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United States
Environmental Protec EPA-540/9-80-005 1982
Agencv
vvEPA Recognition and
Management of
I < Pesticide Poisonings
Third Edition
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RECOGNITION AND MANAGEMENT OF
PESTICIDE POISONINGS
Donald P. Morgan, M.D., Ph.D.*
Support for this publication was provided by the National
Pesticide Hazard Assessment Program, Health Effects
Branch, Hazard Evaluation Division, Office of Pesticide
Programs, U.S. Environmental Protection Agency, Wash-
ington, D.C. 20460.
*lowa Pesticide Hazard Assessment Project, located at University of
Iowa Medical School, Iowa City, Iowa 52240.
Third Edition
US [iV.vi-onrf.pntcil Promotion Agency
Re-p..on V, Lici'.'.y
2'0 ^'.•,:!-, 0 V'ibo.'r; ociCGt. -_ .,-•
Chicago, iiiinois 60604.
For sale by the Superintendent of Documents, U.S Government Printing Office, Washington, D.C. 20402
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U,S. Environmental Protection Agency
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Contents
Page
INTRODUCTION v
CHAPTER 1—ORGANOPHOSPHATE
CHOLINESTERASE-INHIBITING
PESTICIDES 1
CHAPTER 2—CARBAMATE CHOLINESTERASE-
INHIBITING PESTICIDES 9
CHAPTER 3—SOLID ORGANOCHLORINE
PESTICIDES 14
CHAPTER 4—PENTACHLOROPHENOL 19
CHAPTER 5—NITROPHENOLIC AND
NITROCRESOLIC HERBICIDES .... 23
CHAPTER 6—CHLOROPHENOXYCOMPOUNDS.. 27
CHAPTER 7—PARAQUAT AND DIQUAT 31
CHAPTER 8—DITHIOCARBAMATES AND
THIOCARBAMATES 36
CHAPTER 9—PYRETHRUM, PYRETHRINS,
PYRETHROIDS AND PIPERONYL
BUTOXIDE 42
CHAPTER 10—ARSENICAL PESTICIDES 46
CHAPTER 11—RODENTICIDES 54
CHAPTER 12—FUMIGANTS 68
CHAPTER 13—MISCELLANEOUS PESTICIDES OF
HIGHTOXICITY 77
CHAPTER 14—MISCELLANEOUS PESTICIDES OF
LOW OR MODERATE TOXICITY .... 82
INDEX TO PESTICIDE POISONINGS BY
SYMPTOMS AND SIGNS 88
PESTICIDE INDEX 94
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INTRODUCTION
This manual is designed to help professionals responsible for the health of
persons exposed to pesticides to recognize and treat properly poisonings by
these substances. This third edition discusses many more compounds than
were dealt with in previous editions, and it updates particular management
methods according to recently published clinical literature.
No text or manual on so complex a topic can presume to take the place of
good clinical judgment. But it is unrealistic to expect health professionals con-
fronted with a pesticide poisoning emergency to assemble quickly the many
details of toxicology, diagnosis, and treatment that are essential to optimal
management. This manual provides such information in a concise format.
A deliberate effort has been made to suggest treatment that can be imple-
mented (or at least initiated) in small hospitals and clinics where victims of
pesticide poisonings are likely to be received. At the expense of some repeti-
tion, details of treatment have been spelled out sequentially for the common
classes of chemical poisonings.
The author is deeply indebted to the following reviewers who have con-
tributed generously to this edition:
S. H. Sandifer, M.D., Professor J. R. Reigart, M.D., Assoc. Professor
Director, Division of Preventive Medicine Department of Pediatrics
Department of Family Practice College of Medicine
College of Medicine Medical University of South Carolina
Medical University of South Carolina Charleston, South Carolina 29403
Charleston, South Carolina 29403
Harold E. Trammel, Pharm.D., Assoc. Prof. John E. Davies, M.D., M.P.H.
Director of Poison Information Center Professor and Chairman
College of Pharmacy Department of Epidemiology
Medical University of South Carolina and Public Health
Charleston, South Carolina University of Miami School of Medicine
Arthur D. Nelson, M.D. Jon E. Ford, Ph.D.
Director Environmental Toxicologist
Scottsdale Memorial Hospital Chevron Environmental Health Center
Scottsdale, Arizona Standard Oil Company of California
Victor B. Beat, D.V.M., of the Iowa Pesticide Hazard Assessment Project
compiled the many proprietary names of the products listed in the manual.
Mrs. Pamela Mason and Ms. Diane Cornwall of the Iowa Project have pa-
tiently typed the manuscript drafts.
Ms. Martha Finan of the Information Support Services Branch, Manage-
ment Support Division, Office of Pesticides and Toxic Substances of the
United States Environmental Protection Agency has skillfully edited the
manuscript. Staff of the Health Effects Branch, Hazard Evaluation Division
of the Office of Pesticides and Toxic Substances, United States Environmental
Protection Agency, have prepared the index and attended to the details of
publication.
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Chapter 1
ORGANOPHOSPHATE
CHOLINESTERASE-INHIBITING
PESTICIDES
GENERAL CHEMICAL STRUCTURE
C2H5O or CH3O \ ^ S (or O)
. P
C2H5OorCH3O
COMMON COMMERCIAL PESTICIDE PRODUCTS*
Highly toxic: tetraethyl pyrophosphate (TEPP), phorate (Thimet), disulfo-
tonf (Di-Syston), fensulfothion (Dasanit), demetont (Systox), terbufos
(Counter), mevinphos (Phosdrin), methidathion (Supracide), chlormephos
(Dotan, MC2188), sulfotepp (Bladafum, Dithione), chlorthiophos
(Celathion), monocrotophos (Azodrin), fonofos (Dyfonate), prothoate (Fac),
fenamiphos (Nemacur), phosfolan (Cyolane), methyl parathion (Dalf,
Penncap-M), schradan (OMPA), chlorfenvinphos (Birlane), ethyl parathion
(Parathion, thiophos), azinphos-methyl (Guthion), phosphamidon
(Dimecron), methamidophos (Monitor), dicrotophos (Bidrin), isofenphos
(Amaze, Oftanol), bomyl (Swat), carbophenothion (Trithion), EPN, fam-
phur, (Warbex, Bo-Ana, Famfos), fenophosphon (Agritox, trichloronate),
dialifor (Torak), cyanofenphos (Surecide).
Moderately toxic: bromophos-ethyl (Nexagan), leptophos (Phosvel),
dichlorvos (DDVP, Vapona), coumaphos (Co-Ral), ethoprop (Mocap),
quinalphos (Bayrusil), triazophos (Hostathion), demeton-methylt
(Metasystox), propetamphos (Safrotin), chlorpyrifos (Lorsban, Dursban),
sulprofos (Bolstar), dioxathion (Delnav), isoxathion (Karphos), phosalone
(Zolone), thiometon (Ekatin), heptenophos (Hostaquick), crotoxyphos
(Ciodrin), cythioate (Proban), phencapton (G28029), DBF (De-Green, E-Z-
off D), ethion, dimethoate (Cygon, De-Fend), fenthion (Baytex, Entex,
Tiguvon, Spotton, Lysoff), dichlofenthion (Mobilawn), EPBP (S-Seven),
These are listed approximately in order of descending toxicity. "Highly
toxic" organophosphates have listed oral LD50 values (rat) less than 50
mg/kg; "moderately toxic" agents have LD50 values in excess of 50 mg/kg.
These organophosphates are systemic; i.e., they are taken up by the plant
and translocated into foliage and sometimes into the fruit.
1
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diazinon (Spectracide), phosmet (Imidan, Prolate), formothion (Anthio), pro-
fenofos (Curacron), naled (Dibrom), phenthoate, trichlorfon (Dylox, Dipterex,
Neguvon), pyrazophos (Afugan, Curamil), fenitrothion (Agrothion,
Sumithion), cyanophos (Cyanox), pyridaphenthion (Ofunack), propylthio-
pyrophosphate (Aspon), acephate (Orthene), merphos (Folex), malathion
(Cythion), etrimfos (Ekamet), phoxim (Baythion), pirimiphosmethyl (Actellic),
iodofenphos (Nuvanol-N), bromophos (Nexion), tetrachlorvinphos (Gardona,
Rabon), temephos (Abate, Abathion).
TOXICOLOGY
Organophosphates poison insects and mammals primarily by phosphoryla-
tion of the acetylcholinesterase enzyme at nerve endings. The enzyme is critical
to normal transmission of nerve impulses from nerve fibers to innervated
tissues. Some critical proportion of the tissue enzyme mass must be inactivated
by phosphorylation before symptoms and signs of poisoning are manifest. At
sufficient dosage, loss of enzyme function allows accumulation of
acetylcholine (the impulse-transmitter substance) at cholinergic neuroeffector
junctions (muscarinic effects), and at skeletal myoneural junctions and in
autonomic ganglia (nicotinic effects). Organophosphates also impair nerve im-
pulse transmission in the brain, causing disturbances in sensorium, motor
function, behavior, and respiratory drive. Depression of respiration is the
usual cause of death in organophosphate poisoning. Recovery depends ulti-
mately on generation of new enzyme.
Organophosphates are efficiently absorbed by inhalation, ingestion, and
skin penetration. To a degree, toxicity depends on the rate at which specific
Organophosphates are metabolized in the body (principally by hydrolysis in the
liver), thus limiting the amount of pesticide available to attack
acetylcholinesterase enzyme in other tissues.
Many Organophosphates readily undergo conversion from -thions to -oxons
(replacement of sulfur by oxygen). In general, -oxons are much more toxic
than -thions. This conversion occurs in the environment under the influence of
sunlight and in the body, mainly by the action of liver microsomes. Ultimate-
ly, both -oxons and -thions are inactivated by hydrolysis at the ester linkage,
yielding alkyl phosphates and phenols which are readily excreted. The
hydrolysis products present little toxic hazard.
One to two days after organophosphate absorption, depending on the
specific organophosphate, some phosphorylated acetylcholinesterase enzyme
can be de-phosphorylated (reactivated) by certain oxime antidotes. After this
interval, the nature of the enzyme-phosphoryl bond changes, rendering the
enzyme inactivation irreversible. New enzyme must then be generated.
Very rarely, organophosphate pesticides have produced a different type of
neurotoxicity, consisting of damage to the myelin substance of peripheral
nerves. This leads to a protracted peripheral neuropathy, characterized by
numbness, pain, and weakness in the extremities, which persists for months or
years. Organophosphates associated with these chronic illnesses have included
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some whose acute toxic potential is low; i.e., there appears to be no relation-
ship between acute toxicity and the likelihood of a chronic neuropathic effect.
Particularly suspect as neurotoxic agents of this type are the phenylphospho-
nothioate series, cyanofenphos, EPN, leptophos, and EPBP.
Other unusual properties of specific 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 catabolism, thus enhancing its toxicity. Certain organophosphates
are exceptionally prone to storage in fat tissue, prolonging the need for an-
tidote when stored pesticide is released back into the circulation. It is possible
that other unrecognized factors modify the toxicity of organophosphates.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
Symptoms of acute poisoning develop during exposure or within 12 hours
(usually within four hours) of contact. HEADACHE, DIZZINESS, WEAK-
NESS, INCOORDINATION, MUSCLE TWITCHING, TREMOR, NAUSEA,
ABDOMINAL CRAMPS, DIARRHEA, and SWEATING are common early
symptoms. Blurred or dark vision, confusion, tightness in the chest, wheezing,
productive cough, and PULMONARY EDEMA may occur. Incontinence, un-
consciousness and convulsions indicate very severe poisoning. SLOW
HEARTBEAT, salivation, and tearing are common. TOXIC PSYCHOSIS,
with manic or bizarre behavior, has led to misdiagnosis of acute alcoholism.
Slowing of the heartbeat may rarely progress to complete sinus arrest. RESPI-
RATORY DEPRESSION may be fatal. Continuing daily absorption of
organophosphate at intermediate dosage may cause an INFLUENZA-LIKE
ILLNESS characterized by weakness, anorexia, and malaise.
The very few individuals who have suffered peripheral neuropathy follow-
ing organophosphate exposure exhibited diverse clinical courses. Onset of
symptoms was generally slow, sometimes after an asymptomatic interval of
several days following exposure. Principal symptoms have been numbness,
tingling, pain and weakness of the arms and legs. Some recovered fully in a
few weeks; a few others experienced muscle atrophy, leaving a degree of
paresis and sensory loss.
CONFIRMATION OF DIAGNOSIS
CAUTION: If there are strong clinical indications of organophosphate
poisoning, treat patient immediately. DO NOT WAIT for
laboratory confirmation.
Depressions of plasma pseudocholinesterase and/or RBC acetylcholinester-
ase enzyme activities are the most satisfactory and generally available bio-
chemical indices of excessive organophosphate absorption. A minimum
amount of organophosphate must be absorbed to depress blood cholinesterase
activities, but activities are lowered by dosage considerably less than are re-
quired to cause symptomatic poisoning. The enzyme depression is usually ap-
parent immediately after, or within 12-24 hours of, significant absorption of
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organophosphate. Depression of the plasma enzyme generally persists several
days to a few weeks; the RBC enzyme activity usually remains depressed
longer, sometimes 1-3 months. Table 1 lists APPROXIMATE LOWER
LIMITS OF NORMAL FOR PLASMA and RBC CHOHNESTERASE AC-
TIVITIES of human blood, measured by generally available methods.
LOWER LEVELS usually indicate excessive absorption of a cholinesterase-
inhibiting chemical. Whenever possible, comparison of the test sample with a
pre-exposure value offers the best confirmation of organophosphate absorp-
tion: a depression of 25% or more is strong evidence of excessive absorption.
In certain conditions, the activities of plasma and RBC cholinesterase are
depressed in the absence of chemical inhibition. About 3% of individuals have
a genetically determined low level of plasma cholinesterase. These persons are
particularly vulnerable to the action of cholinesterase-inhibiting pesticides and
to the drug succinylcholine, often administered to surgical patients. Patients
with advanced liver disease, malnutrition, chronic alcoholism and dermato-
myositis exhibit low plasma cholinesterase activities. A number of toxicants,
notably carbon disulfide, benzalkonium salts, organic mercury compounds,
ciguatoxins, and solanines may reduce plasma pseudocholinesterase activity.
The RBC acetylcholinesterase is less likely than the plasma enzyme to be af-
fected by factors other than organophosphates. It is reduced, however, in cer-
tain conditions that damage the red cell membrane, such as hemolytic
anemias.
The alkyl phosphates and phenols to which organophosphates are hydro-
lyzed in the body can often be detected in the urine during pesticide absorption
and up to 48 hours thereafter. These analyses are useful in identifying the ac-
tual pesticide to which workers have been exposed. Alkyl phosphate and
phenol analyses can demonstrate organophosphate absorption at lower
dosages than those required to depress cholinesterase activities.
Detection of intact organophosphates in the blood is usually not possible ex-
cept after extreme exposures, such as ingestions of pesticide. Few organophos-
phates remain unhydrolyzed in the blood more than a few minutes or hours,
unless the quantity absorbed is extraordinary or the hydrolyzing liver enzymes
are inhibited.
TREATMENT
CAUTION: Persons attending the victim should avoid direct contact
with heavily contaminated clothing and vomitus. Wear
rubber gloves while washing pesticide from skin and hair.
1. Establish CLEAR AIRWAY by aspiration of secretions. Administer
OXYGEN by mechanically assisted pulmonary ventilation. Improve
tissue oxygenation as much as possible before administering atropine to
minimize the risk of ventricular fibrillation.
2. Administer ATROPINE SULFATE intravenously, or intramuscularly, if
IV injection is not possible. Atropine protects the muscarinic end-organs
from excessive concentrations of acetylcholine. It does not reactivate the
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TABLE 1. Approximate Lower Limits of Normal Plasma and Red Cell
Cholinesterase Activities in Humans*
METHOD
A pH (Michel)
pH Stat (Nabb-
Whitfield)
ChE-tel (Pfizer)
A ChE-tel (Pfizer)
BMC Reagent Set
(Ellman-Boehringer)
1-Test Cholinesterase
(EM Diagnostics)
Acholest Test Paper
Dupont ACA
Garry-Routh (Micro)
Merckotest
GLC Method
(Cranmer)
Technicon
PLASMA RBC
0.45 0.55
2.3
40
1875
3.6
>20
< 8
2.1
2.0
WHOLE
BLOOD
8.0
210
Male 7.8
Female 5.8
3.0
8.2
8.0
UNITS
A pH per hr per ml
per min per ml
ChE-tel units
A ChE-tel units
3000 mU per min per ml
Units per ml
Minutes
Units per ml
/xM-SH per 3 min
per ml
Units per ml
per min per ml
per min per ml
* Because measurement technique varies among laboratories, more accurate
estimates of minimum normal values are usually provided by individual
laboratories.
Cholinesterase enzyme. Recrudescence of poisoning may occur if tissue
concentrations of organophosphate remain high when the effect of
atropine wears off. Atropine is the ideal antidote for muscarinic manifes-
tations; it is ineffective against nicotinic actions: muscle weakness and
twitching, and respiratory depression.
In MODERATELY SEVERE poisoning:
Adult dosage, including 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 poison-
ing. Rales in the lung bases indicate inadequate atropinization. Miosis,
nausea, bradycardia, and other cholinergic manifestations are also in-
dicative.
Dosage for 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.
SEVERELY POISONED individuals may exhibit remarkable tolerance
to atropine; two or more times the dosages suggested above may be
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needed. Persons not poisoned or only slightly poisoned, however, may
develop signs of atropine toxicity from such large dosages: FEVER,
muscle fibrillations, and delirium are the main signs of atropine toxicity.
If these signs appear while the patient is fully atropinized, atropine
administration should be discontinued, at least temporarily.
3. Draw a BLOOD SAMPLE for PLASMA and RBC CHOLINESTERASE
analysis.
4. Administer PRALIDOXIME (Protopam®-Ayerst, 2-PAM) in cases of
severe poisoning by organophosphate pesticides in which respiratory
depression, muscle weakness and twitchings are severe. When adminis-
tered early (usually less than 36 hours after poisoning) pralidoxime
relieves the nicotinic effects of poisoning.
Note: Pralidoxime is of questionable value in poisonings by the cholin-
esterase-inhibiting carbamate compounds. (See Chapter 2).
Adult dosage (including children over 12 years): 1.0 gm intravenously at
no more than 0.5 gm per minute.
Child's dose (under 12 years): 20-50 mg/kg (depending 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.
Note: slow administration of pralidoxime is strongly recommended,
and may be achieved by administering the total dose in 250 ml
5% glucose solution over 30-60 minutes.
If intravenous injection is not possible, pralidoxime may be given by
deep intramuscular injection.
CAUTION: Be prepared to assist pulmonary ventilation mechanically
if respiration is depressed during and after pralidoxime in-
jection.
5. 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 wears off. In very severe poisonings by ingested
organophosphates, particularly the more lipophilic and slowly hydro-
lyzed compounds, metabolic disposition of toxicant may require as many
as 5-10 days, during which atropinization must be maintained. 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.
6. BATHE and SHAMPOO victim with soap and water if there is any
chance that SKIN and HAIR are contaminated.
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7. IF PESTICIDE HAS BEEN INGESTED in quantity sufficient to cause
poisoning, empty the stomach and intestine.
A. IF victim is ALERT and respiration is not depressed, give SYRUP
OF IPECAC, followed by 1-2 glasses of water to induce vomiting.
Adults (12 years and over): 30 ml; children under 12 years: 15 ml.
CAUTION: OBSERVE victim closely AFTER administering
IPECAC. If consciousness level declines, or if vomit-
ing has not occurred in 15 minutes, proceed immedi-
ately to INTUBATE the stomach.
Following emesis, have victim drink a suspension of 30-50 gm
ACTIVATED CHARCOAL in 3-4 ounces of water to limit absorp-
tion of toxicant remaining in the gut.
B. IF victim is OBTUNDED or respiration is depressed, empty stomach
by INTUBATION, ASPIRATION, and LAV AGE, using isotonic
saline or 5% sodium bicarbonate. Because many pesticides are
dissolved in petroleum distillates, emesis and intubation of the
stomach involve a serious risk that solvent will be aspirated, leading
to chemical pneumonitis. For this reason:
(a). If victim is unconscious or obtunded and facilities are at hand,
insert ENDOTRACHEAL TUBE (cuffed, if available) prior
to gastric intubation.
(b). Keep victim's HEAD BELOW LEVEL OF STOMACH dur-
ing intubation and lavage (Trendelenburg, or left lateral
decubitus, with head of table tipped downward). Keep
victim's head turned to left.
(c). ASPIRATE PHARYNX as regularly as possible to remove
gagged or vomited stomach contents.
After aspiration of gastric contents and washing of stomach,
instill 30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces
of water through stomach tube to limit absorption of remain-
ing toxicant.
C. SAVE A SAMPLE of emesis, or the initial gastric washings, for
chemical analysis.
D. If bowel movement has not occurred in 4 hours, and if patient is
fully conscious, give SODIUM SULFATE, 0.25 gm/kg, in 1-6
ounces water, as a cathartic. Magnesium sulfate and citrate are
equally suitable at similar dosage if renal function is adequate. Re-
tained magnesium may depress CNS function.
8. DO NOT give morphine, aminophylline, phenothiazines, reserpine,
furosemide, or ethacrynic acid in poisonings by organophosphates.
9. Give adrenergic amines ONLY if there is a specific indication, such as
marked hypotension.
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10. Rarely, in severe organophosphate poisonings, CONVULSIONS occur
which are unresponsive to atropine and pralidoxime. Insure that causes
unrelated to pesticide toxicity are not responsible: head trauma, cerebral
anoxia, or mixed poisoning. DIAZEPAM (Valium), 5-10 mg for adults,
0.1 mg/kg for children under 6 years or 23 kg is probably the safest and
most reliable anticonvulsant to use under these circumstances. Give
SLOWLY (no more than half the total dose per minute) intravenously.
Se-vere protracted convulsions may require additional medication, as sug-
gested in the chapter on Solid Organochlorine Pesticides.
CAUTION: Be prepared to assist pulmonary ventilation mechanically
if respiration is depressed; to intubate the trachea, if
laryngospasm occurs; and to counteract hypotensive reac-
tions.
11. 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 cholines-
terase 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 envi-
ronment.
12. DO NOT administer atropine or pralidoxime prophylactically to workers
exposed to organophosphate pesticides. It is neither practical nor
medically sound to do so.
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Chapter 2
CARBAMATE
CHOLINESTERASE-INHIBITING
PESTICIDES
GENERAL CHEMICAL STRUCTURE
o
H
H3C
-C—O—
LEAVING
GROUP
COMMON COMMERCIAL PESTICIDE PRODUCTS*
Highly toxic**: aldicarbf (Temik), oxamyl (Vydate), carbofuran
(Furadan), methomyl (Lannate, Nudrin), formetanate HC1 (Carzol, Dicarzol),
aminocarb (Matacil), dimetilan (Snip Fly Bands).
Moderately toxic***: promecarb (Carbamult), methiocarb (Mesurol,
Draza), propoxur (Baygon), pirimicarb (Pirimor, Aphox, Rapid), bufencarb
(Bux), carbaryl (Sevin).
TOXICOLOGY
Insecticides of this class cause reversible carbamylation of acetylcholinester-
ase enzyme, allowing accumulation of acetylcholine at cholinergic neuroeffec-
tor junctions (muscarinic effects), and at skeletal muscle myoneural junctions
and in autonomic ganglia (nicotinic effects). Poison also impairs CNS func-
tion. The carbamyl-enzyme combination dissociates more readily than the
phosphorylated enzyme produced by organophosphate insecticides. This
lability tends to mitigate the toxicity of carbamates, but also limits the useful-
ness of blood enzyme measurements in diagnosis of poisoning. Carbamates
are absorbed by inhalation, ingestion, and dermal penetration. They are ac-
tively metabolized by the liver, and the degradation products are excreted by
the liver and kidneys.
* Listed approximately in order of decreasing toxicity.
** Acute oral LD5o in the rat less than 50 mg/kg.
*** Acute oral LD50 in the rat above 50 mg/kg.
t This carbamate is a systemic, i.e., it is taken up by the plant and trans-
located into foliage and sometimes into the fruit.
9
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A few carbamate insecticides are formulated in methyl (wood) alcohol. In
cases of ingestion of these formulations, the toxicology of the methanol must
be taken fully into consideration: severe gastroenteric irritation, acidosis, CNS
injury, and neuropathy.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
DIARRHEA, NAUSEA, VOMITING, ABDOMINAL PAIN, PROFUSE
SWEATING, SALIVATION, and BLURRED VISION are frequently
reported. Other common symptoms have been dyspnea, tremor, muscle
twitching, ataxia, and headache. Temporary paralysis of the extremities has
also occurred. Most reported illnesses have not exceeded a few hours, and the
prognosis is generally better than in organophosphate intoxications. However,
in severe poisonings, one should anticipate the possibility of RESPIRATORY
DEPRESSION, pulmonary edema, and convulsions. Continuing absorption
of intermediate quantities may cause protracted MALAISE, weakness, and
anorexia, resembling influenza.
CONFIRMATION OF DIAGNOSIS
CAUTION: If there is strong clinical evidence of poisoning, treat pa-
tient immediately. DO NOT WAIT for laboratory confir-
mation.
Depressions of plasma and/or RBC cholinesterase activities may be observed
following absorption of extraordinary amounts of carbamate insecticide.
However, enzyme activities commonly revert to normal within a few minutes
or hours. They are not, therefore, reliable detectors of carbamate poisoning;
i.e., intoxication may exist when blood cholinesterase activities are normal.
The rapid methods for cholinesterase estimation (ACHOLTEST, ChE-tel,
MERCKOTEST) are more likely to detect depressions than the longer test
methods.
Table 1 in the chapter on ORGANOPHOSPHATE PESTICIDES lists the
approximate lower limits of normal plasma and red cell cholinesterase-
inhibiting carbamates. A normal value does not preclude carbamate insecticide
poisoning. Whenever possible, comparison of the test sample with pre-
exposure values offers the best confirmation of excessive carbamate absorp-
tion: a depression of 25% or more is strong evidence of excessive absorption.
Consult the chapter on ORGANOPHOSPHATE PESTICIDES for detailed
interpretation of the blood cholinesterase tests.
Measurement of carbamate metabolites in urine within 48 hours of exposure
represents a specific and sensitive method for confirming absorption of several
pesticides of this class. A number of government and university laboratories in
contact with poison control centers can perform these tests. Specimens for
such analysis should be collected as promptly as possible after exposure.
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TREATMENT
CAUTION: Persons attending the victim should avoid direct contact
with heavily contaminated clothing and vomitus. Wear
rubber gloves while decontaminating skin and hair.
1. Establish CLEAR AIRWAY and TISSUE OXYGENATION by aspira-
tion of secretions, and if necessary, by assisted pulmonary ventilation
with oxygen. Improve tissue oxygenation as much as possible before ad-
ministering atropine to minimize the risk of ventricular fibrillation.
2. Administer ATROPINE SULFATE intravenously, or intramuscularly if
IV injection is not possible. Atropine protects the end-organs from ex-
cessive concentrations of acetylcholine. It does not reactivate the cholin-
esterase enzyme. Recrudescence of poisoning may occur if tissue concen-
trations of carbamate remain high when the effect of atropine wears off.
Atropine is the ideal antidote for muscarinic symptoms; it is ineffective
against nicotinic actions such as muscle weakness and twitching, and
respiratory depression.
In MODERATELY SEVERE poisoning: Adult dosage, including
children over 12 years: 0.4-2.0 mg repeated every 15 minutes until
atropinization is achieved (tachycardia, flushing, dry mouth, mydriasis).
Maintain atropinization by repeated doses for 2-12 hours, or longer,
depending on severity of poisoning. The appearance of rales in the lung
bases, miosis, salivation, nausea, bradycardia, are all indications of in-
adequate atropinization.
Dosage for children under 12 years: 0.05 mg/kg body weight repeated
every 15 minutes until atropinization is achieved. Maintain atropiniza-
tion with repeated dosage of 0.02-0.05 mg/kg.
