United States
           Environmental Protection
           Agency
            EPA-540/9-88-001
            March 1989
vvEPA
Recognition and
Management of
Pesticide Poisonings
          Fourth  Edition

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          RECOGNITION AND
   MANAGEMENT OF PESTICIDE
              POISONINGS

               Fourth Edition
         Donald P. Morgan, M.D., Ph.D.*
                     1989
Support for this publication was provided by the Health Ef-
fects  Division,  Office of Pesticide Programs,  United States
Environmental  Protection Agency, Washington, D.C. 20460.


*lowa Pesticide Hazard Assessment Project, located at The University of
Iowa College of Medicine, Iowa City, Iowa 52242.

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             TABLE OF CONTENTS
Chapter
Number
         Introduction	     v
  1.     Organophosphate Insecticides	     1
  2.     N-Methyl Carbamate Insecticides	    12
  3.     Solid Organochlorine Insecticides	    17
  4.     Insecticides of Biological Origin	    25
  5.     Other Insecticides, Acaricides, and Repellents	    34
  6.     Arsenical Pesticides	    54
  7.     Chlorophenoxy Herbicides	    63
  8.     Nitrophenolic and Nitrocresolic Herbicides	    68
  9.     Pentachlorophenol	    73
 10.     Paraquat and Diquat	    76
 11.     Other Herbicides	   93
 12.     Fungicides	   89
 13.     Rodenticides	  115
 14.     Fumigants	  131
 15.     Miscellaneous Pesticides, Solvents, and Adjuvants	  146
 16.     Index to Pesticide Poisonings by Symptoms and Signs....  159
         Index of Chemical and Product Names	  169
                             111

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                       Introduction
   This fourth edition of Recognition and Management of Pesticide Poi-
 sonings is an  update and expansion of  the 1982 third  edition.  The
 series,  from 1973, has been sponsored by the Office of Pesticide  Pro-
 grams of the United States Environmental Protection Agency.
   There have been  good  reasons for updated editions. New pesticide
 products are introduced  regularly whose hazard potentials  are not
 generally known to health professionals. The accumulated "use experi-
 ence" of formulators, applicators, and field workers provides an ex-
 panding basis for judging safety or identifying hazards of old and  new
 pesticides. Major episodes of adverse health effects reported in medical
 and scientific periodicals need to be taken into account. This literature
 also contributes importantly to improved understanding of toxic mech-
 anisms. Finally, clinical  toxicology is a dynamic  field  of medicine
 wherein new treatment methods are developed regularly and the effec-
 tiveness of old as well as new modalities undergoes constant critical
 review. The purpose of the fourth edition is to provide health profes-
 sionals with recently available information on the health hazards of
 pesticides currently  in use, and  current  consensus recommendations
 for management of poisonings and injuries caused by them.
  All persons familiar with the clinical toxicology of pesticides agree
 that prevention of poisoning remains a much surer path to safety  and
 health  than reliance on treatment. In addition to the inherent toxic
 hazards of pesticides, none of the procedures or drugs used in treating
 poisonings are risk-free. In fact, many antidotes are plainly "toxic" in
 their own right, and such apparently simple procedures as gastric
 intubation incur substantial risk. The clinical toxicologist must often
 weigh the hazards of various courses of action—sometimes including no
 treatment  at all—against the risks of various interventions, such as
 emptying the stomach, catharsis, giving intravenous fluids, br adminis-
 tering an antidote (when there is one). Management decisions have to
 be made promptly and, as often as  not, on the  basis of limited and
 scientifically insecure information.  The  complex  circumstances  of
 human poisonings rarely allow precise comparisons of alternative man-
 agements. In no sense, then, are the treatment  recommendations in
 this book infallible guides to successful outcomes. They  are no more
 than consensus judgments of the best available management options.
  The book deals almost entirely with short-term (acute) harmful ef-
 fects of pesticides. Although obviously important, the subject of chronic
 effects is too complex to deal with exhaustively in a manual designed
 as guidance  for emergency  management.  Nonetheless,  appropriate
treatment of serious  exposures  to pesticides represents one important
step in avoiding chronic as well as acute disease.
  The amount of pesticide  absorbed is a critical factor in making
treatment decisions,  and estimation of dosage in  many circumstances

                                v

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of pesticide exposure remains difficult. The terms "small amount" and
"large amount" used in this book are obviously ambiguous, but the
quality of exposure information obtainable rarely justifies more specif-
ic terminology. The circumstances of exposure are sometimes a rough
guide. Exposure to spray drift properly diluted for field application is
not likely to convey a large dose unless exposure has been prolonged.
Spills of concentrated technical material onto the skin or clothing may
well represent a large  dose of pesticide unless the contamination is
promptly removed. Brief dermal exposure to foliage residues of cholin-
esterase-inhibiting pesticides is not likely to lead to  poisoning, but
prolonged exposures may well do  so. Except in children, accidental
pesticide ingestions are likely to be spat out or vomited, but suicidal
ingestions almost always involve "large amounts," requiring the  most
aggressive management. Ingestions  of pesticides by children are the
most difficult to evaluate. The therapist usually must base his manage-
ment on "worst case" assumptions of dosage. Childhood poisonings are
still further complicated by the greater vulnerability of the very young
(small body size), not only to pesticides themselves, but to the  drugs
and treatment procedures that must be used to limit the severity of
poisoning.
  The need to protect the airway from aspiration of vomitus cannot be
over-emphasized. Death has occasionally resulted from this  complica-
tion, even following ingestions of substances having relatively low toxic
potential.  In  poisonings by agents which  depress  central nervous
system function or cause  convulsions, early placement of a cuffed
endotracheal tube (even when  this  requires  light general anesthesia)
may be life-saving. Induced emesis is usually safe in alert patients, but
great care must be taken in poisonings by neurotoxic agents that the
airway is still protected when vomiting occurs. Maintenance of ade-
quate pulmonary gas exchange is another essential element of poison-
ing management that deserves constant reemphasis.
  Gastric intubation, with  aspiration and lavage, remains a useful
method for removing poisons from the stomach shortly after they have
been swallowed, but the time  after ingestion during which lavage is
likely to be beneficial is shorter than many clinical toxicologists have
thought. Rarely are significant amounts of swallowed toxicants recov-
ered more than a few hours after ingestion, and, in many instances,
the  bulk of swallowed material passes into the duodenum and beyond
in 15-30 minutes.
  Full advantage  should be taken of new highly adsorbent  charcoals
that are effective in binding some pesticides in the gut.  Unfortunately,
charcoal does not  adsorb all pesticides, and its efficiency against many
of them is not known. Because administration of charcoal is rarely
followed by serious complications, its use is generally recommended if
there is some likelihood that  it will act beneficially.  Sorbitol  is an
effective cathartic which somewhat reduces the distastefulness of char-
coal and does not impair its adsorbency. The only problems  attending

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use of sorbitol are those inherent in catharsis itself: dehydration and
electrolyte disturbances, particularly in children.
  In poisonings caused by large intakes of pesticide, hemodialysis and
hemoperfusion over adsorbents continue to be tested  as  methods for
reducing body burdens. Against some toxicants, these procedures are
valuable. Overall effectiveness appears to depend not only on efficiency
of clearance from the blood, but also on the mobility of toxicant al-
ready distributed to tissue cells before the extracorporeal blood-purifi-
cation procedure is started. The critical determinant of success in using
these systems may well be the speed with which they  can be put into
operation before tissue-damaging stores of toxicant have accumulated.
  There remains a need for systematic reporting of pesticide poisonings
to a central agency so that accurate statistics describing the frequency
and circumstances of poisoning can be compiled, and  efforts to  limit
these occurrences can be properly directed. It is realized that in recent
years there  has been  a tragic increase in the use of pesticides as
instruments of suicide and even homicide, particularly in  the develop-
ing countries. Producers are now devoting considerable effort to modifi-
cations  in  formulation and packaging  that  will deter these misuses.
This work is important because suicidal ingestions are by far the  most
difficult pesticide poisonings to treat successfully.
  Among persons who encounter pesticides in the course of their occu-
pational activities, dermal injuries, rather than systemic poisonings are
the most common adverse effects.
  An effort has been made to format this book for quick reference by
thorough indexing and minimal references to other pages  or chapters.
However,  some procedures are commonly used in treating poisonings
by many different agents and it is not practical to repeat these proto-
cols in  every chapter. Methods for  limiting toxicant absorption  from
the gastrointestinal tract are described in Chapter 1,  TREATMENT,
Section  6  (page 8). Control of  convulsions is discussed in Chapter 3,
TREATMENT, Section  4 (page 21). Management of pulmonary edema
is considered in Chapter 14, TREATMENT, Section 4 (page 139). These
sections have been referenced in several other chapters.
  The contents of this book have  been  derived from  many sources:
published texts, current medical, toxicologic, and pesticide product lit-
erature, valuable instructional materials from the Iowa Poison Control
Center,  and direct communications with experts having knowledge of
clinical  toxicology in general and pesticide toxicology in particular. A
list of the major text sources follows this introduction.
                                vu

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  Critical reviews of draft material by experts in clinical toxicology
have provided the real strength of this publication. Reviewers include:

John E. Davies, M.D., M.P.H., F.R.C.P.,
Professor Emeritus
[Department of Epidemiology and
  Public Health
University of Miami School of Medicine
Miami, Florida                           William F. Durham, Ph.D.
                                      Senior Research Advisor
                                      Health Effects Research Laboratory
                                      United States Environmental Protection
                                      Agency
                                      Research Triangle Park, North Carolina
Wayne Snodgrass, M.D., Ph.D.
Head, Clinical Pharmacology-Toxicology Unit
Medical Director, Texas Poison Center
University of Texas Medical Branch
Galveston, Texas                        William G. Troutman, Pharm.D.
                                      Professor of Pharmacy and Director,
                                      New Mexico Poison and Drug Information
                                      Center
                                      The University of New Mexico
                                      Albuquerque, New Mexico
Sheldon L Wagner, M.D.
Professor of Clinical Toxicology
Department of Agricultural Chemistry
Oregon State University
Corvallis, Oregon
   In addition to the expert reviewers, many individuals have contribut-
ed their time and skill to this fourth  edition.  Jerome M. Blondell,
biostatistician for the Health Effects Division,  Office  of Pesticide Pro-
grams,  United States Environmental  Protection Agency, has super-
vised the review  process, accomplished the indexing, and overseen the
process of publication. The principal author is indebted to Mrs. Carol
Hradek for skillful editorial assistance, to Ms. Joan McLaughlin,  and
to others of the  secretarial staff of the Division of Occupational  and
Environmental Health,  Department of Preventive Medicine and Envi-
ronmental Health, The University of Iowa  College  of Medicine, for
typing the manuscript.
                                    vui

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        Texts and Handbooks on Pesticides,
   Pesticide Toxicology and Clinical Toxicology

Clinical Toxicology of Commercial Products
    Fifth Edition
    Robert E. Gosselin, Roger P. Smith and Harold C. Hodge,
      with assistance of Jeannette E. Braddock
    Williams and Wilkins, Baltimore, MD
Pesticides Studied in Man

    Wayland J. Hayes, Jr.
    Williams and Wilkins, Baltimore, MD

Toxicology of Pesticides

    Wayland J. Hayes, Jr.
    Williams and Wilkins, Baltimore, MD

Handbook of Poisoning

    Twelfth Edition
    Robert H. Dreisbach and William O. Robertson
    Appleton and Lange, East Norwalk, CT
1984
1982
1975
1987
Medical Toxicology: Diagnosis and Treatment of Human Poisoning
    Matthew J. Ellenhorn and Donald G. Barceloux
    Elsevier, New York, NY

Clinical Toxicology of Agricultural Chemicals

    Sheldon L. Wagner, M.D.
    Oregon State University Press
    Corvallis, Oregon

Farm Chemicals Handbook

    Charlotte Sine, Editorial Director
    Meister Publishing Company
    Willoughby, Ohio

Poisondex

    Barry H. Rumack, Editor
    Microdex, Incorporated, Denver, Colorado
1988
1981
1989
                              IX

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Biological Monitoring Methods for Industrial Chemicals

    Randall C. Baselt
    Biomedical Publications, Davis, CA                        1980

The Pharmacological Basis of Therapeutics

    Seventh Edition
    Louis S. Goodman and Alfred Oilman
    Macmillan Publishing Company, Inc., New York, NY        1985

Patty's Industrial Hygiene and Toxicology

    Third Revised Edition
    George D. Clayton and Florence E. Clayton
    Wiley Interscience, New York, NY                         1982

Casarett  and DoulPs Toxicology

    Third Edition
    John Doull, Curtis D. Klaassen and Mary O. Amdur
    Macmillan Publishing Company, New York, NY             1986

Poisoning:  A Guide to  Clinical Diagnosis and Treatment

    W. F. Von Oettingen
    W. B. Saunders Company, Philadelphia, PA                 1958

The Merck Index

    Tenth Edition
    Martha Windholz and Susan Budavari, Editors
    Merck and Company, Inc., Rahway, NJ                     1983

Agricultural Chemicals Books  I, II, III, IV

    W.T. Thomson
    Thomson Publications, Fresno, CA                    1977-1979

Herbicide Handbook of the

    Weed Science Society of America
    Fifth Edition                                            1983

Chemicals Identified in Human Biological Media, a Data Base

    Compiled by M. Virginia Cone, Margaret F. Baldauf,
    Fay M. Martin, and John T. Ensminger
    Oak Ridge  National Laboratory                            1980
                               x

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                        CHAPTER 1

 ORGANOPHOSPHATE  INSECTICIDES
GENERAL CHEMICAL STRUCTURE

             RO x    ^ S   (or 0)
                    p
             RO '    ^ O
                               [Leaving Group|


  R is usually either ethyl or methyl. Phosphonates contain an alkyl
(R-) in place of one alkoxy group (RO-).

COMMERCIAL PRODUCTS

  Highly toxic*:  tetraethyl pyrophosphate (TEPP), dimefox (Hanane,
Pestox XIV), phorate (Thimet, Rampart, AASTAR), disulfoton+ (Disys-
ton),  fensulfothion (Dasanit), demeton+  (Systox), terbufos  (Counter,
Contraven), mevinphos (Phosdrin, Duraphos), ethyl parathion (E605,
Parathion, Thiophos), azinphos-methyl (Guthion, Gusathion), fosthietan
(Nem-A-Tak), chlormephos (Dotan), sulfotep (Thiotepp, Bladafum, Dith-
ione), carbophenothion (Trithion), chlorthiophos  (Celathion),  fonofos
(Dyfonate, N-2790), prothoate+ (Fac), fenamiphos (Nemacur),  phosfo-
lan+ (Cyolane, Cylan), methyl parathion (E 601, Penncap-M), schradan
(OMPA), mephosfolan+  (Cytrolane),  chlorfenvinphos (Apachlor,  Bir-
lane), coumaphos (Co-Ral, Asuntol), phosphamidon (Dimecron), metha-
midophos  (Monitor),  dicrotophos (Bidrin), monocrotophos (Azodrin),
methidathion (Supracide, Ultracide), EPN, isofenphos (Amaze, Oftanol),
endothion, bomyl (Swat), famphur (Famfos,  Bo-Ana,  Bash), fenophos-
phon (trichloronate, Agritox), dialifor (Torak), cyanofenphos (Surecide),
dioxathion (Delnav), mipafox (Isopestox, Pestox XV).   .
  Moderately toxic*:  bromophos-ethyl (Nexagan),  leptophos (Phosvel),
dichlorvos  (DDVP,  Vapona), ethoprop  (Mocap), demeton-S-methyl+
(Duratox, Metasystox (i)), triazophos (Hostathion), oxydemeton-methyl"*"
(Metasystox-R), quinalphos (Bayrusil), ethion (Ethanox),  chlorpyrifos
(Dursban, Lorsban, Brodan), edifenphos, oxydeprofos"1" (Metasystox-S),
sulprofos (Bolstar, Helothion), isoxathion (E-48,  Karphos), propetam-
 * Compounds are listed approximately in order of descending toxicity. "Highly toxic"
  organophosphates have listed oral LDSO values (rat) less than 50 mg/kg; "moderately
  toxic" agents have LD5o values in excess of 50 mg/kg.
 * These organophosphates are systemic; they are taken up by the plant and translocated
  into foliage and sometimes into the fruit.

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phos (Safrotin), phosalone (Zolone), thiometon (Ekatin), heptenophos
(Hostaquick), crotoxyphos (Ciodrin, Cypona), phosmet (Imidan, Prolate),
trichlorfon  (Dylox,  Dipterex, Proxol, Neguvon),  cythioate  (Proban,
Qyflee), phencapton (G 28029), pirimiphos-ethyl (Primicid), DBF (De-
Green, E-Z-Off D), methyl trithion, dimethoate (Cygon, DeFend), fenth-
ion (mercaptophos, Entex, Baytex, Tiguvon), dichlofenthion (VC-13 Ne-
macide), bensulide (Betasan, Prefar), EPBP (S-Seven), diazinon (Spec-
tracide),  profenofos  (Curacron),  formothion  (Anthio),   pyrazophos
(Afugan,  Curamil),  naled  (Dibrom), phenthoate  (dimephenthoate,
Phenthoate), IBP  (Kitazin),  cyanophos (Cyanox), crufomate (Ruelene),
fenitrothion  (Accothion, Agrothion, Sumithion),   pyridaphenthion
(Ofunack), acephate (Orthene), malathion (Cythion), ronnel (fenchlor-
phos, Korlan),  etrimfos (Ekamet), phoxim (Baythion), merphos (Folex,
Easy off-D), pirimiphos-methyl (Actellic),  iodofenphos  (Nuvanol-N),
chlorphoxim (Baythion-C), propyl thiopyrophosphate (Aspon), bromo-
phos (Nexion),  tetrachlorvinphos (Gardona, Appex, Stirofos), temephos
(Abate, Abathion).

TOXICOLOGY

  Organophosphates poison  insects  and mammals primarily  by phos-
phorylation of  the acetylcholinesterase enzyme (AChE)  at nerve end-
ings. The enzyme is critical  to normal control of nerve impulse trans-
mission from nerve fibers to muscle  and gland cells, and also to other
nerve cells in autonomic ganglia and in the brain. Some critical pro-
portion of the tissue enzyme mass must be inactivated by phosphoryla-
tion before symptoms and signs of poisoning become manifest. At suffi-
cient dosage, loss of enzyme  function allows accumulation of acetylcho-
line (ACh, the  impulse-transmitting  substance) at cholinergic neuroef-
fector junctions (muscarinic  effects), at skeletal nerve-muscle junctions
and autonomic  ganglia (nicotinic effects), and in the brain. At choliner-
gic nerve junctions  with smooth muscle  and gland cells, high  ACh
concentration causes muscle contraction and secretion, respectively. At
skeletal muscle junctions, excess ACh may be excitatory (cause muscle
twitching), but may also weaken or paralyze the cell by depolarizing
the end-plate. In the brain, high ACh concentrations cause sensory and
behavioral disturbances, incoordination and depressed motor function.
Depression of respiration and pulmonary edema are the usual causes
of death from organophosphate poisoning. Recovery depends ultimately
on generation of new enzyme in all critical tissues.
  Organophosphates are efficiently  absorbed by inhalation, ingestion,
and skin penetration. To a degree, the occurrence of poisoning depends
on the  rate at which  the  pesticide is absorbed. Breakdown occurs
chiefly by hydrolysis in the liver; rates of hydrolysis vary widely from
one  compound  to another.  In the  case of certain Organophosphates
whose breakdown is relatively slow, significant temporary storage in
body fat may occur.

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  Many  organophosphates readily  undergo conversion from -thions
(P=S) to -oxons (P=O). Conversion occurs in the environment under
the influence  of oxygen and light, and, in the body, chiefly by the
action of liver microsomes. -Oxons are much more toxic than -thions,
but -oxons break down more readily than -thions.  Ultimately, both
-thions and -oxons are hydrolyzed at the ester linkage, yielding alkyl
phosphates and leaving groups. These are of relatively low toxicity.
They are either excreted or further transformed in the body before
excretion.
  Within one to two days of initial organophosphate binding to acetyl-
cholinesterase,  some phosphorylated acetylcholinesterase enzyme can
be de-phosphorylated (reactivated) by the oxime antidote pralidoxime.
As time  progresses, the enzyme-phosphoryl bond is strengthened by
loss of one alkyl group from the phosphoryl adduct. Pralidoxime reacti-
vation is thereafter no longer possible ("aging").
  Barely, certain organophosphates have caused a  different  kind  of
neurotoxicity consisting  of damage to  the axons of peripheral and
central nerves and  associated with inhibition of "neurotoxic esterase"
(NTE). Manifestations have been chiefly weakness  or paralysis and
paresthesia of the extremities,  predominantly the legs, persistent for
weeks to years. Most of these rare occurrences have followed (8-21
days) an acute poisoning episode of the anticholinesterase type, but
some have not been preceded by acute poisoning. Only a  few of the
many  organophosphates used as pesticides have been implicated  as
causes of delayed neuropathy in humans. EPA guidelines require that
organophosphate and carbamate compounds which are candidate pesti-
cides be tested in susceptible animal species for this neurotoxic property.
  Other specific properties of individual organophosphates may render
them more hazardous than basic toxicity data suggest. By-products can
develop in long-stored malathion which strongly inhibit the hepatic
enzymes operative in malathion degradation, thus enhancing its toxici-
ty. Certain organophosphates are exceptionally prone to storage in fat
tissue, prolonging the need for  antidote as stored pesticide  is released
back into the circulation.  Animal studies have demonstrated potentia-
tion  of effect when two or more organophosphates are absorbed simul-
taneously: enzymes critical to the degradation of one are inhibited by
the other. Whether this interaction is a significant factor in human
poisonings is not known.


SYMPTOMS AND  SIGNS OF POISONING

  Symptoms of acute  organophosphate poisoning develop during expo-
sure, or within 12 hours (nearly always within 4 hours) of contact. The
most commonly reported early symptoms are HEADACHE, NAUSEA,
and  DIZZINESS. Anxiety  and  restlessness are prominent.  Worsening
of the poisoned state is manifest as MUSCLE  TWITCHING,  WEAK-

                                3

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NESS, tremor, incoordination, vomiting, abdominal cramps, and diar-
rhea. HYPERSECRETION is often  prominent:  sweating, salivation,
tearing, rhinorrhea, and bronchorrhea. Blurred and/or dark vision
may be reported, and MIOSIS is often a helpful diagnostic sign. Tight-
ness in the chest, wheezing, and productive cough may progress to
frank  PULMONARY EDEMA.  Bradycardia may  progress  to  sinus
arrest, or may be superseded by tachycardia and hypertension from
nicotinic (sympathetic ganglia) stimulation. Toxic psychosis,  manifest
as confusion or bizarre behavior, has been misdiagnosed as acute alco-
holism. Toxic myocardiopathy has been a prominent feature of some
severe organophosphate  poisonings.  Unconsciousness,  incontinence,
convulsions, and depression of respiratory drive signify a life-threaten-
ing severity of poisoning.
  Repeated absorption of organophosphate at significant dosage, but in
amounts not sufficient to cause acute poisoning, may cause persistent
anorexia, weakness, and malaise.
  Some recently reported cases of organophosphate poisoning, mostly
from suicidal ingestion of large quantities, have been characterized by
prolonged (1-3 weeks) paralysis  of muscles of the head,  neck, limbs,
and thorax, commencing one to four days following apparent resolution
of acute cholinergic manifestations. Continuous mechanical support of
pulmonary ventilation was necessary to sustain life  in  these  cases.

CONFIRMATION  OF ORGANOPHOSPHATE ABSORPTION

     CAUTION:  If there are strong clinical indications  of acute or-
                ganophosphate poisoning, treat patient immediately.
                DO NOT WAIT for laboratory confirmation.

  Depressions of plasma pseudocholinesterase and/or  RBC acetylcho-
linesterase enzyme activities are generally available biochemical indi-
cators of excessive  organophosphate absorption. A minimum amount of
organophosphate must be absorbed to depress blood cholinesterase ac-
tivities, but enzyme activities are lowered by dosages considerably less
than are required to cause symptomatic poisoning. The enzyme depres-
sion is usually apparent within a few minutes or hours of significant
absorption of organophosphate. Depression of the plasma  enzyme gen-
erally persists several days to a few weeks;  the RBC enzyme activity
may not reach its minimum  for several days, and usually remains
depressed longer, sometimes  1-3 months, until new enzyme replaces
that inactivated by  organophosphate. Table 1 lists APPROXIMATE
LOWER LIMITS OF NORMAL FOR PLASMA AND  RBC CHOLIN-
ESTERASE ACTIVITIES of human blood, measured by several  meth-
ods. LOWER LEVELS usually indicate excessive absorption  of a cho-
Imesterase-inhibiting chemical. Whenever possible, comparison of the
test sample value  with a pre-exposure value offers the best confirma-
tion of organophosphate absorption.  A cholinesterase depression of
25% or more is generally regarded as evidence of excessive absorption.

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  TABLE 1. Approximate Lower Limits of Normal Plasma and Red Cell
                 Cholinesterase Activities in Humans*
METHOD
pH (Michel)
pHStat(Nabb-
Whitfield)
BMC Reagent Set
(Ellman-
Boehringer)
Dupont ACA
Garry-Routh (Micro)

Technicon
PLASMA
0.45
2.3
1875

<8

2.0
RBC
0.55
. 8.0




8.0
WHOLE
BLOOD

3000

Male 7.8
Female 5.8

UNITS
ApH per ml per hr
p,M per ml per min
mU per ml per
min

Units per ml
fiM-SH. per 3 ml
per min
fiM. per ml per min
  * Because measurement technique varies among laboratories, more accurate estimates
 of minimum normal values are usually provided by individual laboratories.

  In certain conditions, the  activities of plasma and RBC choliriester-
 ase are depressed in the absence of chemical inhibition. About 3% of
 individuals  have a genetically  determined low level of plasma pseudo-
 cholinesterase. These persons are particularly vulnerable to the action
 of the muscle-paralyzing drug succinylcholine, often administered to
 surgical patients. They may be unusually sensitive to organophosphate
 toxicity, although this has not been proven. Patients with advanced
 liver  disease, malnutrition,  chronic alcoholism, and dermatomyositis
 exhibit low plasma Cholinesterase activities. A number of toxicants,
 notably carbon disulfide, benzalkonium salts,  organic  mercury com-
 pounds, ciguatoxins, and solanines may reduce plasma pseudocholines-
 terase activity. Early pregnancy and birth control pills may also cause
 some depression. The RBC acetylcholinesterase is less likely than  the
 plasma enzyme to be affected by factors other than organophosphates.
 It is reduced, however, in certain rare conditions that damage the  red
 cell membrane, such as the hemolytic anemias.
  The alkyl phosphates and phenols to which organophosphates  are
 hydrolyzed  in  the body can often be detected in the urine during
 pesticide absorption and up to  about 48 hours thereafter. These analy-
 ses are sometimes useful in  identifying the  actual pesticide to which
 workers have been exposed. Urinary alkyl phosphate and phenol anal-
 yses can  demonstrate organophosphate absorption at lower dosages
 than those required to depress Cholinesterase  activities and at much
 lower dosages  than those  required  to produce symptoms  and signs.
  Detection  of intact  organophosphates in  the blood is usually  not
possible except during or soon after absorption of substantial amounts.
In general, organophosphates do not remain unhydrolyzed in the blood
more  than a few  minutes or hours,  unless  the quantity absorbed is
large or the  hydrolyzing liver enzymes are inhibited.

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TREATMENT OF ORGANOPHOSPHATE POISONING

     CAUTION:  Persons attending the victim should avoid direct con-
                 tact with heavily contaminated clothing and vomi-
                 tus. Wear  rubber gloves while  washing  pesticide
                 from skin and hair.
 1.  Insure that a CLEAR AIRWAY exists by aspiration of secretions,
     if necessary. Administer OXYGEN by mechanically assisted pul-
     monary ventilation if respiration is depressed. Improve tissue oxy-
     genation as much as possible before administering atropine, so as
     to minimize the risk of ventricular fibrillation.
     In SEVERE  poisonings, it may be necessary to  support pulmo-
     nary ventilation mechanically for several days.
 2.  Administer ATROPINE SULFATE intravenously, or intramuscu-
     larly if intravenous  injection is not possible.
     The objective of atropine  antidotal therapy is to antagonize the
     effects of excessive  concentrations of acetylcholine at end-organs
     having muscarinic receptors. Depending on the severity of poison-
     ing, doses of atropine ranging from small to very large may be
     required. Atropine does not reactivate the cholinesterase enzyme
     or accelerate disposition  of organophosphate.  Recrudescence of
     poisoning  may occur if tissue concentrations of organophosphate
     remain high when  the effect  of atropine wears  off. Atropine is
     effective against muscarinic manifestations, but  it is ineffective
     against nicotinic actions, specifically muscle weakness and twitch-
     ing,  and respiratory depression. Despite  these limitations, atro-
     pine is often a lifesaving agent in  organophosphate poisonings.
     Favorable response  to a test dose of atropine (1 mg in adults, 0.01
     mg/kg in children under  12 years)  can help differentiate poison-
     ing by anticholinesterase agents from other conditions.
     In MODERATELY SEVERE poisoning (hypersecretion and other
     end-organ manifestations  without central nervous system depres-
     sion) the following dosage  schedules have proven effective:

     Dosage of ATROPINE:
         Adults and children over 12 years: 0.4-2.0 mg repeated every
         15 minutes until atropinization is achieved:  flushing, dry
         mouth, dilated pupils, and tachycardia (pulse of 140 per
         minute). Maintain  atropinization by repeated doses for 2-12
         hours or longer depending on severity of poisoning. Rales in
         the lung bases nearly always indicate inadequate atropiniza-
         tion. Miosis, nausea, bradycardia, and other cholinergic mani-
         festations also signal the need for more atropine.
         Children under 12 years: 0.05 mg/kg body weight, repeated
         every  15 minutes until atropinization is achieved. Maintain
         atropinization with repeated dosage of 0.02-0.05 mg/kg body
         weight.

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    SEVEKELY POISONED individuals may exhibit remarkable tol-
    erance to atropine; two or more times the dosages suggested above
    may be  needed. The dose of atropine may be increased and the
    dosing interval decreased as needed to control symptoms. Continu-
    ous intravenous infusion of atropine may be necessary when atro-
    pine requirements are massive.  REVERSAL OF MUSCARINIC
    SYMPTOMS  AND  SIGNS,  not  an arbitrary dose limit, is  the
    desired end-point. Preservative-free atropine products should be
    used whenever possible.
    Note: Persons not poisoned  or only slightly poisoned by organo-
    phosphates may develop signs of atropine toxicity from such large
    doses: FEVER, muscle fibrillations, and delirium are the main
    signs of atropine toxicity. If these appear while the patient is fully
    atropinized, atropine administration should be  discontinued, at
    least temporarily, while the severity of poisoning is reevaluated.
3.   Draw a BLOOD SAMPLE (heparinized) for cholinesterase analy-
    sis before  administration of pralidoxime, which  tends to reverse
    the cholinesterase depression.
4.   Administer PRALIDOXIME (Protopam, 2-PAM), a cholinesterase
    reactivator, in cases of severe poisoning by organophosphate pesti-
    cides  in  which respiratory depression,  muscle weakness, and
    twitching are severe. When administered early (usually less than
    48 hours after  poisoning) pralidoxime relieves  the  nicotinic as
    well as the muscarinic effects of poisoning.
    Note: Pralidoxime is of limited value, and  may be hazardous, in
    poisonings by the  cholinesterase-inhibiting carbamate compounds
    (see Chapter 2).

    Dosage of PRALIDOXIME:
        Adults and children over 12 years: 1.0-2.0 gm intravenously
        at no more than 0.2 gm per minute.
        Children  under 12 years: 20-50 mg/kg body weight (depend-
        ing on severity of poisoning) intravenously, injecting no more
        than half the total dose per minute.
    Dosage of pralidoxime may be repeated in  1-2 hours, then at
    10-12 hour intervals if needed. In very severe poisonings, dosage
    rates may be  doubled. Repeated doses of pralidoxime are usually
    required. In cases that involve continuing  absorption of organo-
    phosphate (as after ingestion of a large amount), or continuing
    transfer of highly lipophilic organophosphate from fat into blood,
    it may be necessary to continue administration of pralidoxime for
    several days beyond the 48  hour post-exposure  interval usually
    cited as the limit of its effectiveness.
    Slow administration of pralidoxime is strongly recommended and
    may be  achieved  by administering the total dose in 250 ml  5%
    glucose solution over 30 minutes, or longer.  Blood pressure should
    be monitored  during administration because of the occasional oc-

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    currence of hypertensive crisis. Administration should be slowed
    or stopped if blood pressure rises to hazardous levels. Be prepared
    to assist pulmonary ventilation mechanically if respiration  is de-
    pressed during or after pralidoxime administration.
    If intravenous injection is not possible, pralidoxime may be  given
    by deep intramuscular injection.
5.  In patients who have been poisoned by organophosphate contami-
    nation of skin, clothing, hair, and/or eyes, DECONTAMINATION
    MUST PROCEED CONCURRENTLY with whatever resuscitative
    and antidotal measures are necessary to preserve life. Contamina-
    tion of the eyes  should be  removed  by flushing with  copious
    amounts of clean water. If no symptoms are evident in a patient
    who remains alert  and  physically able, a  prompt shower and
    shampoo  may be  appropriate, provided  the patient is carefully
    observed  to insure  against sudden appearance  of  poisoning. If
    there are any indications of weakness, ataxia, or other neurologic
    impairment,  clothing should  be removed and a complete BATH
    AND SHAMPOO given while the victim is recumbent, using copi-
    ous amounts of soap and water. Attendants should wear rubber
    gloves. Surgical green soap is excellent for this purpose, but ordi-
    nary soap is about as good. The possibility of pesticide sequestered
    under fingernails or in skin folds should not be overlooked. CON-
    TAMINATED CLOTHING should be promptly bagged and not
    returned until it has been thoroughly laundered. Contaminated
    leather shoes  should be discarded.  The possibility that pesticide
    has contaminated  the inside  surfaces of gloves, boots, and  head-
    gear should be kept in mind.
6.  IF ORGANOPHOSPHATE HAS BEEN  INGESTED in quantity
    probably sufficient to cause poisoning, the stomach and intestine
    must be emptied.
    Because central nervous system depression may develop rapidly,
    gastric LAVAGE through a large bore orogastric tube, with rigor-
    ous protection of the airway, is probably preferable to emesis in
    nearly all cases of poisoning by ingested organophosphate. Effec-
    tiveness of lavage diminishes rapidly with the passage of  tune.
    A. Empty the  stomach  by INTUBATION, ASPIRATION, and
       LAVAGE, using a slurry of activated charcoal in isotonic
       saline  (see below). Rigorous precautions must  be taken to
       PROTECT THE AIRWAY from aspiration  of  regurgitated
      gastric contents:
        (a)  If victim is unconscious or obtunded,  insert a cuffed
            ENDOTRACHEAL  TUBE prior to gastric intubation.
        (b)  KEEP VICTIM'S HEAD BELOW LEVEL OF  STOM-
            ACH during gastric intubation and lavage (Trendelen-
            burg, or left lateral  decubitus, with head of table tipped
            downward). Keep victim's head turned to the left.

                              8

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         (c)  ASPIRATE  PHARYNX  as regularly as possible  to
             remove gagged or vomited stomach contents.
    B.  After aspiration of stomach contents and lavage, instill ACTI-
        VATED CHARCOAL  ("preferably >3000"  m2 surface  area
        per gm) together with  a CATHARTIC in the charcoal slurry.
        Even though adsorption  of organophosphates on charcoal is
        not very efficient, charcoal instillation may be of some value.
        Dosage of CHARCOAL as an aqueous slurry:
             Adults and  children  over  12 years: 50-100 gm  in
             300-800 ml water.
            Children under 12 years: 15-30 gm in 100-300 ml water.
        Dosage of SORBITOL (the preferred agent) added to charcoal
        slurry:
            Adults and children over 12 years: 1.0-2.0 gm/kg body
            weight to a maximum of 150 gm per dose.
             Children under 12  years: 1.0-1.5 gm/kg body weight to
             a maximum of 50 gm per dose.
        Alternative cathartics that may be used instead are sodium or
        magnesium sulfate or citrate:
        Dosage of SODIUM or MAGNESIUM SULFATE:
             Adults and children over 12 years: 20-30 gm.
             Children under 12 years: 250 mg/kg body weight.
        Dosage of MAGNESIUM CITRATE solution:
             Adults and children: 4 ml/kg body weight of proprie-
             tary solution, up to a maximum of 300 ml.
        CAUTION: Do not instill fluid so rapidly that overloading of
        the stomach leads to vomiting or regurgitation. Serious elec-
        trolyte disturbances may  follow catharsis, especially in young
        children. Monitor serum electrolytes regularly, including mag-
        nesium levels, if magnesium salts have been used.
    C.   If gastric aspiration and lavage is not performed due to delay
        in treatment, and if patient is fully alert, ADMINISTER doses
        of CHARCOAL AND CATHARTIC ORALLY, as indicated  in
        6.B. When sorbitol is given orally, it should be diluted with an
        equal volume of water to yield a 35% solution.
    D.   SAVE a sample of emesis or initial gastric washings for chem-
       ical analysis.
    E.  In  some cases of organophosphate ingestion there may be
       benefit from REPEATED ADMINISTRATION OP ACTIVAT-
       ED CHARCOAL, either by ingestion  or stomach tube,  at
       doses approximating those recommended in 6.B. above. While
       charcoal incurs little risk, repeated catharsis may cause seri-
       ous dehydration  and electrolyte depletion, especially in chil-
       dren. Cathartic should  not be  administered after a charcoal
       stool appears.
7.  'OBSERVE PATIENT CLOSELY for at least 72  hours (longer  in
    cases of organophosphate  ingestion) to  insure  that  symptoms

                               9

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    (sweating, visual disturbances, vomiting, diarrhea, chest and ab-
    dominal distress, and sometimes PULMONARY EDEMA) do not
    recur as atropinization is withdrawn. In very severe poisonings by
    ingested organophosphates, particularly the more lipophilic and
    slowly hydrolyzed  compounds, metabolic disposition of toxicant
    may require  as  many as 5-14  days. In some cases,  this  slow
    elimination may combine with profound cholinesterase inhibition
    to require atropinization for several days or even weeks. Rising
    levels  of blood cholinesterase activity are a  useful signal  that
    atropine dosage can be tapered off by lengthening the intervals
    between doses. As dosage is  reduced, the lung bases  should be
    checked frequently for rales.  If rales  are heard, or if  there is  a
    return of miosis, bradycardia, sweating or other cholinergic signs,
    atropinization must be re-established promptly.
 8.  Particularly in poisonings by large ingested doses of organophos-
    phate, MONITOR PULMONARY VENTILATION carefully,  even
    after recovery from muscarinic symptomatology, to forestall respi-
    ratory failure. In  some cases, respiratory failure has developed
    several days following organophosphate ingestion, and has persist-
    ed for days to weeks.
 9.  In severely poisoned patients, MONITOR CARDIAC STATUS by
    continuous  EGG recording. Some organophosphates have signifi-
    cant cardiac toxicity.
10.  Furosemide may be considered for relief of pulmonary edema  if
    rales persist in the lungs even after full atropinization. It should
    not  be used  until the maximum benefit of  atropine has  been
    realized. Consult package insert  for dosage and  administration.
11.  The following drugs  are probably contraindicated in  nearly all
    organophosphate poisoning cases: morphine, theophylline, phen-
    othiazines, and reserpine. Adrenergic amines should be given only
    if there is a specific indication, such as marked hypotension.
12.  Rarely,  in  severe  organophosphate poisonings, CONVULSIONS
    occur despite therapy with atropine and pralidoxime. Insure that
    causes  unrelated to pesticide toxicity are not responsible:  head
    trauma, cerebral  anoxia, or mixed poisoning. Drugs useful in
    controlling convulsions are discussed in Chapter 3, TREATMENT,
    Section 4, p.  21. The benzodiazepines  diazepam or lorazepam are
    probably the agents of choice as initial therapy.
13.  Persons who have been clinically poisoned by organophosphate
    pesticides  should  not be  re-exposed  to cholinesterase-inhibiting
    chemicals until symptoms and signs have resolved completely and
    blood cholinesterase activities have returned to at least 80 percent
    of pre-poisoning levels. If blood cholinesterase was not measured
    prior to poisoning, blood enzyme activities should reach at least
     minimum normal levels (Table 1) before the patient is returned  to
     a pesticide-contaminated environment.

                                10

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14.  DO NOT ADMINISTER ATROPINE OR PRALIDOXIME PRO-
    PHYLACTICALLY to workers exposed to organophosphate pesti-
    cides. Prophylactic  dosage  with either atropine or pralidoxime
    may mask early signs and symptoms of organophosphate poison-
    ing and thus allow the worker to continue exposure and possible
    progression  to more severe poisoning. Atropine itself may  en-
    hance the health hazards of the agricultural work setting:  im-
    paired heat  loss  due to reduced sweating and impaired ability to
    operate  mechanical equipment due to blurred vision (mydriasis).
                              11

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                        CHAPTER 2

           N-METHYL  CARBAMATE
                    INSECTICIDES
GENERAL CHEMICAL STRUCTURE
  H3C
    H
        \
      /
0
           N   —   C  —   O
                          Leaving
                          Group
COMMERCIAL PRODUCTS

  Highly toxic*: aldicarb* (Temik),  oxamyl (Vydate L, DPX  1410),
methiocarb (Mesurol,  Draza), carbofuran (Furadan, Curaterr, Cris-
furan), isolan (Primin), methomyl (Lannate, Nudrin, Lanox), formetan-
ate (Carzol),  aminocarb  (Matacil), cloethocarb  (Lance),  bendiocarb
(Ficam, Dycarb, Multamat, Niomil, Tattoo, Turcam).
  Moderately toxic*:  dioxacarb (Elocron, Famid), promecarb (Carba-
mult), bufencarb (metalkamate, Bux), propoxur (aprocarb, Baygon), tri-
methacarb (Landrin, Broot), pirimicarb (Pirimor, Abol, Aficida, Aphox,
Fernos, Rapid), dimetan (Dimethan), carbaryl (Sevin, Dicarbam), isopro-
carb (Etrofolan, MIPC).

TOXICOLOGY

  The  N-methyl carbamate  esters cause reversible  carbamylation of
acetylcholinesterase enzyme,  allowing accumulation of acetylcholine,
the neuromediator substance, at parasympathetic neuroeffector junc-
tions (muscarinic effects),  at skeletal muscle myoneural junctions and
autonomic ganglia (nicotinic  effects), and in the brain  (CNS effects).
The carbamyl-acetylcholinesterase combination dissociates more read-
ily  than the phosphoryl-acetylcholinesterase complex produced by or-
ganophosphate compounds. This  lability has several important conse-
quences: 1) it tends to limit the  duration of N-methyl carbamate poi-
sonings, 2) it accounts for the greater span between symptom-produc-
ing and lethal doses than exists  in the case of most organophosphate
* Compounds are listed approximately in order of descending toxicity. "Highly toxic" N-
 methyl carbamates have listed oral LD6o values (rat) less than 50 mg/kg body weight;
 "moderately toxic" agents have LD50 values in excess of 50 mg/kg.
+ This pesticide is taken up by some plants into the foliage and sometimes into the fruit.
                              12

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 compounds, and 3) it frequently invalidates the measurement of blood
 cholinesterase activity as a diagnostic index of poisoning (see below). N-
 methyl carbamates are absorbed by inhalation and ingestion and some
 by skin penetration.  Dermal absorption of particular compounds (nota-
 bly  carbofuran) is very  slight. N-methyl carbamates  are  hydrolyzed
 enzymatically by the liver and the degradation products are excreted
 by the kidneys and the liver.
   At cholinergic nerve junctions with smooth muscle  and gland cells,
 high acetylcholine concentration causes muscle contraction and secre-
 tion, respectively. At skeletal muscle  junctions,  excess acetylcholine
 may be excitatory (cause muscle twitching), but may also  weaken or
 paralyze the cell by  depolarizing the end-plate. In the brain, elevated
 acetylcholine concentrations may cause sensory and behavioral disturb-
 ances, incoordination, and depressed motor function (rarely seizures),
 even though the N-methyl carbamates do not penetrate the central
 nervous system very efficiently.  Depression  of respiration combined
 with pulmonary edema is the usual  cause of death from poisoning by
 N-methyl carbamate  compounds.

 SYMPTOMS AND SIGNS OP POISONING

  MALAISE, MUSCLE WEAKNESS,  DIZZINESS, and  SWEATING
 are commonly reported early symptoms of poisoning. Headache, saliva-
 tion, nausea, vomiting, abdominal pain, and diarrhea are often promi-
 nent. Miosis, incoordination, and slurred speech are reported. Dyspnea,
 bronchospasm, and chest  tightness may eventuate in  PULMONARY
 EDEMA. Blurred  vision,  muscle twitching, and spasms  characterize
 some cases. Severe neurologic manifestations, including convulsions,
 are  less  common  than  in organophosphate  poisonings.  Bradycardia
 occurs infrequently. Poisonings by N-methyl carbamates tend to be of
 shorter duration than poisonings by organophosphates, but they are
 not easily differentiated from organophosphate poisoning in the acute
 phase in the absence  of an accurate exposure history.

