacidad en la cornea.
Estudios basados en animales de laboratorio y en los efectos de compuestos
similares, puede esperarse que altas dosis causen dano hepatico, opacidad en la
cornea, pirexia y posiblemente metahemoglobinemia. Ningunos de estos efec-
tos han sido observados en humanos expuestos a DCNA.
Hexaclorobenceno. Las formulaciones principales son polvos y suspenciones
en polvos. El hexaclorobenceno difiere quimicamente y toxicologicamente del
hexaclorociclohexano, cuyo isomero de gamma (lindano) es aun un pesticida
ampliamente utilizado.
Aunque este fungicida protector de semillas solamente tiene efectos irritantes
leves y una toxicidad relativamente baja en dosis individuales, durante una in-
Productos Comerdales
BENCENOS SUSTITUIDOS
cloroneb
Terraneb SP
Clorotalonil
Bravo
Clorto Caffaro
Clortosip
Daconil 2787
Extherm Termil
Tuffcide
Otros
dicloran
Allisan
Clortran
DCNA
hexaclorobenceno*
Anticarie
Ceku C.B.
HCB
No Bunt
hentacloronitrobenceno
Avicol
Earthcide
Folosan
Kobu
Kobutol
PCNB
Pentagen
Quintozen
Tri-PCNB
otros
* Uso supendido en los Estados
Unidos.
FUNGICIDAS 153
-------
gestion prolongada de granos tratados con HCB por campesinos en fincas tur-
cas a finales de la decada del 1950, causo miles de casos de porfiria toxica
parecida a la porfiria cutanea tardia.2 Esta condicion dio resultado a un dano en
la sintesis de hemoglobina, conducente a productos toxicos terminales (porfirinas)
en los tejidos corporales. La enfermedad fue caracterizada por la excrecion de
orina tenida de rojo (contenido de porfirina), lesiones de ampollas en la piel
expuesta al sol, cicatrices y atrofia de la piel y proliferacion excesiva de cabello,
higado recrecido, anorexia, artritis y perdida de la rnasa muscular esqueletica. A
pesar de que la mayoria de los adultos se recuperaron despues de suspender el
consumo de granos tratados con HCB, algunos infantes de madres lactantes
afectadas murieron.
El hexaclorobenceno pierde el cloro y se oxida eficazmente en los humanos;
los triclorofenoles son los mayores productos de excrecion urinaria. La predisposicion
es lo suficientemente pronta para que los trabaj adores que entran en contacto ocu-
pacional generalmente muestren una elevacion en la concentracion de HCB en la
sangre.Algunas veces el HCB se encuentra presente en especimenes de sangre de
personas "no expuestas ocupacionalmente" en concentraciones hasta de 5 meg por
litro. La causa probable es el residue en los alimentos.
Pentacloronitrobenceno es usado para cubrir las semillas y tratar la tie-
rra. Las formulaciones incluyen emulsificantes concentrados, en polvo liquido
absorbente y en granules. El hexaclorobenceno es un contaminante menor del
PCNB tecmco.
El contacto dermico prolongado a altas concentraciones ha causado sensi-
bilidad en algunos voluntaries examinados, pero no se han informado sensibi-
lidad ni irritacion en trabajadores expuestos ocupacionalmente. Ocurrio un
caso de conjuntivitis y uno de queratitis como consecuencia de contaminacion
ocular. Esto se resolvio completamente pero lentamente.
No se han informado envenenamientos sistemicos. La eliminacion en ani-
males de laboratorio es lenta, probablemente debido a la recirculacion
enterohepatica. La excrecion es mayormente por via biliar, con una poca con-
version de pentacloroanilina, pentaclorofenol y otros metabolitos en el higado.
Aunque pueda sospecharse un efecto metahemoglobinemico (como en
nitrobenceno), no se ha informado en humanos o en animates, como tampoco
se ha informado porfiria toxica (como en hexaclorobenceno).
Confirmacion de Envenenamiento
El hexaclorobenceno (HCB) puede medirse en la sangre por medio de la
cromatografia de gases. Los metabolitos clorofenolicos pueden medirse en la ori-
na.A pesar de que las enfermedades hereditarias y un numero de agentes exogenos
pueden causar la aparicion de porfirinas en la orina, una prueba de porfirinas
resultaria util para un diagnostico toxicologico si se supiese del contacto con
HCB, o si un paciente exhibiese senales que sugieran porfiria cutanea tardia.
PB FUNGICIDAS
-------
La cromatografia de gases se puede usar para medir el PCNB y los
metabolites clorotalonil y cloroneb, pero el analisis no se encuentra amplia-
mente disponible. Se han descrito los metodos para el analisis de dicloran, pero
no se encuentran ampliamente disponibles.
Tratamiento
1. Descontaminacion dermica. La contaminacion dermica debe ser lavada con
agua y jabon. Enjuague la contaminacion ocular con abundante cantidad de agua.
Si la irritacion persiste, obtenga cuidado medico especializado.Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Si se ha ingerido una gran cantidad
de fungicida durante las ultimas horas, y no ha ocurrido vomito copioso, seria
razonable considerar el metodo de descontaminacion gastrointestinal. Puede
usarse carbon activado anadiendole el catartico sorbitol a la suspension de carbon.
Si se administra sorbitol separadamente, este debe diluirse con una cantidad
equitativa de volumen de agua antes de ser administrado. No se recomienda
mas de una dosis del catartico sorbitol y debe usarse con cautela en los ninos y
ancianos.Vease el Capitulo 2 para la dosificacion apropiada.
Si el contacto con el toxico ha sido minimo (como por ejemplo, contami-
nacion oral solamente, enjuague la boca rapidamente) probablemente el trata-
miento mas adecuado es la administracion de carbon sin catartico, y vigilar al
paciente cuidadosamente.
3. Porfiria. Las personas afectadas con porfiria deben evitar la luz solar, la cual
agrava el dano epicureo debido a la porfirina.
TIOCARBAMATOS
Los tiocarbamatos son comunmente formulados como suspencion en polvo, pol-
vos liquido absorbentes o en suspencion liquida. Se usan para proteger semillas,
semilleros, plantas ornamentales, el cesped, vegetales, frutas y manzanas. Los
tiocarbamatos, contrario a los carbamicos N-metilo (Capitulo 5), poseen un po-
tencial pesticida muy bajo.Varios de ellos exhiben una actividad anticolinesterasica
debil, pero la mayoria no posee un efecto significante hacia esta enzima. En gene-
ral, no posan riesgo a la salud humana tanto como los insecticias carbamicos. Los
fungicidas tiocarbamatos son discutidos en esta seccion, mientras que aquellos
usados como herbicidas son discutidos en el Capitulo 13.
METAM-SODIO
El metam-sodio es formulado en solucion acuosa para aplicarse como un
biocida de la tierra y como fumigante para matar el hongo, bacteria, semillas de
Productos Comerdales
TIOCARBAMATOS
ferbam
Carbamate WDG
Ferbam
Ferbek
Hexaferb
Knockmate
Trifungol
metam sodico
A7 Vapam
Busan 1020
Karbation
Maposol
Metam-fluido BASF
Nemasol
Solasan 500
Sometam
Trimaton
Vapam
VPM
thiram
Aules
Chipco Thiram 75
Fermide 850
Fernasan
Hexathir
Mercuram
Nomersam
Polyram-Ultra
Pormasol forte
Spotrete-F
Spotrete WP75
Tetrapom
Thimer
Thioknock
Thiotex
Thiramad
Thirasan
Thiuramin
Tirampa
TMTD
Tirametan
Tripomol
Tuads
ziram
Cuman
Hexazir
Mezene
Tricarbamix
Triscabol
Vancide MZ-96
Zincmate
Ziram F4
Ziram Technical
Zirberk
Zirex 90
Ziride
Zitox
FUNGICIDAS 155
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yerbajos, nematodos e insectos. Todo uso en el hogar ha sido cancelado en los
E.E.U.U.
Toxicologia
El metam-sodio puede ser altamente irritante a la piel. No se han informa-
do envenenamientos mediante la ingestion. Aunque en estudios realizados so-
bre la ingestion de metam-sodio en la alimentacion de animates no indiquen
una toxicidad extraordinaria, la descomposicion de este en agua produce
isotiocianato de metilo, un gas extremadamente irritante a las membranas mucosas
respiratorias, los ojos y los pulmones. La inhalacion del isotiocianato de metilo
puede causar edema pulmonar (severa afliccion respiratoria, tos con esputo
espumoso y sangriento). For esta razon, el metam-sodio es considerado como
fumigante. Debe ser usado solo exteriormente, y suma precaucion debe ser
tomada para evitar la inhalacion del gas que se desarrolla.
Teoricamente, puede ocurrir una predisposicion a reacciones de tipo
Antabuse si el individuo expuesto ingiere alcohol posteriormente al contacto.
(Vease Thiram) Sin embargo, no se han informado dichas ocurrencias.
Confirmacion de Envenenamiento
No existen pruebas disponibles en el metam-sodio o de su descomposi-
cion en los fluidos corporales.
Tratamiento
1. Descontaminacion de dermica. La contaminacion dermica debe ser
lavada inmediatamente con agua y jabon. Enjuague la contaminacion ocular
con abundante cantidad de agua para evitar quemaduras y lesion en la cornea.
Si la irritacion dermica y ocular persiste, obtenga cuidado medico especializa-
do.Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Si se ha ingerido una gran cantidad
recientemente, debe considerarse vaciado gastrico o el uso de carbon y catarti-
co.Vease el Capitulo 2 para la dosificacion apropiada.
3. Edema pulmonar. Si ocurriera irritacion pulmonar o edema como resul-
tado de inhalacion de isotiocianato de metilo, transporte a la victima rapida-
mente a la facilidad medica mas cercana. El tratamiento para edema pulmonar
debe proceder segun fuera delineado en el Capitulo 16,bajo Fumigantes.
4. Contraindicacion: El metam-sodio no es un inhibidor de la colinesterasa.
La atropina no es un antidoto.
PB FUNGICIDAS
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THIRAM
Thiram es un componente comun del latex y posiblemente el responsable
de algunas alergias atribuidas al latex.
Toxicologia
Thiram en polvo es moderadamente irritante a la piel humana, los ojos y
las membranas mucosas. Los trabajadores expuestos ocupacionalmente a este
han sufrido dermatitis. Varies individuos han experimentado sensibilidad al
thiram.3
Han ocurrido muy pocos envenenamientos sistemicos en humanos por el
compuesto de thiram en si, probablemente debido a la absorcion limitada en la
mayoria de los casos de contacto humano. Aquellos casos que han sido infor-
mados, han resultado ser clinicamente similares a la reaccion toxica de disulfiram
(Antabuse), el etilico analogo al thiram, el cual ha sido extensamente utilizado
para la terapia de rechazo de alcohol.3 En animales de laboratorio, el thiram, en
altas fracciones, tiene efectos similares a aquellos del disulfiram (actividad exce-
siva, ataxia, la perdida de tono muscular, disnea y convulsiones), pero el thiram
parece ser 10 veces mas toxico que el disulfiram.
Ni el thiram ni el disulfiram son inhibidores de la colinesterasa. Sin embargo,
ambos inhiben la enzima deshidrogenasa, critica para la conversion de acetaldehido
en el acido acetico. Esta es la base para la "reaccion Antabuse" que ocurre cuando
una persona en tratamiento regular con disulfiram consume etanol. La reaccion
incluye sintomas de nausea, vomito, dolor de cabeza agudo, mareo, desmayo, con-
fusion mental, disnea, dolor abdominal y del pecho, sudor profuso y erupcion de
la piel. La reaccion Antabuse ha ocurrido en raros casos donde los trabajadores
han ingerido alcohol despues de haber sido expuestos al thiram.
Confirmacion de Envenenamiento
La excrecion urinaria del acido xanturenico es usada para monitorear a los
trabajadores expuestos al thiram. La prueba no se encuentra generalmente dis-
ponible.
Tratamiento: Toxicosis de Thiram
1. Descontaminacion dermica. Lave el thiram de la piel con agua y jabon.
Enjuague la contaminacion ocular con abundante cantidad de agua limpia. Si la
irritacion ocular y dermica persiste, obtenga cuidado medico especializado.
2. Descontaminacion gastrointestinal. Si se ha ingerido una gran cantidad
de thiram durante los ultimos 60 minutos despues de la presentacion, y no han
FUNGICIDAS 157
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ocurrido vomitos efectivos, se debe vaciar el estomago mediante intubacion,
aspiracion y lavado, tornando precaucion para que el paciente no aspire el vo-
mito a traves de la via respiratoria. Seguido del lavado, probablemente lo mas
aconsejable seria la administracion de carbon activado y un catartico.
3. Fluidos intravenosos. La infusion de fluidos es apropiada, especialmente si
el vomito y diarrea son severos. Se deben de monitorear los electrolitos sericos
y la glucosa y debe ser reemplazado segun sea necesario.
Tratamiento: Toxicosis de Acetaldehidos
(Reaccion Antabuse)
1. Tratamiento inmediato. La inhalacion de oxigeno, la posicion de
Trendelenburg y fluidos intravenosos son generalmente los tratamientos efecti-
vos para aliviar las manifestaciones de las reacciones tipo Antabuse.
2. Prevencion de alcohol. Las personas que han absorbido una cantidad
significante de tiocarbamatos tienen que evitar la ingestion de bebidas alcoho-
licas por tres semanas. Los tiocarbamatos tienden a ser lentos y sus efectos
inhibidores en las enzimas son lentamente reversibles.
ZIRAM Y FERBAM
Estos estan formulados en polvos liquido absorbentes e irrigables, y se usan
frecuentemente en las frutas, los nogales, manzanas, vegetales y tabaco.
Toxicologia
El polvo de estos fungicidas causa irritacion a la piel, el tracto respiratorio
y los ojos. Se dice que la inhalacion prolongada del ziram ha causado disturbios
neurologicos y visuales, y en un caso aislado de envenenamiento, a causado una
reaccion hemolitica fatal. Teoricamente, el contacto con ziram o ferbam puede
predisponer al individuo a reacciones tipo Antabuse si se ingiere alcohol poste-
riormente a su contacto. (Vease Thiram.) Sin embargo, no se han informado
tales consecuencias.
Confirmacion de Envenenamiento
No existen pruebas disponibles para estos fungicidas o de la descomposi-
cion de sus productos en los fluidos del cuerpo.
PB FUNGICIDAS
-------
Tratamiento
Productos Comerdales
1. Descontaminacion dermica. La contaminacion dermica debe ser lavada
con agua y jabon. Enjuague la contaminacion ocular con abundante cantidad
de agua. Si la irritacion ocular y dermica es persistente, obtenga cuidado medi-
co especializado.Vease el Capitulo 2.
2. Descontaminacion gastroinstestinal. Si se ha ingerido recientemente
una cantidad considerable de ferbam o ziram, debe considerarse el vaciado
gastrico. Si la fraccion ingerida ha sido minima y/o ha habido un lapso de varias
horas desde la ingestion, lo mas aconsejable es la administracion de carbon y un
catartico.
3. Hemolisis. Si ocurre hemolisis, deben administrarse fluidos intravenosos y
debe considerarse la induccion de diuresis.
ETILEN BIS DITIOCARBAMATOS
(COMPUESTOS EBDC)
MANEB, ZINEB, NABAM, Y MANCOZEB
El maneb y zineb estan formulados en polvos liquido absorbentes e irrigables.
El nabam se provee en polvo soluble y en solucion acuosa. El mancozeb es un
producto en coordinacion de ion de zinc y maneb. Esta formulado en polvo y
como en polvo liquido absorbente irrigable.
ETILEN BIS
DITIOCARBAMATOS
(COMPUESTOS EBDC)
mancozeb
Dithane
Mancozin
manzeb
Manzin
Nemispor
Penncozeb
Ziman-Dithane
maneb
Kypman 80
Maneba
Manex
Manex 80
M-Diphar
Sopranebe
Trimangol
naban
Chem Bam
DSE
Parzte
Spring Bak
zineb
Aspor
Dipher
Hexathane
Kypzin
Parzate C
Tritoftorol
Zebtox
Toxicologia
Estos fungicidas pueden causar irritacion de la piel, del tracto respiratorio y
los ojos.Ambos el maneb y el zineb han sido responsables por algunos casos de
enfermedades cronicas de la piel en trabajadores expuestos ocupacionalmente,
posiblemente debido a la sensibilizacion.
A pesar de que han ocurrido evidentes efectos adversos en pruebas realiza-
das con animales luego de haber sido inyectados con compuestos de EBDC, la
toxicidad sistemica por via oral o epicurea es relativamente baja. El nabam
exhibe la mayor toxicidad, probablemente debido a su gran absorbencia y
solubilidad en agua. El maneb es moderadamente soluble en agua, pero el
mancozeb y el zineb son esencialmente insolubles en agua. La absorcion de
estos ultimos fungicidas a traves de la piel y las membranas mucosas es proba-
blemente bien limitada. Los envenenamientos sistemicos en humanos han sido
extremadamente raros. Sin embargo, aparentemente el zineb precipito un epi-
sodic de anemia hemolitica en un trabajador con una predisposicion debido a
FUNGICIDAS 159
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Productos Comerdales
TIOFTALAMIDAS
catafol*
Crisfolatan
Difolatan
Foltaf
Haipen
Merpafol
My cod if o I
Sanspor
captan
Captaf
Captanex
Merpan
Orthocide
Vondcaptan
folpet
Folpan
Fungitrol II
Phaltan
Thiphal
deficiencias multiples de enzimas en las celulas rojas.4 Se ha informado un caso
de una persona que desarrollo fallo renal critico y fue tratada con hemodialisis.5
Otra persona desarrollo sintomas neurologicos y de comportamiento que inclu-
yeron convulsiones tonico-clonicas despues de haber entrado en contacto con
maneb. Esta persona se recupero sin grandes problemas bajo cuidado sostenido.6
Los compuestos EBDC no son inhibidores de colinesterasa o del
acetaldehido deshidrogenasa. Tampoco inducen enfermedades colinergicas o
reacciones de tipo "Antabuse."
Confirmacion de Envenenamiento
No existen pruebas disponibles para estos fungicidas o de la descomposi-
cion de sus productos en los fluidos del cuerpo.
Tratamiento
Vease el tratamiento para Bencenos sustituidos, pagina 155.
TIOFTALAMIDAS
CAPTAN, CAPTAFOL Y FOLPET
Estos agentes se utilizan extensamente para proteger semillas, cultivos de campo
y productos almacenados. Estan formulados en polvos y polvos liquido absorben-
tes. El captafol ya no se encuentra registrado para uso en los Estados Unidos.
Toxicologia
Todos estos fungicidas irritan moderadamente la piel, ojos y el tracto respi-
ratorio. Puede causar sensibilizacion cutanea; el captafol parece haber sido la
causa de varies episodios de dermatitis por contacto ocupacional.7>8 No se han
informado envenenamientos sistemicos de tioftalamidas en humanos, aunque
se ha informado el captafol en el agravamiento de asma despues del contacto
ocupacional.9 En grandes dosis administradas en animales de laboratorio el captan
demuestra hipotermia, irritabilidad, desgano, anorexia, hiporeflexia y oliguria,
esta ultima acompaiiada de glicosuria y hematuria.
Confirmacion de Envenenamiento
El fungicida captan se metaboliza en el cuerpo y rinde dos metabolitos que
pueden ser medidos en la orina.10
PB
FUNGICIDAS
-------
Tratamiento
Vease el tratamiento para Bencenos sustituidos, p. 155.
COMPUESTOS DE COBRE
COMPUESTOS INORGAlMICOS Y ORGAlMICOS
Los compuestos insolubles estan formulados en polvos y en polvos liquido
solubles. Las sales solubles se preparan conio soluciones acuosas. Algunos com-
puestos organometalicos son solubles en aceites minerales.
Existe una gran cantidad de fungicidas comerciales que contienen cobre.
Algunos son mezclas de compuestos de cobre. Otros incluyen cal, otros metales
y otros fungicidas. La composicion de productos especificos se encuentra dis-
ponible generalmente mediante los fabricantes o los centres de control de en-
venenamiento.
Compuestos de cobre y arsenico, como el Verde de Paris, aun pueden ser
utilizados para la agricultura fuera de los EE.UU. La toxicidad de estos com-
puestos se debe principalmente a su contenido de arsenico. (Vease el Capitulo
14, Pesticidas Arsenicales).
Toxicologia
Las preparaciones en polvo de los compuestos de cobre irritan la piel, el
tracto respiratorio y, en principalmente, los ojos. Las sales solubles de cobre (asi
como el sulfato y el acetato) son corrosivas a las membranas mucosas y la cor-
nea. La solubilidad y absorcion limitadas probablemente justifican la baja toxi-
cidad sistemica que presentan la mayoria de los compuestos. Los compuestos de
cobre organico con mayor absorbencia son los que posan una mayor toxicidad
sistemica en animales de laboratorio. Han ocurrido frecuentemente bastantes
efectos de irritacion debido al contacto ocupacional fungicidas con contenido
de cobre. La mayoria de la informacion disponible sobre los compuestos toxi-
cos de cobre en mamiferos ha sido a traves de la toxicologia veterinaria (los
animales de cria parecen ser excepcionalmente vulnerables) y el envenena-
miento en humanos debido a la ingestion deliberada de sulfato de cobre o por
el consumo de agua o alimentos guardados en recipientes de cobre.
Los sintomas y manifestaciones en las primeras etapas del envenenamiento
de cobre incluyen: un sabor metalico, nausea, vomitos y dolor epigastrico. En
casos mas severos, la irritacion gastrointestinal se empeora con hematemesis y
feces de color oscuro. Es comun que ocurra ictericia y hepatomegalia.1U2Pue-
de ocurrir hemolisis, conducente a un colapso circulatorio y shock. En estos
casos se ha informado metahemoglobinemia.1U3'14Tambien puede ocurrir un
Productos Comerciales
COMPUESTOS DE COBRE
Compuestos Inorganicos De
Cobre
acetato de cobre
carbonate basico de cobre
carbonate de cobre y amonio
hidroxido de cobre
oxicloruro de cobre
oxido cuprico
oxido cuproso
polvo de cobre y cal
silicato de cobre
sulfato de cobre
sulfuro de cobre y potasiol
tribasic
Mezcla Bordeaux
Compuestos organicos de
cobre
fenilsalicilato de cobre
linoleato de cobre
naftenato de cobre
oleato de cobre
quinolinolato de cobre
resinato de cobre
* Uso suspendido en los
Estados Unidos
FUNGICIDAS 161
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fallo renal critico acompanado con oliguria. La causa primordial de muerte
durante las primeras etapas del transcurso de las manifestaciones es el shock;
fallo renal y hepatico contribuyen a la muerte a las 24 horas o mas despues del
Tratamiento
Las tecnicas para el tratamiento del envenenamiento por ingestion de
fungicidas que contienen cobre dependen enteramente de la naturaleza quimi-
ca del compuesto: las sales altamente ionizadas posan el mayor riesgo; los 6xi-
dos, hidroxidos, oxicloruros y oxidosulfatos posan un menor riesgo en la causa
de envenenamiento sistemico severo.
1. Descontaminacion dermica. Los polvos y polvillos deben lavarse con
agua yjabon. Enjuague toda solucion, polvo o polvillo irritante de los ojos con
agua limpia o una solucion salina. Si la irritacion dermica y ocular persiste,
obtenga cuidado medico especializado. La irritacion ocular puede ser severa.
Vease el Capitulo 2.
2. Anticorrosivo. Para diluir el toxico y mitigar la accion corrosiva en la boca,
esofago e intestino, de a beber agua o leche lo mas pronto posible.
3. Descontaminacion gastrointestinal. En casos de ingestion aguda de co-
bre los vomitos ocurren por lo general espontaneamente. No es recomendable
la induccion adicional de emesis debido a la naturaleza corrosiva de algunas de
las sales de cobre, las cuales pueden causar mas dano al esofago. Descontamina-
cion gastrointestinal adicional debe ser determinada segun el caso particular, asi
como fuera delineado en el Capitulo 2. El lavado gastrico puede causar dano
adicional. 15 No se ha estudiado extensamente la efectividad de la absorbencia
del carbon en el envenenamiento con metales.
Advertencia. La intubacion gastrica puede representar un riesgo serio de
perforacion en el esofago si la accion corrosiva ha sido severa. En este caso, seria
mejor evitar la intubacion gastrica.
4. Fluidos intravenosos. Si aparecen indicaciones de enfermedades sistemicas,
administre fluidos intravenosos que contengan glucosa y electrolitos. Monitoree
el balance de fluidos y corrija las concentraciones de electrolitos sanguineos
segun sea necesario. Si se desarrolla shock, administre aminas vasopresoras y
transfusiones de sangre segun sea requerido.
5. Hemolisis. Monitoree el plasma para la evidencia de hemolisis
(hemoglobinemia) y las celulas rojas para la indicacion de metahemoglobina. Si
ocurriera hemolisis anada bicarbonate de sodio a la infusion intravenosa, para
PB FUNGICIDAS
-------
alterar el pH de la orina a una alcalinidad de 7,5.Tambien debe considerarse la
induccion de diuresis con manitol. Si la metahemoglobinemia es severa ( >30%),
o si el paciente se encuentra cianotico, administre azul de metileno. La dosis para
adultos/ninos es 1-2 nig/kg per dosis, administrada lentamente via intravenosa a
lo largo de varies minutos, cada cuatro horas segun sea necesario.15
6. Control del dolor. El dolor severe puede que requiera la administracion de
morfina.
7. Agentes quelantes. El valor de los agentes quelantes en el envenenamiento
con cobre aun no ha sido establecido.16 Sin embargo, BAL parece acelerar la
excrecion de cobre y puede aliviar la enfermedad. El tratamiento de la enferme-
dad de Wilson por la toxicidad cronica con cobre es D-penicilamina; sin embar-
go, dentro del contexto de vomitos severos y/o cambios del estatus mental debi-
do a una ingestion aguda, BAL seria la decision inicial mas recomendable.13'15 La
recomendacion para la fraccion de la terapia inicial con BAL y la administracion
subsecuente de penicilamina, vease el Capitulo 14, bajo Pesticidas arsenicales.
8. Hemodialisis. Aunque se recomienda la hemodialisis para pacientes con
fallo renal, el cobre no es removido efectivamente en el dialisado.11
COMPUESTOS ORGANOMERCURICOS
COMPUESTOS DE METILMERCURIO Y
COMPUESTOS DE METOXIETIL MERCURICO,
ACETATO DE FENILMERCURIO
Estos fungicidas han sido formulados como soluciones acuosas y polvillos.
Su uso principal es como protector de semillas. El uso de fungicidas de alquilo
mercurio ha sido prohibido en los Estados Unidos por varies anos. El uso del
acetato de fenil mercurico no esta permitido en los Estados Unidos.
Toxicologia
Los fungicidas mercuricos figuran entre los pesticidas de mayor toxicidad
que jamas se hayan desarrollado, tanto en terminos de danos cronicos como
severos. Las epidemias de severas enfermedades neurologicas, frecuentemente
fatales, han ocurrido cuando residentes indigentes en paises menos desarrolla-
dos han consumido granos tratados con metil mercurio para propositos de
cultivo.17>18Tambien han ocurrido envenenamientos debido a la ingestion de
carnes de animales que han sido alimentados con semillas tratadas con mercu-
rio.19 La mayor parte de lo que se conoce acerca de los envenenamientos con
pesticidas mercuriales organicos ha surgido de estas ocurrencias.
Productos Comerdales
COMPUESTOS
ORGANOMERCURICOS
Compuestos de Metilmercurio
acetato de metilmercurio
propionato
quinolinolato
Compuestos de
Metoxietilmercurio
acetato de metoxietilmercurio
MEMA
Panogen
Panogen M
cloruro de metoxietilmercurio
Cresan
Emisan 6
MEMC
Acetato de Fenilmercurio
Agrosan
Setrete
Gallotox
PMAA
Shimmer-ex
Tag HL 331
Unisan
FUNGICIDAS 163
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Los compuestos de mercuric organico son absorbidos eficientemente a
traves del intestino y posiblemente a traves de la piel. El mercuric organico
volatil es facilmente absorbido a traves de la membrana pulmonar. El metil
mercurio se concentra selectivamente en el tejido del sistema nervioso y tam-
bien en las celulas sanguineas. Otros compuestos alquilo mercurio se distribu-
yen probablemente de forma similar. La excrecion ocurre casi enteramente por
via biliar al intestino. La vida media del metilo de mercurio en los seres huma-
nos es alrededor de 65 dias.20 En las celulas rojas ocurre una conversion signifi-
cativa de mercurio organico a mercurio inorganico.
Los sintomas iniciales de envenenamiento son sabor metalico en la boca,
entumecimiento y comezon en los dedos y la cara, temblores, dolor de cabeza,
fatiga, inestabilidad emocional y problemas de razonamiento. Las manifestacio-
nes de envenenamiento severe son la falta de coordinacion, dificultad del habla,
perdida del sentido de orientacion, perdida de la audicion, constriccion del
campo visual, espasmos o rigidez de movimientos musculares y deterioro de la
capacidad mental. Muchos envenenamientos causados mediante la ingestion de
compuestos organicos de mercurio han terminado en fatalidades, y un alto por
ciento de los sobrevivientes han sufrido danos neurologicos permanentes.17"19
El acetato de fenil mercurio no es extremadamente toxico como los com-
puestos de mercurio alcalino. No es absorbido en el intestino tan eficazmente
como el metil mercurio.21 Se han presentado informes de acrodinia en perso-
nas expuestas al vapor de mercurio como resultado del uso de pintura para
interiores a base de latex. Los sintomas incluyen: fiebre, eritema y la descama-
cion de las manos y los pies, musculos debilitados, calambre en las piernas y
cambios en la personalidad.22 Como resultado de esto se ha prohibido el uso de
los compuestos de fenil mercurio en las pinturas a base de latex.20 El acetato de
fenilo mercurico se ha utilizado para prevenir el crecimiento micotico en las
pinturas a base de latex.20
Confirmacion de Envenenamiento
El contenido de mercurio en la sangre y los tejidos se puede medir via
espectrometria de absorcion atomica. Se considera contacto agudo cuando los
niveles en la sangre son de 5 mcg/dL o mayores.21 Se necesitan unos procedi-
mientos especiales para la medicion y extraccion especificamente de los com-
puestos de mercurio organicos.
Tratamiento
Debe tomarse toda posible precaucion para evitar el contacto con los com-
puestos de mercurio organicos. La ingestion de un compuesto organico de
mercurio, aun en fracciones bajas, constituye una amenaza para la vida, y resulta
PB FUNGICIDAS
-------
dificil de manejar. Es muy poco lo que puede hacerse para mitigar el dano
neurologico causado por los mercuries organicos.
Aquellas personas que experimenten sintomas (sabor metalico en la boca)
despues de haber ocurrido inhalacion de compuestos organicos volatiles de
mercuric (metil mercurio es el mas volatil) deben ser removidos inmediata-
mente del ambiente contaminado y deben ser observados de cerca para reco-
nocer senales de deterioro neurologico. A continuacion los pasos basicos para el
manejo de envenenamiento.
1. Descontaminacion dermica. La piel y cabello contaminado con solucio-
nes o polvos que contienen mercurio deben ser lavados con agua y jabon.
Enjuague la contaminacion ocular con agua limpia. Si persiste la irritacion,
obtenga cuidado medico especializado.Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Considere la descontaminacion
gastrointestinal como fuera explicado en el Capitulo 2.
3. Agentes quelantes. Esto es una parte esencial del manejo del envenenamien-
to con mercurio. Las fracciones de agentes especificos se encuentran el Capitulo
14, bajo Pesticidas Arsenicales. Succimer (DMSA) parece ser el agente mas efec-
tivo disponible en los Estados Unidos. Dimercaprol (BAL) esta contraindicado
para este tipo de envenenamiento debido al potencial que tiene de aumentar los
niveles de mercurio en el cerebro. 20 El EDTA aparentemente tiene un valor
insignificante en el envenenamiento con mercurio organico. La D-penicilamina
es probablemente mas util, y esta disponible en los Estados Unidos, tambien ha
probado ser efectiva en la reduccion de la vida media del metil mercurio en
envenenamientos de seres humanos.20 El 2,3 dimercaptopropano-1-sulfonato acido
(DMPS) y la N-acetilo-D,L-penicilamina (NAP) son probablemente utiles pero
no estan aprobados para uso en los Estados Unidos.
4. Hemodialisis. Puede considerarse la hemodialis extracorporea y la transfu-
sion de sangre, aunque toda la corriente experiencia no ha sido muy alentadora.
Productos Comerdales
COMPUESTOS
ORGANOESTANICOS
acetato de fenilestano*
Batasan
Brestan
Phenostat-A
Phentinoacetato
Suzu
TPTA
cloruro de fenilestano*
Tinmate
hidroxido de fenilestano
Super Tin
Suzu-H
Tubotin
trifenilestano
Uso suspendido en los
Estados Unidos
COMPUESTOS ORGANOESTANICOS
Estos compuestos son formulados en polvos rociables y liquidos absorben-
tes como fungicidas y para el control de plagas en los campos de cultivo y en los
huertos de arboles. El cloruro de fenilestano tambien fue preparado como un
concentrado emulsificable que se usa como molusquicida (Aquatin 20 EC,fue-
ra de circulacion desde 1995). Las sales de tributilestano se utilizan como
fungicidas y agentes anticorrosivo en barcos. Estos compuestos son algo mas
toxicos por via oral que el trifenilestano, pero sus acciones toxicas son proba-
blemente similares.
FUNGICIDAS 165
-------
Productos Comerdales
COMPUESTOS DE CADMIO
cloruro de cadmio*
Caddy
succinato de cadmio*
Cadminate
sulfato de cadmio*
Cad-Trete
Crag Turf Fungicide
Kromad
Miller 531
Uso suspendido en los Estados
Unidos
Toxicologia
Estos agentes causan irritacion en los ojos, el tracto respiratorio y la piel.
Estos probablemente son absorbidos, hasta cierto punto, a traves de la piel y el
tracto gastrointestinal. Las manifestaciones toxicas se deben principalmente a
los efectos que tiene en el sistema nervioso central: dolor de cabeza, nausea,
vomitos, niareo y a veces convulsiones y perdida del conocimiento. Ocurren
disturbios mentales y fotofobia. Se ha reportado dolor epigastrico, aun en
envenenamientos causados por inhalacion. En algunos casos ha ocurrido aumento
del azucar en la sangre, suficiente para causar glicosuria. Los fungicidas
compuestos de fenilestano son nienos toxicos que los compuestos de etilestano,
los cuales causan edema cerebral, dano neurologico, y muerte en aquellos
individuos envenenados que sufrieron contacto cutaneo con un compuesto
medicinal de este tipo.23 No se han reportado muertes y muy pocos casos de
envenenamiento como resultado de contacto ocupacional se han reportado de
compuestos de fenilestano.
Tratamiento
1. Descontaminacion dermica. Remueva la contaminacion de la piel la-
vando con agua y jabon. Enjuague los ojos con agua limpia o salina. Si la irrita-
cion persiste obtenga cuidado medico especializado.Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Si se han ingerido altas cantidades
del compuesto fenilestano dentro del lapso de una hora, se deben de tomar
medidas para descontaminar el tracto gastrointestinal, segun se ha explicado en
el Capitulo 2.
3. Agentes quelantes. El BAL, la penicilamina, ni otros agentes guelantes han
resultado efectivos para disminuir el almacenamiento de compuestos
organoestanicos en la experimentacion con animales.
COMPUESTOS DE CADMIO
Las sales de cadmio han sido usadas para el tratamiento de enfermedades
micoticas que afectan el cesped y la corteza de los huertos de arboles. Fueron
formulados como soluciones y emulsiones. Los fungicidas Miller 531 y Crag
Turf 531 fueron complejos oxidos de cadmio, calcio, cobre, cromio y zinc.
Actualmente estan comercializados bajo fungicidas genericos. El Kromad es
una mezcla de sebacato de cadmio, cromato de potasio y thiram. El Cad-Trete
es una mezcla de cloruro de cadmio y thiram. Todos los fungicidas derivados
del cadmio se encuentran fuera de circulacion en los Estados Unidos.
PB
FUNGICIDAS
-------
Toxicologia
Las sales y oxidos de cadmio causan mucha irritacion en los tractos respira-
torio y gastrointestinal. La inhalacion de polvos y gases pueden causar toxicidad
respiratoria despues de un periodo de latencia de varias horas, incluyendo una
enfermedad leve, unicamente limitada a la fiebre, tos, malestar, dolor de cabeza
y estomacal, similar a la fiebre causada por enfermedades de gases metalicos.
Una forma mas severa de toxicidad incluye neumonitis quimica, y esta asociada
con dificultad al respirar, dolor de pecho, y en algunos casos edema pulmonar
hemorragica letal.24'25 Los sintomas puede prevalecer durante semanas.
La ingestion de cadmio causa nausea, vomitos, diarrea, dolor abdominal y
tenesmo. La inhalacion e ingestion de dosis relativamente pequenas producen
sintomas complicados. La absorcion prolongada de cadmio ha causado dano
renal (proteinuria y azotemia), anemia, dano hepatico (ictericia),y defectos a la
estructura osea (fracturas patologicas) en aquellas personas cronicamente ex-
puestas. La inhalacion prolongada de polvos de cadmio ha contribuido a enfer-
medades de obstruccion cronica del pulmon.26
Confirmacion de Envenenamiento
El cadmio se puede medir en los fluidos del cuerpo mediante apropiada
extraccion, seguido por una espectrometria de absorcion de flama. Se ha repor-
tado que las concentraciones de cadmio en la sangre tienden a ser directamente
proporcionales con la severidad del contacto y los niveles en la orina tienden a
reflejar la carga total del cuerpo. Los niveles de la sangre que excedan 5 mcg/dL
reflejan una exposicion excesiva.25 La excrecion urinaria que exceda 100 meg
por dia refleja una carga inusitadamente alta para el cuerpo.