SEVERELY POISONED individuals may exhibit remarkable tolerance
to atropine; twice the doses suggested above may be needed. Persons not
poisoned, or only slightly poisoned, may develop signs of atropine toxici-
ty if large doses are given: FEVER, muscle fibrillations, and delirium. If
these appear while the patient is fully atropinized, atropine should be dis-
continued, at least temporarily.
3. Pralidoxime (Protopam®-Ayerst, 2-PAM) is of doubtful value in
poisonings by carbamate inhibitors of cholinesterase. Atropine alone is
almost always an adequate antidote. Pralidoxime is probably contrain-
dicated in poisonings by carbaryl, specifically. If victim of carbamate
poisoning exhibits severe muscle weakness and/or respiratory depres-
sion, or if poisoning involves a combination of carbamate and organo-
phosphate, a dilute solution of pralidoxime (total dose in 250 ml 5°/o
glucose solution) may be given cautiously IV. The infusion should be ter-
minated if patient's condition worsens. Pralidoxime dosage: adults, 1.0
gm; for children under 12 years, 20-50 mg/kg.
4. OBSERVE treated patients closely at least 24 HOURS to insure that
symptoms (possibly pulmonary edema) do not recur as atropinization
wears off. In very severe poisonings, metabolic disposition of toxicant
11
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may require several hours or days during which atropinization must be
maintained. Markedly lower levels of urinary metabolites indicate that
atropine dosage can be tapered off. As dosage is reduced, check the lung
bases frequently for rales. If rales are heard, or if nausea, salivation, or
bradycardia returns, RE-ESTABLISH ATROPINIZATION promptly.
5. BATHE and SHAMPOO victim with soap and water if there is any
chance that SKIN and HAIR are contaminated.
6. If pesticide has been INGESTED in quantity sufficient to cause poison-
ing, empty the stomach and intestine.
A. If victim is alert and respiration is not depressed, give SYRUP OF
IPECAC, followed by 1-2 glasses of water to induce vomiting;
adults (including children over 12), 30 ml; children (under 12 years),
15ml.
CAUTION: OBSERVE victim closely AFTER administering
IPECAC. If consciousness level declines, or if vomit-
ing has not occurred in 15 minutes, proceed immedi-
ately to INTUBATE the stomach.
Following emesis, have victim drink a suspension of 30-50 gm
ACTIVATED CHARCOAL in 3-4 ounces of water to bind toxicant
remaining in the gastrointestinal tract.
B. If victim is OBTUNDED or respiration is depressed, empty stomach
by INTUBATION, ASPIRATION, and LAV AGE, using isotonic
saline or 5% sodium bicarbonate. Because many pesticides are
dissolved in petroleum distillates, emesis and intubation of the
stomach involve a serious risk that solvent will be aspirated, leading
to chemical pneumonitis. For this reason:
(a). If victim is unconscious or obtunded and facilities are at hand,
insert ENDOTRACHEAL TUBE (cuffed, if available) prior
to gastric intubation.
(b). Keep victim's HEAD BELOW LEVEL OF STOMACH dur-
ing intubation and lavage (Trendelenburg, or left lateral
decubitus, with head of table tipped downward). Keep
victim's head turned to left.
(c). ASPIRATE PHARYNX as regularly as possible to remove
gagged or vomited stomach contents.
After aspiration of gastric contents and washing of stomach, instill
30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces of water
through the tube to limit absorption of remaining toxicant.
C. SAVE A SAMPLE of emesis or initial gastric washings for chemical
analysis.
D. If bowel movement has not occurred in 4 hours and patient is fully
conscious, give SODIUM SULFATE, 0.25 gm/kg in 1-6 ounces of
water, as a cathartic. Magnesium sulfate or citrate is equally suitable
if renal function is satisfactory.
12
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7. DO NOT give morphine, aminophylline, phenothiazines, reserpine,
furosemide, or ethacrynic acid.
8. Give adrenergic amines ONLY if there is a specific indication, such as
severe hypotension.
9. CONVULSIONS are RARE manifestations of poisoning by carbamates.
If they occur, causes other than direct carbamate action should be con-
sidered: cerebral anoxia, head trauma, mixed poisoning. Although not
tested in these circumstances, DIAZEPAM (Valium) is probably the an-
ticonvulsant of choice. Dosage for adults and children over 6 years or 23
kg body weight is 5-10 mg given slowly intravenously (no more than half
total dose per minute), or intramuscularly (deep). Dosage for children
under 6 years or 23 kg body weight is 0.1 mg/kg. Repeat this dosage
every 2-4 hours if needed to control convulsions. Be prepared to intubate
and to assist pulmonary ventilaton mechanically if respiration is depressed.
Hypotensive reactions may also occur.
10. Persons who have been clinically poisoned by carbamate pesticides
should not be re-exposed to cholinesterase-inhibiting chemicals until
symptoms and signs have resolved completely, and normal blood cholin-
esterase activities have been demonstrated.
11. DO NOT administer atropine prophylactically to workers exposed to car-
bamate insecticides. It is neither practical nor medically sound to do so.
13
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Chapters
SOLID ORGANOCHLORINE PESTICIDES
CHEMICAL STRUCTURES
HEXACHLOROBENZENE
ENDOSULFAN HEPTACHLOR
METHOXYCHLOR
*
COMMON COMMERCIAL PESTICIDE PRODUCTS
Highly toxic: endrin (Hexadrin), a stereoisomer of dieldrin.
Moderately toxic: aldrin (Aldrite, Drinox), endosulfan (Thiodan), dieldrin
(Dieldrite), toxaphene (Toxakil, Strobane-T), lindane (Gammexane), benzene
hexachloride (BHC, HCH), DDT (chlorophenothane), heptachlor, kepone,
terpene polychlorinates (Strobane), chlordane (Chlordan), dicofol (Kelthane),
chlorobenzilate (Acaraben), mirex, methoxychlor (Marlate), dienochlor (Pen-
tac), hexachlorobenzene (HCB), ethylan (Perthane). All except HCB are insec-
ticides or acaricides; HCB is a fungicide.
The U.S. Environmental Protection Agency has sharply curtailed the
availability of many organochlorines, particularly DDT, dieldrin, and chlor-
dane. Others, however, are still the active ingredients of various home and
garden products and some agricultural and structural pest control agents. Hex-
achlorobenzene is used as a seed protectant. Lindane may no longer be used in
continuous vaporizers, but it is the active ingredient of many products for pest
control in the home and on the farm. It is the active ingredient of the scabicide
Kwell®.
TOXICOLOGY
Most organochlorines are efficiently absorbed from the gut and across the
skin. In adequate dosage, they interfere with axonic transmission of nerve im-
pulses and, therefore, disrupt the function of the nervous system, principally
that of the brain. This results in behavioral changes, sensory and equilibrium
disturbances, involuntary muscle activity, and depression of vital centers, par-
ticularly those controlling respiration. Adequate doses of some organo-
chlorines increase myocardial irritability, and stimulate synthesis of hepatic
drug-metabolizing enzymes.
Listed approximately in order of decreasing toxicity.
14
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Chlordane has apparently induced a few cases of self-limited megaloblastic
anemia after protracted low-level exposures. The condition has resolved
following termination of exposure.
Kepone has caused nervousness, tremor, incoordination, weakness and in-
fertility in excessively exposed workers. Clinical improvement has occurred as
the pesticide was excreted.
Endrin is more toxic to the liver and kidneys than the other organochlorines
at comparable dosages.
Prolonged ingestion of HCB-treated grain produced porphyria cutanea tar-
da in several thousand Turkish citizens who mistakenly ate the seed grain.
Disease was manifest as excretion of red urine, bullous dermatitis, hyper-
pigmentation, generalized hair growth, muscle wasting and liver enlargement.
Slow improvement occurred when HCB ingestion was stopped.
A series of anecdotal reports of bone marrow injury has tended to indict lin-
dane as a hematotoxic agent in certain predisposed individuals, but no rela-
tionship has been proved.
Lindane, methoxychlor, terpene poly chlorinates, chlorobenzilate, dicofol,
and the constituents of chlordane, except heptachlor and oxychlordane, are
excreted rapidly by humans, usually within 3-4 days of ingestion. Dieldrin,
aldrin, endrin, hexachlorobenzene, heptachlor, and oxychlordane are excreted
within weeks to several months of absorption by humans. DDT, kepone,
mirex, and the beta isomer of benzene hexachloride are excreted very slowly,
requiring months or years for elimination. The excretion kinetics of perthane,
kelthane, and dienochlor are not known. Because of their lipophilicity, all
organochlorines are likely to be excreted in the milk of lactating women.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
APPREHENSION, EXCITABILITY, DIZZINESS, HEADACHE, DIS-
ORIENTATION, WEAKNESS, PARESTHESIAE, muscle twitching,
tremor, tonic and clonic CONVULSIONS (often epileptiform), and uncon-
sciousness are the major manifestations. Soon after ingestion, nausea and
vomiting commonly occur. When chemicals are absorbed dermally, apprehen-
sion, twitching, tremors, confusion, and convulsions may be the first symp-
toms. Respiratory depression is caused by the pesticide and by the petroleum
solvents in which these pesticides are usually dissolved. Pallor occurs in
moderate to severe poisoning. Cyanosis may result as convulsive activity in-
terferes with respiration.
Even though convulsive activity may be severe, the prognosis in poisonings
by these agents is far from hopeless. Although fatalities have occurred follow-
ing absorption of large amounts of some organochlorines, there is a substan-
tial likelihood of complete recovery if convulsions can be controlled, and vital
functions sustained.
15
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CONFIRMATION OF DIAGNOSIS
Pesticide and/or metabolites can usually be identified in blood or urine by
gas-liquid chromatographic examination of samples taken within 72 hours of
poisoning. These tests can be performed by some private laboratories, and by
state health department and university laboratories supported by the U.S. En-
vironmental Protection Agency. Such laboratories can be reached through
poison control centers. Some chlorinated hydrocarbon pesticides (notably
DDT) persist in the serum for weeks or months after absorption, but most are
excreted in a few days. DO NOT DELAY TREATMENT of acute poisoning
pending confirmatory blood analysis. Detection of chlorinated hydrocarbon
residues in blood or tissues does not, of itself, indicate poisoning; actual con-
centrations are critical to a diagnosis of poisoning.
TREATMENT
1. Establish CLEAR AIRWAY and TISSUE OXYGENATION by aspira-
tion of secretions, and, if necessary, by assisted pulmonary ventilation
with oxygen.
2. CONTROL CONVULSIONS. DIAZEPAM (VALIUM®) is a valuable
anticonvulsant.
Adult dosage, including children over 6 years of age or 23 kg in weight:
5-10 mg (1-2 ml) slowly, intravenously (no faster than one ml per
minute), or give total dose intramuscularly (deep). Repeat in 2-4 hours if
needed.
Dosage for children under 6 years or 23 kg in weight: 0.1 mg/kg
(0.02 ml/kg) intravenously, no faster than half the total dose per
minute, or give total dose intramuscularly (deep). Repeat in 2-4 hours if
needed.
CAUTION: Administer intravenous diazepam slowly to avoid irrita-
tion of the vein, hypotension, and respiratory depression.
A. Persons suffering SEVERE PROTRACTED CONVULSIONS may
require additional anticonvulsant medication. Agents that have
been used successfully in the past are pentobarbital (Numbutal®),
phenytoin (Dilantin®), thiopental (Pentothal®), and succinyl-
choline (Anectine®).
CAUTION: Be prepared to maintain pulmonary ventilation me-
chanically if respiration is depressed during adminis-
tration of anticonvulsants. Laryngospasm sometimes
occurs during anticonvulsant therapy, and may neces-
sitate tracheostomy.
(a). PENTOBARBITAL: 5 mg/kg body weight, or 0.20 ml/kg
body weight, using the usual 2.5% solution. If possible, inject
solution intravenously, at a rate not exceeding 25 mg (one ml)
16
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per minute until convulsions are controlled. If intravenous ad-
ministration is not possible, give total dose rectally, not ex-
ceeding 5 mg/kg body weight (0.20 ml/kg of 2.5% solution).
(b). PHENYTOIN: loading dose 15-18 mg/kg. Maintenance dose
4-8 mg/kg q 4-24 hours as needed. Intramuscular administra-
tion is not recommended. Give IV slowly at no more than 20%
total dose per minute.
(c). THIOPENTAL (PENTOTHAL): a solution of one gm in 500
ml of 5% glucose in water is given by intravenous drip at a
rate just sufficient to suppress convulsions.
(d). SUCCINYLCHOLINE: occasionally, curarization may be re-
quired to stop seizures. Prior to curarization, the trachea must
be intubated, and pulmonary ventilation maintained mechani-
cally. Blood gases and pH must be monitored. A person expe-
rienced in general anesthesia should conduct these procedures.
3. BATHE and SHAMPOO the victim vigorously with soap and water if
skin and hair have been contaminated.
4. IF PESTICIDE HAS BEEN INGESTED in quantity sufficient to cause
poisoning, the stomach and intestine must be emptied.
A. IF victim is ALERT and gag reflex is not depressed, give SYRUP
OF IPECAC to induce vomiting (adults and children 12 years and
older: 30 ml; children under 12: 15 ml), followed by 1-2 glasses of
water.
CAUTION: OBSERVE the VICTIM closely after administering
IPECAC. If consciousness level declines, or if
vomiting has not occurred in 15 minutes, proceed im-
mediately to INTUBATE stomach.
Following emesis, have victim drink a suspension of 30-50 gm AC-
TIVATED CHARCOAL in 3-4 ounces of water to limit absorption
of toxicant remaining in the gut.
B. If the victim is NOT FULLY ALERT, empty the stomach immedi-
ately by INTUBATION, ASPIRATION, and LAV AGE, using
isotonic saline or 5% sodium bicarbonate. Because many pesticides
are dissolved in petroleum distillates, emesis and intubation of the
stomach involve a serious risk that solvent will be aspirated, leading
to chemical pneumonitis. For this reason:
(a). If victim is unconscious or obtunded and if facilities are at
hand, insert an ENDOTRACHEAL TUBE (cuffed, if avail-
able) prior to gastric intubation.
(b). Keep victim's HEAD BELOW LEVEL OF STOMACH and
turned to left during intubation and lavage. (Trendelenburg,
or left lateral decubitus, with head of table tipped downward).
(c). ASPIRATE PHARYNX as regularly as possible to remove
gagged or vomited stomach contents.
17
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C. After aspiration of gastric contents and washing of stomach, instill
30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces of water
through stomach tube to limit absorption of remaining toxicant.
DO NOT instill milk, cream, or other substances containing
vegetable or animal fats, which enhance absorption of chlorinated
hydrocarbons.
D. -SAVE A SAMPLE of emesis or gastric washings for chemical
analysis.
E. If bowel movement has not occurred in 4 hours and if patient is fully
conscious, give SODIUM SULFATE, 0.25 gm/kg in 1-6 ounces of
water, as a cathartic. Magnesium sulfate and citrate are as suitable
as sodium sulfate if renal function is adequate. Retained magnesium
may depress CNS function.
5. DO NOT give epinephrine or other adrenergic amines, because of the
enhanced myocardial irritability induced by chlorinated hydrocarbons.
6. CHOLESTYRAMINE resin may accelerate the biliary-gastrointestinal
excretion of the more slowly eliminated organochlorine compounds. This
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. Prolonged
treatment (several weeks or months) may be necessary.
7. During convalescence, enhance CARBOHYDRATE, PROTEIN, and
VITAMIN intake by diet or parenteral therapy to minimize injury to the
liver.
18
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Chapter 4
PENTACHLOROPHENOL
CHEMICAL STRUCTURE
Cl Cl
Cl Cl
COMMON COMMERCIAL PESTICIDE PRODUCTS
Pentachlorophenol or Sodium Pentachlorophenate, PCP, Dow Pentachlo-
rophenol, Dowicide EC-7, Penchlorol, Pentacon, Penwar, Veg-I-Kill, penta,
Wood Preserver, Wood Tox 140, Purina Insect Oil Concentrate, Garden Ter-
mi Tox, Usol Cabin Oil, Certified KiltroI-74 Weed Killer, Ciba-Geigy On-
track OSS, 4 or 5, Ortho Triox Liquid Vegetation Killer, Black Leaf Grass
Weed and Vegetation Killer Spray, DP-2 Antimicrobial, Priltox, Sinituho.
Pentachlorophenol is used as an herbicide, defoliant, wood preservative,
germicide, fungicide, and molluscicide. It is an ingredient of many formulated
mixtures sold for one or more of these purposes.
Pentachlorophenol volatilizes from treated wood and fabric. Excessively
treated interior surfaces may represent a source of intensive PCP exposure.
TOXICOLOGY
Pentachlorophenol irritates the skin, eyes, and upper respiratory mucous
membranes. It is efficiently absorbed across the skin, the lung, and the gastro-
intestinal lining. Like the nitrophenolic compounds, it stimulates cellular ox-
idative metabolism by uncoupling phosphorylation. In common with other
phenols, it is toxic to the liver, kidney, and central nervous system. Impurities
in the technical formulation may be responsible for chloracne in workers
regularly exposed.
Most severe poisonings have occurred in workers exposed to hot environ-
ments. However, a major epidemic of poisoning occurred in an American
hospital among newborn infants who absorbed PCP from treated diapers.
Dehydration and metabolic acidosis are important features of poisoning in
children.
Albuminuria, glycosuria, and elevated BUN reflect renal injury. Liver
enlargement has been observed in some cases. Anemia and leukopenia have
occurred in some chronically exposed workers, but leukocytosis is more com-
monly found in acute poisoning.
19
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FREQUENT SYMPTOMS AND SIGNS OF POISONING
IRRITATION of nose, throat, eyes, and skin is the most common symptom
of exposure to PCP. Severe or protracted exposure may result in CONTACT
DERMATITIS. Intensive occupational exposure has resulted in chloracne.
PROFUSE SWEATING, HEADACHE, WEAKNESS, and NAUSEA are
the most consistent presenting symptoms of systemic poisoning by absorbed
PCP. FEVER is usually present but may be minimal or absent. TACHYCAR-
DIA, TACHYPNEA, and PAIN in the CHEST and ABDOMEN are often
prominent. THIRST is usually intense, but may be masked by nausea and
vomiting. DECLINING MENTAL ALERTNESS may progress to stupor
and/or convulsions. Protracted exposure may result in WEIGHT LOSS from
increased basal metabolic rate.
CONFIRMATION OF DIAGNOSIS
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. Based on studies of per-
sons occupationally exposed to PCP, manifestations of systemic toxicity prob-
ably do not appear in adults until blood and urine concentrations reach at least
one part per million (0.1 mg%, or 1,000 parts per billion).
If poisoning is strongly suspected on grounds of exposure, symptoms, and
signs, DO NOT POSTPONE TREATMENT until diagnosis is confirmed.
TREATMENT
1. BATHE and SHAMPOO contaminated SKIN and HAIR promptly with
soap and water, or water alone if soap is not available.
2. FLUSH chemical from EYES with copious amounts of clean water.
3. IN EVENT OF SYSTEMIC POISONING:
A. REDUCE ELEVATED BODY TEMPERATURE BY PHYSICAL
MEANS. Administer sponge baths and cover victim with low-
temperature blankets. In fully conscious patients, administer cold,
sugar-containing liquids by mouth as tolerated.
B. Administer OXYGEN continuously by mask to minimize tissue
anoxia.
C. Unless there are manifestations of cerebral edema, administer IN-
TRAVENOUS FLUIDS at maximum tolerated rates to enhance
urinary excretion of toxicant and to support physiologic mechan-
isms for heat loss. Monitor fluid balance, blood electrolytes and
sugar, adjusting IV infusions to stabilize electrolyte concentra-
tions, Follow urine contents of albumin and cells. In the presence of
CEREBRAL EDEMA, intravenous FLUIDS must be administered
very CAUTIOUSLY to avoid increasing the cerebral injury.
20
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D. Administer SEDATIVES, if necessary, to control apprehension and
excitement. DIAZEPAM® (Valium) should be valuable, although
its use has not been reported in this type of poisoning. Give slowly,
intravenously, 5-10 mg in the adult, 0.1 mg/kg in children.
Amobarbital or pentobarbital, 100-200 mg IM or slowly IV, every
4-6 hours may be needed. (Children's dose: up to 5 mg/kg.)
CAUTION: Be prepared to assist pulmonary ventilation mechani-
cally in event of respiratory depression, and to
counteract hypotensive reactions.
4. If toxicant has been INGESTED, evacuate the stomach and intestine.
A. If victim is alert and respiration is not depressed, give SYRUP OF
IPECAC, followed by 1-2 glasses of water, to induce vomiting.
(Adults, 12 years and older: 30 ml; children under 12: 15 ml).
CAUTION: OBSERVE the victim closely AFTER administering
IPECAC. If consciousness level declines, or if vomit-
ing has not occurred in 15 minutes, proceed im-
mediately to INTUBATE the stomach.
Following emesis, have the victim drink a suspension of 30-50 gm
ACTIVATED CHARCOAL in 3-4 ounces of water to bind toxicant
remaining in the gastrointestinal tract.
B. If victim is not fully alert, empty the stomach immediately by IN-
TUBATION, ASPIRATION, and LAV AGE, using isotonic saline
or 5% sodium bicarbonate. Because PCP is commonly dissolved in
petroleum distillates, emesis and intubation of the stomach involve
a serious risk that solvent will be aspirated, leading to chemical
pneumonitis. For this reason:
(a). If victim is unconscious or obtunded and facilities are at hand,
insert an ENDOTRACHEAL TUBE (cuffed, if available)
prior to gastric intubation.
(b). Keep victim's HEAD BELOW LEVEL OF THE STOMACH,
turned to left, during intubation and lavage. (Trendelenburg,
or left lateral decubitus, with head of table tipped downward).
(c). ASPIRATE PHARYNX as regularly as possible to remove
gagged or vomited stomach contents.
(d). After aspiration of gastric contents and washing of stomach,
instill 30 gm of ACTIVATED CHARCOAL in 3-4 ounces of
water through a stomach tube to limit absorption of remain-
ing toxicant. Do NOT instill milk, cream, or other materials
containing vegetable or animal fats, which are likely to
enhance absorption.
C. If bowel movement has not occurred in 4 hours and patient is fully
conscious, give SODIUM SULFATE as a cathartic: 0.25 gm/kg
body weight in 1-6 ounces of water. Magnesium sulfate and citrate
21
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are equally suitable unless renal function is impaired; retention of
magnesium may depress CNS function and alter myocardial irrita-
bility.
5. DO NOT administer atropine, aspirin, or other antipyretics to control
fever. These are likely to enhance the toxicity of phenolic compounds.
6. During convalescence, administer high-calorie, high-vitamin diet to
restore body fat and carbohydrate.
7. Discourage subsequent contact with the toxicant for at least 4 weeks to
allow full restoration of normal metabolic processes.
8. HEMODIALYSIS and HEMOPERFUSION may be considered in PCP
poisoning, although phenols are extensively bound to plasma protein.
EXCHANGE TRANSFUSION was used to rescue the infants inadver-
tently poisoned by PCP in a hospital. Unless renal and liver functions are
impaired, PCP is rapidly eliminated from the blood and tissues.
22
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Chapter 5
NITROPHENOLIC AND
NITROCRESOLIC HERBICIDES
GENERAL CHEMICAL STRUCTURE
NO2
O2N V ^O—H (or ESTER)
(ALKYL) (ALKYL)
COMMON COMMERCIAL PESTICIDE PRODUCTS
Dinitrophenol (Chemox PE), dinitrocresol (DNOC, DNC, Sinox, Chemsect
DNOC, Elgetol 30, Nitrador, Selinon, Trifocide), dinoseb (DNBP, Dinitro,
Basanite, Caldon, Chemox General, Chemox PE, Chemsect DNBP,
Dinitro-3, Dinitro General, Dow General Weed Killer, Dow Selective Weed
Killer, Dynamyte, Elgetol 318, Gebutox, Kiloseb, Nitropone C, Premerge 3,
Sinox General, Subitex, Unicrop DNBP, Vertac Dinitro Weed Killer),
dinosam (DNAP), dinoprop, dinoterbon, dinoterb, dinosulfon, bmapacryl
(Morocide, Endosan, Ambox, Dapacryl), dinobuton (Acrex, Dessin, Dinofen,
Drawinol, Talan), dinopenton, dinocap (Crotothane, Karathane). Several
combinations are widely used: Dyanap and Klean Krop = dinoseb + nap-
talam; Ancrack = sodium salts of dinoseb + naptalam; Naptro =
dinitrophenol + naptalam.
TOXICOLOGY
These materials should be regarded as highly toxic to humans and animals.
Most nitrophenols and nitrocresols are well absorbed from the gastrointestinal
tract, across the skin, and by the lung when fine droplets are inhaled. Except in
a few sensitive individuals, aromatic nitro-compounds are only moderately
irritating to the skin. Like other phenols, they are toxic to the liver, kidney,
and nervous system. The basic mechanism of toxicity is a stimulation of oxida-
tive metabolism in cell mitochondria, by interference with the normal coupling
of carbohydrate oxidation to phosphorylation (ADP to ATP). Increased oxi-
dative metabolism leads to pyrexia, tachycardia, and dehydration, and ulti-
mately depletes carbohydrate and fat stores. Most severe poisonings from
absorption of these compounds have occurred in workers who were concur-
rently exposed to hot environments. Pyrexia and direct action on the brain
cause cerebral edema, manifest clinically as a toxic psychosis and sometimes
23
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convulsions. Liver parenchyma and renal tubules show degenerative changes.
Albuminuria, pyuria, hematuria, and increased BUN are often prominent
signs of renal injury.
Agranulocytosis has occurred in humans following large doses of
dinitrophenol. Cataracts have occurred in some chronically poisoned
laboratory species, but this effect has not been observed in humans.
Nitrophenols and nitrocresols are efficiently excreted by the kidneys, and
there is some hepatic excretion into the bile. Unless the absorbed dose was ex-
tremely high, or kidney function is impaired, nearly complete elimination
from the body can be expected within 3-4 days.
Death in nitrophenol poisoning is followed promptly by intense rigor mortis.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
YELLOW STAINING of skin and hair often signify contact with a nitro-
phenolic chemical. Staining of the sclerae and urine indicate absorption of
potentially toxic amounts. PROFUSE SWEATING, HEADACHE, THIRST,
MALAISE, and LASSITUDE are the common early symptoms of poisoning.
WARM, FLUSHED SKIN, TACHYCARDIA, and FEVER characterize a
serious degree of poisoning. APPREHENSION, restlessness, anxiety, manic
behavior, or unconsciousness reflect severe cerebral injury. CONVULSIONS
occur in the most severe poisonings. Cyanosis, tachypnea and dyspnea result
from stimulation of metabolism, pyrexia, and tissue anoxia. Weight loss oc-
curs in persons chronically poisoned at low dosages.
CONFIRMATION OF DIAGNOSIS
Unmetabolized nitrophenols and nitrocresols can be identified spectro-
photometrically, or by gas-liquid chromatography, in the serum and urine at
concentrations well below those necessary to cause poisoning. If poisoning is
probable, DO NOT AWAIT CONFIRMATION before commencing treat-
ment.
TREATMENT
1. WASH contaminated SKIN and HAIR promptly with soap and water, or
with water alone if soap is not available.
2. FLUSH chemical from EYES with copious amounts of clean water.
3. IN EVENT OF SYSTEMIC POISONING:
A. REDUCE ELEVATED BODY TEMPERATURE BY PHYSICAL
MEANS. Administer sponge baths and cover victim with Idw-
temperature blankets. In fully conscious patients, administer cold,
sugar-containing liquids by mouth as tolerated.
B. Administer OXYGEN continuously by mask to minimize tissue
anoxia.
24
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C. Unless there are manifestations of cerebral edema, administer IN-
TRAVENOUS FLUIDS at maximum tolerated rates to enhance uri-
nary excretion of toxicant and to support physiologic mechanisms
for heat loss. IN the presence of CEREBRAL EDEMA, intravenous
FLUIDS must be administered very CAUTIOUSLY to avoid increas-
ing the cerebral injury. Monitor fluid balance, blood electrolytes and
sugar, adjusting IV infusions to stabilize electrolyte concentrations.
Follow urine contents of albumin and cells. Follow serum alkaline
phosphatase, GOT, and LDH to evaluate liver injury.
