United States
Environmental Protection
Agency
EPA-540/9-88-001
March 1989
vvEPA
Recognition and
Management of
Pesticide Poisonings
Fourth Edition
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RECOGNITION AND
MANAGEMENT OF PESTICIDE
POISONINGS
Fourth Edition
Donald P. Morgan, M.D., Ph.D.*
1989
Support for this publication was provided by the Health Ef-
fects Division, Office of Pesticide Programs, United States
Environmental Protection Agency, Washington, D.C. 20460.
*lowa Pesticide Hazard Assessment Project, located at The University of
Iowa College of Medicine, Iowa City, Iowa 52242.
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TABLE OF CONTENTS
Chapter
Number
Introduction v
1. Organophosphate Insecticides 1
2. N-Methyl Carbamate Insecticides 12
3. Solid Organochlorine Insecticides 17
4. Insecticides of Biological Origin 25
5. Other Insecticides, Acaricides, and Repellents 34
6. Arsenical Pesticides 54
7. Chlorophenoxy Herbicides 63
8. Nitrophenolic and Nitrocresolic Herbicides 68
9. Pentachlorophenol 73
10. Paraquat and Diquat 76
11. Other Herbicides 93
12. Fungicides 89
13. Rodenticides 115
14. Fumigants 131
15. Miscellaneous Pesticides, Solvents, and Adjuvants 146
16. Index to Pesticide Poisonings by Symptoms and Signs.... 159
Index of Chemical and Product Names 169
111
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Introduction
This fourth edition of Recognition and Management of Pesticide Poi-
sonings is an update and expansion of the 1982 third edition. The
series, from 1973, has been sponsored by the Office of Pesticide Pro-
grams of the United States Environmental Protection Agency.
There have been good reasons for updated editions. New pesticide
products are introduced regularly whose hazard potentials are not
generally known to health professionals. The accumulated "use experi-
ence" of formulators, applicators, and field workers provides an ex-
panding basis for judging safety or identifying hazards of old and new
pesticides. Major episodes of adverse health effects reported in medical
and scientific periodicals need to be taken into account. This literature
also contributes importantly to improved understanding of toxic mech-
anisms. Finally, clinical toxicology is a dynamic field of medicine
wherein new treatment methods are developed regularly and the effec-
tiveness of old as well as new modalities undergoes constant critical
review. The purpose of the fourth edition 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.
All persons familiar with the clinical toxicology of pesticides agree
that prevention of poisoning remains a much surer path to safety and
health than reliance on treatment. In addition to the inherent toxic
hazards of pesticides, none of the procedures or drugs used in treating
poisonings are risk-free. In fact, many antidotes are plainly "toxic" in
their own right, and such apparently simple procedures as gastric
intubation incur substantial risk. The clinical toxicologist must often
weigh the hazards of various courses of action—sometimes including no
treatment at all—against the risks of various interventions, such as
emptying the stomach, catharsis, giving intravenous fluids, br adminis-
tering an antidote (when there is one). Management decisions have to
be made promptly and, as often as not, on the basis of limited and
scientifically insecure information. The complex circumstances of
human poisonings rarely allow precise comparisons of alternative man-
agements. 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 management options.
The book deals almost entirely with short-term (acute) harmful ef-
fects of pesticides. Although obviously important, the subject of chronic
effects is too complex to deal with exhaustively in a manual designed
as guidance for emergency management. Nonetheless, appropriate
treatment of serious exposures to pesticides represents one important
step in avoiding chronic as well as acute disease.
The amount of pesticide absorbed is a critical factor in making
treatment decisions, and estimation of dosage in many circumstances
v
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of pesticide exposure remains difficult. The terms "small amount" and
"large amount" used in this book are obviously ambiguous, but the
quality of exposure information obtainable rarely justifies more specif-
ic terminology. The circumstances of exposure are sometimes a rough
guide. 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 cholin-
esterase-inhibiting pesticides is not likely to lead to poisoning, but
prolonged exposures may well do so. Except in children, accidental
pesticide ingestions are likely to be spat out or vomited, but suicidal
ingestions almost always involve "large amounts," requiring the most
aggressive management. Ingestions of pesticides by children are the
most difficult to evaluate. The therapist usually must base his manage-
ment on "worst case" assumptions of dosage. Childhood poisonings are
still further complicated by the greater vulnerability of the very young
(small body size), not only to pesticides themselves, but to the drugs
and treatment procedures that must be used to limit the severity of
poisoning.
The need to protect the airway from aspiration of vomitus cannot be
over-emphasized. Death has occasionally resulted from this complica-
tion, even following ingestions of substances having relatively low toxic
potential. In poisonings by agents which 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. Induced emesis is usually safe in alert patients, but
great care must be taken in poisonings by neurotoxic agents that the
airway is still protected when vomiting occurs. Maintenance of ade-
quate pulmonary gas exchange is another essential element of poison-
ing management that deserves constant reemphasis.
Gastric intubation, with aspiration and lavage, remains a useful
method for removing poisons from the stomach shortly after they have
been swallowed, but the time after ingestion during which lavage is
likely to be beneficial is shorter than many clinical toxicologists have
thought. Rarely are significant amounts of swallowed toxicants recov-
ered more than a few hours after ingestion, and, in many instances,
the bulk of swallowed material passes into the duodenum and beyond
in 15-30 minutes.
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. Because administration of charcoal is rarely
followed by serious complications, its use is generally recommended if
there is some likelihood that it will act beneficially. Sorbitol is an
effective cathartic which somewhat reduces the distastefulness of char-
coal and does not impair its adsorbency. The only problems attending
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use of sorbitol are those inherent in catharsis itself: dehydration and
electrolyte disturbances, particularly in children.
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 are
valuable. Overall effectiveness appears to depend not only on efficiency
of clearance from the blood, but also on the mobility of toxicant al-
ready distributed to tissue cells before the extracorporeal blood-purifi-
cation procedure is started. 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 circumstances of poisoning can be compiled, and efforts to limit
these occurrences can be properly directed. It is realized that in recent
years there has been a tragic increase in the use of pesticides as
instruments of suicide and even homicide, particularly in the develop-
ing countries. Producers are now devoting considerable effort to modifi-
cations in formulation and packaging that will deter these misuses.
This work is important because suicidal ingestions are by far the most
difficult pesticide poisonings to treat successfully.
Among persons who encounter pesticides in the course of their occu-
pational activities, dermal injuries, rather than systemic poisonings are
the most common adverse effects.
An effort has been made to format this book for quick reference by
thorough indexing and minimal references to other pages or chapters.
However, some procedures are commonly used in treating poisonings
by many different agents and it is not practical to repeat these proto-
cols in every chapter. Methods for limiting toxicant absorption from
the gastrointestinal tract are described in Chapter 1, TREATMENT,
Section 6 (page 8). Control of convulsions is discussed in Chapter 3,
TREATMENT, Section 4 (page 21). Management of pulmonary edema
is considered in Chapter 14, TREATMENT, Section 4 (page 139). These
sections have been referenced in several other chapters.
The contents of this book have been derived from many sources:
published texts, current medical, toxicologic, and pesticide product lit-
erature, valuable instructional materials from the Iowa Poison Control
Center, and direct communications with experts having knowledge of
clinical toxicology in general and pesticide toxicology in particular. A
list of the major text sources follows this introduction.
vu
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Critical reviews of draft material by experts in clinical toxicology
have provided the real strength of this publication. Reviewers include:
John E. Davies, M.D., M.P.H., F.R.C.P.,
Professor Emeritus
[Department of Epidemiology and
Public Health
University of Miami School of Medicine
Miami, Florida William F. Durham, Ph.D.
Senior Research Advisor
Health Effects Research Laboratory
United States Environmental Protection
Agency
Research Triangle Park, North Carolina
Wayne Snodgrass, M.D., Ph.D.
Head, Clinical Pharmacology-Toxicology Unit
Medical Director, Texas Poison Center
University of Texas Medical Branch
Galveston, Texas William G. Troutman, Pharm.D.
Professor of Pharmacy and Director,
New Mexico Poison and Drug Information
Center
The University of New Mexico
Albuquerque, New Mexico
Sheldon L Wagner, M.D.
Professor of Clinical Toxicology
Department of Agricultural Chemistry
Oregon State University
Corvallis, Oregon
In addition to the expert reviewers, many individuals have contribut-
ed their time and skill to this fourth edition. Jerome M. Blondell,
biostatistician for the Health Effects Division, Office of Pesticide Pro-
grams, United States Environmental Protection Agency, has super-
vised the review process, accomplished the indexing, and overseen the
process of publication. The principal author is indebted to Mrs. Carol
Hradek for skillful editorial assistance, to Ms. Joan McLaughlin, and
to others of the secretarial staff of the Division of Occupational and
Environmental Health, Department of Preventive Medicine and Envi-
ronmental Health, The University of Iowa College of Medicine, for
typing the manuscript.
vui
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Texts and Handbooks on Pesticides,
Pesticide Toxicology and Clinical Toxicology
Clinical Toxicology of Commercial Products
Fifth Edition
Robert E. Gosselin, Roger P. Smith and Harold C. Hodge,
with assistance of Jeannette E. Braddock
Williams and Wilkins, Baltimore, MD
Pesticides Studied in Man
Wayland J. Hayes, Jr.
Williams and Wilkins, Baltimore, MD
Toxicology of Pesticides
Wayland J. Hayes, Jr.
Williams and Wilkins, Baltimore, MD
Handbook of Poisoning
Twelfth Edition
Robert H. Dreisbach and William O. Robertson
Appleton and Lange, East Norwalk, CT
1984
1982
1975
1987
Medical Toxicology: Diagnosis and Treatment of Human Poisoning
Matthew J. Ellenhorn and Donald G. Barceloux
Elsevier, New York, NY
Clinical Toxicology of Agricultural Chemicals
Sheldon L. Wagner, M.D.
Oregon State University Press
Corvallis, Oregon
Farm Chemicals Handbook
Charlotte Sine, Editorial Director
Meister Publishing Company
Willoughby, Ohio
Poisondex
Barry H. Rumack, Editor
Microdex, Incorporated, Denver, Colorado
1988
1981
1989
IX
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Biological Monitoring Methods for Industrial Chemicals
Randall C. Baselt
Biomedical Publications, Davis, CA 1980
The Pharmacological Basis of Therapeutics
Seventh Edition
Louis S. Goodman and Alfred Oilman
Macmillan Publishing Company, Inc., New York, NY 1985
Patty's Industrial Hygiene and Toxicology
Third Revised Edition
George D. Clayton and Florence E. Clayton
Wiley Interscience, New York, NY 1982
Casarett and DoulPs Toxicology
Third Edition
John Doull, Curtis D. Klaassen and Mary O. Amdur
Macmillan Publishing Company, New York, NY 1986
Poisoning: A Guide to Clinical Diagnosis and Treatment
W. F. Von Oettingen
W. B. Saunders Company, Philadelphia, PA 1958
The Merck Index
Tenth Edition
Martha Windholz and Susan Budavari, Editors
Merck and Company, Inc., Rahway, NJ 1983
Agricultural Chemicals Books I, II, III, IV
W.T. Thomson
Thomson Publications, Fresno, CA 1977-1979
Herbicide Handbook of the
Weed Science Society of America
Fifth Edition 1983
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
x
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CHAPTER 1
ORGANOPHOSPHATE INSECTICIDES
GENERAL CHEMICAL STRUCTURE
RO x ^ S (or 0)
p
RO ' ^ O
[Leaving Group|
R is usually either ethyl or methyl. Phosphonates contain an alkyl
(R-) in place of one alkoxy group (RO-).
COMMERCIAL PRODUCTS
Highly toxic*: tetraethyl pyrophosphate (TEPP), dimefox (Hanane,
Pestox XIV), phorate (Thimet, Rampart, AASTAR), disulfoton+ (Disys-
ton), fensulfothion (Dasanit), demeton+ (Systox), terbufos (Counter,
Contraven), mevinphos (Phosdrin, Duraphos), ethyl parathion (E605,
Parathion, Thiophos), azinphos-methyl (Guthion, Gusathion), fosthietan
(Nem-A-Tak), chlormephos (Dotan), sulfotep (Thiotepp, Bladafum, Dith-
ione), carbophenothion (Trithion), chlorthiophos (Celathion), fonofos
(Dyfonate, N-2790), prothoate+ (Fac), fenamiphos (Nemacur), phosfo-
lan+ (Cyolane, Cylan), methyl parathion (E 601, Penncap-M), schradan
(OMPA), mephosfolan+ (Cytrolane), chlorfenvinphos (Apachlor, Bir-
lane), coumaphos (Co-Ral, Asuntol), phosphamidon (Dimecron), metha-
midophos (Monitor), dicrotophos (Bidrin), monocrotophos (Azodrin),
methidathion (Supracide, Ultracide), EPN, isofenphos (Amaze, Oftanol),
endothion, bomyl (Swat), famphur (Famfos, Bo-Ana, Bash), fenophos-
phon (trichloronate, Agritox), dialifor (Torak), cyanofenphos (Surecide),
dioxathion (Delnav), mipafox (Isopestox, Pestox XV). .
Moderately toxic*: bromophos-ethyl (Nexagan), leptophos (Phosvel),
dichlorvos (DDVP, Vapona), ethoprop (Mocap), demeton-S-methyl+
(Duratox, Metasystox (i)), triazophos (Hostathion), oxydemeton-methyl"*"
(Metasystox-R), quinalphos (Bayrusil), ethion (Ethanox), chlorpyrifos
(Dursban, Lorsban, Brodan), edifenphos, oxydeprofos"1" (Metasystox-S),
sulprofos (Bolstar, Helothion), isoxathion (E-48, Karphos), propetam-
* Compounds are listed approximately in order of descending toxicity. "Highly toxic"
organophosphates have listed oral LDSO values (rat) less than 50 mg/kg; "moderately
toxic" agents have LD5o values in excess of 50 mg/kg.
* These organophosphates are systemic; they are taken up by the plant and translocated
into foliage and sometimes into the fruit.
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phos (Safrotin), phosalone (Zolone), thiometon (Ekatin), heptenophos
(Hostaquick), crotoxyphos (Ciodrin, Cypona), phosmet (Imidan, Prolate),
trichlorfon (Dylox, Dipterex, Proxol, Neguvon), cythioate (Proban,
Qyflee), phencapton (G 28029), pirimiphos-ethyl (Primicid), DBF (De-
Green, E-Z-Off D), methyl trithion, dimethoate (Cygon, DeFend), fenth-
ion (mercaptophos, Entex, Baytex, Tiguvon), dichlofenthion (VC-13 Ne-
macide), bensulide (Betasan, Prefar), EPBP (S-Seven), diazinon (Spec-
tracide), profenofos (Curacron), formothion (Anthio), pyrazophos
(Afugan, Curamil), naled (Dibrom), phenthoate (dimephenthoate,
Phenthoate), IBP (Kitazin), cyanophos (Cyanox), crufomate (Ruelene),
fenitrothion (Accothion, Agrothion, Sumithion), pyridaphenthion
(Ofunack), acephate (Orthene), malathion (Cythion), ronnel (fenchlor-
phos, Korlan), etrimfos (Ekamet), phoxim (Baythion), merphos (Folex,
Easy off-D), pirimiphos-methyl (Actellic), iodofenphos (Nuvanol-N),
chlorphoxim (Baythion-C), propyl thiopyrophosphate (Aspon), bromo-
phos (Nexion), tetrachlorvinphos (Gardona, Appex, Stirofos), temephos
(Abate, Abathion).
TOXICOLOGY
Organophosphates poison insects and mammals primarily by phos-
phorylation of the acetylcholinesterase enzyme (AChE) at nerve end-
ings. The enzyme is critical to normal control of nerve impulse trans-
mission from nerve fibers to muscle and gland cells, and also to other
nerve cells in autonomic ganglia and in the brain. Some critical pro-
portion of the tissue enzyme mass must be inactivated by phosphoryla-
tion before symptoms and signs of poisoning become manifest. At suffi-
cient dosage, loss of enzyme function allows accumulation of acetylcho-
line (ACh, the impulse-transmitting substance) at cholinergic neuroef-
fector junctions (muscarinic effects), at skeletal nerve-muscle junctions
and autonomic ganglia (nicotinic effects), and in the brain. At choliner-
gic nerve junctions with smooth muscle and gland cells, high ACh
concentration causes muscle contraction and secretion, respectively. At
skeletal muscle junctions, excess ACh may be excitatory (cause muscle
twitching), but may also weaken or paralyze the cell by depolarizing
the end-plate. In the brain, high ACh concentrations cause sensory and
behavioral disturbances, incoordination and depressed motor function.
Depression of respiration and pulmonary edema are the usual causes
of death from organophosphate poisoning. Recovery depends ultimately
on generation of new enzyme in all critical tissues.
Organophosphates are efficiently absorbed by inhalation, ingestion,
and skin penetration. To a 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.
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Many organophosphates 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 than -thions. Ultimately, both
-thions and -oxons are hydrolyzed at the ester linkage, yielding alkyl
phosphates and leaving groups. These are of relatively low toxicity.
They are either excreted or further transformed in the body before
excretion.
Within one to two days of initial organophosphate binding to acetyl-
cholinesterase, some phosphorylated acetylcholinesterase enzyme can
be de-phosphorylated (reactivated) by the oxime antidote pralidoxime.
As time progresses, the enzyme-phosphoryl bond is strengthened by
loss of one alkyl group from the phosphoryl adduct. Pralidoxime reacti-
vation is thereafter no longer possible ("aging").
Barely, certain organophosphates have caused a different kind of
neurotoxicity consisting of damage to the axons of peripheral and
central nerves and associated with inhibition of "neurotoxic esterase"
(NTE). Manifestations have been chiefly weakness or paralysis and
paresthesia of the extremities, predominantly the legs, persistent for
weeks to years. Most of these rare occurrences have followed (8-21
days) an acute poisoning episode of the anticholinesterase type, but
some have not been preceded by acute poisoning. 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 pesti-
cides be tested in susceptible animal species for this neurotoxic property.
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 toxici-
ty. Certain organophosphates are exceptionally prone to storage in fat
tissue, prolonging the need for antidote as stored pesticide is released
back into the circulation. Animal studies have demonstrated potentia-
tion of effect when two or more organophosphates are absorbed simul-
taneously: enzymes critical to the degradation of one are inhibited by
the other. Whether this interaction is a significant factor in human
poisonings is not known.
SYMPTOMS AND SIGNS OF POISONING
Symptoms of acute organophosphate poisoning develop during expo-
sure, or within 12 hours (nearly always within 4 hours) of contact. The
most commonly reported early symptoms are HEADACHE, NAUSEA,
and DIZZINESS. Anxiety and restlessness are prominent. Worsening
of the poisoned state is manifest as MUSCLE TWITCHING, WEAK-
3
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NESS, tremor, incoordination, vomiting, abdominal cramps, and diar-
rhea. HYPERSECRETION is often prominent: sweating, salivation,
tearing, rhinorrhea, and bronchorrhea. Blurred and/or dark vision
may be reported, and MIOSIS is often a helpful diagnostic sign. Tight-
ness in the chest, wheezing, and productive cough may progress to
frank PULMONARY EDEMA. Bradycardia may progress to sinus
arrest, or may be superseded by tachycardia and hypertension from
nicotinic (sympathetic ganglia) stimulation. Toxic psychosis, manifest
as confusion or bizarre behavior, has been misdiagnosed as acute alco-
holism. Toxic myocardiopathy has been a prominent feature of some
severe organophosphate poisonings. Unconsciousness, incontinence,
convulsions, and depression of respiratory drive signify a life-threaten-
ing severity of poisoning.
Repeated absorption of organophosphate at significant dosage, but in
amounts not sufficient to cause acute poisoning, may cause persistent
anorexia, weakness, and malaise.
Some recently reported cases of organophosphate poisoning, mostly
from suicidal ingestion of large quantities, have been characterized by
prolonged (1-3 weeks) paralysis of muscles of the head, neck, limbs,
and thorax, commencing one to four days following apparent resolution
of acute cholinergic manifestations. Continuous mechanical support of
pulmonary ventilation was necessary to sustain life in these cases.
CONFIRMATION OF ORGANOPHOSPHATE ABSORPTION
CAUTION: If there are strong clinical indications of acute or-
ganophosphate poisoning, treat patient immediately.
DO NOT WAIT for laboratory confirmation.
Depressions of plasma pseudocholinesterase and/or RBC acetylcho-
linesterase enzyme activities are generally available biochemical indi-
cators of excessive organophosphate absorption. A minimum amount of
organophosphate must be absorbed to depress blood cholinesterase ac-
tivities, but enzyme activities are lowered by dosages considerably less
than are required to cause symptomatic poisoning. The enzyme depres-
sion is usually apparent within a few minutes or hours of significant
absorption of organophosphate. Depression of the plasma enzyme gen-
erally 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. Table 1 lists APPROXIMATE
LOWER LIMITS OF NORMAL FOR PLASMA AND RBC CHOLIN-
ESTERASE ACTIVITIES of human blood, measured by several meth-
ods. LOWER LEVELS usually indicate excessive absorption of a cho-
Imesterase-inhibiting chemical. Whenever possible, comparison of the
test sample value with a pre-exposure value offers the best confirma-
tion of organophosphate absorption. A cholinesterase depression of
25% or more is generally regarded as evidence of excessive absorption.
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TABLE 1. Approximate Lower Limits of Normal Plasma and Red Cell
Cholinesterase Activities in Humans*
METHOD
pH (Michel)
pHStat(Nabb-
Whitfield)
BMC Reagent Set
(Ellman-
Boehringer)
Dupont ACA
Garry-Routh (Micro)
Technicon
PLASMA
0.45
2.3
1875
<8
2.0
RBC
0.55
. 8.0
8.0
WHOLE
BLOOD
3000
Male 7.8
Female 5.8
UNITS
ApH per ml per hr
p,M per ml per min
mU per ml per
min
Units per ml
fiM-SH. per 3 ml
per min
fiM. per ml per min
* Because measurement technique varies among laboratories, more accurate estimates
of minimum normal values are usually provided by individual laboratories.
In certain conditions, the activities of plasma and RBC choliriester-
ase are depressed in the absence of chemical inhibition. About 3% of
individuals have a genetically determined low level of plasma pseudo-
cholinesterase. These persons are particularly vulnerable to the action
of the muscle-paralyzing drug succinylcholine, often administered to
surgical patients. They may be unusually sensitive to organophosphate
toxicity, although this has not been proven. Patients with advanced
liver disease, malnutrition, chronic alcoholism, and dermatomyositis
exhibit low plasma Cholinesterase activities. A number of toxicants,
notably carbon disulfide, benzalkonium salts, organic mercury com-
pounds, ciguatoxins, and solanines may reduce plasma pseudocholines-
terase activity. Early pregnancy and birth control pills 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 reduced, however, in certain rare conditions that damage the red
cell membrane, such as the hemolytic anemias.
The alkyl phosphates and phenols to which organophosphates are
hydrolyzed in the body can often be detected in the urine during
pesticide absorption and up to about 48 hours thereafter. These analy-
ses are sometimes useful in identifying the actual pesticide to which
workers have been exposed. Urinary alkyl phosphate and phenol anal-
yses can demonstrate organophosphate absorption at lower dosages
than those required to depress Cholinesterase activities and at much
lower dosages than those required to produce symptoms and signs.
Detection of intact organophosphates in the blood is usually not
possible except during or soon after absorption of substantial amounts.
In general, organophosphates do not remain unhydrolyzed in the blood
more than a few minutes or hours, unless the quantity absorbed is
large or the hydrolyzing liver enzymes are inhibited.
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TREATMENT OF ORGANOPHOSPHATE POISONING
CAUTION: Persons attending the victim should avoid direct con-
tact with heavily contaminated clothing and vomi-
tus. Wear rubber gloves while washing pesticide
from skin and hair.
1. Insure that a CLEAR AIRWAY exists by aspiration of secretions,
if necessary. Administer OXYGEN by mechanically assisted pul-
monary ventilation if respiration is depressed. Improve tissue oxy-
genation 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 pulmo-
nary ventilation mechanically for several days.
2. Administer ATROPINE SULFATE intravenously, or intramuscu-
larly if intravenous injection is not possible.
The objective of atropine antidotal therapy is to antagonize the
effects of excessive concentrations of acetylcholine at end-organs
having muscarinic receptors. Depending on the severity of poison-
ing, doses of atropine ranging from small to very large may be
required. Atropine does not reactivate the cholinesterase enzyme
or accelerate disposition of organophosphate. Recrudescence of
poisoning may occur if tissue concentrations of organophosphate
remain high when the effect of atropine wears off. Atropine is
effective against muscarinic manifestations, but it is ineffective
against nicotinic actions, specifically muscle weakness and twitch-
ing, and respiratory depression. Despite these limitations, atro-
pine is often a lifesaving agent in organophosphate poisonings.
Favorable response to a test dose of atropine (1 mg in adults, 0.01
mg/kg in children under 12 years) can help differentiate poison-
ing by anticholinesterase agents from other conditions.
In MODERATELY SEVERE poisoning (hypersecretion and other
end-organ manifestations without central nervous system depres-
sion) the following dosage schedules have proven effective:
Dosage of ATROPINE:
Adults and children over 12 years: 0.4-2.0 mg repeated every
15 minutes until atropinization is achieved: flushing, dry
mouth, dilated pupils, and tachycardia (pulse of 140 per
minute). Maintain atropinization by repeated doses for 2-12
hours or longer depending on severity of poisoning. Rales in
the lung bases nearly always indicate inadequate atropiniza-
tion. Miosis, nausea, bradycardia, and other cholinergic mani-
festations also signal the need for more atropine.
Children under 12 years: 0.05 mg/kg body weight, repeated
every 15 minutes until atropinization is achieved. Maintain
atropinization with repeated dosage of 0.02-0.05 mg/kg body
weight.
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SEVEKELY POISONED individuals may exhibit remarkable tol-
erance to atropine; two or more times the dosages suggested above
may be needed. The dose of atropine may be increased and the
dosing interval decreased as needed to control symptoms. Continu-
ous intravenous infusion of atropine may be necessary when atro-
pine requirements are massive. REVERSAL OF MUSCARINIC
SYMPTOMS AND SIGNS, not an arbitrary dose limit, is the
desired end-point. Preservative-free atropine products should be
used whenever possible.
Note: Persons not poisoned or only slightly poisoned by organo-
phosphates 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.
3. Draw a BLOOD SAMPLE (heparinized) for cholinesterase analy-
sis before administration of pralidoxime, which tends to reverse
the cholinesterase depression.
4. Administer PRALIDOXIME (Protopam, 2-PAM), a cholinesterase
reactivator, in cases of severe poisoning by organophosphate pesti-
cides in which respiratory depression, muscle weakness, and
twitching are severe. When administered early (usually less than
48 hours after poisoning) pralidoxime relieves the nicotinic as
well as the muscarinic effects of poisoning.
Note: Pralidoxime is of limited value, and may be hazardous, in
poisonings by the cholinesterase-inhibiting carbamate compounds
(see Chapter 2).
Dosage of PRALIDOXIME:
Adults and children over 12 years: 1.0-2.0 gm intravenously
at no more than 0.2 gm per minute.
Children under 12 years: 20-50 mg/kg body weight (depend-
ing on severity of poisoning) intravenously, injecting no more
than half the total dose per minute.
Dosage of pralidoxime may be repeated in 1-2 hours, then at
10-12 hour intervals if needed. In very severe poisonings, dosage
rates may be doubled. Repeated doses of pralidoxime are usually
required. In cases that involve continuing absorption of organo-
phosphate (as after ingestion of a large amount), or continuing
transfer of highly lipophilic organophosphate from fat into blood,
it may be necessary to continue administration of pralidoxime for
several days beyond the 48 hour post-exposure interval usually
cited as the limit of its effectiveness.
Slow administration of pralidoxime is strongly recommended and
may be achieved by administering the total dose in 250 ml 5%
glucose solution over 30 minutes, or longer. Blood pressure should
be monitored during administration because of the occasional oc-
-------
currence 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 de-
pressed during or after pralidoxime administration.
If intravenous injection is not possible, pralidoxime may be given
by deep intramuscular injection.
5. In patients who have been poisoned by organophosphate contami-
nation of skin, clothing, hair, and/or eyes, DECONTAMINATION
MUST PROCEED CONCURRENTLY with whatever resuscitative
and antidotal measures are necessary to preserve life. Contamina-
tion of the eyes should be removed by flushing with copious
amounts of clean water. If no symptoms are evident in a patient
who remains alert and physically able, a prompt shower and
shampoo may be appropriate, 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 copi-
ous amounts of soap and water. Attendants should wear rubber
gloves. Surgical green soap is excellent for this purpose, but ordi-
nary soap is about as good. The possibility of pesticide sequestered
under fingernails or in skin folds should not be overlooked. CON-
TAMINATED CLOTHING should be promptly bagged and not
returned until it has been thoroughly laundered. Contaminated
leather shoes should be discarded. The possibility that pesticide
has contaminated the inside surfaces of gloves, boots, and head-
gear should be kept in mind.
6. IF ORGANOPHOSPHATE HAS BEEN INGESTED in quantity
probably sufficient to cause poisoning, the stomach and intestine
must be emptied.
Because central nervous system depression may develop rapidly,
gastric LAVAGE through a large bore orogastric tube, with rigor-
ous protection of the airway, is probably preferable to emesis in
nearly all cases of poisoning by ingested organophosphate. Effec-
tiveness of lavage diminishes rapidly with the passage of tune.
A. Empty the stomach by INTUBATION, ASPIRATION, and
LAVAGE, using a slurry of activated charcoal in isotonic
saline (see below). Rigorous precautions must be taken to
PROTECT THE AIRWAY from aspiration of regurgitated
gastric contents:
(a) If victim is unconscious or obtunded, insert a cuffed
ENDOTRACHEAL TUBE prior to gastric intubation.
(b) KEEP VICTIM'S HEAD BELOW LEVEL OF STOM-
ACH during gastric intubation and lavage (Trendelen-
burg, or left lateral decubitus, with head of table tipped
downward). Keep victim's head turned to the left.
8
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(c) ASPIRATE PHARYNX as regularly as possible to
remove gagged or vomited stomach contents.
B. After aspiration of stomach contents and lavage, instill ACTI-
VATED CHARCOAL ("preferably >3000" m2 surface area
per gm) together with a CATHARTIC in the charcoal slurry.
Even though adsorption of organophosphates on charcoal is
not very efficient, charcoal instillation may be of some value.
Dosage of CHARCOAL as an aqueous slurry:
Adults and children over 12 years: 50-100 gm in
300-800 ml water.
Children under 12 years: 15-30 gm in 100-300 ml water.
Dosage of SORBITOL (the preferred agent) added to charcoal
slurry:
Adults and children over 12 years: 1.0-2.0 gm/kg body
weight to a maximum of 150 gm per dose.
Children under 12 years: 1.0-1.5 gm/kg body weight to
a maximum of 50 gm per dose.
Alternative cathartics that may be used instead are sodium or
magnesium sulfate or citrate:
Dosage of SODIUM or MAGNESIUM SULFATE:
Adults and children over 12 years: 20-30 gm.
Children under 12 years: 250 mg/kg body weight.
Dosage of MAGNESIUM CITRATE solution:
Adults and children: 4 ml/kg body weight of proprie-
tary solution, up to a maximum of 300 ml.
CAUTION: Do not instill fluid so rapidly that overloading of
the stomach leads to vomiting or regurgitation. Serious elec-
trolyte disturbances may follow catharsis, especially in young
children. Monitor serum electrolytes regularly, including mag-
nesium levels, if magnesium salts have been used.
C. If gastric aspiration and lavage is not performed due to delay
in treatment, and if patient is fully alert, ADMINISTER doses
of CHARCOAL AND CATHARTIC ORALLY, as indicated in
6.B. When sorbitol is given orally, it should be diluted with an
equal volume of water to yield a 35% solution.
D. SAVE a sample of emesis or initial gastric washings for chem-
ical analysis.
E. In some cases of organophosphate ingestion there may be
benefit from REPEATED ADMINISTRATION OP ACTIVAT-
ED CHARCOAL, either by ingestion or stomach tube, at
doses approximating those recommended in 6.B. above. While
charcoal incurs little risk, repeated catharsis may cause seri-
ous dehydration and electrolyte depletion, especially in chil-
dren. Cathartic should not be administered after a charcoal
stool appears.
7. 'OBSERVE PATIENT CLOSELY for at least 72 hours (longer in
cases of organophosphate ingestion) to insure that symptoms
9
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(sweating, visual disturbances, vomiting, diarrhea, chest and ab-
dominal distress, and sometimes PULMONARY EDEMA) do not
recur as atropinization is withdrawn. In very severe poisonings by
ingested organophosphates, particularly the more lipophilic and
slowly hydrolyzed compounds, metabolic disposition of toxicant
may require as many as 5-14 days. In some cases, this slow
elimination may combine with profound cholinesterase inhibition
to require atropinization for several days or even weeks. Rising
levels of blood cholinesterase activity are a useful signal that
atropine dosage can be tapered off by lengthening the intervals
between doses. As dosage is reduced, the lung bases should be
checked frequently for rales. If rales are heard, or if there is a
return of miosis, bradycardia, sweating or other cholinergic signs,
atropinization must be re-established promptly.
8. Particularly in poisonings by large ingested doses of organophos-
phate, MONITOR PULMONARY VENTILATION carefully, even
after recovery from muscarinic symptomatology, to forestall respi-
ratory failure. In some cases, respiratory failure has developed
several days following organophosphate ingestion, and has persist-
ed for days to weeks.
9. In severely poisoned patients, MONITOR CARDIAC STATUS by
continuous EGG recording. Some organophosphates have signifi-
cant cardiac toxicity.
10. Furosemide may be considered for relief of pulmonary edema if
rales persist 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.
11. The following drugs are probably contraindicated in nearly all
organophosphate poisoning cases: morphine, theophylline, phen-
othiazines, and reserpine. Adrenergic amines should be given only
if there is a specific indication, such as marked hypotension.
12. Rarely, in severe organophosphate poisonings, CONVULSIONS
occur despite therapy with atropine and pralidoxime. Insure that
causes unrelated to pesticide toxicity are not responsible: head
trauma, cerebral anoxia, or mixed poisoning. Drugs useful in
controlling convulsions are discussed in Chapter 3, TREATMENT,
Section 4, p. 21. The benzodiazepines diazepam or lorazepam are
probably the agents of choice as initial therapy.
13. Persons who have been clinically poisoned by organophosphate
pesticides should not be re-exposed to cholinesterase-inhibiting
chemicals until symptoms and signs have resolved completely and
blood cholinesterase activities have returned to at least 80 percent
of pre-poisoning levels. If blood cholinesterase was not measured
prior to poisoning, blood enzyme activities should reach at least
minimum normal levels (Table 1) before the patient is returned to
a pesticide-contaminated environment.
10
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14. DO NOT ADMINISTER ATROPINE OR PRALIDOXIME PRO-
PHYLACTICALLY to workers exposed to organophosphate pesti-
cides. 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 possible
progression to more severe poisoning. Atropine itself may en-
hance the health hazards of the agricultural work setting: im-
paired heat loss due to reduced sweating and impaired ability to
operate mechanical equipment due to blurred vision (mydriasis).
11
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CHAPTER 2
N-METHYL CARBAMATE
INSECTICIDES
GENERAL CHEMICAL STRUCTURE
H3C
H
\
/
0
N — C — O
Leaving
Group
COMMERCIAL PRODUCTS
Highly toxic*: aldicarb* (Temik), oxamyl (Vydate L, DPX 1410),
methiocarb (Mesurol, Draza), carbofuran (Furadan, Curaterr, Cris-
furan), isolan (Primin), methomyl (Lannate, Nudrin, Lanox), formetan-
ate (Carzol), aminocarb (Matacil), cloethocarb (Lance), bendiocarb
(Ficam, Dycarb, Multamat, Niomil, Tattoo, Turcam).
Moderately toxic*: dioxacarb (Elocron, Famid), promecarb (Carba-
mult), bufencarb (metalkamate, Bux), propoxur (aprocarb, Baygon), tri-
methacarb (Landrin, Broot), pirimicarb (Pirimor, Abol, Aficida, Aphox,
Fernos, Rapid), dimetan (Dimethan), carbaryl (Sevin, Dicarbam), isopro-
carb (Etrofolan, MIPC).
TOXICOLOGY
The N-methyl carbamate esters cause reversible carbamylation of
acetylcholinesterase enzyme, allowing accumulation of acetylcholine,
the neuromediator substance, at parasympathetic neuroeffector junc-
tions (muscarinic effects), at skeletal muscle myoneural junctions and
autonomic ganglia (nicotinic effects), and in the brain (CNS effects).
The carbamyl-acetylcholinesterase combination dissociates more read-
ily than the phosphoryl-acetylcholinesterase complex produced by or-
ganophosphate compounds. This lability has several important conse-
quences: 1) it tends to limit the duration of N-methyl carbamate poi-
sonings, 2) it accounts for the greater span between symptom-produc-
ing and lethal doses than exists in the case of most organophosphate
* Compounds are listed approximately in order of descending toxicity. "Highly toxic" N-
methyl carbamates have listed oral LD6o values (rat) less than 50 mg/kg body weight;
"moderately toxic" agents have LD50 values in excess of 50 mg/kg.
+ This pesticide is taken up by some plants into the foliage and sometimes into the fruit.
12
-------
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
by skin penetration. Dermal absorption of particular compounds (nota-
bly carbofuran) is very slight. N-methyl carbamates are hydrolyzed
enzymatically by the liver and the 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 secre-
tion, respectively. At skeletal muscle junctions, excess acetylcholine
may be excitatory (cause muscle twitching), but may also weaken or
paralyze the cell by depolarizing the end-plate. In the brain, elevated
acetylcholine concentrations may cause sensory and behavioral disturb-
ances, incoordination, and depressed motor function (rarely seizures),
even though the N-methyl carbamates do not penetrate the central
nervous system very efficiently. Depression of respiration combined
with pulmonary edema is the usual cause of death from poisoning by
N-methyl carbamate compounds.
SYMPTOMS AND SIGNS OP POISONING
MALAISE, MUSCLE WEAKNESS, DIZZINESS, and SWEATING
are commonly reported early symptoms of poisoning. Headache, saliva-
tion, nausea, vomiting, abdominal pain, and diarrhea are often promi-
nent. Miosis, incoordination, and slurred speech are reported. Dyspnea,
bronchospasm, and chest tightness may eventuate in PULMONARY
EDEMA. Blurred vision, muscle twitching, and spasms characterize
some cases. Severe neurologic manifestations, including convulsions,
are less common than in organophosphate poisonings. Bradycardia
occurs infrequently. Poisonings by N-methyl carbamates tend to be of
shorter duration than poisonings by organophosphates, but they are
not easily differentiated from organophosphate poisoning in the acute
phase in the absence of an accurate exposure history.
CONFIRMATION OF N-METHYL CARBAMATE ABSORPTION
Unless a substantial amount of N-methyl carbamate has been ab-
sorbed 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 Table 1 of Chapter 1 for methods of
measurement of blood cholinesterase activities, if circumstances appear
to warrant performance of the test.
Absorption of some N-methyl carbamates can be confirmed by analy-
sis of urine for unique metabolites: alpha-naphthol from carbaryl, iso-
propoxyphenol from propoxur, carbofuran phenol from carbofuran, al-
13
-------
dicarb sulfone and nitrile from aldicarb. Unfortunately, analyses for
these excretion end-products are complex and not generally available.
TREATMENT OF N-METHYL CARBAMATE INSECTICIDE
POISONING
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.
1. Insure that a CLEAR AIRWAY exists by aspiration of secretions,
if necessary. Administer OXYGEN by mechanically assisted pul-
monary ventilation as needed. Improve tissue oxygenation as
much as possible before administering atropine, so as to minimize
the risk of ventricular fibrillation. Support pulmonary ventilation
mechanically as long as respiratory drive is depressed.
2. Administer ATROPINE SULFATE intravenously, or intramuscu-
larly, if intravenous injection is not possible. The objective of
atropine antidotal therapy is to antagonize the effects of excessive
concentrations of acetylcholine at end-organs having muscarinic
receptors. Depending on the severity of poisoning, doses of atro-
pine ranging from small to very large may be required. Atropine
does not reactivate the cholinesterase enzyme or accelerate excre-
tion or breakdown of pesticide. Recrudescence of poisoning may
occur if tissue concentrations of toxicant remain high when the
effect of atropine wears off. Atropine is effective against muscar-
inic manifestations, but it is ineffective against nicotinic actions,
specifically muscle weakness and twitching, and respiratory de-
pression. Despite these limitations, atropine is often a lifesaving
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.
In MODERATELY SEVERE poisoning (hypersecretion and other
end-organ manifestations without central nervous system depres-
sion) the following dosage schedules have proven effective:
Dosage of ATROPINE:
Adults and children over 12 years: 0.4-2.0 mg repeated every
15 minutes until atropinization is achieved: tachycardia
(pulse of 140 per minute), flushing, dry mouth, dilated pupils.
Maintain atropinization by repeated doses for 2-12 hours or
longer depending on severity of'poisoning. Rales in the lung
bases nearly always indicate inadequate atropinization.
Miosis, nausea, bradycardia, and other cholinergic manifesta-
tions also signal the need for more atropine.
Children under 12 years: 0.05 mg/kg body weight, repeated
every 15 minutes until atropinization is achieved. Maintain
14
-------
3.
4.
5.
atropinization with repeated doses of 0.02-0.05 mg/kg body
weight.
SEVERELY POISONED individuals may exhibit remarkable tol-
erance to atropine; two or more tunes the dosages suggested above
may be needed. Reversal of muscarinic manifestations, rather
than a specific dosage, is the object of atropine therapy. However,
prolonged intensive intravenous administration of atropine some-
times required in organophosphate poisonings is rarely needed in
treating carbamate poisoning. Note: Persons not poisoned or only
slightly poisoned by N-methyl carbamates may develop signs of
atropine toxicity from such large doses. FEVER, muscle fibrilla-
tions, and delirium are the main signs of atropine toxicity. If
these signs appear while the patient is fully atropinized, atropine
administration should be discontinued, at least temporarily, while
the severity of poisoning is reevaluated.
Save a URINE SAMPLE for metabolite analysis if there is need
to identify the agent responsible for the poisoning. Also, urine
metabolite measurement can be used to follow the progress of
carbamate disposition.
Pralidoxime is probably of little value in N-methyl carbamate
poisonings. Its use is usually unnecessary because atropine alone
is effective, and in some cases of carbamate poisoning, pralidox-
ime administration has been followed by severe reactions, even
sudden death. Both animal studies and experience in human poi-
sonings CONTRAINDICATE USE OF PRALIDOXIME IN CAR-
BARYL POISONINGS. In mixed poisonings involving organo-
phosphates, or in poisonings by unidentified anticholinesterase
agents which produce significant nicotinic effects, cautious admin-
istration of pralidoxime may have to be considered (see Chapter 1
TREATMENT, Section 4, p. 7).
In patients who have been poisoned by carbamate pesticide con-
tamination of skin, clothing, hair, and/or eyes, DECONTAMINA-
TION MUST PROCEED CONCURRENTLY with whatever resus-
citative and antidotal measures are needed to preserve life. Con-
tamination of the eyes should be removed by flushing with copi-
ous amounts of clean water. For asymptomatic individuals who
are alert and physically able, a prompt shower and shampoo may
be appropriate, 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. Surgical
green soap is excellent for this purpose, but ordinary soap is
about as good. The possibility of pesticide sequestered under fin-
gernails or in skin folds should not be overlooked. CONTAMI-
NATED CLOTHING should be promptly removed, bagged, and
15
-------
not returned until it has been thoroughly laundered. Contaminat-
ed leather shoes should be discarded. The possibility that pesticide
has contaminated the inside surfaces of gloves, boots, and head-
gear should be kept in mind.
6. IF N-METHYL CARBAMATE HAS BEEN INGESTED in a
quantity probably sufficient to cause poisoning, the stomach and
intestine must be emptied, and measures taken to limit absorp-
tion from the gut. Procedures for accomplishing this are essential-
ly the same as those used in organophosphate poisonings. See
Chapter 1, TREATMENT, Section 6, p. 8.
7. OBSERVE PATIENT CLOSELY for at least 24 hours to insure
that symptoms (sweating, visual disturbances, vomiting, diarrhea,
chest and abdominal distress, and sometimes PULMONARY
EDEMA) do not recur as atropinization is withdrawn. As the
dosage of atropine is reduced over time, check the lung bases
frequently for rales. If rales are heard, or if there is a return of
miosis, sweating or other signs of poisoning, atropinization must
be re-established promptly.
8. Furosemide may be considered for relief of pulmonary edema if
rales persist in the lungs even after full atropinization. It should
not be considered until the maximum effect of atropine has been
achieved. Consult package insert for dosage and administration.
9. Particularly hi poisonings by large doses of N-methyl carbamates,
MONITOR PULMONARY VENTILATION carefully, even after
recovery from muscarinic symptomatology, to forestall respiratory
failure.
10. In severely poisoned patients, MONITOR CARDIAC STATUS by
continuous EGG recording.
11. The following drugs are probably contraindicated in nearly all N-
methyl carbamate poisoning cases: morphine, theophylline, phen-
othiazines, and reserpine. Adrenergic amines should be given only
if there is a specific indication, such as marked hypotension.
12. Persons who have been clinically poisoned by N-methyl carba-
mate pesticides should not be re-exposed to cholinesterase-inhibit-
ing chemicals until symptoms and signs have resolved completely.
13. DO NOT ADMINISTER ATROPINE PROPHYLACTICALLY to
workers exposed to N-methyl carbamate pesticides. Prophylactic
dosage may mask early symptoms and signs of carbamate poison-
ing and thus allow the worker to continue exposure and possible
progression to more severe poisoning. Atropine itself may en-
hance the health hazards of the agricultural work setting: im-
paired heat loss due to reduced sweating and impaired ability to
operate mechanical equipment due to blurred vision (mydriasis).