 CONFIRMATION  OF N-METHYL CARBAMATE ABSORPTION

  Unless a substantial amount of N-methyl carbamate has been ab-
 sorbed and  a blood  sample is taken  within an hour or  two,  it is
 unlikely that blood cholinesterase activities will be found  depressed.
 Even under the above circumstances, .a rapid test for enzyme activity
 must be used to detect an effect, because enzyme reactivation occurs in
vitro as well as in  vivo.  See Table 1 of Chapter 1  for methods of
measurement of blood cholinesterase activities, if circumstances appear
to warrant performance of the test.
  Absorption of some N-methyl carbamates can be confirmed by analy-
sis of urine for unique metabolites: alpha-naphthol from carbaryl, iso-
propoxyphenol from propoxur, carbofuran phenol from carbofuran, al-

                               13

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dicarb sulfone and nitrile from aldicarb. Unfortunately, analyses for
these excretion end-products are complex and not generally available.

TREATMENT OF N-METHYL CARBAMATE INSECTICIDE
  POISONING

  CAUTION: Persons attending the victim should avoid direct contact
with heavily contaminated clothing and vomitus. Wear rubber gloves
while washing pesticide from skin and hair.
 1.  Insure that a CLEAR AIRWAY exists by aspiration of secretions,
     if necessary. Administer  OXYGEN by mechanically assisted pul-
     monary ventilation as needed.  Improve tissue  oxygenation  as
     much as possible before administering atropine, so as to minimize
     the risk of ventricular fibrillation. Support pulmonary ventilation
     mechanically as long as respiratory drive is depressed.
 2.  Administer ATROPINE SULFATE intravenously, or intramuscu-
     larly, if intravenous  injection is  not possible. The objective of
     atropine antidotal therapy is to antagonize the effects of excessive
     concentrations of acetylcholine at end-organs having muscarinic
     receptors. Depending on the  severity of poisoning, doses of atro-
     pine ranging from small to very large may be required. Atropine
     does not reactivate the cholinesterase enzyme or accelerate excre-
     tion or breakdown of pesticide.  Recrudescence of poisoning may
     occur if tissue concentrations of toxicant remain high when the
     effect of atropine wears off. Atropine is  effective against muscar-
     inic manifestations, but it is ineffective  against nicotinic actions,
     specifically muscle weakness and twitching, and respiratory  de-
     pression. Despite these limitations, atropine is often a  lifesaving
     agent in N-methyl carbamate poisonings. Favorable response to a
     test dose of atropine (1 mg in adults, 0.01 mg/kg in children under
     12 years) given intravenously can help  differentiate poisoning by
     anticholinesterase agents from other conditions.
     In MODERATELY SEVERE poisoning (hypersecretion  and other
     end-organ manifestations without central nervous system depres-
     sion) the following dosage schedules have proven effective:

     Dosage of ATROPINE:
          Adults and children over 12 years: 0.4-2.0 mg repeated every
          15 minutes  until atropinization  is  achieved:  tachycardia
          (pulse of 140 per minute), flushing,  dry  mouth, dilated pupils.
          Maintain atropinization by repeated doses for  2-12 hours or
          longer depending  on severity of'poisoning. Rales in the lung
          bases  nearly  always  indicate inadequate atropinization.
          Miosis, nausea, bradycardia, and other  cholinergic manifesta-
          tions also signal the need for more atropine.
          Children under 12 years: 0.05 mg/kg body  weight, repeated
          every 15 minutes until  atropinization  is achieved. Maintain

                                 14

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3.
4.
5.
     atropinization with repeated doses of 0.02-0.05 mg/kg body
     weight.
 SEVERELY POISONED individuals may exhibit remarkable tol-
 erance to atropine; two or more tunes the dosages suggested above
 may be needed.  Reversal of muscarinic manifestations, rather
 than a specific dosage, is the object of atropine therapy. However,
 prolonged intensive intravenous administration of atropine some-
 times required in organophosphate poisonings is rarely needed in
 treating carbamate poisoning. Note: Persons not poisoned or only
 slightly poisoned  by N-methyl carbamates may develop signs of
 atropine toxicity from such large doses. FEVER, muscle fibrilla-
 tions, and delirium are the main signs of atropine toxicity. If
 these signs appear while the patient is fully atropinized, atropine
 administration should be discontinued, at least temporarily, while
 the severity of poisoning is reevaluated.
 Save a URINE SAMPLE for metabolite analysis if there is need
 to  identify the agent responsible for the poisoning. Also,  urine
 metabolite measurement can be used to follow the progress of
 carbamate disposition.
 Pralidoxime is probably of little value in N-methyl carbamate
 poisonings. Its use is usually unnecessary because atropine  alone
 is effective, and in some cases of carbamate  poisoning,  pralidox-
 ime administration has been followed by severe reactions, even
 sudden death. Both animal studies and experience in human poi-
 sonings CONTRAINDICATE  USE OF PRALIDOXIME  IN  CAR-
 BARYL POISONINGS.  In  mixed poisonings involving organo-
 phosphates, or in poisonings by unidentified anticholinesterase
 agents which produce significant nicotinic effects, cautious admin-
 istration of pralidoxime may have to be considered (see Chapter 1
 TREATMENT, Section 4, p. 7).
 In patients who have been poisoned by carbamate pesticide con-
 tamination of skin, clothing, hair, and/or eyes, DECONTAMINA-
 TION MUST PROCEED CONCURRENTLY with whatever resus-
 citative and antidotal measures are needed to preserve life. Con-
 tamination of the  eyes should be removed by flushing with copi-
 ous amounts of clean water. For asymptomatic  individuals who
 are alert and physically able, a prompt shower and shampoo may
 be  appropriate,  provided the patient  is  carefully observed to
 insure against sudden appearance of poisoning. If there are any
 indications of weakness, ataxia, or other  neurologic impairment,
 clothing should be removed and  a complete  bath  and shampoo
 given while the victim  is recumbent, using copious amounts of
 soap and water. Attendants should wear  rubber  gloves.  Surgical
green soap is excellent for  this  purpose, but ordinary soap is
about as good. The possibility of pesticide sequestered under fin-
gernails or in skin folds should not be overlooked. CONTAMI-
NATED CLOTHING should be promptly removed, bagged, and
                              15

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    not returned until it has been thoroughly laundered. Contaminat-
    ed leather shoes should be discarded. The possibility that pesticide
    has contaminated the inside surfaces of gloves, boots, and head-
    gear should be kept in mind.
6.  IF  N-METHYL  CARBAMATE  HAS BEEN  INGESTED in  a
    quantity probably sufficient to cause poisoning, the stomach and
    intestine must be emptied, and measures taken to limit absorp-
    tion from the gut. Procedures for accomplishing this are essential-
    ly the same  as  those used in organophosphate poisonings. See
    Chapter 1, TREATMENT, Section 6, p. 8.
7.  OBSERVE PATIENT CLOSELY for at least 24 hours to insure
    that symptoms (sweating, visual disturbances, vomiting, diarrhea,
    chest and abdominal  distress,  and sometimes PULMONARY
    EDEMA)  do  not recur  as atropinization is withdrawn. As  the
    dosage of atropine  is reduced over time,  check the lung bases
    frequently for rales. If rales are heard, or if there  is a return of
    miosis, sweating or other signs of poisoning, atropinization must
    be re-established promptly.
8.  Furosemide may be considered for relief of pulmonary edema if
    rales persist in the  lungs even after full atropinization. It should
    not be considered until the maximum effect of atropine has been
    achieved.  Consult package  insert for dosage and administration.
9.  Particularly hi poisonings by large  doses of N-methyl  carbamates,
    MONITOR PULMONARY VENTILATION carefully, even after
    recovery from muscarinic symptomatology, to forestall respiratory
    failure.
10.  In severely poisoned patients, MONITOR CARDIAC  STATUS by
    continuous EGG recording.
11.  The following drugs are probably contraindicated in nearly all N-
    methyl carbamate poisoning cases: morphine, theophylline, phen-
    othiazines, and reserpine. Adrenergic amines should be given only
    if there is a specific indication,  such as  marked hypotension.
12.  Persons who have  been clinically poisoned by N-methyl carba-
    mate pesticides should not be re-exposed to cholinesterase-inhibit-
    ing chemicals until symptoms and signs have resolved completely.
13.  DO NOT ADMINISTER ATROPINE PROPHYLACTICALLY to
    workers exposed to N-methyl carbamate pesticides. Prophylactic
    dosage may mask early symptoms  and  signs of carbamate poison-
    ing and thus allow the worker to continue exposure  and possible
    progression to more severe  poisoning. Atropine itself  may  en-
    hance the health hazards of the  agricultural work setting:  im-
    paired heat loss due to reduced sweating and impaired ability to
    operate mechanical equipment due to  blurred vision (mydriasis).
                                16

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                       CHAPTER 3

          SOLID ORGANOCHLORINE
                   INSECTICIDES
 CHEMICAL STRUCTURES
                           MIREX
                                        Cl   Cl     Cl   Cl

                                            DIENOCHLOR
     CHLORDECONE
COMMERCIAL PRODUCTS

  Endrin (Hexadrin), aldrin (Aldrite, Drinox), endosulfan (Thiodan),
dieldrin  (Dieldrite), toxaphene (Toxakil, Strobane-T), lindane (gamma
BHC or HCH, Isotox), hexachlorocyclohexane (BHC), DDT (chlorophen-
othane),  heptachlor (Heptagran), chlordecone (Kepone), terpene polych-
lorinates (Strobane), chlordane (Chlordan), dicofol (Kelthane), mirex
(Dechlorane), methoxychlor (Marlate), dienochlor (Pentac), TDE (DDD,
Rhothane), ethylan (Perthane).
  The United States Environmental Protection Agency has sharply
curtailed the availability of many organochlorines, particularly DDT,
dieldrin,  heptachlor, mirex, chlordecone, and chlordane. Others, howev-
er, are still the active ingredients of various home and garden products
                            17

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and  some  agricultural,  structural,  and  environmental  pest  control
products. Hexachlorobenzene  is used as  a seed protectant fungicide.
  Technical hexachlorocyclohexane (misnamed  benzene hexachloride,
BHQ includes multiple stereoisomers; only the gamma isomer  (lin-
dane) is insecticidal. Lindane is the active ingredient of some  pest
control  products  used in the  home and garden, on the farm, and in
forestry and animal husbandry. It is also the active agent in the
medicinal Kwell,  used for human ectoparasitic disease.

TOXICOLOGY

  In varying degrees, organochlorines are absorbed from the gut and
also by the lung  and across the skin. The efficiency of dermal absorp-
tion is  variable.  Hexachlorocyclohexane,  including lindane, the cyclo-
dienes (aldrin, dieldrin, endrin, chlordane, heptachlor) and endosulfan
are efficiently absorbed across skin, while dermal absorption efficien-
cies of  DDT,  perthane,  dicofol, methoxychlor, toxaphene, mirex, and
kepone are substantially less. Gastrointestinal, and  probably  dermal,
absorption  of  organochlorines is  enhanced by fat and fat solvents.
While most of the solid organochlorines are not highly volatile, pesti-
cide-laden aerosol or dust particles trapped in respiratory mucous and
subsequently swallowed may be vehicles leading to significant gastroin-
testinal absorption.
  Following exposure to some organochlorines (notably DDT), a signifi-
cant part of the  absorbed dose is stored in fat tissue as the unchanged
parent  compound. Most organochlorines are in  some degree dechlorin-
ated, oxidized, then conjugated. The chief route of excretion is biliary,
although nearly  all organochlorines yield measurable urinary  metabo-
lites. Unfortunately, many of the unmetabolized pesticides are effi-
ciently reabsorbed by the intestine (enterohepatic circulation) substan-
tially retarding fecal excretion. Metabolic dispositions of DDT and DDE
(a DDT degradation product), the beta isomer  of hexachlorocyclohex-
ane, dieldrin, heptachlor epoxide, mirex, and kepone tend to be  slow,
leading to storage in body fat. Storable lipophilic compounds are likely
to be excreted in maternal milk.
   Rapid metabolic  dispositions of lindane,  methoxychlor, dienochlor,
 endrin, chlorobenzilate, dicofol, toxaphene, perthane,  and endosulfan
 reduce the likelihood that these organochlorines will be detected as
 residues in body fat, blood, or milk.
   The cyclodiene aldrin is efficiently epoxidized in the body (and hi the
 environment)  to dieldrin. A similar biotransformation converts hepta-
 chlor to heptachlor epoxide. These conversions have little effect on
 toxicity of the parent compound. The epoxides are sometimes identified
 in body fat, blood, and milk.
   Lindane is partially dechlorinated and oxidized following absorption,
 promptly yielding a series of  conjugated chlorophenols and other oxida-
 tion products in the urine.

                                 18

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   The chief toxic action of the organochlorine pesticides is  on the
 nervous system, where these compounds interfere with fluxes of ca-
 tions  across nerve cell membranes,  increasing neuronal  irritability.
 This effect is manifest mainly  as  convulsions, sometimes limited to
 myoclonic jerking, but often expressed as violent seizures. Convulsions
 caused by the more  slowly metabolized cyclodienes may recur over
 periods of several days.  Convulsions  may cause death by interfering
 with pulmonary  gas  exchange  and  by generating severe metabolic
 acidosis. Various  disturbances of sensation, coordination, and mental
 function are also characteristic of acute organochlorine poisoning. High
 tissue concentrations  of organochlorines increase myocardial irritabil-
 ity, predisposing to cardiac arrhythmias. When tissue organochlorine
 concentrations drop below threshold levels, recovery from  the poison-
 ing occurs. Organochlorines are not cholinesterase inhibitors.
   High tissue levels of some organochlorines (notably DDT, DDE, cyclo-
 dienes, mirex, and kepone) have been shown to induce hepatic microso-
 mal drug-metabolizing enzymes.  This tends to accelerate excretion of
 the pesticides themselves, but may also stimulate biotransformation of
 critical natural substances, such as  steroid hormones and therapeutic
 drugs, occasionally necessitating revaluation of required  dosages in
 persons intensively exposed to organochlorines. Human absorption of
 organochlorine sufficient to cause enzyme induction is likely to occur
 only as a result of prolonged intensive exposure.
   Hexachlorobenzene (a fungicide) has caused porphyria cutanea tarda
 in humans. It does not  cause convulsions. Lindane,  chlordane, and
 dieldrin have been associated anecdotally with certain rare  hematolog-
 ic disorders, including aplastic anemia;  the incidence of these effects
 appears to be extremely low.
   Poisoning by endosulfan has caused blindness in sheep. Mirex at
 high dosage produces  cataracts in rats and mice. The DDT analogue
 known as  ODD is selectively concentrated in  adrenal tissue,  where
 high levels have an inhibitory effect on corticosteroid synthesis, and a
 damaging effect on  the cells. Certain other organochlorines are also
 bioconcentrated in the adrenal cortex.

 SYMPTOMS AND SIGNS OF POISONING BY
   ORGANOCHLORINES

  Early manifestations of poisoning by some organochlorine pesticides,
 particularly DDT, are often  sensory disturbances: hyperesthesia and
 paresthesia of the face and extremities. Headache,  dizziness, nausea,
vomiting, incoordination, tremor, and mental confusion are also report-
ed. More severe poisoning causes myoclonic jerking movements, then
generalized tonic-clonic CONVULSIONS. The seizures may be followed
by coma and respiratory depression.
  Poisoning by the cyclodienes and toxaphene is more  likely to begin
with the sudden onset of convulsions, often not preceded by the pre-

                                19

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monitory manifestations mentioned  above. Seizures caused by cyclo-
dienes may appear as long as 48 hours after exposure, and may then
recur periodically over several days  following the initial episode.  Be-
cause lindane and toxaphene are more rapidly biotransformed in  the
body and excreted, they are less likely than dieldrin, aldrin, and chlor-
dane to cause delayed or recurrent seizures.
  Poisoning by chlordecone has occurred as a result of extraordinary
occupational exposure over many days. Principal manifestations were
weight loss,  tremor, muscle weakness, involuntary eye movements,
pain in the chest and joints, skin rash, slurred speech, mental changes,
and abnormalities of liver function.  Seizures did not occur. Recovery
was slow.
  There have been no well documented reports of acute human poison-
ings by dicofol, mirex, heptachlor, dienochlor, perthane, methoxychlor,
or cblorobenzilate.

CONFIRMATION OF  POISONING  BY ORGANOCHLORINES

  Organochlorine pesticides and/or their metabolites can sometimes be
identified in blood by gas-liquid chromotographic examination of sam-
ples taken within a few days of significant pesticide absorption. Such
tests  are performed by a limited number of government, university,
and private laboratories,  which can  usually  be  contacted  through
poison control centers  or health departments. Some organochlorine
pesticides or their products (notably DDT, dieldrin, mirex, heptachlor
epoxide, chlordecone) persist in tissues and blood for weeks or months
after absorption, but others  are likely to be excreted in a few days,
limiting  the likelihood of detection. Chromatographic methods make
possible  detection of most organochlorines  at concentrations much
lower than those associated with acute poisoning. Therefore, a positive
finding in a tissue  sample does not,  of itself, justify  a  diagnosis of
poisoning.  To confirm  poisoning, the measured concentration must be
compared with those found in previously diagnosed cases of poisoning.
DDT, DDE, and a few other organochlorines are still found at very low
levels in blood samples from the general U.S. population,  presumably
due to past and/or  current low level  contamination of food by these
environmentally persistent pesticides.  There is presently no evidence
that  the  small body burdens of organochlorines  generated  by food-
borne residues cause disease in humans.
   Samples of fat tissue are more likely to reveal stored organochlorines
than blood.  However, amounts of stored pesticides insufficient to be
 identified in blood are not likely to be of clinical significance. Measure-
 ments of urinary metabolites of some organochlorine pesticides can be
 useful in  monitoring occupational exposures; however, the analytical
 methods are complex, and are not likely to detect  amounts of metabo-
 lites generated by minimal exposures.

                                20

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TREATMENT OF ORGANOCHLORINE TOXICOSIS
 1.
 2.
 3.
4.
 Persons exceptionally exposed to organochlorine pesticides by any
 route should be OBSERVED for sensory disturbances, incoordina-
 tion, speech slurring, mental aberrations, and involuntary motor
 activity that would warn of imminent convulsions.
 IF CONVULSIONS OCCUR, place the victim in the left lateral
 decubitus position with the head down.  Move away furniture or
 other solid  objects  that may be a source of injury. If jaw move-
 ments are violent, place padded tongue blades between  the teeth
 to protect the tongue. Whenever possible, remove  dentures  and
 other removable dental work. Aspirate oral and pharyngeal secre-
 tions, and,  when possible, insert an oropharyngeal AIRWAY to
 maintain an open passage unobstructed by the tongue.  Minimize
 noise and any manipulation of the patient that may trigger sei-
 zure activity.
 Administer  OXYGEN by mask. Maintain pulmonary gas  ex-
 change  by mechanically assisted ventilation whenever respiration
 is depressed.
 CONTROL  CONVULSIONS. Drugs that are useful for  this pur-
 pose are diazepam, lorazepam, barbiturates, and muscle-paralyz-
 ing agents such as succinylcholine.
 Benzodiazepine drugs are currently the preferred anticonvulsants.


 DIAZEPAM (Valium) has been  tested  the  most extensively
 against  convulsions and is generally recommended. LORAZEPAM
 (Ativan) may be superior as an anticonvulsant, but there is pres-
 ently less clinical experience with its use for this purpose. It is
 possible that lorazepam or other drugs will prove to be superior in
 the future.  Consult recent clinical  toxicology  texts for updated
 recommendations.

Dosage of DIAZEPAM:
    Adults and children  over 12 years: 5-10 mg given IV at no
    more than 2 mg per  minute. Repeat every 10-15 minutes, if
    necessary, to a maximum of 30 mg.
    Children 5 to 12 years: 0.25-0.40 mg/kg body weight, slowly
    IV,  and  repeat every 10-15 minutes, if necessary, to a maxi-
    mum of  10 mg.
    Children 30 days to  5 years: 0.25-0.40 mg/kg body weight,
    slowly IV, and repeat every 10-15 minutes, if necessary, to a
    maximum of 5 mg.
                              21

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     CAUTION:  Administer slowly to avoid  irritation of the vein,
                 hypotension,  and respiratory depression. Facilities
                 should be immediately available to support pulmo-
                 nary ventilation mechanically and to relieve  laryngo-
                 spasm.
If it is not possible to give the drug intravenously, administer the
following doses undiluted by deep intramuscular injection:
     Adults and children over 5 years: 10 mg. Repeat in 2-4  hours if
     necessary.
     Children under 5 years: 5 mg. Repeat in 2-4 hours if necessary.


     PENTOBARBITAL SODIUM  is an intermediate acting  barbitu-
     rate  that is  sometimes useful in controlling convulsions.  It  is
     supplied in stable injectable solution or may be prepared fresh as
     a 5% sterile aqueous solution (50 mg per ml). It can be given
     either intravenously or intramuscularly.

     Dosage of PENTOBARBITAL SODIUM:
         Adults and  children  over 12 years: 200-500 mg (4-10  ml).
         Initial intravenous dose should be 2-3 ml injected over a  two-
         minute  period. Wait  five minutes  to  observe effect,  then
         repeat if needed to suppress convulsions. If  it is necessary  to
         give pentobarbital intramuscularly,  inject 2 ml deep at two
         different sites, then wait  20-30 minutes to  observe  effect. If
         needed, repeat intramuscular dose or switch to intravenous
         administration.
         Children under 12 years: 3-7 mg/kg body weight injected
         over a five-minute period.  Wait five minutes to observe effect,
         then repeat dose if necessary to suppress convulsions. If it is
         necessary to give  intramuscularly,  inject  1.5  mg/kg body
         weight at two different sites, then  wait 20-30 minutes  to
         observe effect. If necessary,  repeat intramuscular dose  or
         switch to intravenous administration.
     CAUTION:  Respiratory depression and hypotension may follow
                 intravenous use of pentobartibal. Facilities must  be
                 immediately available to support pulmonary ventila-
                 tion mechanically and to intubate the trachea if the
                 upper airway is obstructed.
     PHENYTOIN SODIUM (Dilantin) is effective in controlling epi-
     leptic seizures,  but  is  of uncertain  value against convulsions
     caused by chemical agents. Protocols for its administration can be
     found in medical texts  dealing with  the  management of status
     epUepticus.

                                 22

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 5.
6.
7.
 SUCCINYLCHOLINE (or similar muscle-paralyzing drug) may be
 used if seizures prove intractable. Gain full control of pulmonary
 ventilation (endotracheal tube  or  tracheostomy connected to a
 mechanical ventilator), prepare to monitor blood gases, and secure
 the services of an anesthesiologist or emergency care physician to
 induce general anesthesia and administer the neuromuscular de-
 polarizing agent. This procedure predictably controls seizures, but
 imposes heavy responsibilities for  continuous monitoring of gas
 exchange and blood pH over several hours.
 In patients who have been poisoned by organochlorine contamina-
 tion of skin,  clothing, hair and/or eyes, DECONTAMINATION
 MUST PROCEED CONCURRENTLY with whatever resuscitative
 and anticonvulsive measures are necessary to preserve life. Con-
 tamination of the eyes should be removed by flushing with copi-
 ous  amounts of clean water.  If the pesticide-exposed  person  re-
 mains alert and physically able, a prompt shower and shampoo
 may be appropriate, provided the patient is carefully observed to
 insure against sudden appearance of poisoning.  If there are any
 indications of weakness, ataxia, or other neurologic impairment,
 clothing should be removed and a complete bath  and shampoo
 given while the victim is recumbent, using  copious amounts of
 soap and water. Attendants should wear rubber gloves. Surgical
 green  soap is excellent  for this purpose, but ordinary soap is
 about as good. The possibility of pesticide sequestered  under fin-
 gernails or in  skin folds should not be overlooked. CONTAMI-
 NATED CLOTHING should be promptly bagged and not returned
 until it  has been  thoroughly laundered. Contaminated leather
 shoes should be discarded. The possibility that pesticide has con-
 taminated the inside surfaces  of  gloves, boots, and headgear
 should be considered.
 IF ORGANOCHLORINE HAS BEEN INGESTED in a quantity
 sufficient to cause poisoning, the stomach and intestine must be
 emptied, and measures taken to limit toxicant absorption.
 Because seizure activity  may develop rapidly, LAVAGE, with a
 large bore orogastric tube and  with rigorous protection  of the
 airway, is probably preferable to induced emesis  in most cases. If
 the victim is convulsing, it is  almost always necessary first  to
 control seizures  before attempting gastric intubation. The effec-
 tiveness of lavage in removing pesticide from  the stomach dimin-
 ishes rapidly with the passage of time. Procedures  for emptying
 the stomach and administration of activated charcoal and cathar-
 tic are described in Chapter 1, TREATMENT,  Section 6, p.  8.
Particularly in poisonings by large doses of organochlorine, MON-
 ITOR PULMONARY  VENTILATION carefully to forestall respi-
ratory  failure. Assist pulmonary ventilation  mechanically with
oxygen whenever respiration is depressed.
                              23

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 8.   In severely poisoned patients, MONITOR CARDIAC STATUS by
     continuous EGG recording to detect arrhythmias.
 9.   DO NOT GIVE epinephrine, other adrenergic amines, or atropine
     because of the enhanced myocardial irritability induced by chlor-
     inated hydrocarbons, which predisposes to ventricular fibrillation.
10.   DO NOT GIVE animal or vegetable oils or fats by mouth. They
     enhance gastrointestinal absorption of the lipophilic organochlor-
     ines.
11.   To control  seizures and myoclonic movements that sometimes
     persist for  several days following acute poisoning by the more
     slowly excreted organochlorines, phenobarbital orally is likely to
     be effective. Dosage should be based on manifestations  in the
     individual case  and on information contained in the package
     insert.
12.   CHOLESTYRAMINE resin accelerates the biliary-fecal excretion
     of the more slowly eliminated organochlorine compounds. It is
     usually administered in 4 gm doses, 4 times a day, before meals
     and at bedtime. Dose should be mixed with a pulpy fruit or liquid.
     Prolonged treatment (several weeks or months) may be necessary.
13.   During convalescence,  enhance CARBOHYDRATE, PROTEIN,
     and VITAMIN intake by diet or parenteral therapy.
                                24

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                        CHAPTER 4

       INSECTICIDES OF BIOLOGICAL
                         ORIGIN

   This chapter concerns several widely used insecticidal products of
 natural origin, and also a growth promoting agent, gibberellic acid. It
 discusses, in order, pyrethrum and pyrethrins, nicotine, rotenone, saba-
 dilla, bacillus thuringiensis, and gibberellic acid.

                PYRETHRUM AND PYRETHRINS
 GENERAL CHEMICAL STRUCTURE
          R
               H   H
            = C-C
              CH-C-

                   CH
                                       CH.
C-C-Q-C"

        H C-
          H
                                         C - R'
                                          I
                                         C =0
                     3   PYRETHRIN

SOURCE AND PRODUCTS

  Pyrethrum is the oleoresin extract of dried chrysanthemum flowers.
The extract contains about 50% active insecticidal ingredients known
as pyrethrins. The ketoalcoholic esters of chrysanthemic and pyreth-
roic acids are known  as  pyrethrins, cinerins, and jasmolins. These
strongly lipophilic esters rapidly penetrate many insects and paralyze
their nervous systems. Both  crude  pyrethrum extract and purified
pyrethrins are contained in various commercial products, commonly
dissolved in petroleum distillates.  Some are packaged in pressurized
containers ("bug-bombs"), usually in combination with the synergists
piperonyl butoxide and n-octyl bicycloheptene dicarboximide.  The syn-
ergists  retard enzymatic degradation of pyrethrins. Some commercial
products  also contain organophosphate  or carbamate  insecticides.
These are included because the rapid paralytic  effect of pyrethrins on
insects  ("quick knockdown") is not always lethal.
  Pyrethrum and pyrethrin products are  used mainly for indoor pest
control. They are not sufficiently stable ^in light and heat to remain as
active residues on crops. The  synthetic insecticides known as pyreth-
                             25

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roids (chemically similar to pyrethrins) do have the stability needed for
agricultural application. Pyrethroids are discussed in Chapter 5, p. 34.

TOXICOLOGY OF PYRETHRUM AND PYRETHRINS

  Crude pyrethrum is a dermal and respiratory allergen, probably due
mainly to noninsecticidal ingredients.  Contact dermatitis and allergic
respiratory  reactions (rhinitis and asthma) have occurred  following
exposures. A strong cross-reactivity with ragweed pollen has  been rec-
ognized. Single cases exhibiting anaphylactic and pneumonitic manifes-
tations have also been reported.  The refined pyrethrins are probably
less allergenic, but appear to retain some irritant and/or sensitizing
properties.
  Pyrethrins are absorbed across the  gut and pulmonary membrane,
but only slightly across intact skin. They are very effectively hydro-
lyzed to inert products by mammalian  liver enzymes. This rapid degra-
dation combined with relatively poor bioavailability probably accounts
in  large part for  their relatively low mammalian toxicity.  Dogs fed
extraordinary doses exhibit tremor, ataxia, labored breathing, and sali-
vation. Similar neurotoxicity rarely,  if ever, has been observed in
humans, even in individuals who have used pyrethrins for  body lice
control (extensive contact) or pyrethrum as an anthelmintic (ingestion).
  In cases of human exposure to commercial products, the possible role
of other toxicants in the products should be kept in mind. The syner-
gists piperonyl butoxide and n-octyl bicycloheptene dicarboximide have
low toxic potential in humans, but organophosphates or carbamates
included in the product may have significant toxicity. Pyrethrins them-
selves do not inhibit cholinesterase enzyme.
  There are presently no practical tests for pyrethrin metabolites or
pyrethrin effects on human enzymes or tissues that can be  used to
confirm absorption.

TREATMENT OF PYRETHRUM  OR PYRETHRIN TOXICOSIS

  Antihistamines are  effective in controlling most allergic  reactions.
 Severe asthmatic reactions, particularly in predisposed persons, may
 require administration of epinephrine, theophylline, and/or corticoster-
 oid medicinals. Inhalation exposure should be carefully avoided hi the
 future.
   Contact dermatitis may require extended administration  of topical
 corticosteroid preparations. This should be  done under the supervision
 of a physician. Future  contact  with the  allergen must be  avoided.
   Eye contamination should be removed by copious flushing of the eye
 with  clean water or saline. Specialized care  should be obtained  if
 irritation persists.

                                 26

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  Toxic manifestations caused by other ingredients must be treated
according to their respective toxic actions, independent of pyrethrin-
related effects.
  Even though  most ingestions of pyrethrin products present little
risk, if a large amount of pyrethrin-containing material has been in-
gested, it may be appropriate to  empty the  stomach by  intubation,
aspiration, and lavage, after all precautions have been taken to protect
the respiratory tract from aspiration of stomach contents (see Chapter
1, TREATMENT, Section 6, p. 8). Lavage  should be followed by instilla-
tion of activated charcoal and cathartic (see same reference).
  If retained dosage was small and/or treatment has been delayed, and
if patient is fully alert, ORAL administration of activated CHARCOAL
and CATHARTIC  probably represents   optimal  management.  (See
above reference for recommended dosages.)
                            NICOTINE
CHEMICAL STRUCTURE
SOURCE AND PRODUCTS

  Nicotine is an alkaloid contained in the leaves of many species of
plants, but is usually obtained commercially from tobacco. A 95%
solution of the free alkaloid in organic solvent has been marketed in
the past as a greenhouse fumigant. Another product used for the same
purpose is a 40% aqueous solution of nicotine sulfate. Significant vola-
tilization of nicotine occurs from both products. Commercial nicotine
insecticides have  long been known as Black Leaf 40. Formulations
include sprays and dusts. Very little nicotine insecticide is used in the
United States today; in fact, most nicotine poisonings are the result of
ingestion of tobacco products.

TOXICOLOGY OF NICOTINE

  Nicotine alkaloid is efficiently absorbed by the gut, lung,  and skin.
The sulfate salt is  absorbed by lung and gut, but is poorly absorbed
across the skin. Extensive biotransformation occurs in the liver result-
ing in  a residence  half-life of two hours or less. Both the  liver and

                                27

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kidney participate in the formation and excretion of multiple end-
products, which are excreted within a few hours.
  Toxic action is complex, involving both stimulation and blockade of
autonomic  ganglia and skeletal muscle neuromuscular junctions, as
well as direct effects on the  central nervous system. Paralysis  and
vascular collapse are prominent features of acute poisoning, but death
is  usually  due to  respiratory paralysis,  which may ensue  promptly
after the first symptoms of  poisoning. Nicotine is not an inhibitor of
cholinesterase enzyme.

MANIFESTATIONS  OF NICOTINE POISONING

  Early symptoms of poisoning are salivation, nausea, vomiting,  and
diarrhea. Burning sensations in the mouth and throat and abdominal
pain are reported. If dosage  has been high, vascular collapse, dyspnea
then respiratory failure,  cyanosis and  unconsciousness may  ensue
promptly. Agitation,  sweating, headache, pupillary constriction, dizzi-
ness,  incoordination,  confusion, weakness,  tremor,  and convulsions
occur early in less fulminant  poisoning.  Initial hypertension is prob-
ably due mainly to generalized vasoconstriction. Subsequent shock is
caused by  vasodilatation, often associated with vagotonic asystole or
severe cardiac arrhythmias. Respiratory failure is caused mainly by
paralysis of the muscles of respiration.

CONFIRMATION OF NICOTINE POISONING

  Urine content of the metabolite cotinine can be  used to confirm
absorption of nicotine.

TREATMENT OF NICOTINE TOXICOSIS

 1.  If liquid or aerosol spray has come in contact with skin, wash the
     area thoroughly with soap and water.
 2.  If eyes have been contaminated, flush them thoroughly with clean
     water or saline.  If irritation persists, obtain specialized medical
     treatment.
 3.  If symptoms of poisoning appear during exposure to an airborne
     nicotine insecticide, remove the person from the contaminated
     environment immediately, wash any skin areas that may be  con-
     taminated, then transport the  victim to the nearest treatment
     facility. Although mild poisoning may resolve without treatment,
     it is often difficult to predict the ultimate severity of poisoning at
     the onset.
 4.  If there is any indication of loss of respiratory drive, MAINTAIN
     PULMONARY VENTILATION by mechanical means,  including
     supplemental OXYGEN,  if  available,  by mouth-to-mouth, or
     mouth-to-nose  methods,  if necessary.  Toxic  effects of nicotine
     other than respiratory  depression are usually survivable. The im-

                                28

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    portance of maintaining adequate gas exchange is therefore para-
    mount.
 5.  If a nicotine-containing  product has been  ingested,  immediate
    steps must be taken to limit gastrointestinal absorption.
    A.  IF the patient is fully ALERT, immediate oral administration
        of ACTIVATED CHARCOAL is probably the best initial step
        in management.
        Dosage of ACTIVATED CHARCOAL:
             Adults and children over 12 years: 50-100 gm in 300-800
             ml water.
             Children under  12 years: 15-30 gm in 100-300 ml water.
             Because nicotine itself is very likely to induce diarrhea,
             it is usually not appropriate  to include cathartic with
             the charcoal.
             CAUTION: Because unconsciousness may develop rapid-
             ly in nicotine poisoning, it is essential to position the
             patient after the  charcoal  slurry has been  swallowed
             (recumbent prone, head down) so that vomited material
             will not be aspirated.
    B. If the patient is unconscious or confused, the stomach should
       be  emptied by INTUBATION, ASPIRATION^ and  LAVAGE,
       after all precautions have been taken to protect the respirato-
       ry  tract from aspirated stomach contents (see Chapter 1,
       TREATMENT, Section 6, p. 8). Charcoal slurry should be used
       in washing the stomach, and several ounces should be left in
       the stomach after the lavage. Repeated administration of acti-
       vated charcoal at  half or more  the initial dosage  every 2-4
       hours may be beneficial.
    C. DO NOT administer  Syrup of Ipecac. It may enhance medul-
       lary depressant effects of nicotine, and may induce vomiting
       when the patient is obtunded.
6.   Monitor cardiac status by electrocardiograph^, and measure blood
    pressure  frequently. Cardiopulmonary  resuscitation may some-
    tunes be necessary.
    Vascular collapse may require administration of norepinephrine
    and/or dopamine. Consult package inserts for dosages and routes
    of administration.  Infusions of  electrolyte  solutions,  plasma
    and/or blood may also  be required to combat shock.
7.   There is no specific antidote for nicotine poisoning. Severe hyper-
    secretion (especially salivation and diarrhea) may be controlled by
    intravenous atropine sulfate.
       Dosage of ATROPINE SULFATE:
            Adults and children over 12 years: 0.4-0.5 mg slowly IV,
            repeated every 5 minutes if necessary.
            Children under  12 years: 0.01 mg/kg body weight, slowly
            IV, repeated every 5 minutes if necessary.

                              29

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             CAUTION: Careful EGG monitoring of cardiac rhythm
             should accompany intravenous  administration of atro-
             pine.
 8.   Convulsions should be controlled with diazepam or other benzo-
     diazepine drug. See Chapter 3, TREATMENT,  Section 4 (p. 21)
     for appropriate dosages and methods of administration.
 9.   If the patient survives for four hours, complete recovery is said to
     be likely.

                          ROTENONE

SOURCE  AND PRODUCTS

  Although this natural substance is present in a number of plants,
the source of most  rotenone  used  in the United States is the dried
derris root imported from Central and South America. It is formulated
as dusts, powders, and sprays (less  than 5% active ingredient) for use
in gardens and on food crops. Many products contain piperonyl butox-
ide as synergist, and other pesticides are included in  some commercial
products. Rotenone degrades rapidly in the environment. Emulsions of
rotenone are applied to lakes and ponds to kill fish.

COMMERCIAL PRODUCTS

  Noxfish, Noxfire, Rotacide, Foliafume, Nusyn-Noxfish, PB-Nox, Pren-
tox, Chem-Fish, Rotenone Solution FK-11.

TOXICOLOGY AND MANIFESTATIONS OF POISONING

  Although rotenone is toxic to the nervous  systems of insects, fish,
and birds, commercial rotenone products have presented little hazard
to man over many decades. Neither fatalities nor systemic poisonings
in humans have been reported in relation to ordinary use. Low concen-
tration in commercial products, degradability,  an  intense nauseant
effect in man, and  poor absorption across gut and skin are  probable
factors accounting for the good safety record of rotenone.
  Numbness of oral mucous membranes has been reported hi workers
who got dust from the powdered derris root hi their  mouths. Dermati-
tis and respiratory tract irritation  have also been reported in occupa-
tionally exposed persons.
  When rotenone has been injected into animals, tremors, vomiting,
incoordination, convulsions, and respiratory arrest have been observed.
These  effects  have not  been reported  in  occupationally exposed
humans.
                               30

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TREATMENT OF ROTENONE TOXICOSIS

  Skin contamination should be removed by washing with soap and
water. Eye contamination should be removed by flushing the eye thor-
oughly with clean water or saline. Dust hi the mouth should be washed
out. If irritation persists, medical treatment should be obtained.
  If a rotenone-containing product has been swallowed and retained,
active efforts  to  empty  the stomach should be  undertaken only if
another more  toxic pesticide is contained in the product. If patient is
fully  alert, prompt oral administration of activated charcoal (and ca-
thartic if diarrhea has not already occurred)  is probably the optimal
management of ingestion of a product containing rotenone as the only
insecticidal  ingredient (with or  without synergists). See Chapter 1,
TREATMENT, Section 6, p. 8 for dosages.
                          SABADILLA

SOURCE AND PRODUCTS

  Sabadilla consists of the powdered ripe seeds of a South American
lily. It is used as a dust, with lime or sulfur, or dissolved in kerosene,
mainly to kill ectoparasites on domestic animals and humans. Insectici-
dal alkaloids are those of the veratrin type.  The concentration  of
alkaloids in commercial sabadilla is usually less than 0.5%. Little or no
sabadilla is used in the United States today, but there is probably some
used in other countries.

TOXICOLOGY OF SABADILLA

  Sabadilla dust is very irritating  to the upper respiratory tract, caus-
ing sneezing, and is also irritating to the skin.
  Veratrin alkaloids are apparently absorbed across the skin and gut,
and probably by the lung as well. Veratrin alkaloids have a digitalis-
like  action on the  heart muscle  (impaired conduction and arrhyth-
mias).

MANIFESTATIONS OF SABADILLA POISONING

  Although poisoning by medicinal veratrin  preparations  may have
occurred in the remote past, systemic poisoning by sabadilla prepara-
tions used as insecticides has been very rare or nonexistent.

TREATMENT OF SABADILLA TOXICOSIS

  Contaminated skin  should  be washed thoroughly with soap and
water. If eyes are affected,  they  should be flushed with  copious
amounts of clean water or saline. If skin or eye irritation persists,
medical treatment should be obtained.

                               31

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  If a large amount of sabadilla pesticide product has been ingested in
the past hour and retained, the stomach should be emptied by intuba-
tion, aspiration, and lavage (see Chapter 1, TREATMENT, Section 6). If
only a  small amount of sabadilla pesticide has  been ingested  and
retained, or if treatment is delayed, and if the patient remains fully
alert, immediate oral administration of activated charcoal probably
represents  optimal management. If diarrhea has not already com-
menced, sorbitol should be administered with the charcoal slurry (see
above reference). If there is  a suspicion that significant amounts of
sabadilla alkaloids have been absorbed, EGG monitoring  of cardiac
activity for arrhythmias and conduction defects is appropriate.
                   BACILLUS THURINGIENSIS

SOURCE AND PRODUCTS

  Several strains of the Bacillus thuringiensis are pathogenic to some
insects. The bacterial organisms are cultured, then harvested in spore
form for  use as insecticide. Production methods vary widely. Proteina-
ceous and nucleotide-like toxins generated by the vegetative forms
(which infect insects) are responsible for the insecticidal effect. The
spores are formulated as wettable powders, flowable concentrates and
granules  for application to field  crops and for  control of mosquitoes
and black flies.

COMMERCIAL PRODUCTS

  Variety kurstaki: Bactur, Bactospeine, Dipel, Futura, Sok-Bt, Thuri-
cide, Tribactur. Variety israelensis: Bactimos, Skeetal, Teknar, Vecto-
bac. Variety aizawai: Certan.

TOXICOLOGY OF BACILLUS THURINGIENSIS

  The varieties of Bacillus thuringiensis used  commercially survive
when injected into mice, and at least one of the purified insecticidal
toxins is  toxic to mice. Infections of humans have been extremely rare
(two recognized cases)  and no  occurrences of human  toxicosis have
been reported. From studies involving deliberate ingestion by human
subjects,  it  appears  possible, but not likely, that the organism can
cause gastroenteritis. B. thuringiensis products are exempt from toler-
ance on  raw agricultural commodities  in the United States. Neither
irritative nor sensitizing effects  have  been reported in workers prepar-
ing and applying commercial products.

TREATMENT OF BACILLUS THURINGIENSIS TOXICOSIS

  Skin contamination should be  removed with soap and water. Eye
contamination  should be removed by  flushing  the eyes with clean

                                32

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water or saline. If irritation persists, or if there is any indication of
infection, treatment by a physician should be obtained.
  If a B. thuringiensis product has been ingested, the patient should be
observed for manifestations of bacterial  gastroenteritis:  abdominal
cramps, vomiting,  and diarjrhea. The illness is likely to be self-limited
if it occurs at all.  Kaolin- land pectin-containing medicinals may miti-
gate the symptoms. If dehydration is marked, saline-  and glucose-
containing  fluids may be given orally or intravenously. Buttermilk
may be given to restore normal gut flora.
  A single case of corneal ulcer caused by a splash  of B.  thuringiensis
suspension  into the  eye was successfully treated by subconjunctival
injection of gentamicin (20 mg) and cephazolin (25 mg).


               GIBBERELLIC ACID (Gibberellin, GA3)

SOURCE AND PRODUCTS

  Gibberellic acid is not a pesticide, but it is commonly used in agricul-
tural production as a growth promoting agent. It is a metabolic product
of a cultured fungus, formulated in tablets, granules, and liquid con-
centrates for application to  soil beneath growing plants  and trees.
  Commercial products: Activol, Berelex, Cekugib, Gibberellin, Gibrel,
Grocel, Pro-Gibb, Pro-Gibb Plus, Regulex.

TOXICOLOGY OF GIBBERELLIC ACID

  Experimental animals tolerate large oral  doses  without apparent
adverse effect. No human poisonings have been reported. Sensitization
has not been reported, and irritant effects are not remarkable.

MANAGEMENT OF GIBBERELLIC  ACID EXPOSURE

  Wash contamination from skin with soap and water. Flush contami-
nation from eyes with clean water or saline. If irritation occurs, obtain
medical treatment.
  If gibberellic acid has been swallowed, there is no reason to  expect
adverse effects.
                                33

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                         Chapter 5

  OTHER INSECTICIDES, ACARICIDES,
                AND REPELLENTS
  This chapter concerns insecticides, acaricides, and repellents having
toxicologic characteristics distinct from the insecticides discussed in
previous chapters. It discusses pyrethroids, fluorides, borates, chlordi-
meform, propargite, substituted haloaromatic urea compounds, chloro-
benzilate,  cyhexatin,  methoprene,  sulfur, diethyltoluamide,  alkyl
phthalates, and benzyl benzoate.
                        PYRETHROIDS

  These modern synthetic insecticides are similar chemically to natu-
ral pyrethrins, but modified to increase stability in the natural envi-
ronment. They are now widely used  in agriculture, in homes and
gardens, and for treatment of ectoparasitic disease.