D. Administer SEDATIVES, if necessary, to control apprehension, ex-
citement, and/or convulsions. Although not previously used in this
type of poisoning, DIAZEPAM (Valium® ) should help: adult
dose, 5-10 mg slowly IV, or IM (deep); child's dose, 0.1 mg/kg.
Repeat every 2-4 hours as needed. Amobarbital or pentobarbital
may be needed. Dose in adults: 200 mg, IM or slowly IV, every 4-6
hours; child's dose: up to 5 mg/kg.
CAUTION: Be prepared to counteract respiratory depression and
hypotension which may follow administration of
anticonvulsants and sedatives.
4. If toxicant has been INGESTED, evacuate the stomach and intestine.
A. If victim is alert and respiration is not depressed, give SYRUP of
IPECAC, followed by 1-2 glasses of water, to induce vomiting
(adults 12 years and older: 30 ml; children under 12: 15 ml).
CAUTION: OBSERVE victim closely AFTER administering IP-
ECAC. If consciousness level declines, or if vomiting
has not occurred in 15 minutes, immediately IN-
TUBATE, ASPIRATE, and LAV AGE the stomach.
Following emesis, have victim drink a suspension of 30-50 gm AC-
TIVATED CHARCOAL in 3-4 ounces of water to bind toxicant
remaining in the gastrointestinal tract.
B. IF VICTIM IS NOT FULLY ALERT, empty the stomach immedi-
ately by INTUBATION, ASPIRATION, and LAV AGE, using
isotonic saline or 5% sodium bicarbonate. Because these pesticides
are usually dissolved in petroleum distillates, emesis and intubation
of the stomach involve serious risk that solvent will be aspirated,
leading to chemical pneumonitis. For this reason:
(a). If victim is unconscious or obtunded and facilities are at hand,
insert an ENDOTRACHEAL TUBE (cuffed, if available)
prior to gastric intubation.
(b). Keep victim's HEAD BELOW LEVEL OF THE STOMACH
and turned to the left, during intubation and lavage
(Trendelenburg, or left lateral decubitus, with head of table
tipped downward).
25
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(c). ASPIRATE PHARYNX as regularly as possible to remove
gagged or vomited stomach contents.
(d). After aspiration of gastric contents and washing of stomach,
instill 30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces
of water through the stomach tube to limit absorption of re-
maining toxicant. Do NOT instill cream, milk, or other
materials containing vegetable or animal fats, as these are like-
ly to enhance absorption.
C. If bowel movement has not occurred in 4 hours, and if patient is fully
conscious, give SODIUM SULFATE as a cathartic: 0.25 gm/kg
body weight in 1-6 ounces of water. Magnesium sulfate and citrate
are equally suitable unless renal function is impaired; retention of
magnesium may depress CNS function and alter myocardial irrita-
bility.
5. DO NOT administer atropine, aspirin, or other antipyretics to control
fever. Animal tests indicate that aspirin enhances, rather than reduces,
the toxicity of nitrophenolic and nitrocresolic compounds.
6. During convalescence, administer high-calorie, high-vitamin diet to facil-
itate repletion of body fat and carbohydrate.
7. Discourage subsequent contact with the toxicant for at least 4 weeks, to
allow full restoration of normal metabolic processes.
8. HEMODIALYSIS and HEMOPERFUSION may be considered in
severe poisonings by aromatic nitro-compounds, although most phenols
are extensively bound to plasma proteins. EXCHANGE TRANSFU-
SION is another option in poisonings characterized by impaired renal
function. So long as renal and liver functions are intact, these com-
pounds are efficiently excreted.
26
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Chapter 6
CHLOROPHENOXY COMPOUNDS
GENERAL CHEMICAL STRUCTURE
(or CH3)
Cl
Cl
— O —
(Cl)
O
II
_ C — O — H or
n
COMMON COMMERCIAL PESTICIDE PRODUCTS
Several hundred commercial products contain chlorophenoxy herbicides in
various 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 product label.
2,4-D, or 2,4-dichlorophenoxyacetic acid (Weedonef, Agrotec, Amoxone,
Aqua-Kleen, BH 2,4-D, Chipco Turf Herbicide "D", Chloroxone, Crop
Rider, D50, Dacamine 4D, Ded-Weed, Desormone, Dinoxol, DMA4, Dor-
mone, Emulsamine BK, Emulsamine E-3, Envert DT or 171, Esteron 99 Con-
centrate, Esteron Four, Esteron Brush Killer, Estone, Fernoxone, Fernimine,
Ferxone, Fernesta, Formula 40, Hedonal, Herbidal, Lawn-Keep, Macondray,
Miracle, Netagrone 600, Pennamine D, Planotox, Plantgard, Rhodia, Salvof,
Spritz-Hormin/2,4-D, Spritz-Hormit/2,4-D, Superormone Concentre, Super
D Weedone, Transamine, U46, Verton 2D, Visko-Rhap, Weed-B-Gon,
Weedar, Weed-Rhap, Weed Tox, Weedtrol, De broussaillant 600, Lithate,
Dicotox, Field Clean Weed Killer). 2,4-DB is the butyric acid homologue of
2,4-D. Dichlorprop is the propionic acid homologue.
2,4,5-T or 2,4,5-trichlorophenoxyacetic acid (Brush-Rhap, Dacamine 4T,
Debroussaillant Concentre, Ded-Weed Brush Killer, Esteron 245, Fence Rider,
Forron, Inverton 245, Line Rider, Spontox, Super D Weedone, Tormona,
Transamine, Trinoxol, Trioxone, U46, Veon 245, Verton 2T, Weedar,
Weedone Envert T).
Common mixtures of 2,4-D and 2,4,5-T are: Dacamine 2D/2T, Esteron
Brush Killer, Rhodia Low Volatile Brush Killer No. 2, U46 Special, Tributon,
Visko-Rhap LV2D-2T, and Transamine.
f A product of identical name containing pentachlorophenol (Chapter 4) as
the active ingredient has been discontinued by Amchem Products Co.
t A product of identical name marketed by the Crystal Chemical Company
contains cacodylic acid as the active ingredient (Chapter 10).
27
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2,4,5-TP (Silvex) is the propionic acid homologue of 2,4,5-T. Kuron is a low
volatile ester of 2,4,5-TP. 2,4,5-TB is the butyric acid homologue of 2,4,5-T.
Fenac or chlorfenac is 2,3,6-trichlorophenylacetic acid. Dicamba (Banvel) is
dichloroanisic acid. MCPA, MCPB, MCPB-Ethyl, MCPCA and MCPP
(Mecoprop) are 2-methyl, 4-chlorophenoxy aliphatic acids and esters.
TOXICOLOGY
Some of the chlorophenoxy acids, salts, and esters are moderately irritating
to skin, eyes, and respiratory and gastrointestinal linings. In a few individuals,
local depigmentation has apparently resulted from prolonged and repeated
dermal contact with chlorophenoxy materials.
The chlorophenoxy compounds are absorbed across the gut wall, lung, and
skin. They are not significantly fat storable. Excretion occurs within hours, or
at most, days, primarily in the urine.
Given in large doses to experimental animals, 2,4-D causes vomiting, diar-
rhea, anorexia, weight loss, ulcers of the mouth and pharynx, and toxic injury
to the liver, kidneys, and central nervous system. Myotonia (stiffness and in-
coordination of hind extremities) develops in some species and is apparently
due to CNS damage: demyelination has been observed in the dorsal columns
of the cord, and EEC changes have indicated functional disturbances in the
brains of heavily dosed experimental animals.
Ingestion of large amounts of chlorophenoxy acids has resulted in severe
metabolic acidosis in humans. Such cases have been associated with electro-
cardiographic changes, myotonia, muscle weakness, myoglobinuria, and ele-
vated serum creatine phosphokinase, all reflecting injury to striated muscle.
Because chlorophenoxy acids are weak uncouplers of oxidative phosphoryla-
tion, extraordinary doses may produce hyperthermia from increased produc-
tion of body heat.
PolyChlorinated DibenzoDioxin (CDD) compounds are generated in the
synthesis of 2,4,5-T. The 2,3,7,8-Tetra CDD form is extraordinarily toxic to
multiple mammalian tissues. Hexa- hepta-, and octa-compounds exhibit less
systemic toxicity, but are the likely cause of chloracne (a chronic, disfiguring
skin condition) seen in workers engaged in the manufacture of 2,4,5-T, and
certain other chlorinated organic compounds. Although toxic effects, notably
chloracne, have been observed in manufacturing plant workers, they have not
been observed in formulators or applicators regularly exposed to 2,4,5-T.
The medical literature contains several reports of peripheral neuropathy
following what seemed to be minor dermal exposures to 2,4-D. It is not cer-
tain that exposures to other neurotoxicants were entirely excluded in these
cases. Single doses of 5 mg/kg body weight of 2,4-D and 2,4,5-T have been ad-
ministered to human subjects without any adverse effects. One subject con-
sumed 500 mg of 2,4-D per day for 3 weeks without experiencing symptoms or
signs of illness.
28
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FREQUENT SYMPTOMS AND SIGNS OF POISONING
Chlorophenoxy compounds are moderately IRRITATING to skin and
mucous membranes. Inhalation of sprays may cause burning sensations in the
nasopharynx and chest, and coughing may result. Prolonged inhalation some-
times causes dizziness.
When INGESTED, high concentrations of chlorophenoxy compounds may
irritate the mouth, throat, and gastrointestinal tract. Prompt EMESIS,
CHEST PAIN (from esophagitis), ABDOMINAL PAIN, and DIARRHEA
commonly ensue. Injury to the GI tract does not usually progress to ulceration
or perforation. Absorbed chlorophenoxy compounds have caused
FIBRILLARY MUSCLE TWITCHING, skeletal muscle tenderness, and
MYOTONIA (stiffness of muscles of the extremities). Ingestion of very large
amounts has produced METABOLIC ACIDOSIS, fever, tachycardia, hyper-
ventilation, vasodilatation and sweating. Particular cases have been charac-
terized by coma and convulsions.
CONFIRMATION OF DIAGNOSIS
Gas-liquid chromatographic methods are available for detecting and mea-
suring the chlorophenoxy compounds in blood and urine. These analyses are
useful in confirming and assessing the magnitude of chlorophenoxy absorp-
tion. Urine samples should be collected as soon as possible after exposure
because the herbicides may be almost completely excreted in 24-72 hours,
depending on the extent of toxicant absorption. Analyses can be performed at
special laboratories operated by state health departments, chemical com-
panies, universities, and government facilities. If circumstances indicate
strongly that excessive exposure to any of these compounds has occurred, ini-
tiate appropriate treatment measures immediately, not waiting for chemical
confirmation of toxicant absorption.
TREATMENT
1. BATHE and SHAMPOO with soap and water to remove chemicals from
skin and hair. Individuals with chronic skin disease or known sensitivity
to chemicals should either avoid using these herbicides or take extraordi-
nary measures to avoid contact.
2. FLUSH contaminating chemicals from eyes with copious amounts of
clean water for 10-15 minutes.
3. If symptoms of illness occur during or following inhalation of spray,
REMOVE victim FROM CONTACT with the material for at least two
days. Allow subsequent contact with chlorophenoxy compounds only if
effective respiratory protection is practiced.
4. IF substantial amounts of chlorophenoxy compounds have been IN-
GESTED, spontaneous emesis usually occurs. Ordinarily, this empties
the stomach as effectively as intubation and lavage. If vigorous emesis
29
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has not occurred and IF VICTIM IS FULLY ALERT, induce EMESIS
with SYRUP OF IPECAC (adults 12 years and older, 30 ml; children
under 12 years, 15 ml), followed by 1-2 glasses of water. Following
emesis, administer 30-50 gm of ACTIVATED CHARCOAL in a slurry
of 6-8 ounces tap water, to limit absorption of herbicide remaining in the
gut.
5. IF CONSCIOUSNESS LEVEL IS DEPRESSED or other signs of
NEUROTOXICITY appear, SUSPECT additional or alternative in-
gested toxicants. Evacuate the stomach by INTUBATION, ASPIRA-
TION, and LAV AGE. Because petroleum distillates are commonly in-
cluded in chlorophenoxy formulations, gastric intubation incurs a risk of
hydrocarbon pneumonitis from aspiration. For this reason:
A. If victim is unconscious or obtunded and facilities are at hand, in-
sert an ENDOTRACHEAL TUBE (cuffed, if available) prior to
gastric intubation.
B. Keep victim's HEAD BELOW LEVEL OF THE STOMACH dur-
ing intubation and lavage (Trendelenburg, or left lateral decubitus,
with head of table tipped downward). Keep victim's head turned to
left.
C. ASPIRATE PHARYNX as regularly as possible to remove gagged
or vomited stomach contents.
After aspiration of gastric contents and washing of stomach, instill 30-50
gm of ACTIVATED CHARCOAL in 3-4 ounces of water through the
stomach tube to limit absorption of remaining toxicant. Do NOT instill
milk, cream, or other materials containing vegetable or animal fats, as
these are likely to enhance absorption.
6. If bowel movement has not occurred in 4 hours and patient is fully con-
scious, give SODIUM SULFATE, 0.25 gm/kg, as a cathartic. Magne-
sium sulfate and citrate, in comparable dosages, are equally suitable if
renal function is adequate. Retained magnesium may depress CNS func-
tion.
7. In SEVERE POISONINGS by very large amounts of ingested chloro-
phenoxy acids, forced ALKALINE DIURESIS may save the victim's
life. Assess serum electrolyte concentrations, and serum and urine pH. If
a metabolic acidosis is present, infuse solutions of sodium bicarbonate at
rates sufficient to keep the urine distinctly alkaline, continuing until
plasma concentrations of chlorophenoxy compounds are less than about
10Mg/ml. [Prescott, L F. et al., Br. J. Clin. Pharmacol. 7:11 (1979)]
30
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^\ II iki'\y\-^- f \ f \
\5
Chapter 7
PARAQUAT AND DIQUAT
CHEMICAL STRUCTURES
'CHs v_rv
2Cr ™ **
CH2—CH2 2 Br~
PARAQUAT DIQUAT
COMMON COMMERCIAL PESTICIDE PRODUCTS
Paraquat products: paraquat dichloride (usually as a 21% concentrate).
Other names: Ortho paraquat-CL, Crisquat, Dextrone X, Esgram. Mix-
tures: Priglone, Preeglone, Weedol—with diquat; Simpar, Terraklene—with
simazine; Gramonol, Mofisal—with monolinuron; Pathclear—with diquat
and simazine; TotaCol, Dexuron—with diuron.
Diquat products: diquat (Reglone, Reglox, Aquacide, Dextrone, Weed-
trine-D). Mixtures: Priglone, Preeglone, Weedol—with paraquat; Pathclear—
with paraquat and simazine.
TOXICOLOGY
These dipyridyls injure the epithelial tissues: skin, nails, cornea, liver, kid-
ney, and the linings of the GI and respiratory tracts. In addition to direct irri-
tant effects, injury may involve peroxidation of intracellular and extracellular
phospholipids and inhibition of surfactant synthesis by lung tissue. These toxic
properties may derive from the capacity of dipyridyls to generate free radicals
in tissues. The injury is usually reversible; however, the pulmonary reaction
which follows ingestion of paraquat is often fatal.
Certain injuries have followed occupational contact with paraquat. Contact
with the concentrate may cause irritation and fissuring of the skin of the
hands, and cracking, discoloration, and sometimes loss of the fingernails.
Splashed in the eye, paraquat concentrate causes conjunctivitis and, if not
promptly removed, may result in protracted opacification of the cornea.
Although nearly all systemic intoxications by paraquat have followed inges-
tion of the chemical, occasional poisonings have resulted from excessive dermal
contact. Absorption of toxic amounts is much more likely to occur if the skin
is abraded. Persons who have experienced extraordinary dermal contact with
paraquat (especially the concentrate) should be examined, and tested for
hazardous concentrations of the agent in the blood and urine (see section on
Confirmation of Diagnosis).
31
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Inhalation of dilute spray mist may irritate the upper respiratory passages,
causing a scratchy throat and nosebleed. Effects induced by dilute paraquat
sprays ordinarily resolve promptly following withdrawal from exposure.
If ingested, paraquat produces inflammation of the mouth and GI tract,
sometimes progressing to ulceration within 1-4 days. Once absorbed, it
damages the parenchymal cells of the liver and tubule cells of the kidney. In
most instances, the victim survives these injuries. Paraquat is actively concen-
trated in the pneumocytes of lung tissue. Several days after ingestion these cells
die, after which there is rapid proliferation of connective tissue cells which fill
the alveolar spaces. Although some victims have survived, death from asphyxia
usually occurs once this degree of lung damage has been sustained. In sur-
vivors, recovery of normal lung function requires weeks or months. In a few
instances, ingestion of large quantities of paraquat has induced protracted
pulmonary edema. Myocardial injury has also been noted in some poisonings.
Diquat appears less likely than paraquat to cause death. Information from
suicidal ingestions and from orally dosed monkeys indicates that the principal
target organs in diquat toxicity are the gastrointestinal tract, kidney, and liver.
Diquat produces intense congestion and ulceration of the stomach and bowel.
Fatty liver and acute renal tubular necrosis are produced by adequate doses.
Smaller doses administered chronically have caused lens cataracts in animals.
Diquat is not concentrated in lung tissue as paraquat is, and pulmonary lesions
are limited to punctate hemorrhages. Hemorrhages in brain tissue have been
reported after diquat ingestion.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
The irritant effects of paraquat on skin, eye, and upper respiratory tract
have been described under TOXICOLOGY.
The earliest (1-4 days) symptoms of injury and signs following ingestion of a
toxic dose of PARAQUAT are burning PAIN (oral, substernal, abdominal),
NAUSEA, VOMITING, DIARRHEA, and sometimes melena. Early symp-
toms are sometimes so mild that vigorous treatment is improperly delayed.
From 24-72 hours, indications of renal and hepatic insult appear. Albumin-
uria, hematuria, pyuria, and ELEVATED BUN and CREATININE may occur.
OLIGURIA may develop, and this signals severe poisoning. JAUNDICE and
elevations of serum GOT, GPT, LDH, and alkaline phosphatase reflect
hepatocellular injury. These injuries are usually reversible, although severe
renal tubular damage may require extracorporeal hemodialysis.
A progressive decline in arterial oxygen tension and CO diffusion capacity
commonly precedes the appearance of pulmonary symptomatology. COUGH,
DYSPNEA, and TACHYPNEA usually appear 72-96 hours after paraquat in-
gestion, but may be delayed as long as 14 days. Progressive CYANOSIS
reflects deteriorating gas exchange caused by the fibrogenic reaction in the
alveolar sacs. In a few cases, the production of COPIOUS WATERY SPUTUM
(pulmonary edema) has followed ingestions of large amounts (200 ml) of para-
quat or diquat concentrate.
32
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DIQUAT INGESTION results in intense NAUSEA, VOMITING, and
DIARRHEA, with accompanying dehydration, and in melena and
hematemesis from gastrointestinal ulceration. INCREASED serum BUN and
CREATININE, and ANURIA result from acute tubular necrosis. Serum
GOT, GPT, and LDH and alkaline phosphatase elevations reflect liver injury.
Early COMA has sometimes occurred following suicidal ingestion of large
amounts and has also been noted in experimentally poisoned monkeys. This
could be a consequence of profound dehydration, with electrolyte distur-
bances, or of diffuse hemorrhages in the central nervous system, as noted in
one human poisoning.
CONFIRMATION OF DIAGNOSIS
Qualitative and quantitative methods for paraquat and diquat in blood and
urine are available at some local, private, and government toxicology labora-
tories, and at the Chevron Environmental Health Center, Box 1272, Rich-
mond, California 94802. The Chevron Chemical Company maintains a
24-hour toxicology consultation service through an emergency telephone
number: (415) 233-3737. Sales representatives are prepared to deliver bentonite
to virtually any location in the United States, and to arrange for the prompt
delivery of biologic specimens for dipyridyl analysis to the Environmental
Health Center. Company toxicologists are available 24 hours a day for assis-
tance in management of poisonings by Chevron products.
TREATMENT
1. Contaminated SKIN must be FLUSHED with copious amounts of water.
Material splashed in the EYES must be removed by PROLONGED
IRRIGATION with clean water. Eye contamination should thereafter be
treated by an ophthalmologist. Mild skin reactions usually respond to
simple avoidance of further contact, but the irritation may take several
weeks to resolve. Severe injuries, with cracking, secondary infection, or
nail injury, should be treated by a dermatologist.
2. After a DIPYRIDYL compound has been INGESTED,
EVACUATE the STOMACH, then LOAD the gastrointestinal tract
with an effective ADSORBENT, to minimize toxicant absorption. These
measures must be undertaken immediately, even though the patient is
free of signs of systemic toxicity, and even when, by all accounts, the in-
gested dose was probably small and was taken as long as several days
prior to treatment.
INTUBATE the STOMACH, ASPIRATE contents, then LAV AGE
with at least two liters of a slurry of ADSORBENT in normal saline.
Then, slowly instill several hundred additional ml of adsorbent slurry,
allowing the stomach and intestine to accommodate this volume without
overdistension and vomiting.
33
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A. The ideal adsorbent is BENTONITE, administered as a 7 gm per
100 ml suspension. If not immediately available, use ACTIVATED
CHARCOAL, 30-50 gm in 300-400 ml of water, or any concentra-
tion that will flow through the tube. As soon as bentonite has been
obtained, administer it as rapidly as the patient will tolerate it. If pa-
tient cannot swallow bentonite, administer it by stomach tube at the
highest concentration that will flow through the tube.
B. Initiate SALINE CATHARSIS. Give SODIUM SULFATE, 0.25
gm/kg, and repeat in two hours if no bowel movement has oc-
curred. Magnesium salts are probably contraindicated, because of
the risk of magnesium retention in the presence of impaired renal
function.
C. Continue administering bentonite suspension and sodium sulfate
until the gut has been thoroughly flushed. This may require several
days.
3. Secure samples of blood and urine for dipyridyl analysis. (See Confirma-
tion of Diagnosis.)
4. Commence INTRAVENOUS INFUSIONS of glucose and electrolyte to
minimize toxicant concentrations in the tissues, and expedite excretion of
the dipyridyl. Attempt to establish a diuresis of 10-15 liters per day.
CAUTION: Monitor fluid balance and electrolytes continuously to in-
sure against fluid overload if acute tubular necrosis
supervenes.
5. Although cases of paraquat poisoning have been successfully managed
by forced diuresis regimens alone, it is more effective to use extracorporeal
HEMODIALYSIS and/or HEMOPERFUSION over specially coated
charcoal. This procedure for toxicant removal is best executed in tertiary
care centers where blood levels of paraquat can be monitored regularly,
and various complications of hemoperfusion can be detected and fore-
stalled. The prognosis is generally good when blood levels do not exceed
0.05 to 0.10 ppm by 24-48 hours after paraquat ingestion.
6. DO NOT ADMINISTER SUPPLEMENTAL OXYGEN in paraquat
poisoning. Increased levels of alveolar oxygen accelerate the pathologic
process in the lung caused by paraquat. Some clinicians recommend
maintaining the patient in an atmosphere of 15-16% oxygen as soon as
possible, to retard the fibrogenic process.
7. The tubular necrosis produced by large doses of DIQUAT may require
protracted EXTRACORPOREAL HEMODIALYSIS.
8. The topical injuries to mucous membranes produced by ingested
dipyridyls are painful and may require topical local anesthetic.
9. The effectiveness of various medicines and procedures in paraquat
poisoning remains uncertain. The free-radical scavenger super oxide
dismutase is theoretically appropriate as an antidote, but is unproved.
Corticosteroids are often given, and may be helpful. There is limited
34
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laboratory evidence supporting the use of propranolol and expectorants:
glyceryl guaicolate, anise oil, terpin hydrate, ammonium chloride and
potassium iodide. One victim is thought to have benefited from a com-
bination of azathioprine and potassium aminobenzoate. Lung transplant
in one case of paraquat poisoning was not successful.
35
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Chapters
DITHIOCARBAMATES AND
THIOCARBAMATES
CHEMICAL STRUCTURES AND
COMMON COMMERCIAL PRODUCTS
These functional classes include many fungicides and herbicides. There are
several subclasses:
BIS DITHIOCARBAMATES
s s
CH3 || II CH3
^ N-C-S-S-C-N
THIRAM
COMMERCIAL PRODUCTS
thiram (Arasan, Thiramad, Thirasan, Thylate, Tirampa, Pomarsol forte,
TMTDS, Thiotex, Fernasan, Nomersan, Tersan, Thiuramin, Tuads,
AAtack, Aules, Chipco Thiram 75, Fermide 850, Trametan, Hexathir, Mer-
curam, Polyram-Ultra, Spotrete, Tripomol, Tersan 75, Tetrapom,
Thioknock). Thiram is a fungicide.
METALLO BIS DITHIOCARBAMATES
-CH3
\
/
II
N -C-S
— Zn, Na, or Fe
COMMERCIAL PRODUCTS
ziram (Z-C Spray, Carbazinc, Corozate, Cuman, Drupina 90, Fuclasin
Ultra, Fuklasin, Fungostop, Hexazir, Mezene, Pomarsol Z Forte, Prodaram,
Tricarbamix Z, Triscabol, Zerlate, Vancide MZ-96, Zincmate, Ziram
Technical, Ziramvis, Zirasan 90, Zirberk, Zirex 90, Ziride); nabam (Dithane
D14, Chem Bam, DSE, Nabasan, Parzate, Spring-Bak); ferbam (Ferberk,
Hexaferb, Knockmate, Trifungol, Vancide FE-95). These chemicals are
fungicides.
36
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ETHYLENE BIS DITHIOCARBAMATES
H H S
I I II
HC-N-C-S,
I Mn or Zn
H H S
COMMERCIAL PRODUCTS
maneb (Dithane M22, Griffin Manex, Kypman 80, Manebgan, Manesan,
Manzate, Nespor, Manzeb, Polyram M, Manzin, Tersan LSR, Trimangol,
Tubothane, Vancide Maneb 80); zineb (Aspor, Dipher, Dithane Z-78,
Hexathane, Kypzin, Lonacol, Parzate, Polyram Z, Tiezene, Tritoftorol, Zeb-
tox, Zinosan).
These fungicides are often combined with thiram and with various inorganic
salts of copper, manganese, and zinc in commercial preparations. Mancozeb
(Dithane M45) is essentially a combination of maneb and zineb.
(MONO) THIOCARBAMATES
R o
x II
N - C - S - R"
Aror R'
COMMERCIAL PRODUCTS
butylate (Sutan), cycloate (Ro-Neet), pebulate (Tillam), vernolate (Veraam,
Surpass), EPTC (Eptam), diallate (Avadex), triallate (Far-Go, Avadex-BW).
These chemicals are selective herbicides.
TOXICOLOGY
Although these agents have chemical similarities, the separate classes are
metabolized differently by mammals, and effects on human health are also
different.
In general, mammalian toxicity, as measured by oral dosing studies in
laboratory rodents, is low. Occupational exposures have, however, caused
acute adverse effects, and laboratory investigations have suggested potential
chronic effects from some agents.
37
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None of these agents is a cholinesterase inhibitor.
Thiram is irritating to skin and mucous membranes. It has sensitized some
individuals, generally after contact with rubber products containing residues
of thiram used as a curing agent.
The metallo dithiocarbamates and ethylene dithiocarbamates are moderately
irritating to skin and the respiratory mucous membranes following contact
with sprays or dusts.
Thiram is the methyl analogue of disulfiram (Antabuse), an agent used to
condition alcoholics against beverage alcohol. Much more is known of the tox-
ic effects-of disulfiram than of thiram, although the acute toxicity of thiram in
laboratory animals is substantially greater. Given to animals in extreme doses,
disulfiram has caused gastrointestinal irritation, demyelinization of CNS
tissues, and necrosis of liver, splenic, and kidney tissues. Peripheral neuropa-
thy and psychotic reactions have occurred in humans taking large doses of
disulfiram regularly.
Functional and anatomic CNS damage has been demonstrated in rats on
high chronic dosage regimens of iron and zinc dimethyldithiocarbamates.
Because all of these agents are degraded partly to carbon disulfide in the body,
a role of this metabolite in neurotoxic effects is suspected.