Tratamiento
1. Descontaminacion dermica. La contaminacion dermica debe ser lavada
con agua y jabon. Enjuague la contaminacion ocular con abundante agua lim-
pia o salina. Si la irritacion persistiese, obtenga ayuda medica especializada.Vea-
se el Capitulo 2.
2. Edema pulmonar. La irritacion respiratoria que resulta de la inhalacion de
pequenas cantidades de cadmio puede desaparecer de forma espontanea y pue-
de que no se requiera tratamiento. En reacciones mas severas, que incluyen
edema pulmonar y neumonitis se requieren medidas mas agresivas, que inclu-
yen ventilacion pulmonar mecanica con presion positiva, el monitoreo de gases
sanguineos, el suministro de diureticos, medicamentos a base de esteroides y
antibiotiocos.25 Puede que se requiera el sulfato de codeina para controlar la tos
y el dolor de pecho.
FUNGICIDAS 167
-------
Productos Comerdales
FUNGICIDAS ORGANICOS
DIVERSOS
anilazina*
Dyrene
benomilo
Benex
Benlate
Tersan 1991
cicloheximida*
naramycin
dodina
Carpene
Curitan
Melprex
Venturol
etridiazol
Aaterra
Ethazol
Koban
Pansoil
Terrazol
Truban
iprodiona
Glycophene
Rovral
metalaxil
Ridomil
Subdue
tiabendazol
Apl-Luster
Arbotect
Mertect
Tecto
Thibenzole
triadimefon
Amiral
Bayleton
triforina
Denarin
Funginex
Saprol
Uso suspendido en los
Estados Unidos
3. Descontaminacion gastroinstestinal. La accion irritante de los produc-
tos ingeridos de cadmio resulta tan fuerte que los vomitos y la diarrea esponta-
nea eliminan generalmente casi todo el cadmio que queda sin absorber en el
intestino. Si se sospecha la retencion de parte del cadmio en el tracto
gastrointestinal bajo, debe considerarse descontaminacion adicional, segun se
ha explicado en el Capitulo 2.
4. Fluidos intravenosos pueden ser administrados para superar la deshidrata-
cion causada por los vomitos y la diarrea. Los fluidos tambien limitan la toxici-
dad del cadmio que pueden afectar a los rinones y el higado. Sin embargo, debe
tomarse sumo cuidado en el monitoreo del balance de fluidos y la concentra-
cion de los electrolitos de la sangre, para que el fallo de la funcion renal no
conduzca a una sobrecarga de fluidos.
S.Terapia de quelacion con disodio de calcio EDTA puede ser considerada
en casos de envenenamiento severe, dependiendo de la cantidad de cadmio
medida en la sangre y en la orina, y en el estado de la funcion renal. El valor
terapeutico de esta terapia no ha sido establecido, y el uso de agentes quelantes
conllevan un riesgo de que la rapidez excesiva de la transferencia de cadmio en
los rinones pueda precipitar un fallo renal. Durante esta terapia se deben
monitorear cautelosamente las proteinas en la orina, la creatinina y el nitrogeno
de urea en la sangre. La dosis prescrita es de 75 mg/kg/al dia administrada de
tres a seis dosis divididas por un intervalo de 5 dias. La dosis total en el transcur-
so de 5 dias no debe de exceder de 500 mg/kg.27 Tambien se ha utilizado
Succimer (DMSA) para este tipo de envenenamiento, pero no ha demostrado
ser eficaz.
6. Contraindicaciones: No se recomienda el uso de Dimercaprol (BAL) para
el tratamiento del envenenamiento de cadmio, debido principalmente al riesgo
de que el cadmio movilizado cause dano renal.
7. Funcion hepatica. Monitoree regularmente el contenido de las proteinas
en las celulas, y lleve a cabo pruebas del funcionamiento hepatico para el indi-
cio de dano en estos organos.
DIVERSOS FUNGICIDAS ORGANICOS
Algunos fungicidas organicos modernos son de uso extensive. Existen re-
portes escasos sobre los efectos adversos en seres humanos. Algunas de las pro-
piedades conocidas de estos agentes siguen a continuacion.
Anilazina se suministra en polvo regable y liquido absorbente. Se usa en
los vegetales, cereales, cafe, plantas ornamentales y el cesped. Este producto ha
causado irritacion cutanea en trabajadores expuestos. La toxicidad oral y cuta-
PB
FUNGICIDAS
-------
nea en animales de laboratorio ha sido baja. No se han reportado envenena-
mientos sistemicos en seres humanos.
Benomilo es un fungistato sistemico organico que no posee un efecto
toxico severe en los mamiferos o un efecto toxico bien bajo. No se han repor-
tado envenenamientos sistemicos en seres humanos. A pesar de que la molecula
contiene un grupo carbamato, el benomilo no es inhibidor de la colinesterasa.
Se absorbe a traves la piel con dificultad; y lo que es absorbido es metabolizado
y excretado rapidamente.
Ha causado dano en la piel en individuos expuestos a este compuesto, y se
ha encontrado que causa sensibilidad cutanea entre los trabajadores agricolas
expuestos a residues en el follaje.
Cicloheximida es formulado en polvo liquido absorbente, a veces se com-
bina con otros fungicidas. Cicloheximida es un producto del cultivo de hongos,
y es efectivo contra las enfermedades micoticas en las plantas ornamentales y
gramas. Es selectivamente toxico para las ratas, y mucho menos toxico en pe-
rros y monos. No se han reportado envenenamientos en seres humanos. Causa
salivacion, diarrea sangrienta, tremores, ansiedad, que conducen a coma y muerte
debido al colapso cardiovascular. La hidrocortisona aumenta la tasa de supervi-
vencia en ratas que han sido envenenadas deliberadamente. La atropina, epinefrina,
metoxifenamina y el hexametonio alivian los sintomas de envenenamiento, pero
no mejoran las posibilidades de supervivencia.
Dodina es formulada en polvo liquido absorbente. Es aplicada comun-
mente en manzanas, duraznos, nueces, fresas y arboles que padecen de plagas en
las hojas. Diodina es un surfactante cationico de actividad antimicotica. Es ab-
sorbido a traves de la piel y es irritante para la piel, los ojos y el tracto
gastrointestinal. La toxicidad severa oral y cutanea ha probado ser moderada en
animales de laboratorio. No se han reportado envenenamientos en seres huma-
nos. Segun algunos estudios en animales, probablemente cause nausea, vomitos
y diarrea.
Iprodiona se suple en polvos liquido absorbentes y otros tipos de
formulaciones. Se usa para las moras, uvas, frutas, vegetales, gramas y plantas
ornamentales y para proteger las semillas. La iprodiona exhibe una capacidad
baja para causar una toxicidad oral y cutanea aguda en animales de laboratorio.
Metalaxil se suple en concentrados emulsificables y regables. Se usa para el
control de enfermedades micoticas que provienen del suelo en arboles frutales,
algodon, lupulo, soya, mani, plantas ornamentales y gramas. Tambien se usa para
proteger las semillas. El metalaxil exhibe una capacidad baja para causar toxici-
dad oral y cutanea aguda en animales de laboratorio.
Terrazol se suple en polvo y granules liquido absorbentes para la aplica-
cion del terreno como fungicida e inhibir la nitrificacion. El contacto puede
causar irritacion en la piel y los ojos. La toxicidad sistemica es baja. No se han
reportado casos de envenenamientos en seres humanos.
Tiabendazol se utiliza ampliamente como un fungicida en la agricultura,
pero la toxicologia en humanos proviene de su uso medicinal en el tratamiento
FUNGICIDAS 169
-------
de parasites intestinales. Las dosis orales administradas con este proposito son
mucho mis altas que aquellas que pudieran absorberse en el transcurso del
contacto ocupacional. El tiabendazol es metabolizado y excretado rapidamente
en la orina, la mayor parte como producto de conjugacion de un metabolito
hidroxilado. Los sintomas y signos que usualmente se producen luego de la
ingestion son: mareo, nausea, vomito, diarrea, molestia epigastrica, letargo, fie-
bre, acaloramiento, escalofrio, salpullido y edema local, dolor de cabeza, tinitus,
parestesia e hipotension. Las pruebas enzimaticas de la sangre pueden indicar
dano hepatico. Las personas con enfermedades del higado o del rinon pueden
ser vulnerables a los efectos toxicos. No se han reportado casos de efectos ad-
versos por el uso de tiabendazol como fungicida.
Triadimefon se suple en polvo liquido absorbente, concentrado
emulsificable, suspension concentrada, pasta y polvo seco regable. Se usa en las
frutas, cereales, vegetales, cafe, plantas ornamentales, cana de azucar, pina y en el
cesped. El triadimefon exhibe una toxicidad aguda en animates de laboratorio,
pero su toxicidad cutanea es baja. Causa irritacion cuando contamina los ojos.
El triadimefon es absorbido a traves de la piel. Se dice que el contacto excesivo
en los seres humanos ha causado hiperactividad seguida por sedacion.
Triforina se suple como concentrado emulsificable y en polvo liquido
absorbente. Se usa en moras, frutas, vegetales y plantas ornamentales. La triforina
exhibe una capacidad baja para causar toxicidad oral y cutanea aguda en anima-
les de laboratorio. Los mamiferos la excretan mayormente como un metabolito
en la orina. No se han reportado envenenamientos en seres humanos.
Confirmacion de Envenenamiento
Por lo general, no existen pruebas de laboratorio disponibles de la presen-
cia en los fluidos del cuerpo de estos fungicidas organicos, ni de sus metabolitos.
Tratamiento
Vease el tratamiento para Bencenos sustituidos en la pagina 155.
Referencias
1. Dannaker CJ, Maibach HI, and O'MaUey M. Contact urticaria and anaphylaxis to the fun-
gicide chlorothalonil. Cutis 1993;52:3120-5.
2. Peters HA, Gocmen A, Cripps DJ, et al. Epidemiology of hexachlorobenzene-induced por-
phyria in Turkey: Clinical and laboratory follow-up after 25 years. Arch Neural 1992;39:744-9.
3. Dalvi RR. Toxicology of 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.
PB FUNGICIDAS
-------
5. Koizumi A, Shiojima S, Omiya M, et al. Acute renal failure and maneb (manganouis
ethylenebis[dithiocarbamate]) exposure.JAMA 1979;242:2583-5.
6. Israeli R, Sculsky M, andTiberin P. Acute intoxication due to exposure to maneb and zineb:
A case with behavioral and central nervous system changes. Scand J Work Environ Health
1983;9:47-51.
7. Peluso AM.Tardio M, Adamo F, et al. Multiple sensitization due to bis-dithiocarbamate and
thiophthalimide pesticides. Contact Dermatitis 1991;25:327.
8. Vilaplana J and Romaguera C. Captan, a rare contact sensitizer in hairdressing. Contact Der-
matitis 1993;29:107.
9. Royce S, Wald P, Sheppard D, et al. Occupational asthma in a pesticides manufacturing
worker. Chest 1993;103:295-6.
10. Krieger RI and Thongsinthusak T. Captan metabolism in humans yields two biomarkers,
tetrahydrophthalimide (THPI) and thiazolidine-2-thione-4-carboxylic acid (TTCA) in urine.
Drug ChemToxicol 1993;16:207-25.
11. Agarwal SK.Tiwari SC, and Dash SC. Spectrum of poisoning requiring haemodialysis in a
tertiary care hospital in India. IntJArtif Organs 1993;16:20-3.
12. Lament DL and Duflou JALC. Copper sulfate: Not a harmless chemical. Am] Forensic Med
Pathol 1988;9:226-7.
13. Chugh KS, Singhal PC, and Sharma BK. Methemoglobinemia in acute copper sulfate poi-
soning. Ann Intern Med 1975;82:226-9.
14. Jantsch W, Kulig K, and Rumack BH. Massive copper sulfate ingestion resulting in hepato-
toxicity. ClinToxicol 1984-85;22:585-8.
15. POISINDEXR: Copper poisoning. Englewood, CO: Micromedex, 1998.
16. Hantson P, Lievens M, and Mahieu P. Accidental ingestion of a zinc and copper sulfate
preparation. ClinToxicol 1996;34:725-30.
17. Bakir F, Rustam H.Tikritis S, et al. Clinical and epidemiological aspects of methylmercury
poisoning. Postgrad Med] 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] Med 1971;284:1014-5.
20. ClarksonTW. MercuryAn element of mystery. New Engl] 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. BrJInd Med 1991; 48:136-9.
24. Barnhart S and Rosenstock L. Cadmium chemical pneumonitis. Chest 1984;86:789-91.
25. AndoY, 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, RallTW, Niew AS,
et al (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics, 3rd ed. New
York: Pergamon Press, 1990, pp. 1605-6.
FUNGICIDAS 171
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CAPITULO 16
PUNTOS
IMPORTANTES
Fumigantes
Fadlmente absorbidos en los
pulmones, intestines y piel
Senales y Smtomas:
Altamente variables
dependiendo del agente
Muchos de ellos son
irritantes
El disulfuro de carbono,
cloroformo, cianuro de
hidrogeno y naftaleno
pueden causar efectos CMS
graves
El bromuro de metileno y
fosfuro de aluminio (gas
fosfina) causa edema
pulmonar
El cianuro de hidrogeno
causa hipoxemia sin
cianosis en las etapas
iniciales
Tratamiento:
Descontaminadon dermica
y ocular
Oxfgeno y diuresis debido a
la edema pulmonar
Se necesitan medidas
especfficas para los distintos
agentes
Contraindicaciones:
No se recomienda el uso de
ipecacuana en el
envenenamiento con
Los fumigantes poseen una capacidad excepcional para la difusion, una propiedad
esencial para su funcion. Algunos pueden penetrar con facilidad a traves de la ropa
protectora de hule y de neopreno, asi tambien como de la piel en los seres huma-
nos.Tambien pueden ser absorbidos rapidamente a traves de la membrana pulmonar,
del intestine y de la piel. Se requiere el uso de absorbentes especiales en las
mascaras respiratorias para proteccion de los trabajadores expuestos a los gases
fumigantes en el aire. Aun asi esto no podra proveer una completa proteccion
cuando las concentraciones de fumigantes en el aire son altas.
La formulacion y empaque de los fumigantes es compleja. Aquellos
fumigantes que son gases de temperatura ambiente (broumuro de metilo, oxido
de etileno, bioxido de azufre, cianuro de hidrogeno, fluoruro de sulfurilo) se
suplen en cilindros de gas comprimido. Los fumigantes liquidos se suplen co-
mercialmente en lata o en bidon. Los solidos sublimes, como el naftaleno y el
paradiclorobenceno, deben ser empacados de manera que se evite el contacto
excesivo con el aire antes de ser usados.
Las mezclas fumigantes tienen varias ventajas. El tetracloruro de carbono
reduce la explosividad del disulfuro de carbono del acrilonitrilo. La cloropicrina,
que tiene un fuerte olor y efecto irritante, se anade con frecuencia a otros
fumigantes liquidos como un "agente de alerta" a otros fumigantes liquidos.
Los halocarburos liquidos el disulfuro de carbono se evaporan en el aire
mientras que el nataleno el paradiclorobenceno se subliman. El paraformaldehido
se despolimeriza lentamente hasta formar formaldehido. El fosfuro de aluminio
reacciona lentamente con el vapor de agua presente en el aire liberando fosfina,
un gas extremadamente toxico. El Metam Sodio, tambien un fumigante, esta
cubierto bajo tiocarbamatos en el Capitulo 15, Fungicidas.
Toxicologia
La acrolema (acrilaldehido) es un gas extremadamente irritante que se usa
como fumigante y como herbicida acuatico. El vapor causa lagrimeo e irrita-
ciones del tracto respiratorio superior que puede evolucionar a edema de la
laringe, espasmo bronquial y edema pulmonar tardia. Las consecuencias de la
ingestion son semejantes a aquellas que son causadas por la ingestion de
formaldehido. El contacto con la piel puede causar ampollas.
El acronitrilo se biotransforma en el cuerpo a cianuro de hidrogeno. La
toxicidad y los mecanismos de envenenamiento son esencialmente los mimos
PB
FUMIGANTES
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descritos para el tratamiento de cianuro (bajo cianuro de hidrogeno), excepto
que el acrilonitrilo causa irritacion en los ojos y las vias respiratorias superiores.
El vapor del disulfuro de carbono causa irritacion moderada en las nieni-
branas respiratorias superiores, pero tiene un olor ofensivo a repollo podrido.
La toxicidad aguda se debe mayormente a los efectos que tiene en el sistema
nervioso central. La inhalacion de altas concentraciones por periodos breves
causa dolor de cabeza, rnareo, nausea, alucinaciones, delirio, paralisis progresiva
y muerte por fallo respiratorio. Una exposicion mis prolongada a cantidades
menores ha causado ceguera, sordera, parestesia, neuropatia dolorosa y paralisis.
El disulfuro de carbon es un irritante de la piel potente, que causa frecuente-
mente quemaduras severas. Se ha demostrado que el contacto ocupacional a
largo plazo acelera la arterioesclerosis, que evoluciona a encefalopatia isquemica,
polineuropatia y disfuncion gastrointestinal.1 El daiio toxico al higado y los
rinones puede resultar en una deficiencia funcional severa de estos organos.
Tambien ha ocurrido fallo del sistema reproductor.
El tetracloruro de carbono es menos toxico que el cloroformo como
depresor del sistema nervioso central, pero es mucho mas hepatotoxico, parti-
cularmente si ha sido ingerido. El dafio celular hepatico al parecer se debe a un
radical libre generado durante el proceso inicial de descloracion.2 La inhalacion
de concentraciones elevadas de tetracloruro de carbono o la ingestion del liqui-
do puede conducir a arritmias cardiacas que evolucionan a fibrilacion. Ocurre
daiio del rinon tambien con una toxicidad hepatica minima. El daiio renal
tambien se puede manifestar por necrosis tubular aguda o por azotemia y fallo
renal general. Aun el contacto topico ha dado resultado a una toxicidad renal
aguda.3
El cloroformo tiene un olor dulce y agradable y solamente es levemente
irritante al tracto respiratorio. Posee una buena absorcion en los pulmones y
tambien es absorbido en la piel y el tracto gastrointestinal. Es un potente depre-
sor del sistema nervioso central (de hecho es un anestesico).4 La inhalacion de
concentraciones toxicas en el aire causa mareo, perdida de sensacion y fuerza
motriz y luego inconsciencia. La inhalacion de grandes cantidades causa arrit-
mia cardiaca, que algunas veces da lugar a fibrilacion ventricular. La absorcion
de grandes dosis daria las celulas funcionales del higado y del rinon. Es mas
probable que la ingestion del cloroformo cause danos graves al higado y al
rinon que lo que pueda causar la inhalacion del vapor.
La cloropicrina causa irritacion severa en el tracto respiratorio superior, los
ojos y la piel. La inhalacion de una concentracion irritante algunas veces causa
vomito. Puede esperarse que la ingestion cause una gastroenteritis corrosiva.
El dibromocloropropano causa irritacion en la piel, ojos y el tracto res-
piratorio. Ha ocurrido daiio ocular como consecuencia de la exposicion repe-
tida a los vapores. Cuando es absorbido este causa dolor de cabeza, nausea,
vomito, ataxia y dificultad del habla. El daiio hepatico y renal son caracteristicas
importantes del envenenamiento agudo. La exposicion cronica de concentra-
ciones relativamente bajas ha causado esterilidad temporera o permanente en
Productos Comerdales
HALOCARBUROS
tetraclocuro de carbono*
cloroformo*
triclorometano
cloropicrina
Aquinite
Dojyopicrin
Dolocholor
Larvacide
Pic-Clor
dibromocloropropano*
Nemafume
Nemanax
Nemaset
1,2 dicloropropano*
dicloropropileno
1,3 dicloropropano
D-D92
Telone II Soil Fumigant
dibromuro de etileno*
Bromofume
Celmide
dibromoetano
E-D-Bee
EDB
Kopfume
Nephis
dicloruro de etileno*
dicloroetano
EDC
bromuro de metilo
Celfume
Kayafume
Meth-0-Gas
MeBr
Sobrom 98
cloruro de metileno*
paradiclorobenceno
HIDROCARBUROS
naftaleno
COMPUESTOS DE
NITROGENOS
acrilonitrilo*
cianuro de hidrogeno*
acido cianhidrico*
acido prussico
(Continue en la proxima pagina)
FUMIGANTES 173
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Productos Comerdales
(Continuation)
OXIDOSYALDEHlDOS
acrolefna
Magnacide B
Magnacide H
1,2 epoxietano
oxido de etileno
ETO
formaldehido
oxirano
paraformaldehido
COMPUESTOS DE FOSFORO
Fosfina (liberada del fosfuro de
aluminio o del fosfuro de
magnesio)
Ag toxin
Alphos
Fumex
Fumitoxin
Phostoxin
Quickfos
Sanifume
Shaphos
Otros
COMPUESTOS DE AZUFRE
disulfuro de carbono*
dioxido de azufre
fluoruro de sulfurilo
Vikane
* Uso suspendido en los Estados
Unidos
trabajadores de una planta manufacturera produciendo necrosis difusa en las
celulas de los tubos seminiferos. Es posible que los trabajadores esten expuestos
a concentraciones toxicas de DBCP porque es mucho menos odorifero que el
dibromuro de etileno. El uso del dibromocloropropano ha sido cancelado en
los E.U.A.
El dicloropropano y el dicloropropeno son muy irritantes para la piel,
los ojos y el tracto respiratorio. La inhalacion de concentraciones elevadas pue-
de causar espasmo bronquial. Se han visto casos de intoxicacion renal, hepatica
y cardiaca en animates, pero la informacion en seres humanos es limitada. Tal
parece que el riesgo para tal intoxicacion es relativamente leve en los seres
humanos excepto a traves de la ingestion oral de una abundante cantidad de
estos compuestos.
El dibromoetano causa irritacion severa en la piel, ojos y el tracto respi-
ratorio. El liquido causa ampollas, erosion en la piel y es corrosive para los ojos.
Una vez que se absorbe, puede causar edema pulmonar y depresion del sistema
nervioso central. Ha causado dano testicular en animales.5 El contacto a largo
plazo puede causar efectos daninos sobre el tejido testicular. Las personas enve-
nenadas mediante la ingestion sufren de gastroenteritis quimica, necrosis hepa-
tica y dano en los tubulos renales. La muerte es generalmente causada debido al
fallo respiratorio y circulatorio. Este gas posee un fuerte olor desagradable, ca-
racteristica ventajosa que sirve para alertar a los trabajadores que corren riesgo
por contacto ocupacional.
El dicloroetano es moderadamente irritante para los ojos y el tracto
respiratorio. Los sintomas respiratorios pueden aparecer con retraso. Tambien
deprime el sistema nervioso central, induce arritmia cardiaca y causa dano
hepatico y renal de manera semejante al tetracloruro de carbono. Los sintomas
y signos de intoxicacion incluyen, dolor de cabeza, nausea, vomito, diarrea,
hipotension, cianosis y fait a de conocimiento.
El oxido de etileno y el oxido de propileno causan irritacion en todos
los tejidos expuestos. Las soluciones acuosas el oxido de etileno causan ampo-
llas y erosion de la piel afectada. El area afectada de la piel puede quedar sensible
al fumigante. La inhalacion de concentraciones elevadas es posible que cause
edema pulmonar y arritmia cardiaca. Las primeras manifestaciones de un enve-
nenamiento agudo son dolor de cabeza, nausea, vomito, debilidad y tos persis-
tente. La expectoracion de esputo espumoso y sangriento es caracteristica de la
edema pulmonar.
El formaldehido en el aire irrita los ojos y las membranas del tracto res-
piratorio superior. En algunos individuos tiene un alto potencial de sensibili-
dad y puede causar dermatitis alergica. Ademas, este ha estado asociado con
sintomas parecidos al asma, aunque existe una controversia donde se cuestiona
si estos sintomas representan verdaderamente asma causada por reacciones
alergicas al formaldehido.6'7'8 Las concentraciones elevadas de formaldehido en
el aire pueden causar edema de la laringe, asma o traqueobronquitis; pero apa-
rentemente no causa edema pulmonar. Las soluciones acuosas que entren en
PB
FUMIGANTES
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contacto con la piel causan callosidad y aspereza debido a la coagulacion de la
capa de queratina. El formaldehido ingerido ataca la membrana del estomago y
del instestino, causando necrosis y ulceracion. Despues que el formaldehido es
absorbido, este se convierte en acido formico. Este ultimo es parcialmente res-
ponsable por la acidosis metabolica caracteristica de la intoxicacion con
formaldehido. El colapso circulatorio y fallo renal prosiguen a la devastadora
lista de efectos intestinales debido a la ingestion de formaldehido, que condu-
cen a la muerte. El paraformaldehido es un polimero que libera formaldehido
lentamente en el aire. Su toxicidad es algo menor que la del formaldehido,
debido a la evolucion lenta del gas.
El cianuro de hidrogeno gaseoso causa envenenamiento inactivando la
ultima enzima esencial de la respiracion celular en los mamiferos, citocromo
oxidasa. El paciente mostrara signos de hipoxia severa, sin embargo, en algunos
casos no parece cianotico. Esto se debe a una falla en la reduccion de la hemo-
globina frente a la perdida de respiracion celular. Esto produce un color rosado
o rojo en la piel y arteriolizacion de las venas de la retina. Ademas de estos
descubrimientos fisicos sugestivos se puede encontrar un nivel excepcional de
pO2 de gas toxico en la sangre.9 La cianosis es el ultimo signo que indica colap-
so circulatorio.
Las celulas del cerebro parecen las mas vulnerables a la reaccion del cianuro.
Las primeras senales de envenenamiento son poco especificas y pueden
relacionarse con varies tipos de envenenamientos. La inhalacion de una elevada
concentracion de cianuro puede causar inconsciencia y muerte inmediata,
producido por medio de fallo respiratorio. Otro signo comun es la acidosis
metabolica. Una menor exposicion causa entumecimiento y constriccion en la
garganta, rigidez en la mandibula, salivacion, nausea, vomito, mareo y aprension.
El empeoramiento del envenenamiento se manifiesta como convulsiones tonicas
y clonicas. Las manifestaciones tipicas de un envenenamiento severe son las
pupilas dilatadas y fijas,la bradicardia y la respiracion entrecortada e irregular (o
apnea). Muchas veces el corazon continua latiendo despues de haber cesado la
respiracion.9'10 Una buena serial de envenenamiento es un olor amargo a
almendras en el aliento o el vomito, pero no todo individuo es capaz de detectar
dicho olor.9
El bromuro de metileno es incoloro y casi inodoro, pero es un fuerte
irritante de las vias respiratorias bajas; algunas veces puede inducir edema
pulmonar, hemorragia o neumonia confluente. El inicio del problema respira-
torio puede retrasarse de 4 a 12 horas despues de la exposicion. El compuesto
es un depresor del sistema nervioso central, pero tambien puede causar convul-
siones. Los primeros sintomas del envenenamiento severe incluyen dolor de
cabeza, mareo, nausea, vomito, tremores dificultad del habla y ataxia. En los
casos mas severos de envenenamiento causa convulsiones miclonicas y convul-
siones tonicas generalizadas, las cuales algunas veces no responden a la terapia
inicial. En pacientes severamente intoxicados los residues de la deficiencia
neurologica pueden ser persistentes. Estos incluyen: convulsiones miclonicas,
FUMIGANTES 175
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ataxia, debilidad muscular, temblores, disturbios del comportamiento y reflejos
disminuidos.11'12 Cuando el bromuro de metileno liquido entra en contacto
con la piel causa quemaduras severas, picor y pueden ocurrir ampollas. La necrosis
de la piel puede ser profunda y extensa.
El cloruro de metileno es uno de los halocarburos menos toxicos. Se
absorbe mediante inhalacion y hasta cierto punto limitado, por via cutanea. El
contacto con altas concentraciones puede causar depresion del sistema nervio-
so central, manifestandose como fatiga, debilidad y sopor. En los seres humanos
parte del cloruro de metileno absorbido es degradado a monoxide de carbono,
produciendo un incremento de la carboxihemoglobina en la concentracion de
la sangre. Sin embargo, las concentraciones rara vez son lo suficientemente
elevadas como para causar los sintomas de envenenamiento de monoxide de
carbono. La ingestion ha causado la muerte debido a hemorragias
gastrointestinales, dano severe al higado, coma, shock, acidosis metabolica y
dano renal. Dosis extraordinarias en animates de laboratorio han causado irrita-
bilidad, temblores, y narcosis conducente a la muerte. Cuando es calentado a
punto de descomposicon, uno de sus productos es gas fosgeno, altamente toxi-
co ha causado severa neumonitis aguda.13
El naftaleno es un hidrocarburo solido, de color bianco, que se ha utiliza-
do por mucho tiempo como repelente para las polillas en forma de bolitas, en
hojuelas y en pastillas. Su punto de sublimacion es lento. El vapor tiene un olor
fuerte e irritante para los ojos y el tracto respiratorio. La inhalacion de concen-
traciones elevadas causa dolor de cabeza, mareo, nausea y vomito. El contacto
por medio de inhalacion extensa y prolongada o mediante la ingestion, o por la
via cutanea (a traves del contacto con telas excesivamente tratadas) puede cau-
sar hemolisis particularmente en personas que padecen de una deficiencia de
glucosa-6-fosfato deshidrogenasa.14 La deficiencia de glucosa-6-fosfato
deshidrogenasa es heredada debido a un gene de dominacion intermedia vin-
culado con el sexo. Por esta razon se expresa mayormente en los heterozigotos
masculinos. Sin embargo los heterozigotos femeninos sufren solamente una
depresion leve de esta enzima. Esta enfermedad esta vinculada comunmente a
la raza africana y a los grupos etnicos de la raza africo-americana.Tambien se ha
visto en algunas poblaciones mediterraneas etnicas.
De hecho, el metabolito alfa-naftol es el reponsable de la hemolisis.15 El
naftol y los productos de hemolisis pueden producir dano secundario en los
tubulos renales. Es posible que puedan ocurrir convulsiones y coma, especial-
mente en ninos. En los infantes, los niveles elevados de la hemoglobina,
metahemoglobina y bilirrubina en el plasma pueden conducir a encefalopatia.
Kernicterus ha sido descrita como la complicacion especifica del contacto con
naftaleno, causando hemolisis severa y resultando en un exceso de bilirrubina
en la sangre (hiperbilirrubinemia). Algunos individuos presentan sensibilidad
cutanea a la naftalina.
El paradiclorobenceno es solido a temperatura ambiente y en la actuali-
dad se usa extensamente como repelente de polilla, aromatizante y desodorante
PB FUMIGANTES
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del hogar y en los complejos publicos. El vapor es poco irritante para la nariz y
los ojos. La ingestion de grandes cantidades puede causar dano hepatico y tem-
blores. Aunque la ingestion accidental esta asociada comunmente con los niiios,
la intoxicacion sintomatica en los seres humanos es rara. Otros isomeros del
diclorobenceno son mas toxicos que el isomero para.
El gas fosfina es extremadamente irritante en el tracto respiratorio. Tarn-
bien produce envenenamiento sistematico severo. Su uso corno fumigante en
lugares de almacenamiento de productos alimenticios es mediante la coloca-
cion de fosfuro de aluminio solido (phostoxin). El gas fosfina es liberado lenta-
mente mediante hidrolisis. Los casos mas severos de intoxicacion han envuelto
la ingestion de fosfuro de aluminio solido, el cual se convierte en gas rapida-
mente por la hidrolisis acida que ocurre en el estomago. El envenenamiento
mediante ingestion acarrea una tasa de mortalidad alta (50 a 90%).16>17 Los me-
canismos de toxicidad no se entienden bien. Se han encontrado niveles extra
celulares de magnesio ligeramente elevados, lo que sugiere una merma en el
magnesio intracelular, como resultado de dano miocardico.18 Los envenena-
mientos fueron bastante frecuentes a finales de la decadas de 1980 y a princi-
pios de 1990 en algunas partes de India.16'17 Las manifestaciones principles de
envenenamiento son: fatiga, nausea, dolor de cabeza, mareo, sed, tos, dificultad
para respirar, taquicardia, compresion en el pecho, parestesia e ictericia. En los
casos mas severos se presenta el colapso cardiaco. La edema pulmonar es una
causa comun de muerte. En otros casos letales se desarrollan: arritmia ventricular,
problemas de conduccion y asistolia.16'19 Se dice que el olor del gas es semejante
a pescado podrido.
El bioxido de azufre es un gas altamente irritante y tan desagradable que
las personas que lo inhalan buscan inmediatamente aire no contaminado. Sin
embargo, a veces a ocurrido laringoespasmo y edema pulmonar resultando en
afliccion respiratoria severa y muerte. A veces es la causa de enfermedades de las
vias respiratorias en personal ocupacionalmente expuesto.
El fluoruro de sulfurilo es extensamente usado para la fumigacion en
estructuras de construccion. Aunque la experiencia de su uso ha sido general-
mente buena, han ocurrido fatalidades cuando individuos sin adecuada protec-
cion han regresado antes del tiempo limite a los edificios tratados con este
fumigante.20 Como este material es mas pesado que el aire, puede causar a
hipoxia fatal luego del reingreso antes del tiempo limite. Las manifestaciones
del envenenamiento han sido, irritacion de los ojos, nariz y garganta, debilidad,
nausea, vomito, disnea, tos, agitacion, espasmo nervioso muscular y convulsio-
nes. El dano renal puede causar proteinuria y azotemia.
Confirmacion de Envenenamiento
No existen pruebas practicas que pudieran servir de utilidad para diagnos-
ticar el envenenamiento de la absorcion de las sustancias como los aldehidos,
los oxidos de alquilo, o fosfina.
FUMIGANTES 177
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El disulfuro de carbono se puede medir en la orina por medio de cromatografia
de gases, pero esta prueba no se encuentra generalmente disponible.
El ion del cianuro proveniente del cianuro mismo o del acrilonitrilo se
puede medir completamente en la orina y en la sangre mediante un electrode
especifico para el ion o por medio de colorimetria. Los sintomas de intoxica-
cion pueden aparecer en los niveles de la sangre sobre 0,10 mg por litro.10 El
cianuro en la orina es generalmente menor de 0,30 mg por litro en personas no
fumadoras pero hasta 0,80 mg por litro en fumadores. El tiocianato, un metabolito
del cianuro, tambien puede medirse en la sangre y la orina. El limite superior en
la sangre puede exceder 12 mg por litro.10 El tiocianato de la orina se encuentra
generalmente a menos de 4 mg por litro en no fumadores, pero puede ser llegar
a niveles tan altos como 17 mg por litro en fumadores.
El bromuro de metilo produce bromuro inorganico en el cuerpo. El
bromuro de metilo de por si, tiene una vida media corta y no se detecta gene-
ralmente hasta despues de 24 horas. El anion bromuro se excreta con lentitud
en la orina (la vida media es de alrededor de 10 dias),y el metodo predilecto de
medida liquida.11 El suero de personas que no estan altamente expuestas al
bromuro contiene por lo general menos de 1 mg de ion bromuro por 100 mL.
Debe considerarse la posible contribucion de los bromuros medicinales a la
elevacion del contenido sanguineo y a la excrecion urinaria, pero cuando la
unica fuente es del bromuro de metilo es, y si el bromuro serico excede 6 mg
por 100 mL es probable que exista cierta absorcion, y 15 mg por 100 mL es
compatible con sintomas de envenenamiento severe. El bromuro inorganico es
mucho menos toxico que el bromuro de metilo; por lo general las concentra-
ciones en el suero superiores a los 150 mg por 100 mL se presentan en personas
que han ingerido medicamentos con bromuro inorganico. En algunos paises
europeos donde los trabajadores se encuentran expuestos al bromuro de metilo,
se llevan a cabo pruebas periodicas de las concentraciones sanguineas de bromuro.
Cuando los niveles de sangre exceden 3 mg por 100 mL, es senal de que el
trabajador necesita una medida mas agresiva de proteccion. Cuando los niveles
de concentracion de bromuro exceden 5 mg por 100 mL el trabajador debe ser
removido del ambiente contaminado con el fumigante hasta que el nivel de
concentracion sanguinea baje a menos de 3 mg por 100 mL.
El cloruro de metileno se convierte a monoxido de carbono en el cuerpo
dando origen a carboxihemoglobinemia, la cual puede medirse en laboratories
clinicos.
El naftaleno se transforma principalmente a alfa-naftol en el cuerpo y se
excreta con rapidez en la orina en forma conjugada. El alfa-naftol puede me-
dirse por cromatografia de gases. Muchos halocarburos pueden medirse en la
sangre por metodos de cromatografia de gases. Otros pueden medirse en el aire
expirado.
El paradiclorobenceno se metaboliza principalmente a 2,5-diclorofenol,
el cual se conjuga y se excreta en la orina. Este producto se puede medir por
cromatografia.
PB FUMIGANTES
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En una victima fatal de fumigacion con fluoruro de sulfurilo se midio una
concentracion de 0,5 nig por litro. El suero de fluoruro de personas que no se
encuentran extraordinariamente expuestas, raramente excede 0,1 mg por litro.