COMMERCIAL PRODUCTS

  The following list includes the names of several pyrethroids that are
not currently in  commercial production. These are included because
they may be marketed in the future, if not in the United States, then
possibly in other countries.
  Allethrin (Pynamin), alphametrin, barthrin, bioresmethrin, bioper-
methrin, cismethrin, cyclethrin, cyfluthrin (Baythroid), cypermethrin
(Ammo, Barricade, CCN52, Cymbush, Cymperator, Cyperkill, Folcord,
KafilSuper, NRDC 149, Polytrin, Siperin, Ripcord, Flectron, Ustaad,
Cyrux), deltamethrin  (decamethrin,  Decis), dimethrin, fenpropathrin
(Danitol, Herald,  Meothrin, Ortho Danitol, Rody),  fenvalerate (Pydrin,
Behnark, Sumicidin, Fenkill), flucythrinate (AASTAR, Pay-off), fluva-
linate (Mavrik, Mavrik Aquaflow, Spur), furethrin, indothrin, permeth-
rin (Ambush, BW-21-Z, Ectiban, Eksmin, Kafil, Permasect, Perthrine,
Pounce, Pramex, Outflank,  Talcord), phthalthrin (Neopynamin), res-
methrin (Benzofuroline, Chrysron, Pynosect,  Synthrin),  tetramethrin
(Neopynamin,  Phthalthrin),  tralomethrin   (Scout),  esfenvalerate
(Asana).
  Pyrethroids are formulated as emulsifiable. concentrates, wettable
powders, granules, and concentrates for ultra low volume application.
They may be combined with additional  pesticides (sometimes highly
toxic) in the technical product or tank mixed with other pesticides at
the tune of application. AASTAR is a combination of flucythrinate and
phorate. Phorate is a highly toxic organophosphate.

                              34

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  Nix is a 1% permethrin creme applied to control human ectopara-
sites.
TOXICOLOGY OF PYRETHROIDS

  Although certain pyrethroids exhibit striking neurotoxicity in labo-
ratory animals when administered by intravenous injection, and some
are toxic by the oral route, systemic toxicity by inhalation and dermal
absorption is low. There have been very few systemic poisonings of
humans by pyrethroids.  Although limited absorption may account for
the low toxicity of some  pyrethroids, rapid biodegradation by mamma-
lian liver  enzymes (ester hydrolysis and oxidation) is probably  the
major  factor responsible. Most pyrethroid metabolites are promptly
excreted, at least in part, by the kidney.
  Extraordinary absorbed  doses  may  rarely  cause  incoordination,
tremor, salivation, vomiting,  diarrhea, and irritability to  sound and
touch.  Extreme doses have  caused convulsions hi laboratory animals.
  Apart from systemic neurotoxicity, some  pyrethroids do cause  dis-
tressing  paresthesia  when  liquid  or  volatilized  materials  contact
human skin. Sensations are described as stinging, burning, itching, and
tingling, progressing to  numbness. The skin of the face seems to be
most commonly affected, but the hands, forearms, and  neck are some-
times involved. Sweating, exposure to sun or heat, and application of
water  enhance  the disagreeable sensations.  Sometimes  the effect is
noted within minutes of exposure, but a 1-2 hour delay hi appearance
of symptoms is more common. Sensations rarely persist more than 24
hours.  Little or no inflammatory reaction is apparent where the pares-
thesia  are reported;  the effect is presumed to result from pyrethroid
contact with sensory nerve endings  in the  skin. Not  all pyrethroids
cause a marked paresthetic reaction: it is prominent following expo-
sure to pyrethroids whose structures include cyano-groups: fenvalerate,
flucythrinate, cypermethrin, and fluvalinate. The paresthetic reaction
is not  allergic  in nature: sensitization does not occur. Neither race,
skin type, nor  disposition to  allergic disease affect the likelihood or
severity of the reaction.
  Persons treated with permethrin  for lice or flea infestations some-
times experience itching  and burning at the site of application, but this
is chiefly  an exacerbation of sensations caused by the parasites them-
selves, and is not typical of the paresthetic reaction described above.
  The manifestations of neurologic disorder seen hi laboratory animals
given the  more toxic pyrethroids hi large doses are salivation, irritabil-
ity, tremors, ataxia, choreoathetosis (writhing  convulsions),  fall hi
blood pressure, and death. Severe metabolic acidosis is characteristic.
  Due  to the inclusion of unique solvent ingredients, certain formula-
tions of fluvalinate are corrosive to the eyes (see TREATMENT, Sec-
tion 2, this chapter).
  Pyrethroids are not cholinesterase  inhibitors.

                                35

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TREATMENT OF PYRETHROID TOXICOSIS

 1.   Skin contamination should be removed promptly by washing with
     soap and water. If irritant or paresthetic effects occur, treatment
     by a physician should be obtained. Because volatilization of pyr-
     ethroid apparently accounts  for paresthesia affecting the face,
     strenuous measures should be taken (ventilation, protective face
     mask and hood) to avoid vapor contact with the face  and eyes.
     Vitamin  E  Oil  preparations  (dl-alpha  tocopheryl  acetate) are
     uniquely effective in preventing and stopping the paresthetic re-
     action. They are safe for application to the skin under field condi-
     tions. Corn oil is somewhat effective, but possible side effects with
     continuing use  make it less  suitable. Vaseline is less effective
     than corn oil and zinc oxide actually worsens the reaction.
 2.   Eye contamination should be treated immediately by prolonged
     flushing of the eye with copious amounts of clean water or saline.
     If irritation  persists, professional ophthalmologic care should be
     obtained. Undiluted Mavrik 2E (a formulation  of fluvalinate) is
     corrosive to the eyes. Extraordinary measures should be taken to
     avoid eye and skin contamination with this product. Should acci-
     dental eye  contamination occur,  expert  ophthalmologic care
     should be obtained after flushing  the eye free  of the chemical
     with copious amounts of clean water.
 3.   Ingestion of pyrethroid insecticide  presents relatively little risk.
     However, if large amounts have been ingested, empty the stomach
     by INTUBATION, ASPIRATION, and LAVAGE (see Chapter 1,
     TREATMENT, Section 6, p. 8). Based on observations in laborato-
     ry animals, large ingestions~«f either allethrin, cismethrin, fenva-
     lerate or deltamethrin would be the most likely to generate neu-
     rotoxic manifestations.
 4.   If only small amounts of pyrethroid have been ingested, or if
     treatment has been delayed, oral administration  of activated char-
     coal and cathartic probably represents optimal management (see
     Chapter 1, TREATMENT, Section 6, p. 8 for dosages).
 5.   Several drugs are effective in relieving the pyrethroid neurotoxic
     manifestations observed in deliberately  poisoned laboratory ani-
     mals. None  have been tested hi  human poisonings;  therefore,
     neither efficacy nor safety under these  circumstances is known.
     Furthermore, moderate neurotoxic symptoms and signs  are  likely
     to resolve spontaneously if they do occur. Drugs effective in labo-
     ratory animals  that might  be considered for symptomatic  treat-
     ment are: atropine (relief of salivation), diazepam, and phenobar-
     bital (relief of tremors and convulsions), and mephenesin (relief of
     all poisoning manifestations, except, sometimes, salivation).
                                36

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                             FLUORIDES

 COMMERCIAL PRODUCTS

   Sodium fluoride is a crystalline mineral once widely used in the
 United States  for  control of larvae  and crawling  insects in homes,
 barns, warehouses and other storage areas. It is highly  toxic to all
 plant and animal life.
   Commercial product: Florocid


   Sodium fluosilicate (sodium silico fluoride) has been used to control
 ectoparasites on livestock, as well as crawling insects in homes and
 work buildings. It is approximately as toxic as sodium fluoride.
   Commercial products: Safsan (dust formulation)
                        Prodan (bait formulation)


   Sodium fluoaluminate (sodium  aluminofluoride, cryolite) is a stable
 mineral containing fluoride. It is used  as an insecticide on some vegeta-
 bles and fruits. Cryolite has  very low water solubility, does  not yield
 fluoride ion on  decomposition, and presents  very little  toxic hazard to
 mammals, including man.
   Commercial product: Kryocide
   Hydrofluoric acid is an important industrial toxicant, but is not used
 as a pesticide. Fluoroacetate is discussed in Chapter 1.3:  RODENTI-
 CIDES. Sulfuryl fluoride is discussed in Chapter  14: FUMIGANTS.

 TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
   FLUORIDE

   Sodium fluoride and fluosilicate  used as insecticides present a seri-
 ous toxic hazard to humans because of high inherent toxicity, and the
 possibility  that  children crawling on  floors  of treated dwellings will
 ingest the material.
   Absorption across the skin is probably  slight, and methods of pesti-
 cide use rarely include a hazard of inhalation, but uptake of ingested
 fluoride by the gut is efficient and  potentially  lethal.  Excretion  is
 chiefly in the urine: renal clearance of.fluoride from the blood is rapid.
 However,  large  loads  of absorbed  fluoride poison renal  tubule  cells!
 Functional tubular disturbances and  sometimes  acute renal failure
 result.
  The toxic effects  of fluoride in mammals are multiple  and all may
threaten life. Except for the direct effect  on  ionized calcium in extra-
cellular fluid,  the actions of fluoride result from inhibition of critical
intracellular enzymes.

                                37

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  Ingested fluoride has a corrosive effect on the epithelial lining of the
gastrointestinal tract,  due, in part, to highly corrosive hydrofluoric
acid formed in the stomach. Edema, ulceration, and hemorrhage com-
monly result. Thirst, abdominal pain, vomiting, and  diarrhea, with
blood in vomitus and feces usually occur.
  Absorbed  fluoride  ion  reduces extracellular fluid concentrations of
calcium and magnesium. Hypocalcemia sometimes results in tetany.
Hyperkalemia is sometimes a serious threat to the heart.
  Cardiac arrhythmias and shock are often prominent features of poi-
soning. These probably result from combinations  of effects of fluid and
electrolyte disturbances  and direct actions  of fluoride  on heart and
vascular tissues. Hypotension and severe arrhythmias, sometimes pro-
gressing to ventricular fibrillation, characterize severe poisonings.
  Toxic actions on the brain are manifest as headache, muscular weak-
ness,  salivation, nystagmus, dilated pupils, lethargy, stupor and coma.
  Occasionally, convulsions occur. Respiratory failure is usually the
immediate cause of death.

CONFIRMATION OF POISONING

  Plasma inorganic fluoride  concentrations  in  the  general United
States population are  usually less  than 0.02 milligram per liter and
rarely above 0.10 milligram per liter.  In fatal  cases  of poisoning,
plasma levels from 3.5 to 15.5 milligrams per liter have been recorded.

TREATMENT OF FLUORIDE TOXICOSIS

  1.  Contamination  of the skin should be removed by washing with
     soap and water.  Eye contamination should be removed by pro-
     longed flushing of the eye with copious amounts of clean water or
     saline. If irritation  persists, specialized medical treatment should
     be obtained.
  2.  If SODIUM FLUORIDE OR SODIUM FLUOSILICATE has been
      INGESTED, immediate steps must be taken to remove or neutral-
      ize the toxicant.
      A.  If the victim is fully alert, and if vomiting does not totally
         prevent swallowing of  a neutralizing agent, prompt oral ad-
         ministration  of lime water (0.15% calcium  hydroxide), 1%
         calcium chloride solution, calcium- or magnesium-based antac-
         id or aluminum hydroxide  gel (antacid  gel preparation), or
         milk will precipitate the bulk of fluoride ion in the gut and
         therefore may  be lifesaving. The victim should be given as
         much as can be tolerated.
      B. If the victim  is obtunded or if vomiting precludes oral admin-
         istration, the airway should be protected by endotracheal in-
         tubation, then  the  stomach should be'gently intubated and
         lavaged with several ounces of one of the liquids named hi 2A.

                                38

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        above. Activated charcoal does not bind fluoride ion and is
        therefore of no value in fluoride poisoning.
 3.  A blood specimen should be drawn for blood electrolyte analysis:
     sodium, potassium, calcium, magnesium, fluoride, and bicarbonate
     capacity. Another sample  should be drawn to type and cross-
     match for blood transfusion. Intravenous fluids (initially 5% dex-
     trose  in 0.9% saline) should be  started to combat  dehydration,
     shock and metabolic acidosis. Fluid balance should be monitored
     closely to forestall fluid overload if renal failure occurs. If meta-
     bolic acidosis is detected, sodium bicarbonate should be adminis-
     tered  to keep the urine at pH 7.0-7.5. Intravenous fluids must be
     stopped if anuria or oliguria (less than 25-30 ml per hour) devel-
     ops.  If  urine formation  declines, extracorporeal  hemodialysis
     should be used. It removes fluoride efficiently, but no more rapid-
     ly than a normally functioning kidney.
 4.  Monitor cardiac status by continuous electrocardiography. Ven-
     tricular arrhythmias may necessitate DC cardioversion.
 5.  If overt or latent (Chvostek's sign) tetany occurs, or  if hypocalce-
     mia is demonstrated, or if it appears  likely that a significant
     amount of fluoride has been absorbed, administer 10 ml of 10%
     calcium gluconate intravenously, at  no more  than one ml per
     minute., Initial children's  dose is approximately 0.5 ml/kg body
     weight. Repeat in 10-20 minutes if there are still indications of
     hypoealcemia.  Severe poisonings  may require  administration of
     several hundred milliliters of 10% calcium gluconate.
 6.  OXYGEN by mask should be administered for hypotension, shock,
     cardiac arrhythmias, or cyanosis. Shock may require administra-
     tion of plasma or blood.


     SODIUM FLUOALUMINATE (CRYOLITE) is much less toxic
     than other fluorides. If a very large amount has been ingested, it
     may  be appropriate to  measure serum calcium to insure that
     hypoealcemia has not occurred.  If so, intravenous 10% calcium
     gluconate would be indicated (see  5  above). It is unlikely that
     treatment for fluoride toxicity would be necessary following inges-
     tion of sodium fluoaluminate.


                   BORIC ACID AND BORATES

COMMERCIAL PRODUCTS

  Boric acid, sodium tetraborate decahydrate (borax), sodium pentabor-
ate, boron trioxide, sodium biborate.
  Commercial products: Polybor, Pyrobor

                                39

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  Formulated as tablets and powder to kill larvae in livestock confine-
ment  areas  and  cockroaches in  residences.  Rarely,  solutions are
sprayed as a nonselective herbicide.

TOXICOLOGY  AND MANIFESTATIONS  OF POISONING BY
  BORATE

  Borax  dust is moderately irritating  to  skin. Inhaled dust  causes
irritation of the  respiratory tract: cough and shortness of breath.
  There  have been few poisonings from the pesticidal uses of borates,
although powders and pellets scattered on the floors of homes do
present a hazard to children. Most poisonings have resulted from inju-
dicious uses in human medicine aimed at suppressing bacterial growth,
such as compresses for burns. Many poisonings  of newborns  occurred
in the  1950's and 1960's.
  Borates are well absorbed by the gut and by abraded or burned skin,
but not by intact skin. They are efficiently excreted by the kidney. The
residence half-life  in humans averages  13  hours, in a range of 4-28
hours.
  The  gastrointestinal tract, skin,  vascular system,  and brain are the
principal organs and tissues affected. Nausea, persistent vomiting, ab-
dominal pain, and  diarrhea reflect  a toxic gastroenteritis, which occurs
even when the  borate was absorbed across  damaged  skin. Blood in
vomitus  and  feces reflect hemorrhagic lesions in the gut mucosa. In
severe  poisonings of infants, a beefy red skin rash, most often affecting
palms, soles,  buttocks, and scrotum, has been described. It has been
characterized  as a "boiled lobster appearance." The intense erythema
is followed by extensive exfoliation.
  Cyanosis, weak pulse, and cold clammy skin indicate shock, which is
sometimes the cause of death in borate poisoning.
  Headache,   weakness,  lethargy,  restlessness,  and  tremors may
progress  to intermittent seizures. Unconsciousness and respiratory de-
pression signify life-threatening brain injury.
  Acute  renal failure (oliguria or anuria)  may be a consequence of
shock,  of direct  toxic action on  renal tubule cells,  or both. It  occurs
only in severe borate poisoning. Metabolic acidosis  may be  a  conse-
quence of the acid itself, of seizure activity, or of metabolic derange-
ments. Fever is sometimes present in the absence of infection.
  A recent analysis of 784 cases of ACUTE SINGLE-DOSE BORATE
DIGESTION  (excluding newborns and cases of protracted exposure)
has indicated a  much more favorable prognosis  than that which was
based on neonate poisonings in the  1950's and 1960's (50%-70% mortal-
ity). In the recent survey (Litovitz,  T. L. et al. Am. J. Emergency Med.
6(3):209-213,  1988), only  12% of cases  were even symptomatic,  and
there were no fatalities. In those who became symptomatic, gastroin-
testinal symptoms  (vomiting, abdominal pain,- diarrhea) predominated.

                               40

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Central nervous system manifestations and rash were rare and of brief
duration when they did occur.

CONFIRMATION OF POISONING

  Borate can be measured in serum by a colorimetric procedure, using
carminic acid  as a chromogen.  Blood borate concentrations in non-
exposed individuals are in the range of 0.0-7.2 mg per liter (average 1.4
mg per liter). Excluding newborns and chronically exposed individuals,
serum borate concentrations less than 340 mg per liter have rarely
been associated with significant toxicity.
  A paper spot test for borate in the urine may be helpful in identify-
ing urine borate concentrations  greater than 20 mg per liter. Urine
acidified with  hydrochloric acid and applied  to  turmeric paper pro-
duces a brownish-red color if borate is present. A recent evaluation has
warned, however, that a  significant number of false positives may be
encountered when this test is used.
TREATMENT OF BORATE TOXICOSIS

 1.   Dermal contamination should be removed by washing with soap
     and water. Contamination of the eye should be treated by pro-
     longed flushing with copious amounts of saline or water. If irrita-
     tion persists, specialized medical treatment should be obtained.
 2.   The great majority of pesticidal borate poisonings are likely to be
     acute  (single dose) ingestions  and are unlikely to  occur  in  new-
     borns. A recently recommended protocol for management  of acute
     borate ingestion (excluding newborns and chronically exposed per-
     sons) is as follows (from above reference):
      Patient's Weight, kg
     Less than 30 kg
     Greater than 30 kg
   Dose of Borate
Less than 200
  mg/kg
200-400 mg/kg
Greater than 400
  mg/kg

Less than 6.0 gm
6.0-12.0 gm
Greater than 12.0
  gm
  Recommended Management
Observation only
Syrup of Ipecac
Syrup of Ipecac
  lavage

Observation only
Syrup of Ipecac
Syrup of Ipecac
  lavage
                                                          or gastric
                                                          or gastric
     Dosage of Syrup of Ipecac for adults and children over 12 years is
     30 ml; dosage for children under 12 years is 15 ml. Follow Syrup
     of Ipecac with 2-3 glasses  of water. Watch closely for declining
     consciousness level; insure that victim is in a  head down left
     lateral decubitus position when vomiting ocfcurs. Protocol for gas-
     tric lavage is set forth in  Chapter 1, TREATMENT, Section 6,
                                41

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     page 8. Activated charcoal does not adsorb borate and therefore
     should not be given unless an additional toxicant was ingested
     which is charcoal-adsorbable.
     Obtain a blood sample 2-3 hours post-ingestion to assess severity
     of poisoning, but do not base initial therapy on blood concentra-
     tion.

 3.  IF INGESTION of borate has been MASSIVE (several grams), or
     has extended over several days, administer intravenous glucose
     and electrolyte solutions to sustain urinary excretion of borate.
     Monitor fluid balance and blood electrolytes (including bicarbon-
     ate capaciiy) regularly. Monitor cardiac status by EGG. Test the
     urine for protein and cells to detect  renal injury, and monitor
     serum concentration of borate. If metabolic acidosis  is detected,
     sodium bicarbonate should be added to the infused fluids to keep
     urine pH in the 7.0-7.5 range. If shock develops, it may be neces-
     sary to infuse plasma or whole blood. Administer oxygen continu-
     ously. If oliguria (less than 25-30 ml urine  formed per hour)
     occurs, intravenous fluids must be slowed or stopped to avoid
     overloading the circulation.
     A. Both peritoneal dialysis and extracorporeal hemodialysis have
        been used with apparent success in accelerating elimination of
        borate. If renal failure occurs, hemodialysis may be necessary
        to sustain fluid balance and normal extracellular fluid compo-
        sition. In poisoned infants, exchange blood  transfusion has
        been used successfully.
     B. Control convulsions with benzodiazepine drugs or other anti-
        convulsants, if necessary (see Chapter 3, TREATMENT, Sec-
        tion 4, page 21).
                       CHLORDIMEFORM
STRUCTURE
                      =r\         H
                               N=C-N
                                          \
CH,

CH.
COMMERCIAL PRODUCTS

  Bermat, Fundal, Galecron, Ovatoxin.

                                42

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  Formulations are emulsifiable concentrates and water-soluble pow-
ders. Chlordimeform is an ovicide and acaricide.

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  CHLORDIMEFORM

  In a  reported episode of occupational  exposure  to chlordimeform,
several  workers developed hematuria.  Hemorrhagic cystitis, probably
due  to  chloraniline biodegradation  products, was the source of the
blood in the urine. Symptoms reported by the affected workers were:
gross blood in the urine, painful urination, urinary frequency and
urgency, penile discharge, abdominal  and back pain, a generalized
"hot" sensation, sleepiness, skin rash and  desquamation, a sweet taste,
and  anorexia. Symptoms  persisted for 2-8 weeks after exposure was
terminated.
  Chlordimeform is not a cholinesterase inhibitor. Although methods
do exist for measurement of urinary excretion products, these tests are
not generally available.

TREATMENT OF CHLORDIMEFORM TOXICOSIS

  Strenuous efforts should be made to protect against inhalation and
dermal  contact with  chlordimeform because absorption is evidently
efficient. Skin  contamination should be  washed off with soap and
water. Contamination  of the eye should be treated  by flushing with
copious  amounts of clean water or saline. If irritation persists, special-
ized medical treatment should be obtained.
  If chlordimeform has been ingested no more than several hours prior
to treatment,  and if the  patient is  fully alert, administer Syrup of
Ipecac,  followed by several glasses of water, to  empty the stomach.
Dosage  for adults  and children over 12 years: 30 ml; dosage for chil-
dren under 12 years: 15 ml.
  If the patient is obtunded, the operation of a different or additional
toxicant should  be suspected. In this  event, the stomach should be
emptied by intubation, aspiration and lavage with a slurry of activated
charcoal in water or saline, after measures have been taken to protect
the respiratory tract from aspiration of gastric contents (see Chapter 1,
TREATMENT, Section 6, p. 8).
  After  the stomach has  been emptied, activated charcoal and a ca-
thartic should be administered (see above reference). Repeated doses of
charcoal every 2-4 hours may be beneficial. Because  catharsis may
cause serious dehydration and electrolyte disturbances in young chil-
dren, fluid balance and serum electrolytes should be monitored. An
adequate state of hydration should be maintained by oral and/or intra-
venous fluids to support chlordimeform  excretion.
  Repeated analyses of urine for protein and red cells should be donfex.
to detect injury to the urinary tract. Disappearance of hematuria can-'

                                43

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ordinarily be expected in 2-8 weeks. Relief from other symptoms can
usually be expected earlier.
                        PROPARGITE
STRUCTURE
                           H   H               H
      -c-(\    /o-c-c-o-s-o-c-G=c H
                                  CH-
                                                H
             \\   //

        CH3        H2CX

                        H2C-

COMMERCIAL PRODUCTS

  Omite, Comite, Uniroyal D014.
  Formulations are wettable powders and emulsifiable concentrates.
Propargite is an acaricide with residual action.

TOXICOLOGY AND ADVERSE EFFECTS OF PROPARGITE

  Propargite exhibits very little systemic toxicity in animals. No sys-
temic poisonings have been reported in humans. However, many work-
ers having dermal contact with this acaricide have experienced skin
irritation and possibly sensitization in some  cases. Eye irritation has
also occurred. For this reason, stringent measures should be taken to
prevent inhalation or any skin or eye contamination by propargite.
  There is no readily  available method for detecting absorption of
propargite.

TREATMENT OF PROPARGITE  TOXICOSIS

  Skin contamination should be removed by prompt washing with soap
and water. Eye contamination should be treated by flushing with copi-
ous amounts of clean water or saline. If irritation persists, specialized
medical treatment should be obtained. Sensitization reactions may re-
quire steroid therapy.
  If  large amounts of propargite  have been ingested, and effective
vomiting has not occurred, and if  there are no indications of nervous
system depression, administration  of Syrup of Ipecac, followed by sev-
eral glasses of water, is probably the appropriate method to empty the
stomach. Dosage for adults and children over 12 years: 30 ml;  dosage
for children under 12 years: 15 ml.
  If there  are indications of central nervous system depression, empty
the stomach by intubation,  aspiration,  and lavage-with a slurry of

                             44

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 activated charcoal, having first taken precautions to prevent aspiration
 of stomach contents (see Chapter  1, TREATMENT, Section 6, p. 8).
 Follow the lavage with instillation of activated  charcoal (see above
 reference). Include sorbitol in the charcoal instillation if diarrhea has
 not already commenced.
  If the amount of  propargite ingested was small, or if treatment is
 delayed, oral administration of activated charcoal and sorbitol probably
 represents optimal management.


                        DIFLUBENZURON

 COMMERCIAL PRODUCTS

  Dimilin, Micromite.
  This is a haloaromatic substituted urea which controls insects by
 impairing chitin deposition in the larval exoskeleton. It  is formulated
 in wettable powders, oil dispersible concentrate, and granules for use
 in agriculture and forestry and in settings where fly populations tend
 to be large, such as feedlots.

 TOXICOLOGY OF  DIFLUBENZURON

  There  is limited absorption across the skin and intestinal lining of
 mammals, after  which  enzymatic  hydrolysis  and excretion rapidly
 eliminate the pesticide from tissues. Irritant effects are not reported
 and systemic toxicity is low. Methemoglobinemia is a theoretical risk
 from chloroaniline formed hydrolytically, but no reports of this form of
 toxicity have been reported in humans or animals from diflubenzuron
 exposure.
  Treatment of contamination and ingestions should proceed essential-
 ly as outlined in the  previous section (Propargite).


                        TEFLUBENZURON

 COMMERCIAL PRODUCTS

  Nomolt, Dart, Diaract.
  This is another haloaromatic substituted urea insecticide, apparently
similar in toxicologic properties to diflubenzuron (above). Low systemic
toxicity is reported.
                                45

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                      CHLOROBENZILATE
STRUCTURE
                           0=C-OC2H5
COMMERCIAL PRODUCTS

  Acaraben, Akar, Folbex, Benzilan.
  Chlorobenzilate is a chlorinated hydrocarbon acaricide, usually for-
mulated as an emulsion or wettable powder for application in orchards.
It is presently a Restricted  Use Pesticide because of neoplastic effects
observed in laboratory animals subjected to high dosage over long
periods.

TOXICOLOGY OF CHLOROBENZILATE

  Chlorobenzilate is moderately irritating to the skin and eyes.
  Although structurally similar to DDT, chlorobenzilate is much more
rapidly excreted following absorption, chiefly in the urine as the benzo-
phenone and benzoic  acid derivatives.  No  systemic  poisonings  of
humans have been reported.  Based on observation of dosed animals,
extreme absorbed doses may cause tremors, ataxia, and muscle weak-
ness.
  Chlorobenzilate is not a cholinesterase inhibitor.

TREATMENT OF CHLOROBENZILATE EXPOSURE

  Remove  skin  contamination  by washing  with  soap and water.
Remove eye contamination by flushing with clean  saline or water. If
irritation persists, medical attention must be obtained.
  If a large amount of chlorobenzilate was ingested within a few hours
prior to treatment, and if there are no indications of central nervous
system disturbance, empty the stomach by  administering  Syrup  of
Ipecac followed  by several glasses of  water. Dosage  for adults and
children over 12 years: 30  ml; dosage for children under 12 years:  15
ml.
  After vomiting  stops,  administer activated charcoal and sorbitol
orally  (for dosage, see Chapter 1, TREATMENT, Section 6, p. 8).
  If there  are indications of central nervous system disturbance (de-
pression, ataxia, tremor), empty the stomach by intubation, aspiration,

                               46

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 and lavage, after first taking all precautions to protect the respiratory
 tract from aspiration of gastric contents (see Chapter 1, TREATMENT,
 Section 6, p. 8). Lavage the stomach with a slurry of activated charcoal!
 Leave  charcoal and  an appropriate dose of sorbitol in the  stomach
 before withdrawing the lavage tube.
   If the  absorbed dose of chlorobenzilate was small, if treatment is
 delayed,  and if the patient is asymptomatic, oral administration of
 activated charcoal and sorbitol is probably the optimal management
 (see Chapter 1, TREATMENT, Section 6, p. 8 for dosage). Do  not give
 fats or oils.
                           CYHEXATIN
 STRUCTURE
                                 Sn-OH
COMMERCIAL PRODUCT

  Plictran.
TOXICOLOGY OF CYHEXATIN AND TREATMENT OF TOXICOSIS

  Tricyclohexyl tin hydroxide is formulated as a 50% wettable powder
for control of mites on ornamentals, hops,  nut trees and some fruit
trees. It is moderately irritating, particularly to the eyes. While infor-
mation on the systemic toxicity of this specific tin compound is lacking,
it should probably be assumed that cyhexatin can be absorbed to some
extent across the skin, and that substantial absorbed doses would cause
nervous system injury (see Organotin compounds in Chapter 12: FUN-
GICIDES). Accordingly, dermal contamination should be promptly re-
moved by washing with soap and water, and contamination of the eyes

                               47

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should be treated by prolonged flushing with clean water or saline.
Management of poisonings by ingestion should proceed on the assump-
tion that cyhexatin is highly toxic, even though rodent LD50 values are
fairly high, and no human poisonings have been reported. See Chapter
1, TREATMENT, Section 6, p. 8 concerning measures to limit toxicant
absorption  from the gut.  Neither BAL, penicillamine nor  chelating
agents have been effective in lowering tissue stores  of  organic tin
compounds in experimental animals.

                         METHOPRENE

COMMERCIAL PRODUCTS

  ZR-515, Altosid SR-10 and CP-10,  Apex 5E, Diacon, Dianex, Kabat,
Minex, Pharorid, Precor.
  Methoprene is a long chain hydrocarbon ester active  as  an insect
growth regulator. It is effective against several insect species. Formula-
tions include slow-release briquets, sprays, foggers and baits.

TOXICOLOGY OF METHOPRENE

  Methoprene is neither an irritant nor a  sensitizer in humans or
laboratory  animals.
  Systemic toxicity in laboratory animals is very low. No human poi-
sonings or adverse reactions in exposed workers have been reported.

TREATMENT OF METHOPRENE  TOXICOSIS

  Wash contaminated skin with soap and water. Flush contamination
from eyes  with copious amounts of  clean water or saline. If irritation
persists, medical attention must be obtained.
  If a very large amount of methoprene has been ingested, oral admin-
istration of charcoal may be considered. The hazards of catharsis (dehy-
dration,  electrolyte disturbances) probably outweigh  the hazards of
methoprene.

                             SULFUR
                              s=s
 COMMERCIAL PRODUCTS

   Brimstone, Lacco Sulfur, Clifton Sulfur, Sul-Cide, Cosan, Kumulus S,
 Sofril,  Sulfex. Thiolux,  Thiovit, Magnetic  6, Liquid Sulfur,  Thion,
 Zolvis, Golden Dew.

                                48

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   Elemental sulfur is an acaricide and fungicide widely used on or-
 chard, ornamental, vegetable, grain and other crops. It is prepared as
 dust in various particle sizes and applied as such, or it is formulated
 with various minerals to improve flowability, or is applied as an aque-
 ous emulsion of wettable powder.

 TOXICOLOGY OF SULFUR

   Elemental sulfur is moderately irritating to the skin, and airborne
 dust is irritating to the eyes and the respiratory tract. In hot sunny
 environments, there may be some oxidation of foliage-deposited sulfur
 to irritating gaseous sulfur oxides, which are very irritating to the eyes
 and respiratory tract.
   Ingested sulfur powder induces catharsis, and has been used medici-
 nally (usually with molasses) for that purpose. Some  hydrogen sulfide
 is formed in the large intestine and this may present a degree of toxic
 hazard. However, an adult has survived ingestion of 60 grams.
   Ingested colloidal sulfur is efficiently absorbed by the gut and is
 promptly excreted in the urine as inorganic sulfate.

 TREATMENT OF SULFUR  TOXICOSIS

   Skin contamination should be removed by washing with soap and
 water. Contamination of the eyes should be removed by prolonged
 flushing with clean saline or water.  If irritation persists,  medical atten-
 tion should be obtained.
   Unless an extraordinary amount  of sulfur (several grams) has been
 ingested shortly prior to treatment, there is  probably no need  for
 emptying of the stomach  or administration of a cathartic. Adsorbabil-
 ity of sulfur on activated charcoal has not been tested.
  The most  serious  consequence  of sulfur ingestion is likely to be that
 of catharsis: dehydration and electrolyte depletion, particularly in chil-
 dren. If diarrhea is severe, oral  or  intravenous administration of glu-
 cose and/or electrolyte solutions may be appropriate.
                  DIETHYLTOLUAMIDE (DEBT)
STRUCTURE
                             C-N
/C2H5

\
                               49

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COMMERCIAL PRODUCTS

  Detamide, Metadelphene, MGK, OFF.
  This chemical is a widely used  liquid insect repellent, suitable for
application to skin or to fabrics. It is formulated with ethyl or isopro-
pyl alcohol, usually in pressurized containers.

TOXICOLOGY OF DEBT

  For many years, diethyltoluamide has been effective and generally
well tolerated as an insect repellent applied to human skin, although
tingling, mild irritation, and  sometimes desquamation have followed
repeated application. In some cases, DEBT has caused contact dermati-
tis  and excerbation of preexisting skin disease. It is very irritating to
the eyes, but not corrosive.
  Serious adverse effects have occurred when used under tropical con-
ditions, when it was applied to areas of skin that were occluded during
sleep (mainly the antecubital and  popliteal fossae). Under these condi-
tions, the skin became red and tender, then exhibited blistering and
erosion, leaving painful weeping denuded areas that were slow to heal.
Permanent scarring resulted from most of these severe reactions.
  DEET is efficiently  absorbed across the skin and by the gut. Blood
concentrations of about 3  mg per  liter have been  reported  several
hours after dermal application in the prescribed fashion. Toxic ence-
phalopathic reactions  have apparently  occurred in rare instances fol-
lowing dermal application, mainly in children who  were intensively
treated. The more frequent cause of systemic toxicity has been inges-
tion, deliberate in adults, accidental in young children.
  Manifestations of toxic encephalopathy have been behavioral disor-
ders including headache, restlessness, crying spells, mania, stupor pro-
gressing to  coma, ataxia, hyperreflexia, tachypnea, hypotension, trem-
ors, and writhing convulsions (athetosis). Some cases have shown flac-
cid paralysis and areflexia. Deaths have occurred following very large
doses. Blood levels of DEET  found  in  fatal systemic poisonings have
ranged from 168 to 240 milligrams per liter. Interpretation of DEET
toxicity in some fatal cases has been complicated by effects of simulta-
neously ingested ethanol, tranquilizers, and other drugs. One well doc-
umented case of anaphylactic reaction to DEET has been reported. One
fatal case of  encephalopathy in a  child heterozygous for ornithine
carbamoyl transferase deficiency resembled Reyes syndrome,  but the
postmortem appearance of the liver  was not characteristic of the syn-
 drome.
   Discretion should be exercised  in  recommending DEET for persons
 who have acne, psoriasis, an atopic predisposition, or other chronic
 skin condition. It should not be applied to any skin area that is likely
 to be opposed to another skin surface  for a significant  period of time
 (antecubital and popliteal fossae, inguinal areas).

                                 50

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   Great caution should be exercised in using DEBT on children. Only
 the products containing the lower concentrations (usually 15%) should
 be used,  and application should be limited to exposed areas of skin,
 using as  little repellent as possible. If continuous repellent protection
 is necessary, DEET should be alternated with a repellent having an-
 other active ingredient. If headache or any kind of emotional or behav-
 ioral change occurs, use of DEET should be discontinued immediately.

 CONFIRMATION OF DIETHYLTOLUAMIDE POISONING

   Methods exist for measurement of DEET in blood and tissues and of
 metabolites in urine, but these are not widely available.

 TREATMENT  OF DEET TOXICOSIS

   If a skin reaction occurs,  residual DEET should be removed by
 washing the treated area with soap and water.  Eye contamination
 should be treated by prolonged flushing with clean saline or water. K
 irritation persists, medical treatment should be obtained.
   Steroid or. antimicrobial topical medications may be indicated  for
 severe skin reactions  that occasionally  follow application  of DEET.
   If a substantial amount of DEET has been INGESTED within a few
 hours  of treatment, the stomach should be intubated, aspirated, and
 lavaged with a slurry of activated charcoal, after every precaution has
 been taken to protect  the airway from  aspiration of gastric contents
 (see  Chapter 1, TREATMENT, Section 6, p. 8). A slurry of charcoal,
 including an appropriate dose of sorbitol, should be left in the stomach
 before the tube is withdrawn (see above reference for  dosage). If a very
 large amount of DEET was swallowed, repeated doses  of charcoal every
 2-4 hours may be beneficial.
  If dosage ingested was assuredly small, and the patient is fully alert,
 oral administration of activated charcoal and sorbitol probably repre-
 sents optimal management. If diarrhea has already commenced, the
 sorbitol should be omitted.
  Intravenous electrolytes, plasma and/or whole blood may be  needed
 to combat shock in severe poisonings. Administer oxygen continuously
 by mask if respiratory or circulatory embarrassment  is evident. Adre-
 nergic amines may be indicated.
  If convulsive  activity develops, benzodiazepine or other anticonvul-
sants may be required (see Chapter 3, TREATMENT,  Section 4, p. 21).
  Persons surviving poisoning  by  ingestion of DEET  have usually re-
covered in 2 to 24 hours.
                               51

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                    ALKYL PHTHALATES
STRUCTURE
                        O
                         II
                      -C-O-CH.

                      -C-0-CH.
                         II
                         0
                        DIMETHYL PHTHALATE

COMMERCIAL PRODUCT

  BMP.
  Dimethyl phthalate  has been widely used  as an insect repellent
applied directly to the skin.  Dibutylphthalate is impregnated into
fabric for the same purpose. It is more resistant to laundering than
dimethyl phthalate.

TOXICOLOGY OF ALKYL PHTHALATES

  Dimethyl phthalate  is strongly irritating to the eyes and mucous
membranes. It has caused little or no irritation when applied to skin,
and dermal absorption is apparently minimal. It has not caused sensi-
tization.
  Tests in rodents have indicated low systemic toxicity, but large in-
gested doses cause gastrointestinal irritation, central nervous system
depression (to  coma), and hypotension. One accidental ingestion by a
human resulted in coma, but recovery was prompt.

TREATMENT OF ALKYL PHTHALATE TOXICOSIS

  No antidote is available. Supportive measures (hydration, oxygen if
needed) are probably  adequate  to manage all but the most  severe
poisonings.
                               52

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                       BENZYL BENZOATE
 STRUCTURE
 TOXICOLOGY, MANIFESTATIONS, AND TREATMENT

  Incorporated into lotions and ointments, this agent has been used for
 many years in veterinary and human medicine against mites and lice.
 Apart  from occasional cases of skin irritation,  adverse  effects have
 been few. The efficiency  of skin absorption is not known. Absorbed
 benzyl benzoate is  rapidly biotransformed to hippuric acid  which is
 excreted in the urine. When given in large doses to laboratory animals,
 benzyl benzoate causes excitement,  incoordination, paralysis  of the
 limbs, convulsions, respiratory paralysis, and death. No human poison-
 ings have been reported.  If significant irritant effect appears, medica-
 tion should be discontinued and the skin cleansed  with soap and water.
 Eye contamination should be treated by prolonged flushing with clean
 water or saline. If a potentially toxic  amount has been swallowed and
 retained, steps should be  taken to remove it  from the gastrointestinal
 tract and repeated doses of activated  charcoal should be administered
(see Chapter 1, TREATMENT, Section 6, p. 8). If seizures occur, control
may require anticonvulsant medication  (see Chapter 3, TREATMENT
Section 4, p. 21).                                                '
                              53

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                      CHAPTER  6

        ARSENICAL  PESTICIDES
INORGANIC TRIVALENT

     Arsenic Trioxide

         /°\
       As— O-As
                 "White arsenic," arsenous oxide. The active
                 ingredient in some ant pastes and veterinary
                 preparations.
     Sodium arsenite

      Na-O-As=O


     Calcium arsenite
       O-As=O
        I
       Ca
        I
       O-As=O
(approx.)
                 Chem Pels C. Chem-Sen 56, Kill-All, Penite,
                 Prodalumnol Double.  Used in aqueous
                 solution for weed control; limited use as
                 insecticide.
                 Mono-calcium arsenite.  Flowable powder
                 for insecticidal use on fruit.
     Copper arsenite
   (Acid copper arsenite)

   HO-Cu-O-As=O


   Copper acetoarsenite

            O
    Cu-(O-C-CH3)2
    •
   3Cu—(O—As=O)2

         Arsine

         H   H
           \  /
            As
            I
            H
                 Wettable  powder, for use as  insecticide,
                 wood preservative.
                 Insecticide.   Paris  Green, Schweinfurt
                 green, emerald green, .French green, mitis
                 green.  No longer used in U.S.; still used
                 outside U.S.
                  Not a pesticide. Occasionally generated
                  during manufacture of arsenicals.
                                54

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 INORGANIC PENTAVALENT
           Arsenic acid
               OH
           HO.   I
              >iS=0
           HO
 Dessicant L-10, Hi-Yield Dessicant H-10,
 Zotox. Water solutions used as defoliants,
 herbicides.
        Sodium arsenate
               OH
         NaO.  ||
              ^AS = 0
         NaO
Disodium arsenate.  Jones Ant Killer, Terro
Ant Killer.
        Calcium arsenate
Ca    As-O-Ca-O-As     Ca
   V                  V
                                      Tricalcium arsenate. Pencal, Spra-cal, Turf-
                                      Cal.  Flow/able powder formulations used
                                      against weeds, grubs.
          Lead arsenate

                 OH
             xOv  I
          Pb   NAs = O
Gypsine, Soprabel, Talbot.  Limited use in
U.S.; wettable powder used as insecticide
outside the U.S.
          Zinc arsenate
Zn   As-O— Zn-O-As
                                      Powder one used in U.S. as insecticide on
                                      potatoes and tomatoes.
                                    55

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ORGANIC (PENTAVALENT)


        Cacodylic acid
      (sodium cacodylate)

        CH3     CH3
            \   /
             As
O
                 OH
                  (or Na)
                          Non-selective herbicide, defoliant, silvicide.
                          Bolate,  Bolls-Eye,  Bophy,  Dilie,  Kack,
                          Phytar 560, Rad-E-Cate 25, Salvo.
      Methane arsonic acid

         CH3    OH
             \   /
              As
             •#•   ^
           O    OH

 Monosodium methane arsonate

         CH3     OH
              \  /
                                    MAA. Non-selective herbicide.
   Disodium methane arsonate

          CHs    ONa

             >'
             
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             SOLID ARSENIC COMPOUNDS

 TOXICOLOGY OF ARSENIC

   Arsenic is  a natural element having  both metal  and nonmetal
 physical/chemical properties. In one respect or another,  it resembles
 nitrogen, phosphorus, .antimony, and bismuth in its chemical behavior.
 In nature, it exists in elemental, trivalent (—3 or +3), and pentavalent
 (+5) states. It binds covalently with most nonmetals (notably oxygen
 and sulfur) and with metals (for example,  calcium and lead). It forms
 stable trivalent and pentavalent organic  compounds. In biochemical
 behavior, it resembles  phosphorus, competing with phosphorus analogs
 for chemical binding sites. Toxicity  of the various arsenic compounds
 in mammals extends over a wide range, determined, in part, by unique
 biochemical actions  of each compound, but also by absorbability and
 efficiency of biotransformation and disposition. Overall, arsines present
 the greatest toxic hazard, followed closely by arsenites (inorganic triva-
 lent compounds). Inorganic  pentavalent compounds are somewhat less
 toxic that arsenites, while the organic (methylated) pentavalent com-
 pounds incur the least hazard of the arsenicals that are used as pesti-
 cides.
  The pentavalent arsenicals are relatively water soluble and absorb-
 able  across mucous membranes while  trivalent  arsenicals, having
 greater lipid solubility,  are more readily absorbed across the skin.
 However, poisonings by dermal absorption of either  form have been
 extremely rare. Ingestion has been  the usual basis of poisoning; gut
 absorption efficiency depends on the physical form of the compound, its
 solubility characteristics, the gastric  pH, gastrointestinal motility, and
 gut microbial transformations.  Once absorbed,  many  arsenicals  cause
 toxic injury to cells of  the nervous system,  blood vessels, liver, kidney,
 and  other tissues.  Two biochemical mechanisms of toxicity are recog-
 nized:  1) reversible combination with thiol groups contained in tissue
 proteins and enzymes, and 2) substitution  of arsenic anions for phos-
 phate in many reactions, including those critical to oxidative phosphor-
 ylation. Because there  are many uncertainties regarding the biotrans-
formation of various  arsenicals in the gut and in the body,  and because
 the toxic potentials  of the biotransformation  products are not well
 established, it is generally safest to manage cases of arsenic ingestion
as though all forms of arsenic are highly toxic.
  Mammals, including  humans, detoxify inorganic arsenic  by methyla-
tion, yielding cacodylic acid  (dimethylarsinic acid) as the chief urinary
excretion product.  Disposition by  urinary excretion is  usually prompt.
Elimination of the arsonic acid  (monomethyl) compounds has not been
extensively studied, but urinary excretion of the  unaltered compound
and/or a further methylated form would seem likely.
  The unique toxicology of arsine gas is described later in this chapter.