16
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CHAPTER 3
SOLID ORGANOCHLORINE
INSECTICIDES
CHEMICAL STRUCTURES
MIREX
Cl Cl Cl Cl
DIENOCHLOR
CHLORDECONE
COMMERCIAL PRODUCTS
Endrin (Hexadrin), aldrin (Aldrite, Drinox), endosulfan (Thiodan),
dieldrin (Dieldrite), toxaphene (Toxakil, Strobane-T), lindane (gamma
BHC or HCH, Isotox), hexachlorocyclohexane (BHC), DDT (chlorophen-
othane), heptachlor (Heptagran), chlordecone (Kepone), terpene polych-
lorinates (Strobane), chlordane (Chlordan), dicofol (Kelthane), mirex
(Dechlorane), methoxychlor (Marlate), dienochlor (Pentac), TDE (DDD,
Rhothane), ethylan (Perthane).
The United States Environmental Protection Agency has sharply
curtailed the availability of many organochlorines, particularly DDT,
dieldrin, heptachlor, mirex, chlordecone, and chlordane. Others, howev-
er, are still the active ingredients of various home and garden products
17
-------
and some agricultural, structural, and environmental pest control
products. Hexachlorobenzene is used as a seed protectant fungicide.
Technical hexachlorocyclohexane (misnamed benzene hexachloride,
BHQ includes multiple stereoisomers; only the gamma isomer (lin-
dane) 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
medicinal Kwell, used for human ectoparasitic disease.
TOXICOLOGY
In varying degrees, organochlorines are absorbed from the gut and
also by the lung and across the skin. The efficiency of dermal absorp-
tion is variable. Hexachlorocyclohexane, including lindane, the cyclo-
dienes (aldrin, dieldrin, endrin, chlordane, heptachlor) and endosulfan
are efficiently absorbed across skin, while dermal absorption efficien-
cies of DDT, perthane, dicofol, methoxychlor, toxaphene, mirex, and
kepone are substantially less. Gastrointestinal, and probably dermal,
absorption of organochlorines is enhanced by fat and fat solvents.
While most of the solid organochlorines are not highly volatile, pesti-
cide-laden aerosol or dust particles trapped in respiratory mucous and
subsequently swallowed may be vehicles leading to significant gastroin-
testinal absorption.
Following exposure to some organochlorines (notably DDT), a signifi-
cant part of the absorbed dose is stored in fat tissue as the unchanged
parent compound. Most organochlorines are in some degree dechlorin-
ated, oxidized, then conjugated. The chief route of excretion is biliary,
although nearly all organochlorines yield measurable urinary metabo-
lites. Unfortunately, many of the unmetabolized pesticides are effi-
ciently reabsorbed by the intestine (enterohepatic circulation) substan-
tially retarding fecal excretion. Metabolic dispositions of DDT and DDE
(a DDT degradation product), the beta isomer of hexachlorocyclohex-
ane, dieldrin, heptachlor epoxide, mirex, and kepone tend to be slow,
leading to storage in body fat. Storable lipophilic compounds are likely
to be excreted in maternal milk.
Rapid metabolic dispositions of lindane, methoxychlor, dienochlor,
endrin, chlorobenzilate, dicofol, toxaphene, perthane, and endosulfan
reduce the likelihood that these organochlorines will be detected as
residues in body fat, blood, or milk.
The cyclodiene aldrin is efficiently epoxidized in the body (and hi the
environment) to dieldrin. A similar biotransformation converts hepta-
chlor to heptachlor epoxide. These conversions have little effect on
toxicity of the parent compound. The epoxides are sometimes identified
in body fat, blood, and milk.
Lindane is partially dechlorinated and oxidized following absorption,
promptly yielding a series of conjugated chlorophenols and other oxida-
tion products in the urine.
18
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The chief toxic action of the organochlorine pesticides is on the
nervous system, where these compounds interfere with fluxes of ca-
tions across nerve cell membranes, increasing neuronal irritability.
This effect is manifest mainly as convulsions, sometimes limited to
myoclonic jerking, but often expressed as violent seizures. Convulsions
caused by the more slowly metabolized cyclodienes may recur over
periods of several days. Convulsions may cause death by interfering
with pulmonary gas exchange and by generating severe metabolic
acidosis. Various disturbances of sensation, coordination, and mental
function are also characteristic of acute organochlorine poisoning. High
tissue concentrations of organochlorines increase myocardial irritabil-
ity, predisposing to cardiac arrhythmias. When tissue organochlorine
concentrations drop below threshold levels, recovery from the poison-
ing occurs. Organochlorines are not cholinesterase inhibitors.
High tissue levels of some organochlorines (notably DDT, DDE, cyclo-
dienes, mirex, and kepone) have been shown to induce hepatic microso-
mal drug-metabolizing enzymes. This tends to accelerate excretion of
the pesticides themselves, but may also stimulate biotransformation of
critical natural substances, such as steroid hormones and therapeutic
drugs, occasionally necessitating revaluation 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.
Hexachlorobenzene (a fungicide) has caused porphyria cutanea tarda
in humans. It does not cause convulsions. Lindane, chlordane, and
dieldrin have been associated anecdotally with certain rare hematolog-
ic disorders, including aplastic anemia; the incidence of these effects
appears to be extremely low.
Poisoning by endosulfan has caused blindness in sheep. Mirex at
high dosage produces cataracts in rats and mice. The DDT analogue
known as ODD is selectively concentrated in adrenal tissue, where
high levels have an inhibitory effect on corticosteroid synthesis, and a
damaging effect on the cells. Certain other organochlorines are also
bioconcentrated in the adrenal cortex.
SYMPTOMS AND SIGNS OF POISONING BY
ORGANOCHLORINES
Early manifestations of poisoning by some organochlorine pesticides,
particularly DDT, are often sensory disturbances: hyperesthesia and
paresthesia of the face and extremities. Headache, dizziness, nausea,
vomiting, incoordination, tremor, and mental confusion are also report-
ed. More severe poisoning causes myoclonic jerking movements, then
generalized tonic-clonic CONVULSIONS. The seizures may be followed
by coma and respiratory depression.
Poisoning by the cyclodienes and toxaphene is more likely to begin
with the sudden onset of convulsions, often not preceded by the pre-
19
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monitory manifestations mentioned above. Seizures caused by cyclo-
dienes may appear as long as 48 hours after exposure, and may then
recur periodically over several days following the initial episode. Be-
cause lindane and toxaphene are more rapidly biotransformed in the
body and excreted, they are less likely than dieldrin, aldrin, and chlor-
dane to cause delayed or recurrent seizures.
Poisoning by chlordecone has occurred as a result of extraordinary
occupational exposure over many days. Principal manifestations were
weight loss, tremor, muscle weakness, involuntary eye movements,
pain in the chest and joints, skin rash, slurred speech, mental changes,
and abnormalities of liver function. Seizures did not occur. Recovery
was slow.
There have been no well documented reports of acute human poison-
ings by dicofol, mirex, heptachlor, dienochlor, perthane, methoxychlor,
or cblorobenzilate.
CONFIRMATION OF POISONING BY ORGANOCHLORINES
Organochlorine pesticides and/or their metabolites can sometimes be
identified in blood by gas-liquid chromotographic examination of sam-
ples 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. Chromatographic methods make
possible detection of most organochlorines at concentrations much
lower than those associated with acute poisoning. Therefore, a positive
finding in a tissue sample does not, of itself, justify a diagnosis of
poisoning. To confirm poisoning, the measured concentration must be
compared with those found in previously diagnosed cases of poisoning.
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. There is presently no evidence
that the small body burdens of organochlorines generated by food-
borne residues cause disease in humans.
Samples of fat tissue are more likely to reveal stored organochlorines
than blood. However, amounts of stored pesticides insufficient to be
identified in blood are not likely to be of clinical significance. Measure-
ments of urinary metabolites of some organochlorine pesticides can be
useful in monitoring occupational exposures; however, the analytical
methods are complex, and are not likely to detect amounts of metabo-
lites generated by minimal exposures.
20
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TREATMENT OF ORGANOCHLORINE TOXICOSIS
1.
2.
3.
4.
Persons exceptionally exposed to organochlorine pesticides by any
route should be OBSERVED for sensory disturbances, incoordina-
tion, speech slurring, mental aberrations, and involuntary motor
activity that would warn of imminent convulsions.
IF CONVULSIONS OCCUR, place the victim in the left lateral
decubitus position with the head down. Move away furniture or
other solid objects that may be a source of injury. If jaw move-
ments are violent, place padded tongue blades between the teeth
to protect the tongue. Whenever possible, remove dentures and
other removable dental work. Aspirate oral and pharyngeal secre-
tions, and, when possible, insert an oropharyngeal AIRWAY to
maintain an open passage unobstructed by the tongue. Minimize
noise and any manipulation of the patient that may trigger sei-
zure activity.
Administer OXYGEN by mask. Maintain pulmonary gas ex-
change by mechanically assisted ventilation whenever respiration
is depressed.
CONTROL CONVULSIONS. Drugs that are useful for this pur-
pose are diazepam, lorazepam, barbiturates, and muscle-paralyz-
ing agents such as succinylcholine.
Benzodiazepine drugs are currently the preferred anticonvulsants.
DIAZEPAM (Valium) has been tested the most extensively
against convulsions and is generally recommended. LORAZEPAM
(Ativan) may be superior as an anticonvulsant, but there is pres-
ently less clinical experience with its use for this purpose. It is
possible that lorazepam or other drugs will prove to be superior in
the future. Consult recent clinical toxicology texts for updated
recommendations.
Dosage of DIAZEPAM:
Adults and children over 12 years: 5-10 mg given IV at no
more than 2 mg per minute. Repeat every 10-15 minutes, if
necessary, to a maximum of 30 mg.
Children 5 to 12 years: 0.25-0.40 mg/kg body weight, slowly
IV, and repeat every 10-15 minutes, if necessary, to a maxi-
mum of 10 mg.
Children 30 days to 5 years: 0.25-0.40 mg/kg body weight,
slowly IV, and repeat every 10-15 minutes, if necessary, to a
maximum of 5 mg.
21
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CAUTION: Administer slowly to avoid irritation of the vein,
hypotension, and respiratory depression. Facilities
should be immediately available to support pulmo-
nary ventilation mechanically and to relieve laryngo-
spasm.
If it is not possible to give the drug intravenously, administer the
following doses undiluted by deep intramuscular injection:
Adults and children over 5 years: 10 mg. Repeat in 2-4 hours if
necessary.
Children under 5 years: 5 mg. Repeat in 2-4 hours if necessary.
PENTOBARBITAL SODIUM is an intermediate acting barbitu-
rate that is sometimes useful in controlling convulsions. It is
supplied in stable injectable solution or may be prepared fresh as
a 5% sterile aqueous solution (50 mg per ml). It can be given
either intravenously or intramuscularly.
Dosage of PENTOBARBITAL SODIUM:
Adults and children over 12 years: 200-500 mg (4-10 ml).
Initial intravenous dose should be 2-3 ml injected over a two-
minute period. Wait five minutes to observe effect, then
repeat if needed to suppress convulsions. If it is necessary to
give pentobarbital intramuscularly, inject 2 ml deep at two
different sites, then wait 20-30 minutes to observe effect. If
needed, repeat intramuscular dose or switch to intravenous
administration.
Children under 12 years: 3-7 mg/kg body weight injected
over a five-minute period. Wait five minutes to observe effect,
then repeat dose if necessary to suppress convulsions. If it is
necessary to give intramuscularly, inject 1.5 mg/kg body
weight at two different sites, then wait 20-30 minutes to
observe effect. If necessary, repeat intramuscular dose or
switch to intravenous administration.
CAUTION: Respiratory depression and hypotension may follow
intravenous use of pentobartibal. Facilities must be
immediately available to support pulmonary ventila-
tion mechanically and to intubate the trachea if the
upper airway is obstructed.
PHENYTOIN SODIUM (Dilantin) is effective in controlling epi-
leptic seizures, but is of uncertain value against convulsions
caused by chemical agents. Protocols for its administration can be
found in medical texts dealing with the management of status
epUepticus.
22
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5.
6.
7.
SUCCINYLCHOLINE (or similar muscle-paralyzing drug) may be
used if seizures prove intractable. Gain full control of pulmonary
ventilation (endotracheal tube or tracheostomy connected to a
mechanical ventilator), prepare to monitor blood gases, and secure
the services of an anesthesiologist or emergency care physician to
induce general anesthesia and administer the neuromuscular de-
polarizing agent. This procedure predictably controls seizures, but
imposes heavy responsibilities for continuous monitoring of gas
exchange and blood pH over several hours.
In patients who have been poisoned by organochlorine contamina-
tion of skin, clothing, hair and/or eyes, DECONTAMINATION
MUST PROCEED CONCURRENTLY with whatever resuscitative
and anticonvulsive measures are necessary to preserve life. Con-
tamination of the eyes should be removed by flushing with copi-
ous amounts of clean water. If the pesticide-exposed person re-
mains alert and physically able, a prompt shower and shampoo
may be appropriate, 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. Surgical
green soap is excellent for this purpose, but ordinary soap is
about as good. The possibility of pesticide sequestered under fin-
gernails or in skin folds should not be overlooked. CONTAMI-
NATED CLOTHING should be promptly bagged and not returned
until it has been thoroughly laundered. Contaminated leather
shoes should be discarded. The possibility that pesticide has con-
taminated the inside surfaces of gloves, boots, and headgear
should be considered.
IF ORGANOCHLORINE HAS BEEN INGESTED in a quantity
sufficient to cause poisoning, the stomach and intestine must be
emptied, and measures taken to limit toxicant absorption.
Because seizure activity may develop rapidly, LAVAGE, with a
large bore orogastric tube and with rigorous protection of the
airway, is probably preferable to induced emesis in most cases. If
the victim is convulsing, it is almost always necessary first to
control seizures before attempting gastric intubation. The effec-
tiveness of lavage in removing pesticide from the stomach dimin-
ishes rapidly with the passage of time. Procedures for emptying
the stomach and administration of activated charcoal and cathar-
tic are described in Chapter 1, TREATMENT, Section 6, p. 8.
Particularly in poisonings by large doses of organochlorine, MON-
ITOR PULMONARY VENTILATION carefully to forestall respi-
ratory failure. Assist pulmonary ventilation mechanically with
oxygen whenever respiration is depressed.
23
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8. In severely poisoned patients, MONITOR CARDIAC STATUS by
continuous EGG recording to detect arrhythmias.
9. DO NOT GIVE epinephrine, other adrenergic amines, or atropine
because of the enhanced myocardial irritability induced by chlor-
inated hydrocarbons, which predisposes to ventricular fibrillation.
10. DO NOT GIVE animal or vegetable oils or fats by mouth. They
enhance gastrointestinal absorption of the lipophilic organochlor-
ines.
11. To control seizures and myoclonic movements that sometimes
persist for several days following acute poisoning by the more
slowly excreted organochlorines, phenobarbital orally is likely to
be effective. Dosage should be based on manifestations in the
individual case and on information contained in the package
insert.
12. CHOLESTYRAMINE resin accelerates the biliary-fecal excretion
of the more slowly eliminated organochlorine compounds. It is
usually administered in 4 gm doses, 4 times a day, before meals
and at bedtime. Dose should be mixed with a pulpy fruit or liquid.
Prolonged treatment (several weeks or months) may be necessary.
13. During convalescence, enhance CARBOHYDRATE, PROTEIN,
and VITAMIN intake by diet or parenteral therapy.
24
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CHAPTER 4
INSECTICIDES OF BIOLOGICAL
ORIGIN
This chapter concerns several widely used insecticidal products of
natural origin, and also a growth promoting agent, gibberellic acid. It
discusses, in order, pyrethrum and pyrethrins, nicotine, rotenone, saba-
dilla, bacillus thuringiensis, and gibberellic acid.
PYRETHRUM AND PYRETHRINS
GENERAL CHEMICAL STRUCTURE
R
H H
= C-C
CH-C-
CH
CH.
C-C-Q-C"
H C-
H
C - R'
I
C =0
3 PYRETHRIN
SOURCE AND PRODUCTS
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 pyreth-
roic acids are known as pyrethrins, cinerins, and jasmolins. These
strongly lipophilic esters rapidly penetrate many insects and paralyze
their nervous systems. Both crude pyrethrum extract and purified
pyrethrins are contained in various commercial products, commonly
dissolved in petroleum distillates. Some are packaged in pressurized
containers ("bug-bombs"), usually in combination with the synergists
piperonyl butoxide and n-octyl bicycloheptene dicarboximide. The syn-
ergists retard enzymatic degradation of pyrethrins. Some commercial
products also contain organophosphate or carbamate insecticides.
These are included because the rapid paralytic effect of pyrethrins on
insects ("quick knockdown") is not always lethal.
Pyrethrum and pyrethrin products are used mainly for indoor pest
control. They are not sufficiently stable ^in light and heat to remain as
active residues on crops. The synthetic insecticides known as pyreth-
25
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roids (chemically similar to pyrethrins) do have the stability needed for
agricultural application. Pyrethroids are discussed in Chapter 5, p. 34.
TOXICOLOGY OF PYRETHRUM AND PYRETHRINS
Crude pyrethrum is a dermal and respiratory allergen, probably due
mainly to noninsecticidal ingredients. Contact dermatitis and allergic
respiratory reactions (rhinitis and asthma) have occurred following
exposures. A strong cross-reactivity with ragweed pollen has been rec-
ognized. Single cases exhibiting anaphylactic and pneumonitic manifes-
tations have also been reported. The refined pyrethrins are probably
less allergenic, but appear to retain some irritant and/or sensitizing
properties.
Pyrethrins are absorbed across the gut and pulmonary membrane,
but only slightly across intact skin. They are very effectively hydro-
lyzed to inert products by mammalian liver enzymes. This rapid degra-
dation combined with relatively poor bioavailability probably accounts
in large part for their relatively low mammalian toxicity. Dogs fed
extraordinary doses exhibit tremor, ataxia, labored breathing, and sali-
vation. 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 syner-
gists piperonyl butoxide and n-octyl bicycloheptene dicarboximide have
low toxic potential in humans, but organophosphates or carbamates
included in the product may have significant toxicity. Pyrethrins them-
selves do not inhibit cholinesterase enzyme.
There are presently no practical tests for pyrethrin metabolites or
pyrethrin effects on human enzymes or tissues that can be used to
confirm absorption.
TREATMENT OF PYRETHRUM OR PYRETHRIN TOXICOSIS
Antihistamines are effective in controlling most allergic reactions.
Severe asthmatic reactions, particularly in predisposed persons, may
require administration of epinephrine, theophylline, and/or corticoster-
oid medicinals. Inhalation exposure should be carefully avoided hi the
future.
Contact dermatitis may require extended administration of topical
corticosteroid preparations. This should be done under the supervision
of a physician. Future contact with the allergen must be avoided.
Eye contamination should be removed by copious flushing of the eye
with clean water or saline. Specialized care should be obtained if
irritation persists.
26
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Toxic manifestations caused by other ingredients must be treated
according to their respective toxic actions, independent of pyrethrin-
related effects.
Even though most ingestions of pyrethrin products present little
risk, if a large amount of pyrethrin-containing material has been in-
gested, it may be appropriate to empty the stomach by intubation,
aspiration, and lavage, after all precautions have been taken to protect
the respiratory tract from aspiration of stomach contents (see Chapter
1, TREATMENT, Section 6, p. 8). Lavage should be followed by instilla-
tion of activated charcoal and cathartic (see same reference).
If retained dosage was small and/or treatment has been delayed, and
if patient is fully alert, ORAL administration of activated CHARCOAL
and CATHARTIC probably represents optimal management. (See
above reference for recommended dosages.)
NICOTINE
CHEMICAL STRUCTURE
SOURCE AND PRODUCTS
Nicotine is an alkaloid contained in the leaves of many species of
plants, but is usually obtained commercially from tobacco. A 95%
solution of the free alkaloid in organic solvent has been marketed in
the past as a greenhouse fumigant. Another product used for the same
purpose is a 40% aqueous solution of nicotine sulfate. Significant vola-
tilization of nicotine occurs from both products. Commercial nicotine
insecticides have long been known as Black Leaf 40. Formulations
include sprays and dusts. Very little nicotine insecticide is used in the
United States today; in fact, most nicotine poisonings are the result of
ingestion of tobacco products.
TOXICOLOGY OF NICOTINE
Nicotine alkaloid is efficiently absorbed by the gut, lung, and skin.
The sulfate salt is absorbed by lung and gut, but is poorly absorbed
across the skin. Extensive biotransformation occurs in the liver result-
ing in a residence half-life of two hours or less. Both the liver and
27
-------
kidney participate in the formation and excretion of multiple end-
products, which are excreted within a few hours.
Toxic action is complex, involving both stimulation and blockade of
autonomic ganglia and skeletal muscle neuromuscular junctions, as
well as direct effects on the central nervous system. Paralysis and
vascular collapse are prominent features of acute poisoning, but death
is usually due to respiratory paralysis, which may ensue promptly
after the first symptoms of poisoning. Nicotine is not an inhibitor of
cholinesterase enzyme.
MANIFESTATIONS OF NICOTINE POISONING
Early symptoms of poisoning are salivation, nausea, vomiting, and
diarrhea. Burning sensations in the mouth and throat and abdominal
pain are reported. If dosage has been high, vascular collapse, dyspnea
then respiratory failure, cyanosis and unconsciousness may ensue
promptly. Agitation, sweating, headache, pupillary constriction, dizzi-
ness, incoordination, confusion, weakness, tremor, and convulsions
occur early in less fulminant poisoning. Initial hypertension is prob-
ably due mainly to generalized vasoconstriction. Subsequent shock is
caused by vasodilatation, often associated with vagotonic asystole or
severe cardiac arrhythmias. Respiratory failure is caused mainly by
paralysis of the muscles of respiration.
CONFIRMATION OF NICOTINE POISONING
Urine content of the metabolite cotinine can be used to confirm
absorption of nicotine.
TREATMENT OF NICOTINE TOXICOSIS
1. If liquid or aerosol spray has come in contact with skin, wash the
area thoroughly with soap and water.
2. If eyes have been contaminated, flush them thoroughly with clean
water or saline. If irritation persists, obtain specialized medical
treatment.
3. 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 con-
taminated, then transport the victim to the nearest treatment
facility. Although mild poisoning may resolve without treatment,
it is often difficult to predict the ultimate severity of poisoning at
the onset.
4. If there is any indication of loss of respiratory drive, MAINTAIN
PULMONARY VENTILATION by mechanical means, including
supplemental OXYGEN, if available, by mouth-to-mouth, or
mouth-to-nose methods, if necessary. Toxic effects of nicotine
other than respiratory depression are usually survivable. The im-
28
-------
portance of maintaining adequate gas exchange is therefore para-
mount.
5. If a nicotine-containing product has been ingested, immediate
steps must be taken to limit gastrointestinal absorption.
A. IF the patient is fully ALERT, immediate oral administration
of ACTIVATED CHARCOAL is probably the best initial step
in management.
Dosage of ACTIVATED CHARCOAL:
Adults and children over 12 years: 50-100 gm in 300-800
ml water.
Children under 12 years: 15-30 gm in 100-300 ml water.
Because nicotine itself is very likely to induce diarrhea,
it is usually not appropriate to include cathartic with
the charcoal.
CAUTION: Because unconsciousness may develop rapid-
ly in nicotine poisoning, it is essential to position the
patient after the charcoal slurry has been swallowed
(recumbent prone, head down) so that vomited material
will not be aspirated.
B. If the patient is unconscious or confused, the stomach should
be emptied by INTUBATION, ASPIRATION^ and LAVAGE,
after all precautions have been taken to protect the respirato-
ry tract from aspirated stomach contents (see Chapter 1,
TREATMENT, Section 6, p. 8). Charcoal slurry should be used
in washing the stomach, and several ounces should be left in
the stomach after the lavage. Repeated administration of acti-
vated charcoal at half or more the initial dosage every 2-4
hours may be beneficial.
C. DO NOT administer Syrup of Ipecac. It may enhance medul-
lary depressant effects of nicotine, and may induce vomiting
when the patient is obtunded.
6. Monitor cardiac status by electrocardiograph^, and measure blood
pressure frequently. Cardiopulmonary resuscitation may some-
tunes be necessary.
Vascular collapse may require administration of norepinephrine
and/or dopamine. Consult package inserts for dosages and routes
of administration. Infusions of electrolyte solutions, plasma
and/or blood may also be required to combat shock.
7. There is no specific antidote for nicotine poisoning. Severe hyper-
secretion (especially salivation and diarrhea) may be controlled by
intravenous atropine sulfate.
Dosage of ATROPINE SULFATE:
Adults and children over 12 years: 0.4-0.5 mg slowly IV,
repeated every 5 minutes if necessary.
Children under 12 years: 0.01 mg/kg body weight, slowly
IV, repeated every 5 minutes if necessary.
29
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CAUTION: Careful EGG monitoring of cardiac rhythm
should accompany intravenous administration of atro-
pine.
8. Convulsions should be controlled with diazepam or other benzo-
diazepine drug. See Chapter 3, TREATMENT, Section 4 (p. 21)
for appropriate dosages and methods of administration.
9. If the patient survives for four hours, complete recovery is said to
be likely.
ROTENONE
SOURCE AND PRODUCTS
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 butox-
ide as synergist, and other pesticides are included in some commercial
products. Rotenone degrades rapidly in the environment. Emulsions of
rotenone are applied to lakes and ponds to kill fish.
COMMERCIAL PRODUCTS
Noxfish, Noxfire, Rotacide, Foliafume, Nusyn-Noxfish, PB-Nox, Pren-
tox, Chem-Fish, Rotenone Solution FK-11.
TOXICOLOGY AND MANIFESTATIONS OF POISONING
Although rotenone is toxic to the nervous systems of insects, fish,
and birds, commercial rotenone products have presented little hazard
to man over many decades. Neither fatalities nor systemic poisonings
in humans have been reported in relation to ordinary use. Low concen-
tration in commercial products, degradability, an intense nauseant
effect in man, and poor absorption across gut and skin are probable
factors accounting for the good safety record of rotenone.
Numbness of oral mucous membranes has been reported hi workers
who got dust from the powdered derris root hi their mouths. Dermati-
tis and respiratory tract irritation have also been reported in occupa-
tionally exposed persons.
When rotenone has been injected into animals, tremors, vomiting,
incoordination, convulsions, and respiratory arrest have been observed.
These effects have not been reported in occupationally exposed
humans.
30
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TREATMENT OF ROTENONE TOXICOSIS
Skin contamination should be removed by washing with soap and
water. Eye contamination should be removed by flushing the eye thor-
oughly with clean water or saline. Dust hi the mouth should be washed
out. If irritation persists, medical treatment should be obtained.
If a rotenone-containing product has been swallowed and retained,
active efforts to empty the stomach should be undertaken only if
another more toxic pesticide is contained in the product. If patient is
fully alert, prompt oral administration of activated charcoal (and ca-
thartic if diarrhea has not already occurred) is probably the optimal
management of ingestion of a product containing rotenone as the only
insecticidal ingredient (with or without synergists). See Chapter 1,
TREATMENT, Section 6, p. 8 for dosages.
SABADILLA
SOURCE AND PRODUCTS
Sabadilla consists of the powdered ripe seeds of a South American
lily. It is used as a dust, with lime or sulfur, or dissolved in kerosene,
mainly to kill ectoparasites on domestic animals and humans. Insectici-
dal alkaloids are those of the veratrin 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 there is probably some
used in other countries.
TOXICOLOGY OF SABADILLA
Sabadilla dust is very irritating to the upper respiratory tract, caus-
ing sneezing, and is also irritating to the skin.
Veratrin alkaloids are apparently absorbed across the skin and gut,
and probably by the lung as well. Veratrin alkaloids have a digitalis-
like action on the heart muscle (impaired conduction and arrhyth-
mias).
MANIFESTATIONS OF SABADILLA POISONING
Although poisoning by medicinal veratrin preparations may have
occurred in the remote past, systemic poisoning by sabadilla prepara-
tions used as insecticides has been very rare or nonexistent.
TREATMENT OF SABADILLA TOXICOSIS
Contaminated skin should be washed thoroughly with soap and
water. If eyes are affected, they should be flushed with copious
amounts of clean water or saline. If skin or eye irritation persists,
medical treatment should be obtained.
31
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If a large amount of sabadilla pesticide product has been ingested in
the past hour and retained, the stomach should be emptied by intuba-
tion, aspiration, and lavage (see Chapter 1, TREATMENT, Section 6). If
only a small amount of sabadilla pesticide has been ingested and
retained, or if treatment is delayed, and if the patient remains fully
alert, immediate oral administration of activated charcoal probably
represents optimal management. If diarrhea has not already com-
menced, sorbitol should be administered with the charcoal slurry (see
above reference). If there is a suspicion that significant amounts of
sabadilla alkaloids have been absorbed, EGG monitoring of cardiac
activity for arrhythmias and conduction defects is appropriate.
BACILLUS THURINGIENSIS
SOURCE AND PRODUCTS
Several strains of the Bacillus thuringiensis are pathogenic to some
insects. The bacterial organisms are cultured, then harvested in spore
form for use as insecticide. Production methods vary widely. Proteina-
ceous and nucleotide-like toxins generated by the vegetative forms
(which infect insects) are responsible for the insecticidal effect. The
spores are formulated as wettable powders, flowable concentrates and
granules for application to field crops and for control of mosquitoes
and black flies.
COMMERCIAL PRODUCTS
Variety kurstaki: Bactur, Bactospeine, Dipel, Futura, Sok-Bt, Thuri-
cide, Tribactur. Variety israelensis: Bactimos, Skeetal, Teknar, Vecto-
bac. Variety aizawai: Certan.
TOXICOLOGY OF BACILLUS THURINGIENSIS
The varieties of Bacillus thuringiensis used commercially survive
when injected into mice, and at least one of the purified insecticidal
toxins is toxic to mice. Infections of humans have been extremely rare
(two recognized cases) and no occurrences of human toxicosis have
been reported. From studies involving deliberate ingestion by human
subjects, it appears possible, but not likely, that the organism can
cause gastroenteritis. B. thuringiensis products are exempt from toler-
ance on raw agricultural commodities in the United States. Neither
irritative nor sensitizing effects have been reported in workers prepar-
ing and applying commercial products.
TREATMENT OF BACILLUS THURINGIENSIS TOXICOSIS
Skin contamination should be removed with soap and water. Eye
contamination should be removed by flushing the eyes with clean
32
-------
water or saline. If irritation persists, or if there is any indication of
infection, treatment by a physician should be obtained.
If a B. thuringiensis product has been ingested, the patient should be
observed for manifestations of bacterial gastroenteritis: abdominal
cramps, vomiting, and diarjrhea. The illness is likely to be self-limited
if it occurs at all. Kaolin- land pectin-containing medicinals may miti-
gate the symptoms. If dehydration is marked, saline- and glucose-
containing fluids may be given orally or intravenously. Buttermilk
may be given to restore normal gut flora.
A single case of corneal ulcer caused by a splash of B. thuringiensis
suspension into the eye was successfully treated by subconjunctival
injection of gentamicin (20 mg) and cephazolin (25 mg).
GIBBERELLIC ACID (Gibberellin, GA3)
SOURCE AND PRODUCTS
Gibberellic acid is not a pesticide, but it is commonly used in agricul-
tural production as a growth promoting agent. It is a metabolic product
of a cultured fungus, formulated in tablets, granules, and liquid con-
centrates for application to soil beneath growing plants and trees.
Commercial products: Activol, Berelex, Cekugib, Gibberellin, Gibrel,
Grocel, Pro-Gibb, Pro-Gibb Plus, Regulex.
TOXICOLOGY OF GIBBERELLIC ACID
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.
MANAGEMENT OF GIBBERELLIC ACID EXPOSURE
Wash contamination from skin with soap and water. Flush contami-
nation from eyes with clean water or saline. If irritation occurs, obtain
medical treatment.
If gibberellic acid has been swallowed, there is no reason to expect
adverse effects.
33
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Chapter 5
OTHER INSECTICIDES, ACARICIDES,
AND REPELLENTS
This chapter concerns insecticides, acaricides, and repellents having
toxicologic characteristics distinct from the insecticides discussed in
previous chapters. It discusses pyrethroids, fluorides, borates, chlordi-
meform, propargite, substituted haloaromatic urea compounds, chloro-
benzilate, cyhexatin, methoprene, sulfur, diethyltoluamide, alkyl
phthalates, and benzyl benzoate.
PYRETHROIDS
These modern synthetic insecticides are similar chemically to natu-
ral pyrethrins, but modified to increase stability in the natural envi-
ronment. They are now widely used in agriculture, in homes and
gardens, and for treatment of ectoparasitic disease.
COMMERCIAL PRODUCTS
The following list includes the names of several pyrethroids that are
not currently in commercial production. These are included because
they may be marketed in the future, if not in the United States, then
possibly in other countries.
Allethrin (Pynamin), alphametrin, barthrin, bioresmethrin, bioper-
methrin, cismethrin, cyclethrin, cyfluthrin (Baythroid), cypermethrin
(Ammo, Barricade, CCN52, Cymbush, Cymperator, Cyperkill, Folcord,
KafilSuper, NRDC 149, Polytrin, Siperin, Ripcord, Flectron, Ustaad,
Cyrux), deltamethrin (decamethrin, Decis), dimethrin, fenpropathrin
(Danitol, Herald, Meothrin, Ortho Danitol, Rody), fenvalerate (Pydrin,
Behnark, Sumicidin, Fenkill), flucythrinate (AASTAR, Pay-off), fluva-
linate (Mavrik, Mavrik Aquaflow, Spur), furethrin, indothrin, permeth-
rin (Ambush, BW-21-Z, Ectiban, Eksmin, Kafil, Permasect, Perthrine,
Pounce, Pramex, Outflank, Talcord), phthalthrin (Neopynamin), res-
methrin (Benzofuroline, Chrysron, Pynosect, Synthrin), tetramethrin
(Neopynamin, Phthalthrin), tralomethrin (Scout), esfenvalerate
(Asana).
Pyrethroids are formulated as emulsifiable. concentrates, wettable
powders, granules, and concentrates for ultra low volume application.
They may be combined with additional pesticides (sometimes highly
toxic) in the technical product or tank mixed with other pesticides at
the tune of application. AASTAR is a combination of flucythrinate and
phorate. Phorate is a highly toxic organophosphate.
34
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Nix is a 1% permethrin creme applied to control human ectopara-
sites.
TOXICOLOGY OF PYRETHROIDS
Although certain pyrethroids exhibit striking neurotoxicity in labo-
ratory animals when administered by intravenous injection, and some
are toxic by the oral route, systemic toxicity by inhalation and dermal
absorption is low. There have been very few systemic poisonings of
humans by pyrethroids. Although limited absorption may account for
the low toxicity of some pyrethroids, rapid biodegradation by mamma-
lian liver enzymes (ester hydrolysis and oxidation) is probably the
major factor responsible. Most pyrethroid metabolites are promptly
excreted, at least in part, by the kidney.
Extraordinary absorbed doses may rarely cause incoordination,
tremor, salivation, vomiting, diarrhea, and irritability to sound and
touch. Extreme doses have caused convulsions hi laboratory animals.
Apart from systemic neurotoxicity, some pyrethroids do cause dis-
tressing paresthesia when liquid or volatilized materials contact
human skin. Sensations are described as stinging, burning, itching, and
tingling, progressing to numbness. The skin of the face seems to be
most commonly affected, but the hands, forearms, and neck are some-
times involved. Sweating, exposure to sun or heat, and application of
water enhance the disagreeable sensations. Sometimes the effect is
noted within minutes of exposure, but a 1-2 hour delay hi appearance
of symptoms is more common. Sensations rarely persist more than 24
hours. Little or no inflammatory reaction is apparent where the pares-
thesia are reported; the effect is presumed to result from pyrethroid
contact with sensory nerve endings in the skin. Not all pyrethroids
cause a marked paresthetic reaction: it is prominent following expo-
sure to pyrethroids whose structures include cyano-groups: fenvalerate,
flucythrinate, cypermethrin, and fluvalinate. The paresthetic reaction
is not allergic in nature: sensitization does not occur. Neither race,
skin type, nor disposition to allergic disease affect the likelihood or
severity of the reaction.
Persons treated with permethrin for lice or flea infestations some-
times experience itching and burning at the site of application, but this
is chiefly an exacerbation of sensations caused by the parasites them-
selves, and is not typical of the paresthetic reaction described above.
The manifestations of neurologic disorder seen hi laboratory animals
given the more toxic pyrethroids hi large doses are salivation, irritabil-
ity, tremors, ataxia, choreoathetosis (writhing convulsions), fall hi
blood pressure, and death. Severe metabolic acidosis is characteristic.
Due to the inclusion of unique solvent ingredients, certain formula-
tions of fluvalinate are corrosive to the eyes (see TREATMENT, Sec-
tion 2, this chapter).
Pyrethroids are not cholinesterase inhibitors.
35
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TREATMENT OF PYRETHROID TOXICOSIS
1. Skin contamination should be removed promptly by washing with
soap and water. If irritant or paresthetic effects occur, treatment
by a physician should be obtained. Because volatilization of pyr-
ethroid apparently accounts for paresthesia affecting the face,
strenuous measures should be taken (ventilation, protective face
mask and hood) to avoid vapor contact with the face and eyes.
Vitamin E Oil preparations (dl-alpha tocopheryl acetate) are
uniquely effective in preventing and stopping the paresthetic re-
action. They are safe for application to the skin under field condi-
tions. Corn oil is somewhat effective, but possible side effects with
continuing use make it less suitable. Vaseline is less effective
than corn oil and zinc oxide actually worsens the reaction.
2. Eye contamination should be treated immediately by prolonged
flushing of the eye with copious amounts of clean water or saline.
If irritation persists, professional ophthalmologic care should be
obtained. Undiluted Mavrik 2E (a formulation of fluvalinate) is
corrosive to the eyes. Extraordinary measures should be taken to
avoid eye and skin contamination with this product. Should acci-
dental eye contamination occur, expert ophthalmologic care
should be obtained after flushing the eye free of the chemical
with copious amounts of clean water.
3. Ingestion of pyrethroid insecticide presents relatively little risk.
However, if large amounts have been ingested, empty the stomach
by INTUBATION, ASPIRATION, and LAVAGE (see Chapter 1,
TREATMENT, Section 6, p. 8). Based on observations in laborato-
ry animals, large ingestions~«f either allethrin, cismethrin, fenva-
lerate or deltamethrin would be the most likely to generate neu-
rotoxic manifestations.
4. If only small amounts of pyrethroid have been ingested, or if
treatment has been delayed, oral administration of activated char-
coal and cathartic probably represents optimal management (see
Chapter 1, TREATMENT, Section 6, p. 8 for dosages).
5. Several drugs are effective in relieving the pyrethroid neurotoxic
manifestations observed in deliberately poisoned laboratory ani-
mals. None have been tested hi 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. Drugs effective in labo-
ratory animals that might be considered for symptomatic treat-
ment are: atropine (relief of salivation), diazepam, and phenobar-
bital (relief of tremors and convulsions), and mephenesin (relief of
all poisoning manifestations, except, sometimes, salivation).
36
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FLUORIDES
COMMERCIAL PRODUCTS
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.
Commercial product: Florocid
Sodium fluosilicate (sodium silico fluoride) has been used to control
ectoparasites on livestock, as well as crawling insects in homes and
work buildings. It is approximately as toxic as sodium fluoride.
Commercial products: Safsan (dust formulation)
Prodan (bait formulation)
Sodium fluoaluminate (sodium aluminofluoride, cryolite) is a stable
mineral containing fluoride. It is used as an insecticide on some vegeta-
bles and fruits. Cryolite has very low water solubility, does not yield
fluoride ion on decomposition, and presents very little toxic hazard to
mammals, including man.
Commercial product: Kryocide
Hydrofluoric acid is an important industrial toxicant, but is not used
as a pesticide. Fluoroacetate is discussed in Chapter 1.3: RODENTI-
CIDES. Sulfuryl fluoride is discussed in Chapter 14: FUMIGANTS.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
FLUORIDE
Sodium fluoride and fluosilicate used as insecticides present a seri-
ous toxic hazard to humans because of high inherent toxicity, and the
possibility that children crawling on floors of treated dwellings will
ingest the material.
Absorption across the skin is probably slight, and methods of pesti-
cide 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: renal clearance of.fluoride from the blood is rapid.
However, large loads of absorbed fluoride poison renal tubule cells!
Functional tubular disturbances and sometimes acute renal failure
result.
The toxic effects of fluoride in mammals are multiple and all may
threaten life. Except for the direct effect on ionized calcium in extra-
cellular fluid, the actions of fluoride result from inhibition of critical
intracellular enzymes.
37
-------
Ingested fluoride has a corrosive effect on the epithelial lining of the
gastrointestinal tract, due, in part, to highly corrosive hydrofluoric
acid formed in the stomach. Edema, ulceration, and hemorrhage com-
monly result. Thirst, abdominal pain, vomiting, and diarrhea, with
blood in vomitus and feces usually occur.
Absorbed fluoride ion reduces extracellular fluid concentrations of
calcium and magnesium. Hypocalcemia sometimes results in tetany.
Hyperkalemia is sometimes a serious threat to the heart.
Cardiac arrhythmias and shock are often prominent features of poi-
soning. These probably result from combinations of effects of fluid and
electrolyte disturbances and direct actions of fluoride on heart and
vascular tissues. Hypotension and severe arrhythmias, sometimes pro-
gressing to ventricular fibrillation, characterize severe poisonings.
Toxic actions on the brain are manifest as headache, muscular weak-
ness, salivation, nystagmus, dilated pupils, lethargy, stupor and coma.
Occasionally, convulsions occur. Respiratory failure is usually the
immediate cause of death.
CONFIRMATION OF POISONING
Plasma inorganic fluoride concentrations in the general United
States population are usually less than 0.02 milligram per liter and
rarely above 0.10 milligram per liter. In fatal cases of poisoning,
plasma levels from 3.5 to 15.5 milligrams per liter have been recorded.
TREATMENT OF FLUORIDE TOXICOSIS
1. Contamination of the skin should be removed by washing with
soap and water. Eye contamination should be removed by pro-
longed flushing of the eye with copious amounts of clean water or
saline. If irritation persists, specialized medical treatment should
be obtained.
2. If SODIUM FLUORIDE OR SODIUM FLUOSILICATE has been
INGESTED, immediate steps must be taken to remove or neutral-
ize the toxicant.
A. If the victim is fully alert, and if vomiting does not totally
prevent swallowing of a neutralizing agent, prompt oral ad-
ministration of lime water (0.15% calcium hydroxide), 1%
calcium chloride solution, calcium- or magnesium-based antac-
id or aluminum hydroxide gel (antacid gel preparation), or
milk will precipitate the bulk of fluoride ion in the gut and
therefore may be lifesaving. The victim should be given as
much as can be tolerated.
B. If the victim is obtunded or if vomiting precludes oral admin-
istration, the airway should be protected by endotracheal in-
tubation, then the stomach should be'gently intubated and
lavaged with several ounces of one of the liquids named hi 2A.
38
-------
above. Activated charcoal does not bind fluoride ion and is
therefore of no value in fluoride poisoning.
3. A blood specimen should be drawn for blood electrolyte analysis:
sodium, potassium, calcium, magnesium, fluoride, and bicarbonate
capacity. Another sample should be drawn to type and cross-
match for blood transfusion. Intravenous fluids (initially 5% dex-
trose 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 meta-
bolic acidosis is detected, sodium bicarbonate should be adminis-
tered to keep the urine at pH 7.0-7.5. Intravenous fluids must be
stopped if anuria or oliguria (less than 25-30 ml per hour) devel-
ops. If urine formation declines, extracorporeal hemodialysis
should be used. It removes fluoride efficiently, but no more rapid-
ly than a normally functioning kidney.
4. Monitor cardiac status by continuous electrocardiography. Ven-
tricular arrhythmias may necessitate DC cardioversion.
5. If overt or latent (Chvostek's sign) tetany occurs, or if hypocalce-
mia 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 one ml per
minute., Initial children's dose is approximately 0.5 ml/kg body
weight. Repeat in 10-20 minutes if there are still indications of
hypoealcemia. Severe poisonings may require administration of
several hundred milliliters of 10% calcium gluconate.
6. OXYGEN by mask should be administered for hypotension, shock,
cardiac arrhythmias, or cyanosis. Shock may require administra-
tion of plasma or blood.
SODIUM FLUOALUMINATE (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
hypoealcemia has not occurred. If so, intravenous 10% calcium
gluconate would be indicated (see 5 above). It is unlikely that
treatment for fluoride toxicity would be necessary following inges-
tion of sodium fluoaluminate.
BORIC ACID AND BORATES
COMMERCIAL PRODUCTS
Boric acid, sodium tetraborate decahydrate (borax), sodium pentabor-
ate, boron trioxide, sodium biborate.
Commercial products: Polybor, Pyrobor
39
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Formulated as tablets and powder to kill larvae in livestock confine-
ment areas and cockroaches in residences. Rarely, solutions are
sprayed as a nonselective herbicide.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
BORATE
Borax dust is moderately irritating to skin. Inhaled dust causes
irritation of the respiratory tract: cough and shortness of breath.
There have been few poisonings from the pesticidal uses of borates,
although powders and pellets scattered on the floors of homes do
present a hazard to children. Most poisonings have resulted from inju-
dicious uses in human medicine aimed at suppressing bacterial growth,
such as compresses for burns. Many poisonings of newborns occurred
in the 1950's and 1960's.
Borates are well absorbed by the gut and by abraded or burned skin,
but not by intact skin. They are efficiently excreted by the kidney. The
residence half-life in humans averages 13 hours, in a range of 4-28
hours.
The gastrointestinal tract, skin, vascular system, and brain are the
principal organs and tissues affected. Nausea, persistent vomiting, ab-
dominal pain, and diarrhea reflect a toxic gastroenteritis, which occurs
even when the borate was absorbed across damaged skin. Blood in
vomitus and feces reflect hemorrhagic lesions in the gut mucosa. In
severe poisonings of infants, a beefy red skin rash, most often affecting
palms, soles, buttocks, and scrotum, has been described. It has been
characterized as a "boiled lobster appearance." The intense erythema
is followed by extensive exfoliation.