Una gran preocupacion en el sector industrial algunas veces induce a
monitorear la absorcion humana de halocarbonos mediante el analisis del aire
expirado. Existe una tecnologia similar en algunos departamentos de la
anestesiologia. Sin embargo el historial de la exposicion ayuda a identificar al
toxico de modo, que el analisis casi nunca es necesario. Sin embargo, para ma-
nejar los casos dificiles de intoxicacion, es aconsejable monitorear las concen-
traciones del gas toxico para evaluar la eliminacion del fumigante. Es necesario
analizar la orina para identificar las proteinas y los eritrocitos con el objeto de
detectar algun daiio renal. La hemoglobina libre en la orina probablemente
refleja hemolisis, como en el caso de la naftalina. Las elevaciones de fosfatasa
alcalina, lactato deshidrogenasa (LDH), alanina aminotrasferasa y aspartato
aminotransferasa (GGT,ALT,AST) en suero y ciertas otras enzimas, son indices
sensibles para medir el daiio en las celulas hepaticas. Daiios mas severos aumen-
tan las concentraciones plasmaticas de la bilirrubina. El uso de radiografias es
recomendable para confirmar la ocurrencia de edema pulmonar. La
electromiografia es recomendable para evaluar daiio en la periferia nerviosa. El
recuento espermatico se considera apropiado para los trabajadores expuestos al
dibromocloropropano y dibromuro de etileno.
Actualmente algunas agencias de la salud exigen que se efectuen pruebas
neurologicas y neuropsicologicas periodicamente a los trabajadores severamente
expuestos a fumigantes y disolventes, con el fin de detectar daiio del sistema
nervioso lo antes posible. Esto podria ser una medida especificamente deseable
para casos de contacto con agentes como el bromuro de metilo y el disulfuro de
carbono, los cuales poseen una buena documentacion de efectos neurotoxicos.
Tratamiento
1. Descontaminacion dermica. Lave la contaminacion dermica y ocular con
abundante cantidad de agua o solucion salina por no menos de 15 minutos. Algu-
nos fumigantes resultan ser corrosives para la cornea y pueden causar ceguera.
Obtenga tratamiento medico especializado obtenido inmediatamente despues de
quitar la contaminacion. La contaminacion dermica puede causar ampollas y que-
maduras quimicas profundas. La absorcion de algunos fumigantes a traves de piel
puede ser lo suficientemente severa como para causar envenenamiento sistemico
en la ausencia de la inhalacion. Debido a todas estas razones la descontaminacion
ocular y dermica tienen que ser inmediata y meticulosa.Vease el Capitulo 2.
2. Traslado fisico.Traslade inmediatamente a las victimas de inhalacion a un
area de aire fresco. Aunque los sintomas y seiiales iniciales scan leves, mantenga
a la victima inmovil y en posicion semi-inclinada. La actividad minima reduce
la probabilidad de que ocurra edema pulmonar.
FUMIGANTES 179
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3. Respiracion. Si la victima no esta respirando, despeje las vias respiratorias de
secreciones y resucite con un aparato de oxigeno de presion positiva. Si este no
se encuentra disponible, suministre compresion toraxica para mantener la res-
piracion. Si la victima no tiene pulso, emplee resucitacion cardiaca.
4. Edema pulmonar. Si la edema pulmonar es evidente, existen varias medi-
das para sustento de la vida. No obstante, se debe depender del juicio medico
en el manejo de cada caso. Generalmente se recomiendan los siguientes proce-
dimientos:
Siente a la victima en un asiento con respaldo
Use presion positiva de oxigeno ya sea continua y/o intermitentemente
para aliviar la hipoxemia. (No administre altas concentraciones de
oxigeno o durante periodos mas largos de lo que fuese necesario,
porque puede exagerar el dano causado por el fumigante en los tejidos
pulmonares. Monitoree la presion de oxigeno arterial).
Administre lentamente 40 mg de furosemida por via intravenosa
(0,5-1 mg/kg y en niiios hasta 20 mg), para reducir la carga venosa
e inducir diuresis. Consulte las instrucciones incluidas en el paquete
para direcciones y precauciones adicionales.
Algunos pacientes se pueden beneficiar de la administracion precavida de dro-
gas ansioliticas. Estos pacientes deben manejarse en unidades de cuidado inten-
sive con el personal capacitado para este siempre y cuando sea posible. Limite la
actividad fisica del paciente por lo menos durante 4 horas. Generalmente la
debilidad fisica severa indica un persistente dano pulmonar. Las pruebas
pulmonares de serie resultan ser utiles para evaluar la recuperacion.
5. Shock. Combata el shock colocando a la victima en posicionTrendelenburg
y administre plasma, sangre total y/o soluciones glucosas y de electrolitos por
via intravenosa, con mucho cuidado para evitar edema pulmonar. Monitoree la
presion venosa central continuamente. Las aminas vasopresoras deben de ser
administradas con mucho cuidado para no causar irritabilidad del miocardio.
6. Control de convulsiones. Es probable que ocurran convulsiones cuando
ocurre envenenamiento con bromuro de metilo, cianuro de hidrogeno,
acrilonitrilo, fosfma y disulfuro de carbono.Vease el Capitulo 2 para el manejo
de convulsiones. En algunos casos de envenenamiento con bromuro de metilo
las convulsiones han sido resistentes a benzodiazepinas y difenilidantoinas y el
recurso ha sido usar anestesia tiopental.11
7. Descontaminacion gastrointestinal. Si se ha ingerido algun fumigante
liquido o solido pocas horas antes del tratamiento, elimine lo mas pronto posi-
PB FUMIGANTES
-------
ble las cantidades remanentes en el estomago seguido del tratamiento con car-
bon activado, conio ha sido sugerido en el Capitulo 2.
8. Balance de fluidos. El balance de fluidos debe monitorearse y el sedimento
de la orina se debe revisar regularmente para la indicacion de dano tubular.
Mida el suero de la fosfatasa alcalina, la deshidrogenasa lactica, alanina
aminotransferasa y aspartato aminotransferasa, LDH, ALT, AST y la bilirrubina
para evaluar el dano hepatico.
9. Hemodialis extracorporea. Tal vez esta sea necesaria para regular la com-
posicion de los liquidos extracelulares si ocurre insuficiencia renal. Probable-
mente no sea eficaz para en la remocion de los compuestos lipofilicos de la
sangre, pero es eficaz para el control de la composicion de fluidos extracelulares
en caso de insuficiencia renal.
10. Fumigantes especificos. Se recomiendan ciertas medidas especificas para
algunos fumigantes en especificos (disulfuro de carbono, tetracloruro de carbo-
no, naftaleno, gas fosfma, y cianuro de hidrogeno y acrilonitrilo):
Disulfuro de Carbono: Envenenamientos leves debido a la inha-
lacion del disulfuro de carbono no necesitan nada mas que una ob-
servacion cautelosa, aun cuando alucinaciones sensoriales, delirio, y
aberraciones de conducta scan alarmantes. En casos de envenena-
mientos severos se requieren medidas mas especificas. Si la conducta
maniaca amenaza la seguridad de la victima, administre lentamente
y por via intravenosa diazepan (5-10 mg para adultos, 0,2-0,4 mg/
kg para ninos) puede ayudar a tranquilizar al paciente. Repita cuan-
tas veces sea necesario para obtener sedacion. No administre agentes
estimulantes de catecolaminas asi como anfetaminas, y recepina.
Tetracloruro de Carbono: Para el envenenamiento con tetracloruro
de carbono se han sugerido una serie de medidas para reducir la
necrosis hepatica. El oxigeno hiperbarico se ha usado con un poco
de exito.2 Puede ser conveniente la administracion oral de N-
acetilcisteina (MucomystR) como mecanismo para reducir el dano
causado por los radicales libres.21 Diluya el producto patentado al
20% en una proporcion de 1:4 en bebidas gaseosas y administre
alrededor de 140 mg/kg por peso corporal de la solucion diluida
como dosis de carga. Entonces administre 70 mg/kg cada 4 horas
despues de la dosis de carga por un total de 17 dosis. (Este esquema
de dosificacion se usa para el envenenamiento con acetaminofen.)
En aquellos pacientes que exista una intolerancia de MucomystR es
necesario administracion a traves de un tubo duodenal.22 Puede usarse
N-acetil cisteina via administracion intravenosa; existe mas infor-
macion a traves de los centres del control de envenenamientos.
FUMIGANTES 181
-------
Naftaleno: La intoxicacion causada por la inhalacion de los vapores de
naftaleno se puede manejar trasladando siniplernente al paciente al aire
fresco. Elimine la contaminacion de la piel inmediatamente por medio
de irrigacion con abundante cantidad de agua limpia. La irritacion ocu-
lar puede ser severa,y si persiste,se debe recibir atencion oftalmologica.
Examine el plasma para buscar evidencia de hemolisis: un tinte de color
marron-rojizo,busque especialmente en el frotis de sangre "espectros"y
cuerpos de Heinz. En caso de la presencia de cualquiera de estos,
monitoree el contaje de celulas rojas y de hematocritos para anemia, y
analice la orina para proteinas y celulas. Mida la bilirrubina directa e
indirectamente en el plasma. Monitoree el balance de electrolitos en la
sangre. Si es posible, vigile la excrecion urinaria del naftol para evaluar la
gravedad del envenenamiento y el progreso clinico.
Si la hemolisis es de importancia clinica, administre liquidos
intravenosos para acelerar la excrecion urinaria del metabolito naftol
y proteger al rinon de los productos de la hemolisis. Utilice lactato
de Ringer o bicarbonate de sodio para mantener el pH de la orina
por encima de 7,5. Considere el uso de manitol o de furosemida
para producir diuresis. Si disminuye el flujo de la orina, suspenda las
infusiones intravenosas para evitar la sobrecarga de liquidos y debe
considerarse hemodialisis.15 En caso de anemia severa es necesario
una transfusion de sangre.
Gas Fosfina: Una reciente experiencia en India sugiere que la tera-
pia con sulfato de magnesio puede disminuir la probabilidad de un
resultado fatal.16'19'23 El mecanismo no esta claro, pero posiblemente
se deba a las propiedades que tiene el magnesio de estabilizacion de
membranas, protegiendo al corazon de arritmias fatales. Se encontro
que en una serie de 90 pacientes, el sulfato de magnesio disminuyo la
mortalidad de un 90% a un 52%.16 Se han hecho dos estudios contro-
lados, uno de los cuales mostro una reduccion en la mortalidad de
52% a 22%.23 En el otro estudio no se encontro efecto en la mortali-
dad.24 La dosis para el sulfato de magnesio es: 3 gramos durante las 3
primeras horas como una infusion continua, seguida de 6 gramos por
24 horas dentro de los proximos 3 a 5 dias.16
Cianuro de Hidrogeno y Acrilonitrilo: Los envenenamientos
con cianuro de hidrogeno y acrilonitrilo gaseosos o liquidos se tra-
tan basicamente igual que los envenenamientos con las sales de cia-
nuro. Debido a que el cianuro se absorbe con rapidez despues de la
ingestion, el tratamiento debe de iniciarse con la administracion
inmediata de antidotos. La descontaminacion gastrointestinal debe
ser considerada si el paciente se presenta dentro de un corto inter-
valo despues de la ingestion, y solamente despues que haya co-
menzado el tratamiento previamente discutido, para salvar la vida
PB FUMIGANTES
-------
haya comenzado. Debe evitarse el uso de jarabe de ipecacuana debi-
do al potencial del comienzo rapido (del envenenamiento) y la per-
dida de conciencia.
Los tres antidotes nitrito de amilo, nitrito de sodio, y tiosulfato de
sodio estan disponibles como un botiquin de primeros auxilios
conocidos como Lilly Cyanide Antidote Kit, disponible a traves de la
compania Eli Lilly, en Indianapolis, Indiana. Las dosis varian entre
niiios y adultos y estan explicadas a continuacion.
Dosificacion de los Antidotes de Cianuro
Adultos:
Administre oxigeno de manera continua. El oxigeno hiperbarico ha
sido evaluado como efectivo en esta condicion.25 Si falla la respira-
cion, mantenga la ventilacion pulmonar mecanicamente.
Administre ampolletas de nitrito de amilo por inhalacion durante
15 a 30 segundos por cada minuto, mientras prepara una solucion
fresca de nitrito de sodio a 3%. Esta solucion viene preparada en
botiquines de antidotes de cianuro.
Tan pronto como este lista la solucion, inyecte por via intravenosa
10 mL de una solucion de nitrito de sodio al 3% durante un
intervalo de 5 minutos dejando la aguja en su lugar.
Advertencia: Mida el pulso y la presion sanguinea durante la adminis-
tracion del nitrito de amilo y el nitrito de sodio. Si la presion sanguinea
sistolica cae por debajo de 80 mm de Hg, disminuya la administracion
del nitrito o suspendala hasta que se recupere la presion sanguinea.
Despues de la inyeccion del nitrito de sodio, administre una infu-
sion de 50 mL de una solucion acuosa de tiosulfato de sodio al
25% durante un periodo de 10 minutos. La dosis inicial para adultos
no debe exceder de 12,5 g.
Si los sintomas persisten o reaparecen, repita el tratamiento con ni-
trato de sodio y tiosulfato de sodio a la mitad de la dosis menciona-
da anteriormente.
Mida la hemoglobina y la metahemoglobina en la sangre. Si se ha
convertido mas de 50% de la hemoglobina total en metahemoglobina,
considere la posibilidad de llevar a cabo una transfusion de sangre,
porque el proceso de reconversion a hemoglobina normal es lento.
...Continua
FUMIGANTES 183
-------
Ninos
Administre nitrito de amilo, oxigeno,y apoyo respiratorio mecanico
corno se recomienda para los adultos. Las proximas dosificaciones
de antidotes han sido recomendadas para ninos.26
Ninos de mas de 25 kg de peso corporal deben de recibir dosis de
adultos de nitrito de sodio y de tiosulfato de sodio.
En ninos de menos de 25 kg de peso corporal, tome primero 2
muestras de sangre de 3 a 4 ml y despues a traves de la misma aguja
administre 0,15-0,33 mL/kg hasta 10 mL de una solucion al 3% de
nitrito de sodio inyectado durante un periodo de 5 minutos. Des-
pues del nitrito de sodio, administre una infusion de 1,65 mL/kg de
tiosulfato de sodio al 25% a una tasa de 3 a 5 mL por minuto.
En este momento, determine el contenido de hemoglobina de la mues-
tra sanguinea obtenida antes del tratamiento. Si los sintomas y signos
del envenenamiento persisten o reaparecen, administre infusiones su-
plementarias de nitrito de sodio y tiosulfato de sodio con base en el
nivel de hemoglobina, segun se presenta en la tabla. Las cantidades
que se recomiendan estan calculadas para evitar una
metahemoglobinemia que amenace la vida de los ninos anemicos. Se
intenta convertir con ellas aproximadamente el 40% de la hemoglobi-
na circulante a metahemoglobina. Si es posible mida las concentracio-
nes de metahemoglobina sanguinea segun avance el tratamiento.
DOSIS RECOMENDADAS DE NITRITO DE SODIO Y
TIOSULFATO
EN EL NIVEL
Concentration
Initial de
Hemoglobina
Gramos/100mL
14.0
12.0
10.0
8.0
DE SODIO SUPLEMENTARIAS
DE HEMOGLOBINA
Volumen
de nitrato de sodio
al 3% ml/kg
0.20
0.16
0.14
0.11
BASADAS
Dosis de
Tiosulfato
de sodio
al 25% ml/kg
1.00
0.83
0.68
0.55
PB
FUMIGANTES
-------
Aunque algunas sales de cobaltos, quelatos y combinaciones organicas han
mostrado senates prometedoras como antidotes de cianuro, desafortunadamen-
te no se encuentran disponibles generalmente en los Estados Unidos. Ninguna
sustancia ha mostrado ser mas eficaz que la del regimen de tratamiento con
tiosulfato de nitrito.
Referencias
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;l: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.
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.TsaiJ,Wang LM, et al.The clinical experience of acute cyanide poisoning. Am J Emerg
Med 1995;13:524-8.
11. Hustinx WNM, van de Laar RTH, van Huffelen A, et al. Systemic effects of inhalational
methyl bromide poisoning: A study of nine cases occupationally exposed due to inadvertent
spread during fumigation. BrJ Ind Med 1993;50:155-9.
12. Deschamps FJ andTurpin 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-ll.
16. Katira R, Elhence GP, Mehrotra ML, et al. A study of aluminum phosphide poisoning with
special reference to electrocardiographic changes.J/lssoc 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. IntJ Clin Pharmacol Ther Toxicol 1991;29:82-5.
FUMIGANTES 185
-------
19. Gupta S and Ahlawat SK.Aluminum phosphide poisoning:A review. ClinToxicol 1995;33:19-24.
20. Scheuerman EH. Suicide by exposure to sulfuryl fluoride.J Forensic Sci 1986;31:1154-8.
21. Ruprah M, MantTGK, and Flanagan RJ. Acute carbon tetrachloride poisoning in 19 pa-
tients: Implications for diagnosis and treatment. Lancet 1985;l:1027-9.
22. Anker AL and Smilkenstein MJ. Acetominophen: Concepts and controversies. Emerg Med
CUn 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. JAssoc 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.
PB FUMIGANTES
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CAPITULO 17
Rodenticidas
Una amplia variedad de materiales se usan como rodenticidas. Estos posan ries-
gos especificos de envenenamiento accidental por varias razones. En primer
lugar, como agentes disenados especificamente para la eliminacion de mamife-
ros, muchas veces su toxicidad es muy similar para su objetivo - los roedores, asi
como para los humanos. (La warfarina y otros rodenticidas anticoagulantes fue-
ron desarrollados desde un principio para veneer este problema; se crearon
estos compuestos que eran altamente toxicos para los roedores, especificamente
despues del contacto repetido, pero mucho menos toxico hacia los humanos.)
En segundo lugar, debido a que los roedores comparten el ambiente general-
mente con los humanos y otros mamiferos, el riesgo de contacto accidental es
parte integral en la colocacion de carnadas para roedores. Finalmente, segun los
roedores han ido desarrollando resistencia a los rodenticidas existentes, hay una
necesidad continua para desarrollar nuevos rodenticidas con un potencial toxi-
co mas alto. Por ejemplo, segun los roedores desarrollan mayor resistencia a las
carnadas de warfarina, el desarrollo de las "superwarfarinas" ha aumentado el
riesgo a los seres humanos.1'2 Es importante conocer los patrones y el desarrollo
de los compuestos mas toxicos y hacer todo lo posible por identificar el agente
de uso actual de manera que se instituya el tratamiento mas apropiado para
estos envenenamientos.
PUNTOS
IMPORTANTES
Las nuevas "superwarfarinas"
se encuentran ampliamente
disponibles y son toxicas en
dosificadones mucho mas
bajas que las warfarinas
convencionales
Senales y Smtomas:
Son variables dependiendo
del agente
Los compuestos de warfarina
causan hemorragia
El gas fosfina causa edema
pulmonar (debido al forfuro
de zinc)
Efectos cardiovasculares, Gl y
CMS predominan con el talio
Las convulsiones son las
principales manifestaciones
de estricnina y
fluoroacetamida
CUMARINAS E INDANDIONAS
Toxicologia
La warfarina y compuestos relacionados (cumarinas e indandionas) son los
rodenticidas ingeridos mas comunmente en los Estados Unidos, con un infor-
me de 13,345 contactos en 1996.3 La absorcion gastrointestinal de estos toxicos
es eficiente. La warfarina puede ser absorbida a traves de la piel, pero esto solo
ha ocurrido bajo circunstancias extraordinarias.
Las cumarinas e indandionas deprimen la sintesis hepatica de los factores
esenciales para la coagulacion sanguinea dependientes de vitamina K (II
(protrombina),VII, IX y X). El efecto antiprotrombina es el mas conocido y
proporciona la base para detectar y evaluar un envenenamiento clinico. Estos
agentes tambien aumentan la permeabilidad de los capilares a traves del cuerpo,
predisponiendo al animal a una hemorragia interna masiva. Esto ocurre gene-
Tratamiento:
Especffico al agente
Vitamina K1 (fitonadiona)
para cormpuestos
relacionados a la warfarina
Control de convulsiones
Proceda con la
descontaminadon
simultaneamente a las
medidas para salvar la vida
Contraindicaciones:
No use vitaminas K3 y K4 como
sustituto de la vitamina K,
Los agentes quelantes no
son efectivos en
envenenamiento con talio
RODENTICIDAS 187
-------
Productos Comerdales
CUMARINAS
brodifacum
Havoc
Klerat
Ratak Plus
Talon
Volid
bromadiolona
Bromone
Contrac
Maki
cumaclor
Famarin
cumatetralilo
Racumin
difenacum
Frunax-DS
Ratak
warfarina
Co-Rax
cumafeno
Cov-R-Tox
Rax
Tox-Hid
Zoocumarina
INDANDIONAS
clorfacinona
Caid
Liphadione
Microzul
Ramucide
Ratomet
Raviac
Rozol
Topitox
difacinona
difacin
Ditrac
Ramik
Tomcat
pivalin*
pindona
pival
pivaldiona
* Uso suspendido en los Estados
Unidos
ralmente en el roedor varies dias despues de la ingestion de warfarina debido a
la larga vida-media que tienen los factores coagulantes dependiente de la vita-
mina K,1>2aunque despues de la ingestion de pequenas dosificacion de los coni-
puestos modernos mas toxicos puede presentarse una hemorragia letal.1
El tiempo prolongado de la protrombina (PT) por una dosificacion toxica
de cumarinas o indandionas puede hacerse evidente durante 24 horas, pero
puede llegar a un maximo de 36 a 72 horas.1'4'5 El tiempo prolongado ocurre
en respuesta a dosificacion mucho mas bajas que las necesarias para causar he-
morragia. Existe una preocupacion de que los compuestos modernos mas toxi-
cos como el brodifacum y el difenacum, puedan causar un envenenamiento
grave en dosificacion mucho mas bajas en mamiferos, incluyendo a los huma-
nos. El brodifacum, una de las superwarfarinas, puede causar intoxicacion con
una dosificacion lo suficientemente baja como de Img en un adulto 6 0,014mg/
kg en un niiio.l
Envenenamientos sintomaticos, con sintomas prolongados debido a la vida-
media larga de las superwarfarinas, han sido informados aun por contacto sim-
ple; sin embargo estos son generalmente intencionales y son altas dosificaciones.2
Debido a su relacion toxica con la warfarina, se requieren altas dosificacion de
vitamina K en los pacientes y se requiere un monitoreo mayor de la PT. Un
paciente requirio vitamina K despues de haberse dado de alta del hospital.6
Otro paciente fue dado de alta del hospital con un mejoramiento clinico
significante y solamente una coagulacion ligeramente elevada despues de haber
ingerido brodifacum. Dos semanas mas tarde se aparecio en estado comatoso y
se encontro que tenia una hemorragia intracraneal masiva.7
Los efectos clinicos de estos agentes empiezan generalmente despues de
varies dias de la ingestion, debido a la larga vida-media que tienen los factores.
Las primeras manifestaciones incluyen hemorragia nasal, encias sangrientas,
hematuria, melena y esquimosis severa.1'2'6'7'8 Los pacientes tambien pueden
presentar sintomas de anemia, incluyendo fatiga y disnea bajo esfuerzo.8 Si el
envenenamiento es severe el paciente puede progresar a shock y muerte.
Contrario a los compuestos de cumarina, algunas indandionas causan sena-
les y sintomas de danos neurologicos y cardiopulmonares en ratas de laborato-
rio conduciendo a la muerte antes de que ocurra hemorragia. Estas acciones
pueden explicar la mayor toxicidad de las indandionas en los roedores. No se
han informado manifestaciones neurologicas ni cardiopulmonares en envene-
namientos de seres humanos.
Confirmacion de Envenenamiento
El envenenamiento por cumarina o indandiona ha resultado en un aumen-
to en el tiempo de protrombina debido a la reduccion de la concentracion de
protrombina en el plasma. Esta es una prueba confiable en la absorcion de
dosificacion de importancia fisiologica. La reduccion reveladora de la protrombina
PB
RODENTICIDAS
-------
ocurre entre las 24-48 horas desde la ingestion y persiste de 1-3 semanas.1'4'5
Los manufactureros pueden medir frecuentemente los niveles sanguineos de las
Tratamiento
1. Determine la cantidad ingerida. Si se sabe con certeza que el paciente
no ha ingerido mas de dos bocados o dos carnadas de warfarina- o carnadas
tratadas con indandiona, o ha ocurrido simplemente una deglucion, o la canti-
dad ha sido menos de una carnada tratada con brodifacum mas toxico o com-
puestos de bromadiolona, es probable que no se necesite tratamiento medico.
2.Vitamina Kr Un paciente que se presenta dentro de 24 horas despues de
haber ocurrido la ingestion, probablemente tendra un nivel de PT normal. Sin
embargo, en un estudio hecho de 110 niiios intoxicados con superwarfarinas,
especificamente con brodifacum, se encontro que el nivel de PT tendio a pro-
longarse significativamente a 48 horas, despues de haber tenido una PT normal
a las 24 horas.5 Por consiguiente, para las victimas de suicidio por ingestion,
donde generalmente se desconoce cuan grande fue la cantidad de carnada in-
gerida o la salud general de la victima, la fitonadiona (vitamina Kj) administra-
da por via oral protege en contra de los efectos anticoagulantes de estos
rodenticidas, esencialmente sin riesgos para el paciente. En caso de ingestion
accidental con niiios saludables donde solo ha ocurrido una deglucion singular,
no se requiere tratamiento medico, pero deben mantenerse bajo observacion
en caso de que ocurra hemorragia o moretones. Si se sospecha que se ha inge-
rido una mayor cantidad, la PT debe mantenerse bajo observacion a las 24 y a
las 48 horas y se debe iniciar una terapia con fitonadiona en caso de un incre-
mento de la PT o de senales clinicas de hemorragia,.
Advertencia: Se requiere el uso especifico de la fitonadiona. Ni la vitami-
na K3 (menadiona, HykinonaR), o la vitamina K4 (menadiol) se consideran
antidotes para estos anticoagulantes.
3. Descontaminacion gastrointestinal. Si se han ingerido grandes cantida-
des de anticoagulante varias horas previas al tratamiento, considere los procedi-
mientos de descontaminacion gastrica, como fuera delineado en el Capitulo 2.
4. Determinacion del tiempo de la protrombina. Si el anticoagulante se
ha ingerido en algun momento durante los 15 dias anteriores, la determinacion
del tiempo de protrombina proporciona las bases para juzgar la gravedad del
envenenamiento. Los pacientes que han ingerido grandes cantidades, especial-
mente de compuestos de superwarfarina, probablemente tendran un gran pe-
riodo prolongado de baja actividad de protrombina. Los pacientes tendran que
ser tratados por un largo periodo de 3 a 4 meses.6'7
RODENTICIDAS 189
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Si el tiempo de la protrombina se prolonga significativamente, administre
AquamephytonR por via intramuscular. Refierase a la proxima tabla de dosificacion.
Dosificacion de la Fitonadiona (oral):
Adultos y nines mayores de 12 anos: 15-25 mg.
Ninos menores de 12 anos: 5-10 mg.
Puede administrarse alternativamente una preparacion coloidal de
fitonadiona, AquamephytonR por via intramuscular. Para adultos y ni-
nos mayores de 12 anos, administre de 5-10 mg; para ninos menores de
12 anos, administre de 1-5 mg.
Asegurese de que los pacientes (especialmente los niiios) se en-
cuentren bajo observacion cuidadosa por lo menos de 4 a 5 dias des-
pues de la ingestion. Las indandionas y algunas de las cumarinas intro-
ducidas recientemente pueden causar otros efectos toxicos.
Dosificacion de AquamephytonR (intramuscular):
Adultos y nines mayores de 12 anos: 5-10 mg.
Nines menores de 12 anos: 1-5 mg.
Decida la dosificacion de acuerdo a esta escala de acuerdo al grado del
tiempo prolongado de la protrombina y, en los ninos, de acuerdo a la
edad y peso del nino. Se han requerido dosificacion sustancialmente
altas de fitonadiona (de 50 a 125 mg) en algunos envenenamientos con
brodifacum cuando la hemorragia y el aumento de la PT han persisti-
do a pesar de la terapia.6'7'9
Repita el tiempo de la PT en 24 horas. Si este no ha disminuido
de su valor original, repita la dosificacion de AquamephytonR.
5. Hemorragia. Si la victima esta sangrando como resultado del envenena-
miento con anticoagulante, administre AquamephytonR intravenosamente: hasta
10 mg en adultos y ninos mayores de 12 anos, y hasta 5 mg en ninos menores
de 12 anos. La dosificacion inicial debe ser decidida mayormente a base de la
severidad de la hemorragia. Las dosificaciones subsiguientes pueden necesitar
ajuste de acuerdo a como el paciente responda, especialmente en el caso de las
superwarfarinas.6'7'9 Repita la dosificacion intravenosa de AquamephytonR en
24 si continua la hemorragia. Inyecte a intervales que no excedan el 5% de la
dosificacion total por minuto. Se recomienda administrar una infusion intravenosa
PB
RODENTICIDAS
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de AquamephytonR diluido en solucion salina o glucosada. For lo general, la
hemorragia se controla de 3 a 6 horas.
Advertencia: Han ocurrido reacciones adversas, algunas fatales, debido a
la inyeccion intravenosa de fitonadiona, incluso cuando se han observado los
limites de dosificaciones recomendadas y los intervales de la inyeccion. For esta
razon, la via intravenosa debe utilizarse solo en casos de envenenamiento grave.
Las caracteristicas de las reacciones adversas son: rubor, rnareo, hipotension,
disnea y cianosis.
En casos de hemorragia severa, la terapia con un antidote debe suplemen-
tarse con transfusiones de sangre fresca o de plasma. El uso de sangre fresca o de
plasma es el metodo mas eficaz y rapido para detener la hemorragia originada
por estos anticoagulantes, aunque pueda que el efecto no sea duradero. For lo
tanto, es importante que se realicen las transfusiones en conjunto con la terapia
de fitonadiona.
Determine el tiempo de la FT y las concentraciones de la hemoglobina
cada 6 a 12 horas, con el fin de evaluar la efectividad de las medidas
antihemorragicas.Tan pronto se restaure la coagulacion normal de la sangre, se
recomienda drenar los hematomas grandes.
Durante el periodo de recuperacion una terapia con sulfato ferroso es ade-
cuada para ayudar a restaurar la masa de eritrocitos perdida.
Productos Comerdales
INORGANICOS
sulfato de talio
fosforo amarillo
fosfuro de zinc
Phosvin
Ridall-Zinc
Zinc-Tox
El fosforo amarillo no esta
disponible para la venta en los
Estados Unidos. El fosfuro de zinc
aun se encuentra registrado en
los Estados Unidos y esta
disponible en tiendas al detal. El
sulfato de talio no se esta
registrado para el uso pesticida,
pern solamente se encuentra
disponible para el uso de las
agendas del gobierno.
RODENTICIDAS INORGANICOS
Toxicologia
El sulfato de talio es bien absorbido por el intestine y la piel. Exhibe un
alto volumen de distribucion (absorcion en los tejidos) y se distribuye princi-
palmente al rinon y el higado, ambos participantes de su propia excrecion. La
mayor parte del talio en la sangre se localiza en las celulas rojas. La vida media
para eliminarlo de la sangre en un adulto es de 1 a 9 dias. Muchos autores
informan que la (dosificacion letal) DL50 en los seres humanos es entre 10 y 15
mg/kg.10
Contrario a otros rodenticidas inorganicos como el fosforo amarillo y el
fosfuro de zinc, el envenenamiento con talio tiende a desarrollar gradualmente
sin producir sintomas obvios y posee una gran variedad de manifestaciones
toxicas. La alopecia es una caracteristica bastante consistente del envenena-
miento con talio que muchas veces es util para propositos diagnosticos; sin
embargo, ocurre dos semanas o mas despues del envenenamiento y no es util en
la presentacion inicial.10'11 Ademas de la perdida del cabello, el sistema
gastrointestinal, el sistema nervioso central, el sistema cardiovascular, el sistema
renal y la piel son afectados prominentemente debido a la ingestion toxica.
Los primeros sintomas incluyen, dolor abdominal, nausea, vomito, diarrea
sangrienta, estomatitis y salivacion. Mas tarde puede aparecer ileo. Puede ocu-
RODENTICIDAS 191
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rrir un incremento en las enzimas hepaticas, que indica dano en los tejidos.
Otros pacientes pueden experimentar senales de intoxicacion en el sistema
nervioso central que incluyen, dolor de cabeza, letargo, debilidad muscular,
parestesia, temblores, ptosis y ataxia. Estas ocurren generalmente varies dias o
despues de una semana del contacto.10'12 Parestesias extremadamente dolorosas,
con la presencia o ausencia de senales gastrointestinales, pueden ser la queja
principal.11'13 Movimientos mioclonicos, convulsiones, delirio y coma reflejan
un severe envolvimiento neurologico. La fiebre es un pronostico desfavorable
que indica dano cerebral.
Los efectos cardiovasculares incluyen hipotension temprana, por lo menos
debido en parte a una miocardiopatia toxica. Pueden ocurrir arritmias
ventriculares. La hipertension ocurre mas tarde y probablemente es un resulta-
do de la vasoconstraccion. Puede aparecer proteina y celulas rojas en la orina.
Los pacientes pueden desarrollar tambien edema alveolar y la formacion de la
membrana hialina en los pulmones, consistente con un diagnostico de Sindro-
me de Dificultad Respiratoria Aguda.14 La muerte causada por el envenena-
miento con talio puede ser debido a una paralisis respiratoria o al colapso
cardiovascular. La absorcion de dosificacion no letales de talio ha causado
neuropatias dolorosas y paresis, atrofia del nervio ocular, ataxia persistente, de-
mencia, convulsiones y coma.11
El fosforo amarillo (tambien conocido como fosforo bianco) es un agente
corrosivo que dana todos los tejidos con los que entra en contacto, incluyendo la
piel y la capa intestinal. Los primeros sintomas generalmente reflejan dano en la
membrana mucosa y ocurren durante los primeros minutos hasta 24 horas des-
pues de la ingestion. Los primeros sintomas incluyen, vomito severe y dolor
ardiente en la garganta, el pecho y el abdomen. La emesis puede ser sangrienta
(roja, marron, o negra),15 y en ocasiones puede tener un olor a ajo.16'17 En algunos
casos, unos de los primeros sintomas del sistema nervioso central que pueden
aparecer son senales como el letargo, inquietud e irritabilidad, seguido de los
sintomas de dano gastrointestinal. El shock y paro cardiopulmonar conducentes a
la muerte pueden ocurrir inicialmente durante una ingestion severa.17
Si el paciente sobrevive, puede presentarse un periodo de unas cuantas
horas o dias, mas o menos libre de sintomas, aunque este no siempre es el caso.15
La tercera etapa de intoxicacion subsigue con senales sistemicas que indican
lesion severa al higado, miocardio y cerebro. Esto se debe al gas fosfamina (PH3)
formado en, y absorbido en del intestino. La nausea y vomito puede recurrir. La
hemorragia que aparece en varies lugares refleja una depresion del factor de la
sintesis de coagulacion en el higado danado. Tambien puede contribuir a una
trombocitopenia y puede aparecer hepatomegalia e ictericia. Puede desarro-
llarse un shock hipobulemico y una miocarditis toxica. El dano cerebral es
manifestado por convulsiones, delirio y coma. El dano renal anurico se desarro-
lla comunmente debido al shock y a los efectos toxicos de los productos de
fosforo y la acumulacion de bilirrubina en los tubulos renales. La taza de mor-
talidad de los envenenamientos con fosforo puede ser tan alta como de 50%.15
PB RODENTICIDAS
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El fosfuro de zinc es mucho menos corrosive para la piel y las membra-
nas mucosas que el fosforo amarillo, pero la inhalacion del polvo puede inducir
edema pulmonar. El efecto emetico del zinc liberado en el intestino puede
proporcionar una medida de proteccion; sin embargo, puede producirse fosfamina
en el intestino y ser absorbido con el zinc. La nausea, vomito, agitacion, escalo-
frios, o constriccion del pecho, disnea y tos pueden progresar a edema pulmonar.
Los pacientes pueden enfrentarse a muchas de las mismas intoxicaciones sistemicas
encontradas con el fosforo amarillo, incluyendo fallo hepatico con ictericia y
hemorragia, delirio, convulsiones y coma (por la encefalopatia toxica), tetania
por hipocalcemia, y anuria por el dano a los tubulos renales. Arritmias
ventriculares debido a la cardiomiopatia y el shock tambien pueden ocurrir y
son otra causa comun de muerte.16> 18 La inhalacion del gas fosfamina debido al
uso inapropiado de rodenticidas de fosfuro ha resultado en edema pulmonar,
dano miocardial y el envolvimiento de sistemas multiples.19 Para mas informa-
cion acerca del envenenamiento por gas fosfamina vease la seccion de fosfamina
en el Capitulo 16, bajo Fumigantes.
Confirmacion de envenenamiento
Los fosforos y fosfuros a veces imparten un olor a pescado podrido en el
vomito, las heces fecales y a veces el aliento. La luminiscencia del vomito o de
las heces es ocasionalmente una caracteristica de la ingestion de fosforo. En
algunos casos, ocurre hiperfosfatemia e hipocalcemia pero no son consistentes
con todos los hallazgos.
El talio se puede medir en el suero, la orina y el cabello. El analisis del
cabello probablemente sea util para establecer una previa absorcion prolongada.