Both thiram and disulfiram inhibit aldehyde dehydrogenase, and are there-
fore capable of inducing "Antabuse" reactions in persons who consume
beverage alcohol following substantial absorption of dithiocarbamates. Reac-
tions may have occurred rarely in workers who imbibed after extraordinary oc-
cupational exposure to thiram. Theoretically, the metallo dithiocarbamates
may also predispose to an "Antabuse" reaction. Peripheral vasodilation is the
main pathophysiologic feature of the disulfiram-alcohol reaction, probably
due to high tissue levels of acetaldehyde. This may occasionally lead to shock,
and even more rarely, to myocardial ischemia, cardiac arrhythmias, circula-
tory failure, and death. Animal experimentation has suggested certain other
biochemical mechanisms of toxicity involving reaction products of ethanol
and disulfiram.
The ethylene bis dithiocarbamates do not inhibit aldehyde dehydrogenase,
and there is no evidence of neurotoxicity from them. They do, however,
degrade in the environment, and in mammalian tissues, to ethylene thiourea, a
compound known as a goitrogen and carcinogen in laboratory animals. This
feature mandates extra care in the protection of harvesters, and in removal of
residues from harvested crops.
Except for some moderate irritant effects on skin, respiratory tract, and
eyes, the (mono) thiocarbamate herbicides do not appear to be highly toxic.
Extreme doses in laboratory animals do produce paralysis. There is a very
remote possibility of "Antabuse" reactions from ethanol following extraor-
dinary exposure to these (mono) thiocarbamates. They do not form ethylene
thiourea on degradation.
38
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SYMPTOMS AND SIGNS OF POISONING
Thiram and metallo bis dithiocarbamates
Itching, redness, and eczematoid DERMATITIS have resulted when predis-
posed individuals have come into contact with these agents. Inhaled sprays and
dusts have caused NASAL STUFFINESS, hoarseness, cough, and, rarely,
pneumonitis. Repeated contact may produce sensitization. Ingestion of large
amounts may produce nausea, VOMITING, and DIARRHEA. HYPO-
THERMIA and ataxia are characteristic of poisoning. Muscle WEAKNESS
and/or ascending paralysis may progress to respiratory paralysis if absorbed
dosages are equivalent to those tested in experimental animals.
The reaction to beverage alcohol that may follow exceptional absorption of
thiram and metallo bis dithiocarbamates is characterized by FLUSHING,
HEADACHE, SWEATING, warm sensations, weakness, nasal congestion,
labored breathing, tightness in the chest, tachycardia, palpitation, and hypo-
tension. Extreme dosages may result in shock, convulsions, respiratory depres-
sion, and/or unconsciousness. Reactions are not likely to occur unless the
absorbed dose is extraordinary.
Ethylene bis dithiocarbamates and (mono) thiocarbamates
Some of these agents are irritating to skin and respiratory mucous mem-
branes, causing ITCHING, SCRATCHY THROAT, SNEEZING, and
COUGH, if excessive amounts of spray or dust are inhaled. Apart from this
effect, toxic potential is low. Neurotoxic and post-ethanol "Antabuse" reac-
tions are not known to occur as a result of contact with these particular com-
pounds.
CONFIRMATION OF DIAGNOSIS
Skin testing may be useful in identifying sensitization to these agents.
In general, these compounds are so rapidly metabolized in the body and ex-
creted, that detection in blood is rarely possible. There are methods for detec-
tion of ethylene thiourea (from the ethylene bis dithiocarbamates) in urine.
TREATMENT
1. WASH contaminating chemical from SKIN and HAIR with soap and
water. Persons sensitive to thiram (rubber-sensitive) should be per-
manently REMOVED FROM CONTACT with compounds of this
nature.
2. FLUSH contaminant from EYES with fresh water for 10-15 minutes.
3. If THIRAM or METALLO DITHIOCARBAMATE compounds have
been INGESTED:
39
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A. If vigorous emesis has not already occurred and victim is fully alert,
give SYRUP OF IPECAC, followed by 1-2 glasses of water to in-
duce vomiting (adults, 12 years and older: 30 ml; children under 12:
15 ml).
CAUTION: OBSERVE victim closely AFTER administering
IPECAC. If CONSCIOUSNESS level declines or
vomiting has not occurred in 15 minutes, empty the
stomach by INTUBATION, ASPIRATION, and
LAVAGE.
B. IF consciousness level or respiration is DEPRESSED, empty the
stomach by INTUBATION, ASPIRATION, and LAVAGE, using
all available means to avoid aspiration of vomitus: left lateral
Trendelenburg position, frequent aspiration of the pharynx and, in
unconscious victims, tracheal intubation (using a cuffed tube) prior
to gastric intubation.
After aspiration of the stomach and washing with isotonic saline or
sodium bicarbonate, instill 30-50 gm of ACTIVATED CHAR-
COAL in 3-4 ounces of water through the stomach tube to limit
absorption of remaining toxicant.
C. If the irritant properties of the toxicant fail to produce a bowel
movement in 4 hours, administer SODIUM or MAGNESIUM
SULFATE as a cathartic: 0.25 gm/kg body weight in 1-6 ounces of
water.
D. Administer glucose-containing fluids intravenously to accelerate ex-
cretion of toxicant.
E. For adults and children over 12 years, inject 1.0 gm ASCORBIC
ACID (Vitamin C) intravenously at a rate not exceeding 0.2
gm/minute. For children under 12, give 10-20 mg/kg body weight.
As a hydrogen-donor, ascorbic acid may have significant antidotal
action against absorbed, but unreacted, dithiocarbamate com-
pounds.
F. The victim must AVOID consumption of any ALCOHOLIC bever-
age for 3 weeks. Gastrointestinal absorption of these substances is
slow, and the enzyme inhibition which they cause is slowly reversed.
4. Management of a reaction to ETHANOL, following absorption of a
DITHIOCARBAMATE:
A. Administer 100% OXYGEN as long as the reaction continues. Ox-
ygen usually gives substantial relief from the distressing symptoms
of vasodilation and hypotension.
CAUTION: If respiration is depressed, administer oxygen by an
intermittent positive pressure breathing device and
observe the victim closely to maintain pulmonary
ventilation mechanically in case of apnea.
40
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B. Gastric evacuation, charcoal administration, catharsis, intravenous
fluids, and ascorbic acid administration (3 A,B,C,D, and E) may be
appropriate, depending on the amount of dithiocarbamate absorbed,
the time interval between exposure and treatment, and the severity
of symptoms.
C. If the victim has suffered from arteriosclerosis, myocardial insuffi-
ciency, diabetes, neuropathy, cirrhosis, or other severe chronic
disease, OBSERVE him CAREFULLY for 48 hours to insure that
complications (especially myocardial infarction, toxic psychosis,
and neuropathy) are treated promptly.
5. If an ETHYLENE BIS DITHIOCARBAMATE, or (mono) THIOCAR-
BAM ATE have been ingested:
A. Give SYRUP OF IPECAC, followed by 1-2 glasses of water, to in-
duce vomiting (adults: 30 ml; children under 12 years: 15 ml). Fol-
lowing emesis, administer 30-50 gm ACTIVATED CHARCOAL
to bind toxicant remaining in the gut.
B. Follow charcoal with SODIUM or MAGNESIUM SULFATE, 0.25
gm/kg, to remove toxicant from the gut by catharsis.
41
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Chapters
PYRETHRUM, PYRETHRINS,
PYRETHROIDS, AND PIPERONYL
BUTOXIDE
Pyrethrum is the partly refined extract of the chrysanthemum flower which
has been used as an insecticide for more than 60 years. Pyrethrins are the insec-
ticidally active ingredients of pyrethrum, now known to consist of keto-
alcohol esters of pyrethric and chrysanthemic acids. The alcohols are pyrethro-
lone, cinerolone, and jasmololone, whose respective esters are known as
pyrethrins, cinerins, and jasmolins. Pyrethroids are synthetic compounds
based structurally on the pyrethrin molecule but modified to improve stability
in the natural environment (light, heat, etc.)
GENERAL CHEMICAL STRUCTURE
R H H CH3
11 I H O H '
C = C - C I II \ /<%
I |^C-C-0-C C-R'
CH3 CHa-C^ | |
I H C — C = O
CH3 H
COMMON COMMERCIAL PESTICIDE PRODUCTS
Pyrethrins: There are several hundred commercial products containing
pyrethrins and pyrethroids. Commonly, these products combine pyrethrins or
pyrethroids with a synergist, such as piperonyl butoxide, and an additional
pesticide, for increased killing power. Many of these combinations are pack-
aged with a propellant in a spray can or bug-bomb.
Pyrethroids: Allethrin (Pynamin), barthrin, bioresmethrin, cypermethrin
(Ripcord), decamethrin, fenothrin, fenpropanate, fenvalerate (Belmark,
Pydrin), permethrin (Ambush, Ectiban, Pounce), phthalthrin or tetramethrin
(Neo-Pynamin), resmethrin (Synthrin, Chrysron).
TOXICOLOGY
These esters rapidly paralyze the insect nervous system, making them
famous for their quick "knockdown" effect. Mammalian toxicity, however, is
extraordinarily low for pyrethrins and pyrethroids. Oral LD5o values for these
compounds in rats are several hundred or thousand mg/kg body weight. There
is apparently less efficient absorption of pyrethrins across the GI lining and
42
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skin than across insect chitin, and much more rapid biodegradation
(hydrolysis and oxidation) by the mammalian liver than by insect tissues.
Some of the less purified pyrethrum extracts contain allergenic substances
that induce attacks of allergic rhinitis and asthma in humans. Rarely, hyper-
sensitivity pneumonitis has followed pyrethrum inhalation.
Administered orally to rodents in extraordinary dosage, pyrethrins and
pyrethroids cause nervous irritability, tremors, and motor ataxia. Bloody tears
and urinary incontinence have also been observed. Manifestations of toxicity
occur at much lower dosage following intravenous administration than after
oral dosing. Chronic feeding of these chemicals induces an increase in liver size
and bile duct hyperplasia. To date, neither pyrethrins nor pyrethroids have
been identified as mutagenic, carcinogenic, or teratogenic.
Piperonyl butoxide inhibits the mixed function oxidase enzymes of the liver
which catabolize pyrethrins and pyrethroids. The amount absorbed by humans
during ordinary exposure is not likely to affect liver function measurably.
FREQUENT SYMPTOMS AND SIGNS OF UNDUE EXPOSURE
A STUFFY, RUNNY NOSE and scratchy throat from inhalation of partly
purified pyrethrum extract is the most common adverse effect of these agents.
Asthmatic WHEEZING may be precipitated by exposure of predisposed indi-
viduals.
Sudden bronchospasm, swelling of oral and laryngeal mucous membranes,
and shock (anaphylaxis) have been reported after pyrethrum inhalation.
Delayed appearance of dyspnea, cough and fever, with patchy lung infiltrates
on x-ray, suggest hypersensitivity pneumonitis.
Nervous irritability, tremors, and ataxia have occurred rarely in persons
who have had massive inhalation exposure to pyrethrins.
Halocarbon propellents in bug-bomb products present a risk of CARDIAC
ARRHYTHMIA and possibly fibrillation if inhaled to excess. Hydrocarbons
used as solvents in spray products are likely to result in COUGH, FEVER, and
CHEST PAIN (hydrocarbon pneumonitis) if these liquids are inadvertently
aspirated.
CONFIRMATION OF DIAGNOSIS
Skin tests sometimes identify sensitivity to pyrethrum. Neither pyrethrins
nor pyrethroids inhibit cholinesterase enzymes. There are gas-chromato-
graphic methods for identifying some of these insecticides in environmental
samples, but they are not likely to be useful in diagnosing poisoning because of
the rapid metabolism of the esters following absorption. There are no methods
for identifying urinary metabolites.
43
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TREATMENT
1. WASH contaminating pesticide from the EYE with copious amounts of
water. Wash contaminated SKIN with soap and water.
2. For life-threatening allergic reaction to pyrethrum (severe ASTHMA or
ANAPHYLAXIS), give 0.1 to 0.5 ml of 1:1000 ADRENALIN intramus-
cularly, or slowly intravenously. Repeat if necessary to relieve respiratory
distress and maintain blood pressure. Intravenous AMINOPHYLLINE
(10 ml, slowly) may be indicated. Give HYDROCORTISONE (50-100
mg), or equivalent steroid, intravenously.
Less severe allergic reactions (rhinitis) can be managed with ANTI-
HISTAMINES and DECONGESTANTS, given orally.
HYPERSENSITIVITY PNEUMONITIS may require oxygen, ste-
roids, antibiotics and several days bedrest, depending on severity.
3. INGESTION of a SMALL AMOUNT of a pyrethrin or pyrethroid for-
mulation is not likely to cause poisoning. EXAMINE THE LABEL to
identify additional insecticides, which may be more toxic. BASE
TREATMENT ON THE MOST TOXIC ingredients.
A. If a formulation contains ONLY pyrethrins, or pyrethroids, and
synergists, ingestion of a small amount (up to about 5 mg/kg) is
probably best treated by large doses of ACTIVATED CHAR-
COAL, 30-50 gm in 3-4 ounces of water, followed by cathartic doses
of SODIUM or MAGNESIUM SULFATE, 0.25 gm/kg body
weight in 1-6 ounces of water.
4. If LARGE AMOUNTS of pyrethrin or pyrethroid formulation have
been INGESTED, the stomach and intestine must be evacuated:
A. IF victim is ALERT and respiration is not depressed, give SYRUP
OF IPECAC, followed by 1-2 glasses of water, to induce vomiting
(adults and children 12 years and older: 30 ml; children under 12
years: 15 ml).
CAUTION: OBSERVE VICTIM closely AFTER administering
IPECAC. If consciousness level declines or vomiting
has not occurred in 15 minutes, INTUBATE the
stomach immediately.
Following emesis, have victim drink a suspension of 30-50 gm AC-
TIVATED CHARCOAL in 3-4 ounces of water to limit absorption
of toxicant remaining in the gut.
B. IF victim is NOT FULLY ALERT, empty stomach immediately by
INTUBATION, ASPIRATION, and LAVAGE, using isotonic
saline or 5% sodium bicarbonate. Because many pesticides are dis-
solved in petroleum distillates, emesis and intubation of the stomach
involve a risk that solvent will be aspirated, leading to chemical
pneumonitis. For this reason:
44
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(a). If victim is unconscious or obtunded and facilities are at hand,
insert an ENDOTRACHEAL TUBE (cuffed, if available) prior
to gastric intubation.
(b). Keep victim's HEAD BELOW LEVEL OF THE STOMACH
during intubation and lavage (Trendelenburg, or left lateral
decubitus, with head of table tipped downward). Keep
victim's head turned to left.
(c). ASPIRATE PHARYNX as regularly as possible to remove
gagged or vomited stomach contents.
(d). After aspiration of gastric contents and washing of stomach,
instill 30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces
of water through stomach tube to limit absorption of remain-
ing toxicant.
(e). If bowel movement has not occurred in 4 hours and patient is
fully conscious, give SODIUM or MAGNESIUM SULFATE
as a cathartic: 0.25 gm/kg body weight in 1-6 ounces of water.
5. Do NOT administer or instill milk, cream, or other substances containing
vegetable or animal fats, which enhance absorption of lipophilic sub-
stances, such as pyrethrins and pyrethroids.
6. DIAZEPAM (Valium®), 5-10 mg in adults, 0.1 mg/kg in children, given
orally or slowly IV, should control nervousness and tremors in rare cases
having these symptoms after extraordinary exposure to pyrethrins and
pyrethroids.
45
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Chapter 10
ARSENICAL PESTICIDES
CHEMICAL STRUCTURES
INORGANIC ARSENICALS
Extremely Toxic
As - O - As
Na - O - As = O
K - O - As = O
ARSENIC
TRIOXIDE
SODIUM
ARSENITE
POTASSIUM
ARSENITE
Cu - (O - C - CH3) 2
n
• 0
3Cu - (As O2)2
COPPER
ACETOARSENITE
Highly Toxic
Ca3(As 04) 2
CALCIUM ARSENATE
Moderately Toxic
Ca (As O2) 2
CALCIUM ARSENITE
Cu - (AsO2)
I
O
H
COPPER ARSENITE
(HO)3 AS = O
ARSENIC ACID
Pb As = O
O
H
LEAD ARSENATE
46
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ORGANIC ARSENICALS
Moderately Toxic
CH3 ^ CH3
/ AS\
O^ OH
CACODYLIC ACID
As
METHANE ARSONIC ACID
(MAA)
. As
<> \
O OH
MONOSODIUM
METHYL ARSONATE
(MSMA)
CH3x ^ONa
s- As
° ONa
DISODIUM
METHYL ARSONATE
(DSMA)
,\ /ONH4
As
O^ OH
MONOAMMONIUM
METHANE ARSONATE
47
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COMMON COMMERCIAL ARSENIC PRODUCTS
1. Arsenic trioxide
2. Sodium arsenite:
3. Calcium arsenite:
4. Copper arsenite:
5. Copper acetoarsenite:
6. Arsenic acid:
7. Sodium arsenate:
8. Calcium arsenate:
9. Lead arsenate:
10. Methane arsonic acid:
11. Monosodium methyl arsonate:
12. Disodium methyl arsonate:
13. Monoammonium methyl arsonate:
14. Calcium acid methanearsonate:
15. Cacodylic acid:
"White arsenic," arsenious oxide
(registered only for ant pastes,
veterinary medicinals, and marine
antifouling preparations).
Chem Pels C, Chem-Sen 56, Kill-
All, Penite, Prodalumnol Double.
Mono-calcium arsenite.
Chemonite.
Paris green, Schweinfurt green,
emerald green, French green, mitis
green.
Desiccant L-10, Hi-Yield Desic-
cant H-10.
Jones Ant Killer, Terro Ant Killer.
Pencal, Spra-cal, Security.
Gypsine, Security, Soprabel,
Talbot.
MAA.
MSMA, Ansar 17OHC, methane
arsonate, Ansar 529HC, Arsonate
liquid, Bueno 6, Daconate 6, Dal-
E-Rad, Herb-All, Merge 823,
Mesamate, Target MSMA, Trans-
Vert, Weed-E-Rad, Weed-Hoe.
DSMA, Ansar 8100, methane ar-
sonate, Ansar DSMA liquid, Ar-
rhenal, Arsinyl, Chipco Crab
Kleen, Crab-E-Rad, Dal-E-Rad
100, Di-Tac, DMA, DMA 100,
Methar, Namate, Sodar, Weed-E-
Rad, Weed-E-Rad 360, Weed-E-
Rad DMA Powder, Weed-Hoe.
MAMA, monoammonium meth-
anearsonate.
CAMA, Super Crab-E-Rad-Calar,
Super Dal-E-Rad "Calar".
Dilic, Phytar 560, Rad-E-Cate 25,
Salvo, f [Crystal Chemical Com-
pany)
A product of identical name marketed by Crystal Chemical Company
contains 2,4-D as the active ingredient (Chapter 6).
48
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TOXICOLOGY
Although there may be some degree of dermal and pulmonary absorption of
arsenical liquids and sprays, ingestion is the route of intake involved in virtual-
ly all acute poisonings by the solid arsenicals.
Inhalation of arsine gas (sometimes generated inadvertently in pesticide
manufacturing plants) has caused serious illness and death by hemolytic action.
Generally, the organic (methylated) pentavalent arsenicals are considerably
less toxic than the trivalent inorganic arsenicals. In fact, methylation is the
principal mechanism of detoxification of inorganic arsenicals in mammals.
The less soluble inorganic forms (notably lead arsenate, and even arsenic triox-
ide) present less hazard than the highly soluble salts such as sodium arsenite
and copper acetoarsenite. But because gastric pH, gastrointestinal motility,
and gut bacterial action can enhance the absorption and toxicity of ingested
compounds, it is safest to manage cases of arsenic ingestion as though all
forms of arsenic are highly toxic.
Trivalent arsenicals (or, more likely, an arsenious acid metabolite) bind effi-
ciently to the functional thiol groups of many tissue components, including en-
zymes. The affinity for thiol groups in keratin accounts for the accumulation
of arsenic in skin, nails, and hair in cases of chronic poisoning. When absorbed
across the gut wall, these arsenicals injure the splanchnic vasculature, causing
abdominal pain, colic, and diarrhea. Once absorbed into the blood, they cause
toxic damage to the liver, kidneys, brain, bone marrow, and peripheral nerves.
Liver injury is manifest as hepatomegaly, jaundice, and increase in circulating
hepatocellular enzymes LDH and GOT. Renal damage is reflected in albumin-
uria, hematuria, pyuria, cylindruria, then azotemia. Acute tubular necrosis
may occur in severe poisoning. Injury to blood-forming tissues can take the
form of agranulocytosis, aplastic anemia, thrombocytopenia, or pancytopenia.
Toxic encephalopathy may be manifest as speech and behavioral disturbances.
Peripheral neuropathy occurs in both acute and chronic forms.
Sequelae of arsenic poisoning include cirrhosis, hypoplastic bone marrow,
renal insufficiency, and peripheral neuropathy. Excessive exposures to arseni-
cals have caused hyperkeratosis and skin cancers. Excessive inhalation of dusts
may cause bronchitis and pneumonia; protracted inhalation has been asso-
ciated epidemiologically with increased occurrence of lung cancer.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
ACUTE arsenic poisoning
COLIC, BURNING ABDOMINAL PAIN, VOMITING, and WATERY or
BLOODY DIARRHEA are the primary manifestations of ingestion of solid
arsenical poisons. Symptoms following ingestion of inorganic arsenicals are
much more severe than those resulting from ingestion of pentavalent organic
arsenicals. Symptoms are sometimes delayed for minutes or even hours after
ingestion. HEADACHE, DIZZINESS, MUSCLE SPASMS, DELIRIUM,
49
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and sometimes CONVULSIONS reflect direct injury to the central nervous
system, as well as extracellular electrolyte disturbances and shock. A GARLIC
ODOR to the breath and feces helps to identify the responsible toxicant.
SHOCK, TOXIC NEPHROSIS, HEPATITIS (hepatomegaly and jaundice),
and NEUROLOGIC INJURY (delirium, paralysis, respiratory depression)
may progress to a fatal outcome.
SUBACUTE arsenic poisoning
Repeated intakes less than those necessary to produce severe acute symp-
toms are known to cause CHRONIC HEADACHE, ABDOMINAL DIS-
TRESS, SALIVATION, LOW-GRADE FEVER, and PERSISTENT symp-
toms of UPPER RESPIRATORY IRRITATION. Stomatitis and garlicky
breath are characteristic.
CHRONIC arsenic poisoning
Prolonged low intakes of arsenic cause peripheral neuropathy (PARES-
THESIAE, PAIN, anesthesia, paresis, ataxia), encephalopathy (APATHY,
disorientation), dermatologic disorders (KERATOSES, pigmentation,
eczema, brittle nails, loss of hair), toxic hepatitis (HEPATOMEGALY, some-
times progressing to cirrhosis with ascites), and bone marrow injury
(ANEMIA, leukopenia, WEAKNESS). Local EDEMA, frequently of the eye-
lids, characterizes some poisonings.
ACUTE arsine gas poisoning
The gas causes hemolysis of red blood cells, in addition to inhibition of
cellular sulfhydryl respiratory enzymes. Hemolysis causes HEMOGLOBINE-
MIA and HEMOGLOBINURIA. This in turn, causes acute tubular necrosis.
Early symptoms of poisoning (CHILLS, weakness, burning sensations) are
followed by abdominal CRAMPS, vomiting, and prostration. Failing renal
function deteriorates to ANURIA.
CONFIRMATION OF DIAGNOSIS
Measurement of 24-hour urinary excretion of arsenic is probably the best
way to confirm excessive arsenic absorption, although methods for blood
arsenic concentration are available. Persons on ordinary diets usually excrete
less than 20 Mg/day but diets rich in seafood may generate as much as 200
Mg/day. Excretions above 100 Mg/day should be viewed with suspicion and
tests should be repeated. Excretions above 200 Mg/day reflect a toxic intake,
unless seafood was ingested. (The arsenic in seafood is apparently bound firm-
ly to an organic moiety that renders the arsenic essentially nontoxic and highly
excretable.)
The qualitative Gutzeit test for arsenic in the urine is available in most
hospital laboratories, and is useful in identifying acute poisonings promptly.
50
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Chronic storage of arsenic can be detected by analysis of hair or fingernails.
The hemoglobinuria caused by arsine is identified by finding free hemoglo-
bin in fresh urine.
TREATMENT OF POISONING BY SOLID ARSENICALS
1. Flush contaminated EYES, HAIR and SKIN with copious amounts of
fresh water. WASH SKIN and HAIR with soap and water.
2. In poisonings by INGESTED ARSENICALS
A. INTUBATE the stomach, ASPIRATE, and LAV AGE with 3 liters
of isotonic saline or 5% sodium bicarbonate. Use all possible pre-
cautions to avoid aspiration of vomitus:
(1) If victim is unconscious or obtunded, insert an ENDO-
TRACHEAL TUBE (cuffed, if available) prior to gastric intu-
bation.
(2) Keep victim's HEAD BELOW LEVEL OF THE STOMACH
during intubation (Trendelenburg, or left lateral decubitus,
with head of table tipped downward). Keep victim's head
turned to the left.
(3) ASPIRATE pharynx as regularly as possible to remove gagged
or vomited stomach contents.
B. After lavage, INSTILL 30-50 gm ACTIVATED CHARCOAL in
the smallest amount of water necessary to deliver the charcoal
through the tube.
C. If diarrhea or colic has not ensued within an hour of gastric lavage
and charcoal administration, give SODIUM SULFATE as a cathar-
tic 0.25 gm/kg body weight in 1-6 ounces of water.
3. An ABDOMINAL X-RAY film is useful in detecting concretions of the
less soluble arsenicals (As2O3 and lead arsenate) in the gut. If not re-
moved these may become a repository of slowly absorbed toxicant.
4. Administer INTRAVENOUS ELECTROLYTE and GLUCOSE solu-
tions to maintain hydration and to accelerate toxicant excretion. COM-
BAT SHOCK with TRANSFUSIONS of WHOLE BLOOD, and by in-
halation of 100% OXYGEN.
CAUTION: Monitor urine flow via catheter. Monitor fluid balance,
body weight, and/or central venous pressure to guard
against fluid overload that may result if tubular necrosis
(anuria) supervenes.
5. Administer DIMERCAPROL (BAL) and PENICILLAMINE to acceler-
ate arsenic excretion.
A. Give dimercaprol, 3-5 mg/kg q4h intramuscularly until abdominal
pain and diarrhea subside and patient is regularly passing admin-
istered charcoal in the feces. IF victim is ALLERGIC to
51
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PENICILLIN, continue dimercaprol therapy at 3-5 mg/kg q6h x 4
doses, then q!2h x 2 doses, then q24h x 10 doses, monitoring
urine arsenic excretion periodically to judge effectiveness.
CAUTION: DIMERCAPROL can cause troublesome side effects
(hypertension, tachycardia, nausea, headache, pares-
thesiae and pain, lacrimation, sweating, anxiety, and
restlessness). Although usually not so severe as to
preclude treatment, they may require antihistaminic
therapy.
B. IF victim is NOT ALLERGIC to PENICILLIN, oral d-PENICIL-
LAMINE is the therapy of choice and should REPLACE dimer-
caprol treatment as soon as the feces are laden with charcoal, limiting
gut absorption of arsenic. Adult dosage is 0.5 gm four times daily (2
gm/day), given before meals, for 5 days. Dosage for children is
0.025 gm/kg four times daily, not to exceed 2 gm/day for 5 days.
CAUTION: Although oral d-penicillamine therapy is usually better
tolerated than intramuscular dimercaprol, serious
reactions to it have occurred: the most common has
been maculopapular rash, with fever, leukopenia,
thrombocytopenia, eosinophilia, arthralgia and lym-
phadenopathy. It has also induced the nephrotic syn-
drome on occasion, and has caused thrombophlebitis,
cheilosis, angioneurotic edema, and even fatal agran-
ulocytosis in particular patients given the drug over
long periods for conditions unrelated to arsenic poi-
soning. Penicillin sensitive individuals are likely to be
sensitive to d-penicillamine.
(a). A single 5 day course of d-penicillamine therapy is usually suf-
ficient. However, if symptoms recur after treatment, addi-
tional d-penicillamine should be given at a dosage just suffi-
cient to abolish symptoms.