Cyanosis, weak pulse, and cold clammy skin indicate shock, which is
sometimes the cause of death in borate poisoning.
Headache, weakness, lethargy, restlessness, and tremors may
progress to intermittent seizures. Unconsciousness and respiratory de-
pression signify life-threatening brain injury.
Acute renal failure (oliguria or anuria) may be a consequence of
shock, of direct toxic action on renal tubule cells, or both. It occurs
only in severe borate poisoning. Metabolic acidosis may be a conse-
quence of the acid itself, of seizure activity, or of metabolic derange-
ments. Fever is sometimes present in the absence of infection.
A recent analysis of 784 cases of ACUTE SINGLE-DOSE BORATE
DIGESTION (excluding newborns and cases of protracted exposure)
has indicated a much more favorable prognosis than that which was
based on neonate poisonings in the 1950's and 1960's (50%-70% mortal-
ity). In the recent survey (Litovitz, T. L. et al. Am. J. Emergency Med.
6(3):209-213, 1988), only 12% of cases were even symptomatic, and
there were no fatalities. In those who became symptomatic, gastroin-
testinal symptoms (vomiting, abdominal pain,- diarrhea) predominated.
40
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Central nervous system manifestations and rash were rare and of brief
duration when they did occur.
CONFIRMATION OF POISONING
Borate can be measured in serum by a colorimetric procedure, using
carminic acid as a chromogen. Blood borate concentrations in non-
exposed individuals are in the range of 0.0-7.2 mg per liter (average 1.4
mg per liter). Excluding newborns and chronically exposed individuals,
serum borate concentrations less than 340 mg per liter have rarely
been associated with significant toxicity.
A paper spot test for borate in the urine may be helpful in identify-
ing urine borate concentrations greater than 20 mg per liter. Urine
acidified with hydrochloric acid and applied to turmeric paper pro-
duces a brownish-red color if borate is present. A recent evaluation has
warned, however, that a significant number of false positives may be
encountered when this test is used.
TREATMENT OF BORATE TOXICOSIS
1. Dermal contamination should be removed by washing with soap
and water. Contamination of the eye should be treated by pro-
longed flushing with copious amounts of saline or water. If irrita-
tion persists, specialized medical treatment should be obtained.
2. The great majority of pesticidal borate poisonings are likely to be
acute (single dose) ingestions and are unlikely to occur in new-
borns. A recently recommended protocol for management of acute
borate ingestion (excluding newborns and chronically exposed per-
sons) is as follows (from above reference):
Patient's Weight, kg
Less than 30 kg
Greater than 30 kg
Dose of Borate
Less than 200
mg/kg
200-400 mg/kg
Greater than 400
mg/kg
Less than 6.0 gm
6.0-12.0 gm
Greater than 12.0
gm
Recommended Management
Observation only
Syrup of Ipecac
Syrup of Ipecac
lavage
Observation only
Syrup of Ipecac
Syrup of Ipecac
lavage
or gastric
or gastric
Dosage of Syrup of Ipecac for adults and children over 12 years is
30 ml; dosage for children under 12 years is 15 ml. Follow Syrup
of Ipecac with 2-3 glasses of water. Watch closely for declining
consciousness level; insure that victim is in a head down left
lateral decubitus position when vomiting ocfcurs. Protocol for gas-
tric lavage is set forth in Chapter 1, TREATMENT, Section 6,
41
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page 8. Activated charcoal does not adsorb borate and therefore
should not be given unless an additional toxicant was ingested
which is charcoal-adsorbable.
Obtain a blood sample 2-3 hours post-ingestion to assess severity
of poisoning, but do not base initial therapy on blood concentra-
tion.
3. IF INGESTION of borate has been MASSIVE (several grams), or
has extended over several days, administer intravenous glucose
and electrolyte solutions to sustain urinary excretion of borate.
Monitor fluid balance and blood electrolytes (including bicarbon-
ate capaciiy) regularly. Monitor cardiac status by EGG. Test the
urine for protein and cells to detect renal injury, and monitor
serum concentration of borate. If metabolic acidosis is detected,
sodium bicarbonate should be added to the infused fluids to keep
urine pH in the 7.0-7.5 range. If shock develops, it may be neces-
sary to infuse plasma or whole blood. Administer oxygen continu-
ously. If oliguria (less than 25-30 ml urine formed per hour)
occurs, intravenous fluids must be slowed or stopped to avoid
overloading the circulation.
A. Both peritoneal dialysis and extracorporeal hemodialysis have
been used with apparent success in accelerating elimination of
borate. If renal failure occurs, hemodialysis may be necessary
to sustain fluid balance and normal extracellular fluid compo-
sition. In poisoned infants, exchange blood transfusion has
been used successfully.
B. Control convulsions with benzodiazepine drugs or other anti-
convulsants, if necessary (see Chapter 3, TREATMENT, Sec-
tion 4, page 21).
CHLORDIMEFORM
STRUCTURE
=r\ H
N=C-N
\
CH,
CH.
COMMERCIAL PRODUCTS
Bermat, Fundal, Galecron, Ovatoxin.
42
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Formulations are emulsifiable concentrates and water-soluble pow-
ders. Chlordimeform is an ovicide and acaricide.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
CHLORDIMEFORM
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 were:
gross blood in the urine, painful urination, urinary frequency and
urgency, penile discharge, abdominal and back pain, a generalized
"hot" sensation, sleepiness, skin rash and desquamation, a sweet taste,
and anorexia. Symptoms persisted for 2-8 weeks after exposure was
terminated.
Chlordimeform is not a cholinesterase inhibitor. Although methods
do exist for measurement of urinary excretion products, these tests are
not generally available.
TREATMENT OF CHLORDIMEFORM TOXICOSIS
Strenuous efforts should be made to protect against inhalation and
dermal contact with chlordimeform because absorption is evidently
efficient. Skin contamination should be washed off with soap and
water. Contamination of the eye should be treated by flushing with
copious amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
If chlordimeform has been ingested no more than several hours prior
to treatment, and if the patient is fully alert, administer Syrup of
Ipecac, followed by several glasses of water, to empty the stomach.
Dosage for adults and children over 12 years: 30 ml; dosage for chil-
dren under 12 years: 15 ml.
If the patient is obtunded, the operation of a different or additional
toxicant should be suspected. In this event, the stomach should be
emptied by intubation, aspiration and lavage with a slurry of activated
charcoal in water or saline, after measures have been taken to protect
the respiratory tract from aspiration of gastric contents (see Chapter 1,
TREATMENT, Section 6, p. 8).
After the stomach has been emptied, activated charcoal and a ca-
thartic should be administered (see above reference). Repeated doses of
charcoal every 2-4 hours may be beneficial. Because catharsis may
cause serious dehydration and electrolyte disturbances in young chil-
dren, fluid balance and serum electrolytes should be monitored. An
adequate state of hydration should be maintained by oral and/or intra-
venous fluids to support chlordimeform excretion.
Repeated analyses of urine for protein and red cells should be donfex.
to detect injury to the urinary tract. Disappearance of hematuria can-'
43
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ordinarily be expected in 2-8 weeks. Relief from other symptoms can
usually be expected earlier.
PROPARGITE
STRUCTURE
H H H
-c-(\ /o-c-c-o-s-o-c-G=c H
CH-
H
\\ //
CH3 H2CX
H2C-
COMMERCIAL PRODUCTS
Omite, Comite, Uniroyal D014.
Formulations are wettable powders and emulsifiable concentrates.
Propargite is an acaricide with residual action.
TOXICOLOGY AND ADVERSE EFFECTS OF PROPARGITE
Propargite exhibits very little systemic toxicity in animals. No sys-
temic poisonings have been reported in humans. However, many work-
ers having dermal contact with this acaricide have experienced skin
irritation and possibly sensitization in some cases. Eye irritation has
also occurred. For this reason, stringent measures should be taken to
prevent inhalation or any skin or eye contamination by propargite.
There is no readily available method for detecting absorption of
propargite.
TREATMENT OF PROPARGITE TOXICOSIS
Skin contamination should be removed by prompt washing with soap
and water. Eye contamination should be treated by flushing with copi-
ous amounts of clean water or saline. If irritation persists, specialized
medical treatment should be obtained. Sensitization reactions may re-
quire steroid therapy.
If large amounts of propargite have been ingested, and effective
vomiting has not occurred, and if there are no indications of nervous
system depression, administration of Syrup of Ipecac, followed by sev-
eral glasses of water, is probably the appropriate method to empty the
stomach. Dosage for adults and children over 12 years: 30 ml; dosage
for children under 12 years: 15 ml.
If there are indications of central nervous system depression, empty
the stomach by intubation, aspiration, and lavage-with a slurry of
44
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activated charcoal, having first taken precautions to prevent aspiration
of stomach contents (see Chapter 1, TREATMENT, Section 6, p. 8).
Follow the lavage with instillation of activated charcoal (see above
reference). Include sorbitol in the charcoal instillation if diarrhea has
not already commenced.
If the amount of propargite ingested was small, or if treatment is
delayed, oral administration of activated charcoal and sorbitol probably
represents optimal management.
DIFLUBENZURON
COMMERCIAL PRODUCTS
Dimilin, Micromite.
This is a haloaromatic substituted urea which controls insects by
impairing chitin deposition in the larval exoskeleton. It is formulated
in wettable powders, oil dispersible concentrate, and granules for use
in agriculture and forestry and in settings where fly populations tend
to be large, such as feedlots.
TOXICOLOGY OF DIFLUBENZURON
There is limited absorption across the skin and intestinal lining of
mammals, after which enzymatic hydrolysis and excretion rapidly
eliminate the pesticide from tissues. Irritant effects are not reported
and systemic toxicity is low. Methemoglobinemia is a theoretical risk
from chloroaniline formed hydrolytically, but no reports of this form of
toxicity have been reported in humans or animals from diflubenzuron
exposure.
Treatment of contamination and ingestions should proceed essential-
ly as outlined in the previous section (Propargite).
TEFLUBENZURON
COMMERCIAL PRODUCTS
Nomolt, Dart, Diaract.
This is another haloaromatic substituted urea insecticide, apparently
similar in toxicologic properties to diflubenzuron (above). Low systemic
toxicity is reported.
45
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CHLOROBENZILATE
STRUCTURE
0=C-OC2H5
COMMERCIAL PRODUCTS
Acaraben, Akar, Folbex, Benzilan.
Chlorobenzilate is a chlorinated hydrocarbon acaricide, usually for-
mulated as an emulsion or wettable powder for application in orchards.
It is presently a Restricted Use Pesticide because of neoplastic effects
observed in laboratory animals subjected to high dosage over long
periods.
TOXICOLOGY OF CHLOROBENZILATE
Chlorobenzilate is moderately irritating to the skin and eyes.
Although structurally similar to DDT, chlorobenzilate is much more
rapidly excreted following absorption, chiefly in the urine as the benzo-
phenone and benzoic acid derivatives. No systemic poisonings of
humans have been reported. Based on observation of dosed animals,
extreme absorbed doses may cause tremors, ataxia, and muscle weak-
ness.
Chlorobenzilate is not a cholinesterase inhibitor.
TREATMENT OF CHLOROBENZILATE EXPOSURE
Remove skin contamination by washing with soap and water.
Remove eye contamination by flushing with clean saline or water. If
irritation persists, medical attention must be obtained.
If a large amount of chlorobenzilate was ingested within a few hours
prior to treatment, and if there are no indications of central nervous
system disturbance, empty the stomach by administering Syrup of
Ipecac followed by several glasses of water. Dosage for adults and
children over 12 years: 30 ml; dosage for children under 12 years: 15
ml.
After vomiting stops, administer activated charcoal and sorbitol
orally (for dosage, see Chapter 1, TREATMENT, Section 6, p. 8).
If there are indications of central nervous system disturbance (de-
pression, ataxia, tremor), empty the stomach by intubation, aspiration,
46
-------
and lavage, after first taking all precautions to protect the respiratory
tract from aspiration of gastric contents (see Chapter 1, TREATMENT,
Section 6, p. 8). Lavage the stomach with a slurry of activated charcoal!
Leave charcoal and an appropriate dose of sorbitol in the stomach
before withdrawing the lavage tube.
If the absorbed dose of chlorobenzilate was small, if treatment is
delayed, and if the patient is asymptomatic, oral administration of
activated charcoal and sorbitol is probably the optimal management
(see Chapter 1, TREATMENT, Section 6, p. 8 for dosage). Do not give
fats or oils.
CYHEXATIN
STRUCTURE
Sn-OH
COMMERCIAL PRODUCT
Plictran.
TOXICOLOGY OF CYHEXATIN AND TREATMENT OF TOXICOSIS
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 infor-
mation on the systemic toxicity of this specific tin compound is lacking,
it should probably be assumed that cyhexatin can be absorbed to some
extent across the skin, and that substantial absorbed doses would cause
nervous system injury (see Organotin compounds in Chapter 12: FUN-
GICIDES). Accordingly, dermal contamination should be promptly re-
moved by washing with soap and water, and contamination of the eyes
47
-------
should be treated by prolonged flushing with clean water or saline.
Management of poisonings by ingestion should proceed on the assump-
tion that cyhexatin is highly toxic, even though rodent LD50 values are
fairly high, and no human poisonings have been reported. See Chapter
1, TREATMENT, Section 6, p. 8 concerning measures to limit toxicant
absorption from the gut. Neither BAL, penicillamine nor chelating
agents have been effective in lowering tissue stores of organic tin
compounds in experimental animals.
METHOPRENE
COMMERCIAL PRODUCTS
ZR-515, Altosid SR-10 and CP-10, Apex 5E, Diacon, Dianex, Kabat,
Minex, Pharorid, Precor.
Methoprene is a long chain hydrocarbon ester active as an insect
growth regulator. It is effective against several insect species. Formula-
tions include slow-release briquets, sprays, foggers and baits.
TOXICOLOGY OF METHOPRENE
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 OF METHOPRENE TOXICOSIS
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.
If a very large amount of methoprene has been ingested, oral admin-
istration of charcoal may be considered. The hazards of catharsis (dehy-
dration, electrolyte disturbances) probably outweigh the hazards of
methoprene.
SULFUR
s=s
COMMERCIAL PRODUCTS
Brimstone, Lacco Sulfur, Clifton Sulfur, Sul-Cide, Cosan, Kumulus S,
Sofril, Sulfex. Thiolux, Thiovit, Magnetic 6, Liquid Sulfur, Thion,
Zolvis, Golden Dew.
48
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Elemental sulfur is an acaricide and fungicide widely used on or-
chard, ornamental, vegetable, grain and other crops. It is prepared as
dust in various particle sizes and applied as such, or it is formulated
with various minerals to improve flowability, or is applied as an aque-
ous emulsion of wettable powder.
TOXICOLOGY OF SULFUR
Elemental sulfur is moderately irritating to the skin, and 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 irritating gaseous sulfur oxides, which are very irritating to the eyes
and respiratory tract.
Ingested sulfur powder induces catharsis, and has been used medici-
nally (usually with molasses) for that purpose. Some hydrogen sulfide
is formed in the large intestine and this may present a degree of toxic
hazard. However, an adult has survived ingestion of 60 grams.
Ingested colloidal sulfur is efficiently absorbed by the gut and is
promptly excreted in the urine as inorganic sulfate.
TREATMENT OF SULFUR TOXICOSIS
Skin contamination should be removed by washing with soap and
water. Contamination of the eyes should be removed by prolonged
flushing with clean saline or water. If irritation persists, medical atten-
tion should be obtained.
Unless an extraordinary amount of sulfur (several grams) has been
ingested shortly prior to treatment, there is probably no need for
emptying of the stomach or administration of a cathartic. Adsorbabil-
ity of sulfur on activated charcoal has not been tested.
The most serious consequence of sulfur ingestion is likely to be that
of catharsis: dehydration and electrolyte depletion, particularly in chil-
dren. If diarrhea is severe, oral or intravenous administration of glu-
cose and/or electrolyte solutions may be appropriate.
DIETHYLTOLUAMIDE (DEBT)
STRUCTURE
C-N
/C2H5
\
49
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COMMERCIAL PRODUCTS
Detamide, Metadelphene, MGK, OFF.
This chemical is a widely used liquid insect repellent, suitable for
application to skin or to fabrics. It is formulated with ethyl or isopro-
pyl alcohol, usually in pressurized containers.
TOXICOLOGY OF DEBT
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 dermati-
tis and excerbation of preexisting skin disease. It is very irritating to
the eyes, but not corrosive.
Serious adverse effects have occurred when used under tropical con-
ditions, when it was applied to areas of skin that were occluded during
sleep (mainly the antecubital and popliteal fossae). Under these condi-
tions, the skin became red and tender, then exhibited blistering and
erosion, leaving painful weeping denuded areas that were slow to heal.
Permanent scarring resulted from most of these severe reactions.
DEET is efficiently absorbed across the skin and by the gut. Blood
concentrations of about 3 mg per liter have been reported several
hours after dermal application in the prescribed fashion. Toxic ence-
phalopathic reactions have apparently occurred in rare instances fol-
lowing dermal application, mainly in children who were intensively
treated. The more frequent cause of systemic toxicity has been inges-
tion, deliberate in adults, accidental in young children.
Manifestations of toxic encephalopathy have been behavioral disor-
ders including headache, restlessness, crying spells, mania, stupor pro-
gressing to coma, ataxia, hyperreflexia, tachypnea, hypotension, trem-
ors, and writhing convulsions (athetosis). Some cases have shown flac-
cid paralysis and areflexia. Deaths have occurred following very large
doses. Blood levels of DEET found in fatal systemic poisonings have
ranged from 168 to 240 milligrams per liter. Interpretation of DEET
toxicity in some fatal cases has been complicated by effects of simulta-
neously ingested ethanol, tranquilizers, and other drugs. One well doc-
umented case of anaphylactic reaction to DEET has been reported. One
fatal case of encephalopathy in a child heterozygous for ornithine
carbamoyl transferase deficiency resembled Reyes syndrome, but the
postmortem appearance of the liver was not characteristic of the syn-
drome.
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).
50
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Great caution should be exercised in using DEBT on children. Only
the products containing the lower concentrations (usually 15%) should
be used, and application should be limited to exposed areas of skin,
using as little repellent as possible. If continuous repellent protection
is necessary, DEET should be alternated with a repellent having an-
other active ingredient. If headache or any kind of emotional or behav-
ioral change occurs, use of DEET should be discontinued immediately.
CONFIRMATION OF DIETHYLTOLUAMIDE POISONING
Methods exist for measurement of DEET in blood and tissues and of
metabolites in urine, but these are not widely available.
TREATMENT OF DEET TOXICOSIS
If a skin reaction occurs, residual DEET should be removed by
washing the treated area with soap and water. Eye contamination
should be treated by prolonged flushing with clean saline or water. K
irritation persists, medical treatment should be obtained.
Steroid or. antimicrobial topical medications may be indicated for
severe skin reactions that occasionally follow application of DEET.
If a substantial amount of DEET has been INGESTED within a few
hours of treatment, the stomach should be intubated, aspirated, and
lavaged with a slurry of activated charcoal, after every precaution has
been taken to protect the airway from aspiration of gastric contents
(see Chapter 1, TREATMENT, Section 6, p. 8). A slurry of charcoal,
including an appropriate dose of sorbitol, should be left in the stomach
before the tube is withdrawn (see above reference for dosage). If a very
large amount of DEET was swallowed, repeated doses of charcoal every
2-4 hours may be beneficial.
If dosage ingested was assuredly small, and the patient is fully alert,
oral administration of activated charcoal and sorbitol probably repre-
sents optimal management. If diarrhea has already commenced, the
sorbitol should be omitted.
Intravenous electrolytes, plasma and/or whole blood may be needed
to combat shock in severe poisonings. Administer oxygen continuously
by mask if respiratory or circulatory embarrassment is evident. Adre-
nergic amines may be indicated.
If convulsive activity develops, benzodiazepine or other anticonvul-
sants may be required (see Chapter 3, TREATMENT, Section 4, p. 21).
Persons surviving poisoning by ingestion of DEET have usually re-
covered in 2 to 24 hours.
51
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ALKYL PHTHALATES
STRUCTURE
O
II
-C-O-CH.
-C-0-CH.
II
0
DIMETHYL PHTHALATE
COMMERCIAL PRODUCT
BMP.
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 OF ALKYL PHTHALATES
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 sensi-
tization.
Tests in rodents have indicated low systemic toxicity, but large in-
gested doses cause gastrointestinal irritation, central nervous system
depression (to coma), and hypotension. One accidental ingestion by a
human resulted in coma, but recovery was prompt.
TREATMENT OF ALKYL PHTHALATE TOXICOSIS
No antidote is available. Supportive measures (hydration, oxygen if
needed) are probably adequate to manage all but the most severe
poisonings.
52
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BENZYL BENZOATE
STRUCTURE
TOXICOLOGY, MANIFESTATIONS, AND TREATMENT
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 of skin absorption is not known. Absorbed
benzyl benzoate is rapidly biotransformed to hippuric acid which is
excreted in the urine. When given in large doses to laboratory animals,
benzyl benzoate causes excitement, incoordination, paralysis of the
limbs, convulsions, respiratory paralysis, and death. No human poison-
ings have been reported. If significant irritant effect appears, medica-
tion should be discontinued and the skin cleansed with soap and water.
Eye contamination should be treated by prolonged flushing with clean
water or saline. If a potentially toxic amount has been swallowed and
retained, steps should be taken to remove it from the gastrointestinal
tract and repeated doses of activated charcoal should be administered
(see Chapter 1, TREATMENT, Section 6, p. 8). If seizures occur, control
may require anticonvulsant medication (see Chapter 3, TREATMENT
Section 4, p. 21). '
53
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CHAPTER 6
ARSENICAL PESTICIDES
INORGANIC TRIVALENT
Arsenic Trioxide
/°\
As— O-As
"White arsenic," arsenous oxide. The active
ingredient in some ant pastes and veterinary
preparations.
Sodium arsenite
Na-O-As=O
Calcium arsenite
O-As=O
I
Ca
I
O-As=O
(approx.)
Chem Pels C. Chem-Sen 56, Kill-All, Penite,
Prodalumnol Double. Used in aqueous
solution for weed control; limited use as
insecticide.
Mono-calcium arsenite. Flowable powder
for insecticidal use on fruit.
Copper arsenite
(Acid copper arsenite)
HO-Cu-O-As=O
Copper acetoarsenite
O
Cu-(O-C-CH3)2
•
3Cu—(O—As=O)2
Arsine
H H
\ /
As
I
H
Wettable powder, for use as insecticide,
wood preservative.
Insecticide. Paris Green, Schweinfurt
green, emerald green, .French green, mitis
green. No longer used in U.S.; still used
outside U.S.
Not a pesticide. Occasionally generated
during manufacture of arsenicals.
54
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INORGANIC PENTAVALENT
Arsenic acid
OH
HO. I
>iS=0
HO
Dessicant L-10, Hi-Yield Dessicant H-10,
Zotox. Water solutions used as defoliants,
herbicides.
Sodium arsenate
OH
NaO. ||
^AS = 0
NaO
Disodium arsenate. Jones Ant Killer, Terro
Ant Killer.
Calcium arsenate
Ca As-O-Ca-O-As Ca
V V
Tricalcium arsenate. Pencal, Spra-cal, Turf-
Cal. Flow/able powder formulations used
against weeds, grubs.
Lead arsenate
OH
xOv I
Pb NAs = O
Gypsine, Soprabel, Talbot. Limited use in
U.S.; wettable powder used as insecticide
outside the U.S.
Zinc arsenate
Zn As-O— Zn-O-As
Powder one used in U.S. as insecticide on
potatoes and tomatoes.
55
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ORGANIC (PENTAVALENT)
Cacodylic acid
(sodium cacodylate)
CH3 CH3
\ /
As
O
OH
(or Na)
Non-selective herbicide, defoliant, silvicide.
Bolate, Bolls-Eye, Bophy, Dilie, Kack,
Phytar 560, Rad-E-Cate 25, Salvo.
Methane arsonic acid
CH3 OH
\ /
As
•#• ^
O OH
Monosodium methane arsonate
CH3 OH
\ /
MAA. Non-selective herbicide.
Disodium methane arsonate
CHs ONa
>'
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SOLID ARSENIC COMPOUNDS
TOXICOLOGY OF ARSENIC
Arsenic is a natural element having both metal and nonmetal
physical/chemical properties. In one respect or another, it resembles
nitrogen, phosphorus, .antimony, and bismuth in its chemical behavior.
In nature, it exists in elemental, trivalent (—3 or +3), and pentavalent
(+5) states. It binds covalently with most nonmetals (notably oxygen
and sulfur) and with metals (for example, calcium and lead). It forms
stable trivalent and pentavalent organic compounds. In biochemical
behavior, it resembles phosphorus, competing with phosphorus analogs
for chemical binding sites. Toxicity of the various arsenic compounds
in mammals extends over a wide range, determined, in part, by 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 triva-
lent compounds). Inorganic pentavalent compounds are somewhat less
toxic that arsenites, while the organic (methylated) pentavalent com-
pounds incur the least hazard of the arsenicals that are used as pesti-
cides.
The pentavalent arsenicals are relatively water soluble and absorb-
able across mucous membranes while trivalent arsenicals, having
greater lipid solubility, are more readily absorbed across the skin.
However, poisonings by dermal absorption of either form have been
extremely rare. Ingestion has been the usual basis of poisoning; gut
absorption efficiency depends on the physical form of the compound, its
solubility characteristics, the gastric pH, gastrointestinal motility, and
gut microbial transformations. Once absorbed, many arsenicals cause
toxic injury to cells of the nervous system, blood vessels, liver, kidney,
and other tissues. Two biochemical mechanisms of toxicity are recog-
nized: 1) reversible combination with thiol groups contained in tissue
proteins and enzymes, and 2) substitution of arsenic anions for phos-
phate in many reactions, including those critical to oxidative phosphor-
ylation. Because there are many uncertainties regarding the biotrans-
formation of various arsenicals in the gut and in the body, and because
the toxic potentials of the biotransformation products are not well
established, it is generally safest to manage cases of arsenic ingestion
as though all forms of arsenic are highly toxic.
Mammals, including humans, detoxify inorganic arsenic by methyla-
tion, yielding cacodylic acid (dimethylarsinic acid) as the chief urinary
excretion product. Disposition by urinary excretion is usually prompt.
Elimination of the arsonic acid (monomethyl) compounds has not been
extensively studied, but urinary excretion of the unaltered compound
and/or a further methylated form would seem likely.
The unique toxicology of arsine gas is described later in this chapter.
57
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SYMPTOMS AND SIGNS OF POISONING BY SOLID
ARSENICALS
Manifestations of acute poisoning (large amount absorbed over a
short time) are distinguishable from those of chronic poisoning (lesser
doses absorbed over a longer tune interval).
The symptoms and signs of ACUTE ARSENIC POISONING 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 responsible toxicant in a severely poisoned patient. Gastrointesti-
nal effects include inflammation of the mouth, pharynx, and esopha-
gus, burning abdominal pain, thirst, vomiting, and rice-water or bloody
diarrhea. These effects result from the action of an arsenical metabo-
lite on blood vessels generally, but the splanchnic vasculature particu-
larly, causing dilation and increased capillary permeability.
Renal injury is manifest as proteinuria, hematuria, glycosuria, oligu-
ria, casts in the urine, and, in severe poisoning, acute tubular necrosis.
Central nervous system effects include headache, dizziness, muscle
weakness and spasms, hypothermia, lethargy, delirium, coma, and con-
vulsions. Cardiovascular manifestations include shock, cyanosis, and
cardiac arrhythmias, which are due to direct toxic action and electro-
lyte disturbances. Liver damage may lead to increased concentrations
of circulating hepatocellular enzymes and to jaundice. Injury to blood-
forming tissues may cause anemia, leukopenia, and thrombocytopenia.
Death usually occurs one to three days following symptom onset and is
usually the result of circulatory failure.
CHRONIC ARSENIC POISONING from repeated absorption of toxic
amounts generally has an insidious onset of clinical effects and may be
difficult to diagnose. Dermal manifestations are usually more promi-
nent than the gastrointestinal effects which characterize acute poison-
ing: hyperkeratosis, hyperpigmentation, exfoliative dermatitis, subcuta-
neous edema of the face, eyelids and ankles, white striations across the
nails (Mees lines), and sometimes loss of nails or hair. Stomatitis,
anorexia, and weight loss are typical. Peripheral neuropathy (paresthe-
sia, pain, anesthesia, paresis, ataxia) may be a prominent feature.
Liver injury reflected in hepatomegaly and jaundice may progress to
cirrhosis, portal hypertension, and ascites. Nephropathy is indicated
principally by proteinuria. Electrocardiographic abnormalities and pe-
ripheral vascular disease have been reported. Anemia, leukopenia, and
thrombocytopenia are characteristic. Late sequelae of protracted high
intakes of arsenic include skin cancer, an increased risk of lung cancer,
and, rarely, encephalopathy (ophthalmoplegia, chronic headache,
speech and mental disturbances).
58
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CONFIRMATION OF POISONING BY ARSENICALS
Measurement of 24-hour urinary excretion of arsenic (micrograms
per day) is probably the best way to confirm excessive absorption,
although methods for blood arsenic concentration are available (see
below). Persons on non-seafood diets usually excrete less than 20 micro-
grams (meg) per day, but diets rich in seafood may generate as much
as 200 meg per day and sometimes more. (The arsenic in seafood is
apparently bound firmly to betaine, which renders the arsenic essen-
tially nontoxic and highly excretable.) Arsenic excretion above 100 meg
per day should be viewed with suspicion and the test should be repeat-
ed. Excretions above 200 meg per day reflect a toxic intake, unless
seafood was ingested.
In acute poisonings that require a prompt indication as to whether
recent arsenic intake has been far in excess of normal, two qualitative
tests of urine are generally available, both sensitive to concentrations
of about 2000 meg per liter of urine:
Gutzeit test: To 5 ml of urine, add a few drops of concentrated
sulfuric acid and a few granules of elemental zinc. Cover the top
of the tube with a piece of filter paper to which a drop or two of
1% silver nitrate solution has been added. Browning or blacken-
ing of the paper indicates that arsine has been evolved from the
urine.
Reinsch test: Concentrate 10 ml of urine to 1 ml by boiling.
Prepare a piece of copper foil or wire by cleaning the surface,
then treating it with concentrated nitric acid, then washing it
with distilled water. Put the copper in a flask with the concen-
trated urine sample and acidify with about 0.1 ml concentrated
hydrochloric acid. Boil for 15 minutes. A dull black stain probably
indicates arsenic. Bismuth, mercury, and antimony cause some-
what different discolorations of the copper. If this occurs, analysis
for arsenic specifically must be carried out.
Lower concentrations of arsenic in blood, urine, or other biologic
materials can be measured by either wet or dry ashing, followed by
colorimetric or atomic absorption spectrometric analysis. (Baselt, R.C.
Biological Monitoring Methods for Industrial Chemicals, Biomedical
Publications, 1980.) Blood concentrations in excess of about 100 meg
per liter probably indicate excessive intake, if seafood was not ingested
before the sample was taken.
Special tests for arsine toxicosis are described below under "Arsine
Gas."
TREATMENT OF ARSENIC COMPOUND TOXICOSIS
The following discussion applies principally to poisonings by arseni-
cals that are in solid or dissolved form. Treatment of poisoning by
59
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2.
8.
arsine gas requires special measures that are described later in this
chapter under "Arsine Gas."
1. Wash arsenical pesticide from skin and hair with copious
amounts of soap and water.
Flush contaminant from eyes with clean water. If irritation per-
sists, specialized medical treatment should be obtained.
If arsenical pesticide has been ingested within a few hours of
treatment, empty the stomach by INTUBATION, ASPIRATION,
and LAVAGE, taking all precautions to protect the respiratory
tract from aspiration of vomitus. The effectiveness of gastric evac-
uation diminishes rapidly with the passage of tune. The procedure
for evacuation of the stomach is described in Chapter 1, TREAT-
MENT, Section 6, p. 8.
Leave activated charcoal in the stomach, as indicated in the above
reference. Repeated administration of charcoal at half or more
the original dose every 2-4 hours may be beneficial.
Because poisoning by ingested arsenic almost always results in
profuse diarrhea, it is generally NOT appropriate to ADMINIS-
TER a CATHARTIC.
If treatment has been delayed, and if the victim remains fully
alert, administer activated charcoal orally at dosages suggested in
Chapter 1, TREATMENT, Section 6. Repeat every 2-4 hours.
Administer INTRAVENOUS FLUIDS to restore adequate hydra-
tion, support urine flow, and correct electrolyte imbalances. Moni-
tor intake/output continuously to guard against fluid overload if
acute renal failure occurs. Monitor blood electrolytes regularly.
Blood transfusions and oxygen by mask may be needed to combat
shock.
Monitor cardiac status by EGG to detect arrhythmias and toxic
myocardiopathy (T wave inversion, long S-T interval).
Administration of DIMERCAPROL (BAL) is usually indicated in
symptomatic arsenic poisonings. The following dosage schedule
has proven to be effective in accelerating arsenic excretion.
4.
5.
6.
7.
8.
9.
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 q12h
(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 Jhe table are in terms of BAL
itself, not of the solution.
60
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CAUTION: Disagreeable side effects often accompany the use of
BAL: nausea, headache, burning and tingling sensations, sweat-
ing, pain in the back and abdomen, tremor, restlessness, tachycar-
dia, hypertension, and fever. Coma and convulsions occur at very
high dosage. Sterile abscesses may form at injection sites. Acute
symptoms usually subside in 30-90 minutes. Antihistamine drugs
or an oral dose of 25-50 mg ephedrine sulfate provide relief. These
are more effective if given a few minutes before the injection of
BAL.
10. After the gastrointestinal tract is reasonably free of arsenic (as
indicated by passage of a charcoal-black stool), oral administra-
tion of D-PENICILLAMINE should probably replace BAL ther-
apy in persons who are not allergic to penicillin.
Dosage of D-PENICILLAMINE:
Adults and children over 12 years: 0.5 gm every 6 hours,
given 30-60 minutes before meals and at bedtime for about 5
days.
Children under 12 years: 0.1 gm/kg body weight, not exceed-
ing 1.0 gm per day, divided into 4 doses, given 30-60 minutes
before meals and at bedtime for about 5 days.
CAUTION: Adverse reactions to short term therapy are rare.
Persons allergic to penicillin may suffer allergic reactions to
D-penicillamine; they should be treated with BAL only.
11. Extracorporeal hemodialysis, used in combination with BAL ther-
apy, has limited effectiveness in removing arsenic from the blood.
Hemodialysis is clearly indicated to enhance arsenic elimination
and maintain extracellular fluid composition if acute renal failure
occurs.
12. MONITOR URINARY ARSENIC EXCRETION while BAL or
D-penicillamine are being administered. When 24-hour excretion
falls below 50 meg per day, it is usually advisable to discontinue
the chelation therapy.
ARSINE GAS
Arsine is not used as a pesticide. However, some poisonings by arsine
have occurred in pesticide manufacturing plants and metal refining
operations when arsenicals came into contact with mineral acids or
strong reducing agents.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
ARSINE
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. Symptoms of poisoning
usually appear 1-24 hours after exposure: headache, malaise, weak-
61
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ness, dizziness, dyspnea, nausea, ABDOMINAL PAIN, and vomiting.
Dark red urine (HEMOGLOBINURIA) is often passed 4-6 hours after
exposure. Usually 1-2 days after hemoglobinuria appears, JAUNDICE
is evident. Hemolytic anemia, sometimes profound, usually provides
diagnostic confirmation and can cause severe weakness. Abdominal
tenderness and liver enlargement are often apparent. Basophilic stip-
pling of red cells, red cell fragments, and ghosts are seen in the blood
smear. Methemoglobinemia and methemoglobinuria are evident. Ele-
vated 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.
Polyneuropathy and a mild psycho-organic syndrome are reported to
have followed arsine intoxication after a latency of 1-6 months.
TREATMENT OF ARSINE TOXICOSIS
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
should not be expected, even in severe poisoning.
4. If poisoning is severe, EXCHANGE BLOOD TRANSFUSION may
be considered. It was successful in rescuing one adult victim of
arsine poisoning.
5. Extracorporeal HEMODIALYSIS may be necessary to maintain
normal extracellular fluid composition and to enhance arsenic
elimination if renal failure occurs, but it is not very effective in
removing the arsine carried in the blood.
6. Administration of BAL (dimercaprol) may be considered, but it
has not proven to be effective in arsine poisonings to date. The
efficacy of D-penicillamine has not been tested.
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CHAPTER 7
CHLOROPHENOXY HERBICIDES
GENERAL CHEMICAL STRUCTURE
Cl (or CH3)
— O —
0
IF
C — O — H
COMMERCIAL PRODUCTS
Several hundred commercial products contain chlorophenoxy herbi-
cides in various forms, concentrations, and combinations. Following are
names of widely advertised formulations. In some cases, the same
name is used for products with different ingredients. Exact composition
must therefore be determined from the product label.
2,4-D or 2,4-dichlorophenoxyacetic acid (Agrotect, Amoxone, Aqua-
Kleen, BH 2,4-D, Chipco Turf Herbicide 'D', Chloroxone, Crisalamina,
Crisamina, Crop Rider, D50, Dacamine, Debroussaillant 600, Ded-Weed
SULV, Desormone, Dinoxol, Emulsamine BK, Emulsamine E-3, Envert
DT, Envert 171, Super D Weedone, Weedone, Estone, Farmco, Fer-
nesta, Fernimine, Fernoxone, Ferxone, Formula 40, Gordon's Amine
400, Gordon's LV 400 2,4-D, Hedonal, Herbidal, Lawn-Keep, Macon-
dray, Miracle, Netagrone 600, Pennamine D, Planotox, Plantgard,
Salvo, Spritz-Hormin/2,4-D, Spritz-Hormit/2,4-D, Superormone Con-
centre, Transamine, Tributon, Tuban, U 46, U 46 D-Ester, U 46 D-
Fluid, Weed-B-Gon, Weedar, Weedatul, Weed-Rhap, Weed Tox, Weed-
trol, Gordon's Dymec Turf Herbicide Amine 2,4-D, Gordon's Phenaban
801, Acme Amine 4, Acme Butyl Ester 4, Acme LV 6, Acme LV 4,
Gordon's Butyl Ester 600, DMA 4, Dormone).
2,4-DP or 2,4-dichlorophenoxypropionic acid (BH 2,4-DP, Desormone,
Hedonal, Hedonal DP, Kildip, Polymone, Seritox 50, U 46, U 46 DP-
Fluid, Weedone DP, Weedone 170).
2,4-DB or 2,4-dichlorophenoxybutyric acid (Butoxon, Butoxone, Bu-
tyrac, Embutox). , -
2,4,5-T or 2,4,5-trichlorophenoxyacetic acid (Amine 2,4,5-T for rice,
Dacamine, Ded-Weed, Farmco Fence Rider, Forron, Inverton 245, Line
Rider, Super D Weedone, T-Nox, Trinoxol, U 46, Weedar, Weedone).
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MCPA (metaxon, Agroxone, Weedone), MCPB (Can-Trol, PDQ, This-
trol), and MCPP (mecoprop, Methoxone M, Mecopex, Gordon's Meco-
mec) are 2-methyl, 4-chlorophenoxy aliphatic acids and esters.
Dicamba (Banvel) is 2-methyl-3,6 dichlorobenzoic acid.
Sodium, potassium, and alkylamine salts are commonly formulated
as aqueous solutions, while the less water soluble esters are applied as
emulsions. Low molecular weight esters are more volatile than the
acids, salts, or long-chain esters.
Chlorophenoxy compounds are sometimes mixed into commercial
fertilizers to control growth of broadleaf weeds.
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.
The chlorophenoxy compounds are absorbed across the gut wall,
lung, and skin. They are not significantly fat storable. Excretion occurs
almost entirely by way of the urine. Apart from some conjugation of
the acids, there is limited biotransformation in the body. The average
residence half-life of 2,4-D in the human is about 18 hours, that of
2,4,5-T about 24 hours. These averages lie within very wide ranges (4-
140 hours in the case of 2,4-D), depending on urinary pH (alkalinity
enhances excretion).
Given in large doses to experimental animals, 2,4-D causes vomiting,
diarrhea, anorexia, weight loss, ulcers of the mouth and pharynx, and
toxic injury to the liver, kidneys, and central nervous system. Myo-
tonia (stiffness and incoordination of hind extremities) develops in
some species and is apparently due to CNS damage: demyelination has
been observed in the dorsal columns of the cord, and EEG changes
have indicated functional disturbances in the brains of heavily dosed
experimental animals.
Ingestion of large amounts of chlorophenoxy acids has resulted in
severe metabolic acidosis in humans. Such cases have been associated
with electrocardiographic changes, myotonia, muscle weakness, myo-
globinuria, and elevated serum creatine phosphokinase, all reflecting
injury to striated muscle. Because chlorophenoxy acids are weak un-
couplers of oxidative phosphorylation, extraordinary doses may
produce hyperthermia from increased production of body heat.
Chlorinated Dibenzo Dioxin (CDD) and Chlorinated Dibenzo Furan
(CDF) compounds are generated in the manufacture of chlorophenoxy
compounds, particularly at excessive temperatures. 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-com-
pounds exhibit less systemic toxicity, but are the likely cause of chlor-
acne (a chronic, disfiguring skin condition) seen in workers engaged in
64
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manufacture of 2,4,5-T and certain other chlorinated organic com-
pounds. 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.
The medical literature contains some reports of peripheral neuropa-
thy following what seemed to be minor dermal exposures to 2,4-D. It is
not certain that exposures to other neurotoxicants were entirely ex-
cluded 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.
SYMPTOMS AND SIGNS OF POISONING
Chlorophenoxy compounds are moderately IRRITATING to skin and
mucous membranes. Inhalation of sprays may cause burning sensa-
tions in the nasopharynx and chest and coughing may result. Pro-
longed inhalation sometimes causes dizziness. Adjuvant chemicals
added to enhance foliage penetration may account for the irritant
effects of some formulations.
Manifestations of systemic toxicity of chlorophenoxy compounds are
known mainly from clinical experience with cases of deliberate suicidal
ingestion of large quantities. 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. Few
cases of deliberate ingestion of chlorophenoxy compounds have termi-
nated fatally.
Irritation of the stomach usually leads to VOMITING soon after
ingestion. Pain in the chest and abdomen and diarrhea may ensue.
Headache, mental confusion, and bizarre behavior are early manifesta-
tions of severe poisoning which may progress to UNCONSCIOUSNESS.
MYOTONIA (muscular stiffness on passive movement of the limbs) has
occurred in persons poisoned by 2,4-D. Areflexia is sometimes observed.
Muscle twitching may or may not be evident. Convulsions occur very
rarely. Respiratory drive is not depressed; hyperventilation is some-
times evident. Body temperature may be moderately elevated, but this
is rarely a life-threatening feature of the poisoning. With effective
urinary excretion of the toxicant, consciousness usually returns in
48-96 hours.
Metabolic acidosis is manifest as a low arterial pH and bicarbonate
content. The urine is usually acid. Skeletal muscle injury, if it occurs,
is reflected in elevated creatine phosphokinase, and sometimes myoglo-
binuria. Moderate temporary elevations of blood urea nitrogen and
serum creatinine are commonly found as the toxicant is excreted, but
acute renal failure is uncommon. Mild leukocytosis and biochemical
changes indicative of liver cell injury have been reported. Both tachy-
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cardia and bradycardia have been observed. T-wave flattening and
inversion may occur.
Myotonia and muscle weakness may persist for months after acute
poisoning. Electromyographic and nerve conduction studies in some
recovering patients have demonstrated a mild proximal neuropathy
and myopathy.
CONFIRMATION OF POISONING
Gas-liquid chromatographic methods are available for detecting and
measuring chlorophenoxy compounds in blood and urine. These analy-
ses are useful in confirming and assessing the magnitude of chloro-
phenoxy absorption. Poisonings characterized by unconsciousness have
shown initial blood chlorophenoxy concentrations ranging from 80 to
more than 1000 mg per liter. Urine samples should be collected as soon
as possible after exposure because the herbicides may be almost com-
pletely excreted in 24-72 hours, depending on the extent of toxicant
absorption and urine pH. Analyses can be performed at special labora-
tories usually known to local poison control centers. If circumstances
indicate strongly that excessive exposure to chlorophenoxy compounds
has occurred, INITIATE appropriate TREATMENT measures immedi-
ately, not waiting for chemical confirmation of toxicant absorption.
TREATMENT OF POISONING BY CHLOROPHENOXY
COMPOUNDS
1. BATHE and SHAMPOO with soap and water to remove chemi-
cals from skin and hair. Obtain medical treatment if irritation
persists. Individuals with chronic skin disease or known sensitivi-
ty to these herbicides should either avoid using them or take
strict precautions to avoid contact (respirator, gloves, etc.).
2. FLUSH contaminating chemicals from eyes with copious amounts
of clean water for 10-15 minutes. If irritation persists, obtain
medical treatment.
3. If any symptoms of illness occur during or following inhalation of
spray, REMOVE victim FROM CONTACT with the material for
at least 2-3 days. Allow subsequent contact with chlorophenoxy
compounds only if effective respiratory protection is practiced.
4. If substantial amounts of chlorophenoxy compounds have been
INGESTED, spontaneous emesis may occur. If vigorous emesis
has not occurred, measures should be taken to empty the stomach
and limit gastrointestinal absorption by GASTRIC INTUBATION,
ASPIRATION, and LAVAGE, following placement of a cuffed
endotracheal tube. Lavage procedure is described in Chapter 1,
TREATMENT, Section 6, page 8. Repeated administration of char-
coal at half or more the original dosage every 2-4 hours may be
beneficial.
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If gastric aspiration and lavage is not performed due to delay in
treatment, and if the patient is fully alert, ADMINISTER CHAR-
COAL AND LAXATIVE ORALLY, at the dosages indicated in
Chapter 1, TREATMENT, Section 6, p. 8.