Las concentraciones sericas no deben exceder 30 meg por litro en personas no
expuestas. La excrecion de orina dentro de las primeras 24 horas se considera el
metodo mas confiable para la diagnosis. El valor normal es menos de 10 mgc/
litro por 24 horas.10'13
Tratamiento: Sulfato de Talio
1. Descontaminacion gastrointestinal. Si el sulfato de talio fue ingerido
pocas horas antes de iniciar el tratamiento, considere una descontaminacion
gastrointestinal, como fuera delineado en el Capitulo 2. Multiples dosificaciones
de carbon activado podrian ser utiles para aumentar la eliminacion del talio.13
2. Soluciones de glucosa y de electrolitos deben ser administradas por
infusion intravenosa para mantener la excrecion urinaria del talio mediante
diuresis. Monitoree el balance de fluidos cuidadosamente para evitar una
sobre carga de liquidos. Si se desarrolla shock, suministre sangre total, plas-
ma, o expansores de plasma. Las aminopresoras deben usarse cuidadosa-
RODENTICIDAS 193
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mente ante la posibilidad de dano en el miocardio. Monitoree el ICG para
identificar las arritmias.
3. Convulsiones. Controle las convulsiones y contracciones mioclonicas como
fuera delineado en el Capitulo 2.
4. Hemoperfusion y hemodialisis combinada han probado ser moderada-
niente efectivas para reducir la carga corporal del talio en las victimas de enve-
nenamiento severe. Hubo un caso, donde el dialisis peritoneal no resulto eficaz.
S.Terapia de quelacion. Se han probado varies metodos de quelacion y/o
disposicion acelerada del talio y se ha encontrado que son relativamente dani-
nos o ineficaces. Los agentes quelantes no son recomendables en envenena-
miento con talio. El cloruro potasico ha sido recomendado. Sin embargo, se ha
informado que ha aumentado la toxicidad al cerebro,11'14 y no ha demostrado
aumentar la eliminacion en algunos casos.20
6. Potasio ferrico ferrocianuro (Prussian Blue) por via oral aumenta la
excrecion de heces del talio, intercambiando el potasio por talio en el intestino.
Su uso no esta disponible ni aprobado en los Estados Unidos. Los informes de
su uso en humanos son anecdoticos y no apoyan su uso fuertemente.
Tratamiento: Fosforo Amarillo y Fosfuro de Zinc
1. Descontaminacion dermica. Cepille o raspe el fosforo que esta sobre la
piel. Lave las quemaduras de la piel con cantidades abundantes de agua. Asegu-
rese de que todas las particulas de fosforo scan eliminadas. Si el area quemada
esta infectada, cubra con una crerna antibacterial.Vease el Capitulo 2.
2. Medidas de apoyo. Los envenenamientos debido a la ingestion del fosforo
amarillo o el fosfuro de zinc son extremadamente dificiles de manejar. El trata-
miento que se aplica es basicamente de apoyo y sintomatico. El control de las
vias respiratorias y las convulsiones deben establecerse previo a cualquier con-
sideracion de descontaminacion gastrointestinal, como fuera delineado en el
Capitulo 2.
Advertencia: El gas fosfamina, altamente toxico, puede evolucionar del
vomito, del fluido del lavado y de las heces fecales de las victimas de estos
envenenamientos. La recamara del paciente debe estar bien ventilada. Las per-
sonas que asisten a estos pacientes deben usar guantes para evitar el contacto
con el fosforo.
3. El lavado con una solucion de permanganato de potasio a razon de 1:5000
se ha usado para el tratamiento de la ingestion de compuestos de fosforo en el
PB RODENTICIDAS
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pasado; sin embargo, no existe suficiente evidencia de su eficacia y no lo reco-
mendamos.
4. Catarsis no es probablemente indicado, pero puede que haya algun benefi-
cio al administrar aceite mineral. La dosificacion es de 100 mL para adultos y
ninos mayores de 12 anos, y de 1,5 mL/kg por peso corporeo para niiios me-
nores de 12 anos. No administre aceites vegetales o grasa.
S.Transfusiones. Combata el shock y la acidosificacion con transfusiones de
sangre completa y fluidos intravenosos apropiados. Monitoree el balance de los
fluidos y la presion venosa central para evitar una sobre carga de liquidos.
Monitoree los electrolitos, la glucosa y el pH para dirigir la seleccion de solu-
ciones intravenosas. Administre oxigeno 100% mediante mascara o tubo nasal.
6. Oxigeno. Combata edema pulmonar con oxigeno mediante presion positi-
va intermitente o continua.
7. Proteccion renal. Monitoree la albumina de la orina, la glucosa y los sedi-
mentos para detectar inmediatamente dano renal. Si ocurre insuficiencia renal
aguda sera necesario llevar a cabo una hemodialisis extracorporea, aunque esta
no incrementa la excrecion del fosforo. Monitoree el EGG para detectar dete-
rioro del miocardio.
8. Daiio hepatico. Monitoree la fosfatasa alcalina serica, LDH, ALT, AST, el
tiempo de la protrombina y la bilirrubina para evaluar el dano hepatico. Adminis-
tre AquamephytonR (vitamina Kj) si los niveles de protrombina disminuyen.
9.Tratatniento del dolor. Es posible que sea necesario administrar sulfato de
morfma para controlar el dolor. La dosificacion de adultos es: de 2-15 mg IM/
IV/SC Q 2-6 horas prn. La dosificacion de niiios es: de 0,1-0,2 mg/kg/dosifi-
cacion Q 2-4 horas.
10. Gas fosfamina. Para la terapia especifica debido al gas fosfamina, refierase
al tratamiento de envenenamiento de fosfamina en el Capitulo 16, bajo
Fumigantes.
Productos Comerdales
CONVULSIVOS
crimidina
Castrix
fluoroacetamida*
Compound 1081
fluoroacetato de sodio
Compound 1080
estricnina
* Uso suspendido en los Estados
Unidos
La estricnina esta permitida
solamente para el uso de personal
con entrenamiento especial.
CONVULSANTES
Toxicologia
La crimidina es un compuesto de pirimidina clorada sintetica que, en
dosificacion adecuada, causa convulsiones violentas similares a las producidas
por la estricnina.
RODENTICIDAS 195
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El fluoacetato de sodio y la fluoroacetamida son absorbidas con facili-
dad por el intestine, pero solamente de nianera limitada a traves de la piel. El
mecanismo toxico es distinto al de las sales de fluoruro. En el higado se combinan
tres moleculas de fluoacetato o fluoroacetamidas para formar una molecula de
fluorocitrato, la cual envenena a las enzimas criticas del ciclo de los acidos
tricarboxilicos (krebs) y por consiguiente, impide la respiracion celular. El cora-
zon, el cerebro y los rinones son los organos mis afectados. El efecto en el cora-
zon es el origen de las arritmias que progresan a fibrilacion ventricular, que es la
causa coniun de muerte.Acidosificacion metabolica, shock, desbalance electrolitico
y afliccion respiratoria son senales de un pronostico inadecuado. La neurotoxicidad
se expresa conio convulsiones tonico-clonicas violentas, espasnios y rigor que, en
ocasiones, no se presentan sino hasta horas despues de la ingestion.21
La estricnina es una toxina natural (Nux vomica) que causa convulsiones
violentas a causa de la excitacion directa de las celulas del sistema nervioso cen-
tral, principalmente del cordon espinal. La muerte es causada por la interferencia
de las convulsiones con la funcion pulmonar, por la depresion de la actividad del
centre respiratorio, o por ambas situaciones. La estricnina es detoxificada en el
higado. La vida media es de alrededor de 10 horas en los seres humanos. La
aparicion de los sintomas ocurre generalmente de 15 a 20 minutos despues de la
ingestion. La dosificacion letal en los humanos es informada entre 50 y 100 mg,
aunque una pequeiia cantidad de 15 mg puede matar a un nino.22
Confirmacion de Envenenamiento
Generalmente no existen pruebas disponibles para confirmar el envenena-
miento por rodenticidas convulsivos.
Tratamiento: Fluoroacetato Sodico y Fluoroacetamida
Los envenenamientos por estos compuestos casi siempre se han presentado
como resultado de ingestiones accidentales o suicidas. Si el veneno fue ingerido
poco antes que el tratamiento y aun no se han presentado convulsiones, el
primer paso en el tratamiento es eliminar el toxico del intestino. Sin embargo,
si la victima ya sufre de convulsiones, es necesario controlarlas antes de realizar
lavado gastrico y catarsis.
1. Controle las convulsiones como fuera delineado en el Capitulo 2. La
actividad convulsiva de estos compuestos puede ser tan severa que es posible
que la dosificacion necesaria para controlar las convulsiones paralicen la respi-
racion. Por esta razon, es mejor intubar la traquea tan pronto como sea posible
en el transcurso del control convulsive, y apoyar la ventilacion pulmonar meca-
nicamente. Esto tiene la ventaja adicional de proteccion de las vias respiratorias
de la aspiracion del contenido gastrico regurgutado.
PB RODENTICIDAS
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2. Descontaminacion gastrointestinal. Si el paciente es visto durante la
primera hora de contacto y no esta convulsando, considere descontaminacion
gastrointestinal como fuera delineado en Capitulo 2.
3. Administre los fluidos intravenosos cuidadosamente para mantener la
excrecion del toxico absorbido. Es especialmente importante evitar una sobre-
carga liquida en presencia de un miocardio debil e irritable.
4. Monitoree el electrocardiograma para indicar arritmias y, si se detecta,
tratela con medicamento antiarritmico apropiado.Tenga disponibles instalacio-
nes y equipo adecuado para la cardioversion por electrochoque. Algunas victi-
nias del envenenaniiento por fluoacetato se han recuperado luego de
cardioversiones repetidas.
5. Gluconato calcico (solucion al 10%) debe ser administrado por via
intravenosa lentamente para aliviar la hipocalcemia. Debe tenerse mucho cui-
dado para evitar la extravacion.
Dosificacion de Gluconato Calcico:
Administrado como 100 mg/mL (una solucion al 10%)
Para adultos y ninos mayores de 12 anos: 10 mL de una solucion al 10%
administrada lentamente por via intravenosa. Repita de ser necesario.
Para ninos menores de 12 anos: de 200 a 500 mg/kg/24 horas dividi-
dos Q 6 hr. Para paro cardiaco, 100 mg/kg/dosificacion. Repita la
dosificacion de ser necesario.
6. Otras terapias. La eficacia antidota del monoacetato glicerol y de etanol
observado en animales, no ha sido corroborada en los seres humanos. Estas
terapias no son recomendables en seres humanos.
Tratamiento: Estricnina o Crimidina
La estricnina y la crimidina causan convulsiones violentas poco despues de
la ingestion de dosificacion toxicas. Es probable que el carbon absorba bien
ambos venenos. Si el paciente se encuentra totalmente consciente y no esta
convulsando momentos despues de la ingestion, se puede obtener un gran be-
neficio inmediato si se administra carbon activado. Si el paciente se encuentra
convulsando o entorpecido, controle la cantidad motora involuntaria antes de
tomar acciones para vaciar el intestine y limitar la absorcion del toxico.
RODENTICIDAS 197
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Productos Comerdales
PRODUCTOS DIVERSOS
colecalciferol
Muritan
Quinox
Rampage
escila roja*
Dethdiet
Rodine
* Uso suspendido en los Estados
Unidos
1. Controle las convulsiones corno fuera delineado en el Capitulo 2.
2. Descontaminacion gastrointestinal. Considere la descontaminacion
gastrointestinal si el paciente es visto dentro de la primera hora de la ingestion.
3. Administre fluidos intravenosos para apoyar la excrecion de las toxinas
absorbidas. Incluya bicarbonate de sodio en la infusion liquida para contrarres-
tar la acidosificacion generada por las convulsiones. La eficacia de la hemodialisis
y la hemoperfusion no ha sido probada.
RODENTICIDAS MISCELAlMEOS:
ESCILA ROJA Y COLECALCIFEROL
Toxicologia
La escila roja es un rodenticida de poco uso, este consiste de las partes
internas de un repollo pequeno cultivado en paises al este del Mediterraneo.
Sus propiedades toxicas han sido conocidas desde la antigiiedad y probable-
niente se deben a los glucosidos cardiacos. El envenenamiento en los mamife-
ros y otros roedores es improbable debido a varias razones: (1) la escila roja es
altamente nauseabunda, por lo cual los animales que vomitan (los roedores no
lo hacen) poseen una probabilidad baja para retener el veneno; (2) el glucosido
no es absorbido eficazmente a partir del intestino; (3) el glucosido absorbido se
excreta rapidamente. La ingestion de los glucosidos produce efectos tipicos a
los del digitalis: alterando la conduccion del impulse cardiaco y arritmias
El colecalciferol es la forma activada de la vitamina D (vitamina D3). Es
probable que su efecto toxico sea el resultado de una combinacion de acciones
en el higado, rinon y, posiblemente, el miocardio. Las dos ultimas toxicidades
son el resultado de la hipercalcemia. Los sintomas y senales iniciales de la
hipercalcemia causada por la vitamina D en los humanos son fatiga, debilidad,
dolor de cabeza y nausea. La poliuria, polidipsia, proteinuria y azotemia son
resultado de una lesion aguda en los tubulos renales debido a la hipercalcemia,
la cual es, en general, la causa de muerte. La hipercalcemia cronica fmalmente
da resultado a una nefrolitiasis y nefrocalcinosis. La azotemia ocurre segun pro-
gresa el dano tubular renal.
Confirmacion de Envenenamiento
La intoxicacion con colecalciferol se puede identificar por la elevada con-
centracion de calcio (principalmente la fraccion no ligada) en el suero. Por lo
PB
RODENTICIDAS
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general, no existen pruebas disponibles para otros rodenticidas o sus productos
de biotransformacion.
Tratamiento: Escila Roja
La escila roja no es probable que cause envenenamiento a nienos que sea inge-
rida en dosificaciones sustanciales. Generalmente el problema se corrige el mismo
debido a su efecto emetico intense. Si por alguna razon, la escila roja es retenida, se
debe administrar jarabe de ipecacuana, seguido por uno o dos vasos de agua para
iniciar el vomito. Monitoree el estado cardiaco con electrocardiograma.
Tratamiento: Colecalciferol
El colecalciferol en altas dosificaciones puede causar un envenenamiento
severe y muerte. No se han informado envenenamientos en seres humanos por
su uso rodenticida, pero ha ocurrido sobredosificacion de vitamina D bajo
circunstancias clinicas. El tratamiento esta dirigido a la absorcion gastrointestinal
limitada,la aceleracion de excrecion y la contrarreccion del efecto hipercalcemico.
1. Descontaminacion gastrointestinal. Si el colecalciferol ha sido ingerido
dentro de la primera hora del tratamiento, considere descontaminacion gastrica
como fuera explicado en el Capitulo 2. La administracion repetida de carbon a
la mitad o mayor que la dosificacion original, de cada dos a cuatro horas resul-
taria beneficioso.
2. Administre fluidos intravenosos (solucion salina normal o 5% glucosa)
en intervales moderados para mantener mecanismos excretoreos y la excre-
cion. Monitoree el balance de fluidos para evitar una sobrecarga, y mida los
electrolitos sericos periodicamente. Mida e ionice los niveles de calcio totales
en la sangre despues de 24 horas de la ingestion de colecalciferol para determi-
nar la severidad de sus efectos toxicos. Monitoree la orina para indicacion de
proteina, y las celulas blancas y rojas para evaluar el dano renal.
3. Furocemida (Lasix), de 20 a 40 mg por via intravenosa, o de 40 a 120 mg
diarios por via oral deben de ser administrados para promover diuresis. La do-
sificacion para niiios menores de 12 anos es aproximadamente 0,5-1,0 mg/kg
por peso corporal intravenosamente, 1,0 a 2,0 mg/kg por peso corporal por via
oral. Monitoree el potasio serico despues de la dosificacion; y si se presenta
hipokalemia, administre cloruro potasico. Consulte las instrucciones incluidas
en el paquete para informacion adicional y advertencias.
4. Prednisona y glucocorticoides similares reducen los niveles de calcio san-
guineo en ciertas enfermedades.Aunque estos medicamentos no han sido pro-
RODENTICIDAS 199
-------
bados ante una sobredosificacion de colecalciferol, es posible que scan de utili-
dad. La dosificacion aproximada es de 1 nig por kg por dia, hasta un niaxinio de
20 mg por dia.
5. Calcitonina (calcitonina de salmon, CalzimarR) es el antidote logico para
las acciones del colecalciferol, pero solamente tiene uso limitado en envenena-
mientos de seres humanos.23 En otras condiciones, la dosificacion usual es de 4
Unidades Internacionales por kg de peso corporeo cada 12 horas, por inyec-
cion intramuscular o subcutanea, continuado durante 2 a 5 dias. La dosificacion
puede duplicarse si el efecto hipocalcemico no es suficiente. Si aparecen indi-
cios de hipocalcemia (espasmos carpopedal, arritmias cardiacas) tenga a mano
gluconato calcico para aplicar una inyeccion intravenosa. Consulte las instruc-
ciones incluidas en el paquete para informacion adicional y advertencias.
6. La colestiramina parece ser efectiva en el tratamiento de intoxicacion con
vitamina D en los animales.24 Se ha visto un uso limitado en seres humanos.25>26
Referencias
1. Mack RB. Not all rats have four legs: Superwarfarin poisoning. N C MedJ 1994;55:554-6.
2. Katona B and Wason S. Superwarfarin poisoning. J Emerg Med 1989;7:627-31.
3. LitovitzTL, Smilkstein M, Felberg L, et al. 1996 Annual Report of the American Association of
Poison Control Centers Toxic Exposure Surveillance System. Am] 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 pro-
spective study. Pediatrics 1989;84:490-4.
6. Lipton RA and Klass EM. Human ingestion of a 'superwarfarin' rodenticide resulting in a
prolonged anticoagulant eSect.JAMA 1984;252:3004-5.
7. Helmuth RA, McCloskey DW, Doedens DJ, et al. Fatal ingestion of a brodifacoum-contain-
ing rodenticide. Lab Med 1989;20:25-7.
8. Norcross WA, Ganiats TG, Ralph LP, et al. Accidental poisoning by warfarin-contaminated
herbal tea. West]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 Neural 1972;26:456-64.
12. Fred HL and Accad ME Abdominal pain, leg weakness, and alopecia in a teenage boy. Hasp
Pract 1997;32:69-70.
13. Meggs WJ, Hoffman RS, Shih RD, et al.Thallium poisoning from maliciously contaminated
food.JToxicol ClinToxicol 1994;32:723-30.
14. Roby DS, Fein AM, Bennett RH, et al. Cardiopulmonary effects of acute thallium poison-
ing. Chest 1984;85:236-40.
PB RODENTICIDAS
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15. McMarron MM and Gaddis GP. Acute yellow phosphorus poisoning from pesticide pastes.
ClinToxicol 1981;18:693-711.
16. Dipalma JR. Human toxicity from rat poison. Am Fam Physician 1981;24:186-9.
17. Simon FA and Pickering LK. Acute yellow phosphorus poisoning: Smoking stool syndrome.
JAMA 1976;235:1343-4.
18. Patial RK, Bansal SK, Kashyap S, et al. Hypoglycaemia follo\ving zinc phosphide poisoning.
JAssoc Physicians India 1990;38:306-7.
19. Schoonbroodt D, Guffens P, Jousten P, et al. Acute phosphine poisoning? A case report and
review. Ada Clin Belg 1992;47:280-4.
20. Koshy KM and Lovejoy FH.Thallium ingestion with survival: Ineffectiveness of peritoneal
dialysis and potassium chloride diuresis. ClinToxicol 1981;18:521-5.
21. Chi CH, Chen KW, Chan SH, et al. Clinical presentation and prognostic factors in sodium
monofluoroacetate intoxication. ClinToxicol 1996;34:707-12.
22. Benomran FA and Henry JD. Homicide by strychnine poisoning. Med Sci Law 1996;36:271-3.
23. Buckle RM, GamlenTR, and Pullen IM.Vitamin D intoxication treated with procine calci-
tonin. BrMedJ1972;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.
BcMe
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CAPITULO 18
Pesticidas Diversos,
Solventes y Adyuvantes
Existe una variedad de pesticidas que no caen bajo las amplias categorias des-
critas en otros Capitulos de este manual. Muchos de ellos son de uso extensive
y por lo tanto estan asociados con una probabilidad alta para el contacto con
seres humanos. Algunos tienen una toxicidad significante asi como la posibili-
dad del contacto con seres humanos. Muchos de los solventes y adyuvantes que
se usan en la formulacion de pesticidas tambien posan una posibilidad del con-
tacto con seres humanos. Dichos contactos pueden resultar en efectos toxicos
significantes que en muchos de los casos exceden la toxicidad de los ingredien-
tes en los pesticidas de uso active. Ademas, a veces es mas dificil obtener infor-
macion acerca de los solventes y adyuvantes, complicando los problemas de
diagnosis y manejo.
4-AMINOPIRIDINA
Toxicologia
La 4-aminopiridina es un polvo bianco altamente toxico que se usa como
repelente de aves.Trabaja de tal manera que cuando uno o dos pajaros se enfer-
man gravemente, sus silbidos de apuro alertan a los pajaros restantes. Es toxico
para todos los vertebrados.1 En general se anade como carnada a los granos en
una concentracion de 0,5% a 3,0%, pero hay disponible concentraciones de
25% a 50% en azucar granulada. Su contacto humano reciente ha ocurrido
como resultado de su uso como medicamento experimental en el tratamiento
de esclerosis multiple.2'3 El intestino la absorbe con rapidez pero no es tan
eficaz a traves de la piel. El mecanismo principal de toxicidad es el aumento de
la transmision colinergica en el sistema nervioso a traves de la liberacion de
acetilcolina tanto central como periferalmente. Debido a una mejor transmi-
sion en las intersecciones neuromusculares, una de las principales manifestacio-
nes puede ser espasmos musculares severos.2 La 4-aminopiridina se metaboliza
y se excreta rapidamente.
No han ocurrido envenenamientos en seres humanos como resultado de
su uso ordinario, pero se han informado efectos de ingestion de alrededor de 60
mg en dos adultos. Cada uno experimento malestar abdominal inmediato, nau-
PUNTOS
IMPORTANTES
Puede ser necesario que
los medicos necesiten
pedir information a los
manufactureros sobre la
constitution de los
"ingredientes inertes"
Senales y Sintomas:
Altamente variables,
basados en el agente
Muchos son irritantes y
corrosives
La creosota (compuestos
fenolicos) produce un
color grisaseo en la orina
El envenenamiento con
clorato de sodio y
creosota puede causar
meta hemoglobinemia
El clorato de sodio
tambien causa dano renal,
arritmia, shock y DIG
La aspiracion del
hidrocarbono causa
neumonitis
Tratamiento:
Descontaminadon
dermica, ocular y Gl
Cuidado suplementario y
control de convulsiones
Se recomienda azul de
metileno para la
metahemoglobinemia
DIVERSOS 203
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Productos Comerdales
PESTICIDAS DIVERSOS
4-Aminopiridina
Avitrol
cianamida de calcio*
Cyanamide
Nitrolime
creosota
endotal
Accelerate
Aquathol
Des-i-cate
Endothall Turf Herbicide
Herbicide 273
Hydrothol
metaldehido
Antimilace
Cekumeta
Halizan
Metason
Namekil
otros
clorato de sodio
Defol
De-Fol-Ate
Drop-Leaf
Fall
KM
Kusatol
Leafex
SINERGICOS
Butoxido de piperonilo
SOLVENTES Y
ADYUVANTES
agentes antiendurecedores
polvillos
emulsificantes
formas granuladas
penetrantes
eteres de petroled
isopropanol
metanol
tolueno
xileno
protectores
adherentes y dispersantes
*Uso suspendido en los Estados
Unidos
sea y vomito, debilidad, mareo y diaforesis copiosa, y uno de ellos desarrollo en
una convulsion tonico clonica que requirio apoyo respiratorio. Se presento
acidosis en anibos casos.1 El mareo, aturdimiento, y tambaleo es comun, y las
convulsiones pueden ser severas, aunque la recuperacion con ayuda de terapia
de apoyo y de ventilacion ha sido el resultado comun.1'2'3
Tratamiento
1. Descontaminacion dermica. Si ha ocurrido contaminacion ocular y
dermica, se recomienda que lave bien la piel o los ojos segun fuera delineado.
Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Si el paciente es tratado dentro de la
primera hora de una ingestion significante del compuesto, debe considerarse
descontaminacion gastrointestinal, como fuera delineado en el Capitulo 2. Si se
atrasa el tratamiento, debe de administrarse inmediatamente carbon y sorbitol
por via oral representando asi un manejo razonable.
3. Las convulsiones pueden requerir el uso de medicamentos anticonvulsantes.
Vease el Capitulo 2 para las dosificaciones.
4. Espasmos musculares. El bloqueo neuromuscular con medicamentos como
d-tubocuarina, metocuarina y bromuro de pancuronium han sido usadas
exitosamente para aliviar los espasmos musculares que ocurren con este agente.
Dicha terapia debe de ser provista en un ambiente de cuidado intensive.1
5. La deshidratacion debe ser tratada con fluidos intravenosos si los fluidos
no pueden ser controlados por via oral.
CIANAMIDA CALCICA
La cianamida calcica es un compuesto sintetico que se encuentra disponible
en el mercado en granules que contienen 44% de cianamida calcica generando
19,5% de nitrogeno. Se incorpora en la tierra en donde actua como fertilizante,
fungicida y herbicida. Libera cianamida de hidrogeno cuando entra en contacto
con el agua. Las condiciones acidicas pueden acelerar esta condicion. La cianamida
de hidrogeno es un solido con una presion de vapor alta. Sus propiedades toxicas
son totalmente diferentes a las del cianuro y no se degrada a cianuro.
Toxicologia
La cianamida calcica es un irritante moderado para la piel, pero la cianamida
de hidrogeno es muy irritante y caustica para la piel y el gas inhalado es un fuerte
PB DIVERSOS
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irritante de las membranas mucosas.4 Ha causado danos cutaneos y lesiones en la
boca,lengua y el esofago superior despues de la exposicion. No se han informado
sintomas sistemicos por contacto cutaneo.5 Despues de inhalar cianamida de hi-
drogeno o de ingerir la sal pueden surgir envenenamientos sistemicos. Las rnani-
festaciones del envenenamiento son rubor, dolor de cabeza, vertigo, disnea,
taquicardia, e hipotension que algunas veces conducen al shock.4 La cianamida es
un inhibidor del acetaldehido deshidrogenasa por lo que si se ingieren bebidas
alcoholicas, los sintomas aumentaran. (Un derivado citrado de la cianamida se ha
usado en lugar de Antabus para la terapia de inhibicion de alcohol).
Tratamiento
1. Descontaminacion de la piel. La contaminacion dermica ya sea por la sal
calcica o por la forma libre, debe de eliminarse lavando el area con agua y jabon.
Enjuague la contaminacion ocular con abundante cantidad de agua limpia. Si la
irritacion dermica y ocular persiste, obtenga atencion medica inmediata.Vease
el Capitulo 2.
2. Descontaminacion gastrointestinal. Si se han ingerido grandes dosis
dentro de la primera hora de contacto, debe considerarse una descontamina-
cion gastrointestinal. Si la dosificacion ingerida es pequena o se retrasa el trata-
miento, debe administrarse de inmediato carbon activado y sorbitol como una
medida razonable para el manejo del envenenamiento.Vease el Capitulo 2 para
informacion sobre dosificacion.
3. La hipotension o las reacciones de tipo antabus deben ser tratadas
colocando al paciente en posicion de Trendelenburg, administrando liquidos
intravenosos, incluyendo plasma o sangre, si fuera necesario asi como medica-
mentos vasopresores por via parenteral.
4. La atropina no es un antidote.
CREOSOTA
La creosota se obtiene por destilacion del alquitran que se forma al calentar
madera o carbon en ausencia de oxigeno. Se purifica por extraccion a aceites.
La creosota que proviene de la madera consiste principalmente de guayacol
(metoxifenol) y cresol (metilfenol). La creosota que se deriva del carbon con-
tiene, ademas, un poco de fenol, piridina y piridinol. La creosota se utiliza
extensamente como conservador de madera, por lo general por medio de satu-
racion a altas temperaturas. Tambien se ha utilizado como bano desinfectante
por inmersion para animales. La mayoria del contacto con seres humanos es en
la forma de varies compuestos de fenol. La creosota irrita la piel, ojos y mem-
DIVERSOS 205
-------
branas mucosas. Los trabajadores que entran en contacto con la creosota tecnica
o con niadera de construccion tratada, algunas veces desarrollan irritacion cu-
tanea, erupciones vesiculares o papulares, pigmentacion de la piel, y ocasional-
mente, gangrena y cancer de la piel.6Tambien se ha informado fotosensibilidad.
La contaminacion ocular a dado lugar a conjuntivitis y queratitis que algunas
veces causa cicatrices en la cornea. Los constituyentes de la creosota son absor-
bidos a traves de la piel eficazmente, pero rara vez han ocurrido envenenamien-
tos sistemicos luego de la absorcion cutanea. La creosota ingerida es absorbida
en el intestine rapidamente y el pulnion absorbe el vapor de rnanera significante.
Los enlazantes de los constituyentes fenolicos absorbidos se excretan mayor-
mente en la orina. Los efectos toxicos severos son semej antes a aquellos efectos
del Lysol, pero la naturaleza corrosiva de la creosota es un poco menor debido
a una mayor dilucion del fenol en la creosota.7 Los principales efectos de la
irritacion gastrointestinal son, encefalopatia toxica y lesion de los tubulos rena-
les. Se ha descrito una toxicosis cronica debido a la absorcion gastrointestinal
continua (la creosota es utilizada medicinalmente) causando gastroenteritis y
disturbios visuales.
Las manifestaciones de un envenenamiento sistemico severe son salivacion,
vomito, disnea, dolor de cabeza, rnareo, perdida de reflejo en la pupila, cianosis,
hipotermia, convulsiones y coma. La muerte es causada debido a un fallo mul-
tiple de organos segun los pacientes van desarrollando shock, acidosis, depre-
sion respiratoria y fallo renal por anuria.
Confirmacion de Envenenamiento
La presencia de productos de oxidacion fenolica imparte un color obscuro
y turbio en la orina.7 Si existe sospecha de envenenamiento, anada unas cuantas
gotas de solucion de cloruro ferrico a la orina; si se torna color violeta o azul
esto es indicacion de la presencia de compuestos fenolicos.
Tratamiento
1. Descontaminacion dermica. Deben tomarse medidas estrictas para evi-
tar la contaminacion dermica, ocular, y la inhalacion de vapor. Lave la contami-
nacion dermica rapidamente con agua y jabon. Enjuague la contaminacion
ocular con abundante cantidad de agua, y obtenga atencion medica especializa-
da lo mas pronto posible ya que puede causar lesion severa en la cornea.Vease
el Capitulo 2.
2. Descontaminacion gastrointestinal. Si se ha ingerido una gran cantidad
de creosota y el paciente se encuentra lo suficientemente alerta y es capaz de
tragar, administre inmediatamente una suspension de carbon activado por via
oral. Los esfuerzos posteriores para limitar la absorcion dependeran si ha ocur-
PB DIVERSOS
-------
rido una lesion corrosiva en el esofago. Si hay evidencia de hinchazon y enro-
jecimiento de la faringe, no induzca el vomito ni realice lavado gastrico debido
al riesgo de volver a exponer al esofago a la creosota o a una perforacion del
esofago con el tubo gastrico. Para mas informacion sobre la descontaminacion
gastrointestinal incluyendo la dosis para el carbon, vease el Capitulo 2.
3. Mantenga la ventilacion pulmonar mecanicamente con oxigeno si fuera
necesario.
4. Muestras de sangre y orina. Obtenga una muestra de sangre para realizar
una prueba de metahemoglobinemia, para medir BUN y los electrolitos san-
guineos, y para detectar seiiales de danos hepaticos (bilirrubina, GGT, LDH,
ALT, AST, y fosfatasa alcalina). Examine la orina para proteina, celulas y la ex-
crecion de productos fenolicos "turbios."
5. Fluidos intravenosos. Administre fluidos intravenosos para corregir la des-
hidratacion y las alteraciones electroliticas. Incluya glucosa si es necesario para
proteger el higado y bicarbonate para aliviar la acidosis metabolica. Monitoree
el balance de los fluidos cuidadosamente para discontinuar los fluidos intravenosos
en caso de fallo renal. Es posible que sea necesario una transfusion sanguinea o
de plasma para evitar el shock.
6. Monitoree el EGG para detectar arritmias y/o defectos en la conduccion
que pueda surgir como manifestaciones de la miocardiopatia toxica.
7. Convulsiones. Puede que sea necesario el uso de anticonvulsantes para el
control de convulsantes, como fuera delineado en el Capitulo 2.
8. La hemodialisis no es eficaz acelerando el proceso de eliminacion del fenol
(presumiblemente, la creosota) pero probablemente la hemoperfusion sobre el
carbon es probablemente eficaz.8 Este tratamiento debe ser considerado en
casos de envenenamientos severos con creosota.
9. La metahemoglobinemia es rara vez severa, pero debe considerarse la
administracion intravenosa de azul de metileno al 1% si la hemoglobina se ha
convertido de un 25 a un 30 %. La dosificacion es 0,1 mL de solucion al 1% por
peso corporeo en kg, administrada en no menos de 10 minutos. Puede ocurrir
nausea, mareo y un incremento transitorio de la presion sanguinea.
ENDOTAL
El endotal, ya sea como acido libre o como sus sales de sodio, potasio o amina,
se utiliza como herbicida de contacto, defoliante, herbicida acuatica y alguicida. Es
formulado en soluciones acuosas y granules en diversas concentraciones.
DIVERSOS 207
-------
Toxicologia
El endotal es irritante a la piel, ojos y membranas mucosas; se absorbe bien
a traves de la piel lacerada y por el tracto gastrointestinal. Los mecanismos de
toxicidad sistemicos reconocidos en los mamiferos son: efectos corrosivos sobre
el tracto gastrointestinal (en particular por concentraciones elevadas del acido
libre); miocardiopatia y lesion vascular que origina shock, y lesion del sistema
nervioso central, que causa convulsiones y depresion respiratoria. Se ha infor-
niado de un caso individual de envenenamiento letal, en el cual un honibre de
21 anos de edad, previamente saludable, niurio luego de haber ingerido entre 7
a 8 grarnos de endotal. En este paciente, se notaron hemorragia y edema en el
tracto gastrointestinal y en los pulmones.9 No existen criterios para los niveles,
y no se consideran utiles para el manejo.
Tratamiento
1. Descontaminacion dermica. Lave la sustancia de la piel con agua y jabon.
Enjuage la contaminacion ocular con abundante cantidad de agua limpia. Ob-
tenga atencion medica si la irritacion persiste.Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Si se ha ingerido una substanciosa
cantidad, y si el paciente es visto durante la primera hora del contacto, y se
encuentra alerta y sin convulsiones, debe considerarse la descontaminacion
gastrointestinal como fuera delineado en el Capitulo 2. Generalmente el lavado
es contraindicado debido a la naturaleza corrosiva de este agente.
3. Intubacion. Si existe alguna indicacion de efectos corrosivos en la faringe,
no debe intentarse la intubacion ya que se corre el riesgo de perforacion. Puede
que sea necesario aplicar procedimientos de tratamientos apropiados para la
ingestion de corrosivos (acidos fuertes y alcalis fuertes). Debe consultarse con
un cirujano o con un gastroenterologo, acerca de la consideracion de una
endoscopia.
4. El oxigeno debe ser administrado con mascarilla. Si el ritrno respiratorio es
debil, apoye la ventilacion pulmonar mecanicamente.
5. Monitoree la presion sanguinea de cerca. Puede que sea necesario admi-
nistrar infusiones de plasma o sangre, u otros dilatantes para evitar el shock.
6. Administre fluidos intravenosos para corregir la deshidratacion, estabili-
zar los electrolitos, proveer azucar y apoyar los mecanismos de la disposicion
toxica. Administre aminas vasoactivas cuidadosamente, debido a la posibilidad
de una miocardiopatia.
PB DIVERSOS
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7. Convulsiones. Las convulsiones pueden requerir la administracion de
diazepam y /otros anticonvulsantes.
8. Hemodialisis. No se sabe si la hemodialisis o la hemoperfusion son eficaces
para eliminar el endotal de la sangre. Esta opcion debe considerarse si la condi-
cion del paciente se deteriora a pesar de los cuidados de apoyo.
METALDEHIDO
Toxicologia
El metaldehido es un polimero ciclico de 4 unidades de acetaldehido ha
sido utilizado desde hace mucho para matar babosas y caracoles, los cuales son
atraidos hacia el sin necesidad de carnadas. Aunque se han presentado envene-
namientos ocasionales de animales y niiios por ingestion de pildoras destinadas
a acabar con moluscos, con mayor frecuencia las tabletas elaboradas como com-
bustibles carburantes han sido los agentes responsables de envenenamientos de
seres humanos.10 Otra forma de contacto es conocida como tabletas "snowstorm",
las cuales el usuario coloca al final de un cigarrillo encendido para crear nieve.
El envenenamiento ocurre a traves de la inhalacion de los gases del metaldehido.11
No se conoce el mecanismo bioquimico del envenenamiento. El acetaldehido
y el metaldehido, ambos producen efectos similares en los perros; sin embargo,
el acetaldehido no fue detectado en el plasma o la orina de los perros envene-
nados con metaldehido.12
La ingestion de una dosis toxica muchas veces produce vomitos y nauseas.