6. Intense abdominal pain may require morphine (adults, 12 years and
older: 4-15 mg; children under 12 years: 0.1-0.2 mg/kg).
7. Severe poisoning (especially when renal function is impaired) may re-
quire HEMODIALYSIS to remove arsenic combined with dimercaprol
from the blood, and to control extracellular fluid composition. HEMO-
PERFUSION may be useful, but its effectiveness has not been reported.
TREATMENT OF POISONING BY ARSINE GAS
1. REMOVE victim to FRESH AIR.
2. MAINTAIN RESPIRATION and CIRCULATION by resuscitation and
cardiac massage, if necessary.
52
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3. Administer INTRAVENOUS FLUIDS promptly to dilute free hemoglo-
bin and minimize tubular injury. Include enough sodium bicarbonate to
keep the urine alkaline.
CAUTION: Monitor urine flow via catheter. Monitor fluid balance,
body weight, and/or central venous pressure to guard
against fluid overload resulting from acute tubular
necrosis.
4. Administer DIMERCAPROL as recommended in 5A even though it has
only limited effect in arsine poisoning.
5. EXCHANGE BLOOD TRANSFUSIONS and PERITONEAL DIALY-
SIS have saved the lives of victims of arsine poisoning suffering acute
tubular necrosis.
53
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Chapter 11
RODENTICIDES
STRUCTURES OF PRINCIPAL COMPOUNDS
ALKYL, PHENYL, i
DIPHENYLACETYL or
CHLORODIPHENYLACETYL
WARFARIN
1,3 INDANDIONE
C = S
a-NAPHTHYL
THIOUREA
H O
I H
F - C - C-ONa
I
H
SODIUM
FLUOROACETATE
Zn
/ \
P - Zn - P
\ /
Zn
ZINC
PHOSPHIDE
\ /
P
YELLOW
PHOSPHORUS
54
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SCILLIROSIDE
(Active principle of Red Squill)
= O
STRYCHNINE
,— C-N-C-N—V \
-NO,
H H II H
O
RH- 787 (Active
ingredient of VACOR and
DLP-787)
CH3-C
II
H -C
'C-CI
I
N
I
N
NORBORMIDE
CRIMIDINE
55
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COMMON COMMERCIAL RODENTICIDE PRODUCTS
Coumarins: warfarin, coumafene, zoocoumarin (Kypfarin, Ratox, RAX,
Rodex, Tox-Hid, Warfarin Plus); coumafuryl (Tomarin, Fumarin);
bromadiolone (Bromone, Super-Caid, Ratimus), coumachlor (Tomorin).
Indandiones: diphacinone (Diphacin, Promar, Ramik); chlorophacinone
(Caid, Drat, Liphadione, Microzul, Ramucide, Ratomet, Raviac, Rozol,
Topitox); pindone or pivaldione (Pival, Pivacin, Pivalyn, Tri-ban).
Other anticoagulant rodenticides of different structure: difenacoum
(Ratak); brodifacoum (Talon).
Sodium fluoroacetate: 1080, Fratol, Yasoknock.
Zinc phosphide: Phosvin, Zinc-Tox.
Yellow phosphorus and strychnine have limited use and are generally identi-
fied by these long established common names.
Crimidine: Castrix.
RH-787: This product is no longer available for sale, but existing stocks
present a continuing threat of poisoning. Commercial products are: Vacor Rat
Killer (2% RH-787 in vehicle resembling corn meal); DLP-787 Bait (2%
RH-787 in vehicle resembling corn meal); DLP-787 House Mouse Tracking
Powder (10% RH-787 in a light green powder).
Red squill: Dethdiet, Rodine.
Antu: Krysid.
Norbormide: Shoxin, Raticate.
TOXICOLOGY
Rodent poisons are generally added to baits, i.e., grain or paste designed to
encourage consumption. Safety for pets, domestic animals, and humans
depends on the toxicity of the agents, concentration of active ingredients in the
baits, and the likelihood that a toxic dose will be consumed by nontarget
species. The coumarins are reasonably effective against pest rodents and have
a good safety record. This is due mainly to the low concentration of active in-
gredient in the bait: about 100 gm of the commercial bait must be ingested to
yield 25 mg of anticoagulant. This is important in evaluating suspected poison-
ings by anticoagulants, which are the most widely available rodenticides for
public use.
Very small amounts of the extremely toxic rodenticides—sodium fluoro-
acetate, zinc phosphide, crimidine, strychnine, and yellow phosphorus—can
cause fatal poisoning.
Vacor should be considered highly toxic. Ingestion of less than 1 gm by an
adult has caused severe poisoning.
Antu, red squill, and norbormide present considerably less toxic hazard to
humans and to domestic animals.
t A rodenticide of identical trade name is still available in some areas which
contains thallium sulfate as the active ingredient. Use of thallium in the
United States is now restricted.
56
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Coumarins, indandiones, and other anticoagulants: Gastrointestinal absorp-
tion of these toxicants is efficient, beginning within minutes of ingestion and
continuing for 2 to 3 days. Apparently warfarin can also be absorbed across
the skin, although the circumstances under which this occurred were extraordi-
nary.
These agents depress the hepatic synthesis of substances essential to blood
clotting: prothrombin (factor II) and factors VII, IX, and X. The antipro-
thrombin effect is best known, and provides the basis for detection and assess-
ment of clinical poisoning. Direct damage to capillary permeability occurs
concurrently. The ultimate effect of these actions is to induce widespread in-
ternal hemorrhage. This generally occurs in the rodent after several days of
bait ingestion, although the modern products (diphacinone, chlorophacinone,
pindone, difenacoum, and brodifacoum) may be lethal after fewer feedings.
These modern agents should be considered more toxic than warfarin.
In rare instances, coumarin-type anticoagulants have caused ecchymosis and
extensive skin necrosis in humans for reasons not related to excessive dosage.
Unlike the coumarin anticoagulants, the indandiones cause symptoms and
signs of neurologic and cardiopulmonary injury in laboratory rats; these often
lead to death before hemorrhage occurs. These actions may account for the
somewhat greater toxicity of this class of anticoagulants. Neither cardiopul-
monary nor neurologic symptoms or signs have been reported in human
poisonings.
Lengthened prothrombin time from a toxic dose is usually evident within 24
hours of ingestion and reaches a maximum in 36 to 72 hours. Without inter-
vention, hypoprothrombinemia may persist 10 to 15 days, depending on the
agent and dosage. Prothrombin depression occurs in response to doses much
lower than those necessary to cause hemorrhage.
Sodium fluoroacetate: the fluorocitrate metabolite of this poison blocks
energy production in mammalian cells at the level of the tricarboxylic acid cy-
cle. The critical sites of toxic effect in humans are the myocardium (where ven-
tricular fibrillation is the usual cause of death) and the brain, where seizures
are induced and respiration is depressed. Seizures, respiratory depression, and
ventricular fibrillation are all causes of death.
Zinc phosphide: this inorganic compound produces severe gastrointestinal
irritation. It degrades in the gut to phosphine gas which, when absorbed,
causes pulmonary edema and severe liver, kidney, CNS, and myocardial
injury.
Yellow phosphorus: this agent causes severe gastrointestinal irritation result-
ing in vomiting, diarrhea, and melena. Circulatory collapse may occur and
prove irreversible. Liver necrosis and acute renal tubular necrosis are equally
ominous threats to life. Hemorrhage, from hypoprothrombinemia, and car-
diac arrest or fibrillation, account for some deaths.
Strychnine: this natural poison acts directly on the cells of the brain and
spinal cord to cause convulsions. Death is caused by convulsive interference
with pulmonary gas exchange, by depression of respiratory center activity, or
both.
57
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Crimidine: this is a synthetic pesticide which, although unrelated chemically
to strychnine, exerts toxic effects similar to those of strychnine, producing
violent convulsions and secondary tissue anoxia by its action on the CNS.
Vacor, DLP-787: the exact mechanism of RH-787 toxicity is not known
although one established effect in rats is interference with nicotinamide
metabolism. RH-787 has no anticoagulant action. Symptoms and signs in
poisoned animals suggest toxic actions on the brain, peripheral nerves,
myoneural junctions, pancreatic islet tissues, autonomic nervous system, and
the conducting tissues of the heart. Abnormalities of renal and vascular func-
tion may be direct effects of poisoning, or they may reflect metabolic and
autonomic nervous system disturbances, impaired vascular reactivity in par-
ticular.
Red squill: this biological agent is unlikely to present a serious toxic hazard
to humans or other vomiting species, because 1) it usually induces prompt
emesis, 2) it is poorly absorbed from the gut, and 3) the active principles are in
low concentration, and are rapidly excreted. Natural squill contains digitalis-
like glycosides, which might, theoretically, produce manifestations of digitali-
zation in humans. The glycoside known as scilliroside is the probable cause of
convulsive death in the rat; convulsions have not been observed in human
poisonings.
Antu: this agent exhibits selective toxicity for the rat, causing pulmonary
edema and pleural effusion. Only one human poisoning is recorded, and it was
induced by a large suicidal dose. Vomiting was followed by dyspnea, cyanosis,
and pulmonary rales, presumably reflecting pulmonary edema. The patient
recovered.
Norbormide: this is selectively toxic to Norway and roof rats, which it kills
by inducing a generalized, sudden, and intense vasoconstriction. Other vari-
eties of rats are resistant, and the chemical is only moderately toxic to other
mammals, including humans. Oral doses of 300 mg cause transient lowering of
blood pressure and body temperature in humans.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
Coumarins, indandiones, and other anticoagulants: In most cases of inges-
tion of anticoagulants, victims have remained asymptomatic, due to the small
dosage taken. Even in cases involving ingestion of substantial amounts of anti-
coagulant compound (more often medication than rodenticide), hypopro-
thrombinemia has occurred without symptoms of poisoning. Hemorrhage ap-
pears only when extraordinary amounts have been absorbed. In reported
cases, the anticoagulants were either taken deliberately, were absorbed over
long periods out of neglect of elementary hygienic standards, or were ingested
by starving indigents who used quantities of rodent bait as food.
Victims of large doses exhibit HEMATURIA, NOSEBLEED, HEMATO-
MATA, BLEEDING GUMS, and MELENA. ABDOMINAL PAIN and
BACK PAIN probably reflect hemorrhage in the abdominal and retroperito-
neal tissues. WEAKNESS occurs as a result of ANEMIA. RENAL COLIC
58
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often complicates severe hematuria. Nasal and gastrointestinal hemorrhages
have occasionally caused death from exsanguination.
Sodium fluoroacetate: A delay of several minutes or even hours may be ex-
pected before symptoms appear. Epigastric distress and vomiting often occur.
Apprehension, PARESTHESIAE and hallucinations are the usual
premonitory symptoms, leading to epileptiform CONVULSIONS. CARDIAC
IRREGULARITIES (ectopic beats, pulsus alternans, ventricular tachycardia
and fibrillation) appear after seizures commence. These are frequently fatal.
Zinc phosphide: Intense NAUSEA, abdominal pain, excitement, and chills
are early symptoms. Tightness in the chest, DYSPNEA and COUGH, produc-
tive of FROTHY SPUTUM, reflect pulmonary edema. SHOCK from toxic
myocarditis is common. If these conditions are survived, JAUNDICE from
liver necrosis, and ANURIA from renal tubular injury are later complications.
Hypocalcemic TETANY and PURPURA have occurred in some poisonings.
Yellow phosphorus: BURNING PAIN in the throat, chest, and abdomen
reflect severe mucosal irritation. Vomiting and diarrhea ensue. Breath has
garlicky odor. Feces may luminesce and "smoke" from phosphorus fumes.
SHOCK often progresses to death in 1 to 2 days. The patient who survives
may then be relatively symptom-free for several hours or even days, after
which the delayed manifestations appear due to liver, CNS, myocardial and
renal injury. Nausea and VOMITING persist. HEMORRHAGE at various
sites reflects mainly depression of clotting-factor synthesis in the liver.
SHOCK may be due to hemorrhage and/or toxic myocarditis. CONVUL-
SIONS, delirium, and coma are common. ANURIA usually ensues as a result
of direct nephrotoxic effect of phosphorus, enhanced by biliary nephrosis
(hepatorenal syndrome).
Strychnine: Within 10 to 60 minutes of ingestion of an adequate dose (as lit-
tle as 16 mg), the victim suffers VIOLENT CONVULSIONS caused by clonic,
then tonic contraction of all the skeletal muscles of the body. Cyanosis
develops promptly. Brief periods of relaxation may occur, followed by even
more severe seizures. Opisthotonus is common, and the muscles of the face are
drawn into a grimace. Death is usually due to ASPHYXIA, a consequence of
convulsive spasm of the respiratory muscles.
Crimidine: Ingestion is followed promptly by VIOLENT CONVULSIONS,
essentially like those caused by strychnine (see preceding paragraph).
Vacor, DLP-787: Minimum toxic and lethal doses in humans are not
known. Ingested amounts less than one gram have proved severely toxic.
Symptoms may not appear for 4 to 48 hours after ingestion. Earliest symp-
toms are usually NAUSEA, vomiting, abdominal cramps, CHILLS, and
CONFUSION. Later manifestations are aching and fine tremors of the ex-
tremities, dilated pupils, plantar hyperesthesia, MUSCLE WEAKNESS,
dysphagia, chest pain, postural hypotension, anorexia, diarrhea, urinary
retention, and HYPOTHERMIA. Subsequently, DIABETES MELLITUS
commonly develops, manifest as glycosuria, polyuria, ketoacidosis, and
dehydration. Death may result from respiratory failure, cardiovascular col-
lapse, or ketoacidosis. Survivors of the acute phase of the poisoning are often
59
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left with permanent sequelae: postural hypotension, diabetes mellitus, bladder
dystonia (retention or frequency), bowel dystonia (constipation or diarrhea),
and peripheral neuropathy.
Abnormal laboratory findings include hyperglycemia, glycosuria, ketosis
(acidosis and electrolyte disturbances), and elevation of serum amylase and
lipase activities.
Red squill: Nausea and VOMITING are the predominant effects. In the
unlikely event that significant amounts of glycosides are absorbed, cardiac ar-
rhythmias and slowing might be expected. Convulsions have not been observed
in humans as they have in rats.
Antu: Pulmonary rales, DYSPNEA and cyanosis may be expected follow-
ing ingestion of large amounts.
Norbormide: No human poisonings have been reported. Ingestion of 300
mg by an individual caused a slight fall in body temperature and blood
pressure.
CONFIRMATION OF DIAGNOSIS
Coumarins, indandiones, and other anticoagulants: Increase of the pro-
thrombin time (Quick) reflects a reduction in serum prothrombin concentra-
tion, and occurs in response to physiologically significant absorption of these
toxicants. This widely available clinical test offers a sensitive and reliable
diagnostic method for detecting a toxic effect of these compounds. Readily
detectable change in prothrombin time appears within 24 to 48 hours of inges-
tion of anticoagulant.
Zinc phosphide and phosphorus: Zinc phosphide smells like rotten fish and
imparts a garlicky odor to the breath. Luminescence of vomitus or feces in-
dicates yellow phosphorus ingestion.
Other rodenticides: There are analytical methods available for identifying
some remaining rodenticides in food or liquids suspected of contamination, in
gastric contents, and sometimes in blood and urine. (See Sunshine, I., Hand-
book of Analytical Toxicology (1969) published by the Chemical Rubber
Company, 18901 Cranwood Parkway, Cleveland, Ohio 44128.) These
methods are generally complex and must be performed by a toxicology labora-
tory experienced in these tests. Analysis is often time-consuming, limiting the
usefulness of the results in clinical management. Analyses may be important,
however, for legal reasons.
TREATMENT
Coumarins, indandiones, and other anticoagulants
1. If only a few grains of anticoagulant bait have been ingested by an adult
or child having no antecedent liver or blood clotting disease, treatment is
probably unnecessary.
60
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A. If there is uncertainty about the amount of bait ingested or the
general health of the patient, PHYTONADIONE (vitamin K,,
Mephyton®) given orally protects against the anticoagulant effect
of these rodenticides. For adults, give 15-25 mg; for children under
12, give 5-10 mg. Alternatively, a colloidal solution of phytona-
dione, Aquamephyton®, may be given intramuscularly. For adults,
give 5-10 mg; for children under 12, give 1-5 mg.
CAUTION: PHYTONADIONE, specifically, is required. Neither
vitamin K3 (menadione, Hykinone®) nor vitamin K4
(menadiol) is an antidote for these anticoagulants.
B. Whatever the doage, insure that patients (especially children) will be
CAREFULLY OBSERVED for 4-5 days after ingestion. The indan-
diones and the more recently introduced anticoagulants have toxic
effects apart from anticoagulation that are not yet well defined.
2. If LARGE AMOUNTS of anticoagulant were ingested in the preceding
2-3 hours, INDUCE VOMITING with SYRUP OF IPECAC, followed
by 1-2 glasses of water. For adults, give 30 ml; for children under 12, 15
ml. Following emesis, give 30-50 gm ACTIVATED CHARCOAL in 4-6
ounces of water to limit absorption of anticoagulant remaining in the
gut.
3. If anticoagulant has been ingested any time in the preceding 15 days,
determination of PROTHROMBIN TIME provides a basis for judging
the severity of poisoning.
A. If the prothrombin time is lengthened, give Aquamephyton®, in-
tramuscularly: adult dose, 5-10 mg; child's dose: 1-5 mg. Decide
dose according to the degree of prothrombin time lengthening and,
in children, the age and weight of the child.
B. Repeat prothrombin time in 24 hours. If it has not decreased from
the original value, repeat Aquamephyton® dosage.
4. If victim shows SYMPTOMS or SIGNS of ANTICOAGULANT POI-
SONING (bleeding) in addition to hypoprothrombinemia, administer
Aquamephyton® intramuscularly, up to 25 mg in the adult, and up to
0.6 mg/kg in children under 12 years. Phytonadione administration may
be repeated in 24 hours if bleeding continues.
A. In cases of SEVERE BLEEDING, it may be necessary to give
Aquamephyton® intravenously. This is especially true if the
bleeding tendency is so severe that intramuscular injection is likely
to cause hematoma formation. Dosage is up to 25 mg in the adult,
up to 0.6 mg/kg in children under 12 years. Repeat this dose in 24
hours if bleeding continues. Inject at rates not exceeding 5% of the
total dose per minute. INTRAVENOUS INFUSION of the
Aquamephyton® DILUTED IN SALINE OR GLUCOSE SOLU-
TION is recommended. Bleeding is usually controlled in 3-6 hours.
61
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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.
B. Antidotal therapy IN cases of SEVERE BLEEDING should be sup-
plemented with TRANSFUSIONS of FRESH BLOOD or FRESH
FROZEN PLASMA. Use of fresh blood or plasma represents the
most rapidly effective method of stopping hemorrhage due to these
anticoagulants.
C. Determine PROTHROMBIN TIMES (and hemoglobin concentra-
tions, if appropriate) every 6-12 hours to assess effectiveness of anti-
hemorrhagic measures.
D. When normal blood coagulation is restored, it may be advisable to
drain large hematomata.
E. Ferrous sulfate therapy may be appropriate in the recuperative
period to rebuild lost erythrocyte mass.
Sodium fluoroacetate
1. If this substance has been INGESTED, empty the stomach immediately
by INTUBATION, ASPIRATION, and LAV AGE, using 5% sodium
bicarbonate. Before withdrawing the lavage tube, instill a slurry of 30-50
gm ACTIVATED CHARCOAL.
2. MONITOR cardiac rhythm by continuous ELECTROCARDIOG-
RAPHY.
3. MONOACETIN (glyceryl monoacetate) has antidotal properties in ex-
perimental animals. The liberated acetate competes successfully with
fluorocitrate in the tricarboxylic acid cycle. However, there is no sterile
pharmaceutical preparation of this compound: high-quality, fresh
laboratory grade material must be used.
A. If victim is fully conscious and not convulsing, administer 100 ml of
monoacetin in 500 ml of water, by mouth. Repeat in one hour.
(Arena, J. M. Poisoning, 1970.)
B. If victim is obtunded, unconscious, or convulsing, give 0.1-0.5
ml/kg of undiluted monoacetin by deep intramuscular injection
every half hour for 4-6 hours, rotating the injection sites to
minimize pain and swelling. Monoacetin can also be given intra-
venously on the same schedule, using a 1:5 dilution in sterile isotonic
saline.
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CAUTION: The use of parenteral monoacetin is hazardous. Tech-
nical grade material contains glycerin which, in ade-
quate dosage, may cause hemolysis, hypotension,
convulsions, and paralysis. If a nonsterile solution is
injected, the monoacetin should be cultured to guide
the administration of antibiotics if sepsis develops.
4. CONTROL CONVULSIONS
A. Administer 100% OXYGEN by positive pressure to provide as
much pulmonary gas exchange as possible, despite seizures.
B. ANTICONVULSANT DRUGS
CAUTION: It may be difficult or impossible to stop the seizure
activity without stopping respiration. Be prepared to
maintain pulmonary ventilation mechanically.
Tracheostomy may be necessary if seizures are pro-
longed.
(a). Diazepam (VALIUM®) usually controls mild convulsions.
For adults, give 5-10 mg, slowly, intravenously; for children
under 6 years or 23 kg body weight, give 0.1 mg/kg body
weight, slowly, IV. Repeat in 4-6 hours if necessary.
(b). Pentobarbital may be needed in addition to control severe
convulsions. Dosage: 5 mg/kg body weight, or 0.20 ml/kg
body weight, using the usual 2.5% solution. If possible, inject
solution intravenously, at a rate not exceeding 25 mg (one ml)
per minute until convulsions are controlled. If intravenous ad-
ministration is not possible, give total dose by deep intramus-
cular injection, not exceeding 5 mg/kg body weight (0.20
ml/kg of 2.5% solution).
(c). Phenytoin (DILANTIN®) has prolonged anticonvulsant ac-
tion. Dosage: loading dose 15-18 mg/kg. Maintenance dose
4-8 mg/kg q 4-24 hours as needed. Intramuscular adminis-
tration is not recommended. Give IV slowly at no more than
20% total dose per minute.
(d). Thiopental (PENTOTHAL®), by continuous intravenous in-
fusion, may help to control severe seizures. Dissolve one gram
in 500 ml of glucose solution, and infuse at a rate just suffi-
cient to stop seizures.
CAUTION: Laryngospasm is a complication of anticonvul-
sant therapy and may require tracheostomy.
(e). In some instances, curari/ation with succinylcholine or a
similar agent is required to stop convulsions. This requires
tracheal intubation or tracheostomy and mechanical pulmo-
nary ventilation, with regular monitoring of blood gases and
pH.
63
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5. Many other agents tested in fluoroacetate poisoning are NOT EFFEC-
TIVE: sodium acetate, calcium chloride, ethanol, propylene glycol,
digitalis glycosides, di- and tri-acetates of glycerol.
6. Administer IV electrolyte solutions cautiously to avoid fluid overload in
presence of a weak and irritable myocardium.
Zinc phosphide and yellow phosphorus
1. WASH SKIN BURNS due to yellow phosphorus with water and a 1%
copper sulfate solution. Make sure all particles of phosphorus have been
removed. Cover burned area with ointment.
2. Poisonings by INGESTED yellow phosphorus or zinc phosphide are ex-
tremely difficult to manage. The mortality rate of 50% is the result of
either shock or pulmonary edema in the first few hours or days, or coma,
seizures, and/or liver, kidney and myocardial damage in the ensuing days
or weeks.
CAUTION: Highly toxic phosphine gas may evolve from emesis,
lavage fluid, and feces of victims of these poisons. The pa-
tient's room should be well ventilated.
A. INTUBATE and ASPIRATE the stomach. LAVAGE with several
quarts of 1:5000 potassium permanganate solution.
CAUTION: Persons attending victim must avoid contact with
yellow phosphorus, which causes skin burns.
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.
C. Administer 100% OXYGEN by mask or nasal tube.
D. Combat pulmonary edema with intermittent or continuous POSI-
TIVE PRESSURE OXYGEN.
E. MONITOR URINE albumin, glucose, and sediment to detect early
renal injury. Monitor EKG to detect myocardial impairment. Moni-
tor serum alkaline phosphatase, LDH, prothrombin time, and
bilirubin to evaluate liver damage.
F. Include Aquamephyton® (vitamin K]) in intravenous infusions if
prothrombin level declines. Dosage of 10-50 mg per day may be re-
quired. Administer Aquamephyton® slowly, intravenously; stop
infusion if Mushing, cyanosis, paresthesiae, hypotension, or dyspnea
occurs.
G. MORPHINE SULFATE, 8-16 mg every few hours may be necessary
to control pain. Child's dose: 0.1-0.2 mg/kg.
H. CONTROL CONVULSIONS with diazepam, barbiturates, and/or
phenytoin as suggested under treatment of sodium fluoroacetate
poisoning.
I. CORTICOSTEROIDS at high dosages may be beneficial.
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Strychnine and crimidine
1. Administer 100% OXYGEN by positive pressure.
2. CONTROL CONVULSIONS. This may be attempted with intravenous
diazepam, barbiturates, and/or phenytoin, as described under manage-
ment of sodium fluoroacetate poisoning.
A. CURARIZATION is often required, using succinylcholine or
similar agent. Tracheal intubation or tracheostomy and continuous
mechanical pulmonary ventilation are necessary. Blood gases and
pH must be monitored.
3. FORCED DIURESIS with mannitol accelerates the excretion of
strychnine. Infusion of SODIUM BICARBONATE relieves metabolic
acidosis. There may be some benefit from peritoneal dialysis,
hemodialysis, and hemoperfusion.
4. Once seizures have been controlled, remove unabsorbed toxicant from
the stomach by gastric INTUBATION, ASPIRATION, and LAV AGE.
Leave a slurry of 30-50 gm ACTIVATED CHARCOAL in the stomach.
Follow charcoal with SODIUM or MAGNESIUM SULFATE, 0.25
gm/kg, in 1-6 ounces of tap water, to induce catharsis. Repeat cathartic
dosage as needed.
Vacor, DLP-787 (Active ingredient RH-787)
1. If toxicant was ingested recently, EVACUATE the STOMACH by IN-
TUBATION, ASPIRATION, and LAVAGE with 2-3 liters isotonic
saline.
A. Before withdrawing stomach tube, instill 30-50 gm of ACTIVATED
CHARCOAL as a slurry in 3-4 ounces of water, to limit absorption
of remaining toxicant.
B. As soon as patient can tolerate oral fluids after withdrawal of
stomach tube, give SODIUM or MAGNESIUM SULFATE, 0.25
gm/kg body weight in 1-6 ounces of water to induce catharsis.
Repeat dose in 4 hours if patient has had no bowel movement.
2. Administer NICOTINAMIDE (niacinamide) intravenously, slowly, or
intramuscularly. For adults and children over 12 years, give 500 mg im-
mediately, then repeat injections of 200-400 mg every 4 hours for 10-12
doses. Within this range, select the dose on the basis of body weight and
the estimated quantity of RH-787 ingested. If manifestations of RH-787
toxicity appear, give nicotinamide by continuous IV infusion at about
100 mg per hour. There is probably no advantage in giving more than
3000 mg per day of nicotinamide.
A. Dosage of nicotinamide for children under 12 years, or 23 kg, is
about half the dosage suggested for adults.
B. After 2-3 days of parenteral therapy, give nicotinamide by mouth,
100 mg four times daily, for 2 weeks.
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3. MONITOR blood and urine sugar concentrations, serum alkaline
phosphatase, amylase, LDH, and GOT activities, urine ketone concentra-
tions, blood electrolytes and BUN. Examine the electrocardiogram for
arrhythmias.
4. Unless the patient is able to void easily, put in place a RETENTION
CATHETER to monitor urine flow and urinary glucose excretion.
5. Infuse ELECTROLYTE SOLUTIONS intravenously to accelerate toxi-
cant excretion and correct errors in specific ion concentrations. If
ketoacidosis appears, use bicarbonate or Ringer's-lactate to control
acidosis.
6. If DIABETIC KETOACIDOSIS appears (ketonuria, metabolic acidosis,
hyperglycemia) administer enough regular insulin to control the acidosis
and hyperglycemia, as in naturally occurring diabetic ketosis. The
diabetes resulting from RH-787 tends to be brittle and correspondingly
difficult to control.