5. 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 desira-
ble. Intravenous saline/dextrose has sufficed to rescue comatose
patients who drank 2,4-D and mecoprop several hours before hos-
pital admission.
CAUTION: Monitor urine protein and cells, BUN, serum creati-
nine, serum electrolytes, and fluid intake/output carefully to
insure that renal function remains unimpaired and that fluid
overload does not occur.
Forced ALKALINE DIURESIS has been used successfully in
management of suicidal ingestions of chlorophenoxy compounds.
Alkalinizing the urine by including sodium bicarbonate (44-88
mEq per liter) in the intravenous solution apparently accelerates
excretion of 2,4-D dramatically and mecoprop excretion substan-
tially. Urine pH should by maintained in the 7.6-8.8 range. In-
clude potassium chloride as needed to offset increased potassium
losses: add 20-40 mEq of potassium chloride to each liter of intra-
venous solution. Monitor serum electrolytes carefully. There may
possibly be some hazard to the kidneys when urine concentrations
of toxicant are very high, so the integrity of renal function and
fluid balance should be monitored carefully as the chlorophenoxy
compound is excreted.
6. Hemodialysis is not likely to be of significant benefit in poisonings
by chlorophenoxy compounds because of the extensive protein
binding of these chemicals.
7. Follow-up clinical examination should include electromyographic
and nerve conduction studies to detect any neuropathic changes
and neuromuscular junction defects.
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CHAPTER 8
NITROPHENOLIC AND
NITROCRESOLEC HERBICIDES
GENERAL CHEMICAL STRUCTURE
02N O—H or
(ALKYL) (ALKYL)
COMMERCIAL PRODUCTS
Dinitrophenol (Chemox PE), dinitrocresol (DNOC, DNC, Chemsect
DNOC, Elgetol 30, Nitrador, Selinon, Sinox, Trifocide), dinoseb (DNBP,
dinitro, Basanite, Caldon, Chemox General, Chemox PE, Chemsect
DNBP, Dinitro, Dinitro-3, Dinitro General, Dynamyte, Elgetol 318, Ge-
butox, Hel-Fire, Kiloseb, Nitropone C, Premerge 3, Sinox General, Su-
bitex, Unicrop DNBP, Vertac, Dinitro Weed Killer 5, Vertac General
Weed Killer, Vertac Selective Weed Killer), dinoseb acetate (Aretit),
dinoseb methacrylate (binapacryl, Morocide, Acricid, Ambox, Dapacryl,
Endosan, FMC 9044, Hoe 002784, Morrocid, NLA 9044), dinosulfon,
dinoterbon, dinoterb acetate, dinoterb salts, dinosam (DNAP, Chemox
General), dinoprop, dinocap (Crotothane, Karathane), dinobuton
(Acrex, Dessin, Dinofen, Drawinol, Talan), dinopenton.
These agents have many uses in agriculture worldwide: herbicides
(weed-killing and defoliation), acaricides, nematocides, ovicides, fungi-
cides. Relatively insoluble in water, most technical products are dis-
solved in organic solvents and are formulated for spray application as
emulsions. There are some wettable powder formulations.
TOXICOLOGY
Nitroaromatic compounds are highly toxic to humans and animals.
Most nitrophenols and nitrocresols are well absorbed from the gastro-
intestinal tract, across the skin, and by the lung when fine droplets are
inhaled. Fatal poisonings have occurred as a result of dermal contami-
nation. Except in a few sensitive individuals, they are only moderately
irritating to the skin and mucous membranes.
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NitropKenols 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 metabo-
lites appear consistently in the urine of poisoned individuals, hepatic
excretion is probably the main route of disposition. Elimination is slow:
residence half-life in humans is 5-14 days. Blood and tissue concentra-
tions tend to increase progressively if an individual is substantially
exposed on successive days.
Nitrophenols and nitrocresols are toxic to the liver, kidney, and
nervous system. The basic mechanism of toxicity is stimulation of
oxidative metabolism in cell mitochondria, by interference with the
normal coupling of carbohydrate oxidation to phosphorylation (ADP to
ATP). The nitrophenols are more active as uncouplers than chloro-
phenols. Increased oxidative metabolism leads to hyperthermia, tachy-
cardia, and dehydration, and in time, depletes carbohydrate and fat
stores. Most severe occupational poisonings from absorption of these
compounds have occurred in workers laboring in hot environments.
Hyperthermia and direct action on the brain cause cerebral edema,
manifest clinically as a toxic psychosis and sometimes convulsions.
Liver parenchyma and renal tubules show degenerative changes. Albu-
minuria, pyuria, hematuria, and azotemia are signs of renal injury.
Neutropenia has occurred in humans following heavy exposure to
dinitrophenol. Cataracts occur in laboratory animals given nitrophen-
ols, and have occurred in humans, both as a result of ill-advised medicr
inal use and as a consequence of occupational exposure. Cataract for-
mation is sometimes accompanied by glaucoma.
SYMPTOMS AND SIGNS OF POISONING
Yellow staining of skin and hair often signify topical contact with a
nitroaromatic chemical. Staining of the sclerae and urine indicate
absorption of potentially toxic amounts. Profuse SWEATING, THIRST,
FEVER, HEADACHE, confusion, malaise, and lassitude are common
early symptoms of poisoning. Warm flushed skin, tachycardia, and
tachypnea indicate a serious degree of poisoning. RESTLESSNESS,
apprehension, anxiety, manic behavior, or unconsciousness reflect cere-
bral injury. CONVULSIONS signify an immediately life-threatening
intoxication. Labored breathing and cyanosis are consequences of the
stimulated metabolism and tissue anoxia. Weight loss occurs in persons
continually exposed to relatively low doses of nitrophenols or nitrocre-
sols.
CONFIRMATION OF POISONING
Unmetabolized nitrophenols and nitrocresols can be identified spec-
trophotometrically, or by gas-liquid chromatography, in the serum and
urine at concentrations well below those that have been associated
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with acute poisonings. Blood analysis is useful in confirming the cause
of poisoning, but has little value in monitoring progress or predicting
outcome. If poisoning is probable, DO NOT AWAIT CONFIRMATION
before commencing treatment, but save urine and blood specimens in
the event confirmation is necessary later on.
TREATMENT OF NITROPHENOL OR NITROCRESOL
POISONING
1. 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. CONTAMINATED CLOTHING should be promptly
removed, bagged, and not returned until it has been thoroughly
laundered. Contaminated leather shoes should be discarded. The
possibility that pesticide has contaminated the inside surfaces of
gloves, boots, and headgear should be kept hi mind.
2. FLUSH chemical from EYES with copious amounts of clean
water. Obtain medical attention if irritation or other injury per-
sists.
3. Systemic poisoning must be treated by controlling body tempera-
ture, providing oxygen, maintaining hydration, and relieving agi-
tation.
A. REDUCE ELEVATED BODY TEMPERATURE BY PHYSI-
CAL MEANS. Administer sponge baths and cover victim with
cool blankets. In fully conscious patients, administer cold,
sugar-containing liquids by mouth as tolerated.
B. DO NOT administer atropine, aspirin, or other salicylates to
control hyperthermia. These agents appear likely to enhance
the toxicity of phenolic substances. Neither the safety nor the
effectiveness of other antipyretics has been tested.
C. Administer OXYGEN continuously by mask to minimize
tissue anoxia.
D. Unless there are manifestations of cerebral or pulmonary
edema or of inadequate renal function, administer INTRAVE-
NOUS FLUIDS to restore hydration and support physiologic
mechanisms for heat loss and toxicant disposition. Monitor
serum electrolytes, adjusting IV infusions to stabilize electro-
lyte concentrations. Follow urine contents of albumin and
cells, and keep an accurate hourly record of intake/output to
forestall fluid overload if renal function declines.
CAUTION: In the presence of cerebral edema and/or un-
paired renal function, intravenous fluids must be adminis-
tered very cautiously to avoid increased intracranial pressure
and pulmonary edema.
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E. In. severe poisonings, monitor pulmonary ventilation carefully
to insure adequate gas exchange, and monitor cardiac status
by EGG to detect arrhythmias. The toxicant itself and severe
electrolyte disturbances may predispose to arrhythmias and
myocardial weakness.
F. To reduce production of heat in the body, CONTROL AGITA-
TION and involuntary motor activity with sedatives. DIAZE-
PAM or other benzodiazepine should be effective, although
use of these drugs in nitroaromatic poisoning has not been
reported. If diazepam is chosen, administer SLOWLY, intra-
venously.
Dosage of DIAZEPAM:
Adults and children over 12 years: 5-10 mg. Repeat if
necessary to a maximum of 30 mg.
Children under 12 years: 0.25-0.40 mg/kg body weight.
Repeat if necessary to a maximum of 10 mg for children
5-12 years and to a maximum of 5 mg for children 30
days to 5 years.
Diazepam can be given by deep intramuscular injection if
intravenous administration is not possible.
CAUTION: Be prepared to assist pulmonary ventilation me-
chanically if respiration is depressed, to intubate the trachea
if laryngospasm occurs, and to counteract hypotensive reac-
tions.
G. Hemodialysis has not proven to be effective hi poisonings by
phenolic substances. Forced diuresis is of little or no benefit hi
reducing body burden. There has been insufficient testing of
hemoperfusion to establish its value in accelerating elimina-
tion of phenols.
4. IF nitrophenol or nitrocresol has been INGESTED in a quantity
sufficient to cause poisoning, the stomach and intestine must be
emptied and measures taken to limit absorption of residual toxi-
cant. The effectiveness of induced emesis and gastric lavage hi
removing toxicant from the stomach diminishes rapidly with the
passage of time.
A. IF ingestion occurred within the last few hours, and IF the
patient is FULLY ALERT, give SYRUP OF IPECAC, fol-
lowed by 1-2 glasses of water, to induce vomiting. The dosage
of Syrup of Ipecac for adults and children over 12 years is 30
ml; the dosage for children under 12 years is 15 ml.
CAUTION: OBSERVE the patient closely AFTER administer-
ing IPECAC. Position the patient hi left lateral decubitus,
head below the level of the stomach. If. consciousness level
declines or if vomiting does not occur in 30 minutes, proceed
immediately to PROTECT THE AIRWAY, then INTUBATE,
ASPIRATE, and LAVAGE the stomach (see below).
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B. IF the patient is NOT FULLY ALERT when first examined,
proceed directly to PROTECT THE AIRWAY, insert a large
bore orogastric tube, and empty to stomach by ASPIRATION
and LAVAGE with a slurry of ACTIVATED CHARCOAL.
See Chapter 1, TREATMENT, Section 6, p. 8.
C. Following emesis or lavage, administer ACTIVATED CHAR-
COAL and CATHARTIC by ingestion or by orogastric tube, as
recommended in Chapter 1, TREATMENT, Section 6, page 8.
D. If several hours have elapsed since ingestion, and if the pa-
tient is fully alert, ADMINISTER ACTIVATED CHARCOAL
AND CATHARTIC ORALLY.
E. REPEATED administration of ACTIVATED CHARCOAL at
half or more the initial dosage every 2-4 hours may be benefi-
cial.
CAUTION: Catharsis may lead to dehydration and electrolyte
disturbances, particularly in children. Fluid balance and
serum electrolytes should be monitored. There may be some
advantage in giving repeated doses of cathartics to adults, but
caution must be exercised hi children. Administration of ca-
thartic should stop when a charcoal stool appears.
F. Save a sample of emesis or initial gastric washings for chemi-
cal analysis.
5. During convalescence, administer a high-calorie, high-vitamin diet
to restore body fat and carbohydrate.
6. Discourage subsequent contact with the toxicant for 4-8 weeks
(depending on severity of poisoning) to allow full restoration of
normal metabolic processes.
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CHAPTER 9
PENTACHLOROPHENOL
CHEMICAL STRUCTURE
Cl
•H
(or Na)
COMMERCIAL PRODUCTS
PGP, Penta, Penchlorol, Santophen, Chlorophen, Pentacon, Penwar,
Sinituho. The sodium salt is sodium pentachlorophenate.
In various products, pentachlorophenol has been used as an herbi-
cide, algacide, defoliant, wood preservative, germicide, fungicide, and
molluscicide. As a wood preservative, it is commonly applied as a 0.1%
solution in mineral spirits, No. 2 fuel oil, or kerosene. It is used in
pressure treatment of lumber at 5% concentration. Weed killers con-
tain higher concentrations. PGP is no longer available for over-the-
counter sale in the United States.
Pentachlorophenol volatilizes from treated wood and fabric. It is
virtually odorless. Excessively treated interior surfaces may be a
source of exposure sufficient to cause irritation of eyes, nose, and
throat.
Technical PGP contains lower chlorinated phenols (4-12%) plus
traces of chlorobenzodioxins, chlorobenzofurans, and chlorobenzenes.
TOXICOLOGY
PGP is efficiently absorbed across the skin, the lung, and the gastro-
intestinal lining. It is rapidly excreted, mainly in the urine as un-
changed PGP and as PGP glucuronide. In the blood, a large fraction of
absorbed PGP is protein-bound.
The residence half-life of PGP in humans is about 27-36 hours.
Because minute amounts of PGP are consistently detectable in the
blood and urine of the general population, a continuing low-level
intake (micrograms per day) of PGP by virtually everyone is implied.
In adequate concentration, PGP is irritating to mucous membranes
and skin. Contact dermatitis occurs commonly in workers having con-
tact with PGP.
Internally, large doses are toxic to the liver, kidneys, and nervous
system. An important mechanism of toxic action is increased cellular
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oxidative metabolism resulting from the uncoupling of oxidative phos-
phorylation. This leads to increased heat production (hyperthermia).
Severe poisoning and death have occurred as a result of intensive
PGP exposure. Dermal absorption has been the basis of virtually all
occupational poisonings. Most adult fatalities have occurred in persons
working in hot environments where hyperthermia is poorly tolerated.
Several infant deaths occurred in a nursery where a PCP-containing
diaper rinse had been used. Chloracne has occurred in production
workers, possibly due to chlorodioxin contaminants. Individual cases of
exfoliative dermatitis of the hands and diffuse urticaria and angioe-
dema of the hands have been reported in intensively exposed workers.
Cases of aplastic anemia, peripheral neuropathy, and leukemia have
been reported which were associated temporally with PCP exposure.
Causal relationships in these cases were not established.
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, GOT, and LDH enzymes indicate significant insult to the
liver, including both cellular damage and some degree of biliary ob-
struction.
SYMPTOMS AND SIGNS OF POISONING
IRRITATION of the nose, throat, and eyes is the most common
effect of airborne PCP, causing stuffy nose, scratchy throat, and tear-
ing. Dermal exposure may lead to contact dermatitis, or more rarely,
diffuse urticaria or chloracne.
Commonly reported symptoms of systemic poisoning by PCP are
profuse SWEATING, weakness, dizziness, anorexia, nausea, and—in
workers exposed over long periods—weight loss. Indications of severe
acute poisoning are HYPERTHERMIA, muscle spasms, tremor, la-
bored breathing, a sense of constriction in the chest, abdominal pain
and vomiting, restlessness, excitement, and mental confusion. Tachy-
cardia and increased respiratory rate are usually apparent. Intense
THIRST is characteristic.
CONFIRMATION OF POISONING
PCP can be measured in blood, urine, and adipose tissue by gas-
liquid chromatography. Up to about 100 parts per billion may be found
in the blood and urine of persons having no recognized exposure. Food
is probably the main source of this microgram-level dosage. In addition
to minute residues of synthetic PCP in food, water, and air, some PCP
may derive from biotransformation of other chlorinated organic com-
pounds. .
Based on studies of persons occupationally exposed to PCP, manifes-
tations of systemic toxicity probably do not appear in adults until blood
74
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and urine concentrations reach at least one part per million (0.1 mg%,
or 1,000 parts per billion). POP serum concentrations of 13 parts per
million have been found in symptomatic occupationally exposed work-
ers. Serum concentrations of 46 and 97 parts per million have been
measured in fatal poisonings.
If poisoning is strongly suspected on the basis of exposure, symp-
toms, and signs, DO NOT POSTPONE TREATMENT until diagnosis is
confirmed.
TREATMENT
Treatment recommendations in poisonings by PCP are essentially
the same as those for poisonings by NITROPHENOLIC and NITRO-
CRESOLIC HERBICIDES, discussed in Chapter 8, page 70.
Exchange transfusion was used to rescue newborns inadvertently
poisoned by PCP in a hospital.
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CHAPTER 10
PARAQUAT AND DIQUAT
CHEMICAL STRUCTURES
PARAQUAT
CH2 CH2
DIQUAT
Paraquat and diquat are identified chemically as DIPYRIDYLS.
COMMERCIAL PRODUCTS
Paraquat is a synthetic nonselective contact herbicide, usually mar-
keted as the dichloride salt. Dimethyl sulfate salts are also produced.
Liquid technical products range from 20% to 50% concentration.
Names of liquid concentrates are: Ortho Paraquat CL, Ortho Paraquat
Plus, Cekuquat,. Crisquat, Herbaxon, Herboxone, Dextrone, Esgram,
Gramocil, Gramoxone, Goldquat 276, Sweep, Osaquat Super, Gramonol,
Toxer Total, Pillarxone, Pillarquat. Paraquat is commonly formulated
in combination with other herbicides:
With diquat: Actor, Preeglone, Preglone, Priglone, Weedol (a 2.5%
soluble granule formulation).
With monolinuron: Gramonol
With diuron: Gramuron, Para-col, Tota-col, Dexuron
With simazine: Terraklene, Pathclear
Diquat is usually prepared as the dibromide monohydrate salt, 20%
to 25% in liquid concentrates. Deiquat and region are alternative
common names. Commercial products are: Ortho Diquat, Aquacide,
Dextrone, Reglone, Reglox, Weedtrine-D. Combinations with paraquat
are listed above. Diquat is still used as a water herbicide, but is now
applied as a dessicant and terrestrial herbicide as well.
TOXICOLOGY AND MANIFESTATIONS OF POISONING
Paraquat
Particularly in concentrated form, paraquat causes injury to tissues
with which it comes into contact. It leaves the skin of the hands dry
and fissured, sometimes resulting in loss of fingernails. Prolonged con-
tact with skin may cause blistering and ulceration, with subsequent
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absorption of paraquat in sufficient dosage to cause systemic poisoning.
Prolonged inhalation of spray droplets may cause nosebleed. Eye con-
tamination results in severe conjunctivitis and sometimes protracted
and even permanent cornea! ©pacification. When ingested in adequate
dosage (see below), paraquat has life-threatening effects on the gastro-
intestinal tract, kidney, liver, heart, and other organs. The first phase
of systemic poisoning consists of swelling, edema, and ulceration of the
mucosal linings of the mouth, pharynx, esophagus, stomach, and intes-
tine. Centrizonal hepatocellular injury along with damage to the proxi-
mal renal tubules, myocardium, and skeletal muscle (sometimes includ-
ing focal necrosis) are the main features of the second phase. The
nervous system and pancreas are affected in some cases. The third
phase—injury to the lung—usually becomes evident 2-14 days follow-
ing ingestion, although, in some cases, pulmonary edema has developed
only a few hours after paraquat has been swallowed. Paraquat is
selectively concentrated in lung tissue where it destroys lung paren-
chymal cells probably by generation of free-radical oxygen and subse-
quent lipid peroxidation. Hemorrhage, edema fluid, and leukocytes
infiltrate the alveolar spaces, after which there is rapid proliferation of
fibroblasts. Severe impairment of gas exchange causes death from an-
oxemia and tissue anoxia. Remarkably, essentially full recovery of
pulmonary function occurs following paraquat poisonings which are
survived. Although absorption across intact skin is slow, abraded or
eroded skin allows efficient absorption. Fatal poisonings are reported
to have occurred as a result of protracted dermal contamination by
paraquat.
The effect of paraquat on renal tubule cells is more likely to be
reversible than the effect on lung tissue, but impaired renal function
may play a critical role in determining the outcome of paraquat poi-
soning. Normal tubule cells actively secrete paraquat into the urine,
clearing it efficiently from the blood. However, high blood concentra-
tions poison the secretory mechanism and may destroy the cells. Be-
cause the kidney is almost the exclusive route of paraquat elimination
from body tissues, renal failure fosters a build-up of tissue concentra-
tions, including those in the lung. Unfortunately, this pathogenetic
sequence may occur in the first several hours following paraquat inges-
tion, generating lethal concentrations of paraquat in lung tissue before
therapeutic measures to limit absorption and enhance disposition have
taken effect. It is probably for this reason that methods for enhancing
paraquat disposition several hours following ingestion have had little
influence on mortality.
The hepatic injury from paraquat may be severe enough to cause
jaundice, but hepatotoxicity is rarely a major determinant of clinical
outcome. Elevated alkaline phosphatase, AST, ALT, and LDH are indi-
cations of hepatocellular insult; jaundice signifies more severe injury.
Early symptoms and signs of poisoning by ingested paraquat are
burning pain in the mouth, throat, chest, and upper abdomen, due to
77
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the corrosive effect of paraquat on the mucosal lining. Giddiness, head-
ache, fever, myalgia, and diarrhea (sometimes bloody) occur. Pancreati-
tis may cause severe abdominal pain. Proteinuria, hematuria, pyuria,
and azotemia reflect renal injury. Oliguria/anuria indicate acute tubu-
lar necrosis.
Progressive declines hi arterial oxygen tension and CO diffusion
capacity commonly precede pulmonary symptomatology. Cough, dysp-
nea, and tachypnea usually appear 2-4 days following paraquat inges-
tion, but may be delayed as long as 14 days. Progressive cyanosis and
air hunger reflect deteriorating gas exchange in the damaged lung.
Coma usually precedes death. 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 (J. A. Vale, et al., Human
Toxicology, 6:41-47,1987):
I. Less than 20 mg paraquat ion per kg body weight (less than 7.5
ml of 20% (w/v) paraquat concentrate). No symptoms, or only
gastrointestinal symptoms occur. Recovery is likely.
n. Twenty to 40 mg paraquat ion per kg body weight (7.5-15.0 ml of
20% (w/v) paraquat concentrate). Gastrointestinal, renal, hepatic
and pulmonary damage by paraquat occurs. Pulmonary fibropla-
sia ensues. Death occurs in most cases, but may be delayed 2-3
weeks.
HI. 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. Mor-
tality is essentially 100% hi 1 to 7 days.
Although much concern has been expressed about effects of smoking
paraquat-contaminated marijuana, toxic effects by this mechanism
have been either very rare or nonexistent. Most paraquat that con-
taminates marijuana is pyrolyzed during smoking to dipyridyl. Dipyri-
dyl is a product of combustion of leaf material itself (including mari-
juana) and presents little toxic hazard.
It is tragic that use of paraquat as a suicidal agent has increased hi
recent years, particularly in Japan and also hi developing countries.
Several strategies are being tested to reduce the frequency of these
occurrences: addition of emetics, stenching agents, gelling substances.
Diquat
Diquat is somewhat less damaging to skin than paraquat, but irri-
tant effects may appear following dermal contamination with the con-
centrate. There is probably significant absorption of diquat across ab-
raded or ulcerated skin.
78
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Systemically absorbed diquat is not selectively concentrated in lung
tissue, as is paraquat, and pulmonary injury by diquat is less promi-
nent. However, diquat has severe toxic effects on the central nervous
system that are not typical of paraquat poisoning although brain
injury has been observed post-mortem in some fatal paraquat poison-
ings. Renal damage is an important feature of poisonings by both
agents. The kidney is the principal excretory pathway for diquat ab-
sorbed into the body.
Early symptoms of poisoning by ingested diquat are similar to those
from paraquat, reflecting its corrosive effect on tissues: burning pain in
the mouth, throat, chest, and abdomen. Intense nausea, vomiting, and
diarrhea are characteristic. If the dosage was small, these symptoms
may be delayed 1-2 days. Blood may appear in the vomitus and feces
Intestinal Ueus, with pooling of fluid in the gut, has characterized
several human poisonings by diquat. Dehydration, hypotension, and
tachycardia may result and shock is a common cause of death. Agita-
tion, restlessness, disorientation, and psychotic behavior have been
early manifestations of some diquat poisonings. Tonic-clonic seizures
and coma may supervene. 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. If the patient survives several hours or days, circulatory func-
tion may fail due to toxic myocardiopathy, or bronchopneumonia mav
develop.
Over the past decade, the great majority of poisonings by paraquat
and diquat have been caused by ingestion—with suicidal intent in most
cases. 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 distressingly high (60%). Avoid-
ance of this mortality will probably have to rely on preventive strate-
gies or on stopping gastrointestinal absorption very soon after the
toxicant has been ingested. Even though intestinal absorption of dipyri-
dyls is relatively slow, lethal uptake by critical organs and tissues
apparently occurs within 18 hours, possibly within 6 hours, following
ingestion of toxic quantities of paraquat or diquat. Dipyridyls have
large volumes of distribution. Once distribution to tissues has occurred,
measures to remove dipyridyls from the blood are very inefficient in
reducing the total body burden.
CONFIRMATION OF ABSORPTION
At some treatment facilities, a simple colorimetric test is used to
identify paraquat and diquat in the urine, and give a rough indication
of the magnitude of absorbed dose. To one volume of urine is added 0.5
volume of freshly prepared 1% sodium dithionite (sodium hydrosulfite)
in one normal sodium hydroxide. Observe color at end of one minute.
Development of a blue color indicates the presence of paraquat in
79
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excess of 0.5 mg per liter. Both positive and negative controls must be
run to insure 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 approximate prognostic value:
concentrations less than one milligram per liter (no color to light blue)
generally predict survival, while concentrations in excess of one milli-
gram per liter (navy blue to dark blue) often foretell a fatal outcome.
Diquat in urine yields a green color. There is less experience with
the dithionite test in diquat poisonings; however, the association of bad
prognosis with intense color is probably similar.
Paraquat and diquat can be measured in blood and urine by spectro-
photometric, gas chromatographic, liquid chromatographic, and ra-
dioimmunoassay methods. These are available in localities where the
frequency of paraquat poisonings (chiefly suicides) has stimulated re-
search aimed at more effective therapy. Paraquat poisonings in which
plasma concentrations do not exceed 2.0, 0.6, 0.3, 0.16, or 0.1 mg per
liter at 4, 6,10,16, and 24 hours, respectively, after ingestion are likely
to survive (Proudfoot, A.T. et al. The Lancet 11:330-332, 1979).
TREATMENT
1. Contaminated SKIN must be FLUSHED immediatley with copi-
ous amounts of water. Material splashed in the EYES must be
removed by PROLONGED IRRIGATION with clean water. Eye
contamination should thereafter be treated by an ophthalmol-
ogist. Mild skin reactions usually respond to simple avoidance of
further contact, 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. If paraquat or diquat have been ingested in any amount, IMME-
DIATE ADMINISTRATION OF ADSORBENT is the one thera-
peutic measure most likely to affect the outcome of paraquat or
diquat ingestion favorably. BENTONITE (7.5% suspension) and
FULLER'S EARTH (30% suspension) are highly effective, but
sometimes not available.
Dosage of BENTONITE AND FULLER'S EARTH:
Adults and children over 12 years: 100-150 gm.
Children under 12 years: 2 gm/kg body weight.
CAUTION: Hypercalcemia and fecaliths have sometimes oc-
curred following administration of fuller's earth.
ACTIVATED CHARCOAL is nearly as effective, and is generally
available. Give as much of a 30 gm per 240 ml suspension as the
patient will swallow. Encourage the victim to swallow the adsorb-
ent even though spontaneous vomiting continues. Then, after
taking precautions to protect the airway (see Chapter 1, TREAT-
MENT, Section 6, p. 8), carefully intubate the stomach and lavage
80
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repeatedly with a slurry of adsorbent. Instill the suspension of
adsorbent as fast as the gut accepts it. Repeated administration of
charcoal or other absorbent every 2-4 hours may be beneficial.!
Include SORBITOL in the first dose of adsorbent suspension.
Dosage of SORBITOL:
Adults and children over 12 years: 1-2 gin/kg body weight to
a maximum of 150 gm.
Children under 12 years: 1.0-1.5 gin/kg body weight to a
maximum of 50 gm.
Seventy percent sorbitol should be diluted half-and-half with
water before administration.
Prompt administration of adsorbent and thorough flushing of the
gut are the measures which offer the best opportunity for surviv-
al.
CAUTION: Because corrosive damage to the esophagus and stom-
ach may render these structures vulnerable to perforation, the
gastric lavage tube must be introduced very gently.
CHECK FREQUENTLY FOR BOWEL SOUNDS. Ileus occurs
commonly in diquat poisoning, less often in paraquat poisoning.
Cathartics should not be administered if the gut is atonic; instilla-
tion of fluid by stomach tube should be slowed or stopped if ileus
is present.
3. Secure a blood sample as soon as possible for paraquat analysis.
4. DO NOT ADMINISTER SUPPLEMENTAL OXYGEN. High con-
centrations 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 environ-
ment, i.e., 15%-16% oxygen, although the benefit of this treat-
ment measure has not been established empirically in human
poisonings. When the lung injury is so far advanced that there is
no expectation of recovery, oxygen may be given to relieve air
hunger.
5. Administer INTRAVENOUS FLUIDS: isotonic saline, Ringer's so-
lution, and 5% glucose in water. This is highly advantageous
early in poisonings as a means of correcting dehydration, acceler-
ating toxicant excretion, reducing tubular fluid concentrations of
paraquat, and correcting metabolic acidosis, when this occurs.
However, fluid balance must be monitored carefully to forestall
fluid overload if renal failure develops. Monitor the urine regular-
ly for protein and cells, to warn of impending tubular necrosis.
Intravenous infusions must be stopped if failure occurs, and EX-
TRACORPOREAL HEMODIALYSIS must be instituted to main-
tain normal extracellular fluid composition. Hemodialysis is not
effective in clearing paraquat or diquat from the blood and tis-
sues.
6. HEMOPERFUSION over cellophane-coated activated charcoal
may be considered. The procedure has been used in many para-
81
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quat 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. The apparent reason for this is the very
small proportion of paraquat body burden carried in the circulat-
ing blood even when only a few hours have elapsed after inges-
tion. Theoretically, a patient who can be hemoperfused within 10
hours of paraquat ingestion may derive some marginal benefit,
but this has not been demonstrated.
If hemoperfusion is attempted, blood calcium and platelet concen-
trations must be monitored. Calcium and platelets must be re-
plenished if these constituents are depleted by the procedure.
7. CONVULSIONS and psychotic behavior sometimes encountered
in diquat poisoning may be best controlled by DIAZEPAM, given
slowly intravenously.
Dosage of DIAZEPAM:
Adults and children over 12 years: 5-10 mg. Repeat every
10-15 minutes, if necessary, to a maximum of 30 mg.
Children 5 to 12 years: 0.25-0.40 mg/kg body weight. Repeat
every 15 minutes if necessary, to a maximum of 10 mg.
Children under 5 years: 0.25-0.40 mg/kg body weight. Repeat
every 15 minutes if necessary, to a maximum of 5 mg.
8. Many drugs have been tested in animals or given in human
dipyridyl poisonings without clear evidence of benefit or harm:
corticosteroids, superoxide dismutase, propranolol, cyclophospha-
mide, vitamin E, riboflavin, niacin, ascorbic acid, clofibrate, des-
ferrioxamine, acetylcysteine, and terpin hydrate.
9. Morphine sulfate is usually required to control the pain associat-
ed with deep mucosal erosions of the mouth, pharynx, and esopha-
gus, as well as abdominal pain from pancreatitis and enteritis.
Dosage for adults and children over 12 years: 10-15 mg subcutan-
eously every 4 hours. Dosage for children under 12 years: 0.1-0.2
mg/kg body weight every 4 hours.
10. Mouthwashes, cold fluids, ice cream, or anesthetic lozenges may
help to relieve pain in the mouth and throat.
82
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CHAPTER 11
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, nitro- and chloro-phenols, arsenicals, and
dipyridyls, which are subjects of separate chapters. Many modern her-
bicides kill weeds selectively by impairing metabolic processes that are
unique to plant life. For this reason, their systemic toxicities in mam-
mals are generally low. Nonetheless, there are some which pose a
significant risk of poisoning if handled carelessly, and many are irritat-
ing 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
hygienic measures that minimize personal contact. Many formulations
contain adjuvants (stabilizers, penetrants, safeners, surfactants) that
may have significant irritating and toxic effects. A number of pre-
mixed formulations contain two or more active ingredients; the com-
panion pesticides may be more toxic than the principal herbicide.
Finally, some individuals exhibit unique sensitivities to chemicals that
are not predictable on the basis of past human exposure experience.
Good hygienic practice should, therefore, not be disregarded because a
pesticide is reported to have a high LDSO in laboratory rodents, or is
said to be "harmless to humans." The rodent LD50 rating is based
solely on lethality; it says nothing of dosage necessary to produce
symptoms or signs, or cause injury or disease after long latency, sub-
clinical biochemical effects, or other nonlethal effects on health.
The fate of these compounds after they have been absorbed by
humans should be understood by health professionals who may need to
assess the consequences of prior exposure. The water-soluble herbicides
are not retained in body tissues for long periods, as were the old
lipophilic organochlorine insecticides, such as DDT. Some undergo bio-
transformation in the body, others do not. Most are excreted, mainly in
the urine, within one to four days.
The following table is a synoptic listing of the more commonly used
herbicides other than those discussed in separate chapters. The rat
acute oral LD5o 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 given is drawn from many
sources, including product labels, textbooks, published case histories,
and some unpublished reports. The listing cannot be considered inclu-
sive, either of herbicide products or of effects.
83
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Chemical Class
Acetamides
Anffldea
Aliphatic acids
Benzamide
Benzole, anisic
acid
derivatives
Benzc-
nitrflee
Benzothia-
diazinone
dioxide
Carbamates
andthio-
carbamates
(faerbi-
ddal)
Carbanl-
lates
Generic
Name
allidocblor
metolachlor
alachlor
propachlor
propanil
trichloro-
acetic acid
dichloro-
propionic
acid, dal-
apon
pronamide
trichloro-
benzoic
acid
chloramben
dicamba
dichlobenil
bentazon
asulam
terbucarb
butylate
cycloate
pebulate
vemolate
EPIC
diallate
trinllate
thiobencarb
barban
chlorpro-
pham
Proprietary Names
Randox, CDAA
Dual, Bicep,
Primagram,
Pennant,
Primextra, Codal
Lasso, Lazo,
Alanox
Ramrod, Bexton
DPA, Erban, Chem
Rice, Propanex,
Riselect, Stam,
Stampede,
Supernox, Surpur
TCA,
NaTA,
Varitox
Dalapon, Basfapon,
Dowpon, Ded-Weed,
Revenge
Kerb
TCBA,
Benzac,
Tribac,
2, S, 6-TBA
Amiben
Banvel
Casoron, Decabane,
Dyclomec, Barrier
Basagran
Asulox
Azac, Azar
Sutan
Ro-Neet
Tfflam, PEBC
Surpass
Eptam, Eradicane
Avadex, Pyradex
Avadex BW
Bolero, Saturn
Carbyne
Furloe, Bud-Nip,
Sprout-Nip, Beet-
Kleen, Chloro-IPC,
Unicrop84,000 irritating to
3,500 eyes, skin, and
2,000 respiratory tract,
921 particularly in
1,800 concentrated form.
1,630 Some may be weak
395 inhibitors of
1,675 cholinesterases.
1,300
1,350 Irritant and
sensitizer. May
generate methemo-
globin at high
dosage. Weak
cholinesterase
inhibitor.
3,800 Skin irritants.
May generate
methemoglobin at
high dosage.
84
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—Continued
Onfeal dan
Chloro-
pyridinyl
Cyclo-
hexenone
derivative
Dinitro-
amino-
benxene
derivatives
Fluorodi-
nitrotolui-
dine com-
pounds
Isoxazo-
Nicotinic
acid-
isopropyl-
amine
derivative
Oxadia-
zolinone
Phoephonateis
Phthalates
Picolinic
compound
Generic
Name
triclopyr
sethoxydim
butralin
isopropalin
pendi-
methalin
oryzalin
benfluraun
dinitramine
ethalflur-
alin
fluchloralin
profluralin
trifluralin
oxadiazon
glyphoeate
fosamine
ammonium
chlorthal-
dimethyl
endothall
picloram
Proprietary Names
Garlon, Crossbow
Turflon
Poast
Amex, Tamex
Paarlan
Prowl, Stomp,
Accotab, Herbodox,
Go-Go-San, Wax Up
Surflan, Dirimal
Benefin, Balan,
Balrtn, Quilan
Cobex
Sonalan
Basalin
Tolban
Treflan, TR-10
Command
Arsenal
Ronstar
Roundup, Glifonox
Krenite
Dacthal, DCPA
Aquathol
Tordon, Grazon
Acute Oral LDw'
mg/kg
630
3,125
12,600
>5,000
1,250
> 10,000
> 10,000
3,000
> 10,000
1,550
1,808
> 10,000
1,369
> 5,000
>3,500
4,300
24,000
> 10,000
51
8,200
Known or Suspected
Adverse Effects
Irritant 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.
Minimal toxic and
irritant properties.
Irritating to eyes,
skin, and upper
respiratory tract
Moderately
irritating to
eyes.
Free acid is
highly toxic.
Irritating to
skin, eyes, and
respiratory tract.
See Chapter 15,
page 153.
Irritating to
skin, eyes, and
respiratory tract.
Low systemic
toxicity.'
Triazines
ametryn
atraton
Ametrex, Evik,
Gesapax
Atratone,
Gesatamin
1,750
1,465
85
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—Continued
Chemical Class
Triazole
Uracib
Urea
derivatives
Generic
Name
ntrazine
cyanazine
desmetryn
isomethiozin
metribuzin
prometryn
propazine
giwgyitiR
terbu-
thylazine
tcrbutryn
prometon
amitrole,
amino-
triazole
bromacil
lenacU
terbacil
chlorimuron
ethyl
chlorc-
toluron
chloroxuron
difenoxuron
diuron
Proprietary Names
AAtrex, Atranex,
Crisazina,
Griffex, Vectal SC
Bladex, Fortrol
Semeron
Tantizon
Sencor, Lexone,
Sencoral, Sencorex
Caparol, Gcsagard,
PrimatolQ,
Prometrex
Gesamil, Milogard,
Mile-Pro,
PrimatolP
Aquazine, Oekusan
Gesatop, Prim-
atol S, Princep,
Caliber 90
Gardoprim,
PrimatolM
Igran, Prebane,
Terbutrex
Gesafram 50,
Ontracic 800,
Pramitol25B
Amerol, AT-90,
Amitrol-T, Azolan,
Azole, Cytrol,
Diurol, Herbizole,
Simazol, Weedazol
Borea, Bromax,
Hyvar, Rout,
Uragan, Urox B
Ban-Hoe, Venzar
Sinbar
Classic
Dicuran, Tolurex
Tenoran
Ldronion
Cekiuron,
Crisuron, Dailon,
Acute Oral LD»' Known or Suspected
mg/k'g Adverse Effects
1,780
288
1,390
> 10,000
1,100
5,235
>5,000
>5,000
2,000
2,500
2,276
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.
24,600 Minimal systemic
toxicity. Slight
irritant effect.
5,200 Irritant to skin,
eyes, and
respiratory tract.
> 11,000 f Moderately
1 irritating.
> 5,000 l
>4,000
> 10,000
3,700
>7,750
3,400
Systemic toxicity
is unlikely unless
86
-------
—Continued
Chemical Class ^"me0
fluometuron
isoproturon
linuron
methabenz-
thiazuron
metobro
muron
metoxuron
monolinuron
monuron
neburon
siduron
sulfometuron
methyl
tebuthiuron
tetrafluoron
Proprietary Names
Diater, Di-on,
Direx, Diurex,
Diurol, Diuron,
Karmex, Rout,
Unidron, Vonduron
Cotoran, Cottonex
Alon, Arelon,
Belgran, Graminon,
IP50, Tolkan
Afalon, Linex 4L,
Linorox, Linurex,
Lorox, Sarclex
Tribunil
Patoran, Pattonex
Deftor, Dosanex,
Dosaflo, Purivel,
Sulerex
Aresin, Afesin,
Arresin
Monuron
Granurex, Neburex
Herbalt
Tupersan
Oust
Spike, Graslan
Tomilon
Acute Oral LDso' Known or Suspected
mg/kg- Adverse 'Effects
8,900
1,826
1,500
> 2,500
2,603
3,200
2,100
3,600
> 11,000
> 7,500
> 5,000
644
1,265
large amounts have
been ingested.
Many substituted
ureas are
irritating to
eyes, skin, and
mucous membranes.
CONFIRMATION OF TOXICANT ABSORPTION
Although there are analytical methods for residues of many of the
herbicides mentioned in this chapter, and for some of the mammalian
metabolites generated from them, these procedures are not generally
available to confirm human absorption of the chemicals. Prior expo-
sure must be determined from a recent history of occupational contact
or accidental or deliberate ingestion.
TREATMENT OF TOXICOSIS
1.
Skin contamination should be removed promptly by washing with
soap and water. Contamination of the eyes should be treated
immediately by prolonged flushing of the eyes with copious
amounts of clean water. If dermal or ocular irritation persists,
medical attention should be obtained without delay.
87
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2. INGESTIONS of these herbicides are likely to be followed by
vomiting and diarrhea due to the irritant properties of most of
the toxicants. Management depends on: 1) the best estimate of
quantity originally ingested, 2) time elapsed since ingestion, 3)
effectiveness of vomiting, and 4) the clinical status of the subject.
ACTIVATED CHARCOAL is probably effective in limiting irri-
tant effects and reducing absorption of most or all of these herbi-
cides. Aluminum hydroxide gels may be useful in neutralizing the
irritant actions of the 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 herbi-
cides. In the case of suicidal ingestions, particularly, the possibili-
ty must always be kept in mind that multiple toxic substances
may have been swallowed.
A. If large amounts of herbicide have been ingested, and if the
patient is fully alert, induce EMESIS with Syrup of Ipecac,
followed by several glasses of water. Dosage for adults and
children over 12 years: 30 ml; dosage for children under 12
years: 15 ml. When vomiting has stopped, give ACTIVATED
CHARCOAL. Add SORBITOL to the charcoal slurry unless
diarrhea has already commenced. If, for some reason, the
patient is not fully alert, put hi place a cuffed endotracheal
tube to protect the airway, then aspirate and lavage the stom-
ach with a slurry of activated charcoal. Leave a quantity of
charcoal, with sorbitol, in the stomach before withdrawing the
stomach tube (see Chapter 1, TREATMENT, Section 6, page
8). Repeated administration of charcoal at half or more the
initial dosage every 2-4 hours may be beneficial.
B. If the amount of ingested herbicides was small, if effective
emesis has already occurred, or if treatment is delayed, ad-
minister the activated charcoal and sorbitol by mouth.
C. If serious dehydration and electrolyte depletion have occurred
as a result of vomiting and diarrhea, monitor blood electro-
lytes 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.
Fluids serve to support excretion of the toxicants.
D. Supportive measures are ordinarily sufficient for successful
management of excessive exposures to these herbicides (en-
dothall is an exception—see Chapter 15, p. 154). If the pa-
tient's condition deteriorates in spite of good supportive care,
the operation of an alternative or additional toxicant should
be suspected.
88
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CHAPTER 12
FUNGICIDES
Fungicides are extensively used in industry, agriculture, the home,
and garden for: 1) protection of seed grain during storage, shipment
and germination; 2) protection of mature crops, berries, seedlings, flow-
ers, and grasses in the field, in storage, and during shipment; 3) sup-
pression of mildews that attack painted surfaces; 4) control of slime in
paper pulps; and 5) protection of carpet and fabrics in the home.
Fungicides vary enormously in their potential for causing adverse
effects in humans. Historically, some of the most tragic epidemics of
pesticide poisoning occurred because of mistaken consumption of seed
grain treated with organic mercury or hexachlorobenzene. However,
most fungicides currently in use are unlikely to cause frequent or
severe systemic poisonings for several reasons: 1) many have low inher-
ent toxicity in mammals and are inefficiently absorbed; 2) many are
formulated as suspensions of wettable powders or granules, from which
rapid, efficient absorption is unlikely; and 3) methods of application
are such that relatively few individuals are intensively exposed. Apart
from systemic poisonings, fungicides as a class have probably caused
disproportionate numbers of irritant injuries to skin and mucous mem-
branes, as well as some dermal sensitizations.
The following discussion considers the recognized adverse effects of
widely used fungicides. In the case of those agents which have caused
systemic poisoning, some recommendations for management of poison-
ings and injuries are set forth. For those fungicides not known to have
caused systemic poisonings in the past, only general guidelines can be
offered.
The discussion of fungicide-related adverse effects proceeds in this
order:
Substituted Benzenes
Thiocarbamates
Ethylene Bis Dithiocarbamates
Thiophthalimides
Copper Compounds
Organomercury Compounds
Organotin Compounds
Cadmium Compounds
Miscellaneous Organic Fungicides
89
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SUBSTITUTED BENZENES
HEXACHLOROBENZENE (HCB, Anticarie, Ceku C.B., No Bunt).
Cl
Cl
Cl
Principal formulations are dusts and powders.
Hexachlorobenzene differs chemically and toxicologically from hex-
achlorocyclohexane, the gamma isomer of which (lindane) is still a
widely used insecticide (see Chapter 3, TOXICOLOGY).
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
HEXACHLOROBENZENE
Although this seed protectant fungicide has only slight irritant ef-
fects and relatively low single-dose toxicity, long-term ingestion of
HCB-treated grain by Turkish farm dwellers in the late 1950's caused
.several thousand cases of hepatic porphyria (porphyria cutanea tarda).
This condition was due to impaired hemoglobin synthesis, leading to
toxic end-products (porphyrins) in body tissues. The disease was charac-
terized by excretion of red-tinged (porphyrin-containing) urine, bullous
lesions of light-exposed skin, scarring and atrophy of skin with over-
growth of hair, liver enlargement, loss of appetite, arthritic disease,
and wasting of skeletal muscle mass. Although most adults ultimately
recovered after they stopped consuming the HCB-treated grain, some
infants nursed by affected mothers died.