Otros efectos primaries de la toxicidad son pirexia, convulsiones generalizadas,
y otros cambios mentales que llevan a la coma.10'13 Otras senales y sintomas que
pueden ocurrir incluyen hipersalivacion, rubolizacion facial, mareo, taquipnea,
y acidosis.10'n Neumonitis ha ocurrido seguido de una inhalacion de
metaldehido.11 Aunque la mayoria de los casos son dramaticos con convulsio-
nes y coma, los eventos fatales no son frecuentes.10'13 Los animales envenenados
muestran temblores, ataxia, hiperestesia, salivacion,y convulsiones.12 Las autop-
sias realizadas en pacientes de envenenamiento han encontrado danos severos
en las celulas del higado y en el epitelio renal tubular.
Confirmacion de Envenenamiento
El metaldehido se puede medir en la sangre y en la orina, aunque existen
muy pocos informes de niveles entre los seres humanos envenenados. Un pa-
ciente quien sufrio convulsiones tonicoclonicas severas y estuvo en coma tuvo
un nivel de metaldehido de 125 nig/L con una vida media de 27 horas. A este
paciente no se le pudo detectar el acetaldehido en el suero.13
DIVERSOS 209
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Tratamiento
1. Descontaminacion gastrointestinal. Si la ingestion ha ocurrido dentro
de la primera hora del tratamiento, considere la descontaminacion gastrointestinal,
conio fuera delineado en el Capitulo 2. El carbon activado puede ser de utili-
dad contra el metaldehido.
2. Convulsiones. Si se presentan convulsiones, administre anticonvulsivos se-
dantes.Vease el Capitulo 2 para la dosificacion.
3. Tratamiento de apoyo. Es conveniente administrar el tratamiento de apo-
yo apropiado incluyendo fluidos intravenosos de soluciones salinas y glucosa.
Puede considerarse el uso de bicarbonate sodico en el evento de una severa
acidosis metabolica. Monitoree cuidadosamente el balance de fluidos y electrolitos
para evitar una sobrecarga de liquidos en caso de insuficiencia renal.
4. Fallo renal. No existe un antidoto especifico para el envenenamiento con
metaldehido. La hemodialisis no es probablemente eficaz para eliminacion del
compuesto, pero debe de instituirse si se presenta insuficiencia renal. No se ha
probado la eficacia de la hemoperfusion.
5. Pruebas de funcion hepatica y de sedimentacion urinaria deben de llevarse
de acabo para evaluar el dano hepatico y renal de los pacientes envenenados.
CLORATO SODICO
El clorato sodico se utiliza en la agricultura como defoliante, herbicida no
selective de contacto y esterilizante semipermanente de la tierra. Debido a su
naturaleza explosiva, es importante que se formule con materiales solubles en
agua que retarden el fuego tales como, el metaborato sodico, ceniza de soda,
cloruro magnesico o urea. En general se aplica en solucion acuosa.
Toxicologia
El clorato sodico es irritante a la piel, ojos y las membranas mucosas de
todo el tracto respiratorio superior.14 La absorcion dermal es leve. A pesar de
que la absorcion gastrointestinal tambien es ineficaz, el envenenamiento critico,
a veces fatal, sigue a la ingestion de dosis toxicas, que se estima es acerca de 20 gr
en el ser humano adulto. La excrecion se lleva a cabo principalmente por via
urinaria. Los principales mecanismos de toxicidad son: hemolisis, formacion de
metahemoglobina, arritmia cardiaca (particularmente secundaria a la
hiperkalemia) y dano en los tubulos renales.14'15
PB DIVERSOS
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La accion irritante sobre el intestine causa nausea, vomito y dolor estonia-
cal. Una vez es absorbida, la hemoglobina se oxida rapidamente a
metahemoglobina, y ocurre hemolisis intravascular.14 La cianosis es prominente
si la metahemoglobina es severa y es la unica serial presente.15 Puede ocurrir
necrosis tubular aguda y hemoglobinuria como resultado de la hemolisis o
dano toxico directo. El plasma y la orina son de color cafe oscuro por la presen-
cia de hemoglobina libre y la metahemoglobina. 14>15>16 La liberacion del potasio
debido a la destruccion de las celulas rojas produce hiperkalemia, lo cual puede
ser lo suficientemente severa como para causar arritmias que pueden amenazar
la vida.16 La hipoxemia puede causar convulsiones. La muerte puede ser resul-
tado de shock, hipoxia de los tejidos, fallo renal, hiperkalemia o coagulacion
intravascular diseminada (DIG).14'15'16
Confirmacion de Envenenamiento
No hay pruebas disponibles ni especificas para el clorato. El color marron
oscuro en el plasma y en la orina indica la accion de un fuerte agente oxidante
en la hemoglobina. Vease el Capitulo 2.
Tratamiento
1. Descontaminacion dermica. Lave la sustancia de la piel con agua y jabon.
Enjuage la contaminacion ocular con abundante cantidad de agua limpia. Obtenga
atencion medica si persiste la irritacion dermica y ocular. Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Si se ha ingerido clorato de sodico
durante la primera hora del tratamiento, considere la descontaminacion
gastrointestinal, como fuera delineado en el Capitulo 2.
3. Oxigeno. Administre oxigeno si la respiracion se encuentra deprimida, pue-
de que el apoyo de ventilacion sea necesario.
4. El tiosulfato sodico ha sido recomendado como un antidoto contra el
clorato sodico absorbido. Se cree que el tiosulfato inactiva al ion de clorato y
forma un ion de cloruro menos toxico. Puede ser administrado por via oral o
como una infusion intravenosa dentro de 60 a 90 minutos. La dosificacion es de
2 a 5gr disueltos en 200mL de bicarbonate sodico al 5%.14
5. Monitoree la presion sanguinea, el balance de los fluidos, los electrolitos
sanguineos, BUN, metahemoglobina y bilirrubina asi como el contenido de la
proteina en la orina y las celulas de hemoglobina libre, y EGG. La dilatacion del
complejo QRS y la prolongacion del intervalo PR indica toxicidad cardiaca
hiperkalemica.
DIVERSOS 211
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6. La leche puede ser util para aliviar el dolor de la irritacion gastrica.
7. Administre fluidos intravenosos para mantener la excrecion del clorato.
Mantenga el pH de la orina en el intervalo alcalino anadiendo bicarbonate de
sodico en el liquido de infusion. Monitoree de cerca la produccion urinaria
para reducir o suspender los fluidos intravenosos si sobreviene una insuficiencia
renal. Puede ser necesario llevar a cabo una transfusion de sangre si la hemolisis
y la metahemoglobinemia son severas. Se ha recomendado una ex-sanguineo
hemofusion para mejorar el aclaramiento y tratar el DIG.16
8. La hemodialisis puede salvar la vida en caso de envenenamiento severo. Es
eficaz en la eliminacion del clorato de la sangre, y adernas proporciona un
mecanismo para controlar la hiperkalemia, y hace posible el control del volu-
nien y la composicion del liquido extracelular mientras la funcion renal perrna-
nece alterada.
9. Metahemoglobinemia. Considere la posibilidad de administrar azul de
metileno para revertir la metohemoglobinemia si la hemoglobina se ha converti-
do entre 25 y 30%. Administre por via intravenosa 0,1 mL/kg por peso corporeo
de una solucion al 1% por un periodo de por lo menos 10 minutos. Puede
aumentar la presion sanguinea, causar nausea y mareo, pero estos efectos son
generalmente transitorios. Como el uso de este agente en envenenamiento por
clorato no ha probado ser beneficioso en el pasado, es recomendable proceder a
una ex-sanguineo transfusion segun se explico en el tratamiento numero 7.
SINERGICOS: BUTOXIDO DE PIPERONILO
Los agentes sinergicos son sustancias quimicas que se anaden a los produc-
tos pesticidas para incrementar el poder mortifero de los ingredientes activos.
El uso extenso de insecticidas sinergicos, como el butoxido de piperonilo actua
inhibiendo la degradacion enzimatica de las piretrinas, rotenona, insecticidas
N-metil carbamicos, y tal vez, de algunos otros insecticidas. Ocurre poca absor-
cion cutanea por contacto. La toxicidad intrinseca en los mamiferos es baja.
Teoreticamente, la absorcion de dosis masivas aumenta el peligro toxico de los
insecticidas de uso actual, debido al rapido metabolismo; aunque no se ha de-
mostrado la inhibicion que estos agentes causan en el efecto de los medica-
mentos en las enzimas metabolicas en los seres humanos. Su presencia en pesti-
cidas a los cuales estan expuestos los humanos no cambia el enfoque basico en
el manejo del envenenamiento, excepto que debe tenerse en mente la posibili-
dad de que aumente la toxicidad de los ingredientes activos de los insecticidas.
PB DIVERSOS
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DISOLVENTES Y ADYUVANTES
Los manufactureros escogen los materiales liquidos en los cuales se disuel-
ven los pesticidas y los materiales solidos en los cuales son absorbidos (algunas
veces referidos como vehiculos o transportes) para asegurar la estabilidad del
ingrediente active, la conveniencia para el manejo y la aplicacion, y para obte-
ner el maximo poder destructive despues de la aplicacion. Es comun que los
solventes y adyuvantes seleccionados por los manufactureros scan los responsa-
bles del exito competitivo de sus productos comerciales. Es por esto que la
inclusion de estos productos comerciales es informacion patentizada la cual no
esta disponible publicamente excepto en casos de emergencia. Si existe una
emergencia causada por un envenenamiento, las companias pesticidas normal-
mente cooperan supliendo la informacion necesaria a los medicos para proveer
el tratamiento adecuado. Algunas companias proporcionan los ingredientes inertes
en la hoja de datos de materiales para medidas de seguridad (MSDS). Los doc-
tores deben de obtener esta informacion para asistir en la evaluacion de todos
los contactos posibles. La manera mas rapida de asegurar esta informacion es
mediante una solicitud directa al manufacturero. Los medicos pueden comuni-
carse con la Agenda de Proteccion Ambiental, EPA, directamente para obtener
esta informacion (tel: 703-305-7090) acerca del manejo de casos.
Los destilados de petroleo son los solventes utilizados mas comunmen-
te en los insecticidas lipofilicos. La mayoria de los insecticidas son lipofilicos.
Los destilados son mezclas de hidrocarburos aromaticos y alifaticos y poseen un
punto de ebullicion bajo.
En ocasiones, se anaden ciertos hidrocarburos especificos, tales como
tolueno o xileno (fuertemente odoriferos) para estabilizar la solucion del insec-
ticida o hacerlo mas emulsificantes. La mayoria de las veces, los pesticidas de
hidrocarburos se encuentran disueltos en cantidades medidas de agua para for-
mar emulsiones.Algunos hidrocarburos dorados pueden estar presentes en ciertas
mezclas tecnicas.A menudo se percibe un olor fuerte y persistente despues de
la aplicacion de un tratamiento en aerosol para controlar plagas en construccio-
nes, esto se debe al disolvente, mas que al ingrediente active.
Algunas veces, los ingredientes lipofilicos menos activos estan disueltos en
mezclas de alcoholes, glicoles, eteres o diferentes solventes clorinados. Es posi-
ble que esto aumente la capacidad de absorcion cutanea de algunos pesticidas.
Algunos solventes, como el metanol e isopropanol, pueden representar el ma-
yor peligro si son ingeridos en dosis considerables.
En las formulaciones granuladas se utilizan varies materiales de arcilla
que absorben el pesticida, lo retienen en una forma mas o menos estable, y
luego liberado lentamente en el suelo tratado. Existe una desabsorcion conside-
rable cuando los granules entran en contacto con la piel en los seres humanos
y aun mas significante cuando entran en contacto con las secreciones
gastrointestinales luego de la ingestion. El material arcilloso en si no es un
toxico danino.
DIVERSOS 213
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El uso de polvillos no es frecuente hoy en dia. Varias fornias de talco
(particulas de silicato-carbonatos) se han usado en el pasado para la absorcion
de pesticidas en la aplicacion al follaje. El tamano de las particulas es tal que al
ser inhaladas, quedan atrapadas generalmente en la membrana mucosa del tracto
respiratorio superior. Una vez la mucosidad se transporta y entra en contacto
con las secreciones gastrointestinales las particulas son liberadas y absorbidas
por estas. For ende, las formulaciones en polvo pueden liberar una considerable
cantidad conio para causar envenenamientos sistemicos.
Los adherentes y dispersantes son sustancias organicas que se anaden a
las formulaciones para dispersar el pesticida sobre las superficies del follaje tra-
tado y aumentar la adhesion. Por lo tanto aumenta la persistencia y disponibi-
lidad del residue sobre la superficie de las hojas. Se usan sustancias que incluyen
materiales proteicos (productos lacteos, harina de trigo, albumina de sangre,
gelatina), aceites, goma, resinas, arcillas, glicoles polioxietilenos, terpenos y otros
productos organicos viscoses. Algunos incluyen tambien alcoholes sulfatados,
esteres acido-grasos y sulfonatos de petroleo y de alquilo. Estos adyuvantes
probablemente anaden poco o ningun peligro a las personas expuestas durante
el transcurso de la formulacion o durante la aplicacion, que el dano intrinseco
en los ingredientes activos de los pesticidas.
Los emulsificantes sirven para estabilizar las emulsiones de agua y aceite
formadas cuando se le anade agua a los concentrados de hidrocarbono tecnico.
Quimicamente son parecidos a los detergentes (una parte de la molecula es lipofilica
y la otra hidrofilica). Las cadenas largas de eteres de alquil sulfanato y el oleato de
polioexietileno son ejemplos de emulsificantes. Poseen una baja toxicidad intrin-
seca hacia los mamiferos, y la presencia de estos probablemente causa poco efecto
en la toxicidad de los productos formulados que los incluyen,
Los penetrantes facilitan la transferencia del herbicida a partir de la super-
ficie del follaje hacia los tejidos interiores. Algunos son lipidos mientras que
otros son detergentes (surfactantes) en la naturaleza. Las sustancias utilizadas
incluyen aceites y eteres pesados de petroleo, esteres grasos de policies, esteres
polietoxilados de acidos grasos, polioxietilenglicoles, acetato de alqulamina,
sulfonatos de arilo y alquilo, alcoholes polihidricos y fosfatos de alquilo. Algu-
nos de ellos son irritantes para la piel, y pueden ser los responsables por los
efectos irritantes de ciertas formulaciones de herbicidas cuyos ingredientes ac-
tivos no tienen esta propiedad.
Los protectores son sustancias que se anaden las mezclas de fertilizantes con
pesticidas (comunmente con herbicidas) que limitan la formacion de productos
de reaccion indeseables. Algunas de las sustancias utilizadas son fulfatos de alco-
holes, diamato de alquil-butan sodio, poliesteres del dioato de tiobutan sodio y
derivados del acetonitrilbenceno. Algunos compuestos son moderadamente
irritantes para la piel y los ojos; la toxicidad sistematica es generalmente baja.
Los agentes antiendurecedores son anadidos en formulaciones granulares
y en polvo para facilitar la aplicacion y prevenir el aglutinamiento y endureci-
miento. Entre los diversos productos utilizados estan la sal de sodio del sufonato
PB DIVERSOS
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de mono y demetil naftaleno y la tierra de diatomaceas. Esta ultima tienen
pocos efectos adversos con excepcion de una accion deshidratante de la piel. Se
dice que los metilnaftalenos son irritantes para la piel y los fotosensibilizantes,
pero se desconoce si sus derivados tienen tal efecto.
Tratamiento
Los destilados de petroleo son hidrocarburos minerales que se someten a
una absorcion limitada a traves del intestino. Los toxicologos quimicos no reco-
miendan generalmente la induccion al vomito o realizar lavado gastrico como
el tratamiento de la ingestion de estos materiales. Esto es debido a un alto
riesgo de que ocurra neumonitis por hidrocarburos, aun cuando solo se aspiren
pequenisimas cantidades de liquido en los pulmones. Sin embargo, este precep-
to en contra del lavado gastrico y la induccion al vomito se deja a un lado
cuando el petroleo destilado es utilizado como el vehiculo de las altas concen-
traciones de pesticidas toxicos. En estos casos, si el paciente llega dentro de la
primera hora del contacto, debe considerarse la descontaminacion gastrointestinal.
Generalmente las indicaciones de una verdadera neumonitis causada por
los hidrocarburos son respiracion rapida, cianosis, taquicardia y fiebre baja. Los
pacientes supuestamente afligidos con neumonitis de hidrocarburos, y quienes
muestran los sintomas, deben ser hospitalizados, preferiblemente en donde haya
disponible una unidad de cuidado intensive. Si el paciente muestra sintomas
pulmonares, debe ser sometido a una prueba de rayos X que confirme la indi-
cacion de neumonitis. Ademas, debe examinarse la orina para la presencia de
proteinas, azucar, acetona, ferulas y celulas. Examine un EGG para detectar
arritmias y defectos de conduccion. Puede ser requerida la asistencia de venti-
lacion pulmonar con 100% de oxigeno. La neumonitis de hidrocarburos es
algunas veces fatal, y los sobrevivientes necesitaran varias semanas de recobro
total. En casos de envenenamientos leves,la mejoria clinica ocurre generalmen-
te durante varies dias, aunque los resultados radiograficos pueden permanecer
anormales por periodos mas largos.17
La presencia de solventes dorados en algunas formulaciones puede au-
mentar el peligro toxico de manera significativa, en especial cuando el produc-
to es ingerido. Algunos adyuvantes irritan la piel, los ojos y las membranas
mucosas, y pueden ser responsables de las irritaciones que producen algunos
productos cuyos ingredientes activos no tienen este efecto. Sin embargo, con
estas excepciones, la presencia de los adyuvantes en la mayoria de los productos
pesticidas probablemente no aumenta ni reduce en gran medida la toxicidad
sitemica de los productos en los mamiferos.
DIVERSOS 215
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Referencias
1. Spyker DA, Lynch C, Shabanowitz J, et al. Poisoning with 4-aminopyridine: Report of three
cases. ClinToxicol 1980;16:487-97.
2. PickettTA and Enns R. Atypical presentation of 4-aminopyridine overdose. Ann Etnerg Med
1996;27:382-5.
3. Stork CM and Hoffman RS. Characterization of 4-aminopyridine in overdose. Clin Toxicol
1994;32:583-7.
4. Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
NJ: Noyes Publications, 1991, pp. 316-7.
5. Torrelo A, Soria C, Rocamora A, et al. Lichen planus-like eruption with esophageal involve-
ment as a result of cya.na.mide.J Am Acad Dermatol 1990;23:1168-9.
6. Sittig M. Handbook ofToxic and Hazardous Chemicals and Carcinogens, 3rd ed. Park Ridge,
NJ: Noyes Publications, 1991, pp. 450-3.
7. Bowman CE, Muhleman MF, andWalters E. A fatal case of creosote poisoning. Postgrad Med
J1984;60:499-500.
8. Christiansen RG and Klaman JS. Successful treatment of phenol poisoning with charcoal
hemoperfusion. Vet Hum Toxicol 1996;38:27-8.
9. AUenderWJ. Suicidal poisoning by endothallj./lซa/ Toxicol 1983;7:79-82.
10. LongstrethWT and Pierson DJ. Metaldehyde poisoning from slug bait ingestion. West J Med
1982;137:134-7.
11. Jay MS, Kearns GL, 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;ll:361-2.
14. Helliwell M and Nunn J. Mortality in sodium chlorate poisoning. Br MedJ 1979;1:1119.
15. Steffen C and Seitz R. Severe chlorate poisoning: Report of a case. Arch Toxicol 1981;48:281-8.
16. Smith EA and Oehme FW. A review of selected herbicides and their toxicities. Vet Hum
Toxicol 1991;33:596-608.
17. Anas N, NamasonthiV, and Ginsburg CM. Criteria for hospitalizing children who have
ingested products containing hydrocarbons.JAMA 1981;246:840-3.
PB DIVERSOS
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CAPITULO 19
Desinfectantes
PUNTOS IMPORTANTES
Una gran variedad de agentes desinfectantes se utilizan para destruir a los
microorganismos y difieren grandemente en sus propiedades toxicas. La rnayo-
ria de los desinfectantes se pueden dividir convenientemente entre varias cate-
gorias, muchas de las cuales estan representadas en otras clases de pesticidas.
Muchos de estos materiales no estan registrados bajo pesticidas debido a su uso
medico o medicinal. Este capitulo resume varies de los desinfectantes mas co-
munes y severamente toxicos.
ALCOHOLES
Los alcoholes poseen un largo historial de uso como desinfectantes. La
mayoria de las veces, las mezclas desinfectantes estan constituidas generalmente
de etanol y de alcohol isopropilico (isopropanol). El alcohol de mayor uso
domestico como desinfectante es el alcohol isopropilico, manufacturado co-
munmente en una solucion comercial al 70%. Este es un liquido claro e inco-
loro con un olor similar al olor del etanol.
Toxicologia del Alcohol Isopropilico
El alcohol isopropilico es absorbido de manera eficaz y rapida en el tracto
gastrointestinal. Tambien es absorbido eficazmente a traves de la piel y mediante
la inhalacion. Es considerado mas toxico que el etanol en el sistema nervioso
central y produce efectos similares. La ingestion e inhalacion de altas concentra-
ciones puede dar lugar a una rapida manifestacion de una depresion CNS, segui-
do por coma y la muerte. El Apnea viene acompanado generalmente de este tipo
de depresion CNS.1>2 Se ha informado una toxicidad neurologica similar a la que
ocurre durante el contacto topico excesivo del alcohol en el ombligo de los
recien nacidos.3 Esto ha resultado en una irritacion en el tracto gastrointestinal
que causa gastritis y vomitos severos. El alcohol isopropilico puede producir un
dano leve al higado en casos de extenso contacto. Se han informado casos de
necrosis tubular extensa con este agente,1 pero la intoxicacion renal no es mayor
que la de los envenenamientos causados por el metanol. Es comun que ocurra
cetosis sin acidosis metabolica pero se destaca la hipoglicemia.2'3 Esta ketosis es el
resultado de un metabolismo directo de este compuesto de acetona.1'3 Es util
examinar los niveles del isopropilo, cuando esten disponibles. Los niveles de acetona
Los compuestos se
encuentran registrados mas
bajo sus usos medicos o
medicinales que por sus
usos pesticidas
Muchos de ellos se
encuentran entre los
envenenamientos mas
frecuentemente reportados
en los Estados Unidos
El yodo se absorbe a traves
de la piel quemada e
irritada
Senales y Smtomas:
Altamente variables y
basadas en los agentes
Muchos son irritantes y
corrosives
El yodo causa sintomas
neurologicos, shock, fallo
renal e hipercalemia
El aceite de pino puede
causar pulmonia aspirada
Tratamiento:
Siga los principles generales
de descontaminadon y de
cuidado suplementario
Contraindicaciones:
Los procedimientos de
vaciamiento gastrico y
descontaminadon son
contraindicados en casos de
envenenamiento debido a
los agentes corrosives y al
aceite de pino
DESINFECTANTES 217
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Productos Comerdales
ALCOHOLES
alcohol isopropilico
ALDEHlDOS
formaldehido
glutaraldehido
DETERGENTES CATIONICOS
benzalkonium chloride
centrimide
cetylpyridium chloride
CLORHEXIDINA
Hibiclens
Hibistat
Peridex
HIPOCLORITOS
hipoclorito calcico
hipoclorito sodico
YODOS
yodo providon
Betadine
loprep
Pharmadine
MERCURIALES
mercurobutol
mercurocromo
mentiolato
nitromersol
acetato fenilomercurico
nitrato fenilmercurico
thimerosol
FENOLES
2-benzil-4-clorofenol
cresol
Lysol
hexaclorofeno
Bilevon
Dermaadex
Exofene
Gamophen
Phisohex
Surgi-Cen
Surofene
Texosan
o-fenilfenol
fenol
4-tert-amilfenol
thymol
triclosan
ACEITE DE PINO
en la sangre y la glucosa deben ser determinados suplementariamente para ayudar
en el nianejo del envenenamiento.
Confirmacion de Envenenamiento
El alcohol isopropilico se puede niedir en la sangre y en la orina. El serico
acetona tambien se puede niedir. Niveles de 128-200 nig/dL de isopropilo en
la sangre han sido asociados con muerte.
Tratamiento: Alcohol Isopropilico
1. Descontaminacion gastrointestinal. Ya que las manifestaciones de coma
son comunmente rapidas con este tipo de envenenamiento, no se recomienda
la induccion de emesis ya que casi siempre ocurre vomito espontaneamente. Si
el paciente ha ingerido una gran cantidad y no ha vomitado, y se ha presentado
dentro de la primera hora del contacto, debe considerarse un vaciado gastrico
por lavado, como fuera delineado en el Capitulo 2.
2. Las medidas de apoyo son criticamente necesarias para controlar la
hipotension y la depresion respiratoria para asegurar la supervivencia y deben
administrarse cuando sea posible en un lugar de cuidado intensive.
3. Si ocurre hipoglicemia, se indica la administracion de glucosa para mante-
ner normoglicemia.
4. Se ha informado que la hemodialisis es beneficiosa en pacientes severa-
mente intoxicados y que se encuentran poco receptivos a la terapia de apoyo
establecida.1'4
ALDEHlDOS
Los dos aldehidos mas comunmente usados son usados como desinfectan-
tes son el formaldehido y el glutaraldehido. El formaldehido se ha discutido en
el Capitulo 17,bajo Fumigantes. El glutaraldehido es muy similar al formaldehido
en su toxicidad y tratamiento, aunque probablemente sea menos toxico. El
glutaraldehido se prepara comunmente como una solucion acuosa concentrada
al 2%, y es levemente alcalino de esta manera. Se ha informado que causa
irritacion respiratoria dando lugar a rinitis5>f> y asma ocupacional.6'7'8 Raramen-
te ha causado palpitaciones y taquicardia en seres humanos. En dosificacion alt a
y por via oral ha causado diarrea, la cual pudiera ser hemorragica, debido a la
irritacion gastrointestinal. Debido a los efectos irritantes del glutaraldehido, se
requiere el uso de un equipo protector para la piel (29 CFR 1910.132) y los
ojos (29 CFR 1910.133). De acuerdo a las normas de la OSHA, los empleados
PB
DESINFECTANTES
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que se encuentren expuestos al glutaraldehido durante los procedimientos de
trabajo rutinario o de emergencia requieren el uso de respiradores apropiados
(29 CFR 1910.134).
Tratamiento: Glutaraldehido
1. Descontaminacion gastroinstestinal. Si se ha ingerido y retenido una
gran cantidad y se ha retenido, y el paciente es visto durante la primera hora del
contact o, considere el vaciado gastrico, corno fuera delineado en el Capitulo 2.
Se deberia condiderar la administracion de carbon activado conio fuera deli-
neado en el Capitulo 2.
2. Oxigeno. Si el paciente ha estado en un area impregnada con un fuerte olor
a glutaraldehido debido a la vaporizacion, remueva a la persona a un area ven-
tilada con aire fresco y administre oxigeno conio fuera necesario.
3. Descontaminacion dermica. Si ocurre irritacion dermica, se recomienda
una vigorosa descontaminacion. Sin embargo, una toxicidad sistemica debido al
contacto cutaneo parece ser improbable.
DETERGENTES CATIONICOS
Varies detergentes cationicos son utilizados como detergentes.Todos com-
parten la capacidad, con suficiente concentracion, para actuar como agentes
causticos, capaces de causar quemaduras causticas severas. Parece ser que en
concentraciones mayores de aproximadamente un 7,5% pueden producir un
significante dano caustico. Sin embargo, existen experiencias muy limitadas de
contacto humano con estos compuestos. Los tres agentes comunmente utiliza-
dos como detergentes desinfectantes son cloruro de benzalconio, cetrimida y
cloruro de cetilpiridinio.
Aunque en los Estados Unidos no se encuentran disponibles concentra-
ciones de cetrimida, algunos se encuentran disponibles en paises de la union
europea. Las soluciones concentradas se encuentran generalmente en lugares
industriales, asi como la produccion de productos al consumidor, o para el
uso de desinfectantes para hospitales. For lo tanto, los envenenamientos son
poco comunes.
Toxicologia
En soluciones de baja concentracion se ha informado que estos agentes son
la causa de erupciones en la piel, irritacion, y malestar en los ojos. A mayores
concentraciones, pueden causar quemaduras severas en la piel y en la cornea. De
igual manera, las concentraciones fuertes pueden dar lugar a quemaduras causti-
DESINFECTANTES 219
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cas en los labios, la mucosa oral, el esofago y en el estomago. 9>1ฐ Se han informado
vomitos, diarrea y dolor abdominal.n Tambien se han informado casos de necrosis
del intestine con peritonitis.12 En casos de exposicion severa, tambien han habi-
do informes de depresion de CNS, dano hepatico y edema pulmonar.9>n
Tratamiento
1. Descontaminacion dermica. Si se ha aplicado una solucion altamente
concentrada en la piel, un tratamiento de descontaminacion dermica para que-
maduras es apropiado. Si una solucion altamente concentrada entra en contacto
con los ojos, se recomienda un enjuague de los ojos prolongado, seguido por un
examen cuidadoso de la cornea. Si han ocurrido quemaduras, debe proveerse
cuidado oftalmologico apropiado.
2. Descontaminacion gastrointestinal. Esta contraindicado el uso de
metodos de descontaminacion gastrointestinal y vaciado gastrico en estos enve-
nenamientos. Algunos expertos recomiendan la dilucion cuidadosa del desin-
fectante con pequeiias cantidades de agua o leche. 9>13Soluciones acidicas como
los jugos nunca deben de ser ofrecidas en la dilucion.
3. Endoscopia. Si se ha ingerido una alta cantidad de la solucion o se notan
quemaduras orales, el paciente necesita urgentemente una endoscopia para recono-
cer el grado de dano caustico. La endoscipia se debe realizar dentro de las primeras
24 horas para minimizar el riesgo de perforacion del procedimiento.12 Un cirujano
competente o un gastroenterologo debe proveer el cuidado apropiado.
4. Otros agentes. Aunque el uso de corticoesteroides es comun en el trata-
miento de estas quemaduras, su uso se mantiene controversial. Se ha informado
el uso de otros agentes, como H2 antagonistas y los sulcralfatos han sido infor-
mados pero el mismo es controversial en estos momentos.
5. CNS pulmonario y otros efectos sistemicos deben ser tratados de acuerdo
a lo sintomaticamente consistente con medidas de practica probadas.
CLORHEXIDINA
La clorhexidina es una biguamina cationica, disponible en concentraciones al
4% como un agente topico que se usa como limpiador de la piel y lavado bucal.
Preparaciones para la piel al 0,5% - 4% se encuentran en el mercado conocidos
por nombres de marca registrada HybiclensR e HibistatR. Tambien se encuentran
en el mercado como lavado bucal en una solucion al 0,12% bajo el nombre de
marca registrada PeridexR. Existen pocas experiencias con envenenamientos de
seres humanos ya que las concentraciones no parecen ser altamente toxicas.
PB DESINFECTANTES
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Toxicologia
La clorhexidina es pobremente absorbida a traves de la piel o el tracto
gastrointestinal. De ahi que la mayoria de sus efectos notables hayan sido prima-
riamente locales. Si una baja concentracion es ingerida o aplicada a la piel,
puede causar una leve irritacion local. El contacto repetido con la piel de este
agente ha causado dermatitis, urticaria y anafilaxis.14'15 En varies casos se han
descritos danos en la cornea despues del contacto ocular inadvertido en con-
centraciones al 4%. Estos danos han dado resultado en cicatrices permanentes
en la cornea.16 Se han informado casos de quemaduras del esofago despues de
haber ingerido grandes cantidades de una solucion al 20% de este agente. 17 Se
ha descrito colitis ulcerativa despues del tratamiento de una enema con una
solucion al 4% mezclada con agua (10 mL en 2 litres de agua).18 Toxicidad
hepatica puede suceder con el contacto extenso.17
Tratamiento
1. Descontaminacion gastrointestinal. Si se han ingerido grandes cantida-
des durante la primera hora y el paciente no ha vomitado, debe considerarse la
descontaminacion gastrointestinal como fuera delineado en el Capitulo 2. Si se
ha ingerido una solucion de alta concentracion, trate la contaminacion segun
las instrucciones descritas para detergentes cationicos, excluyendo la desconta-
minacion gastrointestinal.
2. Un panel de dano hepatico debe llevarse a cabo con ingestiones severas.
3. Descontaminacion ocular. Si ha ocurrido contacto con los ojos, debe
enjuagarlos vigorosamente y llevar a cabo un examen oftalmologico para indi-
car el dano corneo. Si ha ocurrido dano, se debe obtener una consulta
oftalmologica.
HIPOCLORITOS
Los hipocloritos se encuentran implicados en una gran porcion de los en-
venenamientos causados por los desinfectantes que han sido informados a los
centres de control de envenenamientos en los Estados Unidos. La mayoria de
estos han sido soluciones sodicas o de hipoclorito calcico. La cloramina es un
desinfectante usado en muchas reservas de agua municipales y ha sido la causa,
aunque infrecuente, de extensos envenenamientos. El hipoclorito de calcico y
sodico poseen una toxicidad relativamente baja. Son levemente corrosives para
los ojos,19 y se ha informado que causan quemaduras en las membranas mucosas.20
Los envenenamientos severos son muy infrecuentes en estas soluciones con
estos agentes.21
DESINFECTANTES 221
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Cuando soluciones de hipocloritos son mezcladas con acidos o soluciones
de arnonia, se produce cloro o gas cloramino, resultando en un irritante que da
lugar a toxicidad pulmonar. Muchos de los contactos breves han dado lugar a
sintomas transitorios que requieren un cuidado de emergencia limitado. 22 Sin
embargo, en casos de contacto extenso o contacto a altas concentraciones, hay un
potencial para que ocurra neumonitis toxica severa.23 Aun cuando el dano severe
pueda ser una excepcion a la regla, se deben realizar grandes esfuerzos para des-
alentar la mezcla de estos materiales con acido o amonia.
Tratamiento
1. Descontaminacion gastrica. Si ha ocurrido un contacto oral no se reco-
mienda vaciado gastrico. Si el paciente ha ingerido un material granulado y
muestra sintomas de quemadura en la mucosa, refieralo a un cirujano o a un
gastroenterologo para considerar una endoscopia y el tratamiento apropiado.
2. La dilucion con agua o leche es probablemente apropiada si no ha ocurrido
vomito, sin exceder una cantidad de aproximadamente 15mL/kg en los niiios o
120 a 240 mL en los adultos. La administracion de acidos esta contraindicada,
debido al riesgo o al incremento en la generacion del gas de cloro.
3. Descontaminacion ocular. Si los ojos se han expuestos a la contamina-
cion, deben ser extensamente enjuagados con agua o solucion salina. Si se de-
tectan quemaduras en la cornea, refiera a un oftalmologo.
4. Descontaminacion dermica. El contacto dermico tambien debe ser tra-
tado con abundante dilucion con agua.Vease el Capitulo 2.
5. Aire fresco. Si ha ocurrido contacto con los vapores o con el gas cloramina
o de cloro, el paciente debe ser removido inmediatamente a un area ventilada
con aire fresco. Si aparecen o persisten los sintomas, debe evaluarse la oxigena-
cion y se debe de administrar oxigeno si es necesario. Si ocurren sintomas
persistentes, se debe de obtener una radiografia del pecho y debe considerarse
cuidado clinico. Puede que sea necesario el cuidado intensive si ocurren
inhalaciones severas.
YODO
El desinfectante mas comun que contiene yodo es yodo-providon (proviodo),
en soluciones de 7,5 - 10%. El yodo-providon esta descrito como un yodofor,
el cual es un complejo de yodo y polivinilpirrolidona un agente soluble. La
intension de este agente es liberar un radical libre de yodo en solucion para que
haga efecto. Aunque la concentracion informada del yodo en estas soluciones
PB DESINFECTANTES
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es solamente de 80 a 120 ugm/dL, el total del yodo disponible es aproximada-
mente 10% del yodo-providon, por lo tanto una solucion al 10% tendra una
escala de diferenciacion total disponible de yodo de 1%.
Toxicologia de Yodo-providon
Este compuesto posee una baja absorcion gastrointestinal debido a la con-
version rapida libre de yodo en el estomago. Aunque las altas concentraciones
de las sales o de las soluciones yodo son corrosivas para el tracto gastrointestinal,24
las soluciones de yodo-providon poseen un leve potencial caustico. De la mis-
ma manera, el compuesto posee una baja absorcion cutanea.Todos los envene-
namientos sintomaticos que han sido informados han ocurrido luego del con-
tacto repetido en quemaduras de la piel o seguido de una irrigacion en una
herida, coyunturas o superficies serosas como el mediastino.25"28 La unica ex-
cepcion fue en un infante que recibio una enema de yodo-providon en una
solucion de polietilenglicol, seguido de una irrigacion total con polietilenglicol
mezclado con yodo-providon. Este niiio murio de una hipoglicemia severa y
unos niveles altos de yodo.24
Durante el contacto con yodo-providon por medio de estas rutas, las pri-
meras manifestaciones de los sintomas parecen neurologicos, con dolor de ca-
beza, mareo, delirio, alucinaciones y convulsiones.26 La hipotension, arritmias,
cianosis, acidosis metabolica, shock y fallo renal agudo ocurren en casos seve-
ros 25,27,28 -gj (Jano hepatico, manifestado por los niveles elevados de transaminasa
serica, ha sido informado en casos de contacto extenso.27 Ha ocurrido
hiperkalemia, y el cloruro serico puede aparecer supuestamente elevado debido
a la presencia de un segundo haloideo.25
Tratamiento: Yodo-providon
1. Descontaminacion dermica. Remueva la contaminacion lavando vigo-
rosamente con agua y jabon.Vease el Capitulo 2.