7. In all cases of ingestion of Vacor or DLP-787 (whether or not acute
poisoning occurs), follow the patient's clinical status carefully for at least
6 months. Look for indications of diabetes mellitus (glycosuria, hyper-
glycemia), and for consequences of autonomic nervous system damage:
orthostatic hypotension, urinary retention, constipation, diarrhea, ab-
dominal cramping, pain and weakness in the limbs'.
Red squill
1. Significant toxicity is not expected from this agent. If, for some reason, a
significant amount is retained in the stomach, remove it by gastric IN-
TUBATION, ASPIRATION, and LAV AGE, followed by 0.25 gm/kg
SODIUM or MAGNESIUM SULFATE in 1-6 ounces water.
2. Monitor ELECTROCARDIOGRAM for arrhythmias and conduction
disturbances characteristic of digitalis.
Antu
1. Significant toxicity is not expected from this agent. If an extraordinary
amount has been ingested, empty the gut. Administer SYRUP OF
IPECAC, then 1-2 glasses of water, to induce vomiting. Adult dose: 30
ml; dose for children under 12 years: 15 ml. Follow with 30-50 gm ac-
tivated charcoal in 3-4 ounces of water, then 0.25 gm/kg SODIUM or
MAGNESIUM SULFATE in 1-6 ounces water.
2. If dyspnea appears, administer OXYGEN by continuous flow or by
intermittent POSITIVE PRESSURE.
Norbormide
1. Significant toxicity is not expected from this agent. If an extraordinary
amount has been ingested, empty the gut. Administer SYRUP OF
66
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IPECAC, then 1-2 glasses of water, to induce vomiting. Adult dose: 30
ml; dose for children under 12 years: 15 ml. Follow with 30-50 gm AC-
TIVATED CHARCOAL in 3-4 ounces of water, then 0.25 gm/kg
SODIUM or MAGNESIUM SULFATE in 1-6 ounces water.
2. Monitor BLOOD PRESSURE and BODY TEMPERATURE for several
hours, if a large amount has been absorbed.
67
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Chapter 12
FUMIGANTS
CHEMICAL STRUCTURES
HALOCARBONS
Cl
1
CI-C-CI
1
Cl
Carbon
Tetrachloride
Cl
1
CI-C-H
1
Cl
Chloroform
Cl
1
Cl - C - NO2
Cl
Chloropicrm
H
I
1
H - C - Br
1
H
Methyl Bromide
Br Br
1 1
H -C— C-H
1 1
H H
Ethylene
Dibromide
Cl H Cl
1 1 1
H -C - C = C
1 1
H H
1,3-Dichloro-
propene
Br Br Cl
Ii i
1 1
H - C -C - C - H
1 1 1
H H H
Dibromo-
chloropropane
Cl Cl
i i
1 1
H - C -C - H
| |
H H
Ethylene
Dichloride
OXIDES AND
H
ALDEHYDES
O
' ^
CH2- CH2
Ethylene Oxide
O
/ \
GH2 - CH • CHg
Propylene Oxide
H
C= 0
H
Formaldehyde
O
[•f]
L. — 1
Paraformaldehyde
H H H
1 1 1
C = C-C = O
1
H
Acrolein
SULFUR AND
PHOSPHORUS
COMPOUNDS
O = S = O
Sulfur Dioxide
S = C = S
Carbon Disulfide
_
\
S = O
F
Sulfuryl Fluoride
ii ii
p
I
I
H
Phosphme (from
MZP+ H20)
CYANIDES
H-C = N
Hydrogen Cyanide
H H
1 1
C = C-C = N
1
H
Acrylonitrile
68
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COMMON COMMERCIAL FUMIGANT PRODUCTS
Chloroform, carbon tetrachloride, methyl bromide (Brom-O-Gas, Fumi-
gant-1, Kayafume, Me Br, Meth-O-Gas, Pestmaster, Profume); chloropicrin
(Acquinite, Chlor-O-Pic, Pic-Clor, Picfume, Tri-Clor); ethylene dichloride
(EDC), ethylene dibromide (EDB, Bromofume, Celmide, Dowfume W-85,
Kop-Fume, Nephis, Pestmaster EDB-85, Soilbrom); dichloroprop-ene and
-ane (Telone, D-D), sulfuryl fluoride (Vikane), dibromochloropropane
(DBCP).
The Dowfume fumigants manufactured by the Dow Chemical Company are
mixtures of halocarbons, mainly EDC, EDB, carbon tetrachloride, Me Br,
and chloropicrin, formulated to meet specific needs.
Ethylene oxide (ETO, oxirane); propylene oxide (epoxypropane); formalde-
hyde (Formalin is a 40% aqueous solution), propenal (Acrolein, Aqualin,
Acrylaldehyde); carbon di- (or bi-) sulfide; hydrogen cyanide (prussic acid,
Cyclon); acrylonitrile (ingredient of fumigant mixtures Acrylofume, Acritet,
Carbacryl); aluminum phosphide (Phostoxin).
TOXICOLOGY
Fumigants have extraordinary power to penetrate the lining membranes of
the respiratory and gastrointestinal tracts, and the skin. They also penetrate
the rubber and plastics used in protective garb and they are not efficiently
taken up by conventional adsorbents used in ordinary respirators. These prop-
erties make the protection of applicator personnel very difficult, essentially
mandating methods of use that do not require on-site operator handling.
Because these chemicals are either gases or volatile liquids at room tempera-
ture, inhalation is the most common route of absorption. Dermal injury does
follow contact with some fumigants, ranging in severity from a mild chemical
burn to vesiculation and ulceration. Fumigant gases irritate the eyes; liquid
fumigant may cause blindness from corneal ulceration.
Respiratory tract irritation is the most common and serious injury caused by
fumigants. Some agents such as sulfur dioxide, chloropicrin, formaldehyde
and acrolein cause so much irritation of the upper respiratory tract that the ex-
posed individual is unlikely to inhale a quantity of fumigant capable of damag-
ing the lung. Rarely, laryngeal edema or bronchospasm results from inhalation
of high concentrations.
Other gases, such as methyl bromide, phosphine, and ethylene oxide, are
not so irritating to the nose, eyes, throat, and bronchi, but cause serious injury
to the cells lining the fine air sacs of the lung. Thus, they are more likely than
other fumigants to induce pulmonary edema, a major cause of death from
fumigant exposure.
In varying degrees, these fumigants depress the central nervous system. As
in the case of the anesthetic chloroform, adequate dosage may lead to uncon-
sciousness. Depression or cessation of respiration is a major hazard of acute
inhalation exposure to fumigants. Acute exposures to methyl bromide have in-
duced convulsions. Absorbed in lower concentrations over several consecutive
69
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days, methyl bromide has impaired basal ganglion function in humans, caus-
ing ataxia for weeks or months after exposure. Protracted exposure to carbon
disulfide has caused peripheral neuropathy and changes in CNS function
(chronic encephalopathy) of chronically exposed workers.
The halocarbon fumigants increase the irritability of the heart muscle. In-
tensive exposures may lead to sudden death as a result of ventricular fibrilla-
tion.
Liver and kidney damage occurs commonly following excessive exposure to
fumigants. Liver injury may take the form of fatty infiltration, diffuse
necrosis or massive necrosis. Elevated serum levels of GOT, LDH, alkaline
phosphatase, and bilirubin reflect hepatocellular injury. The fumigants may
inflict direct injury on glomerular and tubular elements of the kidney, leading
to functional proteinuria and glycosuria, or to acute renal failure, depending
on severity of toxicant exposure. In addition, hyperbilirubinemia resulting
from liver damage may compound the tubular injury (hepatorenal syndrome).
Inhaled phosphine gas (PH3) and ingested metal phosphides cause
pulmonary edema, CNS depression, toxic myocarditis, and circulatory col-
lapse. Victims who survive these immediate actions suffer liver injury (fatty
degeneration and necrosis) and acute renal tubular necrosis. Unlike its
analogue arsine, phosphine is not hemolytic. Enzymatic mechanisms of toxici-
ty are not known. Ingested metal phosphide (from which phosphine is gener-
ated) causes intense gastrointestinal irritation, followed by degenerative and
necrotizing lesions of the liver, kidney, and heart. Death is often due either to
cardiogenic shock or pulmonary edema.
Hydrogen cyanide (HCN) and its salts poison by inactivating the
cytochrome oxidase of cells in critical tissues, primarily the heart and brain.
Acrylonitrile degrades slowly to HCN in the body, and therefore acts primarily
by the same mechanism, although the slow release of free cyanide renders it
somewhat less toxic than HCN itself. Both HCN and acrylonitrile are suffi-
ciently absorbable across the skin to cause poisoning in the absence of inhala-
tion exposure. Manifestations of poisoning are due mainly to intracellular
anoxia of brain tissue (leading to respiratory failure), and to the circulatory in-
sufficiency that results from myocardial weakness. The liver has substantial
capacity for converting cyanide to the less toxic thiocyanate, a metabolic con-
version that is accelerated by therapeutically administered thiosulfate.
Dibromochloropropane has reportedly caused sterility in manufacturing
plant workers and reduced sperm counts in highly exposed applicators.
FREQUENT SYMPTOMS AND SIGNS OF POISONING
HEADACHE, DIZZINESS, NAUSEA, and vomiting are prominent early
symptoms of excessive exposure to these gases. Sulfur dioxide, formaldehyde,
chloropicrin, and acrolein are strong irritants, causing BURNING SENSA-
TIONS in the nose and throat, TEARING, COUGH, and sometimes hoarse-
ness and wheezing. Exposures to methyl bromide, phosphine and ethylene ox-
ide are more likely to produce prompt pulmonary edema: COUGHING of
70
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copious amounts of FROTHY FLUID, associated with severe SHORTNESS
OF BREATH and cyanosis. The remaining fumigants are less likely to cause
respiratory tract injury.
DROWSINESS, TREMORS, double vision, and weakness are the common
early manifestations of central nervous system impairment. Tremors may
progress to myoclonic movements, then to generalized SEIZURES, UNCON-
SCIOUSNESS, and death. Protracted low level exposure to methyl bromide
causes ATAXIA and impairment of manual coordination.
Injuries to the skin by liquid fumigants may be manifest as areas of redness
or as BLISTERS which rupture, leaving raw skin or deep ulcers.
If ingested, the LIQUID forms of HALOCARBONS often cause pulmonary
edema and SHOCK within a few moments. If victim survives, injuries to the
brain, liver and kidney are life-threatening.
Longer-term low level inhalation of CHLOROCARBONS may cause liver
damage, first manifest as ANOREXIA, then as JAUNDICE. Biochemical
studies confirm hepatocellular injury.
Poisoning by excessive inhalation of CARBON DISULFIDE is character-
ized by DIZZINESS, headache, nausea, and sometimes disorientation, pares-
thesiae, hallucinations, and, rarely, convulsions. Protracted low level exposures
produce PAIN, tingling, WEAKNESS of the extremities, and deterioration of
mental functions.
Poisoning by PHOSPHINE gas is usually heralded by weakness,
TREMORS, vomiting, a sense of pressure in the chest, COUGH, and dyspnea,
sometimes progressing to PULMONARY EDEMA. Intense thirst results from
hypotension and diarrhea. Severe poisonings lead to CONVULSIONS, coma,
and death. Those who survive the acute phase suffer LIVER INJURY (eleva-
tion of serum GOT, LDH, and alkaline phosphatase, and sometimes, reduced
prothrombin concentration, hemorrhage, and jaundice) and kidney damage
(hematuria and sometimes anuria). Chronic exposures to lesser amounts have
caused pain in the eyes and nose, nosebleeds, and abdominal pain.
Ingestion of METAL PHOSPHIDES leads promptly to NAUSEA and
VOMITING, followed by injury to the lung, liver, kidney, heart and central
nervous system. Hypocalcemic tetany (from hyperphosphatemia) and metabolic
acidosis develop several hours after ingestion of solid phosphides.
Excessive inhalation of SULFURYL FLUORIDE may induce muscle twitch-
ing and convulsions. Persons repeatedly exposed risk injury to the lung (im-
paired pulmonary function) and kidney (proteinuria and azotemia).
Poisoning by HYDROGEN CYANIDE or ACRYLONITRILE may pro-
duce sudden UNCONSCIOUSNESS and respiratory arrest without warning
symptoms. Lesser exposures cause HEADACHE, nausea, and a sense of con-
striction in the throat, followed by hyperpnea, dizziness, and apprehension.
Pulse and respiratory movements then become weak, slow, and irregular as
consciousness is lost. CONVULSIONS, either tonic or epileptiform, may
supervene. Opisthotonus and trismus commonly appear, and sphincter control
is usually lost. The heart often continues to beat after respiration has stopped.
The skin generally remains pink.
71
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CONFIRMATION OF DIAGNOSIS
Large industrial concerns monitor human absorption of halocarbons by
analysis of expired air. Similar technology is available in many departments of
anesthesiology. Such analyses are not often needed to identify the offending
toxicant, because this is known from the exposure history. In managing dif-
ficult cases of poisoning, however, it may help to monitor breath concentra-
tions of toxic gas.
Blood bromide concentrations t have some value in identifying poisonings
by methyl bromide, and possibly ethylene dibromide, provided it can be estab-
lished that the person exposed to the fumigant has not recently taken inorganic
bromide medication. A level of organic bromide higher than 5 mg/100 ml in-
dicates excessive absorption of fumigant. A blood concentration of more than
10 mg/100 ml of organic bromide represents a serious threat to health. A
blood level of more than 15 mg/100 ml indicates an immediate threat to life.
Methods for detecting the organic oxides, aldehydes, sulfur dioxide, and
phosphine are not generally available, but they are rarely needed. A simple
method is available for detecting carbon disulfide in urine (Djuric et al. Brit. J.
Indust. Med. 22:321-323. 1965). Cyanide can be detected and measured in
blood and tissues, as can the thiocyanate metabolite in urine and saliva. Odors
of gases on the victim's breath are sometimes helpful diagnostic clues: cyanide
smells like bitter almonds, carbon disulfide like rotten cabbage, and phosphine
somewhat like garlic or acetylene.
TREATMENT
1. FLUSH contaminating fumigant from the SKIN and EYES with copious
amounts of water for at least 15 minutes. Contact with LIQUID
fumigant can cause BLINDNESS or DEATH. Treat injuries IM-
MEDIATELY.
2. REMOVE victims of fumigant inhalation TO FRESH AIR. Even though
initial symptoms and signs are mild, keep victim quiet, in a semireclining
position. Reduction in physical activity reduces the likelihood of pulmo-
nary edema.
3. If victim is not breathing, RESUSCITATE with positive pressure oxygen
breathing apparatus, if available. If apparatus is not available, use
mouth-to-mouth or mouth-to-nose methods. If victim is pulseless,use
cardiac resuscitation.
4. If PULMONARY EDEMA is evident, there are several measures avail-
able to sustain life. Medical judgment must be relied upon, however, in
the management of each case. The following procedures are generally
recommended:
A. Put the victim in a SITTING position with a backrest.
Conway, E. J. Microdiffusion Analysis and Volumetric Error, 3rd edition.
Crosby Lockwood, London 1950.
72
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B. Use intermittent and/or continuous positive pressure OXYGEN to
relieve hypoxemia. (Do not give oxygen at greater concentrations or
longer periods than necessary, because it may exaggerate the fumi-
gant injury to lung tissue. Monitor arterial p O2).
C. Apply TOURNIQUETS in rotation to arms and legs to limit venous
return.
D. Administer AMINOPHYLLINE (0.25-0.50 gm) slowly, intraven-
ously.
E. Administer MORPHINE in small doses (5-10 mg), slowly, intra-
venously, to allay anxiety and promote deeper respiratory excur-
sions. Children's dose, 0.1-0.2 mg/kg.
F. Digitalization may be considered, but be alert to the serious risk of
arrhythmias in an anoxic mycardium.
G. Slowly administer FUROSEMIDE, 40 mg, or SODIUM
ETHACRYNATE, 50 mg, to reduce venous load by inducing
diuresis.
H. TRACHEOSTOMY may be necessary in some cases to facilitate
aspiration of large amounts of edema fluid.
I. Epinephrine, atropine, and expectorants are generally NOT
HELPFUL and may complicate treatment.
J. STEROIDS at high dosage are usually recommended, although
their effectiveness is unproved.
K. If secondary pneumonitis occurs, administer ANTIBIOTICS.
L. Watch for RECURRENT PULMONARY EDEMA, even up to 2
weeks after the initial episode. Limit victim's physical activity for at
least 4 weeks. Severe physical weakness usually indicates persistent
pulmonary injury. Serial pulmonary function testing may be useful
in assessing recovery.
5. Combat SHOCK by placing victim in the Trendelenburg position and ad-
ministering blood plasma and/or electrolyte and glucose solutions intra-
venously, with great care, to avoid pulmonary edema. Central venous
pressure should be monitored continuously. Vasopressor amines must be
given with great caution, because of the irritability of the myocardium.
6. Control CONVULSIONS. Seizures are most likely to occur in poisonings
by methyl bromide, carbon disulfide, phosphine, metal phosphide,
cyanide, and acrylonitrile.
A. Establish pulmonary gas exchange at the best possible level by ad-
ministering 100% OXYGEN by IPPB.
B. In poisoning by CYANIDE and acrylonitrile, proceed directly with
ANTIDOTAL therapy (see below, paragraph IOC).
C. Control convulsions caused by other agents with careful IV injec-
tion of DIAZEPAM, 5-10 mg in the adult, 0.1 mg/kg in children
under 12 years. Repeat dosage in 4-6 hours if necessary.
CAUTION: Be prepared to maintain pulmonary ventilation
mechanically, and to manage hypotension and car-
diac arrhythmias.
73
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D. In methyl bromide poisoning, it may be necessary to give diazepam
or barbiturates orally for some time after the acute poisoning to
control involuntary motor activity,
7. If FUMIGANT LIQUIDS have been INGESTED, quantities remaining
in the gut must be removed as effectively as possible by gastric INTUBA-
TION, ASPIRATION, and LAVAGE.
A. IF victim is UNCONSCIOUS, put in place a cuffed endotracheal
tube prior to gastric intubation.
B. Place conscious victim in a left lateral Trendelenburg position for
intubation, and aspirate the pharynx as effectively as possible to
minimize likelihood of tracheal aspiration.
C. After aspirating stomach contents, LAVAGE the stomach with 2-3
liters 0.9% saline or 5% sodium bicarbonate, containing 30-50 gm
ACTIVATED CHARCOAL. After lavage, leave 30-50 gm activated
charcoal in stomach before withdrawing tube.
D. If diarrhea does not develop spontaneously, give SODIUM
SULFATE orally, 0.25 mg/kg, to induce catharsis.
8. Intravenous INFUSIONS of GLUCOSE are valuable in limiting the
hepatotoxicity of fumigants. Monitor central venous pressure to avoid
precipitating, or aggravating, pulmonary edema by fluid overload.
9. MONITOR fumigant poisoning victims closely for recurrent pulmonary
edema and bronchopneumonia. Chart fluid balance and check urine
sediment regularly to detect incipient tubular necrosis. Measure serum
alkaline phosphatase, LDH, and bilirubin to assess liver injury.
10. Certain SPECIFIC MEASURES are recommended in poisonings by par-
ticular fumigants:
A. If given very soon after exposure to METHYL BROMIDE, there
may be some value in administering DIMERCAPROL (BAL) in
vegetable oil intramuscularly. For adults, give 3-5 mg/kg q6h for 4
doses.
CAUTION: DIMERCAPROL may cause troublesome side ef-
fects (hypertension, tachycardia, nausea, headache,
paresthesiae, pain, lacrimation, sweating, anxiety,
and restlessness). Although usually not so severe as to
preclude treatment, these manifestation may require
antihistamine therapy for adequate control.
B. Mild poisonings by CARBON DISULFIDE inhalation may be man-
aged best by no more than careful observation, even though sensory
hallucinations, delirium, and behavioral aberrations can be alarm-
ing. Severe poisonings may require specific measures:
1. CAFFEINE and sodium benzoate (0.5 gm subcutaneously)
may help to relieve CNS depression.
74
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2. If manic behavior threatens the safety of the victim,
DIAZEPAM, 5-10 mg, 0.1 mg/kg in children, adminis-
tered cautiously, intravenously, may be helpful as a tran-
quilizer. Do not give catecholamine-releasing agents such as
reserpine and amphetamines.
C. Poisonings by HYDROGEN CYANIDE and ACRYLONITRILE
gases are treated in essentially the same way as poisoning by cyanide
salts. In addition to the general treatment described earlier, specific
ANTIDOTES are required. (See line 6 for pediatric regimen).
1. Administer AMYL NITRITE (perles) by inhalation for 15-30
seconds of every minute, while a fresh solution of 3 % sodium
nitrite is being prepared.
2. 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.
CAUTION: Monitor PULSE and BLOOD PRESSURE dur-
ing administration of amyl nitrite and sodium
nitrite. If systolic blood pressure falls below 80
mm Hg, slow or stop nitrite administration un-
til blood pressure recovers.
3. Follow sodium nitrite injection with an infusion of 50 ml of
25% aqueous solution of SODIUM THIOSULFATE admin-
istered over 10-minute period. Initial adult dose should not ex-
ceed 12.5 gm.
4. If symptoms persist or recur, treatment by sodium nitrite and
sodium thiosulfate should be REPEATED AT HALF THE
DOSAGES listed in paragraphs 2 and 3.
5. Measure hemoglobin and methemoglobin in blood. If more
than 50% of total hemoglobin has been converted to methe-
moglobin, BLOOD TRANSFUSION or exchange transfusion
should be considered, because conversion back to normal
hemoglobin proceeds slowly.
6. Dosage of ANTIDOTES in CHILDREN:
C. M. Berlin (Pediatrics 46:793-796, 1970) has recom-
mended the following procedures in case of cyanide poi-
soning in children:
(a) Children over 25 kg body weight should receive adult
dosages of sodium nitrite and sodium thiosulfate.
(b) 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 mg/kg (0.33 ml/kg of 3% solu-
tion) of SODIUM NITRITE injected over a 2-4 minute in-
terval. Following sodium nitrite, administer an infusion of
75
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1.65 ml/kg of 25% SODIUM THIOSULFATE at rate of
3-5 ml per minute.
(c) At this point, determine the hemoglobin content of the
original blood sample. If symptoms and signs of poison-
ing persist or return, give supplemental infusions of
sodium nitrite and sodium thiosulfate based on hemoglo-
bin level, as presented in TABLE 2. (These recommended
quantities are calculated to avoid life-threatening methe-
moglobinemia in anemic children).
TABLE 2.
Initial
Hemoglobin
Concentration,
gm/100 ml
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
Recommended dosages of supplemental sodium nitrite and
sodium thiosulfate based on hemoglobin level.
Supplemental
Volume of 3%
Sodium Nitrite,
ml/kg
0.26
0.21
0.17
0.12
0.07
0.04
0
0
Supplemental
Volume of 25%
Sodium Thiosulfate,
ml/kg
1.28
1.05
0.83
0.60
0.38
0.23
0
0
(d) When possible, monitor BLOOD LEVELS of METHE-
MOGLOBIN to achieve approximately 40% conversion
of hemoglobin to methemoglobin.
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Chapter 13
MISCELLANEOUS PESTICIDES OF
HIGH TOXICITY
Pesticides included in this chapter are not similar in chemical structure or
toxicologic actions to the major classes of pesticidal toxicants (organophos-
phates, arsenicals, etc.) In general, they are not widely used and opportunities
for serious human exposure are rare. However, those included here are charac-
terized by either high toxicity or an important unique mechanism of toxic ac-
tion. Occasional poisonings by these chemicals have occurred in humans and
domestic animals.
4-aminopyridine (Avitrol, 4-AP)
This chemical, now used as a bird repellant, has caused severe poisoning in
adult humans at dosages no greater than about 60 mg. This is only 2-3 times
the dosage employed clinically in managing certain rare neuromuscular dis-
orders. The principal pharmacologic action of 4-aminopyridine is to facilitate
release of transmitter substances at neuroeffector junctions and at synapses
throughout the nervous system.
Human poisonings have been characterized by thirst, nausea, dizziness,
weakness, and intense diaphoresis, followed by toxic psychosis, ataxia,
tremors, dyspnea, and tonic-clonic convulsions. Metabolic acidosis, leukocy-
tosis, and elevations of serum GOT, LDH, and alkaline phosphatase were
notable laboratory findings. EKG may show nonspecific ST-T wave changes.
Treatment
Promptly evacuate gut by intubation, lavage, activated charcoal administra-
tion, and saline catharsis. Control convulsions with diazepam. Initiate diuresis
with intravenous infusions, including mannitol. To date, poisoning victims
have recovered in 24-48 hours without severe sequelae.
Pancuronium is an antagonist of 4-aminopyridine, and can control seizures.
It must be administered under the supervision of an anesthesiologist because
of the likelihood of generalized paralysis. Propranolol may help to limit car-
diac toxicity. Atropine controls the gastrointestinal symptoms.
Chlordimeform (Acaron, Fundal, Fundex, Galecron, Spanone)
Although the acute toxicity of this ovicidal agent is low (oral LDJO in the rat
about 200 mg/kg), it is now known from an incident of excessive respiratory
and dermal exposure to chlordimeform powder that it can cause acute illness
and urinary bladder irritation. In all likelihood, the offending metabolite is
2-methyl-4-chloroaniline. Principal symptoms are dysuria, gross hematuria,
urethral discharge, abdominal and back pain, and a hot sensation all over.
Sleepiness, skin rash, anorexia, and a sweet taste in the mouth have also been
77
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reported. Cystoscopic examination of victims of excessive exposure
demonstrated acute hemorrhagic cystitis.
Methods are available for detecting the 2-methyl-4-chloroaniline metabolite
in the urine.
Treatment
Flush contaminant from eyes and wash from skin. Symptoms resulting from
undue occupational exposure resolve in a few days if exposure is terminated. If
chlordimeform has been recently ingested, it should be removed from the gut
either by administering Syrup of Ipecac, or by gastric intubation, aspiration,
and lavage with 0.9% sodium chloride, followed by activated charcoal and
sodium sulfate catharsis. Serial urinanalyses should be performed to assess in-
jury to the urinary tract.
Copper salts and organic complexes (oxide, hydroxide, arsenite, carbonate,
chloride, oxalate, phosphate, silicate, sulfate, zinc chromate, acetate,
naphthenate, oleate, quinolinolate, and resinate).
These are commonly used as fungicides, either alone or in combination with
other agents. There are several dozen proprietary products.
LDi0 values vary from 6 to 1000 mg/kg, depending mainly on the solubility
and degree of ionization of the copper compound.
Toxicity of copper-arsenite salts is due mainly to the arsenic content.
All of these salts irritate the skin and eyes and damage mucous membranes.
When ingested, they are powerfully emetic: the stomach usually empties
promptly and automatically in fully conscious individuals. When retained and
absorbed, toxic injury affects the gastrointestinal lining, capillaries, brain,
liver, kidney, and formed elements of the blood. Copper salts are hemolytic.
Manifestations of poisoning include burning pain in the chest and abdomen,
intense nausea, vomiting, diarrhea, headache, sweating and shock. Later, the
liver is enlarged. Jaundice may reflect hemolysis or liver damage or both.
Anuria indicates kidney injury by copper and/or free hemoglobin. Death may
occur from convulsions, coma, or hepatorenal failure. Elevated serum copper
levels (maximum normal level is 125 jug per 100 ml) indicate severity of poison-
ing.
Treatment
Wash contaminated skin and flush eyes with copious amounts of water. If
copper salts have been ingested, lavage the stomach with 0.1% potassium
ferrocyanide, then instill a suspension of egg white. Intravenous fluids ac-
celerate excretion. If signs of systemic poisoning develop, give dimercaprol
(see Arsenical Pesticides for dosage) or penicillamine, 0.5 gm orally four times
daily, if patient can retain oral medication. Shock may require blood trans-
fusions and pain may require morphine. Exchange transfusions may be consid-
ered in severe poisonings. Renal failure may require protracted hemodialysis.
Cycloheximide (naramycin, Acti-dione, Actispray, Hizarocin)
This is an antibiotic fungicide of high toxicity: oral LD,0 in rats is 2 mg/kg.