Hexachlorobenzene is effectively dechlorinated and oxidized in
humans; trichlorophenols are the major urinary excretion products.
Disposition is sufficiently prompt that occupationally exposed workers
usually show only slight elevation of blood HCB concentrations. HCB is
sometimes present in blood specimens from "non-occupationally ex-
posed" persons up to concentrations of about 5 meg per liter. Residue
in food is the probable source.
CONFIRMATION OF POISONING BY HEXACHLOROBENZENE
HCB can be measured in blood by gas chromatography. Chlorophenol
metabolites can be measured in the urine.
Although inherited disease and a number of exogenous agents may
cause porphyrins to appear in the urine, a test for porphyrins may be
90
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useful for toxicologic diagnosis if there has been a known exposure to
HCB or if a patient exhibits signs suggestive of porphyria cutanea
tarda.
More than 0.5 mg per liter of porphyrins causes the untreated urine
to exhibit a wine-red color in ordinary light. Somewhat lower concen-
trations can be detected by examining the urine in ultraviolet light
(366 nm emission). Red or orange-red fluorescence indicates presence of
uroporphyrins. However, background fluorescence from other urine
constituents may mask this emission. If the above examination is
negative, therefore, the following screening test for uroporphyrins can
be performed:
1. Acidify the urine to pH 4.0 with acetic acid.
2. Heat for 15 minutes in a 100° C water bath.
3. Cool. Clean the outside of the test tube carefully, and examine for
orange-red fluorescence in UV light (366 nm).
Urinary coproporphyrin excretion is also increased in HCB intoxica-
tion. The following test can be done to detect elevated concentrations:
1. Put 5 ml of clear (filtered) urine in a 16 x 150 mm quartz test
tube.
Add in this order: 1 ml glacial acetic acid, 5 ml ethyl ether, then 3
drops fresh 3% hydrogen peroxide.
Close tube with a clean rubber stopper and invert 12 times to mix
and extract. Allow to stand 10 minutes. (Centrifuge if necessary to
break emulsion.)
Examine the ether layer in UV light for pink, violet, or rose red
emitted light, indicating presence of coproporphyrins.
2.
3.
4.
TREATMENT OF HEXACHLOROBENZENE TOXICOSIS
1. Dermal contamination should be washed off with soap and water.
Contamination of the eyes should be removed by flushing with
copious amounts of water. If irritation persists, specialized medi-
cal care should be obtained.
2. If a large amount of HCB has been ingested in the last few hours,
and if copious vomiting has not already occurred, the stomach
must be emptied and steps taken to limit gastrointestinal absorp-
tion. If the patient is fully alert and nervous system depression is
not anticipated, oral administration of Syrup of Ipecac is probably
the best way to empty the stomach.
Dosage of SYRUP OF IPECAC:
Adults and children over 12 years: 30 ml, followed by 2-3
glasses of water.
Children under 12 years: 15 ml, followed by 1-2 glasses of
water. Children less than one year should receive only 10-15
ml and should be under direct medical supervision if at all
possible.
91
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3.
4.
When vomiting stops after induced emesis, give charcoal and
cathartic orally by adding sorbitol to the charcoal slurry.
Dosage of ACTIVATED CHARCOAL:
Adults and children over 12 years: 50-100 gm in 300-800 ml
water.
Children under 12 years: 15-30 gm in 100-300 ml water.
Dosage of SORBITOL:
Adults and children over 12 years: 1-2 gm/kg body weight to
a maximum of 150 gm per dose.
Children under 12 years: 1.0-1.5 gm/kg body weight to a
maximum of 50 gm per dose.
If sorbitol is given separately, it should be diluted with an equal
volume of water before administration.
If there are any indications of central nervous system depression,
or if the patient fails to vomit within 30 minutes of Syrup of
Ipecac administration, measures should be taken to protect the
respiratory tract from aspiration of gastric contents (preferably a
cuffed endotracheal tube), then the stomach should be emptied by
gastric intubation, aspiration and lavage with a slurry of activat-
ed charcoal (see Chapter 1, TREATMENT, Section 6, page 8).
Instill activated charcoal following lavage. Unless diarrhea has
already commenced, include a cathartic (see above for dosage) to
hasten elimination.
CAUTION: Do not instill fluid so rapidly that overloading of the
stomach leads to vomiting or regurgitation, followed by aspira-
tion. Serious electrolyte disturbances may follow catharsis, espe-
cially in young children. Monitor fluid balance and serum electro-
lytes.
If the amount of ingested HCB was small, or if treatment has
been delayed several hours, or if spontaneous vomiting has effec-
tively emptied the stomach, oral administration' of charcoal and
sorbitol at the doses recommended above probably represents opti-
mal management.
If contact with the toxicant has been minimal (for example, oral
contamination only, promptly flushed out of the mouth) adminis-
tration of charcoal without a cathartic, followed by careful obser-
vation of the patient, probably represents optimal management.
In persons who have experienced significant tissue storage of HCB
(as from protracted uptake of small quantities) administration of
cholestyramine accelerates elimination by interrupting enterohe-
patic recirculation. It is usually administered in 3-8 gm doses, 4
times a day, before meals and at bedtime. Dose should be mixed
with a pulpy fruit or liquid.
Persons affected by porphyria should avoid sunlight, which exac-
erbates the dermal injury by porphyrins.
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PENTACHLORONITROBENZENE (PCNB, quintozene, Terraclor,
Avicol, Botrilex, Earthcide, Folosan, Kobu, Kobutol, Pentagon, Til-
carex, Tri-PCNB).
NO,
Cl
This fungicide is used to dress seed and treat soil. Formulations
include emulsifiable concentrates, wettable powders, and granules.
Hexachlorobenzene is a minor contaminant of technical PCNB.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
PENTACHLORONITROBENZENE
High concentrations in prolonged contact with skin have caused
sensitization in some tested volunteers, but neither irritation nor sensi-
tization 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. Disposition in laborato-
ry animals is slow, probably due to. enterohepatic recirculation. Excre-
tion 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 man or animals, nor has hepatic por-
phyria (as from hexachlorobenzene) been reported.
CONFIRMATION OF ABSORPTION OF
PENTACHLORONITROBENZENE
PCNB and metabolites can be measured in body fluids by gas chro-
matography. The analysis is not widely available.
TREATMENT OF PENTACHLORONITROBENZENE TOXICOSIS
See HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2, and 3 above.
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DICHLORAN (DCNA, . ditranil, Botran, Allisan, Kiwi Lustr 277,
Resisan).
Dichloran is formulated as wettable powder, dusts, and flowable
powders.
TOXICOLOGY AND MANIFESTIONS OF POISONING BY
DICHLORAN
This broad spectrum fungicide is widely used to protect perishable
produce. It is absorbed by occupationally exposed workers, but prompt-
ly eliminated, at least partly in the urine. Residence half-life in man is
probably less than 27 hours. Biotransformation products include dich-
loroaminophenol, which is an uncoupler of oxidative phosphorylation
(enhances heat production). Extraordinary doses of dichloran 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 hi humans exposed to DCNA. Daily oral dosage of 10 mg per
day for 90 days was tolerated by 20 adult male subjects without observ-
able effect.
CONFIRMATION OF ABSORPTION OF DICHLORAN
Methods have been described for analysis of dichloran, but they are
not widely available.
MANAGEMENT OF DICHLORAN EXPOSURE
See HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2, and 3 above.
94
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CHLOROTHALONIL (Bravo, CldrtoCaffaro, Clortosip, Dacohil 2787,
Exotherm Termil, Tuffcide).
CN
Cl
Chorothalonil 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. Rarely, it has caused
dermal sensitization. It is apparently poorly absorbed across the skin
and the gastrointestinal lining. No cases of systemic poisoning in
humans have been reported.
CONFIRMATION OF ABSORPTION OF CHLOROTHALONIL
Chlorothalonil can be measured in blood by gas chromatography, but
the analysis is not widely available.
TREATMENT OF CHLOROTHALONIL TOXICOSIS
See HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2, and 3 above.
CHLORONEB (Terraneb SP).
OCH.
Chloroneb is supplied as wettable powder for treatment of soil and
seed.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
CHLORONEB
This agent exhibits very low oral toxicity in mammals. It may be
moderately irritating to skin and mucous membranes. The metabolite
dichloromethoxyphenol is excreted in the urine. No cases of systemic
poisoning in humans have been reported.
95
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CONFIRMATION OF ABSORPTION OF CHLORONEB
Chloroneb can be measured in body fluids by chromatography, but
the analysis is not widely available.
MANAGEMENT OF CHLORONEB EXPOSURE
See HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2, and 3 above.
THIOCARBAMATES
Unlike the N-methyl carbamates (Chapter 2), thiocarbamates have
very little insecticidal potency. A few exhibit weak anticholinesterase
activity, but most have no significant effect on this enzyme. Overall,
they are less of a threat to human health than the insecticidal carba-
mates. Fungicidal thiocarbamates are discussed in this section while
those used as herbicides are considered in Chapter 11.
THIRAM
S
II
c
— C — S — S — C — N
S
II
C
I
\
CH3
COMMERCIAL PRODUCTS
AAtack, Aules, Chipco Thiram 75, Fermide 850, Fernasan, Hexathir,
Mercuram, Nomersam, Polyram-Ultra, Pomarsol forte, Spotrete-F, Spo-
trete WP 75, Tetrapom, Thimer, Thioknock, Thiotex, Thiramad, Thira-
san, Thiuramin, Tirampa, TMTD, TMTDS, Trametan, Tripomol, Tuads,
Vancide TM.
Thiocarbamates are commonly formulated as dusts, wettable pow-
ders or water suspensions. They are used to protect seeds, seedlings,
ornamentals, turf, vegetables, fruit, and apples.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
THffiAM
Thiram dust is moderately irritating to human skin, eyes, and respi-
ratory mucous membranes. Contact dermatitis has occurred in occupa-
tionally exposed workers. A few individuals have experienced sensitiza-
tion to thiram.
96
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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 ana-
logue of thiram which has been extensively used in alcohol aversion
therapy. In laboratory animals, thiram at high dosage has effects simi-
lar to those of disulfiram (hyperactivity, ataxia, loss of muscle tone,
dyspnea, convulsions), but thiram appears to be about 10 times as toxic
as disulfiram.
Clinical doses of disulfiram (0.25-1.00 gm daily) have caused fatigue,
headache, dizziness, tremor, restlessness, anorexia, and nausea. Rarely,
liver injury, peripheral neuropathy, renal tubular damage, and ence-
phalopathic symptoms have been reported following large and/or pro-
tracted dosage. These effects may be due to one or more thiocarbamate
biotransformation products (including carbon disulfide) formed in the
gut or tissues.
Neither thiram nor disulfiram are cholinesterase inhibitors. Both,
however, inhibit the enzyme acetaldehyde dehyrogenase, which is criti-
cal to the conversion of acetaldehyde to acetic acid. This is the basis for
the "Antabuse" reaction which occurs when ethanol is consumed by a
person on regular disulfiram dosage: nausea, vomiting, pounding head-
ache, dizziness, faintness, mental confusion, dyspnea, chest and abdom-
inal pain, profuse sweating, and skin rash. In rare instances, "Anta-
buse" reactions may have occurred following beverage alcohol inges-
tion by workers previously exposed to thiram.
CONFIRMATION OF ABSORPTION OF THIRAM
Urinary xanthurenic acid excretion has been used to monitor work-
ers exposed to thiram. The test is not generally available.
TREATMENT OF THIRAM TOXICOSIS
Wash thiram from the skin with soap and water. Flush contamina-
tion from the eyes with copious amounts of clean water. If irritation of
skin or eyes persists, medical treatment should be obtained.
If a large amount of thiram has been swallowed and effective vomit-
ing has not already occurred, the stomach should be emptied by intu-
bation, aspiration, and lavage, taking all precautions to protect the
airway from aspiration of vomitus. Lavage should be followed by instil-
lation of activated charcoal and cathartic (see Chapter 1, TREAT-
MENT, Section 6, page 8). Syrup of Ipecac administration is not advisa-
ble because the contained alcohol (2%) may possibly induce an "Anta-
buse" reaction.
If only a small amount of thiram has been ingested and/or treat-
ment has been delayed, oral administration of activated charcoal and
cathartic probably represents optimal management.
97
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In severe poisonings, intravenous infusion of GLUCOSE solution
protects the liver and supports mechanisms of detoxication and excre-
tion. If vomiting and diarrhea are severe, fluid balance and serum
electrolytes should be monitored, and appropriate electrolyte solutions
infused to correct losses.
TREATMENT OP ACETALDEHYDE TOXICOSIS (ANTABUSE
REACTION)
OXYGEN inhalation, Trendelenburg positioning, and intravenous
fluids are usually effective in relieving manifestations of Antabuse
reactions. Persons who have absorbed any significant amount of dithio-
carbamate must avoid alcoholic beverages for at least three weeks.
Disposition of thiocarbamates is slow and their inhibitory effects oh
enzymes are slowly reversible.
METAM-SODIUM (METHAM-SODIUM)
CH
N-C
S
H
COMMERCIAL PRODUCTS
S-Na • 2H 0
A7 Vapam, Busan 1020, Karbation, Maposol, Metam-Fluid BASF,
Nemasol, Solasan 500, Sometam, Trimaton, Vapam, VPM.
Formulated in aqueous solutions for application as a soil biocide to
kill fungi, bacteria, weed seeds, nematodes, and insects.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
METAM-SODIUM
Although animal feeding studies do not indicate extraordinary toxici-
ty of metam-sodium by ingestion, its decomposition in water yields
methyl isothiocyanate, a gas that is extremely irritating to respiratory
mucous membranes, to the eyes, and to the lungs. Inhalation of methyl
isothiocyanate may cause pulmonary edema (severe respiratory dis-
tress, coughing of bloody, frothy sputum). For this reason, metam-
sodium must be used out of doors only, and stringent precautions must
be taken to avoid inhalation of evolved gas.
Theoretically, exposure to metam-sodium may predispose the individ-
ual to Antabuse reactions if alcohol is ingested after exposure. Such
occurrences have not been reported.
98
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CONFIRMATION OP ABSORPTION OF METAM-SODITJM
There are no tests for metam-sodium or its breakdown products in
body fluids.
TREATMENT OF METAM-SODIUM TOXICOSIS
Contamination of the skin and eyes should be treated immediately
with copious amounts of water to avoid burns and corneal injury. If
eye or skin irritation persists, expert medical treatment should be
obtained. Poisonings by ingestion of metam-sodium have not been re-
ported. If a large amount has been ingested recently, empty the stom-
ach by gastric intubation, aspiration, and lavage, after taking all pre-
cautions to protect the airway (see Chapter 1, TREATMENT, Section 6,
page 8). Instill activated charcoal. Also give cathartic unless diarrhea
has already commenced.
If pulmonary irritation or edema occur as a result of inhaling methyl
isothiocyanate, transport the victim promptly to a medical facility.
Treatment for pulmonary edema should proceed as outlined in Chapter
14, FUMIGANTS, page 139.
Metam-sodium is not a cholinesterase inhibitor. Atropine is not anti-
dotal.
ZIRAM AND FERBAM
•CH3
\
S "
11
N -C-S
n
COMMERCIAL PRODUCTS
Ziram (Carbazinc, Corozate, Cuman, Drupina 90, Fungostop, Hexazir,
Mezene, Prodaram, Tricarbamix Z, Triscabol, Zerlate, Vancide MZ-96,
Zincmate, Ziram Technical, Ziram F4, Ziram W76, Ziramvis, Zirasan
90, Zirberk, Zirex 90, Ziride, Zitox).
Ferbam (Carbamate, Ferbam, Ferberk, Hexaferb, Knockmate, Tri-
fungol).
These are formulated as flowable and wettable powders, used widely
on fruit and nut trees, apples, vegetables, and tobacco.
99
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TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
ZIRAM AND FERBAM
Dust is irritating to the skin, respiratory tract, and eyes. Prolonged
inhalation of ziram is said to have caused neural and visual disturb-
ances, and, in a single case of poisoning, a fatal hemolytic reaction.
If absorbed" in sufficient dosage, metallo thiocarbamates may theo-
retically predispose to an Antabuse reaction following ingestion of
alcohol. (See THIRAM.) No occurrences of this have been reported.
CONFIRMATION OF ABSORPTION OF ZIRAM AND FERBAM
No tests for these fungicides or their breakdown products in body
fluids are available.
TREATMENT OF ZIRAM AND FERBAM TOXICOSIS
Skin contamination should be washed off with soap and water. Con-
tamination of the eyes should be removed with copious amounts of
water. If dermal or eye irritation persists, specialized medical treat-
ment should be obtained.
If substantial amounts of ferbam or ziram have been ingested recent-
ly, the stomach should be emptied by gastric intubation, aspiration,
and lavage, after all measures have been taken to protect the airway
(see Chapter 1, TREATMENT, Section 6, page 8). If dosage was small
and/or several hours have elapsed since ingestion, oral administration
of charcoal and a cathartic probably represents optimal management.
If hemolysis occurs, intravenous fluids should be administered, and
induction of diuresis considered (see Chapter 14, TREATMENT OF
NAPHTHALENE TOXICOSIS, page 141).
ETHYLENE BIS DITHIOCARBAMATES (EBDC COMPOUNDS)
MANEB, ZINEB, NABAM, and MANCOZEB
H H S
I I II
HC - N - C - S
Mn or Zn or Na
HC - N - C - S
I I M
H H S
100
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COMMERCIAL, PRODUCTS
Maneb (Akzo Chemie Maneb, BASF-Maneb Spritzpulver, Dithane M-
22, Kypman 80, Manex 80, Maneba, Manesan, Manex, Manzate, Man-
zate D, M-Diphar, Polyram M, Remasan Chloroble M, Rhodianebe,
Sopranebe, Trimangol, Tubothane, Unicrop Maneb).
Zineb (Aspor, Chem Zineb, Devizeb, Dipher, Dithane Z-78, Hexath-
ane, Kypzin, Lonacol, Parzate, Parzate C, Polyram Z, Tiezene, Tritof-
torol, Zebtox, Zineb 75 WP, Zinosan).
Nabam (Chem Bam, DSE, Nabasan, Parzate, Spring Bak).
Maneb and Zineb are formulated as wettable and flowable powders.
Nabam is provided as a soluble powder and in water solution.
Mancozeb (manzeb, Dithane M-45, Manzate 200, Akzo Chemie Man-
cozeb, Mancozin, Manzin, Nemispor, Penncozeb, Policar MZ, Policar S,
Vondozeb Plus, Ziman-Dithane). Mancozeb is a coordination product of
zinc ion and maneb. It is formulated as a dust and as wettable and
liquid flowable powders.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
EBDC COMPOUNDS
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 com-
pounds 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.
The EBDC compounds are not inhibitors of cholinesterase or of
acetaldehyde dehydrogenase. They do not induce cholinergic illness or
"Antabuse" reactions.
CONFIRMATION OF ABSORPTION OF EBDC COMPOUNDS
No tests for these fungicides or their breakdown products in body
fluids are available.
MANAGEMENT OF EBDC EXPOSURE
See this chapter, HEXACHLOROBENZENE,, TREATMENT OF
TOXICOSIS, Sections 1 and 2 above, page 91.
101
-------
TfflOPHTHALIMIDES
CAPTAN, CAPTAFOL, and FOLPET
N-S-C-CI I
Cl
o
II
II
•c\ ci ci
x II s?
N-S-C-C-CI f
/ ll1^
•c ci ci ^
II
1!
O
o
II
II
V^
Cl
N-S-C-CI
\/
||
II
O
1
Cl
CAPTAFOL
FOLPET
CAPTAN
COM1VIERCIAL PRODUCTS
Captan (Captanex, Captaf, Merpan, Orthocide, Vondcaptan).
Captafol (Crisfolatan, Difolatan, Foltaf, Haipen, Merpafol, Mycodifol,
Sanspor).
Folpet (Folpan, Phaltan, Thiophal, Fungitrol II).
These agents are widely used to protect seed, field crops, and stored
produce. They are formulated as dusts and wettable powders.
TOXICOLOGY AND ADVERSE EFFECTS OF
THIOPHTHALIMIDES
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. No systemic poisonings by thiophthalimides have been re-
ported in man. Laboratory animals given very large doses of captan
exhibit hypothermia, irritability, listlessness, anorexia, hyporeflexia,
and oliguria, the latter with glycosuria and hematuria,
CONFIRMATION OF ABSORPTION OF THIOPHTHALIMIDES
There are no tests for these fungicides or their breakdown products
in body fluids.
MANAGEMENT OF THIOPHTHALIMIDE EXPOSURE
See this chapter, HEXACHLOROBENZENE, TREATMENT OF
TOXICOSIS, Sections 1 and 2, above, page 91.
COPPER COMPOUNDS
INORGANIC COPPER COMPOUNDS
Cuprous oxide; cupric oxide; copper hydroxide.
102
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Copper carbonate, basic; copper ammonium carbonate.
Copper acetate; copper sulfate; copper sulfate, tribasic (Bordeaux
Mixture); copper oxychloride; copper silicate.
Copper lime dust; copper potassium sulfide.
ORGANIC COPPER COMPOUNDS
Copper linoleate, naphthenate, oleate, phenyl salicylate, quinolino-
late, and resinate.
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.
There are several copper-arsenic compounds, such as Paris Green,
still used in some agricultures. Toxicity of these is chiefly due to
arsenic content (see Chapter 6, ARSENICAL PESTICIDES).
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
COPPER COMPOUNDS
The dust and powder preparations of copper compounds are irritat-
ing to the skin, respiratory tract, and particularly to the eyes. The
soluble copper salts (such as the sulfate and acetate) are corrosive to
mucous membranes and the cornea. Limited solubility and absorption
probably account for generally low systemic toxicities of most com-
pounds. The more absorbable organic copper compounds exhibit the
greatest systemic toxicity in laboratory animals. While irritant effects
from occupational exposures to copper-containing fungicides have been
fairly frequent, systemic poisonings of humans have been rare. Most of
what is known about mammalian toxicity of copper compounds has
come from veterinary toxicology (livestock seem uniquely vulnerable)
and rare poisonings in man due to deliberate ingestions of copper
sulfate or to consumption of water or food that had been contained in
copper vessels. The principal features of poisoning by ingested copper
compounds have been 1) gastrointestinal irritation (vomiting and burn-
ing pain in the mouth, esophagus and stomach, abdominal pain and
diarrhea, sometimes with blood), 2) headache, sweating, weakness, and
sometimes shock, 3) liver enlargement and jaundice, 4) hemolysis and
methemoglobinemia, and 5) albuminuria, hemoglobinuria, and some-
times acute renal failure.
103
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TREATMENT OF COPPER TOXICOSIS
Contaminating dust and powder should be washed from the skin
with soap and water. The eyes should be flushed free of irritating dust,
powder, or solution, using clean water or saline. If eye or dermal
irritation persists, medical treatment should be obtained. Eye irritation
may be severe.
Management of poisonings by ingestion of copper-containing fungi-
cides depends entirely on the chemical nature of the compound: the
strongly ionized salts present the greatest hazard; the oxides, hydrox-
ides, oxychloride, and oxysulfate are less likely to cause severe system-
ic poisoning.
1. Give water or milk as soon as possible to dilute the toxicant and
mitigate corrosive action on the mouth, esophagus, and gut.
2. Unless vomiting has been vigorous and effective, empty the stom-
ach by intubation, aspiration, and lavage, taking all precautions
to protect the respiratory tract from aspirated stomach contents.
(See Chapter 1, TREATMENT, Section 6, page 8). Activated char-
coal included in the lavage fluid may be of some value against the
organometallic compounds, but is probably less effective against
the inorganic copper compounds.
CAUTION: Gastric intubation may pose a serious risk of esopha-
geal perforation if corrosive action has been severe. In this event,
it may be best not to attempt intubation.
3. If indications of systemic illness appear, administer intravenous
fluids containing glucose and electrolytes. Monitor fluid balance,
and correct blood electrolyte concentrations as needed.. If shock
develops, give blood transfusions and vasopressor amines, as re-
quired.
4. 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 (for dosage, see Chapter 7, TREAT-
MENT, Section 5, page 67). Also, mannitol diuresis may be consid-
ered. Unless methemoglobinemia is severe (30-40%), it is probably
not advisable to administer methylene blue.
5. Severe pain may require the administration of morphine.
6. The value of chelating agents in copper poisoning has not been
established. BAL appears to show some promise in accelerating
copper excretion and alleviating illness. If the severity of poison-
ing appears to warrant its use, a recommended schedule of dosage
for initial therapy with BAL and subsequent penicillamine admin-
istration is offered in Chapter 6, ARSENICAL PESTICIDES,
TREATMENT, Sections 9 and 10, pages 60-61.
104
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ORGANOMERCURY COMPOUNDS
METHYL MERCURY COMPOUNDS
H
I
HC -
H
INORGANIC or
ORGANIC ION
COMMERCIAL PRODUCTS
Methyl mercury hydroxide, nitrile, benzoate, acetate, propionate,
pentachlorophenate, quinolinolate.
METHOXYETHYL MERCURY COMPOUNDS
H
i
HC
i
H
H
C
i
H
H
- 0 - C - C - Hg*
C
i
H
INORGANIC or
ORGANIC ION
COMMERCIAL PRODUCTS
Methoxyethyl mercury acetate (MEMA, Panogen, Panogen M).
Methoxyethyl mercury chloride (MEMC, Emisan 6, Geresan).
PHENYL MERCURIC ACETATE
0 -
0
II
C -
H
GH
H
COMMERCIAL PRODUCTS
Agrosan, Cekusil, Celmer, Hong Nien, Liquiphene, Mersolite, Pa-
misan, Phix, PMAS, Seedtox, Shimmer-ex, Tag HL 331, Unisan.
Setrete (Gallotox, PMAA) is phenyl mercury ammonium 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 still used to control
diseases of turf, but other applications have been sharply restricted.
105
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TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
ORGANOMERCURY COMPOUNDS
The mercurial fungicides are among the most toxic pesticides ever
developed, in terms of chronic as well as acute hazard. 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. Poisoning has also occurred when
meat from animals fed mercury-treated seed was eaten. 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 the red
blood cells. Other alkyl mercury compounds are probably distributed
similarly. Excretion occurs almost entirely by way of the bile into the
bowel. The residence half-life of methyl mercury in the human is about
70 days. There is significant conversion of organic mercury to inorgan-
ic mercury in the red cell.
Early symptoms of poisoning are metallic taste in the mouth, numb-
ness and tingling of the digits and face, tremor, headache, fatigue,
emotional lability, and difficulty thinking. Manifestations of more
severe poisoning are incoordination, slurred speech, loss of position
sense, hearing loss, constriction of visual fields, spasticity or rigidity of
muscle movements, and deterioration of mental capacity. Many poison-
ings caused by ingestion of organic mercurials have terminated fatally,
and a large percentage of survivors have suffered severe permanent
neurologic damage.
Phenyl mercuric acetate is apparently not as extremely toxic as the
alkyl mercury compounds. However, exposure to it has preceded the
appearance of symptoms and signs of neurologic disease resembling
amyotrophic lateral sclerosis in certain reported instances.
CONFIRMATION OF POISONING BY ORGANOMERCURY
COMPOUNDS
Mercury content of blood and tissues can be measured by atomic
absorption spectrometry. Special procedures are needed for extraction
and measurement of organic mercury compounds specifically. These
tests are not generally available.
TREATMENT OF ORGANOMERCURY TOXICOSIS
Skin and hair contaminated by mercury-containing dust or solution
should be cleansed with soap and water. Eye contamination should be
removed by flushing the eye with clean, water, If irritation persists,
specialized medical care should be obtained.
106
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Persons experiencing symptoms (metallic taste in mouth) after inha-
lation 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 impair-
ment. 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. Detailed discussions of
contemporary treatment options are offered in modern clinical toxicol-
ogy texts. Some of these texts are listed in the introduction to this
volume. Following are the basic steps in management of poisoning.
1. Limit gastrointestinal absorption. If a mercurial fungicide has
been ingested in the past few hours, the stomach must be evacuat-
ed by intubation and lavage, taking all precautions to protect the
respiratory tract (see Chapter 1, TREATMENT, Section 6, page 8).
Repeated administration of activated charcoal may be beneficial.
2. Administer a chelating agent. Dimercaprol (BAL) and EDTA are
apparently of little value in poisonings by organic mercury, but
other chelators are effective:
A. D-penicillamine. (This is available in the United States, and
has proven effective in reducing the residence half-life of
methyl mercury in poisoned humans, see Chapter 6, ARSENI-
CAL PESTICIDES, p. 61, for dosage).
B. 2,3-dimercaptopropane-l-sulfonate, and 2,3-dimercaptosuccinic
acid. (Although effective, these agents are not currently ap-
proved for use in the United States.)
C. N-acetyl-D,L-penicillamine. (Effective, but not currently ap-
proved for use in the United States.)
3. Extracorporeal hemodialysis and hemoperfusion may be consid-
ered, although experience to date has not been encouraging. Al-
though the unmodified organic mercurials are not efficiently dia-
lyzable across most membranes, when used in combination with
chelating agents, dialysis may may be of some value in removing
organic mercury from the blood (A.H. Al-Abbasi et al. J. Pharma-
col. Exptl. Therap. 207:249-254, 1978).
Very little can be done to mitigate neurologic damage caused by
organic mercurials.
107
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ORGANOTIN COMPOUNDS
TRIPHENYL TIN
Phenyl tin
Compounds
COMMERCIAL PRODUCTS
Fentin hydroxide (Du-Ter, Outer, Haitin, Phenostat-A H, Suzu-H,
TPTH, TPTOH, Triple Tin, Tubotin).
Fentin chloride (Aquatin, Phenostat-C, Tinmate).
Fentin acetate (Batasan, Brestan, Phenostat-A, Phentinoacetate, Suzu,
Tinestan, TPTA).
All are formulated as wettable and flowable powders for use mainly
as fungicides to control blights on field crops and orchard trees. Fentip
chloride is also prepared as an emulsifiable concentrate for use as,1 a
molluscicide (Aquatin 20 EC).
Tributyltin salts are used as fungicides and antifouling agents on
ships. They are somewhat more toxic by the oral route than triphenyl-
tin, but toxic actions are otherwise probably similar.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
ORGANOTIN COMPOUNDS
These agents are irritating to the eyes, respiratory tract, and skin.
They are probably absorbed to a limited extent by the skin and gastro-
intestinal tract. Manifestations of toxicity are due principally to effects
on the brain: headache, nausea, vomiting, dizziness, and sometimes
convulsions and loss of consciousness. Photophobia and mental disturb-
ances occur. Epigastric pain is reported, even in poisoning caused by
inhalation. Elevation of blood sugar, sufficient to cause glycosuria, has
occurred in some cases. The phenyl tin fungicides are apparently 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. No
108
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deaths and very few poisonings have been reported as a result of
occupational exposures to phenyltin compounds.
TREATMENT OF ORGANOTIN TOXICOSIS
Skin contamination should be removed by washing with soap and
water. Eyes should be flushed free of contaminating material with
clean water or saline. If irritation persists, expert medical treatment
should be obtained.
If large amounts of phenyltin compound have been ingested in the
past few hours, measures should be taken to remove the toxicant from
the gastrointestinal tract and to limit absorption (see Chapter 1,
TREATMENT, Section 6, p. 8). If oral dosage was small and/or treat-
ment has been delayed, and if the patient is fully alert, oral adminis-
tration of activated charcoal with a cathartic probably represents opti-
mal management. (See above reference.) Neither BAL, penicillamine,
or chelating agents have been effective in lowering tissue stores of
organotin compounds in experimental animals.
CADMIUM COMPOUNDS
CHEMICAL STRUCTURES
Cd CI2
Cadmium
Chloride
Cd SO 4
Cadmium
Sulfate
,0 - c -
Cd
o - c -
0
II
e -
c -
II
0
H
C
C
H
Cadmium
succinate
COMMERCIAL PRODUCTS
Cadmium chloride-Caddy, Vi-Cad.
Cadmium sulfate (generic, 14% solution)
Cadmium succinate: Cadminate
Miller 531 and Crag Turf Fungicide 531 are complexes of cadmi-
um, calcium, copper, chromium, and zinc oxides.
Kromad is a mixture of cadmium sebacate, potassium chromate,
and thiram.
Cad-Trete is a mixture of cadmium chloride and thiram.
109
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Cadmium salts are used to treat fungal diseases affecting turf and
the bark of orchard trees. They are formulated as solutions and emul-
sions.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
CADMIUM COMPOUNDS
Cadmium salts and oxides are very irritating to the respiratory and
gastrointestinal tracts. Inhaled cadmium dust or fume has caused pul-
monary edema and pneumonitis, sometimes fatal. Headache, persistent
cough, productive of copious frothy and sometimes bloody sputum, is
accompanied by labored breathing and chest pain. Fever may follow.
Symptoms may persist for weeks. Ingested cadmium causes nausea,
vomiting, diarrhea, abdominal pain, and tenesmus. Relatively small
inhaled and ingested doses produce serious symptoms. Protracted ab-
sorption of cadmium has led to renal damage (proteinuria and azote-
mia), anemia, liver injury (jaundice), and defective bone structure
(pathologic fractures) in chronically exposed persons.
CONFIRMATION OF POISONING BY CADMIUM COMPOUNDS
Cadmium can be measured in body fluids by appropriate extraction,
followed by flame absorption spectrometry. The approximate upper
limit of blood concentration of cadmium in persons not exceptionally
exposed is 10 meg per liter. Poisoned persons have exhibited blood
cadmium concentrations as high as 6,200 meg per liter and urine
cadmium concentrations as high as 2,200 meg per liter.
It is reported that blood cadmium concentration reflects recent expo-
sure while urine cadmium excretion correlates more closely with body
burden. Urinary excretion hi excess of 100 meg per day suggests an
unusually high body burden.
TREATMENT OF CADMIUM TOXICOSIS
1. Skin contamination should be removed by washing with soap and
water. Contamination of the eyes should be removed by copious
flushing with clean water or saline. If irritation persists, medical
treatment should be obtained.
2. Respiratory irritation resulting from inhalation of small amounts
of cadmium dust may resolve spontaneously, requiring no treat-
ment. 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 antibi-
otics (see Chapter 14, TREATMENT, Sections 2-4, pp. 138-139).
Codeine sulfate may be needed to control cough and chest pain.
3. The irritant action of ingested cadmium products on the gastroin-
testinal tract is so strong that spontaneous vomiting and diarrhea
110
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4.
5.
often eliminate nearly all unabsorbed cadmium from the gut.
Give as much milk or egg white orally as the patient will tolerate
as soon as possible to neutralize any residual cadmium. Repeat
every 4 hours. If retention of some cadmium in the lower GI tract
is suspected, administer sorbitol as a cathartic. For dosage, see
this chapter, HEXACHLOROBENZENE, TREATMENT OF TOX-
ICOSIS, Section 2, page 91.
INTRAVENOUS FLUIDS may be required to overcome dehydra-
tion 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 ELEC-
TROLYTE CONCENTRATIONS, so that failing renal function
does not lead to fluid overload.
Chelation therapy with calcium disodium EDTA may be consid-
ered, 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. A
contemporary dosage protocol prescribes 75 mg/kg body weight
per day, given hi 3-6 divided doses by deep intramuscular injec-
tion or slow intravenous infusion for as many as 5 days. Consult a
modern clinical toxicology text for details of this therapy.
Dimercaprol (BAL) is not recommended for treatment of cadmium
poisoning, chiefly because of the risk of renal injury by mobilized
cadmium.
Monitor urine content of protein and cells regularly and perform
liver function tests for indications of injury to these organs.
MISCELLANEOUS ORGANIC FUNGICIDES
Some modern organic fungicides are widely used. Reports of adverse
effects on humans are few. Some of the known properties of these
agents are listed below.
ANILAZINE (Dyrene, Kemate, Triasyn).
Supplied as wettable and flowable powders. Used on vegetables, cere-
als, coffee, ornamentals, and turf.
This product has caused skin irritation in exposed workers. Acute
oral and dermal toxicities in laboratory animals are low. Human sys-
temic poisonings have not been reported.
6.
7.
Ill
-------
BENOMYL (Benlate, Tersan, Benex). :
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, beno-
myl is not a cholinesterase inhibitor. It is poorly absorbed across skin;
that which is absorbed is promptly metabolized and excreted.
Although injuries to exposed individuals have been few, dermal sen-
sitization has occurred in agricultural workers exposed to foliage resi-
dues.
CYCLOHEXIMIDE (Acti-dione, Actispray, naramycin).
Cycloheximide is formulated as wettable powders, sometimes com-
bined 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 re-
ported. Animals given toxic doses exhibit salivation, bloody diarrhea,
tremors, and excitement, leading to coma and death due to cardiovas-
cular collapse. Hydrocortisone increases the rate of survival of deliber-
ately poisoned rats. Atropine, epinephrine, methoxyphenamine, and
hexamethonium all relieved the symptoms of poisoning, but did not
improve survival.
DODINE (Cyprex, Carpene, Curitan, Melprex, Syllit, Venturol,
Vondodine).
Formulated as a wettable powder. Dodine 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 ab-
sorbed across the skin. It is irritating to skin, eyes, and gastrointestinal
tract. Acute oral and dermal toxicity in laboratory animals is moder-
ate. Poisonings ha humans have not been reported. Based on animal
studies, ingestion would probably cause nausea, vomiting, and diar-
rhea.
IPRODIONE (Rovral, Glycophene).
Supplied as wettable powder and other formulations. Used on ber-
ries, grapes, fruit, vegetables, grasses, and ornamentals. Also used as
seed dressing. Exhibits low acute oral and dermal toxicity in laboratory
animals. No human poisonings have been reported.
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METALAXYL (Ridomil, Apron 25 WP, Subdue 2E).
Supplied as emulsifiable and flowable concentrates. Used to control
soilborne fungal diseases on fruit trees, cotton, hops, soybeans, peanuts,
ornamentals, and grasses. Also used as seed dressing. Exhibits low
acute oral and dermal toxicity in laboratory animals. No human poi-
sonings have been reported.
TERRAZOLE (Aaterra, Dwell, Ethazol, Koban, Pansoil, Truban).
Supplied as wettable powder and granules for application to soil as a
fungicide and nitrification inhibitor. Contact may result in irritation of
skin and eyes. Systemic toxicity is low. Human poisonings have not
been reported.
THIABENDAZOLE (Apl-Luster, Arbotect, Mertect, TBZ, Tecto, Thiben-
zole).
Thiabendazole is widely used as an agricultural fungicide, but most
experience with its toxicology in humans has come from medicinal use
against intestinal parasites. Oral doses administered for this purpose
are far greater than those likely absorbed in the course of occupational
exposure. Thiabendazole is rapidly metabolized and excreted in the
urine, mostly as a conjugated hydroxy-metabolite. Symptoms and signs
that sometimes follow ingestion are: dizziness, nausea, vomiting, diar-
rhea, 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 (Bayleton, Amiral).
Supplied as wettable powder, emulsifiable concentrate, suspension
concentrate, paste, and dry flowable powder. Used on fruit, cereals,
vegetables, coffee, ornamentals, sugarcane, pineapple and turf.
Exhibits moderate acute oral toxicity in laboratory animals, but
dermal toxicity is low. 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 (Funginex, Saprol, Denarin, Cela W-524).
Supplied as emulsifiable concentrate and wettable powder. Used on
berries, fruit, vegetables, and ornamentals. It is rapidly excreted by
mammals, chiefly as a urinary metabolite. It exhibits low acute oral
and dermal toxicity in laboratory animals. No human poisonings have
been reported.
113
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CONFIRMATION OF ABSORPTION OF ANILAZINE, BENOMYL,
CYCLOHEXIMIDE, DODINE, METALAXYL, TERRAZOLE,
THIABENDAZOLE, TRIADIMEFON, OR TRIFORINE
There are no generally available laboratory tests for these organic
fungicides or their metabolites in body fluids.
MANAGEMENT OF EXPOSURE TO OR INGESTION OF
ANILAZINE, BENOMYL, CYCLOHEXAMIDE, DODINE,
METALAXYL, TERRAZOLE, THIABENDAZOLE,
TRIADIMEFON, OR TRIFORINE
See treatment protocol in this chapter under HEXACHLOROBEN-
ZENE, TREATMENT OF TOXICOSIS, Sections 1 and 2, page 91.
114
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CHAPTER 13
RODENTICIDES
CHEMICAL STRUCTURES
WARFARIN
;H,-C c-ci
H.Cs^N
CH, CH,
CRIUIOINE
ALKYL, PHENYL,
OIPHENYUCETYlw
CHIORMIPHENYUCETVI
1.3 INOAMOIONE
a
C-N-C-N-
H M . H
STRYCHNINE
H O
I t
f • C • C • ON>
H
SODIUM
FlUOROACETATE
\-HO,
SCIUIROSIOE
(Active pfincipl^ ol R«d Squtlll
f-ln-f
YELLOW
PHOSPHORUS
ZINC
PHOSPHIDE
NOflBORUlOE
115
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COMMERCIAL PRODUCTS
Coumarins: warfarin, coumafene, zoocoumarin (Co-Rax, Cov-R-Tox,
Kypfarin, Liqua-Tox, RAX, Rodex, Rodex-Blox, Tox-Hid, Warfarin Q),
coumafuryl, furmarin, tomarin (Fumarin, Tomarin), coumachlor (To-
morin, RatUan), bromadiolone (Bromone, Canadien 2000, Contrac,
Maki, Ratimus, Tamogam), brodifacoum (Havoc, Klerat, PP581, Ratak
Plus, Talon, Volid), difenacoum (Ratak, Neosorexa PP580, WBA 8107),
coumatetralyl (Racumin), valone (PMP Tracking Powder), prolin
(Eraze, Final, Place-Pax, Warfarin Q Concentrate).
Indandiones: diphacinone, diphacin (Kill-Ko Rat Killer, P.C.Q.,
Rodent Cake), chlorophacinone (Caid, Drat, Liphadione, LM91, Micro-
zul, Ramucide, Ratomet, Raviac, Rozol, Topitox), pindone, pival, pival-
dione (Pivalyn, Pivacin, Tri-ban), radione.
Inorganics: yellow phosphorus, zinc phosphide (Phosvin, Zinc-Tox,
ZP, RidaU-Zinc), thaUium sulfate. Yellow phosphorus is not sold in the
United States. Zinc phosphide is registered, but little used in the
United States. Thallium sulfate is no longer registered for pesticidal
use.
Convulsants: sodium fluoroacetate (Compound 1080, Fratol, Yasok-
nock), strychnine, crimidine (Castrix). Only specially trained personnel
are allowed to use sodium fluoroacetate or strychnine. Crimidine is no
longer registered for use as a pesticide.
Miscellaneous: alpha-naphthyl thiourea (ANTU, Krysid), norbormide
(Shoxin, Raticate), red squill (Dethdiet, Rodine), pyriminil (Vacor, RH-
787, DLP-87), cholecalciferol (Quintox, Rampage). ANTU and red squill
are both registered for rodenticidal use; red squill is little used. Nei-
ther norbormide nor pyriminil are now registered for use in the United
States.
Rodent poisons are usually added to baits (palatable grain or paste
intended to encourage consumption). Safety for animals and humans
depends on the toxicity of the agents, concentration of the active
ingredient in the bait, and the likelihood that a toxic dose will be
consumed by nontarget species. The coumarins, for example, are rea-
sonably effective against pest rodents and they have a good safety
record. Rodents are more likely than domestic animals or humans to
consume quantities of treated bait that will cause manifest poisoning.
Very small amounts of the extremely toxic rodenticides—sodium
fluoroacetate, strychnine, crimidine, yellow phosphorus, zinc phos-
phide, thallium sulfate—can cause severe and even fatal poisoning.
Pyriminil and cholecalciferol are highly toxic agents. The coumarins,
indandiones, alpha-naphthyl thiourea, norbormide, and red squill
present considerably less hazard to humans and domestic animals.
116
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COUMARINS AND INDANDIONES
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
COUMARINS AND INDANDIONES
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 vitamin K depend-
ent synthesis of substances essential to blood clotting: prothrombin
(factor II) and factors VII, IX and X. The antiprothrombin effect is best
known, and is the basis for detection and assessment of clinical poison-
ing. Concurrently, the agents increase permeability of capillaries
throughout the body, predisposing the animal to widespread internal
hemorrhage. This generally occurs in the rodent after several days of
bait ingestion, although lethal hemorrhage may follow smaller doses of
the modern more toxic compounds. Two human fatalities and twelve
nonfatal poisonings occurred in Korea in 1953 when a family mistaken-
ly ate warfarin-treated corn meal (0.25 gm %) over several consecutive
days. The chief manifestations were nosebleed, bleeding gums, hematu-
ria, melena, and extensive ecchymoses. 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. In rare instances, anticoagulant rodenticides have
apparently caused ecchymoses and skin necrosis for reasons not related
to excessive dosage.
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.
Lengthened prothrombin time from a toxic dose of coumarins or
indandiones usually reaches a maximum in 36-72 hours. Lengthened
prothrombin time occurs in response to doses much lower than those
necessary to cause hemorrhage.
CONFIRMATION OF POISONING BY COUMARINS AND
INDANDIONES
Coumarin or indandione poisoning results in an increase in pro-
thrombin time, the result of reduced plasma prothrombin concentra-
tion. 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.
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TREATMENT OF POISONING BY COUMARINS AND
INDANDIONES
1. If amounts of bait ingested were assuredly no more than a few
mouthfuls of coumarin- or indandione-treated bait, or a few grains
of bait treated with the more toxic brodifacoum or bromadiolone
compounds, medical treatment is probably unnecessary.
A. If there is uncertainty about the amount of bait ingested or
the general health of the patient, PHYTONADIONE (vitamin
Ki) given orally protects against the anticoagulant effect of
these rodenticides, with essentially no risk to the patient.
Dosage of PHYTONADIONE:
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.
CAUTION: PHYTONADIONE, specifically, is required. Neither
vitamin Ka (menadione, HykinoneR) nor vitamin K* (menadiol) is
an antidote for these anticoagulants.