                                57

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SYMPTOMS AND SIGNS OF POISONING BY SOLID
  ARSENICALS

  Manifestations  of  acute poisoning (large amount absorbed over a
short time) are distinguishable from those of chronic poisoning (lesser
doses absorbed over a longer tune interval).
  The symptoms and signs of ACUTE ARSENIC POISONING usually
appear within one hour after ingestion, but may be delayed several
hours. GARLIC ODOR of the breath and  feces may help to  identify
the responsible toxicant in a severely poisoned patient. Gastrointesti-
nal effects include inflammation of the mouth, pharynx,  and esopha-
gus, burning abdominal pain, thirst, vomiting, and rice-water or bloody
diarrhea. These effects result from the action of an arsenical  metabo-
lite on blood vessels  generally, but the splanchnic vasculature particu-
larly, causing dilation and increased capillary permeability.
  Renal injury is manifest as proteinuria, hematuria, glycosuria, oligu-
ria, casts in the urine, and, in severe poisoning, acute tubular necrosis.
Central nervous  system  effects include headache, dizziness, muscle
weakness and spasms, hypothermia, lethargy, delirium, coma, and con-
vulsions. Cardiovascular manifestations  include shock, cyanosis, and
cardiac arrhythmias, which are  due to direct toxic  action and electro-
lyte disturbances. Liver damage may lead to increased concentrations
of circulating hepatocellular enzymes and to jaundice. Injury to blood-
forming tissues may cause anemia, leukopenia, and thrombocytopenia.
Death usually occurs one to three days following symptom onset and is
usually the result of circulatory failure.
  CHRONIC ARSENIC POISONING from repeated absorption of toxic
amounts generally has an insidious onset of clinical effects and may be
difficult to diagnose. Dermal manifestations are usually  more promi-
nent than the gastrointestinal effects which characterize acute poison-
ing: hyperkeratosis, hyperpigmentation, exfoliative dermatitis, subcuta-
neous edema of the face, eyelids and ankles, white striations across the
nails (Mees lines), and sometimes loss of nails or hair. Stomatitis,
anorexia, and weight loss are typical. Peripheral neuropathy (paresthe-
sia, pain,  anesthesia,  paresis,  ataxia) may  be a  prominent feature.
Liver injury reflected in  hepatomegaly and jaundice may progress to
cirrhosis, portal  hypertension, and ascites. Nephropathy is indicated
principally by proteinuria. Electrocardiographic abnormalities and pe-
ripheral vascular disease  have been reported. Anemia, leukopenia, and
thrombocytopenia are characteristic.  Late  sequelae of protracted high
intakes of arsenic include skin cancer, an increased risk of lung cancer,
and,  rarely,  encephalopathy   (ophthalmoplegia,  chronic  headache,
speech and mental disturbances).
                                 58

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 CONFIRMATION OF POISONING BY ARSENICALS

   Measurement of 24-hour urinary excretion of arsenic (micrograms
 per day) is probably the  best way to confirm excessive absorption,
 although methods for blood arsenic concentration are available (see
 below). Persons on non-seafood diets usually excrete less than 20 micro-
 grams (meg) per day, but diets rich in seafood may generate as much
 as 200 meg per day and sometimes more.  (The arsenic in seafood is
 apparently bound  firmly to betaine, which  renders the arsenic essen-
 tially nontoxic and highly excretable.) Arsenic excretion above 100 meg
 per day should be viewed with suspicion and the test should be repeat-
 ed.  Excretions above 200 meg  per day reflect a toxic intake, unless
 seafood was ingested.
   In acute  poisonings that require  a prompt indication as to whether
 recent arsenic intake has been far in excess of normal, two qualitative
 tests of urine are generally available, both sensitive to concentrations
 of about 2000 meg per liter of urine:
     Gutzeit test: To 5 ml of urine, add a few drops of concentrated
     sulfuric acid and a few granules of elemental zinc. Cover the top
     of the  tube with a piece of filter paper to which a drop or two of
     1% silver nitrate solution  has been added. Browning or blacken-
     ing of the paper indicates  that arsine has been evolved from the
     urine.
     Reinsch  test:  Concentrate 10  ml of urine to  1  ml by  boiling.
     Prepare a  piece of copper foil or wire by cleaning the surface,
     then treating it with concentrated  nitric acid, then washing it
     with distilled  water. Put the copper in a flask with the concen-
     trated  urine sample and acidify with about 0.1 ml concentrated
     hydrochloric acid. Boil for 15 minutes. A dull black stain probably
     indicates arsenic. Bismuth, mercury, and antimony cause some-
     what different discolorations  of the copper. If this occurs, analysis
     for arsenic specifically must be carried out.
  Lower concentrations  of arsenic  in blood, urine, or  other biologic
materials can be measured by either wet or dry ashing, followed by
colorimetric or atomic absorption spectrometric analysis. (Baselt, R.C.
Biological Monitoring Methods  for Industrial Chemicals, Biomedical
Publications, 1980.) Blood concentrations in excess  of about 100 meg
per liter probably indicate excessive intake, if seafood was not ingested
before the sample was taken.
  Special tests for arsine toxicosis are described below under "Arsine
Gas."

TREATMENT OF ARSENIC COMPOUND TOXICOSIS

  The  following  discussion applies principally to poisonings by arseni-
cals  that are in solid or dissolved  form.  Treatment of poisoning by

                                59

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2.
8.
arsine gas requires special measures that are described later in this
chapter under "Arsine Gas."
 1.   Wash  arsenical pesticide  from skin  and  hair with  copious
     amounts of soap and water.
     Flush contaminant from eyes with clean water. If irritation per-
     sists, specialized medical treatment should be obtained.
     If arsenical  pesticide has been ingested  within  a few hours of
     treatment, empty the stomach  by INTUBATION, ASPIRATION,
     and LAVAGE,  taking all precautions to  protect the respiratory
     tract from aspiration of vomitus. The effectiveness of gastric evac-
     uation diminishes rapidly with the passage of tune. The procedure
     for evacuation of the stomach is described in Chapter 1,  TREAT-
     MENT, Section 6, p. 8.
     Leave activated charcoal in the  stomach, as indicated in the above
     reference. Repeated administration of charcoal at half  or more
     the original dose every 2-4 hours may be beneficial.
     Because poisoning by ingested arsenic  almost always results in
     profuse diarrhea, it is generally NOT appropriate to ADMINIS-
     TER a CATHARTIC.
     If treatment has been delayed, and  if  the victim remains fully
     alert, administer activated charcoal orally at dosages suggested in
     Chapter 1, TREATMENT, Section 6. Repeat every 2-4 hours.
     Administer INTRAVENOUS FLUIDS to restore  adequate hydra-
     tion, support urine flow,  and correct electrolyte imbalances. Moni-
     tor intake/output continuously to guard against  fluid overload if
     acute renal failure occurs.  Monitor blood electrolytes regularly.
     Blood transfusions and oxygen by mask may be needed to combat
     shock.
     Monitor cardiac status  by EGG to  detect arrhythmias and toxic
     myocardiopathy (T wave inversion, long S-T interval).
     Administration of DIMERCAPROL (BAL) is usually indicated in
     symptomatic arsenic poisonings. The following  dosage  schedule
     has proven to be effective in accelerating arsenic excretion.
 4.
 5.
 6.
 7.
 8.
 9.
Recommended Intramuscular Dosage of BAL (DImercaprol) in Arsenic
                            Poisoning
       1st day
       2nd day
       3rd day
       Each of the following
       days for 10 days,
       or until recovery
                              Severe Poisoning
                           3.0 mg/kg q4h
                           (6 injections)
                           3.0 mg/kg q4h
                           (6 injections)
                           3.0 mg/kg q6h
                           (4 injections)
                           3.0 mg/kg q12h
                           (2 injections)
    Mild Poisoning
2.5 mg/kg q6h
(4 injections)
2.5 mg/kg q6h
(4 injections)
2.5 mg/kg q12h
(2 injections)
2.5 mg/kg qd
(1 injection)
  BAL is provided as a 100 mg/ml solution in oil. Dosages-in Jhe table are in terms of BAL
itself, not of the solution.
                                60

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     CAUTION: Disagreeable side effects often accompany the use of
     BAL: nausea, headache, burning and tingling sensations, sweat-
     ing, pain in the back and abdomen, tremor, restlessness, tachycar-
     dia, hypertension, and fever. Coma and convulsions occur at very
     high dosage. Sterile abscesses may form at injection sites. Acute
     symptoms usually subside  in 30-90 minutes. Antihistamine drugs
     or an oral dose of 25-50 mg ephedrine sulfate provide relief. These
     are more effective  if given a few minutes before the injection of
     BAL.
10.  After the gastrointestinal  tract is reasonably free of arsenic (as
     indicated by passage of a charcoal-black stool), oral administra-
     tion  of D-PENICILLAMINE should probably replace BAL ther-
     apy in persons who are not allergic to penicillin.
     Dosage of D-PENICILLAMINE:
         Adults and children over 12 years:  0.5 gm  every 6 hours,
         given 30-60 minutes before meals and at bedtime for  about 5
         days.
         Children under 12 years: 0.1 gm/kg body weight, not exceed-
         ing 1.0 gm per day, divided into 4 doses, given 30-60 minutes
         before meals and at bedtime for about 5 days.
     CAUTION: Adverse  reactions  to short term therapy are rare.
     Persons allergic to penicillin  may suffer allergic  reactions  to
     D-penicillamine; they should be treated with BAL only.
11.  Extracorporeal hemodialysis, used in combination with BAL ther-
     apy, has limited effectiveness in removing arsenic from the blood.
     Hemodialysis is clearly indicated to enhance arsenic elimination
     and maintain extracellular fluid composition if acute renal failure
     occurs.
12.  MONITOR URINARY  ARSENIC EXCRETION while BAL or
     D-penicillamine are being  administered. When 24-hour excretion
     falls below 50 meg  per day, it is  usually advisable to discontinue
     the chelation therapy.


                          ARSINE GAS

  Arsine is not used as a pesticide. However, some poisonings by arsine
have occurred in pesticide manufacturing plants and  metal  refining
operations  when arsenicals came into contact with mineral acids or
strong reducing agents.

TOXICOLOGY AND MANIFESTATIONS OF  POISONING BY
  ARSINE

  Arsine is a powerful HEMOLYSIN, a toxic action not exhibited by
other arsenicals. In some individuals, very little inhalation exposure is
required to cause a serious hemolytic reaction.  Symptoms of poisoning
usually  appear 1-24 hours after exposure: headache, malaise, weak-

                               61

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ness, dizziness, dyspnea,  nausea, ABDOMINAL PAIN, and vomiting.
Dark red urine (HEMOGLOBINURIA) is often passed 4-6 hours after
exposure. Usually 1-2 days after hemoglobinuria appears, JAUNDICE
is  evident.  Hemolytic anemia, sometimes profound,  usually provides
diagnostic confirmation and  can cause severe  weakness. Abdominal
tenderness  and liver enlargement are often apparent. Basophilic stip-
pling of red cells, red cell fragments, and ghosts are seen in the blood
smear. Methemoglobinemia and  methemoglobinuria are evident. Ele-
vated concentrations of arsenic are found in the urine, but these are
not nearly as high  as are  found in poisonings  by solid arsenicals.
Plasma content of unconjugated bilirubin is elevated.
  Renal failure due to direct toxic action of arsine and to products of
hemolysis represents the chief threat to life in arsine poisoning.
  Polyneuropathy and a mild psycho-organic syndrome  are reported to
have followed arsine intoxication after a latency of 1-6 months.

TREATMENT OF ARSINE  TOXICOSIS

 1. Remove the victim to fresh air.
 2. Administer INTRAVENOUS FLUIDS to keep the urine as dilute
    as possible and to support  excretion of arsenic and products of
    hemolysis. Include sufficient sodium bicarbonate to keep the urine
    alkaline (pH greater than 7.5).
    CAUTION: Monitor  fluid balance carefully to avoid fluid overload
    if renal failure supervenes.  Monitor plasma electrolytes to detect
    disturbances (particularly hyperkalemia) as early as possible.
 3. Monitor urinary arsenic excretion to assess severity of poisoning.
    The amount of arsine that must be absorbed to cause poisoning is
    small,  and therefore  high levels of urinary arsenic excretion
    should not be expected, even in severe poisoning.
 4. If poisoning is severe, EXCHANGE BLOOD TRANSFUSION may
    be considered. It was successful in rescuing one  adult victim of
     arsine poisoning.
 5.  Extracorporeal  HEMODIALYSIS may be  necessary to maintain
     normal extracellular fluid  composition  and to enhance  arsenic
     elimination if renal failure occurs, but it is not very effective in
     removing the arsine carried in the blood.
 6.  Administration of BAL (dimercaprol) may be considered, but it
     has not proven to be effective in arsine poisonings to date.  The
     efficacy of D-penicillamine has not been tested.
                                62

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                       CHAPTER 7

     CHLOROPHENOXY HERBICIDES

GENERAL CHEMICAL STRUCTURE
          Cl   (or CH3)
              — O —
    0
    IF
	 C — O — H
COMMERCIAL PRODUCTS

  Several hundred commercial products contain chlorophenoxy herbi-
cides in various forms, concentrations, and combinations. Following are
names of widely advertised formulations. In some cases, the  same
name is used for products with different ingredients. Exact composition
must therefore be determined from the product label.
  2,4-D or 2,4-dichlorophenoxyacetic acid (Agrotect, Amoxone, Aqua-
Kleen, BH 2,4-D, Chipco Turf Herbicide 'D', Chloroxone, Crisalamina,
Crisamina, Crop Rider, D50, Dacamine, Debroussaillant 600, Ded-Weed
SULV, Desormone, Dinoxol, Emulsamine BK, Emulsamine  E-3, Envert
DT, Envert 171, Super D Weedone, Weedone, Estone, Farmco, Fer-
nesta, Fernimine, Fernoxone, Ferxone,  Formula  40, Gordon's Amine
400, Gordon's LV 400  2,4-D,  Hedonal, Herbidal, Lawn-Keep, Macon-
dray,  Miracle, Netagrone 600, Pennamine D,  Planotox,  Plantgard,
Salvo,  Spritz-Hormin/2,4-D,  Spritz-Hormit/2,4-D,  Superormone Con-
centre, Transamine,  Tributon, Tuban, U 46, U 46 D-Ester, U 46 D-
Fluid, Weed-B-Gon, Weedar, Weedatul, Weed-Rhap, Weed  Tox, Weed-
trol, Gordon's Dymec Turf Herbicide Amine 2,4-D, Gordon's Phenaban
801, Acme Amine 4, Acme Butyl Ester 4, Acme  LV 6, Acme LV 4,
Gordon's Butyl Ester 600, DMA 4, Dormone).
  2,4-DP or 2,4-dichlorophenoxypropionic acid (BH 2,4-DP, Desormone,
Hedonal, Hedonal DP, Kildip, Polymone, Seritox 50, U 46, U 46 DP-
Fluid, Weedone DP, Weedone 170).
  2,4-DB or 2,4-dichlorophenoxybutyric  acid (Butoxon, Butoxone, Bu-
tyrac, Embutox).                                   , -
  2,4,5-T or 2,4,5-trichlorophenoxyacetic acid (Amine 2,4,5-T for rice,
Dacamine, Ded-Weed, Farmco Fence Rider, Forron, Inverton 245, Line
Rider, Super D Weedone, T-Nox, Trinoxol, U 46, Weedar, Weedone).
                              63

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  MCPA (metaxon, Agroxone, Weedone), MCPB (Can-Trol, PDQ, This-
trol), and MCPP (mecoprop, Methoxone M, Mecopex, Gordon's Meco-
mec) are 2-methyl, 4-chlorophenoxy aliphatic acids and esters.
  Dicamba (Banvel) is 2-methyl-3,6 dichlorobenzoic acid.
  Sodium, potassium, and alkylamine salts are commonly formulated
as aqueous solutions, while the less water soluble esters are applied as
emulsions.  Low molecular weight esters are more volatile than  the
acids, salts, or long-chain esters.
  Chlorophenoxy compounds  are  sometimes  mixed into commercial
fertilizers to control growth of broadleaf weeds.

TOXICOLOGY

  Some of the chlorophenoxy acids, salts, and esters are moderately
irritating to skin, eyes, and respiratory and gastrointestinal linings. In
a few individuals, local depigmentation has apparently resulted from
protracted dermal contact with chlorophenoxy compounds.
  The chlorophenoxy compounds  are absorbed across  the  gut wall,
lung, and skin. They are not significantly fat storable. Excretion occurs
almost entirely by way of the urine.  Apart from some conjugation of
the acids, there is limited biotransformation in the body. The average
residence half-life of 2,4-D in the human is about 18 hours,  that of
2,4,5-T about 24 hours. These  averages lie within very wide ranges (4-
140 hours in the case  of 2,4-D), depending on urinary pH (alkalinity
enhances excretion).
  Given in large doses to experimental animals, 2,4-D causes vomiting,
diarrhea, anorexia, weight loss, ulcers of the mouth and pharynx, and
toxic injury to the liver, kidneys, and  central nervous system. Myo-
tonia (stiffness and  incoordination of hind  extremities)  develops in
some species and is apparently due to CNS damage: demyelination  has
been observed  in the dorsal columns of the cord, and EEG changes
have indicated functional disturbances in the brains of heavily dosed
experimental animals.
  Ingestion of large  amounts of chlorophenoxy acids has resulted in
severe metabolic acidosis in humans.  Such cases have been associated
with electrocardiographic changes, myotonia, muscle weakness, myo-
globinuria,  and elevated serum creatine phosphokinase, all  reflecting
injury to striated muscle. Because chlorophenoxy acids are  weak  un-
couplers  of  oxidative  phosphorylation,  extraordinary  doses  may
produce hyperthermia from increased  production of body heat.
  Chlorinated Dibenzo Dioxin (CDD)  and Chlorinated Dibenzo Furan
(CDF) compounds are generated in the manufacture of chlorophenoxy
compounds,  particularly at  excessive temperatures.  The 2,3,7,8-tetra
CDD form is extraordinarily toxic to multiple mammalian tissues; it is
formed only in the synthesis of 2,4,5-T. Hexa-, hepta-,  and octa-com-
pounds exhibit less systemic toxicity, but are  the likely cause of chlor-
acne (a chronic, disfiguring skin condition) seen in workers engaged in

                                64

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    manufacture of 2,4,5-T and certain other chlorinated organic com-
pounds. Although toxic effects, notably chloracne, have been observed
in manufacturing plant workers, these effects have not been observed
in formulators or applicators  regularly exposed to 2,4,5-T or other
chlorophenoxy compounds.
  The medical literature  contains some reports  of peripheral neuropa-
thy following what seemed to be minor dermal exposures to 2,4-D. It is
not certain that exposures to other neurotoxicants were entirely  ex-
cluded in these cases. Single doses of 5 mg/kg body weight of 2,4-D and
2,4,5-T have been administered to human subjects without any adverse
effects. One subject consumed 500  mg of 2,4-D per day for 3  weeks
without experiencing symptoms or signs of illness.

SYMPTOMS  AND SIGNS OF POISONING

  Chlorophenoxy compounds are moderately IRRITATING to skin and
mucous membranes. Inhalation of  sprays may cause burning  sensa-
tions in the  nasopharynx and chest and coughing may result. Pro-
longed inhalation  sometimes causes dizziness. Adjuvant  chemicals
added  to enhance foliage penetration may account for the irritant
effects of some formulations.
  Manifestations of systemic toxicity of chlorophenoxy compounds are
known mainly from clinical experience with cases of deliberate suicidal
ingestion of large quantities. The agents most often involved in these
incidents have been 2,4-D and mecoprop. The toxic effects of other
chlorophenoxy compounds are probably similar  but not identical. Few
cases of deliberate ingestion of chlorophenoxy compounds have  termi-
nated fatally.
  Irritation of the stomach usually leads to VOMITING  soon after
ingestion.  Pain in  the chest and abdomen and diarrhea may  ensue.
Headache, mental confusion, and bizarre behavior are early manifesta-
tions of severe poisoning which may progress to UNCONSCIOUSNESS.
MYOTONIA (muscular stiffness on passive movement of the limbs) has
occurred in persons poisoned by 2,4-D. Areflexia  is sometimes observed.
Muscle twitching may or  may not be evident. Convulsions  occur very
rarely. Respiratory drive  is not depressed; hyperventilation is some-
times evident. Body temperature may be moderately elevated, but this
is  rarely a life-threatening feature of the  poisoning.  With effective
urinary excretion  of  the toxicant, consciousness  usually  returns in
48-96 hours.
  Metabolic acidosis is manifest as a low arterial pH and bicarbonate
content. The  urine is usually acid.  Skeletal muscle injury, if it occurs,
is reflected in elevated creatine phosphokinase, and sometimes myoglo-
binuria. Moderate  temporary elevations of blood  urea nitrogen  and
serum creatinine are commonly found as the toxicant is excreted, but
acute renal failure is  uncommon.  Mild leukocytosis and biochemical
changes indicative  of liver cell injury have been reported. Both tachy-

                               65

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cardia and bradycardia have been observed. T-wave flattening and
inversion may occur.
  Myotonia and muscle weakness may persist for months after acute
poisoning. Electromyographic and  nerve conduction studies in some
recovering patients have demonstrated a mild proximal  neuropathy
and myopathy.

CONFIRMATION OF POISONING

  Gas-liquid chromatographic methods are available for detecting and
measuring chlorophenoxy compounds in blood and urine. These analy-
ses are useful in confirming and assessing  the magnitude of chloro-
phenoxy absorption. Poisonings characterized by unconsciousness have
shown initial blood chlorophenoxy  concentrations ranging from 80 to
more than 1000 mg per liter. Urine samples should be collected as soon
as possible after exposure because the herbicides may be almost com-
pletely excreted in 24-72 hours,  depending  on the extent of toxicant
absorption and urine pH. Analyses can be performed at special labora-
tories usually known to local poison control centers. If circumstances
indicate strongly that excessive exposure to chlorophenoxy compounds
has occurred, INITIATE appropriate TREATMENT measures immedi-
ately, not waiting for  chemical  confirmation of toxicant absorption.

TREATMENT OF POISONING BY CHLOROPHENOXY
  COMPOUNDS

 1.   BATHE and SHAMPOO with soap and water to remove chemi-
     cals from skin and hair. Obtain medical treatment if irritation
     persists. Individuals with chronic skin disease or known sensitivi-
     ty  to these herbicides should either avoid using them  or take
     strict precautions to avoid contact (respirator, gloves, etc.).
 2.   FLUSH contaminating chemicals from eyes with copious amounts
     of  clean water for 10-15  minutes.  If irritation persists, obtain
     medical treatment.
 3.   If any symptoms of illness occur during or following inhalation of
     spray, REMOVE victim FROM CONTACT with the material for
     at  least 2-3 days.  Allow subsequent contact with chlorophenoxy
     compounds  only if effective respiratory protection is practiced.
 4.   If substantial amounts of chlorophenoxy compounds have been
     INGESTED, spontaneous emesis may occur. If vigorous emesis
     has not occurred, measures should be taken to empty the stomach
     and limit gastrointestinal absorption by  GASTRIC INTUBATION,
     ASPIRATION, and LAVAGE, following placement of a cuffed
     endotracheal tube. Lavage procedure is described in Chapter 1,
     TREATMENT, Section 6, page  8. Repeated administration of char-
     coal at half or more the original dosage every 2-4 hours may be
     beneficial.

                               66

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    If gastric aspiration and lavage is not performed due to delay in
    treatment, and if the patient is fully alert, ADMINISTER CHAR-
    COAL AND LAXATIVE ORALLY, at the dosages indicated in
    Chapter 1, TREATMENT, Section 6, p. 8.
5.   Administer INTRAVENOUS FLUIDS to accelerate excretion of
    the  chlorophenoxy compound, and to limit concentration of the
    toxicant in the kidney. A urine flow of 4-6 ml/minute is desira-
    ble.  Intravenous saline/dextrose has sufficed to rescue comatose
    patients who drank 2,4-D and mecoprop several hours before hos-
    pital admission.
    CAUTION: Monitor urine protein and cells, BUN, serum creati-
    nine, serum electrolytes, and fluid intake/output carefully to
    insure that renal  function remains unimpaired and  that  fluid
    overload does not occur.
    Forced  ALKALINE  DIURESIS has been  used successfully in
    management of suicidal ingestions of chlorophenoxy compounds.
    Alkalinizing the urine by including sodium bicarbonate (44-88
    mEq per liter) in the intravenous solution apparently accelerates
    excretion of 2,4-D dramatically  and mecoprop excretion substan-
    tially.  Urine pH should by maintained in  the 7.6-8.8  range. In-
    clude potassium chloride as needed to offset increased potassium
    losses: add 20-40 mEq of potassium chloride to each liter of intra-
    venous solution. Monitor serum electrolytes carefully. There may
    possibly be some hazard to the kidneys when urine concentrations
    of toxicant are very high, so the integrity of renal function and
    fluid balance should be monitored carefully as the chlorophenoxy
    compound is excreted.
6.   Hemodialysis is not likely to be of significant benefit in poisonings
    by chlorophenoxy  compounds because of  the  extensive protein
    binding of these chemicals.
7.   Follow-up  clinical examination should include electromyographic
    and nerve conduction studies to detect any neuropathic changes
    and neuromuscular junction defects.
                               67

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                       CHAPTER 8

             NITROPHENOLIC AND
       NITROCRESOLEC HERBICIDES
GENERAL CHEMICAL STRUCTURE
              02N  O—H   or

             (ALKYL)   (ALKYL)
COMMERCIAL PRODUCTS

  Dinitrophenol (Chemox PE), dinitrocresol (DNOC, DNC, Chemsect
DNOC, Elgetol 30, Nitrador, Selinon, Sinox, Trifocide), dinoseb (DNBP,
dinitro, Basanite, Caldon,  Chemox  General, Chemox  PE, Chemsect
DNBP, Dinitro, Dinitro-3, Dinitro General, Dynamyte, Elgetol 318, Ge-
butox, Hel-Fire, Kiloseb, Nitropone C, Premerge 3, Sinox General, Su-
bitex, Unicrop DNBP, Vertac, Dinitro Weed Killer 5, Vertac General
Weed Killer, Vertac  Selective Weed Killer), dinoseb acetate (Aretit),
dinoseb methacrylate (binapacryl, Morocide, Acricid, Ambox, Dapacryl,
Endosan,  FMC 9044, Hoe 002784, Morrocid, NLA 9044),  dinosulfon,
dinoterbon, dinoterb acetate, dinoterb salts, dinosam (DNAP, Chemox
General),  dinoprop,  dinocap (Crotothane,  Karathane),  dinobuton
(Acrex, Dessin, Dinofen, Drawinol, Talan), dinopenton.
  These agents have many uses in  agriculture worldwide: herbicides
(weed-killing and defoliation), acaricides, nematocides, ovicides, fungi-
cides. Relatively insoluble  in water, most technical products are dis-
solved in organic solvents and are formulated for spray application as
emulsions. There are some wettable powder formulations.

TOXICOLOGY

  Nitroaromatic compounds are highly toxic to humans and animals.
Most nitrophenols and nitrocresols are well absorbed from the gastro-
intestinal tract, across the skin, and by the lung when fine droplets are
inhaled. Fatal poisonings have occurred as a result of dermal contami-
nation. Except in a few sensitive individuals, they are only moderately
irritating to the skin and mucous membranes.

                             68

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   NitropKenols and nitrocresols undergo some  biotransformation in
 humans, chiefly reduction (one nitro group to an amino group) and
 conjugation at the phenolic site/Although nitrophenols and metabo-
 lites appear consistently in the urine of poisoned individuals, hepatic
 excretion is probably the main route of disposition. Elimination is slow:
 residence half-life in humans is 5-14 days. Blood and tissue concentra-
 tions tend to increase progressively if an individual is substantially
 exposed on successive days.
   Nitrophenols and nitrocresols are toxic to  the  liver, kidney, and
 nervous system. The  basic  mechanism of toxicity is stimulation of
 oxidative metabolism  in cell mitochondria, by interference with the
 normal coupling of carbohydrate oxidation to phosphorylation (ADP to
 ATP). The nitrophenols are more active  as uncouplers than chloro-
 phenols. Increased oxidative  metabolism leads to hyperthermia, tachy-
 cardia, and dehydration, and in time,  depletes carbohydrate and fat
 stores. Most severe  occupational poisonings from absorption  of these
 compounds  have occurred in workers laboring in  hot environments.
 Hyperthermia  and direct action on the brain cause cerebral edema,
 manifest clinically as a toxic psychosis  and sometimes convulsions.
 Liver parenchyma and renal tubules show degenerative changes. Albu-
 minuria, pyuria, hematuria, and azotemia are signs of renal injury.
   Neutropenia has occurred in humans following heavy exposure to
 dinitrophenol. Cataracts occur in laboratory animals  given nitrophen-
 ols, and have occurred in humans, both as a result of ill-advised medicr
 inal use and as a consequence of occupational  exposure. Cataract for-
 mation is sometimes accompanied by glaucoma.

 SYMPTOMS AND SIGNS OF POISONING

  Yellow staining of skin and hair often signify topical contact with a
 nitroaromatic  chemical. Staining  of the sclerae and  urine  indicate
 absorption of potentially toxic amounts. Profuse SWEATING, THIRST,
 FEVER, HEADACHE, confusion, malaise, and lassitude are common
 early symptoms of poisoning. Warm flushed skin,  tachycardia, and
 tachypnea indicate a serious degree of poisoning.  RESTLESSNESS,
 apprehension, anxiety, manic behavior, or unconsciousness reflect cere-
 bral injury. CONVULSIONS  signify an immediately life-threatening
 intoxication. Labored breathing  and cyanosis are consequences of the
 stimulated metabolism and tissue anoxia. Weight loss occurs in persons
 continually exposed to relatively low doses of nitrophenols or nitrocre-
 sols.

 CONFIRMATION OF  POISONING

  Unmetabolized nitrophenols and nitrocresols  can be identified spec-
trophotometrically, or by gas-liquid chromatography, in the serum and
urine at concentrations well  below  those that have been associated

                                69

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with acute poisonings. Blood analysis is useful in confirming the cause
of poisoning, but has little value in  monitoring progress or predicting
outcome. If poisoning is probable, DO NOT AWAIT CONFIRMATION
before commencing treatment, but save urine and blood specimens in
the event confirmation is necessary later on.

TREATMENT OF NITROPHENOL  OR NITROCRESOL
  POISONING

 1.  If poisoning has been caused by contamination of body surfaces,
     BATHE and SHAMPOO  contaminated SKIN and HAIR promptly
     and thoroughly with soap and water, or water alone if soap is not
     available. Wash  the chemical  from skin  folds and from  under
     fingernails.  CONTAMINATED  CLOTHING  should be promptly
     removed, bagged, and not returned until it has been thoroughly
     laundered. Contaminated leather shoes should be discarded. The
     possibility that pesticide  has contaminated the inside surfaces of
     gloves, boots, and headgear should be kept hi mind.
 2.  FLUSH  chemical from  EYES with  copious amounts of clean
     water. Obtain medical attention if irritation or other injury per-
     sists.
 3.  Systemic poisoning must be treated by controlling body tempera-
     ture, providing oxygen, maintaining hydration, and relieving agi-
     tation.
     A.  REDUCE ELEVATED BODY TEMPERATURE BY PHYSI-
        CAL MEANS. Administer sponge baths and cover victim with
        cool  blankets. In fully  conscious  patients, administer cold,
        sugar-containing liquids by mouth as tolerated.
     B.  DO NOT administer  atropine, aspirin, or other salicylates to
        control hyperthermia. These agents appear likely to enhance
        the toxicity of phenolic substances. Neither the safety nor the
        effectiveness of other antipyretics has been tested.
     C.  Administer  OXYGEN  continuously by  mask to  minimize
        tissue anoxia.
     D.  Unless there are  manifestations  of cerebral or pulmonary
        edema or of inadequate renal function, administer INTRAVE-
        NOUS FLUIDS to restore hydration and support physiologic
        mechanisms for  heat loss and toxicant disposition. Monitor
        serum electrolytes, adjusting IV infusions to stabilize electro-
        lyte  concentrations.  Follow urine contents of albumin and
        cells, and keep an accurate  hourly record of intake/output to
        forestall fluid overload if renal function declines.
        CAUTION: In the presence  of cerebral edema  and/or un-
        paired renal function, intravenous  fluids must be  adminis-
        tered very cautiously to avoid increased intracranial pressure
        and pulmonary edema.

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    E. In. severe poisonings, monitor pulmonary ventilation carefully
       to insure adequate gas exchange, and monitor cardiac status
       by EGG to detect arrhythmias. The toxicant itself and severe
       electrolyte disturbances may predispose to arrhythmias and
       myocardial weakness.
    F. To reduce production of heat in the body, CONTROL AGITA-
       TION and involuntary motor activity with sedatives. DIAZE-
       PAM or other benzodiazepine should be effective,  although
       use of these  drugs in  nitroaromatic  poisoning has  not been
       reported. If diazepam is chosen,  administer SLOWLY, intra-
       venously.
       Dosage of DIAZEPAM:
            Adults and children over 12 years: 5-10 mg. Repeat if
            necessary to a maximum of  30 mg.
            Children under 12 years: 0.25-0.40 mg/kg body weight.
            Repeat if necessary to a maximum of 10 mg for children
            5-12 years and to a maximum of 5 mg  for children 30
            days to 5 years.
       Diazepam can be given  by deep intramuscular injection if
       intravenous administration is not possible.
       CAUTION: Be prepared to assist pulmonary ventilation me-
       chanically if respiration is depressed, to intubate the trachea
       if laryngospasm occurs, and to counteract hypotensive reac-
       tions.
    G. Hemodialysis has not proven to be effective hi poisonings by
       phenolic substances. Forced diuresis is of little or no benefit hi
       reducing body burden.  There has been insufficient testing of
       hemoperfusion to establish its value in accelerating elimina-
       tion of phenols.
4.   IF nitrophenol or nitrocresol  has been INGESTED in a quantity
    sufficient to cause poisoning, the stomach and intestine must be
    emptied  and measures taken to limit absorption of residual toxi-
    cant. The effectiveness  of induced emesis and gastric lavage hi
    removing toxicant from the stomach diminishes rapidly with the
    passage of time.
    A. IF ingestion occurred within the last few hours, and IF the
       patient  is FULLY ALERT, give SYRUP OF IPECAC, fol-
       lowed by 1-2  glasses  of water, to  induce vomiting. The dosage
       of Syrup of Ipecac for adults and children over 12 years is 30
       ml; the dosage for children under  12 years is 15 ml.
       CAUTION: OBSERVE the patient closely AFTER administer-
       ing IPECAC. Position the patient hi left lateral decubitus,
       head below the level of  the  stomach. If. consciousness level
       declines or if vomiting does not occur in 30 minutes, proceed
       immediately to PROTECT THE  AIRWAY, then INTUBATE,
       ASPIRATE, and LAVAGE the stomach (see below).

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    B.  IF the patient is NOT FULLY ALERT when first examined,
       proceed directly to PROTECT THE AIRWAY, insert a large
       bore orogastric tube, and empty to stomach by ASPIRATION
       and LAVAGE with  a slurry of  ACTIVATED CHARCOAL.
       See Chapter 1, TREATMENT, Section 6, p. 8.
    C.  Following emesis or lavage, administer ACTIVATED CHAR-
       COAL and CATHARTIC by ingestion or by orogastric tube, as
       recommended in Chapter 1, TREATMENT,  Section 6, page 8.
    D.  If several hours have elapsed since ingestion,  and if the pa-
       tient is fully alert, ADMINISTER ACTIVATED CHARCOAL
       AND CATHARTIC ORALLY.
    E.  REPEATED  administration of ACTIVATED CHARCOAL at
       half or more the initial dosage every 2-4 hours may be benefi-
       cial.
       CAUTION: Catharsis may lead to dehydration and electrolyte
       disturbances, particularly  in children.  Fluid balance and
       serum electrolytes  should be monitored. There may  be some
       advantage in giving repeated doses of cathartics to adults, but
       caution must be exercised  hi children. Administration of ca-
       thartic should stop when a charcoal stool appears.
    F.  Save a sample of emesis  or initial gastric  washings for chemi-
       cal analysis.
5.   During convalescence, administer a high-calorie, high-vitamin diet
    to restore body fat and  carbohydrate.
6.   Discourage subsequent contact with  the toxicant for 4-8 weeks
    (depending on  severity of poisoning)  to allow full restoration of
    normal metabolic processes.
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                        CHAPTER  9

            PENTACHLOROPHENOL
CHEMICAL STRUCTURE
                              Cl
                                       •H
                                       (or Na)
COMMERCIAL PRODUCTS

  PGP, Penta, Penchlorol, Santophen, Chlorophen, Pentacon, Penwar,
Sinituho. The sodium salt is sodium pentachlorophenate.
  In various products, pentachlorophenol has been used as an herbi-
cide, algacide, defoliant, wood preservative, germicide, fungicide, and
molluscicide. As a wood preservative, it is commonly applied as a 0.1%
solution in mineral spirits, No. 2 fuel oil, or kerosene. It is used in
pressure treatment of lumber at 5% concentration. Weed killers con-
tain higher concentrations. PGP is no longer available for over-the-
counter sale in the United States.
  Pentachlorophenol volatilizes from treated wood  and fabric. It is
virtually odorless.  Excessively treated interior  surfaces  may  be  a
source of exposure  sufficient to cause irritation of eyes, nose, and
throat.
  Technical  PGP contains lower  chlorinated phenols (4-12%)  plus
traces of chlorobenzodioxins, chlorobenzofurans,  and chlorobenzenes.

TOXICOLOGY

  PGP is efficiently absorbed  across the skin, the  lung, and the gastro-
intestinal  lining. It is rapidly excreted,  mainly  in the urine as un-
changed PGP and as PGP glucuronide. In the blood, a large fraction of
absorbed PGP is protein-bound.
  The residence half-life of  PGP  in humans is about 27-36  hours.
Because minute amounts of PGP  are consistently detectable in the
blood and urine of the general population, a  continuing low-level
intake (micrograms per day)  of PGP by virtually everyone is implied.
  In adequate concentration, PGP is irritating to mucous membranes
and skin. Contact dermatitis  occurs commonly in workers having con-
tact with PGP.
  Internally, large  doses are toxic to the liver, kidneys, and nervous
system. An important mechanism of toxic action is increased cellular

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oxidative metabolism resulting from the uncoupling of oxidative phos-
phorylation. This leads to  increased heat production (hyperthermia).
  Severe poisoning and death have occurred as a result of intensive
PGP exposure. Dermal absorption has been the basis of virtually all
occupational poisonings. Most adult fatalities have occurred in persons
working in hot environments where hyperthermia is poorly tolerated.
Several infant deaths occurred in a nursery where a PCP-containing
diaper rinse  had been used. Chloracne  has occurred in production
workers, possibly due to chlorodioxin contaminants. Individual cases of
exfoliative dermatitis of the hands and diffuse urticaria and angioe-
dema of the hands have been reported in intensively exposed workers.
Cases of aplastic anemia, peripheral neuropathy, and leukemia have
been reported which were  associated  temporally with PCP exposure.
Causal relationships in these cases were not established.
  Albuminuria, glycosuria,  aminoaciduria,  and elevated  BUN reflect
renal injury.  Liver enlargement, anemia and leukopenia have been
reported in some intensively exposed workers. Elevated serum alkaline
phosphatase, GOT, and LDH enzymes  indicate significant insult to the
liver, including both cellular damage and some degree  of biliary  ob-
struction.

SYMPTOMS  AND  SIGNS  OF POISONING

  IRRITATION  of the nose, throat,  and eyes is the most common
effect of airborne PCP, causing stuffy nose, scratchy throat, and tear-
ing. Dermal exposure may  lead to contact dermatitis, or more rarely,
diffuse urticaria or chloracne.
  Commonly  reported  symptoms of systemic  poisoning  by PCP  are
profuse SWEATING,  weakness, dizziness, anorexia, nausea,  and—in
workers exposed over long  periods—weight loss. Indications of severe
acute poisoning  are HYPERTHERMIA, muscle  spasms, tremor,  la-
bored breathing, a  sense of constriction in the chest, abdominal pain
and vomiting, restlessness,  excitement, and mental confusion. Tachy-
cardia and increased respiratory rate are usually apparent. Intense
THIRST is characteristic.

CONFIRMATION  OF  POISONING

  PCP can be measured in blood, urine, and adipose tissue by  gas-
liquid chromatography. Up  to about 100 parts per billion may be found
in the blood and urine of persons having no recognized exposure. Food
is probably the main source of this microgram-level dosage. In addition
to minute residues of synthetic PCP in food, water, and air, some PCP
may derive from biotransformation of other chlorinated  organic com-
pounds.                     .
  Based on studies  of persons occupationally exposed to PCP, manifes-
tations of systemic toxicity probably do not appear in adults until blood

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and urine concentrations reach at least one part per million (0.1 mg%,
or 1,000 parts per billion). POP serum concentrations of 13 parts per
million have been found in symptomatic occupationally exposed work-
ers. Serum concentrations of 46 and 97 parts per million have been
measured in fatal poisonings.
  If poisoning is strongly  suspected on the basis of exposure, symp-
toms, and signs, DO NOT POSTPONE TREATMENT until diagnosis is
confirmed.

TREATMENT

  Treatment recommendations in  poisonings by PCP are  essentially
the same as those for poisonings by NITROPHENOLIC and NITRO-
CRESOLIC HERBICIDES, discussed in Chapter 8, page 70.
  Exchange transfusion was used to  rescue  newborns inadvertently
poisoned by PCP in a hospital.
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                       CHAPTER 10

           PARAQUAT AND  DIQUAT
CHEMICAL STRUCTURES
           PARAQUAT
                                             CH2	CH2
                                                DIQUAT

  Paraquat and diquat are identified chemically as DIPYRIDYLS.

COMMERCIAL PRODUCTS

  Paraquat is a synthetic nonselective contact herbicide, usually mar-
keted as the dichloride salt. Dimethyl sulfate salts are also produced.
Liquid technical products  range  from 20% to 50% concentration.
Names of liquid concentrates are: Ortho Paraquat CL, Ortho Paraquat
Plus,  Cekuquat,. Crisquat, Herbaxon, Herboxone,  Dextrone, Esgram,
Gramocil, Gramoxone, Goldquat 276, Sweep, Osaquat Super, Gramonol,
Toxer Total, Pillarxone, Pillarquat. Paraquat is  commonly formulated
in combination with other herbicides:
  With diquat: Actor, Preeglone, Preglone, Priglone,  Weedol (a 2.5%
soluble granule formulation).
  With monolinuron: Gramonol
  With diuron: Gramuron, Para-col, Tota-col, Dexuron
  With simazine: Terraklene, Pathclear
  Diquat is usually prepared as the dibromide monohydrate salt, 20%
to 25% in liquid concentrates. Deiquat and region are alternative
common names. Commercial products  are: Ortho Diquat, Aquacide,
Dextrone,  Reglone, Reglox,  Weedtrine-D. Combinations with paraquat
are listed  above. Diquat is  still used as a water herbicide, but is now
applied as a dessicant and terrestrial herbicide as well.