78
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Dermal absorption is probably not efficient. When ingested, the agent
causes excitement, tremors, salivation, diarrhea, and melena. Mechanisms of
toxicity are not well defined, but probably include irritation of the gut,
stimulation of sympathetic and parasympathetic nervous systems, renal in-
jury, and damage to the adrenal cortex.
There are no chemical tests to confirm cycloheximide poisoning.
Treatment
Remove toxicant from gut by lavage. Instill activated charcoal, then a
cathartic dose of sodium sulfate. Intravenous fluids accelerate excretion.
Hydrocortisone appears to be antidotal, particularly in combination with
the adrenergic agent methoxyphenamine (Orthoxine®). Atropine relieves the
cholinergic symptoms.
Endothall (Accelerate, Aquathol, Des-i-cate, Hydout, Hydrothol)
Acute oral LD50 of this herbicide is 51 mg/kg. Dermal absorption of the
commonly used salts is probably slight. It is irritating to eyes, mucous mem-
branes and skin, but it is not sensitizing. Mechanisms of systemic toxicity are
not clear, but the central nervous system, heart, blood vessels, and gastrointes-
tinal lining appear to be primary targets. Poisoned animals exhibit ataxia, con-
vulsions, shock, and respiratory depression. Erosions and ulcers of the gastro-
intestinal tract follow ingestion.
There are no standard analytical methods for confirming poisoning.
Treatment
Wash contaminated skin and flush eyes with copious amounts of water. In-
stead of gastric evacuation following ingestion, administer cold milk or
aluminum hydroxide gel. This may be followed by saline catharsis. There is no
specific antidote. Shock may require blood transfusions. Use of adrenergic
amines is probably hazardous in view of myocardial irritability.
Nicotine sulfate (Black Leaf 40)
This time-honored natural insecticide is still used in horticulture. Lethal
dose in humans is about 60 mg. Nicotine preparations, especially those
using the free alkaloid, are well absorbed across the gut wall, lung, and skin.
Poisoning symptoms from excessive doses appear promptly. They are due to
transient stimulation, then prolonged depression, of the central nervous
system, autonomic ganglia, and motor end-plates of skeletal muscle. Central
nervous system injury is manifest as headache, dizziness, incoordination,
tremors, then clonic convulsions leading to tonic-extensor convulsions which
are often fatal. In some instances, convulsive activity is minimal and death by
respiratory arrest occurs within a few minutes. Effects on autonomic ganglia
give rise to sweating, salivation, nausea, abdominal pain, diarrhea, and hyper-
tension. The heart is usually slow, and often arrhythmic. Block of skeletal
muscle motor end-plates causes profound weakness, then paralysis. Death
may occur from respiratory depression or from shock.
Nicotine can be measured in blood and urine to confirm poisoning.
79
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Treatment
Promptly wash contaminated skin and flush eyes with water. Ingestion of
nicotine requires immediate gastric intubation, aspiration, and lavage, the lat-
ter preferably with 1.5% tannic acid solution, or 1:5000 potassium perman-
ganate solution. Before withdrawing the lavage tube, instill 3-4 ounces of ac-
tivated charcoal in a slurry of water. Diazepam and/or barbiturates may be re-
quired to control convulsions. Atropine and phenoxybenzamine (Diben-
zaline®) may help to control the autonomic manifestations. Positive pressure
ventilation of the lungs with oxygen may be necessary to sustain life when
respiration is arrested.
Phenylmercuric salts. Most commonly used is phenylmercuric acetate (PMA,
Agrosan, Cekusil, Gallotox, Hong Nien, Luquiphene, Mersolite, Phenmad,
Phix, PMAS, Shimmer-ex)
Phenylmercuric acetate is a widely used fungicide. Acute oral LDSO in the rat
is 22 mg/kg. Other salts are also highly toxic. They probably undergo some
dermal absorption. Because of lower volatility and less penetration of the
brain, they are somewhat less toxic than alkyl mercury compounds.
Early manifestations reflect injury to the central nervous system: ataxia,
muscle weakness, visual impairment, and delirium. After a single moderate ex-
posure, these symptoms usually resolve promptly. Repeated intensive exposures
cause symptoms and signs resembling amyotrophic lateral sclerosis: weakness
and incoordination of the arms, difficulty in swallowing and talking, weakness
and spasticity of the legs. Concurrent or later manifestations of excessive ab-
sorption reflect renal injury: albuminuria, hematuria, azotemia, and some-
times acute tubular necrosis. Induction of nephrotic syndrome has been
reported. This is characterized by massive albuminuria, generalized edema,
and hypercholesterolemia.
Methods are available at specialized toxicology laboratories for measuring
phenylmercuric compounds in urine.
Treatment
Wash contaminated skin and flush eyes with water. If ingested, remove the
chemical from the gut by prompt gastric intubation, aspiration, and lavage
with 5% sodium bicarbonate solution and instillation of activated charcoal,
followed by catharsis with sodium or magnesium sulfate. Intravenous infu-
sions of fluids accelerate excretion of mercurials and limit kidney damage.
There is no specific antidote; dimercaprol is not very effective in limiting tox-
icity.
Sodium chlorate (De-Fol-Ate, Drexel Defol, Drop-Leaf, Fall, Grain Sorghum
Harvest-Aid, Klorex, Kusatol, Tumbleaf)
Although the oral LD30 in the rat is high (1200 mg/kg), there have been sev-
eral deaths from this herbicide-defoliant in the past decade. The principal
mechanisms of toxicity are irritation of the gastrointestinal lining, central ner-
vous system depression, hemolysis, oxidation of free hemoglobin to methemo-
globin, and renal tubular injury. Dermal absorption is minimal. If ingested,
80
-------
chlorate causes swelling of the oral and pharyngeal membranes and pain in the
chest and abdomen. The victim is first restless, then apathetic. On the third or
fourth day after ingestion, lumbar pain, albuminuria, hematuria, then anuria
with azotemia, reflect renal injury. Death may be due to hyperkalemia
(hemolysis), tissue anoxia (methemoglobinemia), or renal failure.
Although chlorate itself is not readily measured in the blood, free
hemoglobin and methemoglobin in the plasma point to poisoning by an oxidiz-
ing agent.
Treatment
Remove from gut by prompt gastric intubation, aspiration, and lavage using
3 gm sodium thiosulfate in 300 ml 5% sodium bicarbonate. Instill 30-50 gm ac-
tivated charcoal in a slurry. Pain may require narcotics. Both hemodialysis
and exchange transfusions have been used successfully in treating poisonings.
Methylene blue is of no value in reducing the extracellular methemoglobin. In-
travenous infusions of 1% sodium thiosulfate (100-500 ml) limit the concen-
tration of circulating chlorate. Monitor serum electrolytes. Hemodialysis may
be needed to sustain life in the event of extensive renal tubular necrosis.
Sodium cyanide (Cymag)
Occasionally, this is used as a rodenticide. Toxicity is extreme, similar to
that of hydrogen cyanide gas used as a fumigant. CONSULT Chapter 12 on
FUMIGANTS (hydrogen cyanide) for toxicology, poisoning manifestations,
diagnosis, and management. Cyanide salts are not adsorbed on activated char-
coal.
81
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Chapter 14
MISCELLANEOUS PESTICIDES OF
LOW OR MODERATE TOXICITY
These compounds are included in the manual because their wide use
generates inquiries as to their potential for causing adverse effects.
Description of the toxic potential of these chemicals as low or moderate does
not preclude the need for cautious handling. Many agents have irritant prop-
erties, and individuals vary widely in their reactions to them. Certain
predisposed persons may suffer dermal and respiratory illness from substances
that have no effect on other persons or experimental animals. It is also true
that the sum total of potential effects of a chemical, and by-products formed
in synthesis and storage, plus the metabolites formed into vivo is never fully
known. Reasonable precautions to avoid contact with pesticides are always
recommended regardless of the reported toxicity of the principal active ingre-
dient.
Lowest reported acute oral LD50 in the rat is cited in this listing as an indica-
tion of overall toxicity, manifest as killing power. The LD50 rating says
nothing of dosages necessary to produce symptoms or signs, disease conditions
characterized by long latency, subclinical biochemical effects, or other non-
lethal effects on health. It is essential that high LD50 ratings not be interpreted
as indications that the subject chemicals are innocuous.
Knowledge of use is sometimes helpful in identifying chemicals. Agents on
this list are used as herbicides (H), fungicides (F), or insecticides (I).
There are many proprietary MIXTURES of these chemicals and it is common
to tank mix many of them according to the grower's requirements. Intelligent
management of exposures requires that the full list of active ingredients in mix-
tures be ascertained from the producer or applicator. In general, management
is aimed at the most toxic ingredient.
Chemical
Clan
Acetamldes
Acetanilides
Generic
Name
allidochlor
metolachlor
alachlor
propachlor
Use
H
H
H
H
"-DSO
750
2,780
1,800
710
Proprietary Known or Suspected
Name Advert* EHeet*
Randox, CDAA
Dual, Bleep, Primagram, ~
Primextra
Moderately Irritating
to skin and eyes.
Lasso, Lazo, Alanex Mild Irritant
Ramrod, Bexton Dermal irritant and
sensltlzer
propanil
1,384 DPA, Propanex, Riselect, Ros- |~~
anil, Stam F34, Strel, Super- I M
nox, Surcopur, Surpur, Vertac H
Mild Irritant
82
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Chemical
Cla»«
Aliphatic Acids
Alumlnofluorlde
salt
Benzenes
Benzole and
Benzlllc Acid
Derivatives
Benzonitrlles
Carbamates
Carbanllate
Dicarboxlmides
Dlnltrotoluldlne
Compounds
Generic
Name
dichloro-
propionic acid
trichloro-
acetic acid
sodium fluoro-
alumlnate
hexachloro-
benzene
(perchloroben-
zene)
paradichloro-
benzene
pentachloro-
nitrobenzene
benzyl benzoate
chlorobenzllate
trichloro-
benzole acid
chlorothalonll
dlchlobenil
asulam
benomyl
chlorpropham
terbucarb
barban
captafol
captan
folpet
(thlophal)
benefin
butralin
dinitroamine
fluchloralm
isopropalin
oryzalin
pendimethalin
profluralin
Use
H
H
1
F
1
F
1
1
H
F
H
H
F
H
H
H
F
F
F
H
H
H
H
H
H
H
H
LD50
970
5,000
>1 0,000
10,000
500
1,700
1,700
960
1,370
10,000
3,160
5,000
10,000
3,800
34,000
600
6,200
10,000
10,000
10,000
12,600
3,700
1,550
5,000
10,000
1,250
1,808
83
Proprietary Known or Suspected
Name Adverse Effects
Dalapon, Dowpon, Crisapon, |~~
Basfapon _] Skin and eye
~"| irritants
TCA L-
Cryolite, Kryocide Slight irritant
HCB, No Bunt, Anticarie I Chronic ingestlon
— causes porphyrla
cutanea tarda
PDB, Paracide [Mild respiratory
— irritant and
Ihepatotoxin
PCNB, Terrachlor Skin irritant
Benzyl benzoate
Acaraben, Akar, Benzllan, Kop~
Mite, Benz-0-Chlor
Benzac, TBA, TCBA, Tribac
Bravo, Daconil 2787
Casoron, Du-Sprex
Asulox 40, Asulox F
Benlate, Tersan 1991
Furloe, Chloro IPC, CIPC, ~~
Sprout Nip, Taterpex, Unicrop
CIPC
Azak, Azac, Azar
Irritating to skin and
eyes.
-
Moderately Irritating
to skin and
respiratory tract
Mild irritants.
These carbamates
do not Inhibit
chollnesterase
enzyme.
-
Carbyne, Neoban, Caryne Irritant and dermal sensltizer.
Oifolatan Skin irritant
Captan, Merpan, Orthocide Skin irritant
Phaltan, Folpan Skin irritant
Benfluralin, Bethrodine, Balfin,
Benefex, Quilan
Amex
Dinitramme, Cobex
Basalm
Paarlan
Surflan, Rycelan, Ryzelan
Prowl, Herbadox, Stomp
Tolban, Pregard
Slightly to
moderately irritating
to skin, eyes, and
mucous membranes.
These agents do not
uncouple oxidatlve
phosphorylation.
„_
-------
Chemical
Class
Oxadiazollnone
Phthalate
Picolinic acid
Derivative
Pyridazinone
Phosphonomethyl
glycine
Thladiazin (ol)
Triazines
Generic
Name
trifluralin
oxadlazon
chlorthal-
dimethyl
picloram
maleic
hydrazide
glyphosate
bentazon
terrazole
ametryn
anilazlne
atraton
atrazine
cyanazine
desmetryn
isomethiozin
metribuzin
prometone
prometryn
propazine
Simazine
Use LD50
H >1 0,000
H 3,500
H 3,000
H 8,200
Growth 6,950
retardant
H 4,300
H 2,063
F 1,077
H 1,750
H 5,000
H 1,465
H 3,080
H 334
H 1,390
H 10,000
H 1,100
H 2,980
H 5,235
H >5,000
H >1 0,000
Proprietary Known or Suspected
Name Adverse Effects
Tteflan, Crisalma, Digermin,
Elancolan, Ipersan
-
Slightly to
to moderately irritating
to skin, eyes, and
mucous membranes.
These agents do not
uncouple oxldatlve
phosphorylation.
Ronstar Irritating to skin and
eyes
Dacthal, DCPA Mild irritant
Tordon, Amdon pTrrltating to skin,
-I eyes, and
Ljespiratory tract
Burtolm, Chemform, De-Cut,
De-Sprout, Regulox, KMH, Slightly Irritating
Maintain, Stunt-Man
Roundup Irritant to eyes and
respiratory tract
Basagran
_
Terrazole
_
Evik, Ametrex, Gesapax
Dyrene, Direz, Kemate, Triasyn
Atratone, Gesatamin
AAtrex, Atranex, Gesaprim,
Primatol A, Atred, Crisazine,
Vectal SC
Bladex, SO 15418
Semeron —
Tantizon
Sencor, Lexone, Sencorex,
Sencoral
Pramitol, Gesafram-50, Pro-
meton, Primatol 25E
Caparol, Gesagard, Primatol Q.
Prometrex
Milogard, Gesamil, Primatol P,
Prozinex
Prmcep, Gasatop, Simadex,
Moderately irritating
to skin, eyes,
respiratory tract. On
ingestion, has
caused vomiting,
diarrhea, dyspnea,
tremors, weakness.
"Moderately Irritating
to skin, eyes, and
respiratory tract.
-
Some triazines are
mildly irritating to
skin, eyes, and up-
per respiratory tract.
Systemic toxicity is
unlikely unless very
large amounts have
been ingested.
Simanex
84
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Chemical
Class
Triazmes
Uracils
Urea Derivatives
'
Generic
Name
terbuthylazme
terbutryn
bromacil
lenacil
terbacil
chloroxuron
chlortoluron
difenoxuron
diflubenzuron
diuron
fluometuron
isoproturon
Imuron
methabenz-
thiazuron
metobromuron
metoxuron
monolmuron
monuron
neburon
siduron
tebuthiuron
tetrafluoron
Use
H
H
H
H
H
H
H
H
1
H
H
H
H
H
H
H
H
H
H
H
H
H
"-DSD
2,610
2,500
5,200
11,000
5,000
3,700
10,000
7,750
4,640
3,400
6,416
1,826
1,500
2,500
3,000
3,200
1,800
3,600
11,000
7,500
644
1,265
Proprietary Known or Suspected
Name Adverse Effects
Pnmatol-M, Gardoprim, GS
13529
Igran, Terbutrex
Some triazmes are
mildly irritating to
skin, eyes, and up-
per respiratory tract
Systemic toxicity is
unlikely unless very
large amounts have
been ingested
Hyvar X, Uragan, Urox B, Urox Irritant to skin, eyes,
HX and respiratory
tract
Venzar
Sinbar
Tenoran, Chloroxifemdim
Dicuran, Tolurex, Clortokem
Lironion
Dimilm
Cekiuron, Crisuron, Gallon,
Dialer, Di-on, Diurex, Dirurol
Dynex, Karmex, Unidron, Urox
D, Vonduron
Cotoran, Lanex, Cottonex
Arelon, Belgran, Grammon,
Tolkan
Atalon, Hoe 2810, Lmurex,
Lorox, Premalm, Sarclex
Tribunil
Patoran, Pattonex
Deftor, Dosanex, Dosaflo,
Punvel
Aresm, Afesm, Arresm,
Premalm
Monurex
Granurex, Kloben, Neburex
Tupersan
Spike
Tomilon
Moderately irritating
Many substituted
ureas are moderate-
ly irritating to skin,
eyes, and mucous
membranes.
85
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TOXICOLOGY
Many of these compounds are primary irritants to skin, eyes, and respira-
tory tract. The ureas and uracils are perhaps the most common offenders,
although captafol and chlorothalonil have apparently caused contact der-
matitis in some agricultural workers. Propachlor is a dermal sensitizer in
predisposed individuals.
Although hexachlorobenzene has low acute toxicity, long-term ingestion of
HCB-treated seed grain caused an epidemic of porphyria cutanea tarda among
Turkish farm families in the 1950's. No such effect has been found in HCB
handlers in the United States.
Given to cattle in extreme dosage, some triazines have caused neuromuscu-
lar abnormalities and damage to internal organs. It is unlikely that domestic
animals would consume these amounts voluntarily, and still less likely that
humans would be exposed to such extreme dosage.
CONFIRMATION OF ABSORPTION
The benzene derivatives and benzonitriles can be identified in plasma by gas-
liquid chromatography. Methods for benzoic acid and triazine metabolites in
urine have been developed. Analytical methods used for agricultural residues
of the remaining compounds might be adapted to analysis of gastric contents
or skin wipings. Samples must be collected within hours of exposure, because
most of these chemicals are promptly excreted.
It is unlikely that such analyses will be required in cases of human exposure
to these agents. In the event that workers experiencing protracted heavy ex-
posure develop suspicious manifestations of injury or toxicity, urine or blood
analyses may help to confirm chemical absorption. Tests may be conducted in
private or university laboratories, or laboratories supported by the state or
federal government, i.e., the United States Environmental Protection Agency
or Occupational Safety and Health Administration.
TREATMENT
1. WASH contaminated SKIN with soap and water.
2. FLUSH contaminated EYES with copious amounts of fresh water for 15
minutes.
3. INGESTIONS of SMALL amounts (less than 10 mg/kg body weight) oc-
curring less than an hour before treatment, are probably best treated by:
A. SYRUP OF IPECAC, followed by 1-2 glasses of water. Dose for
adults and children over 12 years: 30 ml. Dose for children under 12
years: 15 ml.
B. ACTIVATED CHARCOAL
Administer 30-50 gm as a slurry in tap water, after vomiting stops.
C. SODIUM OR MAGNESIUM SULFATE, 0.25 gm/kg in tap water,
as a cathartic.
86
-------
4. INGESTIONS of LARGE amounts (more than 10 mg/kg) occurring less
than an hour before treatment, should probably be treated by gastric
lavage:
A. INTUBATE stomach and ASPIRATE contents.
B. LAVAGE stomach with slurry of ACTIVATED CHARCOAL in
0.9% saline. Leave 30-50 gm activated charcoal in the stomach be-
fore withdrawing tube.
C. SODIUM SULFATE, 0.25 gm/kg in tap water, as a cathartic.
CAUTION: Hydrocarbons (kerosene, petroleum distillates) are
included in some formulations of these chemicals. In-
gestion of very LARGE AMOUNTS may cause CNS
depression. In this case, IPECAC IS CONTRAIN-
DICATED. Also, gastric intubation incurs a risk of
HYDROCARBON PNEUMONITIS. For this reason
observe the following precautions:
(1) If the victim is unconscious or obtunded and
facilities are at hand, insert an ENDOTRA-
CHEAL TUBE (cuffed, if available) prior to
gastric intubation.
(2) Keep victim's HEAD BELOW LEVEL OF
STOMACH during intubation and lavage
(Trendelenburg, or left lateral decubitus, with
head of table tipped downward). Keep victim's
head turned to the left.
(3) ASPIRATE PHARYNX as regularly as possible
to remove gagged or vomited stomach contents.
5. INGESTIONS occurring MORE THAN an HOUR before treatment are
probably best treated only by ACTIVATED CHARCOAL, 30-50 gm,
and SODIUM or MAGNESIUM SULFATE, 0.25 gm/kg, as described
above.
6. There are no specific antidotes for these chemicals. Because manifesta-
tions of toxicity do occasionally occur in peculiarly predisposed individ-
uals, MAINTAIN CONTACT with victim for at least 72 hours so that
unexpected adverse effects can be treated promptly.
87
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INDEX TO PESTICIDE POISONINGS
BY SYMPTOMS AND SIGNS
A listing of pesticides capable of causing specific symptoms and signs may
be of some help to professionals confronted with illnesses possibly caused by
pesticides. However, the limitations of this kind of index should be clearly
understood. Rarely are particular manifestations always present in poisonings
by a given chemical, and many poisonings are characterized by unexpected
symptoms. Furthermore, there are usually many causes of particular symp-
toms and signs.
The purpose of these lists is, therefore, only to direct the professional's at-
tention to a series of chemicals possibly responsible for various symptoms and
signs, based on past experience. Starting from the major presenting feature
of the illness, the interviewer can inquire closely into possible exposures to the
principal causative toxicants, and then, if appropriate, assemble more substan-
tive evidence for or against a poisoning diagnosis, e.g., concurrence of multi-
ple manifestations of specific poisonings, and laboratory test findings.
Not all manifestations of illness are included. Some symptoms, such as
dizziness and weakness, are caused by so many chemicals by either direct or in-
direct mechanisms that they have little value diagnostically.
This approach to clinical toxicology has been developed by Alan K. Done,
M.D., of Wayne State School of Medicine. His general format of classifica-
tion (Solving the Poison Puzzle, Emergency Medicine, February 1979) is used
in the following tables. Chemicals appearing in the lists headed
"Characteristic of These Poisonings" have been substantially consistent in
producing the symptoms or signs identified in the left column. Agents listed in
the column headed "Occurs in These Poisonings" are found with sufficient
frequency to deserve mention, but the association is not highly consistent.
CHARACTERISTIC OF OCCURS IN
MANIFESTATIONS THESE POISONINGS THESE POISONINGS
General
Breath odor of.
Garlic Arsenic
Phosphorus
Phosphides
Phosphine
Bitter almonds Cyanide
Rotten cabbage Carbon disulfide
Fever Nitro-, chloro- phenols Chlorophenoxy compounds
Hypothermia Vacor
Myalgia Chlorophenoxy compounds
Chills Arsine
Vacor
88
-------
MANIFESTATIONS
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN
THESE POISONINGS
Thirst
Anorexia
Hot sensations
Skin and Mucous Membranes
Dry, cracked skin of hands
Loss of nails
Brittle nails
Loss of hair
Sweating
Pallor
Cyanosis
Scratchy throat and Irritated
eyes
Blisters or burns
Rash
Yellow stain
Eccrtymoses
Keratoses
Nitro-, chloro-, phenols
Aminopyridine
Phosphine
Organophosphates
Carbamate Insecticides
Nicotine
Chlordimeform
Arslne
Paraquat
Petroleum distillates
Weed oil
Paraquat
Inorganic arsenicals
Thallium
Inorganic arsenicals
Organosphates
Carbamate insecticides
Nitro-, chloro- phenols
Nicotine
Aminopyridine
Organchlorlnes
Paraquat
Strychnine
Crimidine
Nicotine
Sodium fluoroacetate
Sulfur dioxide
Acrolein
Chloropicrin
Nitro-, chloro- phenols
Formaldehyde
Pyrethrins
Copper compounds
Endothall
Sodium chlorate
Methyl bromide
Phosphorus
Sulfur
Thiram
Propachlor
Barban
Nitrophenols
Anticoagulant rodenticides
Phosphorus
Phosphides
Inorganic arsenicals
Fumlgants
Nitro-, chloro-, phenols
Arsenicals
Anticoagulant rodenticides
Organophosphates
Carbamate insecticides
Organochlorlnes
Paraquat
Blsdlthlocarbamates
Ethylene bisdlthlocarbamates
Chloroallphatlc acids
Liquid methyl bromide or ethylene
oxide
Plcloram
Dlfolatan
Captan
Chlorothalonll
Nitro-, chloro- phenols
Many other herbicides and
fungicides
89
-------
MANIFESTATIONS
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN
THESE POISONINGS
Jaundice
Central Nervous System
Headache
Ataxia
Convulsions
Muscle twitching
Tremors
Mental confusion
Sudden unconsciousness
Central Nervous System
Tingling and numbness in the
extremities
Tetany
Myotonia
Phosphorus
Phosphides
Phosphme
Halocarbon fumigants
Organophosphates
Carbamate insecticides
Organochlorines
Fumigants
Nicotine
Inorganic arsenicals
Organophosphates
Carbamate insecticides
Endothall
Nicotine
Phenyl mercuric acetate
Organochlorines
Strychnine
Crimldine
Phosphorus
Cyanide
Sodium fluoroacetate
Nicotine
Aminopyridine
Endothall
Organophosphates
Carbamate insecticides
Sulfuryl fluoride
Organophosphates
Carbamates insecticides
Phosphine
Aminopyridine
Cycloheximide
Nicotine
Organophosphates
Carbamate insecticides
Nitrophenols
Chlorophenols
Cyanide
Organochlorines
Vacor
Sodium fluoroacetate
Carbon disulfide
Aminopyridine
Cycloheximide
Cyanide
Carbon disulfide
Vacor
Sodium fluoroacetate
Phosphorus
Phosphides
Paraquat
Inorganic arsenicals
Nitrophenols
Chlorophenols
Fumigants
Inorganic arsenicals
Organochlorines
Nitro-, chloro- phenols
Organophosphates
Carbamate insecticides
Sulfuryl fluoride
Chlorophenoxy compounds
Pyrethrins
Nitro-, chloro- phenols
Bentazon
Sulfuryl fluoride
Strychnine
Crimidine
Nicotine
Inorganic arsenicals
Organophosphates
Diquat
Carbamate insecticides
Halocarbon fumigants
Inorganic arsenicals
Chlorophenoxy compounds
90
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MANIFESTATIONS
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN
THESE POISONINGS
Mlosls
Organophosphates
Carbamate insecticides
Gastrointestinal Tract
Nausea, vomiting, abdominal
cramps, diarrhea
Salivation
Respiratory System
Stuffy nose, wheezing
Nosebleed
Coughing frothy sputum
(pulmonary edema)
Rhinorrhea
Tachypnea
Respiratory depression
Labored breathing
Chest pain
Organophosphates
Carbamate insecticides
Diquat
Phosphorus
Phosphides
Phosphine
Inorganic arsenlcals
Arslne
Fumlgants
Red squill
Cyclohexlmide
Endothall
Nicotine
Chlorates
Copper Compounds
Organophosphates
Carbamate Insecticides
Cycloheximlde
Nicotine
Pyrethrum
Bisdithiocarbamates plus alcohol
Methyl bromide
Phosphine
Phosphorus
Phosphides
Ethylene oxide
Organophosphates
Carbamate insecticides
Fumigants
Nitro-, chloro- phenols
Organophosphates
Carbamate insecticides
Fumlgants
Cyanide
Acrylomtrile
Nicotine
Endothall
Sodium chlorate
Methyl bromide
Organophosphates
Carbamate Insecticides
Phosphine
Phosphides
Phosphorus
Fumlgants
Sodium chlorate
Organochlorines
Chloro-, nitro- phenols
Bisdithiocarbamates
Ethylene bisdithiocarbamates
Chlorophenoxy compounds
Organic arsenicals
Paraquat
Bentazon
Chloroaliphatic acids
Paraquat
Organophosphates
Carbamate insecticides
ANTU
Organochlorines
Sulfuryl fluoride
Organophosphates
Carbamate Insecticides
Chlorophenoxy herbicides
Nitro-, chloro- phenols
Chloroaliphatic acids
91
-------
MANIFESTATIONS
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN
THESE POISONINGS
Cardiovascular System
Bradycardia
Hypertension
Renal System
Renal failure
Urinary frequency, dysuria
Renal colic
Blood
Anemia
Leukopenia
Hypoprothrombmernia
Depressed cholmesterase
enzyme activities
Methemoglobinemia
Free hemoglobin in plasma
Elevated alkaline phosphatase,
GOT, LDH
Elevated blood bromide
Hyperbilirubmemia
Organophosphates
Carbamate insecticides
Cyanide
Tachycardia
Hypotension, shock
Irregular heart beat
Nitrophenols
Chlorophenols
Phosphorus
Phosphides
Phosphine
Vacor
Endothall
Cyanide
Sodium fluoroacetate
Halocarbon fumigants
Endothall
Organochlorines
Bisdithiocarbam;
Inorganic arsenic
Anticoagulant ro<
Organochlorines
Red squill
Nicotine
Arsine
Fumigants
Cycloheximide
Chlorates
Chlordimeform
Vacor
Anticoagulant rodenticides
Chlorates
Naphthalene
Anticoagulant rodenticides
Anticoagulant rodenticides
Organophosphates
Chlorates
Naphthalene
Arsine
Copper compounds
Sodium chlorate
Halocarbon fumigants
Inorganic arsenicals
Diquat
Paraquat
Aminopyndine
Methyl bromide
Paraquat
Diquat
Phosphine
Phosphorus
Phosphides
Copper compounds
Inorganic arsenicals
Paraquat
Diquat
Inorganic arsenicals
Copper compounds
Inorganic arsenicals
Nitrophenols
Inorganic arsenicals
Carbamate insecticides
(targe dosage)
Endnn
Halocarbon fumigants
92
-------
MANIFESTATIONS
CHARACTERISTIC OF
THESE POISONINGS
OCCURS IN
THESE POISONINGS
Elevated BUN, creatinine
Hyperkalemia
Urine
Proteinuria
Hematuna
Ketonuria
Hemoglobinuria
Myoglobinuria
Porphyrinuria
Bilirubinuria
Glycosuna
Feces
Blood present (melena)
Luminescence
Semen
Low sperm count
Paraquat
Diquat
Fumigants
Chlorates
Inorganic arsenicals
Naphthalene
Chlorates
Copper compounds
Diquat
Paraquat
Nitro-, chloro-, phenols
Fumigants
Cycloheximide
Copper compounds
Phenyl mercuric acetate
Sodium chlorate
Anticoagulant rodentlcldes
Sodium chlorate
Cycloheximide
Chlordlmeform
Vacor
Aminopyridine
Naphthalene
Arsine
Sodium chlorate
Hexachlorobenzene
Halocarbon fumigants
Phosphorus
Phosphides
Phosphine
Vacor
Diquat
Sodium chlorate
Anticoagulant rodentlcides
Phosphorus
Phosphides
Endothall
Cycloheximide
Phosphorus
Sulfuryl fluoride
Nitro-, chloro-, phenols
Endothall
Sulfuryl fluoride
Chlordimeform
Fumigants
Paraquat
Diquat
Phosphorus
Phosphides
Chlorophenoxy compounds
Paraquat
Dibromochloropropane
Kepone
93
-------
PESTICIDES INDEX
Pagef
1080 .................................... 54
AAtack ................................. 36
AAtrex .................................. 82
Abate ................................... 1
Abathion ................................ 1
Acaraben ................................ 14, 82
Acaron .................................. 77
Accelerate ............................... 77
acephate ................................. 1
Acquinite ................................ 68
Acrex ................................... 23
Acritet .................................. 68
Acrolein ................................. 68
Acrylaldehyde ............................ 68
Acrylofume .............................. 68
acrylonitrile .............................. 68
Actellic .................................. 1
Acti-dione ............................... 77
Actispray ................................ 77
Afalon .................................. 82
Afesin ................................... 82
African .................................. 1
Agritox .................................. 1
Agrosan ................................. 77
Agrotec ................................. 27
Agrothion ............................... 1
Akar .................................... 82
alachlor ................................. 82
Alanex .................................. 82
aldicarb ................................. 9
aldrin ................................... 14
Aldrite .................................. 14
allethrin ................................. 42
allidochlor ............................... 82
alumino fluoride salt ...................... 82
aluminum phosphide ...................... 68
Amaze .................................. 1
tPage number refers to the beginning page of the
chapter in which the pesticide is covered.