2. Descontaminacion gastrointestinal. Si el paciente es visto luego de ha-
ber ingerido una gran cantidad y no ha ocurrido vomito, considere la descon-
taminacion gastrointestinal, como fuera delineado en el Capitulo 2. Considere
una dosis individual de carbon.
3. La eliminacion de yodo aparentemente aumenta los procedimientos que
ayudan a la excrecion del cloruro. Por lo tanto, la diuresis osmotica o colexetica
esta probablemente indicada en estos envenenamientos cuando son sintomaticos.
4. Convulsiones. Trate las convulsiones con anticonvulsantes, como fuera de-
lineado en el Capitulo 2.
DESINFECTANTES 223
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5. Monitoree la funcion de las tiroides siguiendo la recuperacion para
confirmar el estado de la eutiroidea.
MERCURIALES
Una gran variedad de mercuriales organicos han sido utilizados como des-
infectantes y preservatives. Casi todos los usos han sido prohibidos en los Esta-
dos Unidos. La toxicidad y el tratamiento del contacto con estos compuestos se
ha descrito detalladamente en el Capitulo 15,Fungicidas, bajo los compuestos
organomercuricos y no se repetiran aqui.
FENOLES
Varies fenoles se utilizan como desinfectantes. El cresol y timol son alquilos
derivados del fenol, mientras que el hexaclorofeno y el triclosan son fenoles
clorinados. Algunas preparaciones comerciales comunes lo son el LysolR, una
solucion al 50% de cresoles mezclados con jabon, y el hexaclorofeno, que se
conoce comercialmente bajo varias marcas registradas de barras de jabon y
varies cosmeticos. Los cresoles y el hexaclorofeno son discutidos individual-
mente como ejemplos de estos compuestos que son conocidos y por los cuales
existe informacion relacionada a los seres humanos.
Toxicologia de los Cresoles
Los cresoles, conjunto con los fenoles y otros compuesto fenolicos, son alta-
mente corrosives a todas las superficies. La ingestion de formas concentradas causa
dano corrosive severe en la boca y el tracto gastrointestinal superior. Asi tambien,
pueden ocurrir danos severos en los ojos y en la piel a traves del contacto con el
cresol.29 Generalmente los sintomas incluyen nauseas, vomito y diarrea. Tambien
pueden ocurrir hipotension, fallo miocardial, edema pulmonar, y cambios
neurologicos. Tambien se ha informado toxicidad del higado y renal,
metahemoglobinemia, y hemolisis.30'31 Despues del contacto repetido a largo plazo
la dermatitis puede complicar estos sintomas. Estos compuestos son bien absorbidos
en el tracto gastrointestinal y tambien a traves de la piel y por medio de inhalacion.
Tratamiento: Cresoles
1. Descontaminacion gastrointestinal. Debido a la naturaleza corrosiva de
estos compuestos, no se debe intentar la descontaminacion gastrointestinal. Debe
considerarse una dilucion apropiada con leche o agua si no ha ocurrido vomito.
2. Endoscopia. Si ha ocurrido dano corrosive con quemaduras en la boca, o
si hay una clara historia de contacto gastrointestinal, debe considerarse una
PB DESINFECTANTES
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endoscopia y debe de consultarse a un cirujano o a un gastroenterologo para
diagnosis y manejo de tratamiento.
3. Descontaminacion dermica. Si ha ocurrido contamination dermica y
ocular se deben llevar a cabo enjuagues abundantes. Esto debe ser seguido por
un examen cuidadoso de los ojos para seiiales de quemadura en la cornea. Si se
encuentran quemaduras en la cornea, debe consultarse a un oftalmologo.
4. Apoyo respiratorio y circulaterio debe ser provisto de acuerdo con
medidas de practicas probadas. Si persisten los sintomas severos, el paciente
debe ser tratado en una unidad de cuidado intensive cuando sea posible.
Toxicologia del Hexaclorofeno
El hexaclorofeno es absorbido eficazmente por via oral y dermal. El con-
tacto dermal a causado intoxicacion severa y muerte en recien nacidos, debido
a la aplicacion en piel lesionada, contactos repetidos o contacto a altas concen-
traciones.32 El hexaclorofeno nunca debe usarse como desinfectante en heridas
abiertas o superficies de la piel inflamadas o irritadas. En distincion a otros
compuestos fenolicos, este agente no es sumamente caustico y el contacto no
resulta en severos danos causticos como se ha visto con otros quimicos fenolicos.
El hexaclorofeno es un neurotoxicante potente. Causa edema cerebral y
degeneration esponjosa de la materia blanca del cerebro.33 Esta intoxicacion
neurologica se percibe despues del contacto cronico o extenso sea por absor-
cion o por ingestion. Los sintomas del sistema nervioso son complejos. El letar-
go es una manifestation initial, seguido por debilidad muscular, fasciculacion
muscular, irritabilidad, edema cerebral y paralisis, que conducen a coma y muerte.
Las convulsiones ocurren comunmente en casos mas severos.32>34 Se ha infor-
mado ceguera y atrofia optica luego del contacto con hexaclorofeno.35
Ademas de los efectos neurologicos, otros sintomas comunes de envenena-
miento son vomitos, diarrea y anorexia.34 En animales, estos hallazgos han veni-
do acompaiiados de una hepatoxicidad significante.36 Se ha notado a traves de
la exposition dermal una eruption eritematosa exfoliativa de la piel en el lugar
del contacto.34 En la exposition se puede desarrollar dermatitis de contacto. En
envenenamientos severos, se ha notado sintomas cardiovasculares que incluyen
la hipotension y la bradicardia.37 En un caso individual, una enfermera pediatra
contrajo asma despues del contacto repetido con este compuesto.38
Tratamiento: Hexaclorofeno
1. Descontaminacion gastrointestinal. Ya que este agente no es general-
mente caustico, debe considerarse el tratamiento de descontaminacion
gastrointestinal agresivo. Si el paciente ha ingerido una cantidad significante y
DESINFECTANTES 225
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es visto dentro de la primera hora del contacto, vaciado gastrico es probable-
mente lo mas util, corno fuera delineado en el Capitulo 2.
Se cree que hexaclorofeno tiene una recirculacion enterohepatica, y por lo
tanto es posible que repetidas dosis de carbon activado ayuden a la eliminacion
de este compuesto, como fuera delineado en el Capitulo 2. Sin embargo, el
hexaclorofeno no se combina bien con el carbon y no existen ejemplos clini-
cos de esta terapia para este agente.
2. Otras terapias. Aunque este compuesto es sistemicamente bien toxico y los
metodos de eliminacion pueden aparecer beneficiosos, no hay evidencia para
apoyar la eficacia de la hemodialisis, la dialisis peritoneal, hemoperfusion o trans-
fusion. 37
3. Descontaminacion dermica. Si ha ocurrido contacto a traves de la piel,
probablemente sea beneficioso lavar la piel agresivamente con jabon o deter-
gente, para remover los residues que todavia esten en la piel. Como el
hexaclorofeno no es soluble en agua, el agua sola no provee beneficio significante.
Vease el Capitulo 2.
4.Apoyo neurologico y el control de las convulsiones es critico para la super-
vivencia y se debe realizar en una unidad de cuidado intensive, siempre y cuan-
do sea posible. El control de las convulsiones debe de estar de acuerdo con las
recomendaciones en el Capitulo 2.
5. Apoyo respiratorio y cardiovascular son tambien muy importantes para
el exito del tratamiento de envenenamientos severos con este agente debe ser
provisto en una unidad de cuidado intensive con practicas medicas aceptables.
ACEITE DE PINO
Las soluciones desinfectantes y los detergentes de aceite de pino son la
causa de los envenenamientos mas comunes que se reportan en los centres de
control de envenenamiento en los Estados Unidos. Un numero relativamente
alto de estos ha sido informado como serio o fatal. El aceite de pino se encuentra
en una gran variedad de productos domesticos y limpiadores y desinfectantes
comerciales. Es una mezcla de monoterpenos derivados de la destilacion de la
madera de varias especies de pino, con aproximadamente un 57% de alfa-pinene.39
El efecto secundario mas comun en dosificaciones bajas son irritacion de las
membranas mucosas, irritacion gastrointestinal, depresion respiratoria leve y
depresion CNS y toxicidad renal. En altas ingestiones puede causar afliccion
respiratoria severa, colapso cardiovascular y severos efectos CNS. Tambien se
han informado dano renal y mioglobinuria en casos de envenenamientos
severos.40 Debido a que pequenas ingestiones pueden resultar en neumonia
severa, todas las ingestiones deben considerarse potencialmente peligrosas.
PB DESINFECTANTES
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Aun cuando los efectos de envenenamiento informados con este agente
estan relacionados a los efectos irritantes en la membrana niucosa, el tracto
gastrointestinal y los pulmones (debido a la aspiracion), algunos informes sugieren
una absorcion significante por via de contacto oral y rectal. Otros informes
sugieren una taza de absorcion mas baja. 39 Mientras el alfaterpineol puede
medirse en la sangre, no existe informacion relacionada a los niveles de toxicidad.
Consecuentemente, esta medida no se considera util en la guia para el diagnostico
de tratamiento.
Tratamiento
1. Descontaminacion gastrointestinal. Debido a que existe un alto riesgo
de neumonia severa, la induccion de emesis es usualmente contraindicada en
estos envenenamientos. Sin embargo, emesis espontanea puede ocurrir debido
a la irritacion directa a la mucosa gastrica.
Si el paciente recibe tratamiento durante la primera hora de la ingestion y
se ha ingerido una gran cantidad, el vaciado gastrico por intubacion y el lavado
debe ser considerado, como fuera delineado en el Capitulo 2. Sin embargo,
algunos estudios han sugerido una mayor taza de complicaciones con el lavado
que con la induccion de emesis con el jarabe de ipecacuana.40
No existe evidencia de que el carbon activado sea util para estos envenena-
mientos. Por igual, aunque una variedad de metodos mejorados de eliminacion
han sido propuestos y tratados, no existe evidencia que apoye su eficacia.
2. Descontaminacion ocular. Si ha ocurrido ocular, se requiere enjuague
prolongado.
3. Sintomas pulmonares. El paciente debe estar bajo observacion por lo
menos durante 6 horas despues de haber ingerido para observar las manifesta-
ciones de cualquier sintoma, especificamente sintomas pulmonares. Si se obser-
van sintomas pulmonares, el paciente debe obtener una medida de oxigenacion
y una placa de pecho, y hospitalizacion si es apropiada. Cuando los sintomas
pulmonares son severos, es apropiado transferir al paciente a una unidad de
cuidado intensive. Cuando existe aspiracion severa, debe manej arse como en
cualquier caso de neumonia severa, de acuerdo a las practicas medicas acepta-
bles. Otros efectos sistemicos severos tambien deben ser tratados de acuerdo a
las practicas medicas aceptadas.
Referencias
1. Lacouture PG.Wason S, Abrams A, et al. Acute isopropyl alcohol intoxication: Diagnosis and
management. Am J Med 1983;75:680-6.
DESINFECTANTES 227
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2. Rich], Scheife RT, Katz N, et al. Isopropyl alcohol intoxication. Arch Neural 1990;47:322-4.
3. Vivier PM, Lewander WJ, Martin HF, et al. Isopropyl alcohol intoxication in a neonate
through chronic dermal exposure: A complication of a culturally-based umbilical care prac-
tice. Pediatr Emerg Care 1994;10:91-3.
4. Manring E, Meggs W, Pape G, et al.Toxicity of an intravenous infusion of isopropyl alcohol.
JToxicol ClinToxicol 1997;35:503.
5. Norback D. Skin and respiratory symptoms from exposure to alkaline glutaraldehyde in
medical services. ScandJWork Environ Health 1988;!4:366-71.
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 technolo-
gist exposed to glutaraldehyde.J/l//e^y din 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. ChanTY. 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 Spe-
cialty Board. Englewood, CO: Micromedex, 1988.
14. WongWK, Goh CL, and Chan KW. Contact urticaria from chlorhexidine. Contact Dermatitis
1990;22:52.
15. Okano M, Nomura M, Hata S, et al. Anaphylactic symptoms due to chlorhexidine glucon-
atc.Arch Dermatol 1989;125:50-2.
16. Tabor E, Bostwick DC, and Evans CC. Cornea! damage due to eye contact with chlorhexidine
gucona.te.JAMA 1989;261:557-8.
17. Massano G, Ciocatto E, Rosabianca C, et al. Striking aminotransferase rise after chlorhexidine
self-poisoning. Lancet 1982;! :289.
18. Hardin RD andTedesco FJ. Colitis after hibiclens enema. J din 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.
20. French RJ.Tabb HJ, and Rutledge LJ. Esophogeal stenosis produced by ingestion of bleach.
South MedJ1970;63:l 140-4.
21. Landau GD and SaundersWH.The effect of chlorine bleach on the esophagus. Arch Otolaryngol
1964;80:174-6.
22. Mrvos R, Dean BS, Krenzelok EP, et al. Home exposure to chlorine/chloramine gas: review
of 216 cases. South MedJ 1993;86:654-7.
23. Reisz GR and Gammon RS. Toxic penumonitis from mixing household cleaners. Chest
1986:89:49-52.
24. KurtTL, HnilicaV, Bost R, et al. Fatal iatrogenic iodine toxicity in a 9-week old infant. Vet
Hum Toxicol 1992;34:333.
PB DESINFECTANTES
-------
25. Means LJ, Rescorla FJ, and Grosfield JL. Iodine toxicity: An unusual cause of cardiovascu-
lar collapse during anesthesia in an infant with Hirschsprung's Disease. J Pediatr Surg
1990;25:1278-9.
26. Ponn RB. Continuous povidone-iodine irrigation (letter). Ann Thome Surg 1987;43:239.
27. Pietsch J and Meakins JL. Complications of povidne-iodine absorption in topically treated
burn patients. Lancet 1976;7:280-2.
28. Campistol JM, Cipiano A, Nogue S, and Bertran A. Acute renal failure in a patient treated by
continuous povidone-iodine mediastinum irrigation. J Pediatr Surg 1988;29:410-2.
29. Pegg SP and Campbell DC. Children's burning due to cresol. Bums 1985;ll: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 intra-
vascular hemolysis in lysol poisoning. Blood 1971;38:739-44.
32. Mullick FG. Hexachlorophene toxicity Human experience at the Armed Forces Institute
of Pathology. Pediatrics 1973;51 (2)11:395-9.
33. Anderson JM, Cockburn F, Forfar J, et al. Neonatal spongioform myelinopathy after re-
stricted application of hexachlorophane skin disinfectant. J Clin Pathol 1981;34:25-9.
34. Martin-Bouyer G, Lebreton R.Toga M, et al. Outbreak of accidental hexachlorophene poi-
soning in France. Lancet 1982;l:91-5.
35. SlamovitzTL, Burde RM, and KlingeleTG. Bilateral optic atrophy caused by chronic oral
ingestion and topical application of hexachlorophene. Am J Ophthalmol 1980;89:676-9.
36. Prasad GV, Rajendra W, and Indira K. Brain ammonia metabolism in hexachlorophene-
induced encephalopathy. Bull Environ Contain Toxicol 1987;38:561-4.
37. Boehm RM and Czajka PA. Hexachlorophene poisoning and the ineffectiveness of perito-
neal dialysis.JToxicol ClinToxicol 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. ,4rc/i TcraVo/1981;49:73-8.
40. LitovitzTL, SchmidzBF, 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.
DESINFECTANTES 229
-------
Seccion V
INDICES
-------
Indice de Senales y Sintomas
En este capitulo se presenta una lista de pesticidas que han sido senalados como
los causantes de sintomas y senales especificas, o una combinacion de ellos, en
individuos envenenados. La lista puede dirigir, en ocasiones, la atencion de los
profesionales de la salud hacia posibles causas toxicas de varias manifestaciones
de enfermedades, y sugerir la busqueda de la exposicion hacia los compuestos
quimicos enlistados. Si se sospecha de ciertos agentes, pueden buscarse mani-
festaciones tipicas adicionales que scan caracteristicas del envenenamiento por
estas sustancias.
Es importante entender las limitaciones de este enfoque para hacer el diag-
nostico. Primero, todas las manifestaciones de enfermedad tienen causas mul-
tiples, tanto debidas a los pesticidas, como ajenas a estos. Segundo, no existen
sintomas y senales especificas que esten presentes invariablemente en los enve-
nenamientos por ciertos pesticidas. Tercero, muchos envenenamientos se ca-
racterizan por manifestaciones inesperadas.
Por ultimo, es evidente que en este listado no se considera la ruta de expo-
sicion ni la dosis del pesticida. Por ejemplo, los efectos de la ingestion de dosis
elevadas no se distinguen de los efectos de absorcion dermica de dosis relativa-
mente bajas, como tampoco se distinguen los efectos topicos de las manifesta-
ciones cutaneas de origen sistemico. Es claro que las listas de pesticidas solo
pueden considerarse como daves para sugerir una investigacion mas profunda al
profesional que hace la entrevista.
El termino manifestacion significa sintoma o seiial. La palabra "envenena-
miento" se usa ampliamente en estos encabezados para incluir tanto efectos
topicos como sistemicos. Los pesticidas que son relativamente consistentes en
causar ciertas manifestaciones estan enlistados a la mitad de la columna, bajo
"Caracteristica de Estos Agentes." Los agentes que han causado varias condi-
ciones con menos consistencia o con caracteristicas menos notorias de envene-
namiento, estan enlistados en la columna de la derecha bajo el titulo "Ocurre
con estos Agentes." Cabe decir que la distincion no es precisa.
Algunos sintomas (malestar, fatiga, mareo) se presentan frecuentemente en
los individuos envenenados que tienen un valor nulo o escaso para el diagnos-
tico diferencial y, por consiguiente, no se incluyen en estas tablas.
PB SENALES Y SiNTOMAS
-------
General
MANIFESTACION
Olor a huevo podrido
Hipotermia
Hipotermia
(fiebre, pyrexia)
Escalofrios
Sensadon de calor
Mialgia
Sed
Anorexia
Intolerance al alcohol
Sabor dulce en la boca
Sabor metalico en la boca
Sabor salado, sabor
a jabon enla boca
CARACTERISTICAS
DEESTOSAGENTES
Sulfuro
Creosota
Norbormida
Nitrofenoles
Pentaclorofenol
Fosfamina
Arsina
Nitrofenoles
Clordimeform
Paraquat
Compuestos clorofenoxi
Pentaclorofenol
Nitrofenoles
Arsenicales Inorganicos
Fosforo
Fosfuros
Fluoruro sodico
Colecalciferol
Aminopiridina
Organofosfatos
Insecticidas carbamicos
Nicotina
Pentaclorofenol
Hexaclorobenceno
Clordimeform
Colecalciferol
Tiram
Cianamida de calcica
Clordimeformo
Arsenicales inorganicos
Mercuric organico
Fluoruro de sodico
OCURRE CON
ESTOS AGENTES
Borato
Talio
Metaldehido
Arsenicales inorganicos
Compuestos clorofenoxi
Polvos de cadmio
Naftaleno
Pentaclorofenol
Borato
Endotal
Fumigantes halocarbonos
Nitrofenoles
Arsenicales inorganicos
Aminopiridina
SENALES Y SiNTOMAS 233
-------
PIEL
MANIFESTACION
Irritadon,
Erupdon,
Vesicacion, o
Erosion (sin
sensibilizacion)
Dermatitis de
contacto
Ruborizadon
Sensibilidad dermica
Palmas y plantas de los pies
rojizas y carnosas
Urticaria
Ampollas
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Compuestos de cobre,
cadmio y organoestano
Metam sodio
Paraquat
Diquat
Clorato sodico
Foforo
Azufre
Glifosato
Propargita
Hipoclorito sodico
Amonia cuaternaria
Tiram
Clordimeformo
Detergentes cationicos
Hexaclorofeno
6xido de etileno
Formaldehido
Acrolefna
Bromuro de metileno
Dibromuro de etileno
Dibromocloropropano
Dicloropropano
Endotal
Acidos alifaticos
PCP
Paraquat
DEET
Clorhexidina
Creosota
Hexaclorfina
Piretrinas
Clorotalonil
Tiram
Tioftalamidas
Cinamida
Nitrofenoles
Propaclor
Propargita
6xido de etileno
Borato
Clorhexidina
PCP
DEET
Fumigantes liquidos
OCURRE CON
ESTOS AGENTES
Pentaclorofenol
Picloram
Compuestos clorofenoxi
Captan
Rotenona
Dietiltoluamida
Creosota
Fungicidas
Herbicidas con
propiedades irritantes
Destilados de petroleo
Alcohol de Tiram plus
Anilazina
Clorotalonil
Barban
Captafol
Formaldehido
Fluoruro
Pentaclorofenol
Hexaclorobenceno
PB
SENALES YSINTOMAS
-------
Skin (continuacion)
MANIFESTACION
Palidez
Cianosis
Coloradon amarilla
Queratosis, descoloradon
de color pardo
Equimosis
Ictericia
Credmiento excesivo
de cabello
Perdida de cabello
Perdida de las unas
Unas quebradizas,
estrias blancas
Sudor, diaforesis
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Organocloros
Fumigantes
Fluoruro de sodio
Creosota
Clorato de sodio
Paraquat
Polvos de cadmio
Fluoroacetato de sodio
Stricnina
Crimidina
Nicotina
Organocloros
Nitrofenoles
Arsenicales inorganicos
Coumarins
Indandionas
Tetracloruro de carbono
Cloroformo
Fosforo
Fosfanados
Fosfina
Paraquat
Clorato de sodio
Talio
Organofostatos
Carbamatos Insecticidas
Nicotina
Pentaclorofenol
Naftaleno
Aminopiridina
OCURRE CON
ESTOS AGENTES
Cumarinas
Indandionas
Organofosfatos
Carbamatos insecticidas
Agentes que causan shock,
miocardiopatia, arritmias
severas y convulsiones
Fosforos
Fosfonados
Arsenicales inorganicos
Diquat
Compuestos de cobre
Hexaclorobenceno
Arsenicales inorganicos
Paraquat
Arsenicales inorganicos
Arsenicales inorganicos
Talio
Compuestos de cobre
SENALES Y SiNTOMAS 235
-------
OJOS
MANIFESTACION
Conjuntivitis
(irritadon de las
membranas mucosas,
lagrimeo)
Lagrimeo
Esclerotica amarilla
Queratitis
Ptosis
Diplopia
Fotofobia
Estrechez del campo visual
Atrofia optica
Miosis
Dilatacion de pupilas
Pupilas no reactivas
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Compuestos de cobre
Compuestos organoestanicos
Compuestos de cadmio
Metam sodio
Paraquat
Dicuat
Acroleina
Cloropicrina
Dioxido de azufre
Naftaleno
Formaldehido
Oxido de etileno
Bromuro de metilo
Endotal
Tolueno
Xileno
Organofosfatos
Insecticidas carbamicos
Cloropicrina
Acrolefna
Nitrofenoles
Paraquat
Talio
Organo fosfatos
Insecticidas carbamicos
Nicotina
Mercuric organico
Organofosfatos
Insecticidas carbamicos
Cianida
Fluoruro
Cianida
OCURRE CON
ESTOS AGENTES
Tioftalamidas
Tiram
Tiocarbamatos
Pentaclorofenol
Compuestos clorofenoxi
Clorotalonil
Picloram
Creosota
Acidos alifaticos
Pentaclorofenol
Piretrinas
Agentes que causan ictericia
(vease bajo Piel)
Compuestos organoestanicos
Talio
Nicotina (tempranamente)
PB
SENALES YSINTOMAS
-------
Sistema Nervioso
MANIFESTACION
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
OCURRE CON
ESTOS AGENTES
Parestesia
(mayormente facial,
transitoria)
Organofosfatos
Cianopiretroides
Fosfuros
Organocloros
Thiabendazol
Nicotina (tardiamente)
Parestesia de las
extremidades
Arsenicales inorganicos
Mercuric organico
Fluoroacetato de sodico
Disulfato de carbono
Talio
Piretroides (transitorio)
Dolor de cabeza
Organofosfatos
Insecticidas carbamicos
Nicotina
Arsenicales inorganicos
Mercuric organico
Compuestos de cadmio
Compuestos organoestanicos
Compuestos de cobre
Talio
Fluoruro
Boratos
Naftalenos
Fosfamina
Fumigantes halocarbonos
Creosota
Diquat
Colecalciferol
Cianamida
Organocloros
Nitrofenoles
Tiram
Pentaclorofenol
Paraquat
Dietiltoluamida
Disturbios de conducta
del animo
(confusion, excitacion,
mania, desorientacion,
habilidad emocional)
Mercuric organico
Arsenicales inorganicos
Compuestos organoestanicos
Talio
Nicotina
Fluoroacetato sodico
Diquat
Cianuro
Nitrofenoles
Aminopiridina
Disulfuro de carbono
Bromuro de metilo
Organofosatos
Insecticidas carbamicos
Pentaclorofenol
Fluoruro sodico
Dietiltoluamida
Organocloros
Depresion, estupor, coma,
fallo respiratorio, muchas
veces sin convulsiones
Organofosfatos
Insecticidas carbamicos
Fluoruro de sodio
Borato
Diquat
Arsenicales inorganicos
Metaldehido
Fluoruro de sulfurilo
Fumigantes halocarbonos
Fosforo
Fosfamina
Paraquat
Compuestos clorofenoxi
Dietiltoluamida
Ftalatos de alquilo
SENALES Y SiNTOMAS 237
-------
NerviOSO (continuation)
MANIFESTACION
Ataques/convulsiones
(tonico-clonicas) algunas
veces conducen a coma
Espasmos musculares
Miotonfa
Tetania, espasmos
carpopedales
Temblor
Falta de coordination
(incluyendo ataxia)
Paralisis
Paresis, debilidad
muscular
Perdida de la
audicion
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Organocloros
Estricnina
Crimidina
Fluoroacetato sodico
Nicotina
Cianuro
Acrilonitrilo
Metaldehido
Talio
DEET
Clorobenzolato
Disulfuro de carbono
Fosfamina
Yodo-providon
Hexaclorofeno
Clorato sodico
Creosota
Endotal
Fluoruro
Organofosfatos
Insecticidas carbamicos
Nicotina
Fluoruro de sulfurilo
Fluoruro
Fosfuro
Fosforo
Mercuric organico
Talio
Organo fosfatos
Insecticidas carbamicos
Nicotina
Metaldehido
Boratos
Fumigantes halocarbonos
Organofosfatos
Insecticidas carbamicos
Disulfuro de carbono
Nicotina
Talio
Arsenicales inorganicos
Organofosfatos
Insecticidas carbamicos
Nicotina
Mercuric organico
OCURRE CON
ESTOS AGENTES
Nitrofenoles
Pentaclorofenol
Arsenicales inorgancos
Compuestos organoestanicos
Diquat
Borato
Fluoruro de sulfurilo
Bromuro de metilo
Compuestos clorofenoxi
Organofosfatos
Insecticidas carbamicos
Aminopiridina
Mercuric organico
Compuestos clorfenoxi
Compuestos clorofenoxi
Pentaclorofenol
Nitrofenol
Tiram
Mercuric organico
Organocloros
Mercuric organico
Dietiltoluamida
PB
SENALES YSINTOMAS
-------
NerviOSO (continuation)
MANIFESTACION
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
OCURRE CON
ESTOS AGENTES
Hipotension, shock
Fosforo
Fosfuros
Fosfamina
Fluoruro sodico
Clorato sodico
Borato
Talio
Compuestos de cobre
Endotal
Cianamida
Arsenicales inorganicos
Nicotina (tardiamente)
Creosota
Ftalatos de alquilo
Cicloheximida
Formaldehido
Norbormida
Hipertension
Talio (tempranamente)
Nicotina (tempranamente)
Organofosfatos
Sistema Cardiovascular
MANIFESTACION
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
OCURRE CON
ESTOS AGENTES
Arritmias cardiacas
Fluoroacetato sodico
Fumigantes halocarbonos
Nicotina
Fluoruro sodico
Oxido de etileno
Clorato sodico
Talio-ventricular
Yodo-providon
Veratrum alcaloide (sabadilla)
Arsenicales inorganicos
Fosforo
Fosfuros
Fosfamina
Organocloro
Cianuro
Acrilonitrilo
Fluoruro
Bradicardia (algunas veces
hasta asistolia)
Cianuro
Organofosfatos
Insecticidas carbamicos
Nicotina
Taquicardia
Nitrofenoles
Pentaclorofenol
Cianamida
Metaldehido
Organofosfatos
SENALES Y SiNTOMAS 239
-------
Sistema Respiratorio
MANIFESTACION
Irritadon del tracto
respiratorio superior,
rinitis, garganta
irritada, tos
Estornudos
Nariz destilante
Edema pulmonar
(muchos quimicos vienen
empacados en un vehiculo
de hidrocarbono,
reconocido por ser el
causante de edema
pulmonar)
Consolidation pulmonar
Disnea
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Naftaleno
Paraquat
Cloropicrina
Acrolefna
Dicloropropeno
Dibromuro de etileno
Dioxido de azufre
Fluoruro de sulfurilo
Acrilonitrilo
Formaldehido
Polvos de cadmio
ANTU
Cebadilla
Piretrinas
Arsenicales inorganicos
Organofosfatos
Insecticidas carbamicos
Bromuro de metilo
Fosfamina
Fosforo
Fosfuros
Oxido de etileno
Dibromuro de etileno
Acrolefna
Piretoides
Dioxido de azufre
Detergentes cationicos
Creosota
Isotiocianato de metilo
Cadmio
Paraquat
Polvos de cadmio
Bromuro de metilo
Organofosfatos
Insecticidas carbamicos
Nicotina
Paraquat
ANTU
Polvos de cadmio
Cianamida
Fluoruro de sulfurilo
Pentaclorofenol
Bromuro de metilo
Dioxido de azufre
Cloropicrina
OCURRE CON
ESTOS AGENTES
Formulaciones secas de
compuestos de cobre,
estano y zinc
Polvos de tiocarbamato y
otros pesticidas organicos
Compuestos clorofenoxi
Acidos alifaticos
Rotenona
Formulaciones secas de
compuestos de cobre,
estano y zinc
Polvos de tiocarbamato y
otros pesticidas organicos
Compuestos clorofenoxi
Acidos alifaticos
Rotenona
Organofosfatos
Insecticidas carbamicos
Paraquat
Fosfuros
Diquat
Nitrofenoles
Cianuro
Creosota
Piretrinas
PB
SENALES YSINTOMAS
-------
Tracto Gastrointestinal e Hfgado
MANIFESTACION
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
OCURRE CON
ESTOS AGENTES
Nausea, vomito,
comunmente
seguido por diarrea
Organofosfatos
Insecticidas carbamicos
Nicotina
Arsenicales
Fluoruro
Compuestos de cadmio
Compuestos organoestanicos
Compuestos de cobre
Clorato sodico
Borato
Cianuro
Compuestos clorofenoxi
Fosforo
Fosfuros
Fosfamina
Disulfuro de carbono
Cloropicrina
Fumigantes halocarbonos
Endotal
Metaldehido
Talio
Escila roja
Diquat
Naftaleno
Bromuro de metilo
Dibromocloropropano
Veratrum alcalino
Tiram
Pentaclorofenol
B.thuringiensis
Colecalciferol
Tiram
Dicloruro de etileno
Propano
Oxido de etileno
Cresol
Muchos pesticidas
tienen algunas
propiedades irritantes
Diarrea (inicial)
Organofosfatos
Carbamatos
Piretoides
Boratos
Azufre
Nicotina
B.thuringiensis
Tiram
Cadmio
Detergentes cationicos
Cresol
Hexaclorofeno
Compuestos clorofenoxi
Diarrea (sangrienta)
Fluoruro
Paraquat
Diquat
Talio
Cumarinas
Indandionas
Endotal
Arsenicales
Fosforo
Fosfuros
Cicloheximida
SENALES Y SiNTOMAS 241
-------
Tracto Gastrointestinal e Hfgado
MANIFESTACION
Dolor abdominal
Estomatitis
Salivacion
fleo
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Organofosfatos
Insecticidas carbamicos
Paraquat
Diquat
Nicotina
Metaldehido
Fluoruro
Borato
Fosforo
Fosfuros
Arsenicales inorganicos
Compuestos de cadmio
Compuestos de cobre
Talio
Compuestos organoestanicos
Arsenicales inorganicos
Paraquat
Diquat
Compuestos de cobre
Organofosfatos
Insecticidas carbamicos
Nicotina
Aminopiridina
Fluoruro de sodico
Cianuro
Compuestos de cadmio
Talio
Diquat
OCURRE CON
ESTOS AGENTES
Compuestos clorofenoxi
Acidos alifaticos
Clorato sodico
Creosota
Endotal
Aminopiridina
Cumarinas
Indandiona
Fumigantes (ingeridos)
Cicloheximida
Talio
Higado
MANIFESTACION
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
OCURRE CON
ESTOS AGENTES
Agrandamiento
Compuestos de cobre
Clorato sodico
Fosfamina
Tetracloruro de carbono
Cloroformo
Arsenicales inorganicos
Hexaclorobenceno
Ictericia
vease seccion bajo Piel
PB
SENALES YSINTOMAS
-------
Rihon
MANIFESTACION
Proteinuria
Hematuria
algunas veces conducente
a oliguria
Insuficiencia renal
aguda con azotemia
Disuria, hematuria, ?????
Piuria
Hemoglobinuria
Orina de color rojo-vino
(porfirinuria)
Orina turbia
Glicosuria
Cetonuria
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Arsenicales inorganicos
Compuestos de cobre
Fluoruro sodico
Naftaleno
Borato
Nitrofenoles
Pentaclorofenol
Clorato sodico
Fluoruro de sulfirilo
Paraquat
Diquat
Arsina
Dibromuro de etileno
Clordimeform
Colecalciferol
Naftaleno
Clorato sodico
Arsina
Hexaclorobenceno
Creosota
OCURRE CON
ESTOS AGENTES
Compuestos de cadmio
Fosforo
Fosfuros
Fosfamina
Compuestos clorofenoxi
Creosota
Compuestos organoestanicos
Fluoruro
Compuestos organoestanicos
Borato
Sistema Reproductivo
MANIFESTACION
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
OCURRE CON
ESTOS AGENTES
Conteo espermatico bajo
Dibromocloropropano
Kepona
SENALES Y SiNTOMAS 243
-------
Sangre
MANIFESTACION
Hemolisis
Metahemoglobinemia
Hipoprotrombinemia
Hiperkalemia
Hipocalcemia
Hipercalcemia
Carboxihemoglobinemia
Anemia
Leucopenia
Trombocitopenia
LDH elevado
GOT, GPT,
Fosfatasa alcalina,
Enzimas ALT, AST
RBC deprimido
Acetilcolinesterasa y plasma
pseudocolinesterasa
CARACTERlSTICO DE
ESTOS ENVENENAMIENTOS
Naftaleno
Clorato sodico
Arsina
Clorato sodico
Creosota
Cumarinas
Indandionas
Clorato sodico
Naftaleno
Arsina
Fluoruro
Colecalciferol
Naftaleno
Clorato sodico
Arsina
Arsenicales inorganicos
Arsenicales inorganicos
Tetracloruro de carbono
Cloroformo
Fosfamina
Organofosfatos
OCURRE CON
ESTOS AGENTES
Compuestos de cobre
Cresol
Clordimeformo
Cianuro
Cresol
Cobre
Arsina
Fosforo
Fosfuros
Tetraclouro de carbono
Fluoruro sodico
Talio
Fosforo
Fosfuros
Compuestos organoestanicos
Arsenicales inorganicos
Fosforo
Fosfuros
Fosfamina
Clorato sodico
Nitrofenoles
Pentaclorofenoles
Talio
Organocloros
Compuestos clorofenoxi
Insecticidas carbamicos
PB
SENALES YSINTOMAS
-------
Indice de Productos Pesticidas
Simbolos
1,2-dicloropropano 173
1,2-epoxiethano 174
1,3-dicloropropeno 173
2,3,6-TBA 133
2,4,5-acido acetico
triclorofenoxiacetico 107
2,4,5-T 106-107
2,4-acido
didorofenoxiacetico... 107, 111
2,4-acido diclorofenoxibutfrico . 107
2,4-acido
diclorofenoxipropionico... 107
2,4-D 106-107, 110, 111
2,4-DB 107
2,4-DP 107
2-bencyl-4-clorofenol 218
2-methyl-3, 6 acido
diclorobenzoico 107
4-Aminopiridina 203-204,216
4-tert-amilfenol 218
1081 195
1080 195
A
A7 Vapam
Aaterra
Aatrex
Abat
Abathion
Abol
Acaraben
Acaricidas
Acarstfn
Accelerate
Accotab
Accothion
acefato
155
168
135
41
41
56
85
84, 118
85
204
134
41
41
aceitede pino 5-6, 217-218,
226-227
Acetamidas 133
acetato de cobre 161
acetato de dinoseb 119
acetato de dinoterb 119
acetato defenilestano 165
acetato de fenilmercurio 218
acetato de metilmercurio 163
acetato metoxietilmercurio .... 163
acetoarsenito de cobre .. 141,148
acido 2,4,5 acetico
triclorofenoxiacetico 107
acido 2,4-
diclorofenoxiacetico . 107-111
acido 2,4-
diclorofenoxibutmco 107
acido 2,4-
diclorofenoxipropionico... 107
acido 2-methyl-3,6
diclorobenzoico 107
Acido borico 84-86, 102
acido cacodililico 141, 149
Acido cianhfdrico 173
Acido de calcio
metanoarsonico 141,150
acido dicloropropionico 133
Acido Giberelico 73-74
acido metano arsonico .. 141, 149
acido prussico 173
acido tricloroacetico 133
acido triclorobenzoico 133
acohol isopropflico 136
Acrex 119
Acricid 119
acrilonitrilo . 172-173, 177, 182-184
acroleina 172, 174
Actellic 73
Activol 73
Actor 123
adherentesy dispersantes . 204,214
Afalon 136
Aficida 56
Afugan 41
Agree 73
Agri-Micm 17 74
Agritox 41
Agrosan 163
Agrothion 41
Agtoxin 174
Akar 85
alaclor 133
Alanox 133
alcilo ftalatos 84-86
alcoholes 213-214,217,218
aldehidos 174, 177,218
aldicarb 56-57
aldrfn 63-65
aletrina 86, 100
alfos 174
Align 73
Allisan 153
Alon 136
Alphos 174
Altosid 86
Amaze 41
Ambox 119
Ambush 87
Amerol 135
Ametrex 135
ametrina 135
Amex 134
aminocarb 56
4-Aminopiridina 203-204, 216
aminotriazol 135
Amiral 168
amitrol 135
Ammo 86
Anilazina 168
Anilidas 133
Ansar 170 141, 149
Ansar8100 141, 149
Anthio 41
Anticarie 153
antiendurecedores, agentes.. 204,
214
antiendurecedores, rodenticidas .... 5,6
Antimilace 204
Apache 41
Apachlor 41
Apex 86
Aphox 56
Apl-Luster 168
aprocarb 57
Aquabac 73
Aquacide 123
Aquathol 135, 204
Aquinite 173
Arbotect 168
Arelon 136
Aresin 136
Aretit 119
Arrhenal 141, 149
Arsenal 134
arsenato de disodio 142,148
Arsenato de plomo 149
arsenato de plomo 149
arsenato de sodio 142, 148
arsenato de zinc 142, 149
arsenato tricalcico 141, 149
Arseniato de calcio 141, 148
Arsenico, acido 141, 148
Arsenico, trioxidode.. 141,143,148
Arsenito de calcio 141, 148
arsenito de cobre 141
arsenito de sodio 142, 148
arsenito monocalcico 141,148
arsina, gas.. 140-141,143,146-147
Arsinyl 141, 149
Arsonate, Liquid 142, 149
Aspon 41
Aspor 159
asulam 133
Asulox 133
Asuntol 41
Atranex 135
atrazina 135
Aules 155
Auton 85
Avicol 153
Avitrol 204
Azac 133
Azadiractin 72-73
Azar 133
Azatin 73
azinfos metflico 41
Azodrin 41
Azofene 41
Azolan 135
Azole 135
Aztec 41
B
Bad/us thuringiensis .