TOXICOLOGY AND MANIFESTATIONS OF POISONING

Paraquat

  Particularly in concentrated form, paraquat causes  injury to tissues
with which it comes into contact. It leaves the  skin of the hands dry
and fissured, sometimes resulting in loss of fingernails. Prolonged con-
tact with  skin may  cause blistering  and ulceration,  with subsequent

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 absorption of paraquat in sufficient dosage to cause systemic poisoning.
 Prolonged inhalation of spray droplets may cause nosebleed. Eye con-
 tamination results in severe conjunctivitis and sometimes protracted
 and even permanent cornea! ©pacification. When ingested in adequate
 dosage (see below), paraquat has life-threatening effects on the gastro-
 intestinal tract, kidney,  liver, heart, and other organs. The first phase
 of systemic poisoning consists of swelling, edema, and ulceration of the
 mucosal linings of the mouth, pharynx, esophagus, stomach, and intes-
 tine. Centrizonal hepatocellular injury along with damage to the proxi-
 mal renal tubules, myocardium, and skeletal muscle (sometimes includ-
 ing  focal necrosis) are  the  main  features of the second phase.  The
 nervous system and pancreas are affected in some cases. The third
 phase—injury to the lung—usually becomes evident 2-14 days follow-
 ing ingestion, although, in some cases, pulmonary edema has developed
 only a few  hours after paraquat has  been swallowed. Paraquat is
 selectively concentrated in  lung tissue where  it destroys lung paren-
 chymal cells probably by generation of free-radical oxygen and subse-
 quent lipid  peroxidation. Hemorrhage,  edema fluid,  and  leukocytes
 infiltrate the alveolar spaces, after which there is rapid proliferation of
 fibroblasts. Severe impairment of gas exchange causes death from an-
 oxemia and tissue anoxia. Remarkably, essentially full recovery of
 pulmonary  function occurs following paraquat poisonings  which  are
 survived. Although absorption across intact skin is slow, abraded or
 eroded skin  allows efficient absorption. Fatal poisonings are reported
 to have  occurred  as a result of protracted dermal  contamination by
 paraquat.
  The effect of paraquat on renal tubule cells is more likely to be
 reversible than the effect on lung tissue, but impaired renal function
 may play a critical role in  determining  the  outcome of paraquat poi-
 soning. Normal tubule cells actively secrete paraquat into the urine,
 clearing it efficiently from the blood. However, high blood concentra-
 tions poison  the secretory mechanism and may destroy the cells. Be-
 cause the kidney is almost the exclusive  route of paraquat elimination
 from body tissues, renal failure fosters a build-up of tissue concentra-
 tions,  including those in the lung. Unfortunately,  this pathogenetic
 sequence may occur in the first several hours following paraquat inges-
 tion, generating lethal concentrations of paraquat in lung tissue before
 therapeutic measures to  limit absorption and enhance disposition have
 taken  effect. It is probably for this  reason that methods for enhancing
 paraquat disposition several hours  following ingestion have had little
 influence on mortality.
  The hepatic injury from paraquat may be severe enough to cause
jaundice, but hepatotoxicity is  rarely a major determinant of clinical
 outcome. Elevated alkaline phosphatase, AST, ALT, and LDH are indi-
 cations of hepatocellular insult; jaundice signifies more severe injury.
  Early symptoms and signs of poisoning by ingested paraquat  are
burning pain in the  mouth, throat, chest, and upper abdomen, due to

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the corrosive effect of paraquat on the mucosal lining. Giddiness, head-
ache, fever, myalgia, and diarrhea (sometimes bloody) occur. Pancreati-
tis may cause severe abdominal pain. Proteinuria, hematuria, pyuria,
and azotemia reflect renal injury. Oliguria/anuria indicate acute tubu-
lar necrosis.
  Progressive  declines hi arterial oxygen tension and CO diffusion
capacity commonly precede  pulmonary symptomatology. Cough, dysp-
nea, and tachypnea usually  appear 2-4 days following paraquat inges-
tion, but may be delayed as long as 14 days.  Progressive cyanosis and
air hunger  reflect deteriorating gas exchange in  the  damaged lung.
Coma usually precedes death. In some cases, the coughing up of frothy
sputum (pulmonary edema) is  the early and principal manifestation of
paraquat lung injury.
  Clinical experience has offered a rough dose-effect scale on which to
base prognosis in cases of paraquat ingestion (J. A.  Vale, et al., Human
Toxicology, 6:41-47,1987):
  I.  Less than 20 mg paraquat ion per kg body weight (less than 7.5
     ml of  20%  (w/v) paraquat concentrate). No symptoms,  or  only
     gastrointestinal symptoms occur. Recovery is likely.
 n.  Twenty to 40 mg paraquat ion per kg body weight (7.5-15.0 ml of
     20% (w/v)  paraquat concentrate). Gastrointestinal, renal, hepatic
     and pulmonary damage by paraquat occurs. Pulmonary fibropla-
     sia ensues. Death  occurs in most cases, but may be delayed 2-3
     weeks.
 HI. More than 40  mg paraquat ion per kg body weight (more  than
     15.0 ml of 20%  (w/v)  paraquat  concentrate).  Multiple organ
     damage  occurs as  in  class II, but is more  rapidly progressive.
     Often characterized by marked ulceration of the oropharynx.  Mor-
     tality is  essentially 100% hi 1 to 7 days.
   Although much concern has been expressed about effects of smoking
 paraquat-contaminated  marijuana,  toxic effects  by this  mechanism
 have been  either very rare or nonexistent. Most paraquat that con-
 taminates marijuana is pyrolyzed during smoking to dipyridyl. Dipyri-
 dyl is a product of combustion of leaf material itself  (including mari-
 juana) and presents little toxic hazard.
   It is tragic that use of paraquat as a suicidal agent has increased hi
 recent years, particularly in  Japan and also hi developing countries.
 Several strategies are  being  tested to reduce the frequency of  these
 occurrences:  addition of emetics,  stenching agents, gelling substances.

 Diquat

    Diquat is somewhat less damaging to skin than  paraquat, but irri-
 tant effects may appear following dermal contamination with the con-
 centrate. There is probably significant absorption of diquat across ab-
 raded or ulcerated skin.

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    Systemically absorbed diquat is not selectively concentrated in lung
  tissue, as is paraquat, and pulmonary injury by diquat is less promi-
  nent. However, diquat has severe toxic effects on the central nervous
  system that are  not typical of paraquat poisoning although brain
  injury has been observed post-mortem in some fatal paraquat poison-
  ings. Renal  damage is an important feature of poisonings  by both
  agents. The  kidney  is the principal excretory  pathway for diquat ab-
  sorbed into the body.
   Early symptoms of poisoning by ingested diquat are similar to those
  from paraquat, reflecting its corrosive effect on  tissues: burning pain in
  the mouth, throat, chest, and abdomen. Intense nausea, vomiting, and
  diarrhea are characteristic. If the dosage was  small, these symptoms
  may be delayed 1-2  days. Blood may appear in the vomitus and feces
  Intestinal Ueus, with pooling of fluid in  the  gut, has  characterized
  several human poisonings by diquat.  Dehydration, hypotension, and
  tachycardia may result and shock is a common cause of death. Agita-
  tion, restlessness,  disorientation, and psychotic behavior have been
 early manifestations of some diquat poisonings. Tonic-clonic seizures
 and  coma may  supervene. Proteinuria,  hematuria, and  pyuria may
 progress to renal failure and azotemia. Elevations of serum alkaline
 phosphatase, AST, ALT,  and LDH reflect liver injury. Jaundice may
 develop. If the patient survives several hours or days, circulatory func-
 tion may fail due to  toxic myocardiopathy,  or bronchopneumonia mav
 develop.
   Over the past decade, the great majority of poisonings by paraquat
 and diquat have been caused by ingestion—with suicidal intent in most
 cases. Nearly all of the few poisonings caused by occupational exposure
 have been survived, but the mortality rate among persons who have
 swallowed paraquat or diquat remains distressingly high (60%). Avoid-
 ance of this mortality will probably have to rely on preventive strate-
 gies or on  stopping  gastrointestinal absorption very soon after the
 toxicant has been ingested. Even though intestinal absorption of dipyri-
 dyls is relatively slow, lethal uptake by critical organs  and tissues
 apparently occurs within  18 hours, possibly within 6 hours, following
 ingestion  of  toxic quantities  of paraquat or diquat. Dipyridyls have
 large volumes of distribution. Once distribution to tissues has occurred,
 measures to  remove dipyridyls from  the blood are very inefficient in
 reducing the total body burden.

 CONFIRMATION OF ABSORPTION

  At  some treatment facilities,  a simple  colorimetric test is used  to
identify paraquat and diquat in the urine, and give a rough indication
of the magnitude of absorbed dose. To one volume of urine is added 0.5
volume of freshly prepared 1% sodium dithionite (sodium hydrosulfite)
in one normal sodium hydroxide. Observe color at end of one minute.
Development of a blue color indicates the presence of paraquat in

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excess of 0.5 mg per liter. Both positive and negative controls must be
run to  insure  that the dithionite has not undergone oxidation in
storage.
  When urine collected within 24 hours of paraquat ingestion is tested,
the dithionite test appears to have some approximate prognostic value:
concentrations less than one milligram per liter (no color to light blue)
generally predict survival, while concentrations in excess of one milli-
gram per liter (navy blue to dark blue) often foretell a fatal outcome.
  Diquat in urine  yields a green color. There  is less experience with
the dithionite test in diquat poisonings; however, the association of bad
prognosis with intense color is probably similar.
  Paraquat and diquat can be measured in blood and urine by spectro-
photometric,  gas  chromatographic, liquid  chromatographic,  and ra-
dioimmunoassay methods. These are available in localities where the
frequency of paraquat poisonings (chiefly suicides) has stimulated re-
search aimed at more effective therapy. Paraquat poisonings in which
plasma concentrations do  not exceed 2.0, 0.6, 0.3, 0.16, or  0.1 mg per
liter at 4, 6,10,16, and 24 hours, respectively, after ingestion are likely
to survive (Proudfoot, A.T. et al. The Lancet 11:330-332, 1979).

TREATMENT

 1.  Contaminated SKIN  must be FLUSHED  immediatley with copi-
     ous amounts  of water. Material splashed in the EYES must be
     removed by PROLONGED IRRIGATION with clean water.  Eye
     contamination should thereafter  be  treated by  an ophthalmol-
     ogist. Mild skin reactions usually  respond to simple avoidance of
     further contact, but the irritation  may  take several weeks to
     resolve. Severe injuries, with inflammation, cracking, secondary
     infection,  or  nail injury should be treated by a dermatologist.
 2.  If paraquat or diquat have been ingested  in any amount, IMME-
     DIATE ADMINISTRATION OF ADSORBENT is the one thera-
     peutic  measure most likely to affect the outcome of paraquat or
     diquat ingestion favorably. BENTONITE (7.5% suspension)  and
     FULLER'S EARTH  (30% suspension) are  highly effective, but
     sometimes not available.
     Dosage of BENTONITE AND FULLER'S EARTH:
         Adults and children over 12 years: 100-150 gm.
         Children under 12 years: 2 gm/kg body weight.
         CAUTION: Hypercalcemia and fecaliths have sometimes oc-
         curred following administration of fuller's earth.
      ACTIVATED CHARCOAL is nearly as effective, and is generally
      available. Give as much of a 30 gm per 240 ml suspension as the
      patient will swallow. Encourage the victim to swallow the adsorb-
      ent even though spontaneous vomiting continues.  Then,  after
      taking precautions to protect the  airway  (see Chapter 1, TREAT-
      MENT, Section 6, p.  8), carefully intubate the stomach and lavage

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    repeatedly with a slurry of adsorbent.  Instill the suspension of
    adsorbent as fast as the gut accepts it. Repeated administration of
    charcoal or other  absorbent every 2-4 hours may be beneficial.!
    Include SORBITOL in the first dose of adsorbent suspension.
    Dosage of SORBITOL:
        Adults and children over 12 years: 1-2 gin/kg body weight to
        a maximum of 150 gm.
        Children under 12 years:  1.0-1.5 gin/kg  body weight to a
        maximum of 50 gm.
    Seventy  percent sorbitol  should be  diluted half-and-half with
    water before administration.
    Prompt administration of adsorbent and thorough flushing of the
    gut are the measures which offer the best opportunity for surviv-
    al.
    CAUTION: Because corrosive damage to the esophagus and stom-
    ach may render these structures vulnerable to perforation, the
    gastric lavage tube must be introduced very gently.
    CHECK  FREQUENTLY FOR  BOWEL  SOUNDS.  Ileus  occurs
    commonly in diquat poisoning,  less  often in paraquat poisoning.
    Cathartics should not be administered if the gut is atonic; instilla-
    tion of fluid by stomach tube should be slowed  or stopped if ileus
    is present.
3.  Secure a blood sample as soon as possible for paraquat analysis.
4.  DO NOT ADMINISTER SUPPLEMENTAL OXYGEN. High con-
    centrations of oxygen in the lung increase the  injury induced by
    paraquat, and possibly by diquat as  well. There may be  some
    advantage in placing the patient in a moderately hypoxic environ-
    ment, i.e., 15%-16% oxygen, although the benefit of this treat-
    ment  measure has not been  established empirically  in  human
    poisonings. When the lung injury is so far advanced that there is
    no expectation of recovery, oxygen  may  be  given to relieve air
    hunger.
5.  Administer INTRAVENOUS FLUIDS:  isotonic saline, Ringer's so-
    lution, and  5%  glucose in water. This is highly advantageous
    early in poisonings as a means of correcting dehydration, acceler-
    ating toxicant excretion, reducing tubular fluid concentrations of
    paraquat,  and correcting metabolic acidosis, when  this  occurs.
    However, fluid balance must be monitored carefully to forestall
    fluid overload if renal failure develops.  Monitor  the urine regular-
    ly for protein and  cells, to  warn of impending tubular necrosis.
    Intravenous  infusions must be stopped if failure occurs, and EX-
    TRACORPOREAL  HEMODIALYSIS must be instituted to main-
    tain normal extracellular fluid composition. Hemodialysis is not
    effective in clearing paraquat or diquat from the blood and tis-
    sues.
6.  HEMOPERFUSION  over  cellophane-coated  activated charcoal
    may be considered. The procedure has been  used in many para-

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    quat poisonings because  the adsorbent does efficiently remove
    paraquat from the perfused blood.  However, recent reviews of
    effectiveness have failed to show any reduction in mortality as a
    result of hemoperfusion. The apparent reason for this is the very
    small proportion of paraquat body burden carried in the circulat-
    ing blood even when only a few hours have elapsed after inges-
    tion. Theoretically, a patient who can be hemoperfused within 10
    hours of paraquat ingestion may derive some marginal benefit,
    but this has not been demonstrated.
    If hemoperfusion is attempted, blood calcium and platelet concen-
    trations must be  monitored. Calcium and platelets must  be re-
    plenished  if these constituents  are  depleted by  the procedure.
7.  CONVULSIONS and psychotic  behavior sometimes encountered
    in diquat poisoning may be best controlled by DIAZEPAM, given
    slowly intravenously.
    Dosage of DIAZEPAM:
        Adults and children over 12 years: 5-10  mg. Repeat every
        10-15 minutes, if necessary, to a maximum of 30 mg.
        Children 5 to 12 years: 0.25-0.40 mg/kg body weight. Repeat
        every 15 minutes if necessary, to a maximum of 10 mg.
        Children under 5 years: 0.25-0.40 mg/kg body weight. Repeat
        every 15 minutes if necessary, to a maximum of 5 mg.
8.  Many  drugs have been  tested  in  animals  or given  in human
    dipyridyl  poisonings without clear  evidence of benefit or harm:
    corticosteroids, superoxide dismutase, propranolol, cyclophospha-
    mide, vitamin E, riboflavin, niacin, ascorbic acid, clofibrate, des-
    ferrioxamine, acetylcysteine, and terpin hydrate.
9.  Morphine sulfate is usually required to control the pain associat-
    ed with deep mucosal erosions of the mouth, pharynx, and esopha-
    gus, as well as abdominal pain from  pancreatitis and enteritis.
    Dosage for adults and children  over 12 years: 10-15 mg subcutan-
    eously every 4 hours. Dosage for children under 12 years: 0.1-0.2
    mg/kg body weight every 4 hours.
10.  Mouthwashes, cold fluids, ice cream, or anesthetic lozenges may
    help to relieve pain in the mouth and throat.
                                82

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                         CHAPTER 11

                OTHER HERBICIDES

   Many herbicides are now available for  use  in agriculture  and for
 lawn and garden weed control. This chapter discusses herbicides other
 than the chlorophenoxys, nitro- and  chloro-phenols, arsenicals, and
 dipyridyls, which are subjects of separate chapters. Many modern her-
 bicides kill weeds selectively by impairing metabolic processes that are
 unique to plant life. For this reason, their  systemic toxicities in mam-
 mals are generally low.  Nonetheless, there are some  which pose a
 significant risk of poisoning if handled carelessly, and many are irritat-
 ing to eyes, skin, and mucous membranes.
   For several good/reasons, all of the herbicides mentioned  in this
 chapter should  be handled and  applied only  with full attention to
 hygienic measures that minimize personal contact. Many formulations
 contain adjuvants (stabilizers, penetrants,  safeners, surfactants)  that
 may  have significant irritating and toxic  effects. A number  of pre-
 mixed formulations contain two or more active ingredients; the com-
 panion  pesticides  may be more  toxic  than the principal herbicide.
 Finally, some individuals exhibit unique sensitivities to chemicals that
 are not predictable on the basis  of past human exposure experience.
 Good hygienic practice should, therefore, not be disregarded because a
 pesticide is reported to have a high LDSO in laboratory rodents, or is
 said to be "harmless to humans." The rodent LD50 rating is based
 solely on lethality; it says nothing of dosage necessary  to produce
 symptoms or signs, or cause injury or disease after long latency,  sub-
 clinical biochemical effects, or other nonlethal effects on health.
  The fate of these  compounds  after  they  have been absorbed by
 humans should be understood by health professionals who may  need to
 assess the consequences of prior exposure. The water-soluble herbicides
 are not retained in body  tissues for long periods,  as  were the old
 lipophilic organochlorine  insecticides, such as DDT. Some undergo bio-
 transformation in the body, others do not. Most are excreted, mainly in
the urine, within one to four days.
  The following  table is a synoptic listing of the more commonly used
herbicides other than those discussed  in separate chapters. The rat
acute oral LD5o is given as a rough index of  potential lethal toxicity. (If
several values are reported by various sources,  the lowest  is recorded
here.) The adverse  effect information  given  is drawn from many
sources, including  product labels, textbooks, published case histories,
and some unpublished reports. The listing cannot be considered inclu-
sive, either of herbicide products or of effects.

                                83

-------
Chemical Class
Acetamides





Anffldea








Aliphatic acids






Benzamide

Benzole, anisic
acid
derivatives



Benzc-
nitrflee
Benzothia-
diazinone
dioxide
Carbamates
andthio-
carbamates
(faerbi-
ddal)





Carbanl-
lates









Generic
Name
allidocblor

metolachlor



alachlor

propachlor

propanil




trichloro-
acetic acid

dichloro-
propionic
acid, dal-
apon
pronamide

trichloro-
benzoic
acid

chloramben
dicamba
dichlobenil

bentazon


asulam
terbucarb
butylate
cycloate
pebulate
vemolate
EPIC
diallate
trinllate
thiobencarb
barban






chlorpro-
pham


Proprietary Names
Randox, CDAA

Dual, Bicep,
Primagram,
Pennant,
Primextra, Codal
Lasso, Lazo,
Alanox
Ramrod, Bexton

DPA, Erban, Chem
Rice, Propanex,
Riselect, Stam,
Stampede,
Supernox, Surpur
TCA,
NaTA,
Varitox
Dalapon, Basfapon,
Dowpon, Ded-Weed,
Revenge

Kerb

TCBA,
Benzac,
Tribac,
2, S, 6-TBA
Amiben
Banvel
Casoron, Decabane,
Dyclomec, Barrier
Basagran


Asulox
Azac, Azar
Sutan
Ro-Neet
Tfflam, PEBC
Surpass
Eptam, Eradicane
Avadex, Pyradex
Avadex BW
Bolero, Saturn
Carbyne






Furloe, Bud-Nip,
Sprout-Nip, Beet-
Kleen, Chloro-IPC,
Unicrop84,000 irritating to
3,500 eyes, skin, and
2,000 respiratory tract,
921 particularly in
1,800 concentrated form.
1,630 Some may be weak
395 inhibitors of
1,675 cholinesterases.
1,300
1,350 Irritant and
sensitizer. May
generate methemo-
globin at high
dosage. Weak
cholinesterase
inhibitor.
3,800 Skin irritants.
May generate
methemoglobin at
high dosage.
84

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                                             —Continued
Onfeal dan
Chloro-
pyridinyl
Cyclo-
hexenone
derivative
Dinitro-
amino-
benxene
derivatives


Fluorodi-
nitrotolui-
dine com-
pounds
Isoxazo-

Nicotinic
acid-
isopropyl-
amine
derivative
Oxadia-
zolinone
Phoephonateis



Phthalates







Picolinic
compound


Generic
Name
triclopyr
sethoxydim

butralin
isopropalin

pendi-
methalin
oryzalin
benfluraun
dinitramine
ethalflur-
alin
fluchloralin
profluralin
trifluralin






oxadiazon

glyphoeate
fosamine
ammonium

chlorthal-
dimethyl
endothall






picloram



Proprietary Names
Garlon, Crossbow
Turflon
Poast

Amex, Tamex
Paarlan

Prowl, Stomp,
Accotab, Herbodox,
Go-Go-San, Wax Up
Surflan, Dirimal
Benefin, Balan,
Balrtn, Quilan
Cobex
Sonalan
Basalin
Tolban
Treflan, TR-10
Command

Arsenal



Ronstar

Roundup, Glifonox
Krenite


Dacthal, DCPA
Aquathol






Tordon, Grazon



Acute Oral LDw'
mg/kg
630
3,125

12,600
>5,000

1,250
> 10,000
> 10,000
3,000
> 10,000
1,550
1,808
> 10,000
1,369

> 5,000



>3,500

4,300
24,000


> 10,000
51






8,200



Known or Suspected
Adverse Effects
Irritant to skin
and eyes.
Irritating to skin
and eyes.
May be moderately
irritating. These
herbicides do not
uncouple oxidative
phosphorylation or
generate
methemoglobin.
May be mildly
irritating. These
herbicides do not
uncouple oxidative
phosphorylation or
generate
methemoglobin.
May be moderately
irritating.
Irritating to eyes
and skin. Does
not contain

arsenic.
Minimal toxic and
irritant effects.
Minimal toxic and
irritant properties.
Irritating to eyes,
skin, and upper
respiratory tract
Moderately
irritating to
eyes.
Free acid is
highly toxic.
Irritating to
skin, eyes, and
respiratory tract.
See Chapter 15,
page 153.
Irritating to
skin, eyes, and
respiratory tract.
Low systemic
toxicity.'
Triazines
                 ametryn

                 atraton
Ametrex, Evik,
Gesapax
Atratone,
Gesatamin
1,750

1,465
                                               85

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—Continued
Chemical Class






























Triazole



Uracib



Urea
derivatives





Generic
Name
ntrazine


cyanazine
desmetryn
isomethiozin
metribuzin


prometryn

propazine


giwgyitiR



terbu-
thylazine
tcrbutryn

prometon








amitrole,
amino-
triazole


bromacil

lenacU
terbacil
chlorimuron
ethyl
chlorc-
toluron
chloroxuron
difenoxuron
diuron

Proprietary Names
AAtrex, Atranex,
Crisazina,
Griffex, Vectal SC
Bladex, Fortrol
Semeron
Tantizon
Sencor, Lexone,
Sencoral, Sencorex

Caparol, Gcsagard,
PrimatolQ,
Prometrex
Gesamil, Milogard,
Mile-Pro,
PrimatolP
Aquazine, Oekusan
Gesatop, Prim-
atol S, Princep,
Caliber 90
Gardoprim,
PrimatolM
Igran, Prebane,
Terbutrex
Gesafram 50,
Ontracic 800,
Pramitol25B






Amerol, AT-90,
Amitrol-T, Azolan,
Azole, Cytrol,
Diurol, Herbizole,
Simazol, Weedazol
Borea, Bromax,
Hyvar, Rout,
Uragan, Urox B
Ban-Hoe, Venzar
Sinbar
Classic

Dicuran, Tolurex

Tenoran
Ldronion
Cekiuron,
Crisuron, Dailon,
Acute Oral LD»' Known or Suspected
mg/k'g Adverse Effects
1,780


288
1,390
> 10,000
1,100


5,235

>5,000


>5,000



2,000

2,500

2,276



Systemic toxicity
is unlikely
unless large
amounts have been
ingested. Some
triazines are
moderately
irritating to the
eyes, skin, and
respiratory tract.




















This particular
formulation of
prometon is
strongly
irritating to
eyes, skin, and
respiratory tract.
24,600 Minimal systemic
toxicity. Slight
irritant effect.


5,200 Irritant to skin,
eyes, and
respiratory tract.
> 11,000 f Moderately
1 irritating.
> 5,000 l
>4,000

> 10,000

3,700
>7,750
3,400






Systemic toxicity
is unlikely unless
     86

-------
                             —Continued
Chemical Class ^"me0





fluometuron

isoproturon


linuron


methabenz-
thiazuron
metobro
muron
metoxuron


monolinuron

monuron
neburon

siduron
sulfometuron
methyl
tebuthiuron
tetrafluoron
Proprietary Names
Diater, Di-on,
Direx, Diurex,
Diurol, Diuron,
Karmex, Rout,
Unidron, Vonduron
Cotoran, Cottonex

Alon, Arelon,
Belgran, Graminon,
IP50, Tolkan
Afalon, Linex 4L,
Linorox, Linurex,
Lorox, Sarclex
Tribunil

Patoran, Pattonex

Deftor, Dosanex,
Dosaflo, Purivel,
Sulerex
Aresin, Afesin,
Arresin
Monuron
Granurex, Neburex
Herbalt
Tupersan
Oust

Spike, Graslan
Tomilon
Acute Oral LDso' Known or Suspected
mg/kg- Adverse 'Effects





8,900

1,826


1,500


> 2,500

2,603

3,200


2,100

3,600
> 11,000

> 7,500
> 5,000

644
1,265
large amounts have
been ingested.
Many substituted
ureas are
irritating to
eyes, skin, and
mucous membranes.























CONFIRMATION OF TOXICANT ABSORPTION

  Although there are analytical methods for residues of many of the
herbicides mentioned in this chapter, and for some of the mammalian
metabolites generated from them, these procedures are not generally
available to confirm human absorption of the chemicals. Prior expo-
sure must be determined from a recent history of occupational contact
or accidental or deliberate ingestion.

TREATMENT  OF TOXICOSIS
 1.
Skin contamination should be removed promptly by washing with
soap and  water. Contamination of the eyes should be treated
immediately by prolonged flushing of the eyes with copious
amounts of clean water.  If dermal  or ocular irritation persists,
medical attention should be obtained without delay.

                          87

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2.   INGESTIONS of these herbicides  are likely to be followed by
    vomiting and diarrhea due to the  irritant properties  of most of
    the toxicants. Management depends on: 1) the best estimate of
    quantity originally ingested, 2)  time elapsed since ingestion, 3)
    effectiveness of vomiting, and 4) the clinical status of the subject.
    ACTIVATED CHARCOAL is probably effective in limiting irri-
    tant effects and reducing absorption of most or all of these herbi-
    cides. Aluminum hydroxide gels may be useful in neutralizing the
    irritant actions of the more acidic agents. Sorbitol should be given
    to induce catharsis if bowel sounds are present and if spontaneous
    diarrhea has not already commenced. Dehydration and electrolyte
    disturbances may be severe enough to require oral or intravenous
    fluids.
      There are  no specific antidotes  for poisoning by these herbi-
    cides. In the case of suicidal ingestions, particularly, the possibili-
    ty must always be kept in mind that multiple toxic  substances
    may have been swallowed.
    A.  If large amounts of herbicide have been ingested, and  if the
        patient is fully alert,  induce EMESIS with Syrup of Ipecac,
        followed by several glasses  of  water. Dosage for  adults and
        children over 12  years: 30  ml;  dosage for  children under 12
        years: 15 ml.  When vomiting has stopped,  give ACTIVATED
        CHARCOAL. Add SORBITOL  to  the  charcoal slurry unless
        diarrhea  has already  commenced. If, for  some reason,  the
        patient is not fully alert, put hi place a cuffed endotracheal
        tube to protect the airway, then aspirate and lavage the stom-
        ach with a slurry of activated  charcoal. Leave a quantity of
        charcoal, with sorbitol, in the stomach before withdrawing the
        stomach tube (see Chapter 1, TREATMENT, Section 6, page
        8). Repeated administration of charcoal at half or more the
        initial dosage every 2-4 hours may be beneficial.
    B.  If the amount  of ingested herbicides  was small,  if effective
        emesis has already occurred, or if treatment is delayed, ad-
        minister the activated charcoal  and sorbitol by mouth.
    C.  If serious dehydration and electrolyte depletion have occurred
        as a result of vomiting and diarrhea, monitor blood electro-
        lytes and fluid balance and administer intravenous infusions
        of glucose, normal saline, Ringer's solution, or Ringer's-lactate
        to restore extracellular fluid volume and electrolytes. Follow
        this with oral  nutrients as soon as fluids can be retained.
        Fluids serve to support excretion of the toxicants.
    D.  Supportive measures  are ordinarily sufficient for successful
        management of excessive exposures to these herbicides  (en-
        dothall is  an exception—see Chapter 15,  p. 154). If the pa-
        tient's condition deteriorates in spite of good supportive care,
        the operation of an alternative or additional toxicant should
        be suspected.

                                88

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                        CHAPTER 12

                      FUNGICIDES
  Fungicides are extensively used in industry, agriculture, the home,
and garden for: 1) protection of seed grain during storage, shipment
and germination; 2) protection of mature crops, berries, seedlings, flow-
ers, and grasses in the field, in storage, and during shipment; 3) sup-
pression of mildews that attack painted surfaces; 4) control of slime in
paper  pulps; and 5) protection  of carpet and fabrics in the home.
  Fungicides vary enormously in their potential for causing adverse
effects in  humans. Historically, some of the most tragic epidemics of
pesticide poisoning occurred because  of mistaken consumption of seed
grain treated with organic mercury  or hexachlorobenzene. However,
most fungicides currently in use are unlikely to  cause frequent or
severe  systemic poisonings for several reasons: 1) many have low inher-
ent toxicity in  mammals and are inefficiently absorbed; 2) many are
formulated as suspensions of wettable powders or granules, from which
rapid,  efficient  absorption is unlikely; and 3) methods of application
are such that relatively few individuals are intensively exposed. Apart
from systemic poisonings, fungicides  as a class have probably caused
disproportionate numbers of irritant injuries to skin and mucous mem-
branes, as well as some dermal sensitizations.
  The  following discussion considers  the recognized adverse effects of
widely used fungicides. In the case of those agents which have caused
systemic poisoning, some  recommendations for management of poison-
ings and injuries are set forth. For those fungicides not known to have
caused systemic poisonings in the past, only general guidelines can be
offered.
  The  discussion of fungicide-related adverse effects  proceeds in this
order:
  Substituted Benzenes
  Thiocarbamates
  Ethylene Bis Dithiocarbamates
  Thiophthalimides
Copper Compounds
Organomercury Compounds
Organotin Compounds
Cadmium Compounds
Miscellaneous Organic Fungicides
                               89

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                   SUBSTITUTED BENZENES

HEXACHLOROBENZENE (HCB, Anticarie, Ceku C.B., No Bunt).

                                Cl

                         Cl
                                       Cl
  Principal formulations are dusts and powders.
  Hexachlorobenzene differs chemically and toxicologically from hex-
 achlorocyclohexane, the gamma  isomer of which  (lindane) is still a
 widely used insecticide (see Chapter 3, TOXICOLOGY).

 TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  HEXACHLOROBENZENE

  Although this seed protectant  fungicide has only slight irritant ef-
 fects and relatively low single-dose  toxicity, long-term  ingestion  of
 HCB-treated grain by Turkish farm dwellers in the late 1950's caused
.several thousand cases of hepatic porphyria (porphyria cutanea tarda).
 This condition was due  to impaired hemoglobin synthesis, leading  to
 toxic end-products (porphyrins) in body tissues. The disease was charac-
 terized by excretion of red-tinged (porphyrin-containing) urine, bullous
 lesions of light-exposed skin,  scarring and atrophy of skin with over-
 growth of hair,  liver enlargement, loss of appetite,  arthritic disease,
 and wasting of skeletal muscle mass.  Although most adults ultimately
 recovered after they stopped  consuming the HCB-treated grain, some
 infants nursed by affected mothers died.
  Hexachlorobenzene  is effectively  dechlorinated  and  oxidized  in
 humans; trichlorophenols are the  major urinary  excretion products.
 Disposition is sufficiently prompt that occupationally exposed workers
 usually show only slight elevation of blood HCB concentrations. HCB is
 sometimes present in blood  specimens from  "non-occupationally ex-
 posed" persons up to concentrations of about 5 meg per liter. Residue
 in food is the probable source.

 CONFIRMATION  OF POISONING BY HEXACHLOROBENZENE

  HCB can be measured in blood by gas chromatography. Chlorophenol
 metabolites can be measured in the urine.
  Although inherited disease and a number of exogenous agents may
 cause porphyrins to appear in the urine, a test for porphyrins may be

                               90

-------
 useful for toxicologic diagnosis if there has been a known exposure to
 HCB or if  a patient exhibits  signs suggestive of porphyria  cutanea
 tarda.
  More than 0.5 mg per liter of porphyrins causes the untreated urine
 to exhibit a wine-red color in ordinary light. Somewhat lower concen-
 trations can be detected by examining the urine in ultraviolet light
 (366 nm emission). Red or orange-red fluorescence indicates presence of
 uroporphyrins. However,  background  fluorescence from other  urine
 constituents may mask this emission. If the above examination is
 negative, therefore, the following screening test for uroporphyrins can
 be performed:
 1.  Acidify the urine to pH 4.0 with acetic acid.
 2.  Heat for 15 minutes in a 100° C water bath.
 3.  Cool. Clean the outside of the test tube carefully, and examine for
     orange-red fluorescence in  UV light (366 nm).
  Urinary coproporphyrin excretion is  also increased in HCB intoxica-
 tion. The following test can be  done to detect elevated concentrations:
 1.  Put 5 ml  of clear  (filtered) urine in a 16 x 150 mm quartz test
     tube.
     Add in this order: 1 ml glacial acetic acid, 5 ml ethyl ether, then 3
     drops fresh 3% hydrogen peroxide.
     Close tube with a clean rubber stopper and invert 12 times to mix
     and extract. Allow to stand 10 minutes. (Centrifuge if necessary to
     break emulsion.)
     Examine the ether layer in UV light for pink, violet, or rose red
     emitted light, indicating presence of coproporphyrins.
2.
3.
4.
TREATMENT OF HEXACHLOROBENZENE TOXICOSIS

 1.   Dermal contamination should be washed off with soap and water.
     Contamination of the eyes should be removed by flushing with
     copious amounts of water. If irritation persists, specialized medi-
     cal care should be obtained.
 2.   If a large amount of HCB has been ingested in the last few hours,
     and if copious vomiting has not already occurred, the stomach
     must be emptied and steps taken to limit gastrointestinal  absorp-
     tion. If the patient is fully alert and nervous system depression is
     not anticipated, oral administration of Syrup of Ipecac is probably
     the best way to empty the stomach.
     Dosage of SYRUP OF IPECAC:
        Adults and children over  12  years: 30 ml, followed  by 2-3
        glasses of water.
        Children under 12 years: 15 ml, followed by 1-2 glasses of
        water. Children less than one year should receive only 10-15
        ml and should be under direct medical supervision if at all
        possible.
                               91

-------
3.
4.
When  vomiting stops  after induced  emesis, give charcoal and
cathartic orally by adding sorbitol to the charcoal slurry.
Dosage of ACTIVATED CHARCOAL:
    Adults and children over 12 years:  50-100 gm in 300-800 ml
    water.
    Children under 12 years:  15-30 gm in 100-300 ml water.
Dosage of SORBITOL:
    Adults and children over 12 years: 1-2 gm/kg body weight to
    a maximum of 150  gm per dose.
    Children under 12 years:  1.0-1.5 gm/kg body weight to  a
    maximum of 50 gm per dose.
If sorbitol is given separately, it should be diluted with an equal
volume of water before administration.
If there are any indications of central nervous system depression,
or if the patient  fails to vomit within 30 minutes of Syrup of
Ipecac administration,  measures should be taken to protect the
respiratory tract from  aspiration of gastric contents (preferably a
cuffed endotracheal tube), then  the stomach should be emptied by
gastric intubation, aspiration and lavage with a slurry of activat-
ed  charcoal (see Chapter  1, TREATMENT, Section  6,  page 8).
Instill activated charcoal following lavage. Unless diarrhea has
already commenced, include a cathartic (see  above for dosage) to
hasten elimination.
CAUTION: Do not instill fluid  so rapidly that overloading of the
stomach leads to  vomiting or  regurgitation, followed  by aspira-
tion. Serious electrolyte disturbances may follow catharsis, espe-
cially in young children. Monitor fluid balance and serum electro-
lytes.
If the amount of ingested HCB was small,  or if treatment has
been delayed several hours, or  if spontaneous vomiting has effec-
tively emptied the stomach,  oral administration' of charcoal and
sorbitol at the doses recommended above probably represents opti-
mal management.
If contact  with the toxicant has been minimal (for example, oral
contamination only, promptly flushed out of the  mouth) adminis-
tration of  charcoal without a cathartic, followed by careful obser-
vation of the patient,  probably represents optimal management.
In persons who have experienced significant tissue storage of HCB
(as from protracted uptake of small quantities) administration of
cholestyramine accelerates elimination by interrupting enterohe-
 patic recirculation. It  is usually administered in 3-8 gm doses, 4
 times a day, before meals and at bedtime. Dose  should be mixed
 with a pulpy fruit or liquid.
 Persons affected by porphyria  should avoid sunlight, which exac-
 erbates the dermal injury by porphyrins.
                               92

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PENTACHLORONITROBENZENE  (PCNB,  quintozene,  Terraclor,
Avicol,  Botrilex, Earthcide,  Folosan, Kobu,  Kobutol, Pentagon, Til-
carex, Tri-PCNB).

                              NO,
                         Cl
  This fungicide is  used to dress seed and treat soil. Formulations
include emulsifiable concentrates,  wettable powders, and granules.
Hexachlorobenzene is a minor contaminant of technical PCNB.

TOXICOLOGY AND MANIFESTATIONS OF  POISONING BY
  PENTACHLORONITROBENZENE

  High concentrations in prolonged contact with skin  have caused
sensitization in some tested volunteers, but neither irritation nor sensi-
tization has been reported in occupationally exposed workers. One case
of conjunctivitis and keratitis occurred following eye contamination.
This resolved slowly but completely.
  Systemic poisonings have not been reported. Disposition in laborato-
ry animals is slow, probably due to. enterohepatic recirculation. Excre-
tion is  chiefly biliary,  with some  conversion  to pentachloroaniline,
pentachlorophenol, and  other metabolites in  the liver.  Although a
methemoglobinemic  effect might be suspected (as from nitrobenzene),
this has not been reported in man or animals, nor has hepatic por-
phyria (as from hexachlorobenzene) been reported.

CONFIRMATION OF ABSORPTION OF
  PENTACHLORONITROBENZENE

  PCNB and metabolites can be measured in body fluids by gas  chro-
matography. The analysis is not widely available.

TREATMENT  OF PENTACHLORONITROBENZENE TOXICOSIS

  See  HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2, and 3 above.
                              93

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DICHLORAN  (DCNA, . ditranil,  Botran, Allisan,  Kiwi Lustr  277,
  Resisan).
  Dichloran is formulated as wettable powder, dusts, and  flowable
powders.

TOXICOLOGY AND MANIFESTIONS OF POISONING BY
  DICHLORAN

  This broad spectrum fungicide is widely used to protect perishable
produce. It is absorbed by occupationally exposed workers, but prompt-
ly eliminated, at least partly in the urine. Residence half-life in man is
probably less than 27 hours. Biotransformation products include dich-
loroaminophenol, which is an uncoupler  of oxidative phosphorylation
(enhances  heat production). Extraordinary doses of dichloran given to
laboratory animals cause liver injury and corneal opacities.
  Based on laboratory animal studies and effects of similar compounds,
large doses might be expected to cause liver injury, pyrexia, corneal
opacities,  and possibly methemoglobinemia. None of these have been
observed hi humans exposed to DCNA. Daily oral dosage of 10 mg per
day for 90 days was tolerated by  20 adult male subjects without observ-
able effect.

CONFIRMATION OF ABSORPTION OF DICHLORAN

  Methods have been described for analysis of dichloran, but they are
not widely available.

MANAGEMENT OF DICHLORAN EXPOSURE

  See HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2,  and 3 above.
                               94

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CHLOROTHALONIL (Bravo, CldrtoCaffaro,  Clortosip, Dacohil  2787,
Exotherm Termil, Tuffcide).
                                CN
                          Cl
  Chorothalonil is  available  as  wettable powder, water  dispersible
granules, and flowable powders.
  Chlorothalonil has caused irritation of skin and mucous membranes
of the  eye and respiratory tract on contact. Rarely, it has caused
dermal sensitization. It is apparently poorly absorbed across the skin
and the  gastrointestinal lining.  No  cases of systemic  poisoning in
humans have been reported.

CONFIRMATION OF ABSORPTION OF CHLOROTHALONIL

  Chlorothalonil can be measured in blood by gas chromatography, but
the analysis is not widely available.

TREATMENT OF CHLOROTHALONIL TOXICOSIS

  See HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2, and 3 above.

CHLORONEB (Terraneb SP).
                                    OCH.
  Chloroneb is supplied as wettable powder for treatment of soil and
seed.

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  CHLORONEB

  This agent exhibits very low oral toxicity in mammals. It may  be
moderately irritating to skin and mucous membranes. The metabolite
dichloromethoxyphenol is excreted in the urine. No cases of systemic
poisoning in humans have been reported.

                              95

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CONFIRMATION OF ABSORPTION OF CHLORONEB

  Chloroneb can be measured in body fluids by chromatography, but
the analysis is not widely available.

MANAGEMENT OF CHLORONEB EXPOSURE

  See HEXACHLOROBENZENE, TREATMENT OF TOXICOSIS, Sec-
tions 1, 2, and 3 above.
                      THIOCARBAMATES

  Unlike the N-methyl carbamates (Chapter 2), thiocarbamates have
very little insecticidal potency. A few exhibit weak anticholinesterase
activity, but most have no significant effect on this enzyme. Overall,
they are less of a threat to human health than the insecticidal carba-
mates. Fungicidal thiocarbamates are discussed in this section while
those used as herbicides are considered in Chapter 11.

THIRAM
                    S
                    II
                    c
— C  —  S — S  — C — N
S
II
C
    I

\
                                                     CH3
COMMERCIAL PRODUCTS

  AAtack, Aules, Chipco Thiram 75, Fermide 850, Fernasan, Hexathir,
Mercuram, Nomersam, Polyram-Ultra, Pomarsol forte, Spotrete-F, Spo-
trete WP 75, Tetrapom, Thimer, Thioknock, Thiotex, Thiramad, Thira-
san, Thiuramin, Tirampa, TMTD, TMTDS, Trametan, Tripomol, Tuads,
Vancide TM.
  Thiocarbamates are  commonly formulated  as dusts, wettable  pow-
ders  or water suspensions. They are used to  protect seeds, seedlings,
ornamentals, turf, vegetables, fruit, and apples.

TOXICOLOGY  AND MANIFESTATIONS OF POISONING BY
  THffiAM

  Thiram dust is moderately irritating to human skin, eyes, and respi-
ratory mucous membranes. Contact dermatitis has occurred in occupa-
tionally exposed workers. A few individuals have experienced sensitiza-
tion to thiram.
                              96

-------
  Systemic human poisonings by  thiram itself have been  very few,
probably due to limited absorption in most circumstances  involving
human exposure. Those which have been reported have been similar
clinically to toxic  reactions to  disulfiram (Antabuse),  the ethyl  ana-
logue of thiram which has been extensively used in alcohol aversion
therapy. In laboratory animals, thiram at high dosage has effects simi-
lar to those of disulfiram (hyperactivity, ataxia, loss of muscle tone,
dyspnea, convulsions), but thiram appears to be about 10 times as toxic
as disulfiram.
  Clinical doses of disulfiram (0.25-1.00 gm daily) have caused fatigue,
headache, dizziness, tremor, restlessness, anorexia, and nausea. Rarely,
liver injury, peripheral  neuropathy, renal tubular damage,  and ence-
phalopathic symptoms have been reported following large and/or pro-
tracted dosage.  These effects may be due to one or more thiocarbamate
biotransformation  products (including carbon disulfide) formed in the
gut or tissues.
  Neither thiram  nor disulfiram are cholinesterase inhibitors. Both,
however, inhibit the enzyme acetaldehyde dehyrogenase, which is criti-
cal to the conversion of acetaldehyde to acetic acid. This is the basis for
the "Antabuse" reaction which occurs when ethanol is consumed  by a
person on regular disulfiram dosage: nausea, vomiting, pounding head-
ache, dizziness,  faintness, mental confusion, dyspnea, chest and abdom-
inal pain, profuse  sweating, and skin rash.  In rare instances, "Anta-
buse" reactions may have occurred following  beverage alcohol inges-
tion by workers previously exposed to thiram.

CONFIRMATION  OF ABSORPTION OF THIRAM

  Urinary xanthurenic acid excretion has been used to monitor work-
ers exposed to thiram. The test is not generally available.