B. Whatever the dosage, insure that patients (especially children)
will be CAREFULLY OBSERVED for 4-5 days after inges-
tion. The indandiones and some of the more recently intro-
duced coumarins may have other toxic effects.
2. If LARGE AMOUNTS (1.0-1.5 mg/kg of body weight) of antico-
agulant have been ingested within several hours prior to treat-
ment, empty the stomach by giving SYRUP OF IPECAC, followed
by 1-2 glasses of water. Dosage of SYRUP OF IPECAC for adults
and children over 12 years: 30 ml; dosage for children under 12
years: 15 ml. Following emesis, give ACTIVATED CHARCOAL
and SORBITOL (see Chapter 1, TREATMENT, Section 6, p. 8 for
dosage).
3. If treatment has been delayed several hours following ingestion
omit induced emesis, but give activated charcoal and sorbitol
orally.
4. If anticoagulant has been ingested any time in the preceding 15
days, determination of the PROTHROMBIN TIME provides a
basis for judging the severity of poisoning.
A. If the prothrombin time is significantly lengthened, give
AquamephytonR, intramuscularly. Dosage for adults and chil-
dren over 12 years: 5-10 mg; dosage for children under 12
years: 1-5 mg. Decide dose within these ranges according to
the degree of prothrombin tune lengthening and, in children,
the age and weight of the child.
B. Repeat prothrombin tune in 24 hours. If it has not decreased
from the original value, repeat AquamephytonR dosage.
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5.
If victim is BLEEDING as a result of anticoagulant poisoning,
administer AquamephytonR intravenously: up to 10 mg in adults
and children over 12 years, and up to 5 mg in children under 12
years. Initial dosage should be decided chiefly on the basis of the
severity of bleeding. Repeat intravenous AquamephytonR in 24
hours if bleeding continues. Inject at rates not exceeding 5% of
the total dose per minute. INTRAVENOUS INFUSION of the
AquamephytonR DILUTED IN SALINE OR GLUCOSE SOLU-
TION is recommended. Bleeding is usually controlled in 3-6
hours.
CAUTION: Adverse reactions, some fatal, have occurred from
intravenous phytonadione injections, even when recommended
dosage limits and injection rates were observed. For this reason
the INTRAVENOUS route should be used ONLY IN cases of
SEVERE POISONING. Flushing, dizziness, hypotension, dyspnea,
and cyanosis have characterized adverse reactions.
A. Antidotal therapy in cases of SEVERE BLEEDING should be
supplemented with TRANSFUSIONS of FRESH BLOOD or
FRESH FROZEN PLASMA. Use of fresh blood or plasma
represents the most rapidly effective method of stopping hem-
orrhage due to these anticoagulants, but the effect may not
endure. Therefore, the transfusions should be given along
with phytonadione therapy.
B. Determine PROTHROMBIN TIMES and hemoglobin concen-
trations every 6-12 hours to assess effectiveness of antihe-
morrhagic measures.
C. When normal blood coagulation is restored, it may be advisa-
ble to drain large hematomata.
D. Ferrous sulfate therapy may be appropriate in the recupera-
tive period to rebuild lost erythrocyte mass.
INORGANIC RODENTICIDES
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
INORGANIC RODENTICIDES
Yellow phosphorus (also known as white phosphorus) is corrosive to
tissues with which it comes in contact, including skin and the gut
lining. A few minutes to 24 hours following ingestion, the first symp-
toms may be burning pain in the throat, chest, and abdomen reflecting
severe mucosal injury. Vomiting and diarrhea usually ensue. In some
cases, however, lethargy, restlessness, and irritability are the earliest
symptoms, followed by symptoms of gastrointestinal injury. Shock
often progresses to death in 1-2 days. If the patient survives, a relative-
ly symptom-free period of a few hours or days may occur, followed by
indications of severe injury to the liver, myocardium, .and brain. These
effects may be consequences of phosphine formed in and absorbed from
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the gut. Nausea and vomiting recur. Hemorrhage at various sites
reflects depression of clotting factor synthesis in the damaged liver.
Also, thrombocytopenia may contribute. The liver is enlarged and jaun-
dice appears. Shock due to bleeding and toxic myocarditis may be
irreversible. Convulsions, delirium, and coma reflect brain injury, to
which severe hypoglycemia may contribute. Anuria commonly super-
venes due to shock and to the toxic effects of phosphorus products and
accumulating bilirubin on renal tubules. Twenty to 50 percent of cases
of phosphorus ingestion have terminated fatally.
Zinc phosphide is much less irritating to skin and mucous mem-
branes than yellow phosphorus, but great care must be taken to avoid
inhalation of dust, which may induce pulmonary edema. When ingest-
ed, the emetic effect of zinc released in the gut may provide a measure
of protection. The effects of ingestion are probably the consequences of
phosphine and zinc liberated in and absorbed from the gut. Nausea
and vomiting, excitement, chills, chest tightness, dyspnea and cough
may progress to pulmonary edema. If the patient survives, shock from
toxic myocardiopathy, jaundice, and hemorrhage (from liver injury),
delirium, convulsions, and coma (from toxic encephalopathy), tetany
from hypocalcemia, and anuria from renal tubular damage are all life-
threatening manifestations of poisoning.
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. Elimi-
nation half-life from blood in the adult human is about 1.9 days. A
lethal dose for the adult human is probably less than one gram.
The gastrointestinal tract, central nervous system, heart and blood
vessels, kidneys, liver, skin, and hair .are prominently affected by toxic
intakes. One-half to two days following ingestion of a toxic dose, a
hemorrhagic gastroenteritis is often manifest as abdominal pain,
nausea, vomiting, bloody diarrhea, stomatitis, and salivation. Ileus may
appear later on. Headache, lethargy, muscle weakness, paresthesia,
tremor, ptosis, ataxia, myoclonic movements, emotional lability, psy-
chosis, convulsions, delirium, and coma reflect toxic encephalopathy,
which may be delayed 2-5 days. Fever is a bad prognostic indication of
brain damage. Early hypotension is due at least in part to a toxic
myocardiopathy; later, hypertension is probably a result of vasocon-
striction. The urine may show protein and red cells; high levels of
LDH, GOT, ALT, and AST indicate liver injury. Loss of hair (notably,
ALOPECIA) is a fairly consistent feature of thallium poisoning that is
often helpful diagnostically. Death from thallium poisoning may be
caused by respiratory paralysis or cardiovascular collapse. Absorption
of nonlethal doses of thallium has caused protracted painful neuro-
pathies and paresis, optic nerve atrophy, persistent ataxia and chorei-
form movements, as well as dementia.
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CONFIRMATION OF POISONING BY INORGANIC
RODENTICIDES
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. Hy-
perphosphatemia and hypocalcemia occur in some cases, but are not
consistent findings.
Thallium can be measured in the serum, urine and hair. Hair analy-
sis is likely to be useful only in establishing protracted prior absorp-
tion. Serum concentration does not exceed 30 micrograms per liter in
nonexposed persons. Urine concentrations rarely exceed 40 micrograms
per liter in the absence of exceptional exposure. Fifty micrograms per
kilogram of hair is the approximate upper limit of "normal" in persons
not exceptionally exposed. Concentrations roughly 10-100 times these
general population levels have been measured in persons clinically
poisoned by thallium.
TREATMENT OF POISONING BY YELLOW PHOSPHORUS OR
ZINC PHOSPHIDE
1.
2.
Brush or scrape nonadherent phosphorus from the skin. WASH
SKIN BURNS with copious amounts of water. Make sure all
particles of phosphorus have been removed. If burned area is
infected, cover with an antimicrobial creme.
Poisonings by INGESTED yellow phosphorus or zinc phosphide
are extremely difficult to manage. Treatment is basically support-
ive and symptomatic.
CAUTION: Highly toxic phosphine gas may evolve from emesis,
lavage fluid, and feces of victims of these poisons. The patient's
room should be well ventilated. Persons attending the patient
must wear gloves to avoid contact with the phosphorus.
A. INTTJBATE and ASPIRATE the stomach, after taking all
precautions to protect the airway from aspiration of vomitus
(Chapter 1, TREATMENT, Section 6, p. 8). LAVAGE with
several liters of 1:5000 potassium permanganate solution. Ca-
tharsis is probably not indicated, but there may be some
benefit in administering mineral oil. Dosage is 100 ml for
adults and children over 12 years, and 1.5 ml/kg body weight
in children under 12 years. Do not give vegetable oils or fats.
B. Combat shock and acidosis with TRANSFUSIONS of whole
blood and INFUSIONS of glucose and electrolyte solutions.
Monitor fluid balance and central venous pressure to avoid
fluid overload. Monitor blood electrolytes and pH to guide
choice of intravenous solutions. Without administered glucose,
hypoglycemia secondary to liver injury may contribute to
shock.
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C. Administer 100% OXYGEN by mask or nasal tube.
D. Combat pulmonary edema with intermittent or continuous
POSITIVE PRESSURE OXYGEN.
E 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 myo-
cardial impairment. Monitor serum alkaline phosphatase,
LDH, ALT, AST, prothrombin time, and bilirubin to evaluate
liver damage.
F. Include AquamephytonR (vitamin Ki) in intravenous infusions
if prothrombin level declines. Dosage of 10-50 mg per day may
be required. Administer AquamephytonR slowly, intravenous-
ly; stop infusion if flushing, cyanosis, paresthesia, hypoten-
sion, or dyspnea occurs.
G. MORPHINE SULFATE, 8-16 mg subcutaneously every few
hours may be necessary to control pain. Child's dose: 0.1-0.2
mg/kg body weight.
H. CONTROL CONVULSIONS. See Chapter 3, TREATMENT,
Section 4, p. 21.
TREATMENT OF POISONING BY THALLIUM SULFATE
1. If thallium sulfate was swallowed less than a few hours prior to
treatment, and if the patient is fully alert, empty the stomach by
administering SYRUP OF IPECAC, followed by 1-2 glasses of
water. Dosage for adults and children over 12 years: 30 ml; dosage
for children under 12 years: 15 ml. Put in place a cuffed endotra-
cheal tube to protect the airway, then intubate the stomach and
lavage with 1% sodium or potassium iodide, to form insoluble
thallium iodide. Instill a slurry of ACTIVATED CHARCOAL (for
dosage, see Chapter 1, TREATMENT, Section 6, p. 8). Include
sorbitol with the charcoal unless diarrhea is already in progress.
2. If treatment is long delayed, administer the activated charcoal
orally. Include sorbitol unless diarrhea has already commenced.
Repeated administration of charcoal may be of benefit in hasten-
ing elimination of thallium. Give half or more of the original
dosage every 2-4 hours.
3. Give ELECTROLYTE and GLUCOSE solutions by intravenous
infusion to support urinary excretion of thallium by diuresis.
Monitor fluid balance carefully to insure that fluid overload does
not occur. If shock develops, give whole blood, plasma, or plasma
expanders. Pressor amines must be used very carefully in light of
myocardial injury. Monitor EGG for arrhythmias.
4. Inclusion of POTASSIUM CHLORIDE in the infusion 'fluid dis-
places thallium from cells into the extracellular compartment and
thereby accelerates excretion. Care must be taken, however, that
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excessive redistribution of thallium to the brain does not occur.
Concentration of potassium in the infusion fluid should probably
not exceed 10 milliequivalents per liter. Monitor clinical status
carefully, and stop KC1 administration if encephalopathy worsens.
5. CONTROL CONVULSIONS and myoclonic jerking. For dosages
of anticonvulsants, see Chapter 3, TREATMENT, Section 4, p. 21.
Benzodiazepines (diazepam or lorazepam) are the preferred agents
in thallium poisoning. In at least one case, neurologic status
deteriorated when barbiturates were administered.
6. COMBINED HEMODIALYSIS AND HEMOPERFUSION has
proven moderately effective in reducing the body burden of thalli-
um in victims of severe poisoning. In one case, peritoneal dialysis
was not effective.
7. Several methods for chelating and/or accelerating disposition of
thallium have been tested and found either relatively ineffective
or hazardous. Chelating agents are not recommended in thallium
poisoning.
8. Potassium ferric ferrocyanide (Prussian Blue) orally enhances
fecal excretion of thallium by exchange of potassium for thallium
in the gut. However, it is not approved for human use, and
suitably pure material is not generally available for medicinal
purposes.
CONVULSANTS
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
CONVULSANT RODENTICIDES
Sodium fluoroacetate is 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 are combined in the
liver to form a molecule of fluorocitrate, which poisons critical en-
zymes of the tricarboxylic acid cycle, thus impairing cellular respira-
tion. The heart and the brain are the organs most prominently affect-
ed. The effect on the heart is to cause arrhythmias, progressing to
ventricular fibrillation, which is the usual cause of death. Neurotoxi-
city is expressed as violent tonic-clonic convulsions, spasms and rigor,
sometimes not occurring for hours after ingestion.
Strychnine is a natural toxin (nux vomica) which causes violent
epileptiform convulsions by direct excitatory action on the cells of the
central nervous system, chiefly the spinal cord. Death is caused by
convulsive interference with pulmonary function, by depression of res-
piratory center activity, or both. Strychnine is detoxified in the liver.
Residence half-life is about 10 hours in humans. Onset of symptoms is
usually within 15-20 minutes of ingestion. Lethal dose in humans is
5-8 mg/kg body weight.
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Crimidine is a synthetic chlorinated pyrimidine compound which, in
adequate dosage, causes violent convulsions similar to those produced
by strychnine.
CONFIRMATION OF POISONING BY CONVULSANT
RODENTICIDES
There are no generally available tests to confirm poisoning by the
convulsant rodenticides.
TREATMENT OF POISONING BY SODIUM FLUOROACETATE
Sodium fluoroacetate poisonings have occurred almost entirely as a
result of accidental and suicidal ingestions. If the poison was ingested
shortly before treatment and convulsions have not yet occurred, the
first step in treatment is to remove the toxicant from the gut. If the
victim is already convulsing, however, it is necessary first to control
the seizures before gastric lavage and catharsis are undertaken.
1. CONTROL CONVULSIONS by giving OXYGEN, and administer-
ing ANTICONVULSANT medications (see Chapter 3, TREAT-
MENT, Section 4, page 21). Seizure activity from fluoroacetate
may be so severe that doses necessary for seizure control may
paralyze respiration. For this reason, it is best to INTUBATE
THE TRACHEA as early as possible in the course of seizure
control, and support pulmonary ventilation mechanically. This
has the added advantage of protecting the airway from aspiration
of regurgitated gastric contents.
2. Empty the stomach by INTUBATION, ASPIRATION, and
LAVAGE with isotonic saline or tap water (Chapter 1, TREAT-
MENT, Section 6, page 8). There is probably very little adsorption
of sodium fluoroacetate on activated charcoal. Instill SORBITOL
as a cathartic before withdrawing the stomach tube (see reference
above for dosage).
3. Administer INTRAVENOUS FLUIDS cautiously to support excre-
tion of absorbed fluoroacetate. It is especially important to avoid
fluid overload in the presence of a weak and irritable myocardi-
um.
4. Monitor ELECTROCARDIOGRAM for arrhythmias and, if de-
tected, treat with an appropriate antiarrhythmic drug. Consult
package inserts for dosages and recommended methods for admin-
istration. Facilities for electroshock CARDIOVERSION should be
at hand. Some victims of fluoroacetate poisoning have been res-
cued after repeated cardioversions.
5. CALCIUM GLUCONATE (10% solution) given slowly intrave-
nously should be given to relieve carpopedal spasm. Care must be
taken to avoid extravasation.
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Dosage of CALCIUM GLUCONATE:
Adults and children over 12 years: 10 ml of 10% solution,
given slowly, intravenously. Repeat if necessary.
Children under 12 years: 0.05 gm (one-half ml of 10% solu-
tion) per kg body weight, preferably included in intravenous
infusion fluid. Repeat dosage as needed.
TREATMENT OF POISONING BY STRYCHNINE OR CRIMIDINE
Strychnine and crimidine cause violent convulsions shortly following
ingestion of toxic doses. Both poisons are probably well adsorbed on
charcoal. If the patient is seen fully conscious and not convulsing a few
moments after the ingestion, great benefit may derive from the imme-
diate ingestion of ACTIVATED CHARCOAL (see Chapter 1, TREAT-
MENT, Section 6, page 8 for dosage). 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.
1. CONTROL CONVULSIONS. See Chapter 3, TREATMENT, Sec-
tion 4, page 21.
2. LIMIT TOXICANT ABSORPTION from the gut. Induced emesis
is hazardous because of the risk of aspiration of vomitus when
seizures begin. As soon as possible, protect the airway, preferably
with a cuffed ENDOTRACHEAL TUBE, then remove stomach
contents by ASPIRATION and LAVAGE with a slurry of activat-
ed charcoal (see Chapter 1, TREATMENT, Section 6, page 8).
Repeated doses of activated charcoal may be beneficial, giving
half or more the initial dose every 2-4 hours.
3. Administer intravenous fluids to support excretion of absorbed
toxicants. Mannitol diuresis may be considered, and inclusion of
sodium bicarbonate in the infusion fluid counteracts metabolic
acidosis generated by convulsions. Effectiveness of hemodialysis
and hemoperfusion has not been tested.
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MISCELLANEOUS RODENTICIDES
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY:
ANTU, NORBORMIDE, RED SQUILL, PYRIMINYL, AND
CHOLECALCIFEROL
Alpha-naphthyl thiourea (ANTU) appears to have unique toxic ef-
fects on Norway rats. Although dogs are somewhat susceptible, other
species, including man, are resistant to the toxicity of ANTU. Poisoned
Norway rats die of pulmonary edema and pleura! effusion. Several
humans poisoned by deliberate ingestion of ANTU (and chloralose)
developed severe short-lived tracheobronchial hypersecretion, but ap-
parently not pulmonary edema. Although some persons required me-
chanically assisted pulmonary ventilation, the reaction, in most cases,
resolved in a few hours.
Norbormide is a single-dose synthetic organic compound uniquely
toxic to Norway and roof rats, in which it causes an intense general-
ized vasoconstriction, leading to death from tissue anoxia. The most
severe effects observed in human volunteers ingesting 20-300 mg orally
were a brief and moderate lowering of body temperature and a mild
lowering of systolic blood pressure. These effects, which were observed
in the absence of symptoms, were maximal at one hour and were not
apparent two hours after ingestion.
Red squill is an ancient rodenticide, consisting of the inner portions
of a small cabbage plant grown in eastern Mediterranean countries.
The toxic properties are probably due to cardiac glycosides. For several
reasons, mammals other than rodents are unlikely to be poisoned: 1)
red squill is intensely nauseant, so that animals which vomit (rodents
do not) are unlikely to retain the poison; 2) the glycoside is not effi-
ciently absorbed from the gut; 3) absorbed glycoside is rapidly excreted.
Injection of the glycosides leads to effects typical of digitalis: alter-
ations in cardiac impulse conduction and arrhythmias.
Pyriminil (Vacor) is a substituted urea compound that is toxic to
mammals, including humans, by effects on multiple organs and tissues.
It causes severe damage to central and peripheral nervous systems,
including both somatic and autonomic components of the latter. It
destroys beta cells of the pancreas, leading to insulin-deficient diabetes
mellitus. Cardiac arrhythmias probably reflect injury to the impulse
conduction system. Nicotinamide antagonism is a likely biochemical
basis for many of the toxic effects.
Most severe poisonings have resulted from suicidal ingestions. Early
manifestations of poisoning are abdominal pain, nausea, vomiting, leth-
argy, confusion, visual disturbances, painful paresthesia, urinary reten-
tion (or frequency), and orthostatic hypotension (fainting when sitting
up or standing from the reclining position). Later effects are paresis of
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the limbs, areflexia, ataxia, persistent anorexia, and bowel dystonias.
Early hypoglycemia progresses to hyperglycemia, often accompanied by
ketoacidosis. Severe and prolonged orthostatic hypotension is charac-
teristic. Death may result from cardiac arrhythmias, diabetic ketoaci-
dosis, inanition, or aspiration pneumonia.
Cholecalciferol is the activated form of vitamin D (vitamin Ds). Its
toxic effect is probably a combination of actions on liver, kidney, and
possibly the myocardium, the last two toxicities being the result of
hypercalcemia. Early symptoms and signs of vitamin D-induced hyper-
calcemia in humans are fatigue, weakness, headache, and nausea. Po-
lyuria, polydipsia, proteinuria, and azotemia result from acute renal
tubular injury by hypercalcemia. This is commonly the cause of death.
Prolonged hypercalcemia results ultimately in nephrolithiasis and
nephrocalcinosis. Azotemia occurs as renal tubular damage progresses.
CONFIRMATION OF POISONING BY MISCELLANEOUS
RODENTICIDES
Cholecalciferol intoxication is indicated by an elevated concentra-
tion of calcium (chiefly the unbound fraction) in the serum.
There are no generally available tests for the other rodenticides or
their biotransformation products.
TREATMENT OF POISONING BY ALPHA NAPHTHYL
THIOUREA (ANTU)
Alpha naphthyl thiourea is unlikely to cause severe poisoning unless
large amounts have been ingested. If a small amount has been ingest-
ed, or if treatment has been delayed, administer ACTIVATED CHAR-
COAL and SORBITOL orally (see Chapter 1, TREATMENT, Section 6,
p. 8 for dosage).
If a large quantity was ingested, take steps to protect the airway,
then empty the stomach by INTUBATION, ASPIRATION, and
LAVAGE. Instill ACTIVATED CHARCOAL and SORBITOL before
withdrawing the tube (see Chapter 1, TREATMENT, Section 6, p. 8).
If dyspnea develops, support pulmonary ventilation mechanically
using oxygen. Although not tested for efficacy or safety, careful intra-
venous injection of aminophylline might be used to relieve broncho-
spasm and bronchorrhea. See package insert for dosage.
TREATMENT OF POISONING BY NORBORMIDE
Norbormide is unlikely to cause human poisoning unless extraordi-
nary amounts have been ingested. In this event, give activated char-
coal and sorbitol orally (for dosage, see Chapter 1, TREATMENT,
Section 6, p. 8). Monitor body temperature and blood pressure. Use
warm blankets to correct hypothermia. A recumbent position "and cau-
tious doses of a pressor drug may be used to correct hypotension, if this
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develops. To date, no human poisonings by norbormide have occurred,
and therefore, therapeutic procedures have not been tested.
TREATMENT OF POISONING BY RED SQUILL
Red squill is unlikely to cause poisoning unless ingested at substan-
tial dosage. The problem is usually self-correcting due to its intense
emetic effect. If, for some reason, the squill is retained, Syrup of
Ipecac, followed by 1-2 glasses of water, should be administered to
initiate vomiting. Dosage for adults and children qyer 12 years: 30 ml;
dosage for children under 12 years: 15 ml. When vomiting stops, ad-
minister activated charcoal and sorbitol (see Chapter 1, TREATMENT,
Section 6, p. 8 for dosages). Monitor cardiac status electrocardiographi-
cally.
TREATMENT OF POISONING BY PYRIMINYL
Pyriminyl poisonings have resulted from accidental and suicidal in-
gestions. Severe effects have sometimes been caused by very small
doses. Immediate measures to limit absorption are essential.
1. If pyriminyl was ingested, and if the patient is fully conscious,
administer SYRUP OF IPECAC followed by several glasses of
water to induce emesis. Dosage for adults and children over 12
years: 30 ml; dosage for children under 12 years: 15 ml.
If there is reason to believe some pyriminyl remains in the stom-
ach, protect the airway with a cuffed endotracheal tube, then
INTUBATE, ASPIRATE, and LAVAGE the stomach with a
slurry of ACTIVATED CHARCOAL (see Chapter 1, TREATMENT,
Section 6, p. 8 for dosage). Leave activated charcoal and sorbitol in
the stomach before withdrawing the lavage tube. Repeated doses
of charcoal may well be beneficial, giving half or more of the
initial dose every 2-4 hours.
2. Monitor blood and urine glucose concentrations, serum alkaline
phosphatase, amylase, LDH, AST, and ALT activities, urine
ketone concentrations, blood electrolytes, and BUN. Examine the
electrocardiogram for arrhythmias.
3. Infuse ELECTROLYTE SOLUTIONS intravenously to accelerate
toxicant excretion and correct errors in specifier electrolyte con-
centrations. If ketoacidosis appears, include sodium bicarbonate or
Ringer's-lactate to control acidosis.
4. If DIABETIC KETOACIDOSIS appears (ketonuria, metabolic aci-
dosis, hyperglycemia), administer enough regular insulin to con-
trol the acidosis and hyperglycemia, as in naturally occurring
diabetic ketosis. The diabetes resulting from pyriminyl tends to be
brittle and correspondingly difficult to control.
5. The sequelae of pyriminyl poisoning are essentially irreversible.
The diabetes may be controlled with 'insulin, or, in mild cases,
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sulfonylurea drugs. Orthostatic hypotension may be alleviated by
support stockings, sympathomimetic drugs, or dihydroergotamine.
TREATMENT OF POISONING BY 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 circum-
stances. Treatment is directed at limiting gastrointestinal absorption,
accelerating excretion, and counteracting the hypercalcemic effect.
1. If Cholecalciferol has been ingested within a few hours prior to
treatment, and if the patient is fully alert, induce emesis by
SYRUP OF IPECAC, followed by 1-2 glasses of water. Dosage for
adults and children over 12 years: 30 ml; dosage for children
under 12 years: 15 ml. When vomiting stops, give ACTIVATED
'CHARCOAL and SORBITOL (for dosage, see Chapter 1, TREAT-
MENT, Section 6, p. 8). 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, 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 warn-
ings.
4. PREDNISONE and similar glucocorticoids reduce elevated blood
calcium levels in certain diseases. Although they have not been
tested in Cholecalciferol overdosage, it is possible that they would
be beneficial. Dosage is approximately 1 mg per kilogram per day,
to a maximum of 20 mg per day.
5. CALCITONIN (salmon calcitonin, CalcimarR) is a logical antidote
for Cholecalciferol actions, but has not been tested hi human
poisoning. 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. The dose may be
doubled if calcium lowering effect is not sufficient. Calcium gluco-
nate (10%) for intravenous injection should be immediately avail-
able if indications of hypocalcemia (carpopedal spasm, cardiac
arrhythmias) appear. Consult package insert for additional direc-
tions and warnings.
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6. If total serum calcium is markedly elevated (more than about 8
milliequivalents per liter) the intravenous infusion of disodium
edetate (EDTA) may be considered. Although this agent is very
effective in reducing the level of physiologically active serum
calcium by chelation, only moderate overdosage may lead to hypo-
calcemia, tetany, ventricular arrhythmias, respiratory arrest, and
death. A daily dose of 50 mg/kg body weight, to a maximum of 3
gin, may be infused in 500 ml of 5% glucose or 0.9% saline over at
least 4-6 hours, while the EGG and serum calcium are being
monitored. Calcium gluconate (10%) should be immediately at
hand to reverse hypocalcemia if arrhythmias or carpopedal spasm
appear. Disodium edetate is CONTRAINDICATED if there are
any signs of renal insufficiency, congestive heart failure, or hypo-
kalemia (less than 3.5 milliequivalents per liter). Consult package
insert for additional directions and warnings.
130
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CHAPTER 14
FUMIGANTS
CHEMICAL STRUCTURES
HALOCARBONS
Cl * Br Br
1 11
CI-C-CI
1
Cl
Carbon
Tetrachloride
Cl
CI-C-H
1
Cl
Chloroform
Cl
1
Cl - C - NO2
1
Cl
Chloropicrin
H
1
H-C-Br
1
H
Methyl Bromide
r
Cl - C - Cl
I
H
H-C— C-H
1 |
H H
Ethylene
Dibromide
Cl H Cl
1 1 1
H -C — C » C
1 1
H H
1,3-Dichloro-
propane
Br Br Cl
I I I
H -C-C-C - H
I I I
H H H
Dibromo-
chloropropane
Cl Cl
I I
H-C-C-H
i i
i i
H H
Ethylene
Dichloride
OXIDES AND
ALDEHYDES
o
CH2 - CH2
Ethylene Oxide
X^X
CH2 - CH - CH3
Propylene Oxide
H
C= 0
Formaldehyde
H
[-c-o]
Li Jn
1 1 1
H
Paraformaldehyde
H H H
1 1 1
C = C-C = 0
1
H
Acrolein
SULFUR AND
PHOSPHORUS
COMPOUNDS
0 = S = O
Sulfur Dioxide
S = C = S
Carbon Disulfide
F^
F/S = °
Sulfuryl Fluoride
P
1
H
Phosphine (from
Al= P+ H20)
CYANIDES
H - C = N
Hydrogen Cyanide
H H
I i
C = C-C s N
\
H
Acrylonitrile
Methylene Chloride
Hydrocarbon-
Paradichlorobenzene
Naphthalene
131
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COMMERCIAL PRODUCTS
Hydrocarbon: naphthalene (naphthene).
Halocarbons: methylene chloride, methyl bromide (bromomethane,
Brom-O-Gas, Brom-O-Sol, Meth-O-Gas,.'Terr-O-Gas, Brom-O-Gaz, Gel-
fume, Kayafume, MeBr), chloroform (trichloromethane), carbon tetra-
chloride, chloropicrin (nitrochloroform, Chlor-O-Pic, Aquinite, Dojyopi-
crin, Dolochlor, Larvacide, Pic-Clor, Tri-Clor), ethylene dichloride (dich-
loroethane, EDC), ethylene dibromide (dibromoethane, Bromofume,
Cehnide, E-D-Bee, EDB, Kopfume, Nephis), dichloropropene (Telone II
Soil Fumigant, D-D92), dichloropropene plus dichloropropane (D-D), di-
bromochloropropane (Nemafume, Nemanax, Nemaset, DBCP, Nemato-
cide), paradichlorobenzene (PDB, Paracide).
Oxides and Aldehydes: ethylene oxide (epoxyethane, ETO, oxirane),
propylene oxide, formaldehyde (formalin is a 40% aqueous solution),
paraformaldehyde, acrolein (propenal, acrylaldehyde, Aqualin).
Sulfur Compounds: sulfur dioxide, sulfuryl fluoride (Vikane), carbon
disulfide.
Phosphorus Compounds: phosphine (liberated from aluminum phos-
phide: phostoxin, A1P, Fumitoxin).
Nitrogen Compounds: hydrogen cyanide (hydrocyanic acid, prussic
acid, Cyclon), acrylonitrile (Acritet, Carbacryl, Acrylofume—all mix-
tures with carbon tetrachloride).
Packaging and formulation of fumigants is complex. Those which are
gases at room temperature (methyl bromide, ethylene oxide, sulfur
dioxide, hydrogen cyanide, sulfuryl fluoride) are provided in com-
pressed gas cylinders. Liquids are marketed in cans or drums. Solids
which sublime, such as naphthalene and paradichlorobenzene, must be
packaged so as to prevent significant contact with air before they are
used.
Mixtures of fumigants have several advantages. Carbon tetrachloride
reduces the explosiveness of carbon disulfide and acrylonitrile. Chloro-
picrin, having a strong odor and irritant effect, is often added as a
"warning agent" to other liquid fumigants.
Liquid halocarbons and carbon disulfide evaporate into the air while
naphthalene and paradichlorobenzene sublime. Paraformaldehyde
slowly depolymerizes to formaldehyde. Aluminum phosphide slowly
reacts with water vapor in the air to liberate phosphine, an extremely
toxic gas.
Fumigants have remarkable capacities for diffusion (a property es-
sential to their function). Some readily penetrate rubber and neoprene
personal protective gear, as well as human skin. They are rapidly
absorbed across the pulmonary membrane, gut, and skin. Special ad-
sorbents are required in respirator canisters to protect exposed work-
ers from airborne fumigant gases. Even these may not provide com-
plete protection when air concentrations of fumigants are high.
132
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TOXICOLOGY AND MANIFESTATIONS OF POISONING
Naphthalene is a solid white hydrocarbon long used in ball, flake, or
cake form as a moth repellant. It sublimes slowly. The vapor has a
sharp, pungent odor that is irritating to the eyes and upper respiratory
tract. Inhalation of high concentrations causes headache, dizziness,
nausea, and vomiting. Intensive prolonged inhalation exposure, or in-
gestion or dermal exposure (from contact with heavily treated fabric)
may cause hemolysis, particularly in persons afflicted with glucose-6-
phosphate dehydrogenase deficiency. It is actually the alpha-naphthol
metabolite that causes the hemolysis. 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). Some individuals exhibit
dermal sensitivity to naphthalene.
Methylene chloride is one of the less toxic halocarbons. It is ab-
sorbed by inhalation and to a limited extent across the skin. Exposure
to high concentrations may cause central nervous system depression,
manifest as fatigue, weakness, and drowsiness. Some absorbed methyl-
ene chloride is degraded to carbon monoxide in humans, yielding in-
creased blood concentrations of carboxyhemoglobin. However, concen-
trations are rarely high enough to cause symptoms of carbon monoxide
poisoning. Ingestion has caused death from gastrointestinal hemor-
rhage, severe liver damage, coma, shock, metabolic acidosis, and renal
injury. In laboratory animals, extraordinary dosage has caused irrita-
bility, tremor, and narcosis, leading to death.
Methyl bromide is colorless and nearly odorless, but is severely
irritating to the lower respiratory tract, sometimes inducing pulmo-
nary edema, hemorrhage, or a confluent pneumonia. The onset of
respiratory distress may be delayed 4-12 hours after exposure. It is a
central nervous system depressant, but may also cause convulsions.
Early symptoms of acute poisoning include headache, dizziness, nausea,
vomiting, tremor, and ataxia. Repeated prolonged exposures in some
cases have led to a long-lasting syndrome of ataxia, incoordination,
muscle weakness and areflexia. One case of recurrent myoclonic sei-
zures has been reported which required treatment for five years follow-
ing methyl bromide exposure. If liquid methyl bromide contacts the
skin, severe burning, itching, and blister formation occurs. Skin necro-
sis may be deep and extensive.
Chloroform has an agreeable sweet odor and is only slightly irritat-
ing to the respiratory tract. It is a powerful central nervous system
depressant (in fact, an anesthetic). Inhalation of toxic concentrations in
air leads to dizziness, loss of sensation and motor power, and then
unconsciousness. Inhalation of large amounts causes cardiac arrhyth-
mias, sometimes progressing to ventricular fibrillation. Large absorbed
doses damage the functional cells of the liver and kidney. Ingestion is
133
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more likely to cause serious liver and kidney injury than is inhalation
of the vapor.
Carbon tetrachloride is less toxic than chloroform as a central nerv-
ous system depressant, but is much more severely hepatotoxic, particu-
larly following ingestion. Liver cell damage is apparently due to a free
radical generated in the process of initial dechlorination. Kidney injury
also occurs; sometimes this is exaggerated by jaundice. Cardiac ar-
rhythmias, progressing to fibrillation, may follow inhalation of high
concentrations of carbon tetrachloride or ingestion of the liquid.
Chloropicrin is severely irritating to the upper respiratory tract,
eyes, and skin. Inhalation of an irritant concentration sometimes leads
to vomiting. Ingestion could be expected to cause a corrosive gastroen-
teritis.
Ethylene dichloride (correctly, dichloroethane) is moderately irritat-
ing to the eyes and respiratory tract. It depresses the central nervous
system, induces cardiac arrhythmias, and damages the liver and
kidney, in much the same way as carbon tetrachloride. Symptoms and
signs of poisoning include headache, nausea, vomiting, dizziness, diar-
rhea, hypotension, cyanosis, and unconsciousness. In addition to necro-
sis of liver and kidney cells, the adrenal cortex may be destroyed,
especially after poisoning by ingestion.
Ethylene dibromide (correctly, dibromoethane) is a severe irritant to
skin, eyes, and respiratory tract. The liquid causes blistering and ero-
sion of skin, and is corrosive to the eyes. Once absorbed, it may cause
pulmonary edema and central nervous system depression. Long-term
exposure may have some damaging effect on testicular tissue. Persons
poisoned by ingestion have suffered chemical gastroenteritis, liver ne-
crosis, and renal tubular damage. Death is usually due to respiratory
or circulatory failure. A powerful disagreeable odor is advantageous in
warning occupationally exposed workers of the presence of this gas.
Dibromochloropropane is irritating to skin, eyes, and the respirato-
ry 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 permanent sterility of workers in a manufacturing plant, by
causing diffuse necrosis of seminiferous tubule cells. Because it is much
less odiferous than ethylene dibromide, exposure of workers to toxic
concentrations of DBCP is more likely.
Dichloropropene and dichloropropane are strongly irritating to the
skin, eyes, and respiratory tract. Bronchospasm may result from inha-
lation of high concentrations. Liver, kidney, and cardiac toxicity is
probably similar to that produced by carbon tetrachloride.
Paradichlorobenzene is solid at room temperature, and is now
widely used as a moth repellant, 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
134
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of large amounts. Although accidental ingestions, especially by chil-
dren, have been fairly common, symptomatic human poisonings have
been rare. Other stereoisomers of dichlorobenzene are more toxic than
the para-isomer.
Ethylene oxide and propylene oxide are irritants to all tissues they
contact. Aqueous solutions of ethylene oxide cause blistering and ero-
sion of the affected skin. The area of skin may thereafter be sensitized
to the fumigant. Inhalation of high concentrations is likely to cause
pulmonary edema and cardiac arrhythmias. Headache, nausea, vomit-
ing, weakness, and a persistent cough are common early manifesta-
tions of acute poisoning. Coughing of bloody, frothy sputum is charac-
teristic 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 sensitiz-
er, causing asthma and dermatitis. High air concentrations may cause
laryngeal edema, asthma, or tracheobronchitis, but apparently not pul-
monary edema. Aqueous solutions in contact with the skin cause hard-
ening and roughness, due to superficial coagulation of the keratin
layer. Ingested formaldehyde attacks the lining membrane of the stom-
ach and intestine, causing necrosis and ulceration. Absorbed formalde-
hyde is rapidly converted to formic acid. The latter is partly responsi-
ble for the metabolic acidosis that is characteristic of formaldehyde
poisoning. Circulatory collapse and renal failure may follow the devas-
tating effects of ingested formaldehyde on the gut, leading to death.
Paraformaldehyde is a polymer which slowly releases formaldehyde
into the air. Toxicity is somewhat less than that of formaldehyde,
because of the slow evolution of gas.
Acrolein (acrylaldehyde) is an extremely irritating gas, used as a
fumigant, aquatic herbicide, and "tear gas." The vapor causes lacrima-
tion and upper respiratory tract irritation,' which may lead to larynge-
al edema, bronchospasm, and delayed pulmonary edema. The conse-
quences of ingestion are essentially the same as those which follow
ingestion of formaldehyde (see above). Contact with the skin may cause
blistering.
Sulfur dioxide is a highly irritant gas, so disagreeable that persons
inhaling it are usually warned to seek uncontaminated air as soon as
possible. However, laryngospasm and pulmonary edema have occurred
occasionally, leading to severe respiratory distress and death. It is
sometimes a cause of asthma in occupationally exposed persons, even
when air concentrations are low.
Sulfuryl fluoride has been used extensively for structural fumiga-
tion. Although use experience has generally been good, some fatalities
have occurred when fumigated buildings have been prematurely re-
entered by unprotected individuals. Manifestations of poisoning have
been nose, eye, and throat irritation, weakness, nausea, vomiting, dysp-
nea, cough, restlessness, muscle twitching, and seizures. Renal injury
may induce proteinuria and azotemia.
135
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Carbon disulfide vapor is only moderately irritating to upper respi-
ratory membranes, but it has an offensive "rotten cabbage" odor.
Acute toxicity is due chiefly to effects on the central nervous system.
Inhalation of high concentrations for short periods has caused head-
ache, dizziness, nausea, hallucinations, delirium, progressive paralysis
and death from respiratory failure. More prolonged exposure to lesser
amounts has lead to blindness, deafness, paresthesia, painful neuropa-
thy, and paralysis. Long-term occupational exposures have been shown
to accelerate atherosclerosis, leading to ischemic encephalopathy, myo-
cardiopathy, and gastrointestinal dysfunction. Toxic damage to the
liver and kidneys may result in severe functional deficits of these
organs.
Phosphine gas is only slightly irritating to the respiratory tract, but
is at least as toxic systemically as hydrogen cyanide. It is slowly
released into treated produce or storage spaces by hydrolysis of solid
aluminum phosphide (phostoxin). Mechanisms of toxicity are not well
understood. The principal manifestations of poisoning are fatigue,
nausea, headache, dizziness, thirst, cough, shortness of breath, pares-
thesia, and jaundice. Pulmonary edema is a common cause of death.
Odor is said to resemble that of decaying fish.
Hydrogen cyanide gas causes poisoning by inactivating cytochrome
oxidase, the final enzyme essential to mammalian cellular respiration.
The cells of the brain appear to be the most vulnerable to cyanide
action. Unconsciousness and death may occur immediately following
inhalation of a high cyanide concentration, respiratory paralysis being
the principal mechanism. Lesser exposures cause a constriction and
numbness in the throat, stiffness of the jaw, salivation, nausea, vomit-
ing, dizziness, and apprehension. Worsening of the poisoning is mani-
fest as violent tonic or clonic convulsions. Trismus and opisthotonos
occur. Paralysis follows seizure activity. Incontinence is characteristic.
The skin remains pink. Fixed, dilated pupils, bradycardia, and irregu-
lar gasping respiration (or apnea) are typical of profound poisoning.
The heart often continues to beat after breathing has stopped. 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. Similar color of the
retinal arteries and veins may be a useful sign of cyanide poisoning; it
is due to failure of reduction of hemoglobin as blood perfuses poisoned
tissues.
Acrylonitrile is biotransformed in the body to hydrogen cyanide.
Toxicity and mechanisms of poisoning are essentially the same as have
been described for cyanide, except that acrylonitrile is irritating to the
eyes and to the upper respiratory tract.
136
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CONFIRMATION OF POISONINGS BY FUMIGANTS
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 chromatography.
Many halocarbons can be measured in blood by gas chromatographic
methods, some using head space techniques. Some can be measured in
the expired air as well.
Methylene chloride is converted to carbon" monoxide in the body,
generating carboxyhemoglobinemia, which can be measured by clinical
laboratories.
Paradichlorobenzene is metabolized mainly to 2,5-dichlorophenol,
which is conjugated and excreted in the urine. This product can be
measured chromatographically.
Methyl bromide yields inorganic bromide in the body; the anion is
slowly excreted in the urine (half-life in the body is about 12 days). The
serum from persons having no exceptional exposure to bromide usually
contains less than 1 mg bromide ion per 100 ml. The possible contribu-
tions of medicinal bromides to elevated blood content and urinary
excretion must be considered, but if methyl bromide is the exclusive
source, serum bromide exceeding 5 mg per 100 ml probably means
some absorption, and 15 mg per 100 ml is consistent with symptoms of
acute poisoning. Inorganic bromide is considerably less toxic than
methyl bromide; serum concentrations in excess of 150 mg per 100 ml
occur commonly in persons taking inorganic bromide medications.
In some European countries, blood bromide concentrations are moni-
tored routinely in workers exposed to methyl bromide. Blood levels
over 3 mg per 100 ml are considered a warning that personal protec-
tive measures must be improved. A bromide concentration over 5 mg
per 100 ml requires that the worker be removed from the fumigant-
contaminated environment until blood concentrations decline to less
than 3 mg per 100 ml.
Carbon disulfide can be measured in urine by gas chromatography,
but the test is not generally available. A qualitative test for carbon
disulfide metabolites in urine (based on their reducing properties) is
used for monitoring occupational exposure (Djuric D., N. Serducki, and
I. Burkes. lodme-azide test on urine of persons exposed to carbon
disulfide. Brit. J. Indus. Med., 22:321-3, 1965).
Cyanide ion from cyanide itself or acrylonitrile can be measured in
whole blood and urine by an ion-specific electrode or by colorimetry.
The upper limit in whole blood among nonexposed nonsmokers is
about 0.02 mg per liter; it is 0.04 mg per liter in smokers. Symptoms
may appear at levels above 0.10 mg per liter. 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 usually present in plasma at levels
less than 4 mg per liter in non-smokers, but up to 12 mg per liter in
137
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smokers. Urine thiocyanate is usually less than 4 mg per liter in non-
smokers, but may be as high as 17 mg per liter in smokers.
A serum fluoride concentration of 0.5 mg per liter was measured in
one fatality from sulfuryl fluoride fumigation. Serum fluoride in per-
sons not exceptionally exposed rarely exceeds 0.1 mg per liter.
There are no practical tests for absorbed alkyl oxides, aldehydes, or
phosphine that would be helpful in diagnosis of poisoning.
Large industrial concerns sometimes monitor human absorption of
halocarbons by analysis of expired air. Similar technology is available
in some departments of anesthesiology. These analyses are rarely
needed to identify the offending toxicant, because this is known from
the exposure history. In managing difficult cases of poisoning, however,
it may be helpful to monitor breath concentrations of toxic gas to
evaluate disposition of the fumigant. Testing of the urine for protein
and red cells is needed to detect renal injury. Free hemoglobin in urine
most likely reflects hemolysis, as from naphthalene. Elevations of alka-
line phosphatase, lactate dehydrogenase (LDH), serum GOT, 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 hi evaluating peripheral
nerve injury. Sperm counts may be appropriate for workers exposed to
dibromochloropropane and ethylene dibromide.
Some occupational health agencies now urge periodic neurologic and
neuropsychologic testing of workers heavily exposed to fumigants and
"solvents to detect injury to the nervous system as early as possible.
This would be particularly desirable in the case of exposures to such
agents as methyl bromide and carbon disulfide which have well docu-
mented chronic neurotoxic effects.
TREATMENT OF POISONINGS BY FUMIGANTS
1. 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 BLIND-
NESS. Specialized medical treatment should be obtained promptly
following removal of toxicant by copious flushing with clean
water. 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.
2. REMOVE victims of fumigant inhalation to FRESH AIR immedi-
ately. Even though initial symptoms and signs are mild, keep the
victim quiet, hi a semi-reclining position. Minimum physical activ-
ity limits the likelihood of pulmonary edema.