94
-------
Ambox 23
Ambush 42
Amdon 82
Ametrex 82
ametryn 82
Amex 82
aminocarb 9
4-aminopyridine 77
Amoxone 27
Ancrack 23
anilazine 82
Ansar 170 HC 46
Ansar 529 HC 46
Ansar 8100 46
Ansar DSMA liquid 46
Anthio 1
Anticarie 82
Anticoagulent rodenticides 54
antu 54
4-AP 77
Aphox 9
Aquacide 31
Aqua-Kleen 27
Aqualin 68
Aquathol 77
Arasan 36
Arelon 82
Aresin 82
Arresin 82
Arrhenal 46
arsenic 46
arsenic acid 46
arsenic trioxide 46
arsenious oxide 46
arsine 46
Arsinyl 46
Arsonate liquid 46
Aspon 1
Aspor 36
asulam 82
Asulox 40 82
Asulox F 82
Atranex 82
atraton 82
95
-------
atrazine 82
Atred 82
Aules 36
Avadex 36
Avadex-BW 36
Avitrol 77
Azac 82
Azak 82
Azar 82
azinphos-methyl 1
Azodrin 1
—B—
Balfin 82
Banvel 27
barban 82
barthrin 42
Basagran 82
Basalin 82
Basanite 23
Basfapon 82
Baygon 9
Bayrusil 1
Baytex 1
Baythion 1
Belgran 82
Belmark 42
Benefex 82
benefin 82
Benfluralin 82
Benlate 82
benomyl 82
bentazon 82
Benzac 82
benzene hexachloride 14
Benzilan 82
Benz-O-Chlor 82
Benzyl benzoate 82
bethrodine 82
Bexton 82
BH 2,4-D 27
BHC 14
Bicep 82
96
-------
Bidrin 1
binapacryl 23
bioresmethrin 42
Birlane 1
Black Leaf 40 77
Black Leaf Grass, Weed and Vegetation
Killer Spray 19
Bladafum 1
Bladex 82
Bo-Ana 1
Bolstar 1
bomyl 1
Bravo 82
brodifacoum 54
bromacil 82
bromadiolone 54
Bromofume 68
Brom-O-Gas 68
Bromone 54
bromophos 1
bromophos-ethyl 1
Brush-Rhap 27
Bueno 6 46
bufencarb 9
Burtolin 82
butralin 82
butylate 36
Bux 9
r<
cacodylic acid 46
Caid 54
calcium acid methanearsonate 46
calcium arsenate 46
calcium arsenite 46
Caldon 23
CAMA 46
Caparol 82
captafol 82
captan 82
Carbacryl 68
Carbamult 9
Carbamates-cholinesterase-inhibiting 9
97
-------
carbaryl 9
Carbazinc 36
carbofuran 9
carbon bisulfide 68
carbon disulfide 68
carbon tetrachloride 68
carbophenothion 1
Carbyne 82
Caryne 82
Carzol 9
Casoron 82
Castrix 54
CDAA 82
Cekiuron 82
Cekusil 77
Celathion 1
Celmide 68
Certified Kiltrol-74 Weed Killer 19
Chem Bam 36
Chemform 82
Chemonite 46
Chemox General 23
Chemox PE 23
Chem Pels C 46
Chemsect DNBP 23
Chemsect DNOC 23
Chem-Sen 56 46
Chipco Crab Kleen 46
Chipco Thiram 75 36
Chipco Turf Herbicide "D" 27
Chlordan 14
chlordane 14
chlordimeform 77
chlorfenac 27
chlorfenvinphos 1
chlormephos 1
chlorobenzilate 14
chloroform 68
chloro IPC 82
chlorophacinone 54
chlorophenothane 14
Chlorophenoxy compounds 27
Chlor-O-Pic 68
chloropicrin 68
98
-------
chlorothalonil 82
chloroxifenidim 82
Chloroxone 27
chloroxuron 82
chlorpropham 82
chlorpyrifos 1
chlorthaldimethyl 82
chlorthiophos 1
chlortoluron 82
Chrysron 42
Ciba-Geigy Ontrack (OS 3,4 or 5) 19
cinerins 42
Ciodrin 1
CIPC 82
Clortokem 82
Cobex 82
copper acetate 77
copper acetoarsenite 46
copper arsenite 46,77
copper carbonate 77
copper chloride 77
copper hydroxide 77
copper naphthenate 77
copper oleate 77
copper oxalate 77
copper oxide 77
copper phosphate 77
copper quinolinolate 77
copper resinate 77
copper salts 77
copper silicate 77
copper sulfate 77
copper zinc chromate 77
Co-Ral 1
Corozate 36
Cotoran 82
Cottonex 82
coumachlor 54
coumafene 54
coumafuryl 54
coumaphos 1
counter 1
Crab-E-Rad 46
crimidine 54
99
-------
Crisalina 82
Crisapon 82
crisazine 82
Crisquat 31
Crisuron 82
Crop Rider 27
Crotothane 23
crotoxyphos 1
cryolite 82
Cuman 36
Curacron 1
Curamil 1
cyanazine 82
cyanofenphos 1
cyanophos 1
Cyanox 1
cycloate 36
cycloheximide 77
Cyclon 68
Cygon 1
Cymag 77
Cyolane 1
cypermethrin 42
cythioate 1
Cythion 1
—D—
2,4-D 27
D 50 27
decamethrin 42
Dacamine 2D/2T 27
Dacamine 4D 27
Dacamine4T 27
Daconate 6 46
Daconil 2787 82
Dacthal 82
Dailon 82
dalapon 82
Dal-E-Rad 46
Dalf 1
Dapacryl 23
Dasanit 1
2,4-DB 27
100
-------
DBCP 68
DCPA 82
D-D 68
DDT 14
DDVP 1
De broussaillant 600 27
De broussaillant Concentre 27
De-Cut 82
Ded-Weed 27
Ded-Weed Brush Killer 27
DBF 1
De-Fend 1
De-Fol-Ate 77
Deftor 82
De-Green 1
Delnav 1
demeton 1
demeton-methyl 1
Des-I-Cate 77
Desiccant L-10 46
desmetryn 82
Desormone 27
De-Sprout 82
Dessin 23
Dethdiet 54
Dextrone 31
Dextrone X 31
Dexuron 31
dialifor 1
diallate 36
Dialer 82
diazinon 1
Dibrom 1
dibromochloropropane 68
dicamba 27
dicarzol 9
dichlobenil 82
dichloroanisic acid 27
2,4-dichlorophenoxyacetic acid 27
dichloropropene (ane) 68
dichlofenthion 1
dichloropropionic acid 82
dichlorprop 27
dichlorvos 1
101
-------
dicofol 14
Dicotox 27
dicrotophos 1
Dicuran 82
dieldrin 14
Dieldrite 14
dienochlor 14
difenacoum 54
difenoxuron 82
diflubenzuron 82
Difolatan 82
Digermin 82
Dilic 46
Dimecron 1
dimethoate 1
dimetilan 9
Dimilin 82
Dinitramine 82
dinitro 23
Dinitro-3 23
dinitroamine 82
dinitrocresol 23
Dinitro General 23
dinitrophenol 23
dinobuton 23
dinocap 23
Dinofen 23
dinopenton 23
dinoprop 23
dinosam 23
dinoseb 23
dinosulfon 23
dinoterb 23
dinoterbon 23
Dinoxol 27
Di-on 82
dioxathion 1
Diphacin 54
diphacinone 54
Dipher 36
Dipterex 1
diquat 31
Direz 82
disodium methyl arsonate 46
102
-------
disulfoton 1
Di-Syston 1
Di-Tac 46
Dithane (D14, M22, M45, or Z78) 36
Dithiocarbamates 36
Dithione 1
Diurex 82
Diurol 82
diuron 82
DLP-787 54
DMA 46
DMA 4 27
DMA 100 46
DNAP 23
DNBP 23
DNC 23
DNOC 23
Dormone 27
Dosaflo 82
Dosanex 82
Dotan 1
Dow General Weed Killer 23
Dow Pentachlorophenol 19
Dow Selective Weed Killer 23
Dowfume fumigants 68
Dowicide EC-7 19
Dowpon 82
DP-2 Antimicrobial 19
DPA 82
Drat 54
Drawinol 23
Draza 9
Drexel Defol 77
Drinox 14
Drop-Leaf 77
Drupina 90 36
DSE 36
DSMA 46
Dual 82
Dursban 1
Du-Sprex 82
Dyanap 23
Dyfonate 1
Dylox 1
103
-------
Dynamyte 23
Dynex 82
Dyrene 82
—E—
Ectiban 42
EDB 68
EDC 68
Ekamet 1
Ekatin 1
Elancolan 82
Elgetol 30 23
Elgetol318 23
emerald green 46
Emulsamine BK 27
Emulsamine E-3 27
Endosan 23
endosulfan 14
Endothall 77
endrin 14
Entex 1
Envert DT, T or 171 27
EPBP 1
EPN 1
epoxypropane 68
Eptam 36
EPTC 36
Esgram 31
Esteron Brush Killer 27
Esteron Four 27
Esteron 99 Concentrate 27
Esteron 245 27
Estone 27
ethion 1
ethoprop 1
Ethylan 14
ethyl parathion 1
ethylene dibromide 68
ethylene dichloride 68
ethylene oxide 68
ETO 68
etrimfos 1
Evik 82
E-Z-OffD 1
104
-------
—F—
Fac 1
Fall 77
Famfos 1
famphur 1
Far-Go 36
fenac 27
fenamiphos 1
Fence Rider 27
fenitrothion 1
fenophosphon 1
fenothrin 42
fenpropanate 42
fensulfothion 1
fenthion 1
f envalerate 42
ferbam 36
Ferberk 36
Fermide 850 36
Fernasan 36
Fernesta 27
Fernimine 27
Fernoxone 27
Ferxone 27
Field Clean Weed Killer 27
fluchloralin 82
fluometuron 82
Folex 1
Folpan 82
folpet 82
fonofos 1
formaldehyde 68
Formalin 68
formetanate HCI 9
formothion 1
Formula 40 27
Forron 27
Framed 82
Fratol 54
French green 46
Fuclasin Ultra 36
Fuklasin 36
Fumarin 54
Fumigant-1 68
Fumigants 68
105
-------
Fundal 77
Fundex 77
Fungostop 36
Furadan 9
Furloe 82
—G—
G 28029 1
Galecron 77
Gallotox 77
Gammexane 14
Garden Termi Tox 19
Gardona 1
Gardoprim 82
Gebutox 23
Gesafram 50 82
Gesagard 82
Gesamil 82
Gesapax 82
Gesaprim 82
Gesatamin 82
Gesatop 82
glyphosate 82
Grain Sorghum Harvest-Aid 77
Graminon 82
Gramonol 31
Granurex 82
Griffin Manex 36
GS 13529 82
Guthion 1
Gypsine 46
—H—
HCB 82
HCH 14
Hedonal 27
heptachlor 14
heptenophos 1
Herbadox 82
Herb-All 46
Herbidal 27
hexachlorobenzene 82
106
-------
Hexadrin 14
Hexaferb 36
Hexathane 36
Hexathir 36
Hexazir 36
Hi-Yield Desiccant H-10 46
Hizarocin 77
Hoe 2810 82
Hong Nien 77
Hostaquick 1
Hostathion 1
Hydout 77
hydrogen cyanide 68
Hydrothol 77
Hyvar X 82
I
Igran 82
Imidan 1
Inorganic arsenicals 46
Inverton 245 27
iodofenphos 1
Ipersan 82
isofenphos 1
isomethiozin 82
isopropalin 82
isoproturon 82
isoxathion 1
—J_
jasmolins 42
Jones Ant Killer 46
—K—
Karathane 23
Karmex 82
Karphos 1
Kayafume 68
Kelthane 14
Kemate 82
kepone 14
107
-------
Kill-All 46
Kiloseb 23
Klean Krop 23
Kloben 82
Klorex 77
KMH 82
Knockmate 36
Kop-Fume 68
Kop-Mite 82
Kryocide 82
Krysid 54
Kuron 27
Kusatol 77
Kwell 14
Kypfarin 54
Kypman 80 36
Kypzin 36
' winjj^^—
Lanex 82
Lannate 9
Lasso 82
Lawn-Keep 27
Lazo 82
lead arsenate 46
lenacil 82
leptophos 1
Lexone 82
lindane 14
Line Rider 27
Linurex 82
linuron 82
Liphadione 54
Liquiphene 77
Lironion 82
Lithate 27
Lonacol 36
Lorox 82
Lorsban 1
Lysoff 1
108
-------
—M—
MAA 46
Macondray 27
Maintain 82
malathion 1
maleic hydrazide 82
MAMA 46
Mancozeb 36
maneb 36
Manebgan 36
Manesan 36
Manzate 36
Manzeb 36
Manzin 36
Marlate 14
Matacil 9
MC2188 1
MCPA 27
MCPB 27
MCPB-Ethyl 27
MCPCA 27
MCPP 27
MeBr 68
Mecoprop 27
Mercuram 36
Merge 823 46
Merpan 82
merphos 1
Mersolite 77
Mesamate 46
Mesurol 9
Metasystox 1
methabenzthiazuron 82
methamidophos 1
methane arsonate 46
methane arsonic acid 46
Methar 46
methidathion 1
methiocarb 9
Meth-O-Gas 68
methomyl 9
methoxychlor 14
methyl bromide 68
methyl parathion 1
metobromuron 82
109
-------
metolachlor 82
metoxuron 82
metribuzin 82
mevinphos 1
Mezene 36
Microzul 54
Milogard 82
Miracle 27
mirex 14
mitis green 46
Mobilawn 1
Mocap 1
Mofisal 31
Monitor 1
monoammonium methane arsonate 46
monoammonium methyl arsonate 46
mono-calcium arsenite 46
monocrotophos 1
monolinuron 82
monosodium methyl arsonate 46
Monurex 82
monuron 82
Morocide 23
MSMA 46
—N—
nabam 36
Nabasan 36
naled 1
Namate 46
naptalam 23
Naptro 23
naramycin 77
Neburex 82
neburon 82
Neguvon 1
Nemacur 1
Neoban 82
Neo-Pynamin 42
Nephis 68
Nespor 36
Netagrone 600 27
Nexagan 1
110
-------
Nexion 1
nicotine sulf ate 77
Nitrador 23
Nitrophenolic and nitrocresolic herbicides 23
Nitropone C 23
No Bunt 82
Nomersan 36
norbormide 54
Nudrin 9
Nuvanol-N 1
—O—
Oftanol 1
Ofunack 1
OMPA 1
Organochlorines-solid 14
Organophosphates-cholinesterase-inhibiting .. 1
Orthene 1
Orthocide 82
Ortho paraquat CL 31
Ortho Triox Liquid Vegetation Killer 19
oryzalin 82
oxadiazon 82
oxamyl 9
oxirane 68
—P—
Paarlan 82
Paracide 82
paradichlorobenzene 82
paraquat 31
paraquat dichloride 31
parathion 1
paris green 46
Parzate 36
Pathclear 31
Patoran 82
Pattonex 82
PCNB 82
PCP 19
PDB 82
pebulate 36
111
-------
Pencal 46
Penchlorol 19
pendimethalin 82
Penite 46
Pennamine D 27
Penncap-M 1
penta 19
Pentac 14
pentachloronitrobenzene 82
pentachlorophenol 19
Pentacon 19
Penwar 19
perchlorobenzene 82
permethrin 42
Perthane 14
Pestmaster (EDB-85) 68
Phaltan 82
phencapton 1
Phenmad 77
phenthoate 1
phenylmercuric acetate 77
Phix 77
phorate 1
phosalone 1
Phosdrin 1
phosfolan 1
phosmet 1
phosphamidon 1
phosphine 68
phosphonomethyl glycine 82
phosphorus 54
Phostoxin 68
Phosvel 1
Phosvin 54
phoxim 1
phthalthrin 42
Phytar 560 46
Pic-Clor 68
Picfume 68
picloram 82
pindone 54
pirimicarb 9
Pirimor 9
piperonyl butoxide 42
112
-------
pirimiphos-methyl 1
Pivacin 54
Rival 54
pivaldione 54
Pivalyn 54
Planotox 27
Plantgard 27
PMA 77
PMAS 77
Polyram M 36
Polyram Ultra 36
Polyram Z 36
Pomarsol forte 36
Pomarsol Z Forte 36
Pounce 42
Pramitol 82
Preeglone 31
Pregard 82
Premalin 82
Premerge 3 23
Priglone 31
Priltox 19
Primagram 82
Primatol (A, 25E, M, P, Q, or S) 82
Primextra 82
Princep 82
Proban 1
Prodalumnol Double 46
Prodaram 36
profenofos 1
profluralin 82
Profume 68
Prolate 1
Promar 54
promecarb 9
Prometon 82
Prometone 82
Prometrex 82
prometryn 82
propachlor 82
Propanex 82
propanil 82
propazine 82
propenal 68
propetamphos 1
113
-------
prdpoxur 9
propylene oxide 68
propylthiopyrophosphate 1
prothoate 1
Prowl 82
Prozinex 82
prussic acid 68
Purina Insect Oil Concentrate 19
Purivel 82
Pydrin 42
Pynamin 42
pyrazophos 1
pyrethrins 42
pyrethroids 42
pyrethrum 42
pyridaphenthion 1
-Q-
Quilan 82
quinalphos 1
—R—
Rabon 1
Rad-E-Cate25 46
Ramik 54
Ramrod 82
Ramucide 54
Randox 82
Rapid 9
Ratak 54
Raticate 54
Ratimus 54
Ratomet 54
Ratox 54
Raviac 54
Rax 54
Red Squill 54
Reglone 31
Reglox 31
resmethrin 42
RH-787 54
Rhodia 27
Rhodia Low Volatile Brush Killer no. 2 27
114
-------
Ripcord 42
Riselect 82
Rodenticides 54
Rodex 54
Rodine 54
Ro-Neet 36
Ronstar 82
Rosanil 82
Roundup 82
Rozol 54
Rycelan 82
Ryzelan 82
—S—
Safrotin 1
Salvo 27,46
Sarclex 82
schradan 1
Schweinfurt green 46
SD 15418 82
Security 46
Selinon 23
Semeron 82
Sencor 82
Sencoral 82
Sencorex 82
Sevin 9
Shimmer-ex 77
Shoxin 54
siduron 82
Silvex 27
Simadex 82
Simanex 82
simazine 82
Simpar 31
Sinbar 77
Sinituho 19
Sinox General 23
Snip Fly Bands 9
Sodar 46
sodium arsenate 46
sodium arsenite 46
sodium chlorate 77
sodium cyanide 77
115
-------
sodium fluoroacetate 54
sodium fluoroaluminate 82
sodium pentachlorophenate 19
Soilbrom 68
Soprabel 46
Spanone 77
Spectracide 1
Spike 82
Spontox 27
Spotrete 36
Spotton 1
Spra-cal 46
Spring-Bak 36
Spritz-Hormin/2,4-D 27
Spritz-Hormit/2,4-D 27
Sprout Nip 82
S-Seven 1
Stam F34 82
Stomp 82
Strel 82
Strobane 14
Strobane-T 14
strychnine 54
Stunt-Man 82
Subitex 23
sulfotepp 1
sulfuryl fluoride 68
sulprofos 1
Sumithion 1
Super-Caid 54
Super Crab-E-Rad-Calar 46
Super D Weedone 27
Super Dal-E-Rad-Calar 46
Supernox 82
Superormone Concentre 27
Supracide 1
Surcopur 82
Surecide 1
Surflan 82
Surpass 36
Surpur 82
Sutan 36
Swat 1
Synthrin 42
Systox 1
116
-------
—T—
2,4,5-T 27
Talan 23
Talbot 46
Talon 54
Tantizon 82
Target MSMA 46
Taterpex 82
2,4,5-TB 27
TEA 82
TCA 82
TCBA 82
tebuthiuron 82
Telone 68
tempephos 1
Temik 9
Tenoran 82
TEPP 1
terbacil 82
terbucarb 82
terbufos 1
terbuthylazine 82
Terbutrex 82
terbutryn 82
terpene polychlorinates 14
Terrachlor 82
Terraklene 31
Terrazole 82
Tersan 36
Tersan 75 36
Tersan 1991 82
Tersan LSR 36
tetrachlorvinphos 1
tetraethyl pyrophosphate 1
tetrafluoron 82
tetramethrin 42
Tetrapom 36
Thimet 1
Thiodan 14
Thioknock 36
thiometon 1
Thiophal 82
Thiophos 1
Thiotex 36
thiram 36
117
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Thiramad 36
Thirasan 36
Thiuramin 36
Thylate 36
Tiezene 36
Tiguvon 1
Tillam 36
Tirampa 36
TMTDS 36
Tolban 82
Tolkan 82
Tolurex 82
Tomilon 82
Tomorin 54
Topitox 54
Torak 1
Tordon 82
Tormona 27
TotaCol 31
Toxakil 14
toxaphene 14
Tox-Hid 54
2,4,5-TP 27
Trametan 36
Transamine 27
Trans-Vert 46
Treflan 82
triallate 36
Triasyn 82
triazophos 1
Tribac 82
Tri-ban 54
Tribunil 82
Tributon 27
Tricarbamix Z 36
trichlorfon 1
trichloroacetic acid 82
trichloronate 1
2,4,5-trichlorophenoxyacetic acid 27
2,3,6 trichlorophenylacetic acid 27
Tri-Clor 68
trifluralin 82
Trifocide 23
Trifungol 36
118
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Trimangol ............................... 36
Trinoxol ................................. 27
Trioxone ................................ 27
Tripomol ................................ 36
Triscabol ................................ 36
Trithion ................................. 1
Tritoftorol ............................... 36
Tuads ................................... 36
Tubothane ............................... 36
Tumbleaf ................................ 77
Tupersan ................................ 82
— U—
U 46 .................................... 27
U 46 Special .............................. 27
Unicrop CIPC ............................ 82
Unicrop DNBP ........................... 23
Unidron ................................. 82
Uragan .................................. 82
Urox (B, D, or Hx) ........................ 82
Usol Cabin Oil ........................... 4
Vacor Rat Killer .......................... 54
Vancide FE-95 ............................ 36
Vancide Maneb 80 ........................ 36
Vancide MZ-96 ........................... 36
Vapona ................................. 1
Vectal SC ................................ 82
Veg-I-Kill ................................ 19
Venzar .................................. 82
Veon 245 ................................ 27
Vernam ................................. 36
vernolate ................................ 36
Vertac Dinitro Weed Killer ................. 23
Verton 2D ............................... 27
Verton2T ............................... 27
Vikane .................................. 68
Visko-Rhap .............................. 27
Visko-Rhap LV 2D-2T ..................... 27
Vonduron ............................... 82
Vydate .................................. 9
119
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— w—
Warbex ................................. 1
warfarin ................................. 54
Warfarin Plus ............................ 54
Weed-B-Gon ............................. 27
Weed-E-Rad ............................. 46
Weed-E-Rad 360 .......................... 46
Weed-E-Rad DMA Powder ................. 46
Weed-Hoe ............................... 46
Weed-Rhap .............................. 27
Weed Tox ............................... 27
Weedar .................................. 27
Weedol .................................. 31
Weedone ................................ 27
Weedtrine-D ............................. 31
Weedtrol ................................ 27
white arsenic ............................. 46
Wood Preserver .......................... 19
Wood Tox 140 ............................ 19
Yasoknock ............................... 54
yellow phosphorus ........................ 54
— Z—
Z-C Spray ............................... 36
Zebtox .................................. 36
Zerlate .................................. 36
Zincmate ................................ 36
zinc phosphide ........................... 54
Zinc-Tox ................................ 54
zineb .................................... 36
Zinosan ................................. 36
ziram ................................... 36
Ziramvis ................................. 36
Zirasan 90 ............................... 36
Zirberk .................................. 36
Zirex90 ................................. 36
Ziride ................................... 36
Zolone .................................. 1
zoocoumarin ............................. 54
JJ.U.S. GOVERNMENT PRINTING OFFICE. 1 98 2 -3 5 4 - 7 5 0 / 8 2 6 6
120
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U.O. fj^'i'-op.n'?:-,:.:-,! ProlGction Agency
R .-7:0,5 V, ! if-,-ary
230 S'y-th jea:born Street x
Chicago, ijlir.ois .60604; ^^^
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