TREATMENT OF THIRAM TOXICOSIS

  Wash thiram from the skin with soap and water. Flush contamina-
tion from the eyes with  copious amounts of clean water. If irritation of
skin or eyes persists, medical treatment should be obtained.
  If a large amount of thiram has been swallowed and effective vomit-
ing has not already occurred, the stomach should be emptied by intu-
bation, aspiration,  and  lavage, taking all precautions to protect the
airway from aspiration of vomitus. Lavage should be followed by instil-
lation  of  activated charcoal  and  cathartic (see Chapter 1, TREAT-
MENT, Section 6, page 8). Syrup of Ipecac administration is not advisa-
ble because the contained alcohol (2%) may possibly induce  an "Anta-
buse" reaction.
  If only a small  amount of thiram has been ingested  and/or treat-
ment has been delayed, oral administration of activated charcoal and
cathartic probably represents optimal management.

                                97

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  In severe poisonings, intravenous infusion  of GLUCOSE solution
protects the liver and supports mechanisms of detoxication and excre-
tion. If vomiting and diarrhea are severe, fluid balance and  serum
electrolytes should be monitored, and appropriate electrolyte solutions
infused to correct losses.
TREATMENT OP ACETALDEHYDE TOXICOSIS (ANTABUSE
  REACTION)

  OXYGEN inhalation,  Trendelenburg positioning, and  intravenous
fluids are usually  effective in relieving manifestations of Antabuse
reactions. Persons who have absorbed any significant amount of dithio-
carbamate must avoid alcoholic beverages for at least three weeks.
Disposition of thiocarbamates is slow and their  inhibitory  effects oh
enzymes are slowly reversible.

METAM-SODIUM (METHAM-SODIUM)
             CH
                      N-C
                             S
H
COMMERCIAL PRODUCTS
                                 S-Na  • 2H   0
  A7  Vapam, Busan 1020, Karbation, Maposol, Metam-Fluid BASF,
Nemasol, Solasan 500, Sometam, Trimaton, Vapam, VPM.
  Formulated in aqueous solutions for application as a soil biocide to
kill fungi, bacteria, weed seeds, nematodes, and insects.

TOXICOLOGY  AND MANIFESTATIONS OF POISONING BY
  METAM-SODIUM

  Although animal feeding studies do not indicate extraordinary toxici-
ty of metam-sodium by ingestion, its decomposition in  water yields
methyl isothiocyanate, a gas that is extremely irritating to respiratory
mucous membranes, to the eyes, and to the lungs. Inhalation of methyl
isothiocyanate may cause pulmonary edema (severe respiratory dis-
tress, coughing  of bloody,  frothy sputum). For this reason, metam-
sodium must be used out of doors only, and stringent precautions must
be taken to avoid inhalation of evolved gas.
  Theoretically, exposure to metam-sodium may predispose the individ-
ual to Antabuse reactions if alcohol is ingested after exposure.  Such
occurrences have not been reported.

                              98

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CONFIRMATION OP ABSORPTION OF METAM-SODITJM

  There are no tests for metam-sodium or its breakdown products in
body fluids.

TREATMENT OF METAM-SODIUM TOXICOSIS

  Contamination  of the skin and eyes should be treated immediately
with copious  amounts of water to avoid burns and corneal injury. If
eye  or  skin irritation  persists, expert medical treatment should be
obtained. Poisonings by ingestion of metam-sodium have not been re-
ported. If a large  amount has been ingested recently, empty the stom-
ach by gastric intubation, aspiration, and lavage, after taking all  pre-
cautions to protect the airway (see Chapter 1, TREATMENT, Section 6,
page 8). Instill activated charcoal. Also give cathartic unless diarrhea
has already commenced.
  If pulmonary irritation or edema occur as a result of inhaling methyl
isothiocyanate, transport the victim promptly to a medical facility.
Treatment for pulmonary edema should proceed as outlined in Chapter
14, FUMIGANTS, page 139.
  Metam-sodium is not a cholinesterase inhibitor. Atropine is not anti-
dotal.
ZIRAM AND FERBAM

                •CH3
                    \
                           S   "
                           11
                       N -C-S
                                  n
COMMERCIAL PRODUCTS
  Ziram (Carbazinc, Corozate, Cuman, Drupina 90, Fungostop, Hexazir,
Mezene, Prodaram, Tricarbamix Z, Triscabol, Zerlate, Vancide MZ-96,
Zincmate, Ziram Technical, Ziram F4, Ziram W76, Ziramvis, Zirasan
90, Zirberk, Zirex 90, Ziride, Zitox).
  Ferbam (Carbamate,  Ferbam, Ferberk, Hexaferb,  Knockmate, Tri-
fungol).
  These are formulated as flowable and wettable powders, used widely
on fruit and nut trees, apples, vegetables, and tobacco.
                               99

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TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  ZIRAM AND FERBAM

  Dust is irritating to the skin, respiratory tract, and eyes. Prolonged
inhalation of ziram is said to have caused neural and visual disturb-
ances, and, in  a  single  case of poisoning, a fatal hemolytic reaction.
  If absorbed" in  sufficient dosage, metallo thiocarbamates may theo-
retically predispose  to  an Antabuse reaction following  ingestion  of
alcohol. (See THIRAM.) No occurrences of this have been reported.

CONFIRMATION OF ABSORPTION OF ZIRAM AND FERBAM

  No tests for  these fungicides or their breakdown products in body
fluids are available.

TREATMENT  OF ZIRAM AND FERBAM TOXICOSIS

  Skin contamination should be washed off with soap and water. Con-
tamination  of  the eyes  should be removed with copious amounts  of
water.  If dermal or eye irritation persists, specialized medical treat-
ment should be obtained.
  If substantial amounts of ferbam or ziram have been ingested recent-
ly, the stomach should  be emptied by  gastric intubation, aspiration,
and lavage, after all measures have been taken to protect the airway
(see Chapter 1, TREATMENT, Section 6, page 8). If dosage was small
and/or several  hours have elapsed since ingestion, oral administration
of charcoal and a cathartic probably represents optimal management.
  If hemolysis  occurs, intravenous fluids should  be administered, and
induction of diuresis considered (see Chapter 14, TREATMENT OF
NAPHTHALENE TOXICOSIS, page 141).

   ETHYLENE BIS DITHIOCARBAMATES (EBDC COMPOUNDS)

MANEB, ZINEB, NABAM, and MANCOZEB

            H     H     S
            I       I      II
          HC -  N -   C  -  S
                                     Mn or Zn or Na
          HC  -  N  - C -  S
            I       I      M
            H     H     S
                              100

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COMMERCIAL, PRODUCTS

  Maneb (Akzo Chemie Maneb, BASF-Maneb Spritzpulver, Dithane M-
22, Kypman 80, Manex 80, Maneba, Manesan, Manex, Manzate, Man-
zate  D, M-Diphar, Polyram M, Remasan  Chloroble M,  Rhodianebe,
Sopranebe, Trimangol, Tubothane, Unicrop Maneb).
  Zineb (Aspor, Chem Zineb, Devizeb, Dipher, Dithane Z-78, Hexath-
ane,  Kypzin, Lonacol,  Parzate,  Parzate C, Polyram Z, Tiezene, Tritof-
torol, Zebtox, Zineb 75 WP, Zinosan).
  Nabam (Chem Bam, DSE, Nabasan, Parzate, Spring Bak).
  Maneb and Zineb are formulated as wettable and flowable powders.
Nabam is provided as a soluble powder and in water solution.
  Mancozeb (manzeb, Dithane M-45, Manzate 200, Akzo Chemie Man-
cozeb, Mancozin, Manzin, Nemispor, Penncozeb, Policar MZ, Policar S,
Vondozeb Plus, Ziman-Dithane). Mancozeb is a coordination  product of
zinc  ion and maneb.  It is formulated as a dust and as wettable and
liquid flowable powders.

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  EBDC COMPOUNDS

  These fungicides may cause irritation of the skin, respiratory tract,
and eyes. Both maneb and zineb have apparently been responsible for
some cases of chronic  skin disease in  occupationally exposed workers,
possibly by sensitization.
  Although marked adverse effects may follow injection of EBDC com-
pounds into  animals, systemic  toxicity by  oral and dermal routes is
generally low. Nabam exhibits the greatest toxicity, probably due to its
greater water solubility and absorbability. Maneb is moderately soluble
in water,  but mancozeb and zineb are essentially  water  insoluble.
Absorption of the latter fungicides across skin and mucous membranes
is probably very limited. Systemic poisonings of humans have been
extremely rare. However, zineb apparently precipitated an  episode of
hemolytic anemia in one worker predisposed by reason of  multiple red
cell enzyme deficiencies.
  The  EBDC compounds are not  inhibitors of cholinesterase  or of
acetaldehyde dehydrogenase. They do  not induce cholinergic illness or
"Antabuse" reactions.

CONFIRMATION OF ABSORPTION OF EBDC COMPOUNDS

  No tests for these fungicides or their breakdown products in body
fluids are available.

MANAGEMENT  OF EBDC EXPOSURE

  See  this  chapter,   HEXACHLOROBENZENE,, TREATMENT  OF
TOXICOSIS, Sections 1 and 2 above, page 91.

                              101

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                     TfflOPHTHALIMIDES
 CAPTAN, CAPTAFOL, and FOLPET


           N-S-C-CI   I
                Cl
o
II
II
•c\ ci ci
x II s?
N-S-C-C-CI f
/ ll1^
•c ci ci ^
II
1!
O
o
II
II
V^

Cl
N-S-C-CI
\/
||
II
O
1
Cl

                               CAPTAFOL
                                                       FOLPET
             CAPTAN

COM1VIERCIAL PRODUCTS

  Captan (Captanex, Captaf, Merpan, Orthocide, Vondcaptan).
  Captafol (Crisfolatan, Difolatan, Foltaf, Haipen, Merpafol, Mycodifol,
Sanspor).
  Folpet (Folpan, Phaltan, Thiophal, Fungitrol II).
  These agents are widely used to protect seed, field crops, and stored
produce. They are formulated as dusts and wettable powders.

TOXICOLOGY AND ADVERSE  EFFECTS OF
  THIOPHTHALIMIDES

  All of these fungicides are moderately irritating to the skin, eyes,
and respiratory tract. Dermal sensitization may occur; captafol appears
to have been responsible for several episodes of occupational contact
dermatitis. No systemic poisonings by thiophthalimides have been re-
ported  in man. Laboratory  animals given  very large doses of captan
exhibit hypothermia, irritability, listlessness, anorexia, hyporeflexia,
and oliguria, the latter with glycosuria and hematuria,

CONFIRMATION OF ABSORPTION OF  THIOPHTHALIMIDES

  There are no tests for these fungicides or their breakdown products
in body fluids.

MANAGEMENT OF THIOPHTHALIMIDE EXPOSURE

  See  this chapter, HEXACHLOROBENZENE,  TREATMENT  OF
TOXICOSIS, Sections 1  and 2, above, page 91.
                    COPPER COMPOUNDS

INORGANIC COPPER COMPOUNDS

  Cuprous oxide; cupric oxide; copper hydroxide.

                             102

-------
  Copper carbonate, basic; copper ammonium carbonate.
  Copper acetate; copper sulfate;  copper sulfate, tribasic (Bordeaux
Mixture); copper oxychloride; copper silicate.
  Copper lime dust; copper potassium sulfide.

ORGANIC COPPER COMPOUNDS

  Copper linoleate, naphthenate, oleate, phenyl salicylate, quinolino-
late, and resinate.
  Insoluble compounds are formulated as wettable powders and dusts.
Soluble salts are prepared as aqueous solutions. Some organometallic
compounds are soluble in mineral oils.
  A great many commercial copper-containing fungicides are available.
Some are mixtures of copper compounds. Others include  lime, other
metals, and other fungicides.  Compositions of specific  products can
usually be provided by manufacturers or by  poison control  centers.
  There are several copper-arsenic compounds, such as Paris Green,
still used in some agricultures. Toxicity of these  is chiefly  due  to
arsenic content (see Chapter 6, ARSENICAL PESTICIDES).

TOXICOLOGY AND MANIFESTATIONS OF  POISONING BY
  COPPER COMPOUNDS

  The  dust and powder preparations  of copper compounds  are irritat-
ing to  the skin, respiratory tract, and particularly to  the eyes. The
soluble copper salts (such as the sulfate and acetate) are corrosive  to
mucous membranes and the cornea. Limited solubility and absorption
probably account for generally low systemic toxicities of most com-
pounds. The more absorbable organic copper  compounds exhibit the
greatest systemic toxicity in laboratory animals. While irritant effects
from occupational exposures to copper-containing fungicides have been
fairly frequent, systemic poisonings of humans have been rare. Most of
what is known about mammalian toxicity of  copper compounds has
come from veterinary toxicology (livestock seem uniquely vulnerable)
and rare  poisonings in man due to deliberate  ingestions of copper
sulfate or to consumption of water or food that had been contained  in
copper vessels. The principal features of poisoning by ingested copper
compounds have been 1) gastrointestinal irritation (vomiting and burn-
ing pain in the  mouth, esophagus and stomach, abdominal pain and
diarrhea, sometimes with blood), 2) headache, sweating, weakness, and
sometimes shock, 3) liver enlargement and jaundice, 4) hemolysis and
methemoglobinemia,  and 5) albuminuria, hemoglobinuria,  and some-
times acute renal failure.
                               103

-------
TREATMENT OF COPPER TOXICOSIS

  Contaminating dust and powder should be washed from the skin
with soap and water. The eyes should be flushed free of irritating dust,
powder, or solution,  using  clean water or saline. If eye  or  dermal
irritation persists, medical treatment should be obtained. Eye irritation
may be severe.
  Management of poisonings by ingestion  of copper-containing fungi-
cides  depends entirely on the chemical nature of the compound: the
strongly ionized salts present the greatest hazard; the oxides, hydrox-
ides, oxychloride, and oxysulfate are less likely to cause severe system-
ic poisoning.
 1.   Give water or milk as soon as possible to dilute the toxicant and
     mitigate corrosive action on the mouth, esophagus, and gut.
 2.   Unless vomiting has been vigorous and effective,  empty the stom-
     ach by intubation, aspiration,  and lavage, taking all precautions
     to protect the respiratory tract from aspirated stomach contents.
     (See Chapter 1, TREATMENT, Section 6, page 8). Activated char-
     coal included in the lavage fluid may be of some value against the
     organometallic compounds, but is probably less  effective  against
     the inorganic copper compounds.
     CAUTION: Gastric intubation  may pose a serious risk of esopha-
     geal perforation if corrosive action has been severe. In this event,
     it may be best not to attempt intubation.
 3.   If indications of systemic illness appear, administer intravenous
     fluids containing glucose and electrolytes. Monitor fluid balance,
     and correct blood electrolyte concentrations as needed.. If shock
     develops, give blood transfusions  and vasopressor amines, as re-
     quired.
 4.   Monitor plasma for evidence of hemolysis (free hemoglobin) and
     the  red cells for methemoglobin. If hemolysis occurs,  alkalinize
     the  urine to about pH 7.5 by adding sodium  bicarbonate to the
     intravenous infusion fluid (for dosage,  see Chapter 7, TREAT-
     MENT, Section 5, page 67). Also, mannitol diuresis may be consid-
     ered. Unless methemoglobinemia is severe (30-40%), it is probably
     not advisable to administer methylene blue.
 5.   Severe pain may require the administration of morphine.
 6.   The value of chelating agents in copper poisoning  has not been
     established. BAL appears to show some promise in accelerating
     copper excretion and alleviating illness. If the severity of poison-
     ing appears to warrant its use, a recommended schedule of dosage
     for initial therapy with BAL and subsequent penicillamine admin-
     istration  is offered  in Chapter  6,  ARSENICAL PESTICIDES,
     TREATMENT, Sections 9 and 10, pages 60-61.
                                104

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               ORGANOMERCURY COMPOUNDS
METHYL MERCURY COMPOUNDS
                    H
                    I
                  HC -
                    H
                                       INORGANIC or
                                       ORGANIC ION
COMMERCIAL PRODUCTS

  Methyl mercury hydroxide, nitrile, benzoate,  acetate,  propionate,
pentachlorophenate, quinolinolate.

METHOXYETHYL MERCURY COMPOUNDS
        H
        i
       HC
         i
        H
H
C
 i
H
              H
- 0  -  C - C - Hg*
C
 i
H
INORGANIC or
ORGANIC ION
COMMERCIAL PRODUCTS

     Methoxyethyl  mercury acetate (MEMA, Panogen, Panogen  M).
     Methoxyethyl mercury chloride (MEMC, Emisan 6, Geresan).

PHENYL MERCURIC ACETATE


0 -

0
II
C -

H

GH
H
COMMERCIAL PRODUCTS

  Agrosan, Cekusil, Celmer, Hong Nien,  Liquiphene, Mersolite,  Pa-
misan, Phix, PMAS, Seedtox, Shimmer-ex, Tag HL 331, Unisan.
  Setrete  (Gallotox, PMAA) is phenyl mercury ammonium acetate.
  These fungicides have been  formulated as aqueous solutions and
dusts. They have been used chiefly as seed protectants. Use of alkyl
mercury fungicides in the United States has been virtually prohibited
for several  years.  Phenyl mercuric acetate is still  used  to  control
diseases of turf, but  other applications have been sharply restricted.
                              105

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TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  ORGANOMERCURY COMPOUNDS

  The mercurial fungicides are among the most toxic pesticides  ever
developed, in terms of chronic as well as acute hazard. Epidemics of
severe, often fatal,  neurologic disease have occurred when indigent
residents of less developed countries consumed methyl mercury-treated
grain intended for planting of crops. Poisoning has also occurred when
meat from animals fed mercury-treated seed was eaten. Most of what
is known of poisoning by organic mercurial fungicides has come from
these occurrences.
  Organic mercury compounds are efficiently absorbed across the gut
and possibly across the skin. Volatile organic mercury is readily taken
up across the pulmonary  membrane.  Methyl mercury  is selectively
concentrated in the tissue  of the nervous system, and also in the red
blood cells. Other alkyl mercury compounds are probably distributed
similarly. Excretion occurs almost entirely by way of the bile into the
bowel. The residence half-life of methyl mercury in the human is about
70 days. There is significant conversion of organic mercury to inorgan-
ic mercury in the red cell.
  Early symptoms of poisoning are metallic taste in the mouth, numb-
ness and tingling of the digits  and face, tremor, headache, fatigue,
emotional lability,  and  difficulty thinking. Manifestations of more
severe  poisoning are incoordination, slurred speech, loss  of position
sense, hearing loss, constriction of visual fields, spasticity or rigidity of
muscle movements, and deterioration of mental capacity. Many poison-
ings caused by ingestion of organic mercurials have terminated fatally,
and  a large percentage of survivors have suffered severe permanent
neurologic damage.
  Phenyl mercuric acetate is apparently not as extremely toxic as the
alkyl mercury compounds. However, exposure to it has preceded the
appearance of symptoms and signs of neurologic disease  resembling
amyotrophic lateral sclerosis in certain reported instances.

CONFIRMATION OF POISONING BY ORGANOMERCURY
  COMPOUNDS

  Mercury content  of blood and tissues  can be  measured by  atomic
absorption spectrometry. Special procedures are needed for extraction
and  measurement  of organic  mercury compounds specifically. These
tests are not generally available.

TREATMENT OF  ORGANOMERCURY TOXICOSIS

  Skin and hair contaminated by mercury-containing dust or solution
should be cleansed with soap and water. Eye contamination should be
removed  by flushing the eye  with clean, water,  If irritation persists,
specialized medical care should be obtained.

                               106

-------
  Persons experiencing symptoms (metallic taste in mouth) after inha-
lation of volatile organic mercury compounds (methyl mercury is the
most volatile) should  be  removed promptly  from the contaminated
environment, and observed closely for indications of neurologic impair-
ment. Every possible precaution should be taken to avoid exposure to
organic mercury compounds.
  Ingestion  of an organic mercury compound, even at low dosage, is
life-threatening, and management is difficult.  Detailed discussions of
contemporary treatment options are offered in modern clinical toxicol-
ogy texts. Some of these  texts are  listed in the introduction  to this
volume. Following are the basic steps in management of  poisoning.
 1.   Limit gastrointestinal absorption. If a  mercurial fungicide has
     been ingested in the past few hours, the stomach must be evacuat-
     ed by intubation and lavage, taking all precautions to protect the
     respiratory tract (see  Chapter 1, TREATMENT, Section 6, page 8).
     Repeated administration of activated charcoal may be beneficial.
 2.   Administer a chelating agent. Dimercaprol (BAL) and EDTA are
     apparently of little value in poisonings by organic mercury, but
     other chelators are effective:
     A.  D-penicillamine. (This is available in the United States, and
        has proven effective in reducing the residence half-life  of
        methyl mercury in poisoned humans, see Chapter 6, ARSENI-
        CAL PESTICIDES, p. 61, for dosage).
     B.  2,3-dimercaptopropane-l-sulfonate, and 2,3-dimercaptosuccinic
        acid. (Although effective, these agents are not currently ap-
        proved for use in the United States.)
     C.  N-acetyl-D,L-penicillamine. (Effective,  but not currently ap-
        proved for use in the United States.)
 3.   Extracorporeal hemodialysis and  hemoperfusion may be consid-
     ered, although experience to date has not been encouraging. Al-
     though the unmodified organic mercurials are not efficiently dia-
     lyzable across most membranes, when used in combination with
     chelating agents, dialysis may may be of some value in removing
     organic mercury from the blood (A.H. Al-Abbasi et al. J. Pharma-
     col. Exptl. Therap. 207:249-254, 1978).
     Very little can be done to mitigate neurologic damage caused by
     organic mercurials.
                               107

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                   ORGANOTIN COMPOUNDS
TRIPHENYL TIN
                                      Phenyl tin
                                      Compounds
COMMERCIAL PRODUCTS

  Fentin hydroxide (Du-Ter, Outer, Haitin, Phenostat-A H, Suzu-H,
TPTH, TPTOH, Triple Tin, Tubotin).
  Fentin chloride (Aquatin, Phenostat-C, Tinmate).
  Fentin acetate (Batasan, Brestan, Phenostat-A, Phentinoacetate, Suzu,
Tinestan, TPTA).
  All are formulated as wettable and flowable powders for use mainly
as fungicides to control blights on field crops and orchard trees. Fentip
chloride is also prepared as an emulsifiable concentrate for use as,1 a
molluscicide (Aquatin 20 EC).
  Tributyltin salts are  used as fungicides and  antifouling  agents on
ships. They are somewhat more toxic by the oral route than triphenyl-
tin, but toxic actions are otherwise probably similar.

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  ORGANOTIN COMPOUNDS

  These agents are irritating to the eyes, respiratory tract, and skin.
They are probably absorbed  to a limited extent by the skin and gastro-
intestinal tract. Manifestations of toxicity are due principally to effects
on the brain: headache, nausea, vomiting,  dizziness, and  sometimes
convulsions and loss of consciousness. Photophobia and mental disturb-
ances occur. Epigastric pain is reported,  even in poisoning caused by
inhalation. Elevation of blood sugar, sufficient to cause glycosuria, has
occurred in some cases. The phenyl tin fungicides are apparently less
toxic than ethyltin compounds,  which have caused cerebral edema,
 neurologic damage,  and death in severely poisoned individuals who
 were  exposed  dermally to  a medicinal  compound of this type. No

                                108

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deaths and very few  poisonings have been reported as a result of
occupational exposures to phenyltin compounds.

TREATMENT OF ORGANOTIN TOXICOSIS

  Skin contamination  should be removed by washing with soap and
water. Eyes should  be flushed free  of contaminating material with
clean water or saline.  If irritation persists, expert medical treatment
should be obtained.
  If large  amounts of phenyltin compound have been ingested in  the
past few hours, measures should be taken to remove the toxicant from
the gastrointestinal tract  and to limit  absorption (see Chapter 1,
TREATMENT, Section 6, p. 8).  If oral dosage was small and/or treat-
ment  has been delayed, and if the patient is fully alert, oral adminis-
tration of activated charcoal with a cathartic probably represents opti-
mal management. (See above reference.) Neither BAL, penicillamine,
or chelating agents  have been effective in lowering tissue stores of
organotin compounds in experimental animals.


                   CADMIUM COMPOUNDS

CHEMICAL STRUCTURES
Cd CI2

Cadmium
Chloride
Cd SO 4

Cadmium
Sulfate
                                   ,0 - c -
                            Cd
                                   o - c -
0
II
e -
c -
II
0
H
C
C
H
Cadmium
succinate
COMMERCIAL PRODUCTS

    Cadmium chloride-Caddy, Vi-Cad.
    Cadmium sulfate (generic, 14% solution)
    Cadmium succinate: Cadminate
    Miller 531 and Crag Turf Fungicide 531 are complexes of cadmi-
    um, calcium, copper, chromium, and zinc oxides.
    Kromad is a mixture of cadmium sebacate, potassium chromate,
    and thiram.
    Cad-Trete is a mixture of cadmium chloride and thiram.
                              109

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  Cadmium salts are used to treat fungal diseases affecting turf and
the bark of orchard trees. They are formulated as solutions and emul-
sions.

TOXICOLOGY AND MANIFESTATIONS OF  POISONING BY
  CADMIUM COMPOUNDS

  Cadmium salts and oxides are very irritating to the respiratory and
gastrointestinal tracts. Inhaled cadmium dust or fume has caused pul-
monary edema and pneumonitis, sometimes fatal. Headache, persistent
cough, productive of copious frothy and sometimes bloody sputum, is
accompanied by labored breathing and chest pain.  Fever may follow.
Symptoms  may persist for weeks. Ingested cadmium  causes nausea,
vomiting, diarrhea, abdominal pain,  and tenesmus. Relatively small
inhaled and ingested doses produce serious symptoms. Protracted ab-
sorption of cadmium has led  to renal damage  (proteinuria and azote-
mia), anemia, liver injury (jaundice), and defective  bone  structure
(pathologic fractures) in chronically exposed persons.

CONFIRMATION OF POISONING BY CADMIUM COMPOUNDS

  Cadmium can be measured in body fluids by appropriate extraction,
followed by flame absorption spectrometry. The  approximate upper
limit of blood concentration of cadmium in persons not  exceptionally
exposed is  10 meg  per  liter. Poisoned persons have exhibited blood
cadmium concentrations as high as  6,200 meg per liter and urine
cadmium concentrations as high as 2,200 meg per liter.
  It is reported that blood cadmium concentration reflects recent expo-
sure while  urine cadmium excretion correlates more closely with body
burden. Urinary excretion hi excess  of 100 meg per day suggests an
unusually high body burden.

TREATMENT OF CADMIUM TOXICOSIS

  1.  Skin contamination should be removed by washing with soap and
     water. Contamination of the eyes should be removed by copious
     flushing with clean water or saline. If irritation persists, medical
     treatment should be obtained.
  2.  Respiratory irritation resulting from inhalation of small amounts
     of cadmium dust may resolve spontaneously,  requiring no treat-
     ment. More severe reactions, including  pulmonary edema and
     pneumonitis, may require aggressive measures, including positive
     pressure mechanical pulmonary ventilation, monitoring of blood
     gases, administration of diuretics, steroid medications, and antibi-
     otics  (see  Chapter  14, TREATMENT, Sections 2-4, pp. 138-139).
     Codeine sulfate may be needed to control cough  and chest pain.
  3.  The irritant action of ingested cadmium products  on the gastroin-
     testinal tract is so strong that spontaneous vomiting and diarrhea

                               110

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 4.
 5.
      often eliminate nearly all unabsorbed cadmium  from the gut.
      Give as much milk or egg white orally as the patient will tolerate
      as soon as possible to neutralize any residual cadmium. Repeat
      every 4 hours. If retention of some cadmium in the lower GI tract
      is suspected, administer sorbitol as a cathartic. For dosage, see
      this chapter, HEXACHLOROBENZENE, TREATMENT OF TOX-
      ICOSIS, Section 2, page 91.
      INTRAVENOUS FLUIDS may be required to overcome dehydra-
      tion caused by vomiting and diarrhea. Also, fluids limit cadmium
      toxicity affecting the kidneys and liver. However, great  care must
      be taken to MONITOR FLUID BALANCE and BLOOD ELEC-
      TROLYTE  CONCENTRATIONS, so that failing renal function
      does not lead to fluid overload.
      Chelation therapy with calcium disodium EDTA may be consid-
      ered, depending on measured cadmium  in blood and urine, and
      the status of renal  function.  Its therapeutic value in  cadmium
      poisoning has not  been established, and use of the agent carries
      the risk that unduly rapid transfer of cadmium to the kidney may
      precipitate renal failure. Urine protein  and blood urea nitrogen
      and creatinine should be carefully monitored during therapy. A
      contemporary dosage protocol prescribes 75 mg/kg body weight
      per day, given hi 3-6 divided doses  by deep intramuscular injec-
      tion or slow intravenous infusion for as many as 5 days.  Consult a
      modern clinical toxicology text for details of this therapy.
      Dimercaprol (BAL) is not recommended for treatment of cadmium
      poisoning, chiefly because of the risk of renal injury by  mobilized
      cadmium.
     Monitor urine content of protein and cells  regularly and perform
     liver function tests for indications of injury to these organs.


            MISCELLANEOUS ORGANIC FUNGICIDES

  Some modern organic fungicides are widely  used. Reports of adverse
effects on humans are  few. Some of the known properties  of these
agents are listed below.

ANILAZINE (Dyrene, Kemate, Triasyn).

  Supplied as wettable and flowable powders. Used on vegetables, cere-
als, coffee, ornamentals, and turf.
  This product  has caused skin  irritation in  exposed workers. Acute
oral and dermal toxicities in laboratory animals are low. Human sys-
temic poisonings have not been reported.
6.
7.
                             Ill

-------
BENOMYL (Benlate, Tersan, Benex).                             :

  Benomyl is a synthetic organic fungistat having little or no acute
toxic effect in mammals. No systemic poisonings have been reported in
humans. Although the molecule contains a carbamate grouping, beno-
myl is not a cholinesterase inhibitor. It is poorly absorbed across skin;
that which is absorbed is promptly metabolized and excreted.
  Although injuries to exposed individuals have been few, dermal sen-
sitization has occurred in agricultural workers  exposed to foliage resi-
dues.

CYCLOHEXIMIDE  (Acti-dione, Actispray, naramycin).

  Cycloheximide is formulated as wettable powders, sometimes com-
bined with other fungicides.
  Cycloheximide is a product of fungal culture,  effective against fungal
diseases of ornamentals and grasses.  It is selectively toxic to rats, much
less toxic to dogs and monkeys.  No human poisonings have been  re-
ported. Animals given toxic doses exhibit salivation, bloody diarrhea,
tremors, and excitement,  leading to  coma and  death due to cardiovas-
cular collapse. Hydrocortisone increases the rate of survival of deliber-
ately poisoned  rats.  Atropine, epinephrine, methoxyphenamine, and
hexamethonium all  relieved the symptoms of poisoning, but did not
improve survival.

DODINE (Cyprex, Carpene, Curitan, Melprex, Syllit, Venturol,
  Vondodine).

  Formulated as a  wettable powder. Dodine is commonly applied to
berries, nuts, peaches, apples, pears, and to trees afflicted with leaf
blight.
  Dodine is a  cationic surfactant with antifungal activity. It is  ab-
 sorbed across the skin. It  is irritating to skin, eyes, and gastrointestinal
 tract. Acute oral and dermal toxicity in laboratory animals is moder-
 ate. Poisonings ha humans have not been reported. Based on animal
 studies, ingestion would  probably cause nausea, vomiting, and diar-
 rhea.

 IPRODIONE (Rovral, Glycophene).

   Supplied as wettable powder and other formulations. Used on ber-
 ries, grapes, fruit, vegetables, grasses, and ornamentals. Also  used as
 seed dressing. Exhibits low acute oral and dermal toxicity in laboratory
 animals. No human poisonings have been reported.
                                 112

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 METALAXYL (Ridomil, Apron 25 WP, Subdue 2E).

   Supplied as emulsifiable and flowable concentrates. Used to control
 soilborne fungal diseases on fruit trees, cotton, hops, soybeans, peanuts,
 ornamentals, and grasses. Also used as seed dressing.  Exhibits low
 acute oral and dermal toxicity in laboratory animals. No human poi-
 sonings have been reported.

 TERRAZOLE (Aaterra, Dwell, Ethazol, Koban,  Pansoil,  Truban).

   Supplied as wettable powder and granules for application to soil as a
 fungicide and nitrification  inhibitor. Contact may result in irritation of
 skin  and eyes. Systemic toxicity is low. Human poisonings have not
 been reported.

 THIABENDAZOLE (Apl-Luster, Arbotect, Mertect, TBZ, Tecto, Thiben-
   zole).

   Thiabendazole is widely  used as an  agricultural fungicide, but most
 experience with its toxicology in humans has come from medicinal use
 against intestinal parasites. Oral doses administered for  this purpose
 are far greater than those likely absorbed in the course of occupational
 exposure. Thiabendazole is rapidly metabolized and excreted in the
 urine, mostly as a conjugated  hydroxy-metabolite. Symptoms and signs
 that sometimes follow ingestion are: dizziness, nausea, vomiting, diar-
 rhea, epigastric distress, lethargy, fever, flushing, chills, rash and local
 edema, headache, tinnitus,  paresthesia, and hypotension. Blood enzyme
 tests  may indicate liver injury. Persons with liver and kidney disease
 may be unusually vulnerable  to toxic effects. Adverse effects from use
 of thiabendazole as a fungicide have not been reported.

 TRIADIMEFON (Bayleton, Amiral).

  Supplied as wettable powder, emulsifiable  concentrate, suspension
 concentrate,  paste, and dry flowable powder. Used on fruit, cereals,
 vegetables, coffee, ornamentals, sugarcane, pineapple and turf.
  Exhibits moderate  acute oral toxicity in laboratory animals, but
 dermal toxicity  is  low.  Causes irritation  if  eyes are  contaminated.
 Triadimefon is absorbed across the skin. Overexposures of humans are
 said to have resulted in hyperactivity followed by sedation.

 TRIFORINE (Funginex, Saprol, Denarin, Cela W-524).

  Supplied as emulsifiable  concentrate and  wettable powder. Used on
berries, fruit, vegetables, and ornamentals. It is rapidly  excreted by
mammals,  chiefly as a urinary metabolite.  It exhibits low  acute oral
and dermal toxicity in laboratory animals. No human poisonings have
been reported.

                                113

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CONFIRMATION OF ABSORPTION OF ANILAZINE, BENOMYL,
  CYCLOHEXIMIDE, DODINE, METALAXYL, TERRAZOLE,
  THIABENDAZOLE, TRIADIMEFON, OR TRIFORINE

  There are no generally available laboratory tests for these organic
fungicides or their metabolites in body fluids.

MANAGEMENT OF EXPOSURE TO OR INGESTION OF
  ANILAZINE, BENOMYL, CYCLOHEXAMIDE, DODINE,
  METALAXYL, TERRAZOLE, THIABENDAZOLE,
  TRIADIMEFON, OR TRIFORINE

  See treatment protocol in this chapter under HEXACHLOROBEN-
ZENE, TREATMENT OF TOXICOSIS, Sections 1 and 2, page 91.
                          114

-------
                                          CHAPTER 13

                                      RODENTICIDES

                                   CHEMICAL STRUCTURES
                             WARFARIN
                           ;H,-C   c-ci

                           H.Cs^N
                            CH,  CH,


                            CRIUIOINE
                                                       ALKYL, PHENYL,
                                                      OIPHENYUCETYlw
                                                     CHIORMIPHENYUCETVI
                                               1.3 INOAMOIONE
a
                                                             C-N-C-N-
                                                             H M . H
                                           STRYCHNINE
  H O
  I  t
 f • C • C • ON>

  H


SODIUM
FlUOROACETATE
                             \-HO,
                                                          SCIUIROSIOE
                                                          (Active pfincipl^ ol R«d Squtlll
                                                                 f-ln-f
                                                   YELLOW
                                                   PHOSPHORUS
                      ZINC
                      PHOSPHIDE
                               NOflBORUlOE
                                              115

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COMMERCIAL PRODUCTS

  Coumarins: warfarin, coumafene, zoocoumarin (Co-Rax,  Cov-R-Tox,
Kypfarin, Liqua-Tox, RAX, Rodex, Rodex-Blox, Tox-Hid,  Warfarin Q),
coumafuryl, furmarin, tomarin (Fumarin, Tomarin), coumachlor (To-
morin,  RatUan), bromadiolone  (Bromone,  Canadien  2000,  Contrac,
Maki, Ratimus, Tamogam), brodifacoum (Havoc, Klerat, PP581, Ratak
Plus, Talon, Volid), difenacoum (Ratak, Neosorexa PP580, WBA 8107),
coumatetralyl  (Racumin),  valone  (PMP Tracking Powder),  prolin
(Eraze, Final, Place-Pax, Warfarin Q Concentrate).
  Indandiones:   diphacinone,  diphacin (Kill-Ko  Rat  Killer,  P.C.Q.,
Rodent Cake), chlorophacinone (Caid, Drat,  Liphadione, LM91, Micro-
zul,  Ramucide,  Ratomet, Raviac, Rozol, Topitox), pindone, pival, pival-
dione (Pivalyn,  Pivacin, Tri-ban), radione.
  Inorganics: yellow  phosphorus, zinc phosphide (Phosvin,  Zinc-Tox,
ZP, RidaU-Zinc), thaUium sulfate. Yellow phosphorus is not sold in the
United States.  Zinc  phosphide is  registered,  but little used  in the
United States.  Thallium sulfate  is no longer registered  for  pesticidal
use.
  Convulsants: sodium fluoroacetate  (Compound 1080, Fratol,  Yasok-
nock), strychnine, crimidine (Castrix). Only specially trained personnel
are  allowed to  use sodium fluoroacetate or strychnine. Crimidine is no
longer registered for use as a pesticide.
  Miscellaneous: alpha-naphthyl  thiourea (ANTU, Krysid),  norbormide
(Shoxin, Raticate), red squill (Dethdiet, Rodine), pyriminil (Vacor, RH-
787, DLP-87), cholecalciferol (Quintox, Rampage). ANTU  and red squill
are  both registered for rodenticidal use; red squill is  little used.  Nei-
ther norbormide nor pyriminil are now registered for use in the United
 States.
   Rodent poisons are usually added to baits (palatable grain or paste
 intended to  encourage consumption).  Safety for animals and humans
 depends  on the  toxicity of the agents, concentration  of the active
 ingredient in  the bait,  and the likelihood  that a toxic dose will be
 consumed by nontarget species.  The coumarins, for example, are rea-
 sonably  effective against  pest rodents and they have  a  good safety
 record. Rodents are more likely than domestic animals or humans to
 consume quantities of treated bait that will cause manifest poisoning.
   Very small amounts of the  extremely  toxic rodenticides—sodium
 fluoroacetate,  strychnine,  crimidine, yellow  phosphorus, zinc  phos-
 phide, thallium sulfate—can cause  severe  and even fatal  poisoning.
 Pyriminil and cholecalciferol are highly toxic agents. The coumarins,
 indandiones,  alpha-naphthyl  thiourea,  norbormide,  and  red  squill
 present  considerably less hazard to humans and domestic animals.
                                 116

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                 COUMARINS AND INDANDIONES

 TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
   COUMARINS AND INDANDIONES

   Gastrointestinal absorption of these toxicants is efficient. Warfarin
 can be absorbed across the skin, but this has occurred only under
 extraordinary circumstances.
   Coumarins and indandiones depress the hepatic vitamin K depend-
 ent synthesis of substances essential to  blood clotting: prothrombin
 (factor II) and factors VII, IX and X. The antiprothrombin effect is best
 known, and is the basis for detection and assessment of clinical poison-
 ing. Concurrently,  the  agents  increase  permeability  of capillaries
 throughout the body, predisposing the animal to widespread internal
 hemorrhage. This generally occurs in the rodent after several days of
 bait ingestion, although lethal hemorrhage may follow smaller doses of
 the modern more toxic compounds. Two human fatalities and twelve
 nonfatal poisonings occurred in Korea in 1953 when a family mistaken-
 ly ate  warfarin-treated corn meal (0.25 gm %) over several consecutive
 days. The chief manifestations were nosebleed, bleeding gums, hematu-
 ria, melena, and extensive ecchymoses. There is concern that the more
 toxic modern compounds, such as  brodifacoum and difenacoum, may
 cause serious poisoning of nontarget mammals, including  humans, at
 much lower dosage. In rare  instances, anticoagulant rodenticides have
 apparently caused ecchymoses and skin necrosis for reasons not related
 to excessive dosage.
  Unlike the coumarin compounds, some indandiones cause symptoms
 and signs of neurologic and  cardiopulmonary injury in laboratory rats
 leading to death before hemorrhage occurs. These actions may account
 for the greater toxicity of indandiones in  rodents. Neither neurologic
 nor cardiopulmonary manifestations  have been reported in human
 poisonings.
  Lengthened  prothrombin  time from a toxic dose  of coumarins or
 indandiones usually reaches a maximum in 36-72 hours. Lengthened
 prothrombin time occurs in  response to doses much lower than those
 necessary to cause hemorrhage.

 CONFIRMATION OF POISONING BY COUMARINS AND
  INDANDIONES

  Coumarin or indandione  poisoning results in an  increase in pro-
thrombin time, the  result of reduced  plasma prothrombin concentra-
tion. This is a reliable test for absorption of physiologically significant
doses. Detectable reduction in prothrombin occurs within 24-48 hours
of ingestion and persists for 1-3 weeks.

                               117

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TREATMENT OF POISONING BY COUMARINS AND
  INDANDIONES

 1.   If amounts of bait ingested were assuredly no more than a few
     mouthfuls of coumarin- or indandione-treated bait, or a few grains
     of bait treated with the more toxic brodifacoum or bromadiolone
     compounds, medical treatment is probably unnecessary.
     A.  If there is uncertainty  about the amount of bait ingested or
        the general health of the patient, PHYTONADIONE (vitamin
        Ki) given orally protects against the anticoagulant effect of
        these rodenticides, with essentially no risk to  the patient.
        Dosage of PHYTONADIONE:
             Adults and children over 12 years: 15-25 mg.
             Children under 12 years: 5-10 mg.
             Alternatively, a colloidal preparation  of phytonadione,
             AquamephytonR,  may  be  given  intramuscularly.  For
             adults  and children  over  12 years, give 5-10 mg; for
             children under 12, give 1-5 mg.
     CAUTION: PHYTONADIONE, specifically, is required. Neither
     vitamin Ka (menadione, HykinoneR) nor vitamin K*  (menadiol) is
     an antidote for these anticoagulants.
     B.  Whatever the dosage, insure that patients (especially children)
        will be CAREFULLY  OBSERVED for 4-5 days after inges-
        tion. The indandiones  and  some of the more recently intro-
        duced coumarins may have other toxic effects.
  2.  If LARGE AMOUNTS (1.0-1.5 mg/kg of body weight)  of antico-
     agulant have been ingested within several hours prior to treat-
     ment, empty the stomach by giving SYRUP OF IPECAC, followed
     by 1-2 glasses of water. Dosage of SYRUP OF IPECAC for adults
     and  children over 12 years: 30 ml;  dosage for children under 12
     years: 15 ml. Following emesis, give ACTIVATED  CHARCOAL
     and  SORBITOL (see Chapter 1, TREATMENT, Section 6, p. 8 for
     dosage).
  3.  If treatment has been delayed  several hours following ingestion
     omit induced emesis, but give activated  charcoal  and  sorbitol
     orally.
  4.  If anticoagulant has been  ingested  any time in the preceding 15
     days, determination of  the PROTHROMBIN TIME provides  a
     basis for judging the severity of poisoning.
     A.  If the prothrombin time  is significantly lengthened,  give
         AquamephytonR, intramuscularly. Dosage for adults and chil-
         dren over  12 years: 5-10 mg; dosage for children under 12
         years: 1-5 mg. Decide dose within  these ranges according to
         the degree of prothrombin tune lengthening and, in children,
         the age and weight of the child.
     B.  Repeat prothrombin tune in 24 hours. If it has  not decreased
         from the original value, repeat AquamephytonR dosage.