138
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3. 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. If PULMONARY EDEMA is evident, there are several measures
available to sustain life. Medical judgment must be relied upon,
however, in the management of each case. The following proce-
dures are generally recommended:
A. Put the victim in a SITTING position with a backrest.
B. Use intermittent and/or continuous positive pressure
OXYGEN to relieve hypoxemia. (Do not give oxygen at great-
er concentrations or longer periods than necessary, because it
may exaggerate the fumigant injury to lung tissue. Monitor
arterial p02.)
C. Slowly administer FUROSEMIDE, 40 mg, or SODIUM ETH-
ACRYNATE, 50 mg, intravenously, to reduce venous load by
inducing diuresis. Consult package insert for additional direc-
tions and warnings.
D. Administer MORPHINE in small doses (5-10 mg), slowly, in-
travenously, to allay anxiety and promote deeper respiratory
excursions.
E. Administer AMINOPHYLLINE (0.25-0.50 gin) slowly, intrave-
nously. Consult package insert.
F. Digitalization may be considered, but there is a serious risk of
arrhythmias in an anoxic and toxic myocardium.
G. TRACHEOSTOMY may be necessary in some cases to facili-
tate aspiration of large amounts of pulmonary edema fluid.
H. Epinephrine, atropine, and expectorants are generally not
helpful, and may complicate treatment.
I. Watch for RECURRENT PULMONARY EDEMA, even up to
2 weeks after the initial episode. Limit victim's physical activ-
ity for at least 4 weeks. Severe physical weakness usually
indicates persistent pulmonary injury. Serial pulmonary func-
tion testing may be useful in assessing recovery.
5. 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 pulmo-
nary edema. Central venous pressure should be monitored con-
tinuously; Vasopressor amines must be given with great caution,
because of the irritability of the myocardium.
6. Control CONVULSIONS. Seizures are most likely to occur in
poisonings by methyl bromide, hydrogen cyanide, acrylonitrile,
phosphine, and carbon disulfide.
A. Establish pulmonary gas exchange at the best possible level
by administering OXYGEN by continuous positive pressure
ventilation.
139
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B. In poisoning by CYANIDE and ACRYLONITRILE, proceed
directly with ANTIDOTAL therapy (see below paragraph
HE).
C. Control convulsions caused by other agents with careful IV
injection of DIAZEPAM, 5-10 mg in adults and children over
12 years, 0.25-0.40 mg/kg in children under 12 years. (See
Chapter 3, TREATMENT, Section 4, p. 21.) Repeat dosage in
4-6 hours if necessary.
CAUTION: Be prepared to maintain pulmonary ventilation
mechanically, and to manage hypotension and cardiac ar-
rhythmias. Alternative or supplemental anticonvulsive ther-
apy is discussed in the reference cited.
D. In methyl bromide poisoning, it may be necessary to give
benzodiazepines or barbiturates orally for days or weeks after
the poisoning to control involuntary motor activity. Consult
package inserts for appropriate dosages.
7. If a FUMIGANT LIQUID OR SOLID has been INGESTED less
than several hours prior to treatment, quantities remaining in
the stomach must be removed as effectively as possible by gastric
intubation, aspiration, and lavage, after all possible precautions
have been taken to protect the respiratory tract from aspirated
gastric contents.
A. Put in place a cuffed ENDOTRACHEAL TUBE prior to gas-
tric intubation. Administer OXYGEN, using a mechanical
ventilator if respiration is depressed.
B. Lavage the stomach with a slurry of ACTIVATED CHAR-
COAL in saline or water. Leave a volume of the slurry in the
stomach with an appropriate dose of sorbitol as cathartic (for
dosages, see Chapter 1, TREATMENT, Section 6, p. 8).
C. If treatment is delayed and if the patient remains fully alert,
administer activated charcoal and sorbitol orally. For dosage,
see Chapter 1, TREATMENT, Section 6, p. 8. Repeated admin-
istration of charcoal at half or more the initial dosage every
2-4 hours may be beneficial.
D. Do not give vegetable or annual fats or oils, which enhance
gastrointestinal absorption of many of the fumigant com-
pounds.
8. Intravenous infusions of GLUCOSE are valuable in limiting the
hepatotoxicity of many substances. Monitor central venous pres-
sure to avoid precipitating, or aggravating, pulmonary edema by
fluid overload. The victim should be watched closely for indica-
tions of delayed or recurrent pulmonary edema, and for broncho-
pneumonia. Fluid balance should be monitored, and urine sedi-
ment should be checked regularly for 'ndications of tubular
injury. Measure serum alkaline phosphatase, LDH, ALT, AST,
and bilirubin to assess liver injury.
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9. HEMOPERFUSION OVER ACTIVATED CHARCOAL has been
used in, managing a case of carbon tetrachloride poisoning with
apparent success. An extraction efficiency of about 80% was dem-
onstrated for the system employed (Schwarzbeck, A. and Kosters,
W., Arch. ToxicoL, 35:207-211, 1976). It is possible that other
fumigant compounds would be effectively removed from blood by
this method.
10. EXTRACORPOREAL HEMODIALYSIS may be needed to regu-
late extracellular fluid composition if renal failure supervenes. It
is probably not very effective in removing lipophilic fumigant
compounds from blood, but is, of course, effective in controlling
extracellular fluid composition if renal failure occurs.
11. Certain SPECIFIC MEASURES are recommended in poisonings
by particular fumigants (naphthalene, methyl bromide, carbon
tetrachloride, hydrogen cyanide):
A. NAPHTHALENE toxicosis caused by vapor inhalation can
usually be managed simply by removing the individual to
fresh air. Skin contamination should be removed promptly by
washing with soap and water. Eye contamination should be
removed by flushing with copious amounts of clean water.
Irritation may be severe, and if it persists, should receive
medical attention.
If solid naphthalene has been INGESTED and retained
less than several hours prior to treatment, and if the
patient is fully alert, the stomach should be emptied by
administration of Syrup of Ipecac, followed by several
glasses of water. Dosage for adults and children over 12
years: 30 ml; dosage for children under 12 years: 15 ml.
When vomiting subsides, give activated charcoal and
sorbitol (see Chapter 1, TREATMENT, Section 6, p. 8).
If the patient is obtunded or excited, do not give Ipecac,
but take steps to protect the airway, then aspirate and
lavage the stomach with a slurry of activated charcoal.
Leave charcoal and sorbitol in the stomach before with-
drawing the tube (see above reference). Repeated admin-
istration of charcoal every 2-4 hours may be beneficial.
If treatment is delayed more than several hours, admin-
ister as much activated charcoal orally as the patient
will tolerate. Include sorbitol in the charcoal slurry
unless diarrhea has already commenced.
Examine the plasma for evidence of hemolysis: a red-
dish-brown tinge. Examine 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 bilirubin in
the plasma. Monitor fluid balance and blood electro-
a.
b.
c.
141
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lytes. If possible, monitor urinary excretion of naphthol
to assess severity of poisoning and clinical progress.
d. If hemolysis is clinically significant, administer intrave-
nous fluids to accelerate urinary excretion of the naph-
thol metabolite and protect the kidney from products of
hemolysis. Use Ringer's-lactate or sodium bicarbonate
to keep urine pH above 7.5. Consider use of mannitol,
furosemide, or ethacrynic acid to promote diuresis. If
urine flow declines, intravenous infusions must be
stopped to prevent fluid overload. Institute hemodialy-
sis. Consider charcoal hemoperfusion in tandem to ex-
tract naphthalene and end-products.
e. If anemia is severe, blood transfusions may be needed.
f. Hydrocortisone may be of some benefit if significant
hemolysis is present.
B. If given very soon after life-threatening exposure to METHYL
BROMIDE there may be some theoretical value in adminis-
tering DIMERCAPROL (BAL) in vegetable oil intramuscular-
ly. For adults, give 3-5 mg/kg q6h for 4 to 6 doses. Neither
the effectiveness nor the safety of this treatment has been
tested in methyl bromide poisoning.
CAUTION: DIMERCAPROL may cause troublesome side ef-
fects (hypertension, tachycardia, nausea, headache, paresthe-
sia, pain, lacrimation, sweating, anxiety, and restlessness). Al-
though usually not so severe as to preclude treatment, these
effects may require antihistamine therapy.
C. For CARBON TETRACHLORIDE poisoning, several treat-
ment measures have been suggested to limit the severity of
hepatic necrosis. Neither effectiveness nor safety of any of
these measures has been established.
a. Inhalation of oxygen at one or two atmospheres for 2
hours twice daily may have some value.
b. Oral administration of tocopherol (vitamin E) in oral
doses of several hundred milligrams per day has been
suggested on grounds of its action as a free radical
scavenger.
c. Oral administration of N-acetyl cysteine (Mucomyst)
may be worthwhile as a means of reducing free radical
injury. Dilute the proprietary 20% product 1:3 in soda-
pop, and give about 3 ml/kg body weight of the diluted
solution as a loading dose. Give half of this dosage every
4 hours after the loading dose for a total of 17 doses.
(This dosage schedule is used for acetaminophen poison-
ings.) Administration via duodenal tube may be neces-
sary in a few patients who cannot tolerate Mucomyst.
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d. Hemoperfusion over activated charcoal should be con-
sidered. It was apparently effective in one carbon tetra-
chloride poisoning. See Schwarzbeck, A. and Rosters, W.
Arch. Toxicol., 35:207-211, 1976.
D. MM poisonings by CARBON BISULFIDE inhalation may be
managed best by no more than careful observation, even
though sensory hallucinations, delirium, and behavioral aber-
rations can be alarming. Severe poisonings may require specif-
ic measures:
a. If manic behavior threatens the safety of the victim,
DIAZEPAM, 5-10 mg in adults, 0.2-0.4 mg/kg in chil-
dren, administered slowly, intravenously, may be help-
ful as a tranquilizer. Give as much as is necessary to
achieve sedation. Do not give catecholamine-releasing
agents such as reserpine and amphetamines.
b. In severe poisonings by carbon disulfide, pyridoxine hy-
drochloride (vitamin B6) may have some antidotal
action against the neurotoxic effects. Its value is theo-
retical; neither effectiveness nor safety has been tested
in carbon disulfide poisonings. The usual dosage in
other poisonings (ISONIAZID) has been 5 gm in a 10%
solution, given slowly intravenously, or included in a
one liter intravenous solution of 5% glucose. When the
victim can swallow, pyridoxine hydrochloride can be
given orally in daily doses as high as 25 mg/kg body
weight. There is probably little value, and possibly some
hazard, in extending the treatment beyond one or two
weeks.
E. Poisonings by HYDROGEN CYANIDE and ACRYLONI-
TRILE 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 ANTIDOTES, defer-
ring gastric evacuation (in ingestion poisonings) until anti-
dotes have been administered.
If the victim is an ADULT:
Administer OXYGEN continuously. If respiration fails,
maintain pulmonary ventilation mechanically.
Administer AMYL NITRITE (perles) by inhalation for
15-30 seconds of every minute, while a fresh solution of
3% sodium nitrite is being prepared.
As soon as solution is available, inject intravenously 10
ml of 3% SODIUM NITRITE solution .over a 2-4 minute
interval, keeping the needle in place.
a.
b.
c.
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CAUTION: MONITOR PULSE and BLOOD PRES-
SURE 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.
d. Follow sodium nitrite injection with an infusion of 50
ml of 25% aqueous solution of .SODIUM THIOSUL-
FATE administered over a 10-minute period. Initial
adult dose should not exceed 12.5 gm.
e. If symptoms persist or recur, treatment by sodium ni-
trite and sodium thiosulfate should be REPEATED AT
HALF THE DOSAGES listed in paragraphs c and d.
f. Measure hemoglobin and methemoglobin in blood. If
more than 50% of total hemoglobin has been converted
to methemoglobin, BLOOD TRANSFUSION or ex-
change transfusion should be considered, because con-
version back to normal hemoglobin proceeds slowly.
If the victim is a CHILD:
a. Give amyl nitrite, oxygen, and mechanical respiratory
support as recommended for adults.
b. The following dosages of antidotes have been recom-
mended by C.M. Berlin (Pediatrics, 46:793-796, 1970).
i) Children over 25 kg body weight should receive
adult dosages of sodium nitrite and sodium thio-
sulfate.
ii) 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 10 nig/kg
(0.33 ml/kg of 3% solution) of SODIUM NITRITE
injected over a 2-4 minute interval. Following
sodium nitrite, administer an infusion of 1.65
ml/kg of 25% SODIUM THIOSULFATE at rate
of 3-5 ml per minute.
iii) At this point, determine the hemoglobin content
of the pretreatment blood sample. If symptoms
and signs of poisoning persist or return, give sup-
plemental infusions of sodium nitrite and sodium
thiosulfate based on hemoglobin level, as present-
ed in TABLE 2. These recommended quantities
are calculated to avoid life-threatening methe-
moglobinemia in anemic children. They are
aimed at converting approximately 40% of circu-
lating hemoglobin to methemoglobin. If possible,
monitor blood methemoglobin concentrations as
treatment proceeds.
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TABLE 2. Recommended dosages of supplemental sodium nitrite and
sodium thiosulfate based on hemoglobin level.
Initial
Hemoglobin
Concentration
gm/100 ml
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
Supplemental
Volume of 3%
Sodium Nitrite,
ml/kg
0.25
0.21
0.17
0.13
0.09
0.05
0.00
0.00
Supplemental
Volume of
25% Sodium
Thiosulfate,
ml/kg
1.25
1.05
0.85
0.65
0.45
0.25
0.00
0.00
Although various cobalt salts, chelates, and organic combinations
have shown some promise as antidotes to cyanide, they are not gener-
ally available. None have been shown to surpass the nitrite-thoisulfate
regimen in effectiveness.
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CHAPTER 15
MISCELLANEOUS PESTICIDES,
SOLVENTS, AND ADJUVANTS
The following pest control agents are widely used and may occasion-
ally pose a risk of human poisoning.
METALDEHYDE
CHEMICAL STRUCTURE
fa
c —
CH3- C - H
H - C - CH,
V
C
CH,
COMMERCIAL PRODUCTS
Antimilace, Bug-Geta, Cekumeta, Corry's Slug and Snail Death, Ha-
lizan, Metason, Namekil.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
METALDEHYDE
Metaldehyde is a 4-unit cyclic polymer of acetaldehyde long 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 in-
gestion of pellets intended as molluscicide, but tablets designed as fuel
in smokeless lamps have more commonly been the agents responsible
for human poisonings. The biochemical mechanism of poisoning is not
known; acetaldehyde derived from depolymefization does not produce
the dramatic neurologic symptoms and signs of metaldehyde poisoning.
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Furthermore, acetaldehyde is not detectable in the blood or urine of
metaldehyde-poisoned dogs.
Ingestion of a toxic dose is sometimes followed by vomiting due to
gastric irritation. Within a few minutes to several hours following
ingestion, salivation, flushing, abdominal cramps, vomiting, and gener-
alized tremors occur; the latter may progress to violent tonic-clonic
convulsions. Hyperthermia and tachycardia characterize some cases.
Poisoned animals show tremors, ataxia, hyperesthesia, and salivation.
Autopsy findings in fatal human poisonings indicate severe damage to
liver cells and renal tubular epithelium. Metabolic acidosis may be an
important factor leading to death.
CONFIRMATION OF METALDEHYDE POISONING
Chromatographic methods for measurement of metaldehyde in blood
are described but are not generally available. Very little metaldehyde
or acetaldehyde is excreted in the urine of metaldehyde-dosed dogs.
Liver function tests and repeat urinalyses for protein and cells should
be done to assess liver and kidney injury in poisoned patients.
TREATMENT OF METALDEHYDE POISONING
Unless ingestion occurred more than several hours before treatment,
ingested metaldehyde must be removed from the gut, preferably by
gastric lavage and catharsis (see Chapter 1. TREATMENT, Section 6,
p. 8). Activated charcoal may well be useful against metaldehyde. If
seizures occur, sedative anticonvulsants must be administered (see
Chapter 3, TREATMENT, Section 4, p. 21). Intravenous fluids, includ-
ing glucose, should be given to protect the liver, support detoxication,
and facilitate excretion. Add sodium bicarbonate to intravenous fluids
to reverse metabolic acidosis. Fluid balance and electrolytes must be
monitored carefully to avoid fluid overload if renal failure supervenes.
There is no specific antidote for metaldehyde poisoning. Hemodialy-
sis is probably not effective in removing metaldehyde, but must be
instituted if renal failure occurs. Effectiveness of hemoperfusion has
not been tested.
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4-AMINOPYRIDINE
CHEMICAL STRUCTURE
H2N\\ NH
COMMERCIAL PRODUCTS
Avitrol, 4-Ap.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
AMINOPYRIDINE
4-Aminopyridine is a highly toxic white powder used as a bird repel-
lant. (Only occasionally does it kill the poisoned bird: the cries and
excited behavior of the affected bird cause others to take flight). It is
usually added to grain baits in 0.5%-3.0% concentration, but 25% and
50% concentrates in powdered sugar are available. It is rapidly ab-
sorbed by the gut, less effectively across skin. The chief mechanism of
toxicity is enhancement of cholinergic transmission in the nervous
system. 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 by each of two ill-advised adult
humans have been reported. Both experienced immediate abdominal
discomfort, nausea and vomiting, weakness, dizziness, and profuse di-
aphoresis. One patient suffered a tonic-clonic seizure and went into
respiratory arrest. With supportive treatment, both recovered in 3
days. Poisoned laboratory animals commonly exhibit excitability, sali-
vation, tremors, incoordination, convulsions, and cardiac or respiratory
arrest.
TREATMENT OF POISONING BY AMINOPYRIDINE INGESTION
Unless ingestion occurred more than several hours before treatment,
the stomach must be emptied by intubation, aspiration, and lavage
with a slurry of activated charcoal, following placement of cuffed endo-
tracheal tube (see Chapter 1, TREATMENT, Section 6, p. 8). Induced
emesis may be a reasonable alternative if the patient is fully alert, but
there is substantial risk of aspiration of gastric contents if convulsions
or depressed consciousness level and reflexes occur before emesis. Gas-
tric evacuation should be followed by administration of charcoal and
sorbitol. If treatment is delayed, immediate oral administration of
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ckarcoal and sorbitol may represent optimal management. Seizures
may require anticonvulsant medication (see Chapter 3, TREATMENT,
Section 4, page 21). Dehydration should be treated with intravenous
fluids if oral fluids cannot be retained.
CALCIUM CYANAMIDE
CHEMICAL STRUCTURE
Cyanam.de
H2N-C
Hydrogen
Cyanamide
COMMERCIAL PRODUCTS
Cyanamide, nitrolime.
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; the hydrolysis proceeds most rapidly
under acid conditions. 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 AND MANIFESTATIONS OP POISONING BY
CYANAMIDE
Calcium cyanamide is only moderately irritating to skin, but hydro-
gen cyanamide is severely irritating and caustic to skin and the in-
haled gas is strongly irritating to mucous membranes.
The efficiency of dermal absorption of either form of cyanamide is
not known; poisonings by this route have not been reported. Systemic
poisonings have followed inhalation of hydrogen cyanamide and inges-
tion of the salt. Manifestations of poisoning are: flushing, headache,
vertigo, dyspnea, tachycardia, and hypotension, sometimes progressing
to shock. Because cyanamide is an inhibitor of acetaldehyde dehydro-
genase, ingestion of alcohol exaggerates the symptoms. (A titrated
form of cyanamide has been used in place of Antabuse in alcohol
aversion therapy.)
TREATMENT OF CYANAMIDE POISONING
Skin contamination with either the calcium salt or the free form
should be removed by washing with soap and water. Eye contamina-
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tion should be removed by flushing the eyes with copious amounts of
clean water. If skin or eye irritation persists, medical attention should
be obtained promptly.
If large doses have been ingested recently, the stomach should be
emptied with due care to protect the airway (Chapter 1. TREATMENT,
Section 6, p. 8). If dosage was small or treatment is delayed, immediate
oral administration of activated charcoal and sorbitol probably repre-
sents optimal management.
Treat hypotension or Antabuse-type reaction by placing the patient
in Trendelenburg position, giving intravenous fluids, including plasma
or blood, if needed, and, if necessary, vasopressor drugs parenterally.
Atropine is not antidotal.
SODIUM CHLORATE
CHEMICAL STRUCTURE
Na Cl O3
COMMERCIAL PRODUCTS
Atratol, De-Fol-Ate, Dervan, Drexel Defol, Drop-Leaf, Fall, Harvest-
Aid, Klorex, KM, Kusatol, Tumbleaf.
Sodium chlorate is used in agriculture as a defoliant, nonselectiye
contact herbicide, and semipermanent soil sterilant. Because of its
explosive nature, it must be formulated with water-soluble fire retard-
ant material, such as sodium metaborate, soda ash, magnesium chlo-
ride, or urea. It is usually applied in water solution.
TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
SODIUM CHLORATE
Sodium chlorate is irritating to skin, eyes, and mucous membranes
of the upper respiratory tract. Dermal absorption is slight. Even
though gastrointestinal absorption is also inefficient, severe poisoning,
sometimes fatal, follows ingestion of a toxic dose, said to be several
grams in the adult human. Onset of symptoms is sometimes delayed as
much as twelve hours. Excretion is chiefly in the urine. The principal
mechanisms of toxicity are: hemolysis, methemoglobin formation, car-
diac arrhythmia (partly secondary to hyperkalemia), and renal tubular
injury. The irritant action on the gut causes nausea, vomiting, abdomi-
nal pain, and diarrhea. Hypotension may progress to shock. Cyanosis
and dyspnea are prominent if hemolysis and methemoglpbinemia are
severe. Lumbar pain, proteinuria, hemoglobinuria, oliguria, and azote-
mia result from renal injury. Plasma and. urine are dark brown from
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presence of free hemoglobin and methemoglobin. Release of potassium
from red cell destruction results in hyperkalemia; this may be severe
enough to cause life-threatening cardiac conduction defects. The liver
is often enlarged and tender. Anoxemia may lead to convulsions. Death
may be the result of shock, anoxemia, heart failure, or disseminated
intravascular coagulation.
There are no widely available tests for chlorate specifically. Dark
brown staining of the plasma and urine indicates the action of a strong
oxidizing agent on hemoglobin.
TREATMENT OF CHLORATE POISONING
1. Skin contamination should be removed immediately by washing
with soap and water. Medical attention should be sought if irrita-
tion persists.
Eye contamination should be removed by flushing with copious
amounts of clean water, then specialized medical attention should
be obtained promptly, because irritant action may be severe.
2. If sodium chlorate has been ingested within several hours prior to
treatment, put in place a cuffed endotracheal tube to protect the
airway, then intubate the stomach, and lavage with a slurry of
activated charcoal (Chapter 1, TREATMENT, Section 6, p. 8).
After the lavage, instill 200 ml of 5% sodium bicarbonate contain-
ing 2-5 gm of SODIUM THIOSULFATE to decompose any re-
maining chlorate. Sorbitol should be administered if diarrhea has
hot already commenced.
3. Give OXYGEN. If respiration is depressed, maintain pulmonary
ventilation with intermittent positive pressure breathing appara-
tus.
4. SODIUM THIOSULFATE intravenous infusion is an apparently
successful antidote against absorbed sodium chlorate. Infuse 2-5
gm dissolved in 200 ml of 5% sodium bicarbonate over 60-90
minutes.
5. Monitor blood pressure, fluid balance, blood electrolytes, BUN,
methemoglobin, and bilirubin, also urine protein, cells and free
hemoglobin content,'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 excre-
tion. Maintain urine pH in the alkaline range by addition of
sodium bicarbonate to the infusion fluid. Monitor urine produc-
tion closely, so that intravenous fluids can be slowed or discontin-
ued if renal failure occurs. BLOOD TRANSFUSION may be
needed if hemolysis and methemoglobinemia are severe.
8. HEMODIALYSIS may be life-saving in severe poisoning. It is
effective in removing chlorate from the blood, provides a means to
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control hyperkalemia, and makes possible the control of extracel-
lular fluid volume and composition while renal function remains
impaired.
9. Administration of methylene blue to reverse methemoglobinemia
may be considered if as much as 25-30% of hemoglobin is convert-
ed, even though use of this agent in chlorate poisoning has not
proven beneficial in the past. Give intravenously 0.1 ml/kg body
weight of a 1% solution over a period of at least 10 minutes. An
increase in blood pressure, nausea, and dizziness may occur, but
these effects are usually transient.
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.
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 pigmen-
tation, and occasionally gangrene and skin cancer. 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 poison-
ings following dermal absorption have occurred very rarely. Absorption
of ingested creosote from the gut occurs promptly, and there may be
significant absorption of vapor by the lung. Conjugates of absorbed
phenolic constituents are excreted mainly in the urine. Acute toxic
effects are similar to those of phenol, but toxicity is somewhat less.
Irritation of the gastrointestinal tract, toxic encephalopathy, and renal
tubular injury are the principal effects. A chronic toxicosis from con-
tinuing gastrointestinal absorption (creosote used medicinally) has
been described, consisting of gastroenteritis and visual disturbances.
Manifestations of acute systemic poisoning are salivation, vomiting,
dyspnea, headache, dizziness, loss of pupillary reflexes, cyanosis, hypo-
thermia, convulsions, and coma. Moderate hypotension may progress to
shock; vascular collapse is the usual cause of death, although respirato-
ry depression may well be contributory. The presence of phenolic oxi-
dation products imparts a dark, smoky color to the urine. If there is
suspicion of poisoning, addition of a few drops of ferric chloride solu-
tion to the urine yields a violet or blue color indicating the presence of
phenolic compounds.
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TREATMENT OP CREOSOTE POISONING
1.
2.
3.
4.
5.
6.
7.
8.
9.
Stringent measures should be taken to avoid contamination of
skin or eyes and inhalation of vapor. Skin contamination should
be promptly washed off with soap and water. Contamination of
the eyes should be removed by washing with copious amounts of
water, then specialized medical attention should be obtained
promptly because corneal injury may be severe.
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 (for dosage, see Chapter 1,
TREATMENT, Section 6, p. 8). Further efforts to limit absorption
depend on whether there has been corrosive injury to the esopha-
gus. If pharyngeal redness and swelling are evident, neither in-
duced emesis or gastric lavage are advisable: emesis will re-expose
the esophagus to the creosote, and a gastric tube may perforate
the esophagus. If there is minimal evidence of pharyngeal injury,
careful gastric intubation and lavage with activated charcoal may
be undertaken after placement of a cuffed endotracheal tube to
protect the airway. Sorbitol should be administered if diarrhea
has not already developed in response to the creosote. Whether
gastric lavage is accomplished or not, repeated administration of
activated charcoal by mouth, at half or more the initial dose
every 2-4 hours, may well be beneficial.
Maintain pulmonary ventilation mechanically with oxygen, if nec-
essary.
Draw a blood sample to test for methemoglobinemia, to measure
BUN and blood electrolytes, and to check for signs of liver injury
(bilirubin, GOT, LDH, ALT, AST, and alkaline phosphatase). Test
the urine for protein and cells, and for "smoky" phenolic excre-
tion products.
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.
Monitor EGG to detect arrhythmias and/or conduction defects
that may appear as manifestations of a toxic myocardiopathy.
Diazepam may be needed to control tremors or seizures See
Chapter 3, TREATMENT, Section 4, p. 21 for dosage.
Hemodialysis is not effective in accelerating disposition of phenol
(or, presumably, creosote), but HEMOPERPUSION over charcoal
probably is effective. This should be instituted in severe creosote
poisonings.
Methemoglobinemia is rarely severe, but intravenous administra-
tion of 1% methylene blue may be considered if 25-30% of hemo-
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globin is converted. Dose is 0.1 ml of 1% solution per kg body
weight, given over no less than ten minutes. Nausea, dizziness,
and a transient increase in blood pressure may occur.
ENDOTHALL
CHEMICAL STRUCTURE
H
H
COMMERCIAL PRODUCTS
Accelerate, Endothall Weed Killer, Aquathol, Des-i-cate, Endothall
Turf Herbicide, Hydrothol, Herbicide 273.
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 AND MANIFESTATIONS OF POISONING BY
ENDOTHALL
Endothall is irritating to skin, eyes, and mucous membranes. It is
well absorbed across abraded skin and from the gastrointestinal tract.
Recognized systemic toxic mechanisms in mammals are: 1) corrosive
effect on the gastrointestinal tract (particularly from high concentra-
tions of the free acid); 2) myocardiopathy and vascular injury leading
to shock; and 3) central nervous system injury, causing convulsions and
respiratory depression.
No human poisonings by endothall have been reported. There are no
generally available tests to confirm absorption.
TREATMENT OF ENDOTHALL POISONING
1. Wash endothall from the skin with soap and water. Flush con-
tamination from the eyes with copious amounts of clean water.
Obtain, medical attention if irritation of skin or eyes persists.
2. If endothall has been ingested, and if the patient is fully alert and
not convulsing, prompt administration DEACTIVATED CHAR-
COAL may serve to limit toxicant concentration in the gastroin-
testinal tract. See Chapter 1, TREATMENT, Section 6, p. 8 for
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dosage. Repeat charcoal administration every 2-4 hours at half or
more the original dosage.
3. If there is no evidence of corrosive effect on pharyngeal tissues
(or, presumably, on the esophagus), the stomach may be carefully
intubated and lavaged with a slurry of activated charcoal, after
all necessary measures have been taken to protect the airway
from aspiration of vomitus (see Chapter 1, TREATMENT, Section
6, p. 8).
4. If there are indications of corrosive effects in the pharynx, gastric
intubation should not be attempted because of the risk of esopha-
geal perforation. Treatment procedures appropriate for ingestions
of corrosives (strong acids and alkalis) may be necessary. A stand-
ard text of clinical toxicology should be consulted.
5. Oxygen should be given by mask. If respiratory drive is weak,
pulmonary ventilation may have to be supported mechanically.
6. Monitor blood pressure closely. Infusions of plasma or blood may
be needed to combat shock. Administer intravenous fluids to cor-
rect dehydration, stabilize electrolytes, provide sugar, and support
mechanisms for toxicant disposition. Give vasoactive amines very
carefully in light of myocardiopathy.
7. Seizures may require administration of diazepam and/or other
anticonvulsants (see Chapter 3, TREATMENT, Section 4, p. 21).
8. 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 sup-
portive care.
SYNERGISTS: PIPERONYL BUTOXIDE AND N-OCTYL
BICYCLOHEPTENE DICARBOXIMIDE (MGK 264)
Synergists are chemical agents included in pesticide products to
enhance the killing power of the active ingredients. The widely used
insecticide synergists named above act by inhibiting the enzymatic
degradation of pyrethrins, rotenone, N-methyl carbamates, and possi-
bly 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-metaboliz-
ing enzymes by these agents has not actually been demonstrated. Their
presence in pesticide products to which humans are exposed does not
change the basic approach to management of poisoning, except that
some possibility of enhanced toxicity of the .active insecticidal ingredi-
ents should be kept in mind.
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SOLVENTS AND ADJUVANTS
liquid materials in which pesticides are dissolved or the solids on
which they are adsorbed (sometimes called carriers or vehicles), are
chosen by producers to achieve stability of the active ingredient, con-
venience in handling and application, and maximum killing power
following application. It is often the solvents and adjuvants which
pesticide manufacturers choose that give 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 under emergency circumstances. If a poisoning emergency
exists, pesticide companies will usually cooperate in supplying physi-
cians with information needed to provide treatment. A direct request
to the producer is necessary to secure this information.
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 having low boiling
points.
Sometimes specific hydrocarbons, such as toluene or xylene (strongly
odiferous), are added to stabilize the solution of insecticide or make it
more emulsifiable. Hydrocarbon-dissolved pesticides are usually diluted
for application by adding measured amounts of water to form emul-
sions. Some chlorinated hydrocarbons may be present in particular
technical mixtures. A strong odor lingering after application of a struc-
tural pest control spray is often due to the solvent rather than the
active ingredient.
Less lipophilic active ingredients are sometimes dissolved in mix-
tures of alcohols, glycols, ethers, or various chlorinated solvents. It is
possible that these enhance the dermal absorbability of some pesti-
cides. Also, some solvents, for example, methanol and isopropanol, may
represent a significant toxic hazard if swallowed in significant dosage.
Granular formulations utilize various clay materials which adsorb
pesticide, retain it in more or less stable form until application, then
desorb the material slowly into treated soil. There is some significant
desorption when granules are in contact with human skin and very
substantial desorption into gastrointestinal secretions if granules are
swallowed. The clay materials themselves are not a toxic hazard.
Dusts are infrequently used today. Various forms of talc (silicate-
carbonate particles) have been used in the past to adsorb pesticides for
application to 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 gastrointes-
tinal secretions. Dust formulations may, therefore, release enough of
some pesticides to cause systemic poisonings.
Stickers and spreaders (film extenders) are organic substances added
to formulations to disperse pesticide .over treated foliage surfaces and
156
-------
enhance adhesion thereto. 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, alkyl and petroleum sulfonates. For persons exposed in the
course of formulation or application of pesticides, these adjuvants prob-
ably add little or no toxic hazard to that inherent in the active pestici-
dal ingredients.
Emulsifiers serve to stabilize water-oil emulsions formed when water
is added to technical hydrocarbon concentrates. Chemically, they are
detergent-like (one part of the molecule lipophilic, the other hydrophil-
ic). Long-chain alkyl sulfonate ethers of polyethylene glycol and
polyoxyethylene oleate are exemplary emulsifiers. They have low in-
herent 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 (surfac-
tant) in nature. Substances used include heavy petroleum oils and
distillates, polyol fatty acid esters, polyethoxylated fatty acid esters,
aryl alkyl polyoxyethylene glycols, alkyl amine acetate, alkyl aryl
sulfonates, polyhydric alcohols, and alkyl phosphates. Some of these
are eye and skin irritants, and may account for the irritant effects of
particular herbicide formulations whose active ingredients do not have
this property.
Safeners are substances added to mixtures of fertilizers with pesti-
cides (commonly herbicides) to limit the formation of undesirable reac-
tion products. Some substances used are: alcohol sulfates, sodium alkyl
butane diamate, polyesters of sodium thiobutane dioate, and benzene
acetonitrile derivatives. Some are moderately irritating to the skin and
eyes. Systemic toxicities are generally low.
Anticaking agents are added to granular and dust "formulations to
facilitate application by preventing cakes and clumps. Among several
products used are the sodium salt of mono- and di-methyl naphthalene
sulfonate, and diatomaceous earth. Diatomaceous earth has little ad-
verse effect except a drying action on the skin. Methyl naphthalenes
are said to be skin irritants and photosensitizers; whether their deriva-
tives have this effect is not known.
TREATMENT CONSIDERATIONS
Petroleum distillates are mineral hydrocarbons which undergo limit-
ed absorption across the gut. In general, clinical toxicologists do not
recommend induced emesis or gastric lavage in treating ingestions of
these materials, because of the serious risk of hydrocarbon pneumoni-
tis if even tiny amounts of the liquid are aspirated into the lung.
157
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However, this injunction against emptying the stomach must be set
aside when the petroleum distillate is a vehicle for toxic pesticides in
significant concentration. Preferably, a cuffed endotracheal tube
should be put in place before the stomach is aspirated and lavaged
with a slurry of activated charcoal (Chapter 1, TREATMENT, Section
6, p. 8). If this protection is not available, all possible precautions
should be taken (head down position, frequent aspiration of pharynx)
to minimize the likelihood of aspiration of hydrocarbon into the respi-
ratory tract. Rapid respiration, cyanosis; tachycardia, and low-grade
fever are the usual indications of frank hydrocarbon pneumonitis. If
these occur within 6-8 hours of gastric lavage, hospitalization is usual-
ly indicated. Within a few hours following gastric evacuation, a chest
x-ray should be taken to detect or confirm signs of pneumonitis, the
urine should be examined for protein, sugar, acetone, casts, and cells,
and an EGG should be examined for arrhythmias and conduction de-
fects. Mechanically assisted pulmonary ventilation with pure oxygen
may be required. Hydrocarbon pneumonitis is sometimes fatal; survi-
vors usually require several weeks for full recovery.
The presence of chlorinated solvents in some formulations may add
significantly to the toxic hazard, particularly if the product is ingested.
Certain adjuvants are irritants to skin, eyes, and mucous membranes,
and may account for irritancy of some products whose active ingredi-
ents do not have this effect. With these exceptions, however, the pres-
ence of adjuvants in most finished pesticide products probably does not
enhance or reduce systemic mammalian toxicity to any great extent.
158
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CHAPTER 16
INDEX TO PESTICIDE POISONINGS
BY SYMPTOMS AND SIGNS
Presented in this chapter are lists of pesticides reported to have
caused particular symptoms and signs, or combinations thereof, in
poisoned individuals. The lists may on occasion direct the attention of
health professionals to possible toxic causes of the various disease
manifestations, prompting inquiry into likelihood of exposure to the
listed chemicals. If certain agents appear suspect, inquiry can then be
made into the presence of additional manifestations typical of poison-
ing 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, it is evident that 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 sys-
temic dermal manifestations. Clearly, the lists of pesticides can only be
regarded as clues to prompt further inquiry by the interviewing profes-
sional.
The term manifestation means either symptom or sign. The word
"poisoning" is used loosely in these headings to include topical as well
as systemic effects. Pesticides which are relatively consistent in caus-
ing particular manifestations are listed in the middle column, headed
"Characteristic of These Poisonings." Agents that have caused various
conditions with less consistency, or are less prominent features of
poisoning, are listed in the right-hand column, headed "Occurs in
These Poisonings." Obviously, the distinction is not clear-cut.
Some symptoms (malaise, fatigue, dizziness) occur so commonly in
poisoned individuals that they have little or no value in differential
diagnosis, and are therefore not included in these tables.
SYSTEM
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
159
OCCURS IN THESE
POISONINGS
General
Breath odor of:
Garlic
Bitter almonds
Rotten cabbage
Arsenic
Phosphorus
Phosphides
Phosphine
Cyanide
Carbon disulfide
Thiram
-------
—Continued
SYSTEM
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Skin
Rotten egg
Peanuts
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
Irritation,
rash,
blistering,
or erosion
(without
sensitization)
Sulfur
Pyriminyl
Creosote
Norbormide
Nitrophenols
Pentachlorophenol
Phosphine
Arsine
Nitrophenols
Chlordimeform
Paraquat
Chlorophenoxy
compounds
Pentachlorophenol
Nitrophenols
Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Sodium fluoride
Cholecalciferol
Aminopyridine
Organophosphates
Carbamate
insecticides
Nicotine
Pentachlorophenol
Hexachlorobenzene
Chlordimeform
Cholecalciferol
Thiram
Calcium cyanamide
Chlordimeform
Inorganic arsenicals
Organic mercury
Sodium fluoride
Copper, organotin,
cadmium compounds
Metam sodium
Paraquat
Diquat
Sodium chlorate
Phosphorus
Sulfur
Thiram
Borate
Thallium
Metaldehyde
Inorganic arsenicals
Chlorophenoxy compounds
Cadmium dusts
Naphthalene
Pentachlorophenol
Borate
Endothall
Halocarbon fumigants
Nitrophenols
Inorganic arsenicals
Aminopyridine
Pyriminil
Pentachlorophenol
Picloram
Chlorophenoxy compounds
Captan
Rotenone
Diethyltoluamide
Creosote
Fungicides and herbicides
with irritant properties
160
-------
SYSTEM
—Continued
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Flushing
Dermal sensi-
tization
Beefy red palms,
Ethylene oxide
Formaldehyde
Acrolein
Methyl bromide
Eththylene dibromide
Ethylene oxide
Dibromochloropropane
Dichloropropane
EndothaU
Aliphatic acids
Cyanamide
Nitrophenols
Propachlor
Propargite
Ethylene oxide
Borate
Petroleum distillate
Thiram plus alcohol
Anilazine
Chlorothalonil
Barban
Captafol
Formaldehyde
Urticaria
Bullae
Paresthesia
(chiefly
facial,
transitory)
Pallor
Cyanosis
Yellow stain
Keratoses, brown
discoloration
Liquid fumigants
Fenvalerate
Fluvalinate
Cypermethrin
Flucythrinate
Organochlorines
Fumigants
Sodium fluoride
Creosote
Sodium chlorate
Paraquat
Cadmium dusts
Sodium fluoroacetate
Strychnine
Crimidine
Nicotine
Chlorinated
hydrocarbons
Nitrophenols
Inorganic arsenicals
Fluoride
Hexachlorobenzene
Coumarins
Indandiones
Organophosphates
Carbamate insecticides
Agents that cause shock,
myocardiopathy, severe
arrhythmias or
convulsions.
Ecchymoses
Jaundice
Excessive hair
growth
Coumarins
Indandiones
Carbon tetrachloride
Chloroform
Phosphorus
Phosphides
Phosphine
Paraquat
Sodium chlorate
Phosphorus
Phosphides
Inorganic arsenicals
Diquat
Copper compounds
He'xachlorobenzene
161
-------
SYSTEM
—Continued
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCUHS IN THESE
POISONINGS
Loss of hair
Loss of
fingernails
Brittle nails,
white
striations
Sweating,
diaphoresis
Thallium
Eye
Conjunctivitis
(irritation of
mucous mem-
branes,
tearing)
Tearing
Yellow sclerae
Keratitis
Ptoeis
Diplopia
Photophobia
Constricted
visual fields
Optic atrophy
Miosis
Organophosphates
Carbamato
insecticides
Nicotine
Nitrophenols
Pentachlorophenol
Naphthalene
Aminopyridine
Copper compounds
Organotin compounds
Cadmium compounds
Metam sodium
Paraquat
Diquat
Acrolein
Chloropicrin
Sulfur dioxide
Naphthalene
Formaldehyde
Methyl bromide
Ethylene oxide
Endothall
Toluene
Xylene
Organophosphates
Carbamate
insecticides
Chloropicrin
Acrolein
Nitrophenols
Paraquat
Thallium
Organophosphates
Carbamate
insecticides
Nicotine
Organic mercury
Organophosphates
Carbamate
insecticides
Inorganic arsenicals
Paraquat
Inorganic arsenicals
Inorganic arsenicals
Thallium
Copper compounds
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)
162
-------
—Continued
SYSTEM
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Nervous
system
Dilated pupils
Unreactive
pupils
Headache
Behavioral-mood
disturbances
(confusion,
excitement,
mania,
disorien-
tation,
emotional
lability)
Nervous system
depression,
stupor, coma,
respiratory
failure, often
without
convulsions.
Convulsions
(clonic-tonic),
sometimes
leading to coma.
Cyanide
Fluoride
Cyanide
Organophosphates
Carbamate
insecticides
Nicotine
Inorganic arsenicals
Organic mercury
Cadmium compounds
Organotin compounds
Copper compounds
Thallium
Fluoride
Borates
Naphthalene
Phosphine
Halocarbon fumigants
Creosote
Diquat
Cholecalciferol
Cyanamide
Organic mercury
Inorganic arsenicals
Organotin compounds
Thallium
Nicotine
Sodium fluoroacetate
Diquat
Cyanide
Nitrophenols
Pyriminil
Aminopyridine
Carbon disulfide
Methyl bromide
Organophosphates
Carbamate
insecticides
Sodium fluoride
Borate
Diquat
Organochlorines
Strychnine
Crimidine
Sodium fluoroacetate
Nicotine
Cyanide
Acrylonitrile
Metaldehyde
Nicotine (late)
Organochlorines
Nitrophenols
Thiram
Pentachlorophenol
Paraquat
Diethyltoluamide
Organophosphates
Carbamate insecticides
Pentachlorophenol
Sodium fluoride
Diethyltoluamide
Organochlorines
Inorganic arsenicals
Metaldehyde
Sulfuryl fluoride
Halocarbon fumigants
Phosphorus
Phosphides
Phosphine
Paraquat
Chlorophenoxy compounds
Diethyltoluamide
Alkyl phthalates
Nitrophenols
Pentachlorophenol
Inorganic arsenicals
Organotin compounds
Diquat
Borate
Sulfuryl fluoride
Methyl bromide
Chlorophenoxy compounds
Organophosphates
Carbamate insecticides
Aminopyridine
163
-------
—Continued
SYSTEM
MANIFESTATION
CHAEACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Muscle twitching
Myotonia
Tetany,
carpopedal
Tremor
Cardio-
vas-
cular
system
Incoordination
(including
ataxia)
Paralysis,
paresis,
muscle
weakness
Paresthesia of
extremities
Hearing loss
Hypotension,
shock
Hypertension
Cardiac
arrhythmias
Organophosphates
Carbamate
insecticides
Nicotine
Sulfuryl fluoride
Fluoride
Phosphides
Phosphorus
Organic mercury
Thallium
Organophosphates
Carhamate
insecticides
Nicotine
Metaldehyde
Berates
Halocarbon fumigants
Organophosphates
Carbamate
insecticides
Carbon disulfide
Nicotine
Thallium
Inorganic arsenicals
Organophosphates
Carbamate
insecticides
Nicotine
Inorganic arsenicals
Organic mercury
Sodium fluoroacetate
Carbon disulfide
Pyriminil
Thallium
Organic mercury
Phosphorus
Phosphides
Phosphine
Sodium fluoride
Sodium chlorate
Borate
Thallium
Copper compounds
Endothall
Cyanamide
Thallium (early)
Nicotine (early)
Sodium fluoroacetate
Halocarbon fumigants.
Nicotine
Sodium fluoride
Ethylene oxide
JSodium chlorate »
Pyriminil .
Organic mercury
Chlorophenoxy compounds
Chlorophenoxy compounds
Pentachlorophenol
Nitrophenols
Thiram
Organic mercury
Organochlorines
Organic mercury
Diethyltoluamide
Pyrethroids (transitory)
Inorganic arsenicals
Nicotine (late)
Creosote
Alkyl phthalate
Cycloheximide
Formaldehyde
Norbormide
Organophosphates
Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Organochlorines
Cyanide
Acrylonitrile
164
-------
SYSTEM
—Continued
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Respira-
tory
system
Bradycardia
(sometimes to
asystole)
Tachycardia
Upper
respiratory
tract
irritation:
rhinitis,
scratchy
throat, cough
Cyanide
Organophosphates
Carbamate
insecticides
Nitrophenols
Pentachlorophenol
Cyanamide
Naphthalene
Paraquat
Chloropicrin
Acrolein
Dichloropropene
Ethylene dibromide
Sulfur dioxide
Sulfuryl fluoride
Acrylonitrile
Formaldehyde
Cadmium dusts
ANTU
Nicotine
Metaldehyde
Organophosphates
Dry formulations of
copper, tin, zinc
compounds.