Bactimos
Bactospeine
Bactur
Balan
Balfin
Banvel
.... 73,82
73
73
73
134
134
107, 133
INDICE DE PRODUCTOS
PESTICIDAS
-------
Barricade
Barrier
bartrina
Basagran
Basalin
Basanite
Bash
Batasan
Baygon
Bayleton
Bayrusil
Baytex
Baythion
Baythroid
Belmark
86
133
86
133
134
119
41
165
57
168
41
41
41
86
87
Broot
Bueno 6
bufencarb ...
Busan 1020 .
butilato
57
... 142, 149
56
155
133
bencenos substituidos .... 152-155
2-bencyl-4-clorofenol 218
bendiocarb 56
Benefin 134
Benex 168
benfluralina 134
Benlate 168
benomilo 168
bensulide 41
bentason 133
Benzamida 133
Benzilan 85
benzoato de bencilo 85
Benzofuroline 87
Berelex 73
Betadine 218
Betasan 41
Bexton 133
Bidrin 41
Bilevon 218
binapacryl 119
bioallethrin 86
Biologicos 72
biopermetrina 86
bioresmetrina 86
Birlane 41
Black Leaf 40 73-74
Bladafum 41
Bladex 135
Bo-Ana 41
Bolate 141, 149
Bolero 133
Bolls-Eye 141, 149
Bollwhip 73
Bolstar 41
bomil 41
Bophy 141, 149
Borates 84-88
borax 85-86, 102
Bordeaux Mixture 161
Brace 41
Bravo 153
Brestan 165
Brodan 41
brodifacum 188-190,200
bromacilo 136
bromadiolona 188
Bromofos 41
bromofos-etil 41
Bromofume 173
Bromone 188
bromuro de metilo 172-173,
175-176, 178, 185
butoxido de piperonilo 77-79,
204,212
butralin 134
Bux 56
c
cacodilato de sodio 141, 149
Caddy 166
Cadminate 166
Cad-trete 166
cadusafos 41
Caid 188
Calar 141, 150
Caldon 119
Calibre 90 135
CAMA 141, 150
Caparol 135
Captaf 160
captafol 160
captan 161, 171
Captanex 160
CarbamateWDG 155
carbamatos 5, 13-14, 56-57,
61, 78, 133
Carbamult 57
Carbanilatos 134
carbarilo 56-57
carbofenotion 41
carbofuran 55-57
carbonate basico de cobre .... 161
carbonate de cobre y amonio ... 161
Carpene 168
Carzol 56
Casoron 133
Castrix 195
CCN52 86
cebadilla 72-74,80-81
Cekiuron 136
CekuC.B 153
Cekugib 73
Cekumeta 204
Cekuquat 123
Celathion 41
Celfume 173
Celmide 173
Ceresan 163
cetrimida 218-219, 228
Chem-Bam 159
Chem-Fish 73
Chemox General 119
Chemox PE 119
ChemsectDNBP 119
Chemsect DNOC 119
Chermox PE 119
ChipcoThiram 75 155
cianamida calcica 204
cianamida 204, 216
cianazina 135
cianofenfos 41
cianofos 41
cianuro de hidrogeno .... 172-174,
182-184
cicloato 87
cicloheximida 168-169
cihexatin 84-85,90-91
Ciodrin 41
cipermetrina 85, 99
cismetrina 86, 100
citioato 41
Classic 136
doetocarb 56
domazone 134
clorato de sodio 203-204,
210-212,216
dordano 63-65, 70
dordecona 63-65, 71
dordimeformo 84-85,88-89
dorethoxyfos 41
dorfenvinfos 41
dorfoxim 41
dorhexidina 218-221,228
clorido de metileno 173,177,185
dorimuron 136
dormefos 41
dorobencilato 64,84-85,
89-91, 102
dorofacinona 188,200
doroformo 172-173
Cloro-IPC 134
doroneb 152-153
Clorophen 113
doropicrina 172-173
doropirifos 6, 41-42
dorotalonil 152-153, 170
dorotoluron 136
Clorotosip 153
dorprofam 134
dortaldimetil 135
dorthiofos 41
Clorto Caffaro 153
Clortran 153
cloruro de benzalkonium ..218-219
cloruro de cadmio 166
cloruro de cetilpyridium .. 218-219
cloruro de fenilestano 165
cloruro de metoxietilmercurio ... 163
Cobex 134
colecalciferol 198-200
Comite 88
Command 134
Compound 1080 195
Compound 1081 195
compuestos de cadmio 153,
166-169
compuestos de cobre 153,
161-163
compuestos de
metilmercurio 163
compuestos de
metoxietilmercurio 163
compuestos EBDC 159
compuestos
inorganicos de cobre 161
compuestos
organicos de cobre 161
compuestos organoestanicos.. 92,
153, 165-166
compuestos organomercuricos 153,
163-165
Contrac 188
Contraven 41
PB
INDICE DE PRODUCTOS
PESTICIDAS
-------
convulsantes
Co-Ral
Co-Rax
cotonex
Cotoran
Counter
Crab-E-Rad
195
.. 41
136
136
41
141, 149
Crag Turf fungicide 166
creosota 203-207, 207
cresol 119,205, 218,224-225
crimidina 135
Crisazina 135
Crisfolatan 160
Crisfuran 56
Crisquat 123
Crisuron 136
Crotothane 119
crotoxifos 41
crufomato 41
Cryolite 86,93,96
Crysron 87
Cumafeno 188
Cumafos 41
Cuman 155
Cumarinas 187-191
Cumatetralilo 188
Curacron 41
Curamil 41
Curaterr 56
Curitan 168
Cyanox 41
Cybolt 87
Cyflee 41
cyflutrina 86
Cygon 41
Cylan 41
Cymbush 86
Cymperator 86
Cynoff 86
Cyolane 41
Cyperkill 86
Cypona 41
Cyrux 87
Cythion 41
Cytrolane 41
2,4-D 106-107, 110, 111
Dachthal 135
Daconate6 142, 149
Daconil 2787 153
Dailon 136
Dalapon 133
Dal-E-Rad 142, 149
Danitol 87
Dapacryl 120
Dart 85
Dasanit 41
2,4-DB 107
DBCP 30, 173
DCNA 153
DCPA 135
D-D92 173
DDT 63-66,89, 132
DDVP 41
Decis 87
DEET 91-93, 102
DEE 41
DeFend
Defol
De-Fol-Ate
Deftor
De-Green
Delnav
DeltaDust
DeltaGard
deltametrina
Deltex
demetona
41
204
204
136
41
41
87
87
... 87, 100
87
41
dimephenthoate...
dimetan
Dimethan
dimetil ftalato
demetona-S-metilo 41
Demon 87
Denarin 168
Dermaadex 218
Des-i-cate 204
Design 79
desinfectantes 5-6, 217-227
desmetryn 135
Dessin 119
destilados de petroleo .... 77, 213,
215
Detamide 85
detergentes cationicos 218-221
Dethdiet 198
Dextrona 123
Dexuron 123
Diacon 86
dialato 133
dialifor 41
Di-allate 133
Dianex 86
Diaract 85
diatomaceous earth 215
diazinon 41-42
Dibrom 41
dibromodoropropano.. 30,173, 179
dibromoetano 173
dibromuro de etileno 173-174,
179,185
dibutylftalato 84-85
dicamba 107, 133
Dicarbam 56
dichlorprop 107,111
diclobenilo 133
dicloran 152-153
dicloroetano 173
diclorofention 41-42
1,2-dicloropropano 173
1,3-dicloropropeno 173
dicloropropileno 173
dicloruro de etileno 173-174
diclorvos 41
dicofol 63-64
dicrotofos 41
Dicuran 136
dieldrina 63-65
Dieldrita 64
dienoclor 64
dietiltoluamida 84-85,91-93,103
difacin 188
difacinona 188
difenacoum 188
diflubenzuron 85, 97
Difolatan 160
Dilic 141, 149
Dimecron 41
dimefox 41
41
56
56
84-85
dimetoato 41, 43
dimetrina 87
Dimilin 85
dinitramina 134
Dinitro 119
Dinitro General Dynamyte 119
Dinitro Weed Killer 5 119
Dinitro-3 119
dinitrocresol 119
dinitrofenol 119-120
dinobuton 119
dinocap 118-119
Dinofen 119
dinopenton 119
dinoprop 119
dinosalfon 119
dinosam 119
dinoseb 119
dinoseb metilcrilato 119
dinoterbon 119
dioxacarb 56
dioxationa 41
Dioxido de benzotiadiazinona.... 133
dioxido de sulfuro 172, 174,177
Dipel 73
Dipher 159
Dipterex 41
diquat 11-12, 16, 122-131
Direx 136
Dirimal 134
disulfoton 41
disulfuro de carbono 46,
173-176, 177-181
Disyston 41
Di-Tac 141, 149
ditalimfos 41
Dithane 41
Dithione 41
Ditrac 188
Diurex 136
Diuron 136
diuron 136
DMA 141, 149
DMP 86
DNAP 119
DNBP 119
DNC 119
DNOC 119
dodina 168
Dojyopicrin 173
Dolochlor 173
Dosaflo 136
Dotan 41
2,4-DP 107
DPA 133
DPX1410 56
Dragnet 87
Drawinol 119
Draza 56
Drexar 530 142, 149
Drop-Leaf 204
DSE 159
DSMA 141, 149
D-trans 86
INDICE DE PRODUCTOS
PESTICIDAS
247
-------
Dual
Duraphos
Duratox
Dursban
dycarb
dyclomec
Dyfonate
Dylox
Dyrene
E
E 601
E-48
E605
Earthcide
Easy off-D
Ebufos
EDB
E-D-Bee
EDC
edifenfos
Ekamet
Ekatin
133
41
41
41
56
133
41
41
168
41
41
41
153
41
41
173
173
173
41
41
41
Famfos
famfur
Famid
Far-go
Febrek
fenamifos
fencapton
Fenclorfos
fenilfenol
fenilsalicilato
fenitrotion
Fenkill
fenofosfon
fenol(es) .. 5-6,46,57,
208 216
fenothrin
fenoxicarb
fenpropanate
Fenpropar
fenpropatrina
fensulfotion
fention
Fentoato
41
41
56
133
155
41
41
41
218
161
41
87
41
74,112,205,
218 224-226
87
56
87
88
87
41
41,43
41
Eksmin 87
Elecron 56
Elgetol30 119
Elgetol318 119
Elimite 87
Emisan 6 163
emulsificantes 204,214
Endosan 120
endosulfan 63-64
endotal 134, 138,204,
207-209,216
Endothall Turf Herbicide 204
endotiona 41
endrina 63-64
Entex 41
EPBP 41
EPN 41
1,2-epoxiethano 174
EPTC 133
Eradicano 133
escila roja 198
Esgram 123
estreptomicina 74,81-82
estricnina 187, 196-198, 201
etalfluralina 134
Ethanox 41
Ethazol 168
ethoprop 41
etil parationa 41, 43
etion 41
ETO 174
etridiazole 168-169
etrimfos 41
Etrofolan 56
Eugenol 73-74,81
Evik 135
Exofene 218
Exotherm Termil 153
E-ZOff D 41
F
Fac
Fall
Faltan ....
Famarin .
.. 41
204
160
fentoato 41
fenvalerato 87,98, 100, 102
ferbam 155, 158
FermideSSO 155
Fernasan 155
Fernos 56
Ficam 56
Electron 87
flucitrinato 87, 98
flucloralina 134
Fluent 87
fluoaluminato sodico ... 85, 93, 96
fluometuron 136
fluoroacetamida 187, 196
fluoroacetato sodico 195
fluorurodesulfurilo... 93, 172, 174,
177, 178, 186
fluoruro sodico 85, 93-94
fluoruros 84,93-96
fluosilicato sodico 85, 93-94
fluvalinato 87, 98-101
FMC9044 120
Folbex 85
Folcord 87
Folex 41
Folosan 153
Folpan 160
folpet 160
Foltaf 160
fonofos 41
Forato 98
forato 41,98-99
formaldehido 172, 174-175,
185,218
formotion 41
Formulaciones granuladas 213
Fortres 41
Fortrol 135
fosalona 41-42, 53
fosamina 134
fosfamidon 41
fosfamidon 41
fosfina... 172, 174, 177, 179-182,
193, 195,200
fosfolan 41
fosforo amarillo 191-195, 200
fosfurode zinc187, 191-195, 200
fosmet 41
fostietan 41
Foxim 41
Frunax-DS 188
ftaltrina 87
Fumex 174
fumigantes 172-186
fumigantes halocarbonos 172,
173, 176, 178
Fumitoxin 174
fungicidas 118, 152-171
Funginex 168
Fungitrol II 160
Furadan 56
furetrina 87
futura 73
G
G 28029 41
GA3 73-74
Gallotox 163
gammaBHCoHCH 64
Gamophen 218
Gardona 41
Gardoprim 135
Garlon 134
Gebutox 119
Gesafram 50 135
Gesagard 135
Gesapax 135
Gesatop 135
Gibberellin 73-74
Gibrel 73
Glicofen 168
glifosato 6
Glutaraldehido 6,217-218
Glyfonox 134
Glyphosate 134
gnatrol 73
Go-Go-San 134
Goldquat 123
Gramocil 123
Gramonol 123
Gramoxone 123
gramoxone 131
Gramuron 123
Granurex 136
Grocel 73
Gusathion 41
Guthion 41
Gypsine 141, 149
H
Haipen
Halizan
Hanane
Havoc
HCB
HCH
Hel-Fire
Helothion
Heptacloro
heptenofos
Herald
160
204
41
188
152-153
64
119
41
63-65
41
87
PB
INDICE DE PRODUCTOS
PESTICIDAS
-------
Herbi-AII 142, 149
herbicidas clorofenoxi 106-111
herbicidas nitrocresolicos 118-119
herbicidas nitrofenolicos 118-119,
132
herbicidas tiocarbamatos 133
Herbicide 273 204
Herbodox 134
hexacloran 64
hexacloro 64
hexaclorobenceno .... 63-64, 70, 116,
153-155, 170
hexadorofeno .. 218, 224-226, 228
Hexadrfn 64
Hexaferb 155
hexathane 159
Hexathir 155
Hexazir 155
Hibiclens 218,228
Hibistat 218
hidroxido de cobre 161
hidroxido de fenilestano
hiometon 41
hipoclorito calcico 218,221
hipoclorito sodico 6, 217, 228
Hipocloritos 218, 221
Hi-Yield Dessicant H-10.... 141, 148
Hoe002784 120
hosalone 41
Hostaquick 41
Hostathion 41
hydrocianic acid 173
hydrocloruro de formetanto .... 56
Hydrothol 204
Hyvar 136
I
IBP
imazapyr
Imidan
indandionas
41
134
41
187-191
insecticidas tiocarbamatos .... 152,
155-156
iodofenfos 41
loprep 218
IP50 136
iprodiona 168-169
isazofos 41
isofenfos 41
isolan 56
Isopestox 41
isoprocarb 56
isopropanol 204, 213, 217
isoproturon 136
isoxation 41
isoxazolidinona 134
Jones Ant Killer ............. 142, 148
K
Kabat
Kack
Kafil
KafilSuper
Karathane
Karbation
86
141, 149
87
87
119
155
Karmex
Kayafume
Keltano
Kepone
Kerb
Kiloseb
Kitazin
Klerat
Knockmate
Koban
Kobu
Kobutol
Kopfume
Korlan
Krenite
Kromad
Kryocide
Kusatol
Kwell
Kypfarin
Kypman 80
Kypsin
L
Lance
Landrin
Lannate
Lanox
Larvacide
Larvin
Lazo
Leafex
lenacilo
leptofos
Lescosan
Lexone
136
173
64
64,71
133
119
41
188
155
168
153
153
173
41
134
166
86
204
63-64, 70-71
188
159
159
56
57
56
56
173
57
133
204
136
41
41
135
MCPA
MCPB
MCPP
M-Diphar
MeBr
107, 111
107
107
159
173
Karfos 41
lindano 63-66,70-71, 153
Linex 136
linoleato de cobre 161
Linorox 136
Linurex 136
linuron 136
Liphadione 188
Liqua-Tox 188
Londres purpura 141, 148
Lorox 136
Lorsban 41
Lysol 206,218,228
M
MAA 141, 149
Magnacide B 174
Magnacide H 174
Maki 188
malation 41, 43, 53
MAMA 141, 149
mancozeb 159
Mancozin 159
maneb 159, 171
Maneba 159
Manex 159
ManexSO 159
manzeb 159
Manzin 159
Maposol 155
Marlate 63-64
Matacil 56
Mattch 73
mecoprop 107, 110, 111
mefosfolan 41
Melprex 168
MEMA 163
MEMC 163
Meotrin 87
Mercuram 1 55
mercuriales 165-165, 218
mercurobutol 218
mercurocromo 218
merfos 41
Merge 823 142, 149
Merpafol 160
Merpan 160
Mertect 168
mertiolato 218
Mesamate 142, 149
Mesurol 56
Metadelphene 85
Metalaxil 168-169
metaldehido... 204,209-210,216
metalkamate 56
Metam-Fluid BASF 155
metamidofos 41
metam-sodio 155-156
metanoarsonato
disodico 141, 149
metanoarsonato
monoamonico 141,149
metanoarsonato
monosodico 141, 149
metanol 204,213,217
Metaran 85
Metason 204
Metasystoxl 41
Metasystox-R 41
Metasystox-S 41
methabenzthiazuron 136
Methar30 141, 149
Meth-0-Gas 173
methoxicloro 64
metidation 41
metil trition 41
metilnaftalenos 215
metobromuron 136
metolaclor 133
metomil 56
metopreno 84, 86, 97-98
metoxuron 136
metribuzina 135
mevinfos 41
mexacarbato 56
Mezene 155
MGK 85
Micromite 85
Microzul 188
Mightikill 88
Miller 531 166
Milo-Pro 135
Minex 86
mipafox 41
MIPC 56
Miral 41
INDICE DE PRODUCTOS
PESTICIDAS
249
-------
Mirex 63-65
Mocap 41
Monitor 41
monocrotofos 41
monolinuron 123, 136
monuron 136
Morrocid 120
MSMA 141, 149
Multamat 56
Muritan 198
Muskol 85
Mycodifol 160
N
N-2790 41
nabam 159
Naftaleno 75, 172-176, 178,
181,182, 185
naftenato 161
naled 41
Namekil 204
naramicin 168
n-carbamato de metilo 55-58,
61, 155,212
Neburex 136
neburon 136
Neemazad 73
Neemazal 73
Neemix 73
Neguvon 41
Nemacur 41
Nemafume 173
Nemanax 173
Nemaset 173
Nemasol 155
Nem-A-Tak 41
Nemispor 159
Neopynamin 88
Nephis 173
Nexagan 41
Nexion 41
NIA9044 120
Nico Soap 73
nicotina 72-77,82-83
Niomil 56
Nitrador 119
nitrato de fenilmercurio 218
nitrolime 204
nitromesol 218
Nitropone C 119
Nix 87
No Bunt 153
Nomersan 155
Nomolt 85
Novodor 73
Noxfire 73
Noxfish 73
NRDC 149 87
Nudrin 56
Nusyn-Foxfish 73
Nuvanol-N 41
o
Off
Oftanol
Ofunack
oleato
Omite
OMPA
o-phenylphenol
organocloros
organofosfatos
Ornamite
Orthene
Ortho Diquat
Orthocida
oryzalina
Oust
Outflank
Oxadiazolinona
Oxadiazo-linona
oxamil
oxiclorido de cobre
oxidemeton-metil ...
oxideprofos
oxido cuprico
oxido cuproso
oxido de etileno
oxirane
Oxotin
P
Panogen
Panogen M
Pansoil
Para-col
41
218
... 5, 14,63-69
5-6, 13-14,
40-54, 55, 78
88
41
123
160
134
136
87
134
134
56
161
41
41
161
161
172, 174
174
85
163
163
168
123
Pharorid
Phenostat-A ....
Phosdrin
phostebupirim .
Phostoxin
phostoxin
Phosvel
Phosvin
165
41
41
174
177
41
191
paradidorobenceno .. 173, 176-178
paraformaldehido 172, 174
paraquat 11-12, 16, 122-131
Parathion 41, 53
paration metilico 41-44, 53
Paris verde 141, 148, 161
Parzate 159
ParzateC 159
Pathclear 123
Pattonex 136
Paushamycin, Tech 74
Payoff 87
PCNB 152-153
PCP 112-117
PEBC 133
pebulato 133
Penchlorol 113
pendimetalina 134
penetrantes 132, 204, 214
Pennant 133
Penncap-M 41
Penncozeb 159
Pennstyl 85
Penta 113
Pentac 64
Pentaclorofenol 112-117, 154
Pentacloronitrobenceno .... 152-153
Pentacon 113
Pentagen 153
Penwar 113
Peridex 218
Permasect 87
permetrina 87,98-100
Perthrine 87
pesticidas arsenicales 140, 161
PestoxXIV 41
PestoxXV 41
Phaltan 160
Pharmadine 218
Phytar560 141, 149
Pic-Color 173
picloran 135
pindona 188
pinene 226
Pinene 135
Pirazofos 41
piretrinas 5-6, 77-79, 98, 212
piretroides 5-6, 77-79, 84,
86,98-101
piridafention 41
pirimicarb 56
pirimifos-etil 41
pirimifos-metil 41
Pirimor 56
pirofosfato de tetraetilo 41
pival 188
pivaldiona 188
pivalyn 188
Plantomicin 74
Plictran 85
PMAA 163
Poast 134
poliborato sodico 85
polvo de cobre y cal 161
polvos 21,75,79, 102, 153,
155, 160, 163,204,214
Polybor 3 85
Polyram-Ultra 155
Polytrin 87
Pomarsol Forte 155
Pounce 87
povidone iodine .... 218, 222-224,
228
Pramex 87
Pramitol 25E 135
Prebane 135
Precor 86
Preeglone 123
Preglone 123
Premerge 3 119
Prenfish 73
Primatol 135
Primatol M 135
Primicid 41
Primin 56
Princep 135
Proban 41
Prodalumnol Doble 142,148
Prodan 86
profenofos 41
profluralina 134
Pro-Gibb 73
Pro-Gibb Plus 73
Prokil 86
Prolate 41
Prolex 133
promecarb 57
prometon 135
Prometrex 135
PB
INDICE DE PRODUCTOS
PESTICIDAS
-------
prometrina
pronamida
propador
Propanex
propanilo
propargita
propazma
propetamfos
propiltiopirofosfato.
propionato
propoxur
protoato
Prowl
Proxol
Prozinex
Purivel
Pynamin
Pynosect
pyrethrum
Q
Quickfos
Quilan
quinalfos
quinolinolato
quintoceno
Quintox
R
Rabon
Racumin
Rad-E-Cate25
Ramik
Rampage
Rampart
Ramrod
Ramucide
Rapid
Rapier
Ratak
Ratak Plus
Ratomet
Raviac
RAX
Reglone
Regulex
repelentes
resinato
resmetrina
Revenge
Ridall-Zinc
Ridomil
Ripcord
Riselect
rodenticidas
Rodine
Rody
Ro-Neet
ronnel
Ronstar
Rotacide
rotenona
Rotenone solution Fl
Roundup
Rovral
Rozol
Ruelene
Rugby
135
133
133
133
133
6,84,98
135
41
41
163
57
41
134
41
135
136
86
87
77-78,82
174
134
41
161, 163
153
198
41
188
141, 149
188
198
41
133
188
56
133
188
188
188
188
188
123
73
5,84, 103
161
87
133
191
168
87
133
. 5-6, 187-201
198
87
41
134
134
74
73, 79-80
<-11 74
134
168
188
41
41
s
safeners
Safrotin
Safsan
SAGA
sales de dinoterb
Salvo
Sanifume
Sanspor
Saprol
Sarclex
Saturn
schradan
Selinon
Semeron
Sencor
Sencoral
Sencorex
sethoxydim
Setrete
Sevin
Shaphos
Shimmer-ex
siduron
silicate de cobre
silicofluoruro sodico
simazina
Sinbar
sinergicos 78,
Sinituho
Sinox
Siperin
Skeetal
Skeeter Beater
Skeeter Cheater
Skintastic for Kids
Snox General
Sobrom98
Sodanit
Sodar
Sok-Bt
Solasan 500
solventes y adjuvantes ...
Sometam
Sonalan
Soprabel
Sopranebe
Spike
Spotrete WP75
Spotrete-F
Spra-cal
Spring Bak
Sprout-Nip
S- Seven
Stam
Stampede
Stomp
Strobane
Subdue
Subitex
succinato de cadmio . . 1 53
Sulerex
sulfato de cadmio
sulfatode cobre 161-
sulfato de talio
sulfometuron-metilo
sulfotep
sulfuro 6,80,84,85
204,217
41
86
88
120
141, 149
174
160
168
136
133
41
119
135
135
135
135
134
163
56
174
163
136
161
... 85,93
123, 135
136
204,212
113
119
87
73
85
85
85
119
173
142, 148
141, 149
73
155
203,213
155
134
141, 149
159
136
155
155
141, 149
159
134
41
133
133
134
64
168
119
,166-169
136
166
162, 171
191-194
136
41
, 101-103
sulfuro de cobre y potasio
sulprofos
Sumicidin
Sumithion
Super Crab-E-Rad-Calar ...
Super Dal-E-Rad
Super Tin
Supracide
Surecide
Surf Ian
Surgi-Cen
Surofene
Suspend
Sutan
Suzu
Suzu-H
Swat
Sypren-Fish
systox
T
2,4,5-T
Tag HL331
Talan
Talcord
Talon
Tamex
Target MSMA
Tattoo
2,3,6-TBA
TCA
TCBA
Tebusan
tebutiuron
Tecto
teflubenzuron
Teknar
Telone II Soil Fumigant ....
temefos
Temik
TEPP
terabacilo
terbucarb
terbufos
terbutilazina
Terbutrex
Ternit
terpenos policlorados
Terraklene
Terraneb SP
Terrazol
Tersan 1991
4-tert-amilfenol
tertutryn
tetraborato de sodio
decahidratado
tetracloruro de carbono ..
tetraclorvinfos
tetraethyl pyrof osf ato
tetrametrina
Tetrapom
Texosan
Thibenzole
Thimer
thimerosol
Thimet
thiodicarb
161
41
87
41
141, 150
141, 150
165
41
41
134
218
218
87
133
165
165
41
74
41
106-107
163
119
87
188
134
142, 149
56
133
133
133
136
136
168
... 85,97
73
173
41
56
41
136
133
41
135
135
135
64
123
153
168
168
218
135
85
173-174,
181, 185
41
41
88
155
218
168-169
155
218
41
133
INDICE DE PRODUCTOS
PESTICIDAS
251
-------
Thioknock 155
Thiophal 160
thiophos 41
Thiotepp 41
Thiotex 155
Thiramad 155
Thirasan 155
Thiuramin 155
Thuricide 73
thymol 218,224
tiabendazol 168, 169
Tiguvon 41
Tillam 133
Tinmate 165
tiobencarb 133
tioftalimidas 153, 160-161
Tiram 157-158
Tirampa 155
TMTD 155
Tolban 134
Tolkan 136
toluene 204, 213
Tolurex 136
Tomcat 188
Topitox 188
Torak 41
Tordon 135
Torus 56
Tota-col 123
toxafeno 63-65
Tox-Hid 188
TPTA 165
Tralex 88
tralometrina 88
Trametan 155
Trans-Vert 142, 149
Treflan 134
triadimefon 168-170
trialato 133
triazinas 135
triazofos 41
Triazoles 135
Tribac 133
Tribactur 73
Tribunil 136
Tricarbamix 155
triclopyr 134
triclorofon 41
triclorometano 173
tricloronato 41
triclosan 218, 224
trifenil estano
trifluralina 134
Trifocide 119
Triforine 168
triforine 168, 170
Trifungol 155
Trimangol 155
Trimanton 155
trimetacarb 57
Tri-PCNB 153
Tripomol 155
Triscabol 155
Trithion 41
Tritoftorol 159
Triumph 41
Truban 168
Tuads 155
Tubotin...
Tuffcide ...
Tupersan
Turcam ...
165
153
136
56
Turf-Cal 141, 149
Turflon 134
Turplex 73
u
Ultracide
Unicrop DNBP
Unidron
Unisan
uracilos
.. 41
119
136
163
136
ureas haloaromaticas substituidas
96
Ustadd 87
V
Vancide MZ-96 155
Vapam 155
Vapona 41
VC-13 Nemacide 41
Vectobac 73
Vectocide 73
Venturol 168
Venzar 136
Veratrum alcaloide 80
Verde esmeralda 141, 148
Verde Frances 141, 148
verde mitis 141, 148
verde Paris 141, 148, 161
Verde Schweinfurt 141, 148
Vernam 133
vernolato 133
Vertac 119
Vertac General Weed Killer.... 119
Vertac Selective Weed Killer... 119
Vigilante 85
Vikane 74
Volid 188
Vondcaptan 160
Vonduron 136
VPM 155
VydateL 56
w
Wafarina
Wax Up
Weedazol
Weed-E-Rad .
.... 187-188,200
134
135
142,149
Weed-E-Rad 360 141, 149
Weed-Hoe 142, 149
Weedol 123
X
Xen Tari.
xylene ...
73
204,213
Y
Yodo 218
Yodo-providon 218,222-224,228
z
Zebtox
Zectran
Ziberk
Ziman-Dithane
159
.. 56
155
159
Zincmate
Zinc-Tox
zineb
ziram
Ziram F4
Ziram Technical
Zirex 90
Ziride
Zitox
Zolone
zoocoumarina
Zotox
155
191
159 171
155 158
155
155
155
155
155
41
188
141, 148
PB
INDICE DE PRODUCTOS
PESTICIDAS
-------
CDC
MORBIDITY AND MORTALITY
WEEKLY REPORT
April 21, 2000/Vol. 49 / No. RR-4
Recommendations
and
Reports
Biological and Chemical Terrorism
Strategic Plan for Preparedness
and Response
Recommendations of the CDC Strategic
Planning Workgroup
U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES
Centers for Disease Control and Prevention (CDC)
Atlanta, GA 30333
-------
The MMWR series of publications is published by the Epidemiology Program Office,
Centers for Disease Control and Prevention (CDC), U.S. Department of Health and
Human Services, Atlanta, GA 30333.
SUGGESTED CFTATION
Centers for Disease Control and Prevention. Biological and Chemical Terrorism:
Strategic Plan for Preparedness and Response. Recommendations of the CDC
Strategic Planning Workgroup. MMWR 2000;49(No. RR-4):[inclusive page numbers].
Centers for Disease Control and Prevention Jeffrey P. Koplan, M.D., M.P.H.
Director
The material in this report was prepared for publication by
Agency for Toxic Substances and Disease Registry Jeffrey P. Koplan, M.D., M.P.H.
Administrator
Epidemiology Program Office Barbara R. Holloway, M.P.H.
Acting Director
National Centerfor Environmental Health Richard J. Jackson, M.D., M.P.H.
Director
National Centerfor Infectious Diseases James M. Hughes, M.D.
Director
National Institute for Occupational Safety and Health .... Linda Rosenstock, M.D., M.P.H.
Director
Public Health Practice Program Office Edward L. Baker, M.D.
Director
The production of this report as an MMI/l//?serial publication was coordinated in
Epidemiology Program Office Barbara R. Holloway, M.P.H.
Acting Director
Office of Scientific and Health Communications John W. Ward, M.D.
Director
Editor, MMWR Series
Recommendations and Reports Suzanne M. Hewitt, M.P.A.
Managing Editor
C.Kay Smith-Akin, M.Ed.
Project Editor
Martha F. Boyd
Visual Information Specialist
-------
Vol. 49 / No. RR-4 MMWR i
Contents
Introduction 1
U.S. Vulnerability to Biological and Chemical Terrorism 2
0vert Versus CovertTerorist Attacks 3
Focusing Preparedness Activities 4
Key Focus Areas 8
Preparedness and Prevention 8
Detection and Surveillance 9
Diagnosis and Characterization of Biological and Chemical Agents 9
Response 9
Communication Systems 11
Partnerships and Implementation 11
Recommendations 13
Conclusion 13
References 14
Use oftrade names and commercial sources is for identification onlyand does not
imply endorsement by the U.S. Department of Health and Human Services.
Copies can be purchased from Superintendent of Documents, U.S. Government
Printing Office, Washington, DC 20402-9325. Telephone: (202) 512-1800.
References to non-CDC sites on the Internet are provided as a service to MMWR
readers and do not constitute or imply endorsement of these organizations or their
programs by CDC orthe U.S. Department of Health and Human Services. CDC is
not responsible for the content of pages found at these sites.
-------
MMWR April 21, 2000
The following CDC staff members prepared this report:
Ali S. Khan, M.D.
Alexandra M. Levitt, M.A., Ph.D.
National Center for Infectious Diseases
Michael J. Sage, M.P.H.
National Center for Environment Health
in collaboration with the CDC Strategic Planning Workgroup
Samuel L. Groseclose, D.V.M., M.P.H.
Epidemiology Program Office
Edwin Kent Gray
Elaine W. Gunter
Alison B. Johnson, M.P.A.
Anne L. Wilson, M.S.
National Center forEnvironmental Health
David A. Ashford, D.V.M., M.P.H., D.Sc.
Robert B. Craven, M.D.
Robert P. Gaynes, M.D.
Stephen A. Morse, Ph.D.
Clarence J. Peters, M.D.
Richard A. Spiegel, D.V.M., M.P.H.
David L. Swerdlow, M.D.
National Center for Infectious Diseases
Scott D. Deitchman, M.D., M.P.H.
National Institute for Occupational Safety and Health
Paul K. Halverson, Dr.P.H., M.H.S.A.
Public Health Practice Program Office
Joseph Hughart, M.P.H.
Agency for Toxic Substances and Disease Registry
Patricia Quinlisk, M.D.
Iowa Department of Health
Des Moines, Iowa
-------
Vol. 49 / No. RR-4 MMWR
Biological and Chemical Terrorism:
Strategic Plan for Preparedness and Response
Recommendations of the CDC Strategic Planning Workgroup
". ..and he that will not apply new remedies must expect new evils; for time is the
greatest innovator...."
-The Essays by Sir Francis Bacon, 1601
Summary
The U.S. national civilian vulnerability to the deliberate use of biological and
chemical agents has been highlighted by recognition of substantial biological
weapons development programs and arsenals in foreign countries, attempts to
acquire or possess biological agents by militants, and high-profile terrorist
attacks. Evaluation of this vulnerability has focused on the role public health will
have detecting and managing the probable covert biological terrorist incident with
the realization that the U.S. local, state, and federal infrastructure is already
strained as a result of other important public health problems. In partnership with
representatives for local and state health departments, other federal agencies,
and medical and public health professional associations, CDC has developed a
strategic plan to address the deliberate dissemination of biological or chemical
agents. The plan contains recommendations to reduce U.S. vulnerability to
biological and chemical terrorism preparedness planning, detection and
surveillance, laboratory analysis, emergency response, and communication
systems. Training and research are integral components for achieving these
recommendations. Success of the plan hinges on strengthening the relationships
between medical and public health professionals and on building new partner-
ships with emergency management, the military, and law enforcement professionals.