                               118

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   5.
 If victim is  BLEEDING as a result of anticoagulant poisoning,
 administer AquamephytonR intravenously: up to 10 mg in adults
 and children over 12 years, and up to 5 mg in children under 12
 years. Initial dosage should be decided chiefly on the basis of the
 severity of bleeding. Repeat intravenous AquamephytonR in  24
 hours if bleeding continues. Inject at rates not exceeding 5% of
 the total dose per minute. INTRAVENOUS INFUSION of the
 AquamephytonR DILUTED IN SALINE OR GLUCOSE  SOLU-
 TION is  recommended.  Bleeding is usually controlled  in 3-6
 hours.
 CAUTION: Adverse reactions,  some fatal, have occurred from
 intravenous  phytonadione  injections, even when recommended
 dosage limits and injection rates were observed. For this reason
 the INTRAVENOUS route should  be used ONLY IN cases  of
 SEVERE  POISONING. Flushing, dizziness, hypotension, dyspnea,
 and cyanosis  have characterized adverse reactions.
 A.  Antidotal therapy in cases of SEVERE BLEEDING should be
    supplemented with TRANSFUSIONS of FRESH BLOOD or
    FRESH FROZEN PLASMA.  Use of fresh blood or plasma
    represents the most rapidly effective method of stopping hem-
    orrhage due to these anticoagulants, but the effect may not
    endure. Therefore,  the  transfusions  should  be given along
    with phytonadione therapy.
B.  Determine PROTHROMBIN TIMES and hemoglobin concen-
    trations every 6-12 hours to  assess  effectiveness of antihe-
    morrhagic measures.
C.  When  normal blood coagulation is restored, it may be advisa-
    ble to drain large hematomata.
D.  Ferrous sulfate therapy  may be appropriate in the recupera-
    tive period to rebuild lost erythrocyte mass.
                  INORGANIC RODENTICIDES

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  INORGANIC RODENTICIDES

  Yellow phosphorus (also known as white phosphorus) is corrosive to
tissues with which  it comes in contact, including skin and the  gut
lining. A few minutes to 24 hours following ingestion, the first symp-
toms may be burning pain in the throat, chest, and abdomen reflecting
severe mucosal injury. Vomiting and diarrhea usually ensue. In some
cases, however, lethargy, restlessness, and irritability are the earliest
symptoms,  followed by symptoms of  gastrointestinal  injury. Shock
often progresses to death in 1-2 days. If the patient survives, a relative-
ly symptom-free period of a few hours or days may occur, followed by
indications of severe injury to the liver, myocardium, .and brain. These
effects may be consequences of phosphine formed in and absorbed from

                              119

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the gut. Nausea and vomiting recur.  Hemorrhage  at  various  sites
reflects depression of clotting factor  synthesis in the damaged liver.
Also, thrombocytopenia may contribute.  The liver is enlarged and jaun-
dice appears.  Shock due to  bleeding and toxic myocarditis  may be
irreversible. Convulsions, delirium, and coma reflect brain injury, to
which severe hypoglycemia may contribute. Anuria commonly super-
venes due to shock and to the toxic effects of phosphorus products and
accumulating bilirubin on renal tubules. Twenty to 50 percent of cases
of phosphorus ingestion have terminated fatally.
  Zinc phosphide is  much less irritating to  skin  and mucous mem-
branes than yellow phosphorus, but great care must be taken to avoid
inhalation of dust, which may induce pulmonary edema. When ingest-
ed, the emetic effect of zinc released in the gut may provide a measure
of protection. The effects of ingestion are probably the consequences of
phosphine and zinc liberated in and absorbed from the gut. Nausea
and vomiting, excitement, chills, chest tightness, dyspnea and cough
may progress to pulmonary edema. If the patient survives, shock from
toxic myocardiopathy, jaundice, and hemorrhage  (from liver injury),
delirium, convulsions, and coma (from toxic encephalopathy), tetany
from hypocalcemia, and  anuria from renal tubular damage are all life-
threatening manifestations of poisoning.
   Thallium sulfate is well absorbed from the gut and across the skin.
It exhibits a very large volume of distribution (tissue uptake) and is
distributed chiefly to the kidney and liver, both of which participate in
thallium excretion. Most blood-borne  thallium is in the red cells. Elimi-
 nation half-life from blood in the adult  human is about 1.9 days. A
 lethal dose for the adult human is probably less than one gram.
   The gastrointestinal tract, central nervous system, heart and blood
 vessels, kidneys, liver, skin, and hair .are  prominently affected by toxic
 intakes. One-half to two days following ingestion of a toxic dose,  a
 hemorrhagic  gastroenteritis is often  manifest  as abdominal  pain,
 nausea, vomiting, bloody diarrhea, stomatitis, and salivation. Ileus may
 appear later on. Headache, lethargy, muscle weakness, paresthesia,
 tremor, ptosis,  ataxia, myoclonic movements, emotional lability, psy-
 chosis, convulsions, delirium, and coma  reflect toxic encephalopathy,
 which may be delayed 2-5 days. Fever  is  a bad prognostic indication of
 brain damage.  Early hypotension is due  at least in part to a toxic
 myocardiopathy; later,  hypertension is probably  a  result of vasocon-
 striction.  The urine may show protein  and red  cells; high levels of
 LDH, GOT, ALT, and AST indicate  liver injury. Loss of hair (notably,
 ALOPECIA) is a fairly consistent feature of thallium poisoning that is
 often helpful diagnostically. Death  from  thallium  poisoning may be
 caused by respiratory paralysis or cardiovascular collapse. Absorption
 of nonlethal doses of thallium has caused protracted painful  neuro-
 pathies and paresis, optic nerve atrophy, persistent ataxia and chorei-
 form movements, as well as dementia.

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 CONFIRMATION OF POISONING BY INORGANIC
  RODENTICIDES

  Phosphorus and phosphides sometimes impart  a foul rotten fish
 odor to vomitus, feces,  and sometimes  the breath. Luminescence of
 vomitus or feces is an occasional feature of phosphorus ingestion. Hy-
 perphosphatemia and hypocalcemia occur in some  cases, but are not
 consistent findings.
  Thallium can be measured in the serum, urine and hair. Hair analy-
 sis is likely to be useful only in establishing protracted prior absorp-
 tion. Serum concentration does not exceed 30 micrograms per liter in
 nonexposed persons. Urine concentrations rarely exceed 40 micrograms
 per liter in the absence  of exceptional exposure. Fifty micrograms per
 kilogram of hair is the approximate upper limit of "normal" in persons
 not exceptionally exposed. Concentrations roughly 10-100 times these
general population levels  have been measured in  persons  clinically
poisoned by thallium.

TREATMENT OF POISONING BY YELLOW PHOSPHORUS OR
  ZINC PHOSPHIDE
 1.
 2.
Brush or scrape nonadherent phosphorus from the skin.  WASH
SKIN BURNS with copious amounts  of water. Make sure all
particles of phosphorus have been removed. If burned area is
infected, cover with an antimicrobial creme.
Poisonings by INGESTED yellow phosphorus or zinc phosphide
are extremely difficult to manage. Treatment is basically support-
ive and symptomatic.
CAUTION: Highly toxic phosphine gas may evolve from emesis,
lavage fluid, and feces of victims of these poisons. The patient's
room should be well ventilated.  Persons attending the patient
must wear gloves to avoid contact with the phosphorus.
A. INTTJBATE  and ASPIRATE  the stomach,  after taking all
   precautions to protect the airway from aspiration of vomitus
   (Chapter 1, TREATMENT, Section 6, p. 8). LAVAGE with
   several liters of 1:5000 potassium permanganate solution. Ca-
   tharsis is  probably not indicated,  but  there may  be some
   benefit in  administering mineral oil. Dosage is 100 ml for
   adults and children over 12 years, and 1.5 ml/kg body weight
   in children under 12 years. Do not give vegetable oils or fats.
B. Combat shock and acidosis with TRANSFUSIONS of whole
   blood and  INFUSIONS of glucose and  electrolyte solutions.
   Monitor fluid balance and central venous pressure to  avoid
   fluid  overload.  Monitor blood electrolytes and  pH to  guide
   choice of intravenous solutions. Without administered glucose,
   hypoglycemia secondary to  liver injury may contribute to
   shock.
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    C. Administer 100% OXYGEN by mask or nasal tube.
    D. Combat pulmonary edema with intermittent or continuous
       POSITIVE PRESSURE OXYGEN.
    E MONITOR URINE albumin, glucose, and sediment to detect
       early renal injury. EXTRACORPOREAL HEMODIALYSIS
       will be required if acute renal failure occurs, but it does not
       enhance excretion of phosphorus. Monitor EGG to detect myo-
       cardial impairment. Monitor serum  alkaline phosphatase,
       LDH, ALT, AST, prothrombin time, and bilirubin to evaluate
       liver damage.
    F. Include AquamephytonR (vitamin Ki) in intravenous infusions
       if prothrombin level declines. Dosage of 10-50 mg per day may
       be  required. Administer AquamephytonR slowly, intravenous-
       ly;  stop infusion if flushing,  cyanosis, paresthesia, hypoten-
       sion, or dyspnea occurs.
    G. MORPHINE SULFATE,  8-16 mg subcutaneously every few
       hours  may be necessary to control pain. Child's dose: 0.1-0.2
       mg/kg body weight.
    H. CONTROL  CONVULSIONS.  See Chapter 3,  TREATMENT,
       Section 4, p. 21.

TREATMENT  OF POISONING BY THALLIUM SULFATE

 1.  If thallium sulfate was swallowed less than  a few hours prior to
    treatment, and if the patient is fully alert, empty the stomach by
    administering SYRUP OF IPECAC, followed by  1-2 glasses of
    water. Dosage for adults and children over 12 years: 30 ml; dosage
    for children under 12 years: 15 ml. Put in place a cuffed endotra-
    cheal tube to protect the airway, then intubate the stomach and
    lavage with 1%  sodium  or potassium iodide, to form insoluble
    thallium iodide. Instill a slurry of ACTIVATED CHARCOAL (for
    dosage, see Chapter 1, TREATMENT,  Section 6, p.  8). Include
    sorbitol with the  charcoal unless diarrhea is already in progress.
 2.  If treatment is long delayed,  administer the activated charcoal
    orally. Include sorbitol unless diarrhea has already commenced.
    Repeated administration of charcoal may be of benefit in hasten-
    ing  elimination of thallium.  Give  half or more  of the original
    dosage every 2-4 hours.
 3.  Give ELECTROLYTE and GLUCOSE solutions  by intravenous
    infusion to support urinary  excretion of thallium by diuresis.
    Monitor fluid balance carefully to insure that fluid overload does
    not  occur. If shock develops, give whole blood, plasma, or plasma
     expanders. Pressor amines must be used very carefully in light of
     myocardial injury. Monitor EGG for arrhythmias.
 4.  Inclusion of POTASSIUM CHLORIDE in the infusion 'fluid dis-
     places thallium from cells into the extracellular compartment and
     thereby accelerates excretion.  Care must be taken, however, that

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     excessive redistribution of thallium to the brain does not occur.
     Concentration of potassium in the infusion fluid should probably
     not exceed 10 milliequivalents per liter. Monitor clinical status
     carefully, and stop KC1 administration if encephalopathy worsens.
 5.  CONTROL CONVULSIONS and myoclonic jerking. For dosages
     of anticonvulsants, see Chapter 3, TREATMENT, Section 4, p. 21.
     Benzodiazepines (diazepam or lorazepam) are the preferred agents
     in thallium poisoning.  In at least one case,  neurologic  status
     deteriorated when barbiturates were administered.
 6.  COMBINED HEMODIALYSIS AND   HEMOPERFUSION has
     proven moderately effective in reducing  the body burden of thalli-
     um in victims of severe poisoning. In one case, peritoneal dialysis
     was not effective.
 7.  Several methods for chelating and/or accelerating disposition of
     thallium have been tested and found either relatively ineffective
     or hazardous. Chelating agents are not recommended in thallium
     poisoning.
 8.  Potassium  ferric ferrocyanide  (Prussian Blue)  orally enhances
     fecal excretion of thallium by exchange  of potassium for thallium
     in the gut. However,  it  is not approved  for  human use, and
     suitably pure material  is not generally available for medicinal
     purposes.
                         CONVULSANTS

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  CONVULSANT RODENTICIDES

  Sodium fluoroacetate is readily absorbed by the gut, but only to a
limited extent across skin. The toxic mechanism is distinct from that of
fluoride salts. Three  molecules of fluoroacetate are combined in the
liver to form a molecule of fluorocitrate, which  poisons critical en-
zymes  of the tricarboxylic acid cycle, thus impairing cellular respira-
tion. The heart and the brain are the organs most prominently affect-
ed. The effect on  the heart is to cause arrhythmias, progressing to
ventricular fibrillation, which is the usual cause of death. Neurotoxi-
city is  expressed as violent tonic-clonic convulsions, spasms and rigor,
sometimes not occurring for hours after ingestion.
  Strychnine  is a natural toxin (nux vomica)  which causes violent
epileptiform convulsions by direct excitatory action on the cells of the
central nervous system,  chiefly the spinal cord. Death  is caused by
convulsive interference with pulmonary function, by depression of res-
piratory center activity, or both. Strychnine is detoxified in the liver.
Residence half-life is about 10 hours in humans. Onset of symptoms is
usually within 15-20 minutes of ingestion. Lethal dose in humans is
5-8 mg/kg body weight.

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  Crimidine is a synthetic chlorinated pyrimidine compound which, in
adequate dosage, causes violent convulsions similar to those produced
by strychnine.

CONFIRMATION OF POISONING BY CONVULSANT
  RODENTICIDES

  There are no generally available tests to confirm poisoning by the
convulsant rodenticides.

TREATMENT OF POISONING BY SODIUM FLUOROACETATE

  Sodium fluoroacetate poisonings have occurred almost entirely as a
result of accidental and suicidal ingestions. If the poison was ingested
shortly before treatment  and convulsions have not yet occurred, the
first step in treatment is to remove the toxicant from the gut. If the
victim is already convulsing, however, it is necessary first to  control
the seizures before gastric lavage and catharsis are undertaken.
 1.  CONTROL CONVULSIONS by giving OXYGEN, and administer-
     ing  ANTICONVULSANT medications (see  Chapter 3, TREAT-
     MENT, Section 4, page  21). Seizure activity from fluoroacetate
     may be so severe that  doses necessary for seizure  control may
     paralyze respiration. For this reason, it is best  to INTUBATE
     THE TRACHEA as early as  possible  in the course  of  seizure
     control, and support pulmonary  ventilation mechanically. This
     has the added advantage of protecting the airway from aspiration
     of regurgitated gastric contents.
 2.  Empty   the  stomach  by INTUBATION,  ASPIRATION,  and
     LAVAGE  with isotonic saline or tap water (Chapter 1, TREAT-
     MENT, Section 6, page 8). There is probably very little  adsorption
     of sodium fluoroacetate on activated charcoal. Instill SORBITOL
     as a cathartic before withdrawing the stomach tube (see reference
     above for dosage).
 3.  Administer INTRAVENOUS FLUIDS cautiously to support excre-
     tion of absorbed  fluoroacetate. It is especially important to avoid
     fluid overload in the presence of a weak and irritable myocardi-
     um.
 4.  Monitor ELECTROCARDIOGRAM for  arrhythmias and, if de-
     tected,  treat with an appropriate antiarrhythmic drug.  Consult
     package inserts for dosages and recommended methods for admin-
     istration. Facilities for electroshock CARDIOVERSION should be
     at hand. Some victims of fluoroacetate  poisoning have been res-
     cued after repeated cardioversions.
 5.  CALCIUM GLUCONATE (10%  solution)  given  slowly  intrave-
     nously should be given to relieve carpopedal spasm. Care must be
     taken to avoid extravasation.

                               124

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     Dosage of CALCIUM GLUCONATE:
         Adults  and children over 12 years: 10 ml of 10% solution,
         given slowly, intravenously. Repeat if necessary.
         Children under 12 years: 0.05 gm (one-half ml of 10% solu-
         tion) per kg body weight, preferably included in intravenous
         infusion fluid. Repeat dosage as needed.

TREATMENT OF POISONING BY STRYCHNINE OR CRIMIDINE

  Strychnine and crimidine cause violent convulsions shortly following
ingestion of toxic doses. Both poisons are probably well adsorbed on
charcoal. If the patient is seen fully conscious and not convulsing a few
moments after the ingestion, great benefit may derive from the imme-
diate ingestion of ACTIVATED CHARCOAL (see Chapter 1, TREAT-
MENT, Section 6, page 8 for dosage). If the patient is already obtunded
or convulsing, the involuntary motor activity must be controlled before
steps are taken to empty the gut and limit toxicant absorption.
 1.  CONTROL  CONVULSIONS. See Chapter 3, TREATMENT, Sec-
    tion 4, page 21.
 2.  LIMIT TOXICANT ABSORPTION from the gut. Induced emesis
    is hazardous because of the  risk of aspiration of vomitus when
    seizures begin. As soon as possible, protect the  airway, preferably
    with a cuffed ENDOTRACHEAL TUBE,  then remove stomach
    contents by  ASPIRATION and LAVAGE with a slurry of activat-
    ed  charcoal (see Chapter 1,  TREATMENT, Section 6, page  8).
    Repeated doses  of activated  charcoal may be beneficial, giving
    half or more the initial dose every 2-4 hours.
 3.  Administer  intravenous  fluids  to support excretion of absorbed
    toxicants. Mannitol diuresis may  be considered, and inclusion of
    sodium bicarbonate in the infusion fluid counteracts  metabolic
    acidosis generated by convulsions. Effectiveness of hemodialysis
    and hemoperfusion has not been tested.
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                 MISCELLANEOUS RODENTICIDES
TOXICOLOGY AND  MANIFESTATIONS OF POISONING BY:
     ANTU, NORBORMIDE, RED SQUILL, PYRIMINYL, AND
                      CHOLECALCIFEROL

  Alpha-naphthyl thiourea (ANTU) appears to have unique toxic ef-
fects on Norway rats. Although dogs are somewhat susceptible, other
species, including man, are resistant to the toxicity of ANTU. Poisoned
Norway rats die of pulmonary edema  and pleura!  effusion. Several
humans poisoned by  deliberate ingestion of ANTU (and chloralose)
developed severe short-lived tracheobronchial hypersecretion, but  ap-
parently not pulmonary edema. Although some persons required me-
chanically assisted pulmonary ventilation, the reaction, in most cases,
resolved in a few hours.
  Norbormide is a single-dose synthetic organic compound uniquely
toxic to Norway and roof rats, in which it causes an intense general-
ized vasoconstriction,  leading  to death  from tissue anoxia.  The most
severe effects observed in human volunteers ingesting 20-300 mg orally
were a brief and moderate lowering of body temperature and a mild
lowering of systolic blood pressure. These effects, which were observed
in the absence of symptoms, were maximal at one hour and were  not
apparent two hours after ingestion.
  Red squill is an ancient rodenticide, consisting of the inner portions
of a small cabbage plant grown in eastern Mediterranean  countries.
The toxic properties are probably due to cardiac glycosides. For several
reasons, mammals other than rodents are unlikely to be poisoned: 1)
red squill is  intensely nauseant, so that animals which vomit (rodents
do  not) are unlikely to retain the poison; 2) the glycoside is not effi-
ciently absorbed from the gut; 3) absorbed glycoside is rapidly excreted.
Injection of  the glycosides leads to effects typical of digitalis:  alter-
ations in cardiac impulse conduction and arrhythmias.
  Pyriminil  (Vacor) is  a substituted urea compound that is toxic to
mammals, including humans, by effects  on multiple organs and tissues.
It causes severe damage to central and peripheral nervous systems,
including both  somatic  and autonomic components of the latter. It
destroys beta cells of the pancreas, leading to insulin-deficient diabetes
mellitus. Cardiac arrhythmias probably reflect injury to the impulse
conduction system. Nicotinamide antagonism is a likely biochemical
basis for many of the toxic effects.
  Most severe poisonings have resulted from suicidal ingestions. Early
manifestations of poisoning are abdominal pain, nausea, vomiting, leth-
argy, confusion, visual disturbances, painful paresthesia, urinary reten-
tion (or frequency), and orthostatic hypotension (fainting when sitting
 up or standing from the reclining position). Later effects are paresis of

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the limbs, areflexia, ataxia, persistent anorexia, and bowel dystonias.
Early hypoglycemia progresses to hyperglycemia, often accompanied by
ketoacidosis. Severe and prolonged orthostatic hypotension is charac-
teristic. Death may result from cardiac arrhythmias, diabetic ketoaci-
dosis, inanition, or aspiration pneumonia.
  Cholecalciferol is the activated form of vitamin D (vitamin Ds). Its
toxic effect is probably a combination of actions on liver, kidney, and
possibly the myocardium, the last two toxicities being the result of
hypercalcemia. Early symptoms and signs of vitamin D-induced hyper-
calcemia in humans are fatigue, weakness, headache, and nausea. Po-
lyuria, polydipsia, proteinuria, and azotemia result from acute renal
tubular injury by hypercalcemia. This is commonly the cause of death.
Prolonged hypercalcemia  results ultimately  in nephrolithiasis  and
nephrocalcinosis. Azotemia occurs  as renal tubular damage progresses.

CONFIRMATION OF POISONING BY MISCELLANEOUS
  RODENTICIDES

  Cholecalciferol intoxication is indicated by an elevated  concentra-
tion of calcium (chiefly the unbound fraction) in the serum.
  There are no generally available tests for the other  rodenticides or
their biotransformation products.

TREATMENT OF POISONING BY ALPHA NAPHTHYL
  THIOUREA (ANTU)

  Alpha naphthyl thiourea is unlikely to cause severe poisoning unless
large amounts have been ingested. If a small amount has been ingest-
ed,  or if treatment has been delayed, administer ACTIVATED CHAR-
COAL and SORBITOL orally (see Chapter 1, TREATMENT, Section 6,
p. 8 for dosage).
  If a  large quantity was ingested, take  steps to protect the airway,
then  empty  the  stomach  by INTUBATION, ASPIRATION,  and
LAVAGE. Instill ACTIVATED CHARCOAL  and  SORBITOL before
withdrawing the tube (see Chapter 1, TREATMENT, Section 6, p. 8).
  If dyspnea develops, support pulmonary ventilation mechanically
using oxygen. Although not tested for efficacy or safety, careful intra-
venous injection of aminophylline might  be used  to relieve broncho-
spasm and bronchorrhea. See package insert for dosage.

TREATMENT OF POISONING BY NORBORMIDE

  Norbormide is unlikely to cause human poisoning unless extraordi-
nary amounts have been ingested. In this event, give  activated char-
coal and  sorbitol orally  (for dosage, see Chapter 1,  TREATMENT,
Section 6, p. 8). Monitor body  temperature and blood pressure.  Use
warm blankets to correct hypothermia. A  recumbent position "and cau-
tious doses of a pressor drug may be used to correct hypotension, if this

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develops. To date, no human poisonings by norbormide have occurred,
and therefore, therapeutic procedures have not been tested.

TREATMENT OF POISONING BY RED SQUILL

  Red squill is unlikely to cause poisoning unless ingested at substan-
tial dosage. The problem  is usually self-correcting due to its intense
emetic effect. If, for  some  reason, the squill  is  retained,  Syrup of
Ipecac, followed by 1-2 glasses of  water, should be administered to
initiate vomiting. Dosage for adults  and children qyer 12 years: 30 ml;
dosage for children under 12 years: 15  ml. When vomiting stops, ad-
minister activated charcoal and sorbitol  (see Chapter 1,  TREATMENT,
Section 6, p. 8 for dosages). Monitor cardiac status electrocardiographi-
cally.

TREATMENT OF POISONING BY PYRIMINYL

  Pyriminyl poisonings have resulted  from accidental and suicidal in-
gestions.  Severe effects have sometimes been  caused  by very small
doses. Immediate measures to limit absorption are essential.
 1.   If pyriminyl was ingested, and if the patient is fully conscious,
     administer  SYRUP OF IPECAC followed by several glasses of
     water to induce emesis. Dosage for adults and  children over 12
     years: 30 ml; dosage for children under 12 years: 15 ml.
     If there  is reason to believe some pyriminyl remains in the stom-
     ach,  protect the airway with  a  cuffed endotracheal tube,  then
     INTUBATE, ASPIRATE,  and LAVAGE  the stomach with  a
     slurry of ACTIVATED CHARCOAL (see Chapter 1, TREATMENT,
     Section 6, p. 8 for dosage). Leave activated charcoal and sorbitol in
     the stomach before withdrawing the lavage tube. Repeated doses
     of charcoal may well be beneficial, giving half or more of the
     initial dose  every 2-4 hours.
 2.   Monitor blood and urine glucose concentrations, serum alkaline
     phosphatase,  amylase, LDH,  AST,  and  ALT  activities,  urine
     ketone concentrations, blood electrolytes, and BUN. Examine the
     electrocardiogram for arrhythmias.
 3.   Infuse ELECTROLYTE SOLUTIONS intravenously to accelerate
     toxicant excretion and correct errors  in specifier electrolyte con-
     centrations. If ketoacidosis  appears, include sodium bicarbonate or
     Ringer's-lactate to control acidosis.
 4.   If DIABETIC KETOACIDOSIS appears (ketonuria, metabolic aci-
     dosis, hyperglycemia), administer enough regular  insulin to con-
     trol the acidosis and hyperglycemia, as in naturally occurring
     diabetic ketosis. The diabetes resulting from pyriminyl tends to be
     brittle and correspondingly difficult to control.
 5.   The sequelae of pyriminyl poisoning are essentially irreversible.
     The diabetes may  be controlled  with 'insulin, or, in mild cases,

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     sulfonylurea drugs. Orthostatic hypotension may be alleviated by
     support stockings, sympathomimetic drugs, or dihydroergotamine.

TREATMENT OF POISONING BY CHOLECALCIFEROL

  Cholecalciferol at  high dosage  may  cause severe poisoning and
death. Human poisonings from its use as a rodenticide have not been
reported, but vitamin D overdosage has occurred under clinical circum-
stances. Treatment is directed at limiting gastrointestinal absorption,
accelerating excretion, and counteracting the hypercalcemic effect.
 1.   If Cholecalciferol has been  ingested within a few hours prior to
     treatment,  and if the  patient is fully  alert, induce emesis  by
     SYRUP OF IPECAC, followed by 1-2 glasses of water. Dosage for
     adults  and children  over 12 years: 30  ml;  dosage for children
     under 12 years:  15 ml. When  vomiting  stops, give ACTIVATED
     'CHARCOAL and SORBITOL (for dosage, see Chapter 1, TREAT-
     MENT, Section 6, p. 8). Repeated administration of charcoal at
     half or more the initial dosage every 2-4 hours may be beneficial.
 2.   Administer intravenous fluids (normal saline or 5%  glucose) at
     moderate rates to support  excretory mechanisms and excretion.
     MONITOR FLUID BALANCE to avoid overload, and measure
     serum electrolytes periodically. Measure total and ionized calcium
     levels in  the blood  24  hours after Cholecalciferol ingestion  to
     determine severity of toxic effect. Monitor urine for  protein, red
     and white cells to assess renal injury.
 3.   FUROSEMIDE (Lasix),  20-40 mg intravenously, or  40-120  mg
     daily by mouth  may be given to promote diuresis. Dosage  for
     children under 12 is approximately 0.5-1.0  mg/kg body weight
     intravenously,  1.0-2.0 mg/kg body weight orally. Monitor serum
     potassium  after dosage; give potassium  chloride if hypokalemia
     occurs. Consult package insert for additional directions and warn-
     ings.
 4.   PREDNISONE and similar glucocorticoids reduce elevated blood
     calcium levels  in certain diseases. Although they have not been
     tested in Cholecalciferol overdosage, it is  possible that they would
     be beneficial. Dosage is approximately 1 mg per kilogram per day,
     to a maximum of 20 mg per day.
 5.   CALCITONIN  (salmon calcitonin, CalcimarR) is a logical antidote
     for Cholecalciferol actions,  but has not  been tested hi human
     poisoning. In other conditions, the usual dosage is 4 International
     Units per  kg body weight  every 12 hours, by intramuscular  or
     subcutaneous injection,  continued for 2-5 days. The dose may be
     doubled if calcium lowering effect is not sufficient. Calcium gluco-
     nate (10%) for  intravenous injection should be immediately avail-
     able  if indications of hypocalcemia (carpopedal spasm,  cardiac
     arrhythmias) appear. Consult package  insert for additional direc-
     tions and warnings.

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6.   If total serum calcium is markedly elevated (more than about 8
    milliequivalents per liter) the intravenous infusion of disodium
    edetate (EDTA) may be considered. Although this agent is very
    effective in reducing  the level of physiologically active  serum
    calcium by chelation, only moderate overdosage may lead to hypo-
    calcemia, tetany, ventricular arrhythmias, respiratory arrest, and
    death. A daily dose of 50 mg/kg body weight, to a maximum of 3
    gin, may be infused in 500 ml of 5% glucose or 0.9% saline over at
    least 4-6 hours, while the EGG  and serum  calcium are being
    monitored.  Calcium gluconate (10%) should be immediately at
    hand to reverse hypocalcemia if arrhythmias or carpopedal spasm
    appear. Disodium edetate is CONTRAINDICATED if there are
    any signs of renal insufficiency, congestive heart failure, or hypo-
    kalemia (less than 3.5 milliequivalents per liter). Consult package
    insert for additional directions and warnings.
                              130

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                    CHAPTER 14
                   FUMIGANTS
 CHEMICAL STRUCTURES
HALOCARBONS
Cl * Br Br
1 11
CI-C-CI
1
Cl
Carbon
Tetrachloride

Cl
CI-C-H
1
Cl
Chloroform
Cl
1
Cl - C - NO2
1
Cl
Chloropicrin
H
1
H-C-Br
1

H
Methyl Bromide


r
Cl - C - Cl
I
H
H-C— C-H
1 |
H H
Ethylene
Dibromide

Cl H Cl
1 1 1
H -C — C » C
1 1
H H
1,3-Dichloro-
propane
Br Br Cl
I I I
H -C-C-C - H
I I I
H H H
Dibromo-
chloropropane
Cl Cl
I I
H-C-C-H
i i
i i
H H
Ethylene
Dichloride





OXIDES AND
ALDEHYDES

o

CH2 - CH2
Ethylene Oxide


X^X
CH2 - CH - CH3
Propylene Oxide
H
C= 0

Formaldehyde

H
[-c-o]
Li Jn
1 1 1
H
Paraformaldehyde


H H H
1 1 1
C = C-C = 0
1
H
Acrolein


SULFUR AND
PHOSPHORUS
COMPOUNDS


0 = S = O
Sulfur Dioxide

S = C = S
Carbon Disulfide
F^
F/S = °
Sulfuryl Fluoride
P
1
H
Phosphine (from
Al= P+ H20)

CYANIDES

H - C = N
Hydrogen Cyanide

H H
I i
C = C-C s N
\
H
Acrylonitrile

Methylene Chloride
                         Hydrocarbon-
Paradichlorobenzene
Naphthalene
                          131

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COMMERCIAL PRODUCTS

  Hydrocarbon: naphthalene (naphthene).
  Halocarbons: methylene  chloride, methyl bromide (bromomethane,
Brom-O-Gas,  Brom-O-Sol,  Meth-O-Gas,.'Terr-O-Gas, Brom-O-Gaz,  Gel-
fume, Kayafume, MeBr), chloroform (trichloromethane), carbon tetra-
chloride, chloropicrin (nitrochloroform, Chlor-O-Pic, Aquinite, Dojyopi-
crin, Dolochlor, Larvacide, Pic-Clor, Tri-Clor), ethylene dichloride (dich-
loroethane, EDC), ethylene dibromide (dibromoethane,  Bromofume,
Cehnide, E-D-Bee, EDB, Kopfume, Nephis), dichloropropene (Telone II
Soil Fumigant, D-D92), dichloropropene plus dichloropropane (D-D), di-
bromochloropropane  (Nemafume, Nemanax, Nemaset, DBCP, Nemato-
cide), paradichlorobenzene (PDB, Paracide).
  Oxides and Aldehydes: ethylene oxide (epoxyethane,  ETO, oxirane),
propylene oxide, formaldehyde (formalin is a 40% aqueous solution),
paraformaldehyde, acrolein (propenal, acrylaldehyde, Aqualin).
  Sulfur Compounds: sulfur dioxide, sulfuryl fluoride (Vikane), carbon
disulfide.
  Phosphorus  Compounds: phosphine (liberated from aluminum phos-
phide: phostoxin, A1P, Fumitoxin).
  Nitrogen Compounds: hydrogen cyanide (hydrocyanic acid,  prussic
acid, Cyclon),  acrylonitrile (Acritet, Carbacryl, Acrylofume—all mix-
tures with carbon tetrachloride).
  Packaging and formulation of fumigants is complex. Those which are
gases at room temperature (methyl bromide, ethylene oxide, sulfur
dioxide, hydrogen cyanide, sulfuryl fluoride) are provided in  com-
pressed gas cylinders. Liquids are marketed in cans or drums. Solids
which sublime, such  as naphthalene and paradichlorobenzene, must be
packaged so as to prevent significant contact with air before they are
used.
  Mixtures of fumigants have several advantages. Carbon tetrachloride
reduces the explosiveness of carbon disulfide and acrylonitrile. Chloro-
picrin, having a strong odor and irritant effect,  is often added as a
"warning agent" to other liquid fumigants.
  Liquid halocarbons and carbon disulfide evaporate into the air while
naphthalene   and paradichlorobenzene  sublime.  Paraformaldehyde
slowly depolymerizes to formaldehyde. Aluminum phosphide slowly
reacts with water vapor in  the air to liberate phosphine, an extremely
toxic gas.
  Fumigants  have remarkable capacities for diffusion  (a property es-
sential to their function). Some readily penetrate rubber and neoprene
personal protective  gear,  as well as  human  skin. They  are  rapidly
absorbed across the  pulmonary membrane, gut, and skin. Special ad-
sorbents are required in respirator canisters to protect exposed work-
ers from airborne fumigant gases. Even these may not provide com-
plete protection when air concentrations of fumigants are high.

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 TOXICOLOGY AND MANIFESTATIONS OF POISONING

   Naphthalene is a solid white hydrocarbon long used in ball, flake, or
 cake form as a moth repellant. It sublimes slowly.  The vapor has a
 sharp, pungent odor that is irritating to the eyes and upper respiratory
 tract.  Inhalation of high  concentrations causes  headache,  dizziness,
 nausea, and vomiting. Intensive prolonged inhalation exposure, or in-
 gestion or dermal exposure (from contact with heavily treated fabric)
 may cause hemolysis,  particularly in persons afflicted with glucose-6-
 phosphate dehydrogenase deficiency. It is actually the alpha-naphthol
 metabolite that causes the hemolysis. Secondary renal tubular damage
 may ensue from the naphthol and from  the products  of hemolysis.
 Convulsions and coma may occur, particularly in children. In infants,
 high levels of hemoglobin, methemoglobin, and bilirubin in the plasma
 may lead to encephalopathy (kernicterus). Some individuals exhibit
 dermal sensitivity to naphthalene.
  Methylene chloride  is one of the less toxic halocarbons. It is  ab-
 sorbed by inhalation and to a limited extent across the skin. Exposure
 to high concentrations may cause central nervous system depression,
 manifest as fatigue, weakness, and drowsiness. Some absorbed methyl-
 ene  chloride is degraded to carbon monoxide in  humans, yielding in-
 creased blood concentrations of carboxyhemoglobin. However, concen-
 trations are rarely high enough to cause symptoms of carbon monoxide
 poisoning.  Ingestion has caused death from gastrointestinal  hemor-
 rhage, severe liver damage, coma, shock, metabolic acidosis, and renal
 injury. In laboratory animals, extraordinary  dosage has caused irrita-
 bility, tremor, and narcosis, leading to death.
  Methyl  bromide  is colorless  and nearly odorless, but is  severely
 irritating  to  the  lower respiratory tract, sometimes  inducing pulmo-
 nary edema, hemorrhage,  or a confluent pneumonia. The onset of
 respiratory distress may be delayed 4-12 hours after  exposure. It is a
 central nervous system depressant,  but may also cause  convulsions.
 Early symptoms of acute poisoning include headache, dizziness, nausea,
vomiting,  tremor, and ataxia. Repeated prolonged exposures  in some
 cases have led to a long-lasting syndrome of ataxia, incoordination,
 muscle weakness and areflexia. One case of recurrent myoclonic sei-
zures has been reported which required treatment for five years follow-
ing methyl bromide exposure. If liquid methyl bromide contacts the
skin, severe burning, itching, and blister formation occurs. Skin necro-
sis may be deep and extensive.
  Chloroform has an agreeable sweet odor and is only slightly irritat-
ing to the respiratory  tract.  It is a  powerful central nervous system
depressant (in fact, an anesthetic). Inhalation of toxic concentrations in
air leads to dizziness,  loss of sensation and motor power,  and then
unconsciousness. Inhalation of large amounts causes  cardiac arrhyth-
mias, sometimes progressing to ventricular fibrillation. Large absorbed
doses damage the functional cells of the liver and kidney. Ingestion is

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more likely to cause serious liver and kidney injury than is inhalation
of the vapor.
  Carbon tetrachloride is less toxic than chloroform as a central nerv-
ous system depressant, but is much more severely hepatotoxic, particu-
larly following ingestion. Liver cell damage is apparently due to a free
radical generated in the process of initial dechlorination. Kidney injury
also occurs; sometimes this is exaggerated by jaundice. Cardiac ar-
rhythmias, progressing to fibrillation, may follow inhalation of high
concentrations of carbon tetrachloride or ingestion of the liquid.
  Chloropicrin is severely irritating to the upper respiratory tract,
eyes, and skin. Inhalation of an irritant concentration sometimes leads
to vomiting. Ingestion could be expected to cause a corrosive gastroen-
teritis.
  Ethylene dichloride (correctly, dichloroethane) is moderately irritat-
ing to the eyes and respiratory tract. It depresses the central nervous
system,  induces  cardiac  arrhythmias,  and damages the liver  and
kidney, in much the same way as carbon tetrachloride. Symptoms and
signs of poisoning include headache,  nausea, vomiting, dizziness, diar-
rhea, hypotension, cyanosis, and unconsciousness. In addition  to necro-
sis  of liver  and kidney cells,  the  adrenal cortex may be destroyed,
especially after poisoning by ingestion.
  Ethylene dibromide (correctly, dibromoethane) is a severe irritant to
skin, eyes, and respiratory tract. The liquid causes blistering and ero-
sion of skin, and is corrosive to the eyes. Once absorbed, it may cause
pulmonary edema and  central nervous  system depression. Long-term
exposure may have some  damaging effect on testicular tissue. Persons
poisoned by ingestion have suffered chemical gastroenteritis,  liver ne-
crosis, and renal tubular  damage. Death is usually due to respiratory
or circulatory failure. A powerful disagreeable odor is advantageous in
warning  occupationally exposed workers of the presence of  this gas.
  Dibromochloropropane is irritating to skin, eyes, and the respirato-
ry tract. Eye damage  has resulted  from repeated exposure to  the
vapors. When absorbed, it causes headache, nausea, vomiting, ataxia,
and slurred speech. Liver and kidney damage are prominent features
of acute  poisoning. Chronic exposure to relatively low concentrations
has led to permanent sterility of workers in a manufacturing plant, by
causing diffuse necrosis of seminiferous tubule cells. Because it is much
less  odiferous than ethylene dibromide, exposure of workers to toxic
concentrations of DBCP is more likely.
  Dichloropropene and dichloropropane are strongly irritating to  the
skin, eyes, and respiratory tract. Bronchospasm may result from inha-
lation of high concentrations. Liver, kidney,  and cardiac toxicity is
probably similar to that produced by carbon tetrachloride.
  Paradichlorobenzene is solid  at  room  temperature, and is now
widely used  as  a  moth  repellant, air  freshener, and deodorizer in
homes and in public facilities. The vapor is only mildly irritating to  the
nose and eyes. Liver injury and tremor  may occur following ingestion

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of large  amounts. Although accidental ingestions, especially by chil-
dren, have been fairly common, symptomatic human poisonings have
been rare. Other stereoisomers of dichlorobenzene are more toxic than
the para-isomer.
  Ethylene oxide and propylene oxide are irritants to all tissues they
contact. Aqueous  solutions of ethylene oxide cause blistering and ero-
sion of the affected skin. The area of skin may thereafter be sensitized
to the fumigant.  Inhalation of high concentrations is likely to cause
pulmonary edema and cardiac arrhythmias. Headache, nausea, vomit-
ing, weakness,  and a persistent cough are common early manifesta-
tions of acute poisoning. Coughing of bloody, frothy sputum is charac-
teristic of pulmonary edema.
  Airborne formaldehyde  is irritating to the eyes and to membranes of
the upper respiratory tract. In some individuals, it is a potent sensitiz-
er,  causing asthma and dermatitis. High air concentrations may cause
laryngeal edema,  asthma,  or tracheobronchitis, but apparently not pul-
monary edema. Aqueous solutions in contact with the skin cause hard-
ening and roughness, due to superficial coagulation of the keratin
layer. Ingested formaldehyde attacks the lining membrane of the stom-
ach and intestine, causing necrosis and ulceration. Absorbed formalde-
hyde is rapidly converted  to formic acid. The latter is  partly responsi-
ble for the  metabolic acidosis that is characteristic of formaldehyde
poisoning. Circulatory collapse and renal failure may follow the devas-
tating effects of ingested  formaldehyde on the gut, leading to death.
Paraformaldehyde is  a polymer which slowly releases formaldehyde
into the air. Toxicity is  somewhat less  than that of formaldehyde,
because of the slow evolution of gas.
  Acrolein (acrylaldehyde) is an extremely irritating gas, used as  a
fumigant, aquatic herbicide, and "tear  gas." The vapor causes lacrima-
tion and upper respiratory tract irritation,' which may  lead to larynge-
al edema, bronchospasm,  and delayed pulmonary edema. The  conse-
quences  of ingestion  are  essentially the  same as those which  follow
ingestion of formaldehyde (see above). Contact with the skin may cause
blistering.
  Sulfur dioxide  is a highly irritant gas, so disagreeable that persons
inhaling it are usually warned to  seek uncontaminated air as soon as
possible. However, laryngospasm and pulmonary edema have occurred
occasionally, leading  to severe  respiratory distress and  death. It is
sometimes a cause of asthma in occupationally  exposed persons, even
when air concentrations are low.
  Sulfuryl fluoride has been used extensively for structural fumiga-
tion. Although  use experience has generally been good, some fatalities
have occurred  when  fumigated buildings have  been  prematurely re-
entered by  unprotected individuals. Manifestations of poisoning have
been nose, eye, and throat irritation, weakness, nausea, vomiting, dysp-
nea, cough, restlessness, muscle twitching, and  seizures. Renal  injury
may induce proteinuria and azotemia.

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   Carbon disulfide vapor is only moderately irritating to upper respi-
 ratory  membranes, but  it has an  offensive "rotten cabbage"  odor.
 Acute toxicity is due chiefly to effects on the central nervous system.
 Inhalation of high concentrations for short periods has caused head-
 ache, dizziness, nausea, hallucinations, delirium, progressive paralysis
 and death from respiratory failure. More prolonged exposure to lesser
 amounts has lead to blindness, deafness, paresthesia, painful neuropa-
 thy, and paralysis. Long-term occupational exposures  have been shown
 to accelerate atherosclerosis, leading to ischemic encephalopathy, myo-
 cardiopathy, and gastrointestinal dysfunction.  Toxic damage to the
 liver and kidneys may result in severe functional  deficits  of these
 organs.
  Phosphine gas is only slightly irritating to the respiratory tract, but
 is at least as toxic systemically as hydrogen  cyanide. It  is slowly
 released into treated produce  or  storage spaces  by hydrolysis of solid
 aluminum phosphide (phostoxin). Mechanisms of toxicity are not well
 understood. The  principal manifestations of poisoning are fatigue,
 nausea, headache, dizziness, thirst, cough, shortness  of breath, pares-
 thesia, and jaundice. Pulmonary edema  is a common cause of death.
 Odor is said to resemble that of decaying fish.
  Hydrogen cyanide gas  causes poisoning by inactivating cytochrome
 oxidase, the final enzyme essential to mammalian cellular respiration.
 The cells of the brain appear to be the most vulnerable to cyanide
 action.  Unconsciousness and death may occur immediately following
 inhalation of a high cyanide concentration, respiratory paralysis being
 the principal  mechanism. Lesser exposures cause  a  constriction and
 numbness in the throat, stiffness  of the jaw, salivation, nausea, vomit-
 ing, dizziness, and apprehension.  Worsening of the  poisoning is mani-
 fest as  violent tonic or clonic convulsions. Trismus and opisthotonos
 occur. Paralysis follows seizure activity. Incontinence is characteristic.
 The skin remains pink. Fixed, dilated pupils, bradycardia, and irregu-
 lar gasping respiration (or apnea) are typical of profound  poisoning.
 The heart often continues to beat after breathing has  stopped. A bitter
 almond odor to the breath or vomitus may be a  clue to poisoning, but
 not all  individuals are able to detect this odor. Similar color of the
 retinal arteries and veins may be a useful sign of cyanide poisoning; it
 is due to failure of reduction of hemoglobin as blood perfuses poisoned
tissues.
  Acrylonitrile  is biotransformed in the body  to  hydrogen cyanide.
Toxicity and mechanisms  of poisoning are essentially the same as have
been described for cyanide, except that acrylonitrile is irritating to the
eyes and to the upper respiratory tract.
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 CONFIRMATION OF POISONINGS BY FUMIGANTS

   Naphthalene is converted mainly to alpha naphthol in the body and
 promptly excreted  in conjugated form  in the urine. Alpha naphthol
 can be measured by gas chromatography.
   Many halocarbons can be measured in blood by gas chromatographic
 methods, some using head space techniques. Some can be measured in
 the expired air as well.
   Methylene chloride  is converted to carbon" monoxide in the body,
 generating carboxyhemoglobinemia, which can be measured by clinical
 laboratories.
   Paradichlorobenzene is metabolized  mainly to 2,5-dichlorophenol,
 which is conjugated and  excreted in the urine. This product can be
 measured chromatographically.
   Methyl  bromide yields inorganic bromide in the body; the anion is
 slowly excreted in the urine (half-life in the body is about 12 days). The
 serum from persons having no exceptional exposure to bromide usually
 contains less  than 1 mg bromide ion per 100 ml. The  possible contribu-
 tions  of medicinal  bromides to elevated  blood  content and urinary
 excretion  must be considered, but if methyl bromide is the exclusive
 source,  serum bromide exceeding 5 mg per  100 ml probably  means
 some  absorption, and 15 mg per 100 ml is consistent with symptoms of
 acute poisoning. Inorganic  bromide  is considerably less toxic than
 methyl bromide; serum concentrations in excess of 150 mg per 100 ml
 occur commonly in persons taking inorganic bromide medications.
  In some European countries, blood bromide concentrations are moni-
 tored  routinely in workers  exposed to  methyl bromide. Blood levels
 over 3 mg per 100 ml are considered a  warning that personal protec-
 tive measures must be improved. A bromide concentration over 5 mg
 per 100 ml requires that the worker be removed from the fumigant-
 contaminated environment until blood  concentrations decline to less
 than 3 mg per 100 ml.
  Carbon  disulfide can be measured in  urine by gas chromatography,
but the test  is not  generally available.  A qualitative test for carbon
disulfide metabolites in urine (based  on their reducing properties)  is
used for monitoring occupational exposure (Djuric D., N. Serducki, and
I.  Burkes.  lodme-azide  test on  urine of  persons exposed to  carbon
disulfide. Brit. J. Indus. Med., 22:321-3, 1965).
  Cyanide ion from cyanide itself or acrylonitrile can be measured in
whole blood and urine by an ion-specific electrode or by colorimetry.
The upper limit in whole  blood  among  nonexposed nonsmokers  is
about 0.02 mg per liter; it is 0.04 mg per liter in smokers. Symptoms
may appear at levels above 0.10 mg per  liter. Urine cyanide is usually
less than 0.30 mg per liter in nonsmokers, but as much as 0.80 mg per
liter in smokers. Thiocyanate, the metabolite of cyanide, can also be
measured in blood and urine. It is usually present in plasma at levels
less than 4 mg per liter in non-smokers, but up to 12 mg per liter in

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smokers. Urine thiocyanate is usually less than 4 mg per liter in non-
smokers, but may be as high as 17 mg per liter in smokers.
  A serum fluoride concentration of 0.5 mg per liter was measured in
one fatality from sulfuryl fluoride fumigation. Serum fluoride in per-
sons not exceptionally exposed rarely exceeds 0.1 mg per liter.
  There are no practical tests for absorbed alkyl oxides, aldehydes, or
phosphine that would be helpful in diagnosis of poisoning.
  Large industrial concerns sometimes monitor human absorption of
halocarbons by analysis of expired air. Similar technology is available
in some departments  of anesthesiology.  These analyses  are rarely
needed  to identify the offending toxicant, because this is known from
the exposure history. In managing difficult cases of poisoning, however,
it may  be helpful  to monitor breath concentrations of toxic gas to
evaluate disposition of the fumigant.  Testing of the urine for  protein
and red cells is needed to detect renal  injury. Free hemoglobin in urine
most likely reflects hemolysis, as from naphthalene. Elevations of alka-
line phosphatase, lactate  dehydrogenase (LDH), serum GOT,  ALT,
AST, and certain other enzymes are sensitive indices of insult to liver
cells. More severe damage increases plasma concentrations of bilirubin.
The chest x-ray may be used to confirm  the occurrence of pulmonary
edema.  Electromyography may  be  useful  hi evaluating  peripheral
nerve injury. Sperm counts may be appropriate for workers exposed to
dibromochloropropane and ethylene dibromide.
   Some occupational health agencies now urge periodic neurologic and
neuropsychologic testing of workers heavily exposed to fumigants and
"solvents to detect injury to the nervous system as early  as possible.
This would be particularly desirable  in the case of exposures  to such
agents  as methyl bromide and carbon disulfide which have well docu-
mented chronic neurotoxic effects.