Dusts of thiocarbamate
and other organic
pesticides.
Chlorophenoxy compounds
Aliphatic acids
Rotenone
Runny nose
Sabadilla
Pyrethrins
Inorganic arsenicals
Organophosphates
Carbamate
insecticides
(Irritants listed above)
Pulmonary edema
Pulmonary
consolidation
Dyspnea
Gastro-
intes-
tinal
tract
and
liver
Nausea, vomiting
commonly
followed by
diarrhea
Methyl bromide
Phosphine
Phosphorus
Phosphides
Ethylene oxide
Ethylene dibromide
Acrolein
Paraquat
Cadmium dusts
Methyl bromide
Organophosphates
Carbamate
insecticides
Nicotine
Paraquat
ANTU
Cadmium dusts
Cyanamide
Sulfuryl fluoride
Pentachlorophenol
Methyl bromide
Sulfur dioxide
Chloropicrin
Organophosphates
Carbamate
insecticides
Nicotine
Arsenicals
Fluoride
Cadmium compounds
Organophosphates
Carbamate Insecticides
Paraquat
Phosphides
Diquat
Nitrophenols
Cyanide
Creosote
Pyrethrins
Pentachlorophenol
B. thuringiensis
Cholecalciferol
Thiram
Many pesticides having
some irritant property.
165
-------
SYSTEM
—Continued
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Bloody diarrhea
Abdominal pain
Stomatitis
Salivation
Liver
Ileus
Constipation
Enlargement
Organotin compounds
Copper compounds
Sodium chlorate
Borate
Cyanide
Chlorophenoxy
compounds
Phosphorus
Phosphides
Phosphine
Carbon disulfide
Chloropicrin
Halocarbon fumigants
Endothall
Fluoride
Paraquat
Diquat
Thallium
Coumarins
Indandiones
Endothall
Arsenicals
Organophosphates
Carbamate insecticides
Paraquat
Diquat
Nicotine
Metaldehyde
Fluoride
Borate
Phosphorous
Phosphides
Inorganic arsenicals
Cadmium compounds
Copper compounds
Thallium
Organotin compounds
Inorganic aresenicals
Paraquat
Diquat
Copper compounds
Organophosphates
Carbamate
insecticides
Nicotine
Aminopyridine
Sodium fluoride
Cyanide
Cadmium compounds
Thallium
Diquat
Pyriminil
Copper compounds
Sodium chlorate
Phosphine
Carbon tetrachloride
Cholorform
Phosphorus
Phosphides
Cycloheximide
Chlorophenoxy compounds
Aliphatic acids
Sodium chlorate
Creosote
Endothall
Aminopyridine
Coumarins
Indandiones
Fumigants (ingested)
Cycloheximide
Thallium
Inorganic arsenicals
Hexachlorobenzene
Other organochlorines
166
-------
SYSTEM
—Continued
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Kidney
Blood
Jaundice—see
section on
"Skin"
Proteinuria,
hematuria,
sometimes
leading to
oliguria,
acute renal
failure with
Dysuria,
hematuria,
pyuria
Urinary
retention
Polyuria
Hemoglobinuria
Wine-red urine
(porphyrinuria)
Smoky urine
Glycosuria
Ketonuria
Hemolysis
Methemoglo-
binemia
Hypopro-
thrombinemia
Hyperkalemia
Inorganic arsenicals
Copper compounds
Sodium fluoride
Naphthalene
Borate
Nitrophenols
Pentachlorophenol
Sodium chlorate
Sulfuryl fluoride
Paraquat
Diquat
Arsine
Ethylene dibromide
Chlordimeform
Pyriminil
Cholecalciferol
Naphthalene
Sodium chlorate
Arsine
Hexachlorobenzene
Creosote
Pyriminil
Pyriminil
Naphthalene
Sodium chlorate
Arsine
Sodium chlorate
Creosote
Coumarins
Indandiones
Sodium chlorate
Naphthalene
Arsine
Cadmium compounds
Phosphorus
Phosphides
Phosphine
Chlorophenoxy compounds
Creosote
Organotin compounds
Fluoride
Organotin compounds
Borate
Copper compounds
Phosphorus
Phosphides
Carbon tetrachloridc
Sodium fluoride
167
-------
SYSTEM
—Continued
MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN THESE
POISONINGS
Hypocalcemia
Hypercalcemia
Fluoride
Cholecalciferol
Thallium
Phosphorus
Phosphides
Repro-
ductive
system
Carboxyhemo-
globinemia
Hyperglycemia
Ketoacidosis
Anemia
Leukopenia,
thrombocyt-
openia
Elevated LDH,
GOT, OPT,
alkaline
phosphatase,
ALT, AST
enzymes
Depressed RBC
acetylcholin-
plasma pseudo-
cholinesterase
Low sperm count
Pyriminil
Pyriminil
Naphthalene
Sodium chlorate
Arsine
Inorganic arsenicals
Inorganic arsenicals
Carbon tetrachloride
Chloroform
Phosphine
Organophosphates
Dibromochloropropane
Methylene chloride
Organotin compounds
Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Sodium chlorate
Nitrophenols
Pentachlorophenol
Thallium
Organochlorines
Chlorophenoxy compounds
Carbamate insecticides
Kepone
168
-------
Index of Chemical and Product Names
Page
1080 116
2,3,6-TBA 84
2,4,5 trichlorophenoxyacetic acid 63
2,4,5-T 63
2,4-D 63
2,4-DB 63
2,4-dichlorophenoxyacetic acid 63
2,4-dichlorophenoxybutyric acid 63
2,4-dichIorophenoxypropionic acid 63
2,4-DP .„ 63
2-methyl-3,6 dichlorobenzoic acid 64, 84
2-methyl-4-chlorophenoxy aliphatic acids and
esters 64
4-Aminopyridine 148
4-Ap 148
A7 Vapam 98
AASTAR 1,34
AAtack ......*... 96
Aaterra... 113
AAtrex 86
Abate 2
Abathion 2
Abol „ 12
Acaraben 51 46
Acaricides 34
Accelerate , 154
Accotab 85
Accothion 2
acephate , 2
Acetamides 84
Acme Amine 4 63
Acme Butyl Ester 4 63
Acme LV 4 ....: 63
Acme LV 6 .^.. 63
Acrex., 68
Acricid 68
Acritet 132
acrolein 132, 135
acrylaldehyde 132, 135
Acrylofume 132
acrylonitrile 132
Actellic : 2
Acti-dione :...; 112
Actispray , 112
169
-------
Activol 33
Actor 76
Adjuvants 156
Afalon 87
Afesin 87
Aficida 12
Afugan 2
Agritox 1
Agrosan 105
Agrotect 63
Agrothion 2
Agroxone 64
Akar 46
Akzo Chemie Mancozeb 101
Akzo Chemie Maneb 101
alachlor 84
Alanox 84
alcohol sulfates :. 157
aldicarb 12
aldrin 17
Aldrite 17
Aliphatic acids 84
alkyl amine acetate 157
alkyl aryl sulfonates 157
alkyl phosphates 157
alkyl phthalates 52
alkyl sulfonates 157
Allethrin 34
allidochlor 84
Allisan 94
Alon 87
AIP 132
alpha-naphthyl thiourea 116, 126
alphametrin 34
Altosid CP-10 48
Altosid SR-10 48
aluminum phosphide 132
Amaze.. 1
Ambox 68
Ambush 34
Amerol 86
Ametrex : 85
ametryn 85
Amex 85
Amiben 84
Amine 2,4,5-T for rice 63
aminocarb 12
170
-------
Page
4-Aminopyridine 148
amino-triazole 86
Amiral 113
AmitroI-T 86
amitrole 86
Ammo 34
Amoxone 63
Anilazine : 111
Anilides 84
anisic acid derivatives 84
Ansar 170 56
Ansar8100 56
Anthio 2
Anticaking agents 157
Anticarie 90
Antimilace 146
ANTU 116, 126
4-Ap 148
Apachlor 1
Apex 5E 48
Aphox 12
Apl-Luster 113
Appex ... 2
aprocarb 12
Apron 25 WP 113
Aquacide 76
Aqua-Kleen 63
Aqualin 132
Aquathol 85, 154
Aquatin 108
Aquazine 86
Aquinite 132
Arbotect, 113
Arelon 87
Aresin 87
Aretit..... 68
Arresin 87
Arrhenal 56
Arsenal 85
Arsenic acid 55
Arsenic Compounds 54
Arsenic Trioxide 54
Arsenical Pesticides 54
arsenous oxide 54
Arsine ; 54
Arsinyl 56
Arsonate Liquid 56
171
-------
Page
aryl alkyl polyoxyethylene glycols 157
Asana 34
Aspon 2
Aspor 101
asulam 84
Asulox 84
Asuntol 1
AT-90 86
Atranex 86
Atratol 150
atraton 85
Atratone 85
Atrazine 86
Aules 96
Avadex 84
AvadexBW 84
Avicol 93
Avitrol 148
Azac 84
Azar 84
azinphos-methyl 1
Azodrin 1
Azolan 86
Azole 86
bacillus thuringiensis 32
Bactimos 32
Bactospeine 32
Bactur 32
Balan 85
Balfin 85
Banamite 161
Ban-Hoe 86
Banvel 64, 84
barban 84
Barricade 34
Barrier. 84
barthrin 34
Basagran 84
Basalin 85
Basanite 68
Basfapon 84
BASF-Maneb Spritzpulver 101
Bash 1
Batasan 108
Baygon 12
Bayleton 113
172
-------
Page
Bayrusil 1
Baytex 2
Baythion 2
Baythion-C 2
Baythroid 34
Beet-Kleen 84
Belgran.. 87
Belmark 34
bendiocarb 12
Benefin 85
Benex 112
benfluralin 85
Benlate 112
Benomyl 112
bensulide 2
bentazon 84
Benzac 84
Benzamide 84
benzene acetonitrile derivatives 157
Benzilan 46
Benzofuroline 34
Benzoic, anisic acid derivatives 84
Benzonitriles 84
benzothiadiazinone dioxide 84
Benzyl Benzoate 53
Berelex 33
Bermat 42
Betasan 2
Bexton 84
BH 2,4-D ",["''", 63
BH2.4-DP 63
BHC 17
Bicep 84
Bidrin 1
binapacryl 68
Biological Insecticides 25
biopermethrin 34
bioresmethrin.... 34
Birlane 1
Black Leaf 40 27
Bladafum •)
Bladex 86
Bo-Ana 1
Bolate "" 56
Bolero , 84
Bolls-Eye ,55
Bolstar 1
173
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Page
bomyl 1
Bophy 56
borates 39
borax 39
Bordeaux Mixture 103
Borea 86
Boric acid 39
boron trioxide 39
Botran 94
Botrilex 93
Bravo 95
Brestan 108
Brimstone 48
Brodan 1
brodifacoum 116
bromacil 86
bromadiolone 116
Bromax 86
Bromofume 132
Brom-O-Gas 132
Brom-O-Gaz 132
bromomethane 132
Bromone 116
bromophos 2
bromophos-ethyl 1
Brom-O-Sol 132
Broot 12
Bud-Nip 84
Bueno 6 56
bufencarb..; 1.2
Bug-Geta 146
Busan 1020 98
Butoxon 63
Butoxone 63
butralin 85
butylate 84
Butyrac 63
Bux 12
BW-21-Z 34
Cacodylic acid 56
Caddy 109
Cadminate 109
Cadmium chloride 109
Cadmium Compounds 109
Cadmium sebacate 109
Cadmium succinate 109
174
-------
Cadmium sulfate ..... ........... . ............................. •( QQ
Cad-Trete...: .................................. ZZZZZ""96, 109
! 16
. ...................... . ................ 56
Calcium acid methane arsonate ................................. 55
Calcium arsenate ............................................. ."."."."..... 55
Calcium Arsenite ............................................ .".......".". 54
Calcium Cyanamide ...................................... .""........". 149
Caldon ................................................ ............. gg
Caliber 90 ................ ............................... ' ............... 86
CAMA ......................................... ZZi:::::ZZi:: 56
Canadien 2000 [[[ 1 16
Can-Trol [[[ ............. ...... 64
Caparol [[[ "".....".... ......... 86
Captaf .................................................. !!"!!"™"""ZZ 102
Captafol [[[ ...... 102
Captan [[[ !....""."."........... 102
Captanex [[[ '"""" 1Q2
Carbacryl .................................................. ["."'".'.'.'.'. .......... 132
Carbamate (ferbam) ............................. ."."".'."."I""."!!!"" 99
Carbamate Herbicides .............................. ".".".""."....... 84
Carbamate Insecticides ................................................ -\ 2
Carbamult [[[ ................ 12
Carbanilates ....................... ................... ..."!!..."."....... 84
carbaryl.. ............................................... ......."...."... 12
Carbazinc ............................................. ....."."........"... ...... 99
carbofuran ............ . .............................. !."....."...."... ......... 12
carbon disulfide .......................................... ".".".'"."."."!.".' 1 32
carbon tetrachloride .................... . .......................... """ -132
carbophenothion .............................. . ......... "' .......... ..... -j
Carbyne ...................................... ""!!!"•!."".'.'.".'.".'."".".'.'.'.".'" 84
Carpene [[[ " 1 12
Carzol [[[ .................. _I2
Casoron ............................................... I!."."."!.".".".".'.' ........ 84
Castrix ............... ....... 116
CCN52 ....................... [[[ 34
CDAA .................................... izzz::::::::::::::::::::: 84
Cekiuron [[[ gg
CekuC.B ............................ .•...".'.'."!.'."."!!.'.'."".'.'.'.'.'.".'.'.'.'."! ....... 90
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Page
Celmer 105
Celmide 132
Ceresan 105
Certan 32
Chem Bam 101
Chem Fish - 30
Chem Pels C - 54
Chem Rice 84
ChemZineb 101
Chemox General 68
ChemoxPE 68
ChemsectDNBP 68
Chemsect DNOC 68
Chem-Sen 56 54
Chipco Thiram 75 96
Chipco Turf Herbicide "D" 63
chloramben 84
Chlordan -17
chlordane 17
chlordecone •• 17
chlordimeform 42
chlorfenvinphos 1
chlorimuron ethyl 86
chlorinated hydrocarbons 17
chlorinated solvents 158
chlormephos • 1
chlorobenzilate 46
chloroform . 132
Chloro-IPC 84
chloroneb 95
chlorophacinone 116
Chlorophen • 73
chlorophenothane 17
Chlorophenoxy Herbicides 63
Chlor-O-Pic , 132
chloropicrin 132
chloropyridinyl 85
Chlorothalonil 95
chlorotoluron - 86
Chloroxone 63
chloroxuron 86
chlorphoxim 2
chlorpropham 84
chlorpyrifos • 1
chlorthal-dimethyl 85
chlorthiophos 1
cholecalciferol 116, 127
176
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Page
Chrysron 34
cinerins 25
Ciodrin.... 2
cismethrin 34
Classic 86
Clifton Sulfur. "."."."".'. 48
cloethocarb 12
ClortoCaffaro 95
Clortosip 95
Cobex 85
Codal 84
Comite .. 44
Command 85
Compound 1080 116, 123
Contrac 1 is
Contraven •)
Copper acetate 103
Copper acetoarsenite 54
copper ammonium carbonate 103
Copper Arsenite 54
Copper carbonate 103
Copper Compounds 102
copper hydroxide 102
Copper lime dust 103
Copper linoleate 103
Copper naphthenate 103
Copper oleate 1Q3
copper oxychloride 103
Copper phenyl salicylate 103
copper potassium sulfide 103
copper quinolinolate 103
copper resinate 1Q3
copper silicate 103
copper sulfate 103
copper sulfate, tribasic 103
Co-Ral 1
Co-Rax 11 e
Corozate 99
Corry's Slug and Snail Death 146
Cosan 48
Cotoran 87
Cottonex 87
coumachlor -\-\Q
coumafene -\-\Q
coumafuryl , -\-\Q
coumaphos..... -\
Coumarins -\-\Q
177
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Page
coumatetralyl 116
Counter 1
Cov-R-Tox 116
Crab-E-Rad 56
Crag Turf Fungicide 531 109
Creosote 152
crimidine 116, 124
Crisalamina 63
Crisamina 63
Crisazina 86
Crisfolatan 102
Crisfuran 12
Crisquat 76
Crisuron 86
Crop Rider 63
Crossbow 85
Crotothane 68
crotoxyphos 2
crufomate 2
cryolite 37
Cuman 99
cupric oxide 102
Cuprous oxide 102
Curacron 2
Curamil 2
Curaterr 12
Curitan 112
Cyanamide 149
cyanazine 86
Cyanide 136
cyanofenphos 1
cyanophos 2
Cyanox 2
cyclethrin 34
cycloate 84
Cyclohexenone derivative 85
Cycloheximide 112
Cyclon 132
Cyflee 2
cyfluthrin 34
Cygon 2
cyhexatin 47
Cyian 1
Cymbush 34
Cymperator 34
Cyolane 1
Cyperkill 34
178
-------
cypermethrin 34
Cypona 2
Cyprex -J •) 2
Cyrux 34
cythioate 2
Cythion 2
Cytrol , ...!Z""™""i 86
Cytrolane -)
2,4-D 63
2,4-DB 63
D50 63
Dacamine 63
Daconate 6 . 55
Daconil 2787 95
Dacthal 35
Dailon 36
dal-apon 34
Dal-E-Rad ;. ""."!!"""".'." 56
Dalapon 34
Danitol ]]" 34
Dapacryl ...""!!!!!!..". 68
Dart 45
Dasanit -)
DBCP 132
DCNA 94
DCPA IZZZI 85
D-D 132
D-D92 132
ODD 17
DDT ::::::::::::::::::::::::::::: ^ 7
DDVP 1
Debroussaillant 600 '."'."".'.". 63
Decabane "_""" 34
decamethrin .".."." 34
Dechlorane ".""".". 17
Decis 34
Ded-Weed ;...Z"Z""ZZZ" 63, 84
Ded-Weed SULV 63
DEET ilZZI 49
DEF 2
DeFend ....[ "'" 2
De-Fol-Ate ""!!""!Z!""!!Z"!!Z! 150
Dettor !."!""!!.'""!!!! 37
DeGreen 2
Deiquat " 75
Delnav "...".'".'"!!""!!!! 1
179
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Page
deltamethrin 34
demeton "I
demeton-S-methyl 1
Denarin 113
Dervan , 15°
Des-i-cate 154
desmetryn 86
Desormone — 63
Dessicant L-10 55
Dessin • 68
Detamide 50
Dethdiet 116, 126
Devizeb 101
Dextrone • ^6
Dexuron 76
di-methyl naphthalene sulfonate 157
Di-on 87
Di-Tac 56
Diacon •• 48
dialifor - 1
diallate 84
Dianex • 48
Diaract • 45
Diater.. • 87
diatomaceous earth 157
diazinon • 2
Dibrom 2
dibromochloropropane 132
dibromoethane • 132
dibutylphthalate 52
Dicamba 64, 84
Dicarbam 12
dichlobenil 84
dichlofenthion 2
Dichloran • 94
dichloroethane 132
2,4-dichlorophenoxyacetic acid 63
2,4-dichlorophenoxybutyric acid 63
2,4-dichlorophenoxypropionic acid 63
dichloropropane 132
dichloropropene 132
dichloropropene plus dichloropropane 132
dichloropropionic acid 84
dichlorvos 1
dicofol • 17
dicrotophos 1
Dicuran .•• 86
180
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Page
dieldrin . 17
Dieldrite 17
dienochlor . 17
diethyltoluamide 49
difenacoum 116
difenoxuron . 86
Diflubenzuron 45
Difolatan 102
Dine ;;; 56
Dimecron 1
dimefox -)
dimephenthoate 2
dimetan 12
Dimethan 12
dimethoate 2
dimethrin 34
Dimethyl Phthalate !."""""" 52
Dimilin ; . 45
dinitramine 35
Dinitro., . @8
Dinitro General 68
Dinitro-3 68
Dinitro-amino-benzene derivatives 85
Dinitro Weed Killer 5 68
dinitrocresol . 68
Dinitrophenol 68
dinobuton 68
dinocap 68
Dinofen 68
dinopenton . 68
dinoprop 68
dinosam 68
dinoseb 68
dinoseb acetate 68
dinoseb methacrylate 68
dinosulfon 68
dinoterb 68
dinoterb acetate 68
dinoterb salts 68
dinoterbon 68
Dinoxol 63
Di-on 86
dioxacarb 12
dioxathion f
Dipel ""m""'m 32
diphacin
diphacinone
181
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Page
Cipher 101
Dipterex 2
Dipyridyls 76
Diquat 76
Direx 87
Dirimal... 85
Disodium arsenate 55
Disodium methane arsonate 56
disulfoton 1
Disyston 1
Di-Tac 56
DithaneM-22 101
DithaneM-45 101
Dithane 2-78 101
Dithione 1
ditranil 94
Diurex 87
Diurol 87
diuron 87
DLP-87 116, 126
DMA 56
DMA 4 63
DMP 52
DNAP 68
DNBP 68
DNC 68
DNOC 68
Dodine 112
Dojyopicrin 132
Dolochlor 132
Dormone 63
Dosaflo 87
Dosanex 87
Dotan 1
Dowpon 84
2,4-DP 63
DPA » 84
DPX 1410 12
Drat 116
Drawinol 68
Draza 12
Drexar530 56
Drexel Defol 150
Drinox 17
Drop-Leaf 150
v Drupina 90 , 99
DSE 101
182
-------
Du-Ter 108
Dual 34
Duraphos , -\
Duratox 1
Dursban -\
Outer ""'." 108
Dwell 113
Dycarb 12
Dyclomec 84
Dyfonate 1
Dylox 2
Dynamyte 68
Dyrene 111
E-48 1
E-601 1
E-S05 .'."!".'.'."!!!".'."!!" 1
Earthcide 93
Easy off-D 2
EBDC compounds 100
Ectiban 34
EDB Z!!!Z!!""!Z""™.'.""" 132
E-D-Bee 132
EDO .""I"!!!"";!.'""™";™;"";; ^ 32
edifenphos 1
Ekamet 2
Ekatin 2
Eksmin 34
Elgetol 30 ' 68
Elgetol 318 ' 68
Elocron 12
Embutox 63
emerald green 54
Emisan 6 105
Emulsamine BK 63
Emulsamine E-3 63
Emulsifiers 157
Endosan 68
endosulfan 17
endothall 35, 154
Endothall Turf Herbicide 154
Endothall Weed Killer !"....""...." 154
endothion 1
Endrin 17
Entex 2
Envert 171 . 63
183
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Page
Envert DT [[[ 63
EPBP [[[ 2
EPN ....................... . [[[ 1
epoxyethane ....................... . .......................................... ^32
Eptam [[[ 84
EPTC [[[ 84
Eradicane [[[ 84
Eraze [[[ 116
Erban [[[ 84
esfenvalerate [[[ 34
Esgram [[[ 76
Estone [[[ 63
ethalfluralin ................... . ................................................ 85
Ethanox ........................ .'. ................................................ 1
Bhazol .......................... : ................................................ 1 13
ethion [[[ 1
ethoprop [[[ 1
ethyl parathion [[[ 1
ethylan [[[ 17
Ethylene Bis Dithiocarbamates ................................... 100
ethylene dibromide [[[ 1 32
ethylene dichloride [[[ 132
ethylene oxide [[[ "I32
H OO
ETO [[[ 132
etrimfos [[[ 2
Etrofolan [[[ 1 2
Evik [[[ 85
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Page'
Fentin acetate 108
Fentin chloride 108
Fentin hydroxide 108
fenvalerate 34
Ferbam 99
Fermide 850 96
Fernasan 96
Fernesta 63
Fernimine 63
Fernos 12
Fernoxone 63
Ferxone 63
Ream 12
film extenders 156
Final 116
Flectron 34
Florocid 37
fluchloralin , 85
flucythrinate 34
fluometuron , 87
fluorides 37
Fluorodinitrotoluidine compounds 85
fluvalinate 34
FMC9044 68
Folbex 46
Folcord 34
Folex 2
Foliafume 30
Folosan 93
Folpan 102
Folpet 102
Foltaf 102
fonofos 1
formaldehyde 132
formalin 132
formetanate 12
formothion 2
Formula 40 63
Forron 63
Fortrol 86
fosamine ammonium 85
fosthietan 1
Fratol 116, 123
French green 54
Fumarin 116
Fumigants 131
Fumitoxin 132
185
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Page
Fundal 42
Fungicides • 89
Funginex "I "13
Fungitrolll 102
Fungostop "
Furadan 12
furethrin 34
Furloe 84
furmarin 116
Futura 32
G 28029 2
GAs 33
Galecron 42
Gallotox 105
gamma BHC 17
gamma HCH 17
Gardona 2
Gardoprim 86
Garlon 85
Gebutox 68
Gesafram 50 86
Gesagard 86
Gesamil 86
Gesapax 85
Gesatamin 85
Gesatop r 86
gibberellic acid 33
Gibberellin 33
Gibrel 33
Glifonox 85
Glycophene 112
glyphosate 85
Go-Go-San 85
Golden Dew 48
Goidquat276 76
Gordon's Amine 400 63
Gordon's Butyl Ester 600 v. 63
Gordon's Dymec Turf Herbicide Amine 2,4-D 63
Gordon's LV 400 2,4-D , 63
Gordon's Mecomec 64
Gordon's Phenaban 801 63
Graminon 87
Gramocil 76
Gramonol 76
Gramoxone 76
Gramuron 76
186
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Page
Qranurex 87
Graslan 87
Grazon 85
Griffex 86
Grocel 33
Gusathion 1
Guthion 1
Gypsine 55
Haipen 102
Haitin 108
Halizan 146
Halocarbon Fumigants 132
Hanane 1
Harvest-Aid 150
Havoc 116
HCB 90
Hedonal 63
Hedonal DP 63
Hel-Fire 68
Helothion 1
heptachlor 17
Heptagran 17
heptenophos 2
Herald 34
Herb-All 56
Herbalt 87
Herbaxon 76
Herbicide 273 154
Herbidal 63
Herbizole 86
Herbodox 85
Herboxone 76
hexachlorobenzene 90
Hexachlorocyclohexane 17
Hexadrin 17
Hexaferb 99
Hexathane 101
Hexathir 96
Hexazir 99
Hi-Yield Dessicant H-10 55
Hoe 002784 68
Hong Nien 105
Hostaquick 2
Hostathion 1
hydrocyanic acid 132
Hydrogen Cyanamide 149
187
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Page
hydrogen cyanide 132
Hydrothol 154
Hyvar 86
IBP 2
Igran 86
Imidan 2
Indandiones 116
indothrin 34
Inverton 245 63
iodofenphos 2
IP50 87
Iprodione 112
isofenphos 1
isolan 12
isomethiozin 86
Isopestox 1
isoprocarb 12
isopropalin 85
isopropanol 156
isoproturon 87
Isotox 17
isoxathior) 1
Isoxazolidinone 85
jasmolins 25
Jones Ant Killer 55
Kabat 48
Kack 56
Kafil 34
KafilSuper 34
Karathane 68
Karbation 98
Karmex '. - 87
Karphos 1
Kayafume 132
Kelthane 17
Kemate 111
Kepone ? 17
Kerb 84
Kildip 63
Kill-All 54
Kill-Ko Rat Killer 116
Kiloseb 68
Kitazin 2
Kiwi Lustr 277 94
188
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; Page
Klerat 116
Klorex 150
KM ! so
Knockmate 99
Koban , 113
Kobu 93
Kobutol 93
Kopfume 132
Kprlan 2
Krenite 85
Kromad 96,109
Kryocide 37
Krysid 116,123
Kumulus S 48
Kusatol 150
Kypfarin ne
Kypman 80 101
Kypzin 101
Lacco Sulfur 48
Lance 12
Landrin 12
Lannate 12
Lanox. 12
Larvacide 132
Lasso 84
Lawn-Keep 63
Lazb 84
Lead arsenate 55
lenacil 86
leptophos 1
Lexone QQ
lindane 17
Line Rider 63
Linex 4L 87
Linorox ..... 87
Linurex 87
linuron Q-J
Liphadione 116
Liqua-Tox 116
Liquid Sulfur 48
Liquiphene 105
Lironion 86
L.M91 "~I~2 116
Lonacol 101
Lorox „. 87
Lorsban ',. .„.
189
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Page
MM [[[ • ............ 56
Macondray [[[ 63
Magnetics [[[ 48
Maki [[[ 1 1 6
malathion [[[ 2
MAMA.... [[[ 56
Mancoze'b [[[ ^0
Mancozin [[[ 101
Maneb [[[ 10°
Maneba .............................. . ........................................... 101
Manesan [[[ 101
Manex [[[ • ...................... 101
ManexSO [[[ 101
Manzate [[[ 101
Manzate 200 [[[ 101
Manzate D [[[ 101
manzeb [[[ 1 01
Manzin [[[ 101
Maposol [[[ 98
Marlate [[[ 17
Matacil [[[ 12
Mavrik ....................................... : ..................................... 34
Mavrik Aquaflow ..................... '. ..................................... 34
MCPA [[[ 64
MCPB ........................... '. ................................................. 64
MCPP [[[ 64
M-Diphar [[[ 101
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Page
Metalaxyl 113
Metaldehyde 145
metalkamate 12
Metam-Fluid BASF 98
Metam-Sodium 93
Metason 146
Metasystox * 1
Metasystox (i) 1
Metasystox-R 1
Metasystox-S 1
metaxon 64
methabenzthiazuron 87
methamidophos 1
Metham-Sodium 98
Methane arsonic acid 56
methanol 155
Methar 30 56
methidathion 1
methiocarb 12
Meth-O-Gas 132
methomyl 12
methoprene 48
Methoxone M 64
methoxychlor , 17
Methoxyethyl mercury acetate 105
Methoxyethyl mercury chloride 105
Methoxyethyl Mercury Compounds. 105
methyl bromide 132
methyl carbamate insecticides 12
2-methyl-3,6 dichlorobenzoic acid 64
Methyl mercury acetate 105
Methyl mercury benzoate 105
Methyl Mercury Compounds 105
Methyl mercury hydroxide 105
Methyl mercury nitrile 105
Methyl mercury pentachlorophenate 105
Methyl mercury propionate.. 105
Methyl mercury quinolinolate 105
Methyl naphthalenes 157
methyl parathion 1
methyl trithion 2
methylene chloride 132
metobromuron 87
metolachlor 84
metoxuron 87
metribuzin 86
mevinphos 1
191
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Page
Mezene 99
MGK 50
MGK 264 155
Micromite 45
Microzul 116
Miller 531 109
Milogard 86
Milo-Pro 86
Minex 48
mipafox 1
MIPC 12
Miracle 63
mirex 17
mitis green 54
Mocap 1
Monitor • 1
Monoammonium methane arsonate 56
Mono-calcium arsenite 54
monocrotophos •—• 1
monolinuron 87
mono-methyl naphthalene sulfonate 157
Monosodium methane arsonate 56
Monuron • 87
Morocide 68
Morrocid 68
MSMA 56
Multamat 12
Mycodifol 102
N-2790 1
Nabam 100
Nabasan 101
naled .» 2
Namekil 146
naphthalene 132
naphthene 132
naramycin 112
NaTA 84
Neburex 87
neburon 87
Neguvon 2
Nemacur 1
Nemafume 132
Nemanax • 132
Nemaset 132
Nemasol 98
Nem-A-Tak 1
192
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Page
Nematocide 132
Nemispor 101
Neopynamin 34
Neosorexa PP580 116
Nephis 132
Netagrone 600 63
Nexagan 1
Nexion 2
NIA9044 68
nicotine 27
nicotine sulfate 27
nicotinic acid-isopropylamine derivative 85
Niomil 12
Nitrador.... 68
nitrochloroform 132
Nitrocresolic Herbicides 68
Nitrolime 149
Nitrophenolic Herbicides 68
Nitropone C 68
Nix 35
N-Methyl Carbamate Insecticides 12
N-Octyl Bicycloheptene Dicarboximide 155
No Bunt 90
Nomersam 96
Nomolt 45
norbormide 116, 126
Noxfire 30
Noxfish 30
NRDC 149 34
Nudrin 12
Nusyn-Noxfish 30
Nuvanol-N 2
Octyl bicycloheptene dicarboximide 155
OFF 50
Oftanol 1
Ofunack 2
Omite 44
OMPA... 1
OntracicSOO 86
Organochlorine Insecticides 17
Organomercury Compounds 105
Organophosphate Insecticides 1
Organotin Compounds 108
Orthene 2
Ortho Danitol 34
Ortho Diquat.... , 76
193
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Page
Ortho Paraquat CL 76
Ortho Paraquat Plus 76
Orthocide 102
oryzalin 85
Osaquat Super 76
Oust 87
Outflank 34
Ovatoxin 42
Oxadiazolinone 85
oxadiazon 85
oxamyl 12
oxirane 132
oxydemeton-methyl 1
oxydeprofos 1
Paarlan 85
Pamisan 105
Panogen 105
Panogen M 105
Pansoil 113
Paracide 132
Para-col 76
paradichlorobenzene 132
paraformaldehyde 132
Paraquat 76
parathion 1
Paris Green 54
Parzate 101
Parzate C 101
Pathclear 76
Patoran 87
Pattonex 87
Pay-off 34
PB-Nox 30
PCNB 93
PGP 73
P.C.Q 116
PDB 132
PDQ 64
PEBC 84
pebulate 84
Pencal 55
Penchlorol 73
pendimethalin 85
Penetrants 157
Penite 54
Pennamine D 63
194
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Page
Pennant 84
Penncap-M 1
Penncozeb 101
Penta 73
Pentac 17
Pentachloronitrobenzene 93
Pentachlorophenate 73
PentachlorophenoL. 73
Pentacon ; 73
Pentagen 93
Penwar 73
Permasect 34
permethrin 34
Perthane 17
Perthrine 34
PestoxXIV 1
PestoxXV 1
Petroleum distillates 157
Petroleum oils 157
petroleum sulfonates 157
Phalton 102
Pharorid 48
phencapton 2
Phenostat-A 108
Phenostat-C 108
Phenostat-H 108
phenthoate 2
Phentinoacetate 108
Phenyl mercuric acetate 105
phenyl mercury ammonium acetate 105
Phix 105
phorate 1
phosalone 2
Phosdrin 1
phosfolan 1
phosmet 2
phosphamidon 1
phosphides 121
phosphine 132
Phosphonates 85
phosphorus compounds 121
phostoxin 132
Phosvel 1
Phosvin 116, 120
phoxim 2
phthalates 85
phthalthrin 34
195
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Page
Phytar 560 56
Pic-CIor 132
picloram 85
picolinic acid compound 85
Pillarquat 76
Pillarxone 76
pindone 116
Piperonyl Butoxide 155
pirimicarb 12
pirimiphos-ethyl 2
pirimiphos-methyl 2
Pirimor 12
Pivacin 116
pival 116
pivaldione 116
Pivalyn 116
Place-Pax 116
Planotox 63
Plantgard 63
Plictran 47
PMAA 105
PMAS 105
PMP Tracking Powder 116
Poast 85
Policar MZ 101
Policar S 101
Polybor 39
polyesters of sodium thiobutane dioate 157
polyethoxylated fatty acid esters 157
polyethylene glycol 157
polyhydric alcohols 157
Polymone 63
polyol fatty acid esters 157
polyoxyethylene oleate 157
Polyram M 101
Polyram-Ultra 96
Polyram Z 101
Polytrin 34
Pomarsol forte 96
Pounce 34
PP581 116
Pramex 34
Pramitol25E 86
Prebane 86
Precor ! 48
Preeglone 76
Prefar 2
196
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Page
Preglone 76
Premerge 3 68
Prentox 30
Priglone , 76
Primagram 84
Primatol M 86
Primatol P 86
Primatol Q 86
Primatol S 86
Primextra , 84
Primicid 2
Primin 12
Princep 86
Proban 2
Prodalumnol Double 54
Prodan 37
Prodaram 99
profenofos , 2
profluralin 85
Pro-Gibb 33
Pro-Gibb Plus 33
Prolate 2
prolin 116
promecarb 12
prometon. 86
Prometrex 86
prometryn 86
pronamide 84
propachlor 84
Propanex 84
propanil 84
propargite 44
propazine 86
propenal 132
propetamphos 1
propoxur 12
propylene oxide 132
propyl thiopyrophosphate 2
prothoate 1
Prowl 85
Proxol 2
prussic acid 132
Purivel..., 87
Pydrin 34
Pynamin 34
Pynosect 34
Pyradex 84
197
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pyrazophos 2
pyrethrins 25
pyrethroids 34
pyrethrum 25
pyridaphenthion 2
pyriminil 116, 126
Pyrobor 39
Quilan.: 85
quinalphos 1
Quintox 116, 127
quintozene 93
Racumin 116
Rad-E-Cate 25 56
radione 116
Rampage 116, 127
Rampart 1
Ramrod 84
Ramucide 116
Randox 84
Rapid 12
Ratak 116
Ratak Plus 116
Raticate 116, 126
Ratilan 116
Ratimus 116
Ratomet 116
Raviac 116
RAX 116
red squill 116, 126
Reglone 76
Reglox 76
Regulex 33
Remasan Chloroble M..., 101
Repellents 34
Resisan 94
resmethrin 34
Revenge 84
RH-787 116, 126
Rhodianebe "... 101
Rhothane 17
Ridall-Zinc 116, 120
Ridomil 113
Ripcord 34
Riselect 84
Rodent Cake 116
198
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Page
Roderrticides 115
Rodex 116
Rodex-Blox us
Rodine 116, 126
Rody , 34
Ro-Neet 84
ronnel 2
Ronstar 85
Rotacide 30
rotenone 30
Rotenone Solution FK-11 30
Roundup 85
Rout (bromacil and diuron) 86, 87
Rovral 112
Rozol 11 e
Ruelene 2
sabadilla 31
Safeners 157
Safrotin 2
Safsan 37
Salvo (contains either arsenic) p. 56, or 2, 4-D 63
Sanspor 102
Santophen 73
Saprol 113
Sarclex 87
Saturn 84
schradan 1
Schweinfurt green 54
Scilliroside 115
Scout 34
Seedtox 105
Selinon 68
Semeron 86
Sencor 86
Sencoral 86
Sencorex 86
Seritox 50 63
sethoxydim 85
Setrete 105
Sevin 12
Shimmer-ex 105
Shoxin 116, 126
siduron 87
simazine 86
Simazol 86
Sinbar 86
199
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Page
Sinituho 73
Sinox 68
Sinox General 68
Siperin 34
Skeetal -..., 32
Sodar 56
Sodium alkyl butane diamate 157
sodium aluminofluoride 37
Sodium arsenate 55
Sodium Arsenite 54
sodium biborate 39
sodium cacodylate 56
Sodium Chlorate 150
Sodium fluoaluminate 37
Sodium fluoride 37
sodium fluoroacetate 116,123
Sodium fluosilicate 37
sodium pentaborate 39
sodium pentachlorophenate 73
sodium silico fluoride 37
sodium tetraborate decahydrate 39
Sofril 48
Sok-Bt 32
Solasan 500 98
Solvents 156
Sometam 98
Sonalan 85
Soprabel 55
Sopranebe 101
Spectracide 2
Spike 87
Spotrete WP 75 96
Spotrete-F 96
Spra-cal 55
spreaders 156
Spring Bak 101
Spritz-Hormin/2,4-D 63
Spritz-Hormit/2,4-D 63
Sprout-Nip 84
Spur 34
S-Seven 2
Stam 84
Stampede 84
Stickers 156
Stirofos 2
Stomp 85
Strobane 17
200
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Strobane-T. 17
strychnine 116, 123
Subdue 2E 113
Subitex 68
Substituted Benzenes 90
Sul-Cide 48
Sulerex 87
Sulfated alcohols 157
Sulfex 48
sulfometuron methyl 87
sulfotep 1
sulfur 48
sulfur dioxide 132
sulfuryl fluoride 132
sulprofos 1
Sumicidin 34
Sumithion 2
Super Crab-E-Rad-Calar 56
Super D Weedone 63
Super Dal-E-Rad 56
Supernox 84
Superormone Concentre 63
Supracide .. 1
Surecide 1
Surflan 85
Surpass . 84
Surpur 84
Sutan 84
Suzu 108
Suzu-H. , . 108
Swat 1
Sweep 76
Syllit 112
Synergists 155
Synthrin ; 34
Systox 1
2,4,5-T ; 63
Tag HL331 105
Talan 68
Talbot..., , 55
talc 156
Talcord ;. 34
Talon 116
Tamex 85
Tamogam ne
Tantizon „.... 86
201
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Target MSMA 56
Tattoo 12
2,3,6-TBA 84
TBZ 113
TCA 84
TCBA 84
TDE 17
tebuthiuron 87
Tecto 113
Teflubenzuron 45
Teknar... 32
Telone II Soil Fumigant 132
temephos 2
Temik 12
1080 •• 116
Tenoran 86
TEPP • 1
terbacil 86
terbucarb 84
terbufos 1
terbuthylazine 86
Terbutrex 86
terbutryn 86
terpene polychlorinates 17
Terraclor 93
Terraklene 76
Terraneb SP 95
Terrazole 113
Terra Ant Killer 55
Terr-O-Gas 132
Tersan 112
tetrachlorvinphos 2
tetraethyl pyrophosphate 1
tetrafluoron 87
tetramethrin 34
Tetrapom 96
Thallium 116, 120
thallium sulfate 116, 120
Thiabendazole 113
Thibenzole 113
Thimer 96
Thimet 1
thiobencarb 84
Thiocarbamates 84,96
Thiodan .' 17
Thioknock 96
Thiolux 48
202
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Page
thiometon 2
Thion 48
Thiophal 102
Thiophos 1
Thiophthalimides 102
Thiotepp 1
Thiotex 96
Thiovit 48
Thiram '. 96
Thiramad 96
Thirasan 96
Thistrol i 64
Thiuramin 96
Thuricide 32
Tiezene 101
Tiguvon ;.. 2
Tilcarex 93
Tillam 84
Tinestan 108
Tinmate 108
Tirampa 96
TMTD 96
TMTDS 96
T-Nox • 63
Tolban 85
Tolkan 87
toluene 155
Tolurex 86
Tomarin 116
Tomilon 87
Tomorin 116
Topitox 116
Torak ., 1
Tordon 85
Tota-col 76
Toxakil 17
toxaphene .'. 17
Toxer Total 76
Tox-Hid 116
TPTA 108
TPTH 108
TPTOH 108
TR-10 85
tralomethrin ; 34
Trametan 95
Transamine 63
Trans-Vert 56
203
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Page
Treflan 85
Triadimefon "I "13
triallate 84
Triasyn 111
Triazines - 85
Triazole 86
triazophos 1
Tribac 84
Tribactur 32
Tri-ban 116
Tribunil 87
Tributon 63
Tricalcium arsenate 55
Tricarbamix Z 99
trichlorfon » 2
trichloroacetic acid 84
trichlorobenzoic acid 84
trichloromethane 132
trichloronate 1
2,4,5 trichlorophenoxy acetic acid 63
triclopyr 85
Tri-Clor 132
Tricyclohexyl tin hydroxide 47
trifluralin • 85
Trifocide 68
Triforine 113
Trifungol 99
Trimangol 101
Trimaton 98
trimethacarb 12
Trinoxol 63
Tri-PCNB 93
TriphenylTin 108
Triple Tin 108
Tripomol • 96
Triscabol 99
Trithion 1
Tritoftorol 101
Truban 113
Tuads 96
Tuban 63
Tubothane 101
Tubotin 108
Tuffcide 95
Tupersan .". 87
Turcam 12
Turf-Cal 55
204
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Page
Turflon 85
U46. . 63
U 46 D-Ester 63
U 46 D-Fluid 63
U 46 DP-Fluid 63
Ultracide 1
Unicrop-CIPC 84
Unicrop DNBP 68
Unicrop Maneb 101
Unidron '. 87
Uriiroyal DO14 44
Unisan.... 105
Uracils 86
Uragan 86
Urea derivatives 86
Urox B ;..- 86
Ustaad 34
Vacor 116,126
valone 116
VancideMZ-96 99
Vancide TM 96
Vapam 98
Vapona 1
Varitox 84
VC-13 Nemacide 2
VectaISC 86
Vectobac 32
Venturol 112
Venzar ; 86
Veratrin 31
vernolate 84
Vertac 68
Vertac General Weed Killer 68
Vertac Selective Weed Killer 68
Vi-Cad 109
Vikane 132
Volid 116
Vondcaptan 102
Vondodine 112
Vondozeb Plus 101
Vonduron , 87
VPM 98
VydateL 12
warfarin 116
205
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Warfarin Q 116
Warfarin Q Concentrate 116
Wax Up 85
WBA 8107 116
Weed Tox 63
Weed-B-Gon 63
Weed-E-Rad 56
Weed-E-Rad 360 56
Weed-Hoe 56
Weed-Rhap 63
Weedar 63
Weedatul 63
Weedazol 86
Weedol 76
Weedone 63
Weedone DP , 63
Weedone 170 63, 64
Weedtrine-D 76
Weedtrol 63
White Arsenic 54
white phosphorus 119
xylene 156
Yasoknock 116,123
yellow phosphorus 116,119
Zebtox 101
Zerlate 99
Ziman-Dithane 101
Zinc arsenate 55
zinc phosphide 116, 120
Zinc-Tox 1"16, 120
Zincmate .-. 99
Zineb 100
Zineb 75 WP 101
Zinosan 101
Ziram 99
Ziram F4 99
Ziram Technical 99
Ziram W76 99
Ziramvis 99
Zirasan 90 99
Zirberk 99
Zirex90 99
Ziride 99
Zitox 99
206
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