INTRODUCTION
An act of biological or chemical terrorism might range from dissemination of aero-
solized anthrax spores to food product contamination, and predicting when and how such
an attack might occur is not possible. However, the possibility of biological or chemical
terrorism should not be ignored, especially in light of events during the past 10 years
(e.g., the sarin gas attack in the Tokyo subway [7] and the discovery of military
bioweapons programs in Iraq and the former Soviet Union [2 ]). Preparing the nation to
address this threat is a formidable challenge, but the consequences of being unprepared
could be devastating.
The public health infrastructure must be prepared to prevent illness and injury that
would result from biological and chemical terrorism, especially a covert terrorist attack.
As with emerging infectious diseases, early detection and control of biological or chemi-
cal attacks depends on a strong and flexible public health system at the local, state, and
federal levels. In addition, primary health-care providers throughout the United States
must be vigilant because they will probably be the first to observe and report unusual
illnesses or injuries.
-------
2 MMWR April 21,2000
This report is a summary of the recommendations made by CDC's Strategic Planning
Workgroup in Preparedness and Response to Biological and Chemical Terrorism: A Stra-
tegic Plan (CDC, unpublished report, 2000), which outlines steps for strengthening public
health and health-care capacityto protectthe United States againstthese dangers. This
strategic plan marks the first time that CDC has joined with law enforcement, intelligence,
and defense agencies in additiontotraditional CDC partnersto address a national secu-
rity threat.
As a reflection of the need for broad-based public health involvement in terrorism
preparedness and planning, staff from CDC's centers, institute, and offices participated in
developing the strategic plan, including the
National Center for Infectious Diseases,
National Center for Environmental Health,
Public Health Practice Program Office,
Epidemiology Program Office,
National Institute for Occupational Safety and Health,
Office of Health and Safety,
National Immunization Program, and
National Center for Injury Prevention and Control.
The Agency for Toxic Substances and Disease Registry (ATSDR) is also participating with
CDC in this effort and will provide expertise in the area of industrial chemical terrorism.
In this report, the term CDC includes ATSDR when activities related to chemical terror-
ism are discussed. In addition, colleagues from local, state, and federal agencies; emer-
gency medical services (EMS); professional societies; universities and medical centers;
and private industry provided suggestions and constructive criticism.
Combating biological and chemical terrorism will require capitalizing on advances in
technology, information systems, and medical sciences. Preparedness will also require a
re-examination of core public health activities (e.g., disease surveillance) in light of these
advances. Preparedness efforts by public health agencies and primary health-care pro-
viders to detect and respond to biological and chemical terrorism will have the added
benefit of strengthening the U.S. capacity for identifying and controlling injuries and
emerging infectious diseases.
U.S. VULNERABILITY TO BIOLOGICAL
AND CHEMICAL TERRORISM
Terrorist incidents in the United States and elsewhere involving bacterial pathogens
(3), nerve gas (7), and a lethal plant toxin (i.e., ricin) (4), have demonstrated that the
United States is vulnerable to biological and chemical threats as well as explosives.
Recipes for preparing "homemade" agents are readily available (5), and reports of
arsenals of military bioweapons (2) raise the possibility that terrorists might have ac-
cess to highly dangerous agents, which have been engineered for mass dissemination as
small-particle aerosols. Such agents as the variola virus, the causative agent of small-
pox, are highly contagious and often fatal. Responding to large-scale outbreaks caused
-------
Vol. 49 / No. RR-4 MMWR 3
by these agents will require the rapid mobilization of public health workers, emergency
responders, and private health-care providers. Large-scale outbreaks will also require
rapid procurement and distribution of large quantities of drugs and vaccines, which must
be available quickly.
OVERT VERSUS COVERT TERRORIST ATTACKS
In the past, most planning for emergency response to terrorism has been concerned
with overt attacks (e.g., bombings). Chemical terrorism acts are likely to be overt be-
cause the effects of chemical agents absorbed through inhalation or by absorption
through the skin or mucous membranes are usually immediate and obvious. Such at-
tacks elicit immediate response from police, fire, and EMS personnel.
In contrast, attacks with biological agents are more likely to be covert. They present
different challenges and require an additional dimension of emergency planning that
involves the public health infrastructure (Box 1). Covert dissemination of a biological
agent in a public place will not have an immediate impact because of the delay between
exposure and onset of illness (i.e., the incubation period). Consequently, the first casual-
ties of a covert attack probably will be identified by physicians or other primary health-
care providers. For example, in the event of a covert release of the contagious variola
virus, patients will appear in doctors' offices, clinics, and emergency rooms during the
first or second week, complaining of fever, back pain, headache, nausea, and other symp-
toms of what initially might appear to be an ordinary viral infection. As the disease
progresses, these persons will develop the papular rash characteristic of early-stage
smallpox, a rash that physicians might not recognize immediately. By the time the rash
becomes pustular and patients begin to die, the terrorists would be far away and the
disease disseminated through the population by person-to-person contact. Only a short
window of opportunity will exist between the time the first cases are identified and a
second wave of the population becomes ill. During that brief period, public health officials
will need to determine that an attack has occurred, identify the organism, and prevent
more casualties through prevention strategies (e.g., mass vaccination or prophylactic
treatment). As person-to-person contact continues, successive waves of transmission
could carry infection to other worldwide localities. These issues might also be relevant
for other person-to-person transmissible etiologic agents (e.g., plague or certain viral
hemorrhagic fevers).
BOX 1. Local public health agency preparedness
Because the initial detection of a covert biological or chemical attack will probably
occur at the local level, disease surveillance systems at state and local health
agencies must be capable of detecting unusual patterns of disease or injury,
includingthose caused byunusual or unknown threat agents.
Because the initial response to a covert biological or chemical attack will probably
be madeatthe local level, epidemiologists at state and local health agencies must
have expertise and resources for responding to reports of clusters of rare, unusual,
or unexplained illnesses.
Certain chemical agents can also be delivered covertly through contaminated food or
water. In 1999, the vulnerability of the food supply was illustrated in Belgium, when
-------
4 MMWR April 21,2000
chickens were unintentionally exposed to dioxin-contaminated fat used to make animal
feed (6). Because the contamination was not discovered for months, the dioxin, a
cancer-causing chemical that does not cause immediate symptoms in humans, was
probably present in chicken meat and eggs sold in Europe during early 1999. This
incident underscores the need for prompt diagnoses of unusual or suspicious health
problems in animals as well as humans, a lesson that was also demonstrated by the
recent outbreak of mosquitoborne West Nile virus in birds and humans in New York City
in 1999. The dioxin episode also demonstrates how a covert act of foodborne biological
or chemical terrorism could affect commerce and human or animal health.
FOCUSING PREPAREDNESS ACTIVITIES
Early detection of and response to biological or chemical terrorism are crucial. With-
out special preparation at the local and state levels, a large-scale attack with variola
virus, aerosolized anthrax spores, a nerve gas, or a foodborne biological or chemical
agent could overwhelm the local and perhaps national public health infrastructure.
Large numbers of patients, including both infected persons and the "worried well,"
would seek medical attention, with a corresponding need for medical supplies, diagnos-
tic tests, and hospital beds. Emergency responders, health-care workers, and public
health officials could be at special risk, and everyday life would be disrupted as a result
of widespread fear of contagion.
Preparedness for terrorist-caused outbreaks and injuries is an essential component
of the U.S. public health surveillance and response system, which is designed to protect
the population against any unusual public health event (e.g., influenza pandemics, con-
taminated municipal water supplies, or intentional dissemination of Yersinia pestis, the
causative agent of plague [7]). The epidemiologic skills, surveillance methods, diagnos-
tic techniques, and physical resources required to detect and investigate unusual or
unknown diseases, as well as syndromes or injuries caused by chemical accidents, are
similarto those needed to identify and respond to an attack with a biological or chemical
agent. However, public health agencies must prepare also for the special features a
terrorist attack probably would have (e.g., mass casualties or the use of rare agents)
(Boxes 2-5). Terrorists might use combinations of these agents, attack in more than one
location simultaneously, use new agents, or use organisms that are not on the critical
list (e.g., common, drug-resistant, or genetically engineered pathogens). Lists of critical
biological and chemical agents will need to be modified as new information becomes
available. In addition, each state and locality will need to adapt the lists to local condi-
tions and preparedness needs by using the criteria provided in CDC's strategic plan.
Potential biological and chemical agents are numerous, and the public health infra-
structure must be equipped to quickly resolve crises that would arise from a biological
or chemical attack. However, to best protect the public, the preparedness efforts must
be focused on agents that might have the greatest impact on U.S. health and security,
especially agents that are highly contagious or that can be engineered for widespread
dissemination via small-particle aerosols. Preparing the nation to address these dan-
gers is a majorchallengeto U.S. public health systems and health-care providers. Early
detection requires increased biological and chemical terrorism awareness among front-
line health-care providers because they are in the best position to report suspicious
illnesses and injuries. Also, early detection will require improved communication sys-
tems between those providers and public health officials. In addition, state and local
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Vol. 49 / No. RR-4 MMWR 5
health-care agencies must have enhanced capacity to investigate unusual events and
unexplained illnesses, and diagnostic laboratories must be equipped to identify biologi-
cal and chemical agents that rarely are seen in the United States. Fundamental to these
efforts is comprehensive, integrated training designed to ensure core competency in
public health preparedness and the highest levels of scientific expertise among local,
state, and federal partners.
BOX 2. Preparing public health agencies for biological attacks
Steps in Preparing for Biological Attacks
Enhance epidemiologic capacity to detect and respond to biological attacks.
Supply diagnostic reagentsto state and local public health agencies.
Establish communication programsto ensure delivery of accurate information.
Enhance bioterrorism-related education and training for health-care professionals.
Prepare educational materialsthat will inform and reassure the publicduring and
after a biological attack.
Stockpile appropriate vaccines and drugs.
Establish molecular surveillance for microbial strains, including unusual or drug-
resistant strains.
Supportthe development of diagnostictests.
Encourage research on antiviral drugs and vaccines.
BOX 3. Critical biological agents
Category A
The U.S. public health system and primary health-care providers must be
prepared to address varied biological agents, including pathogens that are rarely
seen in the United States. High-priority agents include organisms that pose a risk
to national security because they
can be easily disseminated ortransmitted person-to-person;
cause high mortality, with potential for major public health impact;
might cause public panic and social disruption; and
require special action for public health preparedness (Box 2).
Category A agents include
variola major (smallpox);
Bacillus anthracis (anthrax);
Yersin ia pestis (p I a g u e);
Clostridium botulinumtox\n (botulism);
Francisella tularensis (tularaemia);
filoviruses,
Ebola hemorrhagic fever,
Marburg hemorrhagic fever; and
arenaviruses,
Lassa (Lassa fever),
Junin (Argentine hemorrhagic fever) and related viruses.
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6 MMWR April 21,2000
BOX 3. (Continued) Critical biological agents
Category B
Second highest priority agents include those that
are moderately easy to disseminate;
cause moderate morbidity and low mortality; and
require specific enhancements of CDC's diagnostic capacity and enhanced
disease surveillance.
Category B agents include
Coxiella burnetti (Q fever);
6ruce//aspecies (brucellosis);
Burkholderia mallei (glanders);
alphaviruses,
Venezuelan encephalomyelitis,
eastern and western equine encephalomyelitis;
ricin toxin from Ricinus communis (castor beans);
epsilon toxin of Clostridiumperfringens; and
Stepfty/ococcusenterotoxin B.
A subset of List B agents includes pathogens that are food- or waterborne.
These pathogens include but are not limited to
Salmonella species,
Shigella dysenteriae,
Escherichia coli 0157:H7,
Vibrio cholerae, and
Cryptosporidium parvum.
Category C
Third highest priority agents include emerging pathogens that could be
engineered for mass dissemination in the future because of
availability;
ease of production and dissemination; and
potential for high morbidity and mortalityand major health impact.
Category C agents include
Nipah virus,
hantaviruses,
tickborne hemorrhagic fever viruses,
tickborne encephalitis viruses,
yellow fever, and
multidrug-resistant tuberculosis.
Preparedness for List C agents requires ongoing research to improve disease
detection, diagnosis,treatment, and prevention. Knowing in advance which newly
emergent pathogens might be employed by terrorists is not possible; therefore,
linking bioterrorism preparedness efforts with ongoing disease surveillance and
outbreak response activities as defined in CDC's emerging infectious disease
strategy is imperative.*
*CDC. Preventing emerging infectious diseases: a strategy for the 21st century. Atlanta,
Georgia: U.S. Department of Health and Human Services, 1998.
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Vol. 49 / No. RR-4 MMWR
BOX 4. Preparing public health agencies for chemical attacks
Steps in Preparing for Chemical Attacks
Enhance epidemiologic capacity for detecting and responding to chemical
attacks.
Enhance awareness of chemical terrorism among emergency medical service
personnel, police officers, firefighters, physicians, and nurses.
Stockpile chemical antidotes.
Develop and provide bioassaysfor detection and diagnosis of chemical injuries.
Prepare educational materials to inform the public during and after a chemical
attack
BOX 5. Chemical agents
Chemical agents that might be used by terrorists range from warfare agents to
toxic chemicals commonly used in industry. Criteria for determining priority
chemical agents include
chemical agents already known to be used as weaponry;
availability of chemical agents to potential terrorists;
chemical agents likely to cause major morbidity or mortality;
potential of agents for causing public panic and social disruption; and
agents that require special action for public health preparedness (Box 4).
Categories of chemical agents include
nerve agents,
tabun (ethyl N,N-dimethylphosphoramidocyanidate),
sarin (isopropyl methylphosphanofluoridate),
soman (pinacolyl methyl phosphonofluoridate),
GF (cyclohexylmethylphosphonofluoridate),
VX(o-ethyl-[S]-[2-diisopropylaminoethyl]-methylphosphonothiolate);
blood agents,
hydrogen cyanide,
cyanogen chloride;
blister agents,
lewisite (an aliphatic arsenic compound, 2-chlorovinyldichloroarsine),
nitrogen and sulfur mustards,
phosgene oxime;
heavy metals,
arsenic,
lead,
mercury;
Volatiletoxins,
benzene,
chloroform,
trihalomethanes;
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8 MMWR April 21,2000
BOX 5. (Continued) Chemical agents
pulmonaryagents,
phosgene,
chlorine,
vinyl chloride;
incapacitating agents,
BZ(3-quinuclidinylbenzilate);
pesticides, persistent and nonpersistent;
dioxins,furans, and polychlorinated biphenyls(PCBs);
explosive nitro compounds and oxidizers,
ammonium nitrate combined with fuel oil;
flammable industrial gases and liquids,
gasoline,
propane;
poison industrial gases, liquids, and sol ids,
cyanides,
nitriles;and
corrosive industrial acids and bases,
nitric acid,
sulfuricacid.
Because of the hundreds of new chemicals introduced internationally each
month, treating exposed persons by clinical syndrome rather than by specific
agent is more useful for public health planning and emergency medical response
purposes. Public health agencies and first responders might render the most
aggressive, timely, and clinically relevant treatment possible by using treatment
modalities based on syndromic categories (e.g., burns and trauma, cardiorespira-
tory failure, neurologic damage, and shock). These activities must be linked with
authorities responsibleforenvironmental sampling and decontamination.
KEY FOCUS AREAS
CDC's strategic plan is based on the following five focus areas, with each area inte-
grating training and research:
preparedness and prevention;
detection and surveillance;
diagnosis and characterization of biological andchemical agents;
response; and
communication.
Preparedness and Prevention
Detection, diagnosis, and mitigation of illness and injury caused by biological and
chemical terrorism is a complex process that involves numerous partners and activities.
Meeting this challenge will require special emergency preparedness in all cities and
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Vol. 49 / No. RR-4 MMWR 9
states. CDC will provide public health guidelines, support, and technical assistance to
local and state public health agencies as they develop coordinated preparedness plans
and response protocols. CDC also will provide self-assessment tools for terrorism pre-
paredness, including performance standards, attacksimulations, and other exercises. In
addition, CDC will encourage and support applied research to develop innovative tools
and strategies to preventer mitigate illness and injury caused by biological and chemical
terrorism.
Detection and Surveillance
Early detection is essential for ensuring a prompt response to a biological or chemical
attack, including the provision of prophylactic medicines, chemical antidotes, or vac-
cines. CDC will integrate surveillance for illness and injury resulting from biological and
chemical terrorism into the U.S. disease surveillance systems, while developing new
mechanisms for detecting, evaluating, and reporting suspicious events that might repre-
sent covert terrorist acts. As part of this effort, CDC and state and local health agencies
will form partnerships with front-line medical personnel in hospital emergency depart-
ments, hospital care facilities, poison control centers, and other offices to enhance detec-
tion and reporting of unexplained injuries and illnesses as part of routine surveillance
mechanisms for biological and chemical terrorism.
Diagnosis and Characterization of Biological and Chemical
Agents
CDC and its partners will create a multilevel laboratory response network for
bioterrorism (LRNB). That network will I ink clinical labs to public health agencies in all
states, districts, territories, and selected cities and counties and to state-of-the-art facili-
ties that can analyze biological agents (Figure 1). As part of this effort, CDC will transfer
diagnostic technology to state health laboratories and others who will perform initial
testing. CDC will also create an in-house rapid-response and advanced technology (RRAT)
laboratory. This laboratory will provide around-the-clock diagnostic confirmatory and
reference support for terrorism response teams. This network will include the regional
chemical laboratories for diagnosing human exposure to chemical agents and provide
links with other departments (e.g., the U.S. Environmental Protection Agency, which is
responsible for environmental sampling).
Response
A comprehensive public health response to a biological or chemical terrorist event
involves epidemiologic investigation, medical treatment and prophylaxis for affected
persons, and the initiation of disease prevention or environmental decontamination
measures. CDC will assist state and local health agencies in developing resources and
expertise for investigating unusual events and unexplained illnesses. In the event of a
confirmed terrorist attack, CDC will coordinate with other federal agencies in accord with
Presidential Decision Directive (PDD) 39. PDD 39 designates the Federal Bureau of In-
vestigation as the lead agency for the crisis plan and charges the Federal Emergency
Management Agency with ensuring thatthe federal response management is adequate
to respond to the consequences of terrorism (8 ). If requested by a state health agency,
CDC will deploy response teams to investigate unexplained or suspicious illnesses or
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10
MMWR
April 21, 2000
FIGURE 1. Multilevel laboratory response network for bioterrorism that will link clinical
labs to public health agencies
Level D laboratories
Agent-
specific
laboratory
Agent-
specific
laboratory
Agent-
specific
laboratory
Rapid-response
and advanced
technology laboratory
Specimen testing and referral
Training and consultation
Functional Levels of the Laboratory Response Network for Bioterrorism
Level A: Early detection of intentional dissemination of biological agents Level A laboratories
will be public health and hospital laboratories with low-level biosafety facilities. Level A laborato-
ries will use clinical data and standard microbiological tests to decide which specimens and
isolates should be forwarded to higher level biocontainment laboratories. Level A laboratory staff
will be trained in the safe collection, packaging, labeling, and shipping of samples that might
contain dangerous pathogens.
Level B: Core capacity for agent isolation and presumptive-level testing of suspect specimens
Level B laboratories will be state and local public health agency laboratories that can test for
specific agents and forward organisms or specimens to higher level biocontainment laboratories.
Level B laboratories will minimize false positives and protect Level C laboratories from overload.
Ultimately, Level B laboratories will maintain capacity to perform confirmatory testing and charac-
terize drug susceptibility.
Level C: Advanced capacity for rapid identification Level C laboratories, which could be located
at state health agencies, academic research centers, or federal facilities, will perform advanced
and specialized testing. Ultimately, Level C laboratories will have the capacity to perform toxicity
testing and employ advanced diagnostic technologies (e.g., nucleic acid amplification and molecu-
lar fingerprinting). Level C laboratories will participate in the evaluation of new tests and reagents
and determine which assays could be transferred to Level B laboratories.
Level D: Highest level containment and expertise in the diagnosis of rare and dangerous biological
agents Level D laboratories will be specialized federal laboratories with unique experience in
diagnosis of rare diseases (e.g., smallpox and Ebola). Level D laboratories also will develop or
evaluate new tests and methods and have the resources to maintain a strain bank of biological
agents. Level D laboratories will maintain the highest biocontainment facilities and will be able to
conduct all tests performed in Level A, B, and C laboratories, as well as additional confirmatory
testing and characterization, as needed. They will also have the capacity to detect genetically
engineered agents.
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Vol. 49 / No. RR-4 MMWR 11
unusual etiologic agents and provide on-site consultation regarding medical manage-
ment and disease control. To ensure the availability, procurement, and delivery of medi-
cal supplies, devices, and equipmentthat might be neededto respond to terrorist-caused
illness or injury, CDC will maintain a national pharmaceutical stockpile.
Communication Systems
U.S. preparedness to mitigate the public health consequences of biological and chemi-
cal terrorism depends on the coordinated activities of well-trained health-care and public
health personnel throughout the United States who have access to up-to-the minute
emergency information. Effective communication with the publicthrough the news me-
dia will also be essential to limit terrorists' ability to induce public panic and disrupt daily
life. During the next 5 years, CDC will work with state and local health agencies to
develop a) a state-of-the-art communication system that will support disease surveil-
lance; b) rapid notification and information exchange regarding disease outbreaks that
are possibly related to bioterrorism; c) dissemination of diagnostic results and emer-
gency health information; and d) coordination of emergency response activities. Through
this network and similar mechanisms, CDC will provide terrorism-related training to
epidemiologists and laboratorians, emergency responders, emergency department per-
sonnel and other front-line health-care providers, and health and safety personnel.
PARTNERSHIPS AND IMPLEMENTATION
Implementation of the objectives outlined in CDC's strategic plan will be coordinated
through CDC's Bioterrorism Preparedness and Response Program. Program personnel
are charged with a) helping build local and state preparedness, b) developing U.S. exper-
tise regarding potential threat agents, and c) coordinating response activities during
actual bioterrorist events. Program staff have established priorities for 2000-2002 re-
garding the focus areas (Box 6).
Implementation will require collaboration with state and local public health agencies,
as well as with other persons and groups, including
public health organizations,
medical research centers,
health-care providers and their networks,
professional societies,
medical examiners,
emergency response units and responder organizations,
safety and medical equipment manufacturers,
the U.S. Office of Emergency Preparedness and other Department of Health and
Human Services agencies,
other federal agencies, and
international organizations.
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12 MMWR April 21,2000
BOX 6. Implementation Priorities Regarding Focus Areas for 2000-2002
Preparedness and Prevention
Maintain a public health preparedness and response cooperative agreementthat
provides supportto state health agencies who are working with local agencies in
developing coordinated bioterrorism plans and protocols.
Establish a national public health distance-learning system that provides
biological and chemical terrorism preparedness training to health-care workers
and to state and local public health workers.
Disseminate public health guidelines and performance standards on biological
and chemical terrorism preparedness planning for use by state and local health
agencies.
Detection and Surveillance
Strengthen state and local surveillance systems for illness and injury resulting
from pathogens and chemical substances that are on CDC's critical agents list.
Develop newalgorithms and statistical methodsforsearching medical databases
on a real-time basis for evidence of suspicious events.
Establish criteria for investigating and evaluating suspicious clusters of human or
animal disease or injury and triggers for notifying law enforcement of suspected
acts of biological or chemical terrorism.
Diagnosis and Characterization of Biological and Chemical Agents
Establish a multilevel laboratory response network for bioterrorism that links
public health agencies to advanced capacity facilities for the identification and
reporting of critical biological agents.
Establish regional chemical terrorism laboratories that will provide diagnostic
capacity during terrorist attacks involving chemical agents.
Establish a rapid-response and advanced technology laboratory within CDC to
provide around-the-clockdiagnosticsupportto bioterrorism response teams and
expedite molecular characterization of critical biological agents.
Response
Assist state and local health agencies in organizing response capacitiesto rapidly
deploy in the event of an overt attack or a suspicious outbreakthat might be the
result of a covert attack.
Ensure that procedures are in place for rapid mobilization of CDC terrorism
response teams that will provide on-site assistance to local health workers,
security agents, and law enforcement officers.
Establish a national pharmaceutical stockpile to provide medical supplies in the
event of a terrorist attackthat involves biological or chemical agents.
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Vol. 49 / No. RR-4 MMWR 13
BOX 6. (Continued) Implementation Priorities Regarding Focus Areas for 2000-2002
Communication Systems
Establish a national electronic infrastructure to improve exchange of emergency
health information among local, state, and federal health agencies.
Implement an emergency communication planthat ensures rapid dissemination
of health informationtothe public during actual,threatened, orsuspected acts of
biological orchemicalterrorism.
Create a website that disseminates bioterrorism preparedness and training
information, as well as other bioterrorism-related emergency information, to
public health and health-care workers and the public.
RECOMMENDATIONS
Implementing CDC's strategic preparedness and response plan by 2004 will ensure
the following outcomes:
U.S. public health agencies and health-care providers will be preparedto mitigate
illness and injuries that result from acts of biological and chemical terrorism.
Public health surveillance for infectious diseases and injuries including events
that might indicate terrorist activity will be timely and complete, and reporting
of suspected terrorist events will be integrated with the evolving, comprehensive
networks of the national public health surveillance system.
The national laboratory response network for bioterrorism will be extended to
include facilities in all 50 states. The network will include CDC's environmental
health laboratory for chemical terrorism and four regional facilities.
State and federal public health departments will be equipped with state-of-the-art
tools for rapid epidemiological investigation and control of suspected or
confirmed acts of biological or chemical terrorism, and a designated stock of
terrorism-related medical supplies will be available through a national
pharmaceutical stockpile.
A cadre of well-trained health-care and public health workers will be available in
every state. Their terrorism-related activities will be coordinated through a rapid
and efficient communication system that links U.S. public health agencies and
their partners.
CONCLUSION
Recent threats and use of biological and chemical agents against civilians have ex-
posed U.S. vulnerability and highlighted the need to enhance our capacity to detect and
control terrorist acts. The U.S. must be protected from an extensive range of critical
biological and chemical agents, including some that have been developed and stockpiled
for military use. Even without threat of war, investment in national defense ensures
preparedness and acts as a deterrent against hostile acts. Similarly, investment in the
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14 MMWR April 21,2000
public health system provides the best civil defense against bioterrorism. Tools devel-
oped in response to terrorist threats serve a dual purpose. They help detect rare or
unusual disease outbreaks and respond to health emergencies, including naturally oc-
curring outbreaks or industrial injuries that might resemble terrorist events in their
unpredictability and ability to cause mass casualties (e.g., a pandemic influenza outbreak
or a large-scale chemical spill). Terrorism-preparedness activities described in CDC's
plan, including the development of a public health communication infrastructure, a mul-
tilevel network of diagnostic laboratories, and an integrated disease surveillance sys-
tem, will improve our ability to investigate rapidly and control public health threats that
emerge in the twenty first century.
References
1. Okumura T, Suzuki K, Fukuda A, et al. Tokyo subway sarin attack; disaster management.
Part 1: community emergency response. Acad Emerg Med 1998;5:613-7.
2. Davis, CJ. Nuclear blindness: an overview of the biological weapons programs of the
former Soviet Union and Iraq. Emerg Infect Dis 1999;5:509-12.
3. Torok TJ, Tauxe RV, Wise RP, et al. Large community outbreak of Salmonellosis caused by
intentional contamination of restaurant salad bars. JAMA 1997;278:389-95.
4. Tucker JB. Chemical/biological terrorism: coping with a new threat. Politics and the Life
Sciences 1996;15:167-184.
5. Uncle Fester. Silent death. 2nd ed. Port Townsend, WA: Loompanics Unlimited, 1997.
6. Ashraf H. European dioxin-contaminated food crisis grows and grows [news]. Lancet
1999;353:2049.
7. Janofsky M. Looking for motives in plague case. New York Times. May 28, 1995:A18.
8. Federal Emergency Management Agency. Federal response plan. Washington, DC:
Government Printing Office, 1999. Available at . Accessed
February 3, 2000.
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CDC
CENTERS FOR DISEASE CONTROL
AND PREVENTION
mm
MORBIDITY AND MORTALITY
WEEKLY REPORT
April 21, 2000/Vol. 49/No. RR-4
Recommendations
and
Reports
Continuing Education Activity
Sponsored by CDC
Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response
Recommendations of the CDC Strategic Planning Workgroup
EXPIRATION APRIL 21. 2001
You must complete and return the response form electronically or by mail by April 21, 2001, to receive
continuing education credit. If you answer all of the questions, you will receive an award letter for 1.0 hour
Continuing Medical Education (CME) credit or 1.2 hours Continuing Nursing Education (CNE) credit. If you return the
form electronically, you will receive educational credit immediately. If you mail the form, you will receive
educational credit in approximately 30 days. No fees are charged for participating in this continuing education
activity.
INSTRUCTIONS
By Internet
1. Readthis/W/WI/l//?(Vol.49, RR-4), which contains the correct answers to the questions that begin on the next
page.
2. Gotothe/W/WI/l//?Continuing Education Internet site at .
3. Select which exam you want to take and select whether you want to register for CME or CNE credit.
4. Fill out and submit the registration form.
5. Select exam questions. To receive continuing education credit, you must answer all of the questions.
Questions with more than one correct answer will instruct you to "Indicate all that apply."
6. Submit your answers no later than April 21, 2001.
7. Immediately print your Certificate of Completion for your records.
By Mail
1. Read this MMWR (Vol. 49, RR-4), which contains the correct answers to the questions beginning on the next
page.
2. Complete all registration information on the response form, including your name, mailing address, phone
number, and e-mail address, if available.
3. Indicate whether you are registering for CME or CNE credit.
4. Select your answers to the questions, and markthe corresponding letters on the response form. To receive
continuing education credit, you must answer all of the questions. Questions with more than one correct
answer will instruct you to "Indicate all that apply."
5. Sign and date the response form or a photocopy of the form and send no later than April 21, 2001, to
Fax:404-639-4198 Mail: MMWRCECredit
Off ice of Scientific and Health Communications
Epidemiology Program Office, MS C-08
Centers for Disease Control and Prevention
1600 Clifton Rd, N.E.
Atlanta, GA30333
6. Your Certificate of Completion will be mailed to you within 30 days.
ACCREDITATION
Continuing Medical Education (CME). CDC is accredited by the Accreditation Council for Continuing Medical Education (ACCME)
to provide continuing medical education for physicians. CDC designates this educational activity for a maximum of 1.0 hour in
category 1 cred it towards the AMA Physician's Recognition Award. Each physician should claim only those hours of credit that
he/she actually spent inthe educational activity.
Continuing Nursing Education (CNE). This activity for 1.2 contact hours is provided by CDC, which is accredited as a provider of
continuing education in nursing bythe American Nurses Credentialing Center's Commission on Accreditation.
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CE-2 MMWR April 21,2000
GOALS and OBJECTIVES
This MMWR provides recommendations and guidance for initiating a national preparedness program for biological
and chemical terrorism. The recommendations were developed by a workgroup with representatives from the
Council of State and Territorial Epidemiologists, Association of State and Territorial Health Officials, and
Association of Public Health Laboratories, with contributions from federal and professional organizations during a
meeting held in August 1999. The goal of this report is to guide United States public health and medical
prepared ness efforts. Upon completing this educational activity, the reader should be able to identify a) criteria
used to designate critical biological and chemical agents; b) five core focus areas for domestic terrorism
preparedness; c) critical components of public health response to terrorism; and d) partners in an effective
response to biological and chemical terrorism.
To receive continuing education credit, please answer all of the following questions.
1. Which of the following are good biological terrorism threats because of substantial
morbidity and mortality, ease of production, efficient dissemination, stability in aerosol,
or high infectivity?
A. Anthrax, chickenpox, botulism, and plague.
B. Anthrax, smallpox, chickenpox, and plague.
C. Anthrax, smallpox, botulism, and plague.
D. Anthrax, smallpox, mumps, and plague.
2. Biological weapons can be considered the ultimate weapon because they . . .
A. cause mass casualties.
B. are inexpensive and easy to produce.
C. can be difficult to detect.
D. can be disseminated at great distances.
E. all of the above.
3. Which of the following diseases have potential for person-to-person transmission?
A. Anthrax and plague.
B. Plague and botulism.
C. Botulism and brucellosis.
D. Smallpox and plague.
4. Which attribute does NOT determine whether or not a biological agent is included on
the CDC critical agent list?
A. The agent's potential for causing morbidity and mortality to the public.
B. The agent's ability to cause disease in animals.
C. The agent's ability for dissemination to a large number of persons.
D. The need for special preparedness in response to the agent's release.
E. The likelihood of person-to-person transmission of an agent because of its release.
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Vol. 49 / No. RR-4 MMWR CE-3
5. Which of the following would be included in a public health response to a biological
terrorism event or any other disease outbreak?
A. Conducting a surveillance.
B. Investigating disease clusters.
C. Testing a hypothesis regarding transmission.
D. Evaluating control strategies.
E. All of the above.
6. Which of the following would NOT be considered a requirement for public health
response preparedness for biological terrorism?
A. Stockpiling a national supply of vaccine, antitoxins, and medical equipment?
B. Vaccinating the civilian population for anthrax.
C. Creating a state emergency response plan for biological terrorism.
D. Establishing a surveillance system for critical biological agents.
7. Which of the following positions are responsible for evaluating or reporting a cluster of
disease that is suspected to be the result of terrorism activity?
A. Epidemiologists.
B. Primary-care providers.
C. Laboratorians.
D. Emergency response personnel (e.g., emergency medical service, fire, or police).
E. All of the above.
8. Which of the following federal agencies has responsibility for crisis management during
a biological or chemical terrorism event?
A. Internal Revenue Service.
B. Federal Bureau of Investigation.
C. Federal Emergency Management Agency.
D. Central Intelligence Agency.
E. Centers for Disease Control and Prevention.
9. Which of the following would NOT have a potential impact on the public health-care
system in case of a biological terrorism event involving anthrax?
A. Fear and panic among the public.
B. Overwhelming number of casualties.
C. Overwhelming demand for intensive care modalities.
D. High potential for patient-to-provider spread of the disease agent.
E. Overwhelming demand for antibiotics.
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CE-4 MMWR April 21,2000
10. Which of the following group(s) need to prepare and test a community emergency
preparedness plan?
A. Public and private health-care providers.
B. Public safety officials.
C. Law enforcement personnel.
D. Elected officials.
E. All of the above.
11. A local preparedness plan should include which of the following?
A. Communication systems between state and local groups.
B. Testing mechanisms in laboratories.
C. Plans to triage and treat mass casualties.
D. Exercises to test community plans.
E. All of the above.
12. The key components of a national preparedness plan include which of the following?
A. Establishing response mechanisms.
B. Strengthening surveillance systems.
C. Strengthening laboratory systems.
D. Enhancing communications and training.
E. All of the above.
13. Indicate your work setting.
A. State/local health department.
B. Other public health setting.
C. Hospital clinic/private practice.
D. Managed care organization.
E. Academic institution.
F. Other.
14. Which of the following best describes your professional activities?
A. Patient care emergency/urgent care department.
B. Patient care inpatient.
C. Patient care primary-care clinic.
D. Laboratory/pharmacy.
E. Administration.
F. Public health.
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Vol. 49 / No. RR-4 MMWR CE-5
15. I plan to use these recommendations as the basis for ... (Indicate all that apply.)
A. Health education materials.
B. Insurance reimbursement policies.
C. Local practice guidelines.
D. Public policy.
E. Other.
16. How much time did you spend reading this report and completing the exam?
A. 1-11/2 hours.
B. More than 11/2 hours but fewer than 2 hours.
C. 2-21/2 hours.
D. More than 21/2 hours.
17. After reading this report, I am confident I can identify criteria used to designate critical
biological and chemical agents.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
18. After reading this report, I am confident I can identify five core focus areas for domestic
terrorism preparedness.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
19. After reading this report, I am confident I can identify critical components of public
health response to terrorism.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
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CE-6 MMWR April 21,2000
20. After reading this report, I am confident I can identify partners in an effective response to
biological and chemical terrorism.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
21. The objectives are relevant to the goal of this report.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
22. The text boxes and figure are useful.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
23. Overall, the presentation of the report enhanced my ability to understand the material.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
24. These recommendations will affect how I conduct or participate in biological and
chemical terrorism preparedness planning.
A. Strongly agree.
B. Agree.
C. Neither agree nor disagree.
D. Disagree.
E. Strongly disagree.
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Vol. 49 / No. RR-4
MMWR
CE-7
MMWR Response Form for Continuing Education Credit
April 21, 2000/Vol. 49/IMo. RR-4
Biological and Chemical Terrorism: Strategic Plan for Preparedness and Response
Recommendations of the CDC Strategic Planning Workgroup
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To receive continuing education credit, you must
1. provide your contact information;
2. indicate your choice of CME or CNE credit;
3. answer all of the test questions;
4. sign and date this form or a photocopy;
5. submit your answer form by April 21, 2001.
Failure to complete these items can result in a delay or rejection of
your application for continuing education credit.
First Name
Check One
n CME Credit
D CNE Credit
Street Address or P.O. Box
Apartment or Suite
City
State
Zip Code
Fill in the appropriate blocks to indicate your answers. Remember, you must answer a// of the questions to receive
continuing education credit!
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[]A []B []C []D []E
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Signature
Date I Completed Exam
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