TREATMENT OF POISONINGS BY FUMIGANTS

  1.  FLUSH  contaminating fumigants from the skin and  eyes with
     copious amounts of water or saline for at least 15 minutes. Some
     fumigants  are corrosive to the  cornea and may cause BLIND-
     NESS. Specialized medical treatment should be obtained promptly
     following removal  of toxicant  by  copious  flushing with  clean
     water. Skin contamination may cause BLISTERING and deep
     chemical burns.  Absorption of  some fumigants across the skin
     may  be  sufficient to cause  systemic poisoning in the absence of
     fumigant inhalation. For all these  reasons, decontamination of
     eyes and skin must be IMMEDIATE and THOROUGH.
  2. REMOVE victims of fumigant inhalation to FRESH AIR immedi-
     ately. Even though initial symptoms and signs are mild, keep the
     victim quiet, hi a semi-reclining position. Minimum physical activ-
     ity limits the likelihood of pulmonary edema.

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3.  If victim is not breathing, clear the airway of secretions and
    RESUSCITATE with positive pressure oxygen apparatus. If this
    is not available, use chest compression to sustain respiration. If
    victim is pulseless, employ cardiac resuscitation.
4.  If PULMONARY EDEMA is evident, there are several measures
    available to sustain life. Medical judgment must be relied upon,
    however,  in the management of each case. The following proce-
    dures are generally recommended:
    A.  Put the victim in a SITTING position with a backrest.
    B.  Use   intermittent  and/or   continuous   positive  pressure
       OXYGEN to relieve hypoxemia. (Do not give oxygen at great-
       er concentrations or longer periods than necessary, because it
       may exaggerate the fumigant injury to lung tissue. Monitor
       arterial p02.)
    C.  Slowly administer FUROSEMIDE, 40 mg, or SODIUM ETH-
       ACRYNATE, 50 mg, intravenously, to reduce venous load by
       inducing diuresis. Consult package insert for additional direc-
       tions and warnings.
    D.  Administer MORPHINE in small doses (5-10 mg), slowly, in-
       travenously, to allay anxiety and promote deeper respiratory
       excursions.
    E.  Administer AMINOPHYLLINE (0.25-0.50 gin) slowly, intrave-
       nously. Consult package insert.
    F.  Digitalization may be considered, but there is a serious risk of
       arrhythmias in an anoxic and toxic myocardium.
    G.  TRACHEOSTOMY may be necessary in some cases to facili-
       tate aspiration of large  amounts of pulmonary edema fluid.
    H.  Epinephrine, atropine, and  expectorants are generally not
       helpful, and may complicate treatment.
    I.  Watch for RECURRENT PULMONARY EDEMA, even up to
       2 weeks after the initial episode. Limit victim's physical activ-
       ity for at least 4 weeks. Severe physical weakness usually
       indicates persistent pulmonary injury. Serial pulmonary func-
       tion testing may be useful in assessing recovery.
5.  Combat SHOCK by placing victim in the Trendelenburg position
    and administering plasma, whole blood,  and/or electrolyte and
    glucose solutions intravenously,  with great care, .to avoid pulmo-
    nary edema. Central  venous pressure should be monitored con-
    tinuously; Vasopressor amines must  be given with great caution,
    because of the irritability of the myocardium.
6.  Control CONVULSIONS. Seizures  are  most likely to  occur  in
    poisonings by methyl bromide,  hydrogen  cyanide,  acrylonitrile,
    phosphine, and carbon disulfide.
    A.  Establish pulmonary gas exchange at the best  possible level
       by administering  OXYGEN by continuous positive pressure
       ventilation.

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    B.  In poisoning by CYANIDE and ACRYLONITRILE, proceed
       directly with ANTIDOTAL therapy  (see  below paragraph
       HE).
    C.  Control convulsions caused by other agents with careful IV
       injection of DIAZEPAM, 5-10 mg in adults and children over
       12 years,  0.25-0.40  mg/kg in children under  12 years. (See
       Chapter 3, TREATMENT, Section 4, p. 21.) Repeat dosage in
       4-6 hours  if necessary.
       CAUTION: Be  prepared to maintain  pulmonary ventilation
       mechanically, and to manage  hypotension and cardiac ar-
       rhythmias. Alternative or supplemental anticonvulsive ther-
       apy is discussed in the reference cited.
    D.  In methyl bromide poisoning, it may be necessary to give
       benzodiazepines or barbiturates orally for days  or weeks after
       the poisoning to control involuntary motor activity. Consult
       package inserts for appropriate dosages.
7.   If a FUMIGANT LIQUID OR SOLID has been INGESTED less
    than several  hours prior to treatment, quantities remaining in
    the stomach must be removed as effectively as possible by gastric
    intubation, aspiration, and lavage, after all possible precautions
    have been taken to protect the respiratory tract from aspirated
    gastric contents.
    A.  Put in place  a cuffed ENDOTRACHEAL TUBE prior to gas-
       tric intubation. Administer  OXYGEN, using  a mechanical
       ventilator if respiration is depressed.
    B.  Lavage the  stomach with a slurry of ACTIVATED CHAR-
       COAL in saline or water. Leave a volume of the slurry in the
       stomach with an appropriate dose of sorbitol as cathartic (for
       dosages, see Chapter 1, TREATMENT, Section 6, p. 8).
    C.  If treatment is delayed and if the patient remains fully alert,
       administer activated charcoal and sorbitol orally. For dosage,
       see Chapter 1, TREATMENT, Section 6, p. 8. Repeated admin-
       istration of charcoal at half or more the initial dosage  every
       2-4 hours  may be beneficial.
    D.  Do not give vegetable or annual fats or oils, which enhance
       gastrointestinal absorption of many  of the fumigant com-
       pounds.
8.   Intravenous infusions of GLUCOSE  are valuable in  limiting the
    hepatotoxicity of many  substances.  Monitor central venous pres-
    sure to avoid  precipitating,  or aggravating, pulmonary edema by
    fluid overload. The victim should be watched closely for indica-
    tions of delayed or recurrent pulmonary edema, and  for broncho-
    pneumonia. Fluid balance  should be monitored, and urine  sedi-
    ment  should  be checked  regularly  for  'ndications of tubular
    injury. Measure  serum alkaline phosphatase,  LDH, ALT, AST,
    and bilirubin to assess liver injury.

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 9.  HEMOPERFUSION OVER ACTIVATED CHARCOAL has been
     used in, managing a case of carbon tetrachloride poisoning with
     apparent success. An extraction efficiency of about 80% was dem-
     onstrated for the system employed (Schwarzbeck, A. and Kosters,
     W.,  Arch. ToxicoL, 35:207-211, 1976).  It is possible that other
     fumigant compounds would be effectively removed from blood by
     this method.
10.  EXTRACORPOREAL  HEMODIALYSIS may be needed to regu-
     late extracellular fluid composition if renal failure supervenes. It
     is probably not very  effective  in removing lipophilic  fumigant
     compounds  from blood, but is, of course, effective in controlling
     extracellular fluid composition if renal failure occurs.

11.  Certain SPECIFIC MEASURES are recommended in poisonings
     by particular fumigants (naphthalene, methyl  bromide,  carbon
     tetrachloride, hydrogen cyanide):

     A. NAPHTHALENE  toxicosis caused by vapor inhalation  can
        usually  be  managed simply by removing the individual to
        fresh air. Skin contamination should be removed promptly by
        washing with soap and water. Eye contamination  should be
        removed by flushing with  copious amounts  of clean water.
        Irritation may be  severe, and if it  persists,  should receive
        medical attention.
             If solid naphthalene has been INGESTED and retained
             less than several hours prior to treatment, and if the
             patient is fully alert, the stomach should be emptied by
             administration of Syrup of Ipecac, followed by several
             glasses of water. Dosage for adults and children over 12
             years: 30 ml; dosage for children under  12 years: 15 ml.
             When vomiting subsides, give activated charcoal and
             sorbitol (see Chapter  1, TREATMENT, Section 6, p. 8).
             If the patient is obtunded or excited, do not give Ipecac,
             but take steps to protect the airway, then aspirate and
             lavage the stomach with a slurry of activated  charcoal.
             Leave charcoal and sorbitol in the stomach before with-
             drawing the tube (see above reference). Repeated admin-
             istration of charcoal every 2-4 hours may be beneficial.
             If treatment is delayed more than several hours, admin-
             ister as much activated charcoal orally as the patient
             will tolerate.  Include sorbitol  in  the  charcoal slurry
             unless diarrhea has already commenced.
             Examine the plasma  for evidence  of hemolysis: a red-
             dish-brown tinge. Examine the blood smear for "ghosts"
             and Heinz bodies.  If present,  monitor red blood cell
             count and hematocrit for anemia, urine for protein and
             cells.  Measure direct- and indirect-reacting bilirubin in
             the plasma. Monitor  fluid balance and blood electro-
a.
b.
c.
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         lytes. If possible, monitor urinary excretion of naphthol
         to assess  severity of poisoning and clinical progress.
     d.   If hemolysis is clinically significant, administer intrave-
         nous fluids to accelerate urinary excretion of the naph-
         thol metabolite and protect the kidney from products of
         hemolysis. Use Ringer's-lactate or sodium bicarbonate
         to keep urine pH above 7.5. Consider use of mannitol,
         furosemide, or  ethacrynic acid to promote  diuresis. If
         urine  flow declines, intravenous  infusions  must  be
         stopped to prevent fluid overload. Institute hemodialy-
         sis. Consider charcoal hemoperfusion in tandem to  ex-
         tract naphthalene and end-products.
     e.   If anemia is severe, blood transfusions may be needed.
     f.   Hydrocortisone may be of  some benefit if  significant
         hemolysis is present.

B.  If given very soon after life-threatening exposure to METHYL
    BROMIDE there may be  some theoretical value in adminis-
    tering DIMERCAPROL (BAL) in vegetable oil intramuscular-
    ly. For adults, give 3-5 mg/kg q6h for 4 to 6 doses. Neither
    the effectiveness nor the  safety of this treatment has been
    tested in methyl bromide poisoning.
    CAUTION: DIMERCAPROL  may cause troublesome  side ef-
    fects (hypertension, tachycardia, nausea, headache, paresthe-
    sia, pain, lacrimation, sweating, anxiety, and restlessness).  Al-
    though usually not so severe as to preclude treatment, these
    effects may require antihistamine therapy.

C.  For  CARBON  TETRACHLORIDE poisoning, several  treat-
    ment measures have been suggested to limit the  severity of
    hepatic necrosis.  Neither effectiveness  nor safety of any of
    these measures has been established.
     a.   Inhalation of oxygen at one or two  atmospheres for  2
          hours twice daily may have some value.
     b.   Oral administration of tocopherol (vitamin E) in oral
          doses  of several hundred milligrams per day has been
          suggested on grounds  of its action as a free radical
          scavenger.
     c.   Oral  administration of N-acetyl cysteine  (Mucomyst)
          may be worthwhile as a means of reducing free radical
          injury. Dilute the proprietary 20% product 1:3  in soda-
          pop, and give about 3 ml/kg body weight of the diluted
          solution as a loading dose. Give half of this dosage every
          4 hours after the loading dose for a total  of 17  doses.
          (This  dosage schedule is used for acetaminophen poison-
          ings.) Administration via duodenal tube may be  neces-
          sary in a few patients who cannot tolerate Mucomyst.

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     d.   Hemoperfusion over activated charcoal should be con-
          sidered. It was apparently effective in one carbon tetra-
          chloride poisoning. See Schwarzbeck, A. and Rosters, W.
          Arch. Toxicol., 35:207-211, 1976.

 D.  MM poisonings by CARBON BISULFIDE inhalation may be
    managed  best by no  more than careful  observation, even
    though sensory hallucinations, delirium, and behavioral aber-
    rations can be alarming. Severe poisonings may require specif-
    ic measures:
     a.   If manic behavior threatens  the  safety of the victim,
          DIAZEPAM, 5-10 mg in adults, 0.2-0.4 mg/kg in chil-
          dren, administered slowly, intravenously, may be help-
          ful as a tranquilizer. Give as much as is necessary to
          achieve  sedation. Do not  give catecholamine-releasing
          agents such as reserpine and amphetamines.
     b.   In severe poisonings by carbon disulfide, pyridoxine hy-
          drochloride (vitamin  B6) may have  some  antidotal
          action against the neurotoxic effects. Its value is theo-
          retical;  neither effectiveness nor safety has been tested
          in carbon disulfide poisonings. The  usual  dosage in
          other poisonings  (ISONIAZID) has been 5 gm in a 10%
          solution, given slowly intravenously, or included in  a
          one liter intravenous solution of 5% glucose. When the
          victim can  swallow,  pyridoxine hydrochloride can be
          given orally in daily doses as high as 25 mg/kg body
          weight.  There is probably little value, and possibly some
          hazard, in extending the treatment beyond one or two
          weeks.
E.  Poisonings  by  HYDROGEN CYANIDE  and  ACRYLONI-
    TRILE gases  or liquids are treated essentially the same as
    poisoning by  cyanide  salts. Because cyanide is  so promptly
    absorbed  following ingestion,  treatment  should commence
    with PROMPT ADMINISTRATION OF  ANTIDOTES,  defer-
    ring gastric evacuation (in ingestion poisonings) until  anti-
    dotes have been administered.
    If the victim is an ADULT:
         Administer OXYGEN continuously. If respiration fails,
         maintain pulmonary ventilation mechanically.
         Administer AMYL NITRITE (perles) by inhalation for
         15-30 seconds of every minute, while a fresh solution of
         3% sodium nitrite is being prepared.
         As soon as solution is available, inject intravenously 10
         ml of 3% SODIUM NITRITE solution .over a 2-4 minute
         interval, keeping the needle in place.
a.
b.
c.
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    CAUTION:  MONITOR  PULSE and  BLOOD  PRES-
    SURE during administration of amyl nitrite and sodium
    nitrite. If systolic blood pressure falls below 80 mm Hg,
    slow or stop nitrite administration until blood pressure
    recovers.
d.   Follow sodium nitrite injection with an infusion of 50
    ml of 25%  aqueous solution  of .SODIUM THIOSUL-
    FATE administered over a  10-minute period. Initial
    adult dose should not exceed 12.5 gm.
e.   If symptoms persist or recur,  treatment by sodium ni-
    trite and sodium thiosulfate should be REPEATED AT
    HALF THE DOSAGES listed in paragraphs c and d.
f.   Measure hemoglobin  and methemoglobin in blood. If
    more than 50% of total hemoglobin has been  converted
    to  methemoglobin, BLOOD  TRANSFUSION  or ex-
    change transfusion should be considered,  because con-
    version back to normal hemoglobin proceeds slowly.
If the victim is a CHILD:
a.   Give  amyl nitrite, oxygen, and mechanical respiratory
    support as recommended for adults.
b.   The following  dosages of antidotes have  been recom-
    mended by C.M.  Berlin (Pediatrics, 46:793-796, 1970).
        i) Children over 25 kg body weight should receive
          adult dosages of sodium nitrite and sodium thio-
          sulfate.
        ii) Children less than 25 kg body weight should first
          have  two  3-4 ml  samples  of blood drawn and
          then, through the same needle, receive 10 nig/kg
          (0.33 ml/kg of 3% solution) of SODIUM NITRITE
          injected  over a 2-4 minute interval.  Following
          sodium  nitrite,  administer  an infusion  of 1.65
          ml/kg of 25% SODIUM THIOSULFATE at rate
          of 3-5 ml per minute.
        iii) At this  point, determine the hemoglobin content
          of the pretreatment blood sample.  If  symptoms
          and signs of poisoning persist or return, give sup-
          plemental  infusions of sodium nitrite and sodium
          thiosulfate based on hemoglobin level, as present-
          ed in TABLE 2. These recommended  quantities
          are calculated to  avoid life-threatening methe-
          moglobinemia  in   anemic   children.   They are
           aimed at converting approximately  40% of circu-
           lating hemoglobin to methemoglobin.  If possible,
          monitor blood  methemoglobin concentrations as
          treatment proceeds.

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   TABLE 2. Recommended dosages of supplemental sodium nitrite and
             sodium thiosulfate based on hemoglobin level.
Initial
Hemoglobin
Concentration
gm/100 ml
14.0
13.0
12.0
11.0
10.0
9.0
8.0
7.0
Supplemental
Volume of 3%
Sodium Nitrite,
ml/kg
0.25
0.21
0.17
0.13
0.09
0.05
0.00
0.00
Supplemental
Volume of
25% Sodium
Thiosulfate,
ml/kg
1.25
1.05
0.85
0.65
0.45
0.25
0.00
0.00
  Although  various cobalt salts,  chelates,  and organic combinations
have shown  some promise as antidotes to cyanide, they are not gener-
ally available. None have been shown to surpass the nitrite-thoisulfate
regimen in effectiveness.
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                   CHAPTER 15

     MISCELLANEOUS PESTICIDES,
      SOLVENTS, AND ADJUVANTS

  The following pest control agents are widely used and may occasion-
ally pose a risk of human poisoning.
                    METALDEHYDE
CHEMICAL STRUCTURE
                           fa
                           c —
          CH3- C - H
                                    H - C - CH,
                           V
                           C
                            CH,
 COMMERCIAL PRODUCTS

  Antimilace, Bug-Geta, Cekumeta, Corry's Slug and Snail Death, Ha-
 lizan, Metason, Namekil.

 TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  METALDEHYDE

  Metaldehyde is a 4-unit cyclic polymer of acetaldehyde long used to
 kill slugs and snails, which are attracted to it without the use of bait.
 Occasional poisonings of animals and children have resulted from in-
 gestion of pellets intended as molluscicide, but tablets designed as fuel
 in smokeless lamps have more commonly been the agents responsible
 for human poisonings. The biochemical mechanism of poisoning is not
 known; acetaldehyde derived from depolymefization does not produce
 the dramatic neurologic symptoms and signs of metaldehyde poisoning.
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 Furthermore, acetaldehyde is not detectable in the blood or urine of
 metaldehyde-poisoned dogs.
   Ingestion of a toxic dose is sometimes followed by vomiting due to
 gastric irritation. Within  a few minutes  to  several hours  following
 ingestion, salivation, flushing, abdominal cramps, vomiting, and gener-
 alized tremors occur; the  latter may progress to violent tonic-clonic
 convulsions.  Hyperthermia and tachycardia characterize some  cases.
 Poisoned animals show tremors, ataxia, hyperesthesia, and salivation.
 Autopsy findings in fatal human poisonings indicate severe damage to
 liver cells and renal tubular epithelium. Metabolic acidosis may be an
 important factor leading to death.

 CONFIRMATION OF METALDEHYDE POISONING

   Chromatographic methods for measurement of metaldehyde in blood
 are described but are not generally available.  Very little metaldehyde
 or acetaldehyde is  excreted  in the urine of metaldehyde-dosed dogs.
 Liver function tests and repeat urinalyses for protein and cells should
 be done to assess liver and kidney injury in poisoned patients.

 TREATMENT OF METALDEHYDE  POISONING

   Unless ingestion occurred more than several hours before treatment,
 ingested metaldehyde must be removed  from the gut, preferably by
 gastric lavage and catharsis (see Chapter 1. TREATMENT, Section 6,
 p. 8). Activated charcoal may well be useful against metaldehyde. If
 seizures  occur, sedative anticonvulsants must be  administered (see
 Chapter 3, TREATMENT, Section 4, p. 21). Intravenous fluids, includ-
 ing glucose, should  be given to protect the  liver, support detoxication,
 and facilitate excretion. Add  sodium bicarbonate to intravenous fluids
to reverse metabolic acidosis. Fluid balance and electrolytes  must be
monitored carefully to avoid fluid overload if renal failure supervenes.
  There is no specific antidote for metaldehyde poisoning. Hemodialy-
sis is probably not effective  in removing metaldehyde, but  must be
instituted if renal failure occurs. Effectiveness of hemoperfusion has
not been tested.
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                      4-AMINOPYRIDINE

CHEMICAL STRUCTURE
                    H2N\\      NH
COMMERCIAL PRODUCTS

  Avitrol, 4-Ap.

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  AMINOPYRIDINE

  4-Aminopyridine is a highly toxic white powder used as a bird repel-
lant. (Only occasionally  does  it kill the poisoned bird:  the cries and
excited behavior of the affected bird cause others to take flight). It is
usually added to grain baits in 0.5%-3.0% concentration, but 25% and
50% concentrates in powdered sugar are available. It  is rapidly ab-
sorbed by the gut, less effectively across skin. The chief mechanism of
toxicity  is  enhancement of cholinergic transmission in the nervous
system.  4-Aminopyridine is  rapidly metabolized and  excreted. No
human poisonings  have  occurred as a result of ordinary use, but the
effects of ingestion of about  60 mg by each of two ill-advised adult
humans have been reported.  Both experienced immediate  abdominal
discomfort, nausea and vomiting, weakness, dizziness, and  profuse di-
aphoresis. One patient suffered a  tonic-clonic seizure  and went  into
respiratory arrest. With supportive treatment,  both recovered in 3
days. Poisoned laboratory animals commonly exhibit excitability,  sali-
vation, tremors, incoordination, convulsions, and cardiac or respiratory
arrest.

TREATMENT OF POISONING BY AMINOPYRIDINE INGESTION

  Unless ingestion occurred more than several hours before treatment,
the stomach must be emptied by intubation, aspiration, and lavage
with a slurry of activated charcoal, following placement of cuffed endo-
tracheal tube (see  Chapter 1, TREATMENT, Section 6, p. 8). Induced
emesis may be a reasonable alternative  if the patient is fully alert, but
there is substantial risk of aspiration of gastric contents if convulsions
or depressed consciousness level and reflexes occur before emesis.  Gas-
tric evacuation should be followed by administration of charcoal and
sorbitol.  If treatment is delayed,  immediate oral administration of

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 ckarcoal  and sorbitol  may represent optimal management. Seizures
 may require anticonvulsant medication (see Chapter 3, TREATMENT,
 Section 4, page 21). Dehydration should be treated with intravenous
 fluids if oral fluids cannot be retained.
                     CALCIUM CYANAMIDE

 CHEMICAL STRUCTURE
Cyanam.de
                                            H2N-C

                                           Hydrogen
                                           Cyanamide
 COMMERCIAL PRODUCTS

  Cyanamide, nitrolime.
  This synthetic compound is  marketed as granules containing 44%
 calcium cyanamide, yielding 19.5% nitrogen. It is incorporated into soil
 to serve as fertilizer, fungicide, and herbicide. In contact with water,
 hydrogen cyanamide is released; the hydrolysis proceeds most rapidly
 under acid conditions. Hydrogen cyanamide is a solid with considerable
 vapor pressure. It has toxic properties totally different from those of
 cyanide, and it does not degrade to cyanide.

 TOXICOLOGY AND MANIFESTATIONS OP POISONING BY
  CYANAMIDE

  Calcium cyanamide is only moderately irritating to skin, but hydro-
 gen cyanamide  is severely irritating and caustic to skin and the in-
 haled gas is strongly irritating to mucous membranes.
  The efficiency of dermal absorption of either form of cyanamide is
 not known; poisonings by this route have not been reported. Systemic
 poisonings have followed inhalation of hydrogen cyanamide and inges-
 tion of the salt. Manifestations of poisoning are: flushing, headache,
vertigo, dyspnea, tachycardia, and hypotension, sometimes progressing
to shock. Because cyanamide is an inhibitor of acetaldehyde dehydro-
genase, ingestion of alcohol exaggerates the symptoms. (A titrated
form of cyanamide  has been used in place of  Antabuse in alcohol
aversion therapy.)

TREATMENT OF CYANAMIDE POISONING

  Skin contamination with either  the  calcium salt or  the free form
should be removed by washing with soap and water. Eye contamina-

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tion should be removed by flushing the eyes with copious amounts of
clean water. If skin or eye irritation persists, medical attention should
be obtained promptly.
  If large doses have been ingested recently, the stomach  should be
emptied with due care to protect the airway (Chapter 1. TREATMENT,
Section 6, p. 8). If dosage was small or treatment is delayed, immediate
oral administration of activated charcoal and sorbitol probably repre-
sents optimal management.
  Treat hypotension or Antabuse-type reaction by placing the  patient
in Trendelenburg position, giving intravenous fluids, including  plasma
or blood, if needed, and,  if necessary, vasopressor drugs parenterally.
  Atropine is not antidotal.

                      SODIUM CHLORATE

CHEMICAL STRUCTURE

                           Na Cl O3
 COMMERCIAL PRODUCTS

   Atratol, De-Fol-Ate, Dervan, Drexel Defol, Drop-Leaf, Fall, Harvest-
 Aid, Klorex, KM, Kusatol, Tumbleaf.
   Sodium chlorate is used in agriculture as a defoliant, nonselectiye
 contact  herbicide,  and semipermanent soil sterilant.  Because of its
 explosive nature, it must be formulated with water-soluble fire retard-
 ant material, such as sodium metaborate, soda ash, magnesium chlo-
 ride, or urea. It is usually applied in water solution.

 TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
   SODIUM CHLORATE

   Sodium chlorate is irritating to skin, eyes,  and mucous membranes
 of the  upper  respiratory tract. Dermal  absorption  is  slight.  Even
 though gastrointestinal absorption  is also inefficient, severe poisoning,
 sometimes fatal, follows ingestion  of a toxic  dose, said to be several
 grams in the adult human. Onset of symptoms is sometimes delayed as
 much as twelve hours. Excretion is chiefly in the urine. The principal
 mechanisms of toxicity are: hemolysis, methemoglobin formation, car-
 diac arrhythmia (partly secondary to hyperkalemia), and renal tubular
 injury. The irritant action on the gut causes nausea, vomiting, abdomi-
 nal pain, and diarrhea. Hypotension may progress to shock. Cyanosis
 and dyspnea are prominent if hemolysis and methemoglpbinemia are
 severe.  Lumbar pain, proteinuria, hemoglobinuria, oliguria, and azote-
 mia result from renal injury. Plasma and. urine  are dark brown from

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presence of free hemoglobin and methemoglobin. Release of potassium
from red cell destruction results in hyperkalemia; this may be severe
enough to cause life-threatening cardiac conduction defects. The liver
is often enlarged and tender. Anoxemia may lead to convulsions. Death
may be the result of shock, anoxemia,  heart failure,  or  disseminated
intravascular coagulation.
  There are no widely  available tests for  chlorate specifically. Dark
brown staining of the plasma and urine indicates the action of a strong
oxidizing agent on hemoglobin.

TREATMENT OF CHLORATE POISONING

 1.   Skin contamination should be removed immediately by washing
     with soap and water. Medical attention should be sought if irrita-
     tion persists.
     Eye contamination should be removed by flushing with copious
     amounts of clean water, then specialized medical attention should
     be obtained promptly, because irritant action may be severe.
 2.   If sodium chlorate has been ingested within several hours prior to
     treatment, put in place a cuffed endotracheal tube to protect the
     airway, then intubate the stomach, and lavage with a slurry of
     activated  charcoal  (Chapter 1, TREATMENT, Section 6,  p. 8).
     After the lavage,  instill 200 ml of 5% sodium bicarbonate contain-
     ing 2-5 gm of SODIUM  THIOSULFATE to  decompose any re-
     maining chlorate. Sorbitol should be administered if diarrhea has
     hot already commenced.
 3.   Give OXYGEN. If respiration is  depressed,  maintain pulmonary
     ventilation with intermittent positive pressure breathing appara-
     tus.
 4.   SODIUM THIOSULFATE intravenous infusion is an apparently
     successful antidote  against absorbed sodium chlorate. Infuse 2-5
     gm dissolved in  200 ml of 5% sodium  bicarbonate  over  60-90
     minutes.
 5.   Monitor blood  pressure,  fluid balance, blood  electrolytes,  BUN,
     methemoglobin, and bilirubin, also urine protein, cells and free
    hemoglobin content,'and EGG. Widening of the QRS complex and
    prolongation  of the PR  interval indicate hyperkalemic cardiac
    toxicity.
 6.  MILK may be helpful in relieving  the pain of gastric irritation.
 7.  Administer INTRAVENOUS FLUIDS  to sustain  chlorate excre-
    tion. Maintain urine pH in the alkaline range  by addition of
    sodium bicarbonate to the infusion fluid. Monitor urine produc-
    tion closely, so that  intravenous fluids can be slowed or discontin-
    ued  if renal failure occurs. BLOOD  TRANSFUSION may be
    needed if hemolysis  and methemoglobinemia are severe.
8.  HEMODIALYSIS may be life-saving in severe  poisoning. It is
    effective in removing chlorate from the  blood, provides a means to

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     control hyperkalemia, and makes possible the control of extracel-
     lular fluid volume and composition while renal function remains
     impaired.
 9.   Administration of methylene blue to reverse methemoglobinemia
     may be considered if as much as 25-30% of hemoglobin is convert-
     ed, even though use of this agent in chlorate poisoning has not
     proven beneficial in the past. Give intravenously 0.1 ml/kg body
     weight of a 1% solution over a period of at least 10 minutes. An
     increase in blood pressure, nausea, and dizziness may occur, but
     these effects are usually transient.
                            CREOSOTE

  Creosote is obtained by distillation of the tar formed by heating wood
or coal in the absence of oxygen. It is purified by extraction into oils.
Creosote from wood consists mainly of guaiacol (methoxy phenol) and
cresol  (methyl phenol). Coal-derived  creosote  contains,  in addition,
some phenol, pyridine, and pyridinol. Creosote is extensively used as a
wood preservative, usually by high-pressure impregnation of lumber. It
has also been used as an animal dip and disinfectant.
  Creosote is irritating to skin, eyes, and mucous membranes. Workers
in contact with technical creosote  or with treated timbers sometimes
develop skin irritation, vesicular or papular eruptions, dermal pigmen-
tation, and occasionally gangrene and skin cancer. Photosensitization
has  been reported.  Eye contamination has resulted in conjunctivitis
and  keratitis, sometimes resulting in corneal scarring. The constituents
of creosote are efficiently absorbed across the skin, but systemic poison-
ings following dermal absorption have occurred very rarely. Absorption
of ingested creosote from the gut occurs  promptly, and there  may be
significant absorption of vapor by the lung. Conjugates of absorbed
phenolic constituents are excreted mainly in the urine. Acute toxic
effects are similar to those of phenol, but toxicity is somewhat less.
Irritation of the gastrointestinal tract, toxic encephalopathy, and renal
tubular injury are the principal effects. A chronic toxicosis from con-
tinuing  gastrointestinal absorption  (creosote used medicinally)  has
been described, consisting of gastroenteritis and visual disturbances.
   Manifestations of acute systemic poisoning are salivation, vomiting,
dyspnea, headache,  dizziness, loss of pupillary reflexes, cyanosis, hypo-
thermia, convulsions, and coma. Moderate hypotension may progress to
shock; vascular collapse is the usual cause of death, although respirato-
ry depression may well be contributory. The presence of phenolic oxi-
dation products imparts a dark, smoky color to the urine. If there is
suspicion of poisoning, addition of a few drops of ferric chloride solu-
tion to the urine yields a violet or blue color indicating the presence of
phenolic compounds.

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TREATMENT OP CREOSOTE POISONING
 1.
 2.
 3.
4.
5.
6.
7.
8.
9.
 Stringent measures should be taken to avoid contamination  of
 skin or eyes and inhalation of vapor. Skin contamination should
 be promptly washed off with soap and water. Contamination  of
 the eyes should be removed by washing with copious amounts  of
 water, then specialized medical  attention should  be obtained
 promptly because corneal injury may be severe.
 If a significant amount of creosote has been ingested and the
 patient is alert and able to swallow, immediately administer a
 slurry of activated charcoal by mouth (for dosage, see Chapter  1,
 TREATMENT, Section 6, p. 8). Further efforts to limit absorption
 depend on whether there has been corrosive injury to the esopha-
 gus. If pharyngeal redness and swelling are evident, neither in-
 duced emesis or gastric lavage are advisable: emesis will re-expose
 the esophagus to the creosote, and a gastric tube may perforate
 the esophagus. If there is minimal evidence of pharyngeal injury,
 careful gastric intubation and lavage with activated charcoal may
 be undertaken  after placement of a cuffed endotracheal tube to
 protect the  airway. Sorbitol should be administered if diarrhea
 has not already developed  in response to the creosote. Whether
 gastric lavage is accomplished or not, repeated administration of
 activated charcoal by mouth, at half or more  the initial  dose
 every 2-4 hours, may well be beneficial.
 Maintain pulmonary ventilation mechanically with oxygen, if nec-
 essary.
 Draw a blood sample to test for methemoglobinemia, to measure
 BUN and blood electrolytes, and to check for signs of liver injury
 (bilirubin, GOT, LDH, ALT, AST, and alkaline phosphatase).  Test
 the urine for protein and cells, and for  "smoky"  phenolic excre-
 tion products.
 Give fluids  intravenously to correct dehydration and electrolyte
 disturbances. Include glucose to protect the liver and bicarbonate
 to relieve metabolic acidosis, as necessary. Monitor fluid balance
 carefully  to signal discontinuation  of intravenous fluids if renal
 failure  occurs.  Plasma  or blood transfusion may be needed to
 overcome shock.
 Monitor EGG to detect arrhythmias and/or conduction defects
 that may appear  as manifestations of a toxic myocardiopathy.
 Diazepam may  be needed  to  control tremors or seizures  See
 Chapter 3, TREATMENT, Section 4, p. 21 for dosage.
 Hemodialysis is not effective in accelerating disposition of phenol
 (or, presumably, creosote), but HEMOPERPUSION over charcoal
probably is effective. This should be instituted  in severe creosote
poisonings.
Methemoglobinemia is rarely severe, but intravenous administra-
tion of 1% methylene blue may be considered if 25-30% of hemo-
                              153

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    globin is converted. Dose is 0.1  ml of 1% solution per kg body
    weight, given over no less than ten minutes. Nausea, dizziness,
    and a transient increase in blood pressure may occur.


                          ENDOTHALL
CHEMICAL STRUCTURE
                       H
                                H
COMMERCIAL PRODUCTS

  Accelerate, Endothall Weed Killer, Aquathol, Des-i-cate, Endothall
Turf Herbicide, Hydrothol, Herbicide 273.
  As the free acid or as sodium, potassium or amine salts, endothall is
used as a contact herbicide, defoliant, aquatic herbicide and algacide. It
is formulated in aqueous solutions and granules at various strengths.

TOXICOLOGY AND MANIFESTATIONS OF POISONING BY
  ENDOTHALL

  Endothall is irritating to skin,  eyes,  and  mucous membranes. It is
well absorbed across abraded  skin and from the gastrointestinal tract.
Recognized systemic toxic mechanisms in mammals are: 1) corrosive
effect on the gastrointestinal  tract (particularly from high concentra-
tions of the free acid);  2) myocardiopathy and vascular injury leading
to shock; and 3) central nervous system injury, causing convulsions and
respiratory depression.
  No human poisonings by endothall have been reported. There are no
generally available tests to confirm absorption.

TREATMENT OF ENDOTHALL  POISONING

  1.   Wash endothall from the skin with soap  and water.  Flush  con-
     tamination from the eyes with copious amounts of clean water.
     Obtain, medical attention if irritation of skin or eyes persists.
  2.   If endothall has been ingested, and if the patient is fully alert and
     not convulsing, prompt  administration DEACTIVATED CHAR-
     COAL may serve to limit toxicant concentration in the gastroin-
     testinal tract.  See Chapter 1, TREATMENT, Section 6, p.  8 for

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     dosage. Repeat charcoal administration every 2-4 hours at half or
     more the original dosage.
  3.  If there is no evidence of corrosive effect on pharyngeal tissues
     (or, presumably, on the esophagus), the stomach may be carefully
     intubated and lavaged with a slurry of activated charcoal, after
     all necessary measures have been taken to protect the airway
     from aspiration of vomitus (see Chapter 1, TREATMENT, Section
     6, p. 8).
  4.  If there are indications of corrosive effects in the pharynx, gastric
     intubation should not be attempted because of the risk of esopha-
     geal perforation. Treatment procedures appropriate for ingestions
     of corrosives (strong acids and alkalis) may be necessary. A stand-
     ard text of clinical toxicology should be consulted.
  5.  Oxygen should be given by mask. If respiratory drive is weak,
     pulmonary ventilation may  have to be supported mechanically.
  6.  Monitor blood pressure closely. Infusions of plasma or blood may
     be needed to combat shock. Administer intravenous fluids to cor-
     rect dehydration, stabilize electrolytes, provide sugar, and support
     mechanisms for toxicant disposition. Give vasoactive amines very
     carefully in light of myocardiopathy.
  7.  Seizures may require administration of  diazepam and/or other
     anticonvulsants (see Chapter 3, TREATMENT, Section 4, p. 21).
  8.  It is not known whether hemodialysis or hemoperfusion would be
     effective in removing endothall from the blood. This option should
     be considered if the patient's condition deteriorates despite sup-
     portive care.


      SYNERGISTS: PIPERONYL BUTOXIDE AND N-OCTYL
         BICYCLOHEPTENE DICARBOXIMIDE (MGK 264)

  Synergists are chemical agents included in pesticide products  to
enhance the killing power of the active ingredients. The widely used
insecticide synergists named  above  act by  inhibiting the enzymatic
degradation  of  pyrethrins, rotenone, N-methyl carbamates, and possi-
bly some other insecticides. There  is limited dermal absorption on
contact.  Inherent toxicity in mammals is low. Large absorbed doses
may theoretically enhance the toxic hazard of the rapidly metabolized
insecticides used today, although inhibition of human drug-metaboliz-
ing enzymes by these agents has not actually been demonstrated. Their
presence in  pesticide products to which humans are exposed does not
change the  basic approach to management  of poisoning, except that
some possibility of enhanced toxicity of the .active insecticidal ingredi-
ents should be kept in mind.
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                  SOLVENTS AND ADJUVANTS

  liquid materials in which pesticides are dissolved or the solids on
which they are adsorbed (sometimes called carriers  or vehicles), are
chosen by producers to achieve stability of the active ingredient, con-
venience in handling and  application, and maximum killing power
following application. It  is often the solvents and adjuvants which
pesticide manufacturers choose that give their commercial products a
competitive edge. For this reason, their inclusion in marketed products
is usually proprietary information, not available to  the general public
except under emergency  circumstances.  If a  poisoning  emergency
exists, pesticide companies  will usually cooperate in  supplying physi-
cians with information needed to provide  treatment.  A direct request
to the producer is necessary to secure this information.
  Petroleum distillates are  the most commonly used solvents for lipo-
philic pesticides. Most insecticides are lipophilic.  The distillates are
mixtures of aliphatic  and aromatic hydrocarbons  having low boiling
points.
  Sometimes specific hydrocarbons, such as toluene or xylene (strongly
odiferous), are added  to stabilize the solution of insecticide or make it
more emulsifiable. Hydrocarbon-dissolved pesticides are usually diluted
for  application by adding measured  amounts  of water to form  emul-
sions. Some chlorinated hydrocarbons may be present in particular
technical mixtures. A strong odor lingering after application of a struc-
tural pest control spray is often due to  the solvent rather than the
active ingredient.
  Less lipophilic active ingredients are sometimes dissolved in mix-
tures of alcohols, glycols, ethers, or various chlorinated solvents. It is
possible that these enhance the dermal absorbability of some  pesti-
cides. Also, some solvents, for example, methanol and isopropanol, may
represent a significant toxic hazard if swallowed in significant dosage.
  Granular formulations utilize various  clay  materials which adsorb
pesticide, retain it in  more or  less stable form until application, then
desorb the material slowly  into treated soil. There is some significant
desorption when granules are in contact  with human skin and very
substantial desorption into gastrointestinal  secretions if granules are
swallowed. The clay materials themselves are not a toxic hazard.
  Dusts  are infrequently used today. Various forms of talc (silicate-
carbonate particles) have been  used in the past to adsorb pesticides for
application  to  foliage. Particle  sizes are such  that these dusts are
usually trapped in the upper respiratory mucous when inhaled.  When
the mucous is swallowed, the particles desorb pesticide into gastrointes-
tinal secretions. Dust formulations may, therefore, release enough of
some pesticides to cause systemic poisonings.
  Stickers and spreaders (film extenders) are organic substances added
to formulations to disperse pesticide .over treated foliage surfaces and

                                156

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 enhance adhesion thereto. The availability and persistence of residue
 on  the leaf surfaces  is thereby  increased. Substances used  include
 proteinaceous materials (milk products, wheat flour, blood albumin,
 gelatin), oils, gums, resins, clays, polyoxyethylene glycols, terpenes, and
 other viscid  organics.  Some also include sulfated alcohols, fatty  acid
 esters, alkyl and  petroleum  sulfonates. For persons  exposed in the
 course of formulation or application of pesticides, these adjuvants prob-
 ably add little or no toxic hazard to that inherent in the active pestici-
 dal ingredients.
   Emulsifiers serve to  stabilize water-oil emulsions formed when water
 is added to  technical hydrocarbon  concentrates. Chemically, they are
 detergent-like (one part of the molecule lipophilic, the other hydrophil-
 ic).  Long-chain  alkyl  sulfonate ethers  of  polyethylene  glycol  and
 polyoxyethylene oleate are  exemplary emulsifiers. They have low in-
 herent mammalian  toxicity,  and their presence  probably has little
 effect on the overall  toxicity of formulated products which include
 them.
   Penetrants facilitate the transfer of herbicide from foliage surface to
 the interior tissues. Some are  lipids while others are detergent (surfac-
 tant) in nature. Substances used include heavy petroleum  oils  and
 distillates, polyol fatty acid esters, polyethoxylated fatty acid esters,
 aryl alkyl polyoxyethylene glycols, alkyl amine  acetate,  alkyl aryl
 sulfonates, polyhydric  alcohols,  and alkyl phosphates. Some of these
 are  eye and  skin irritants, and may account for the irritant effects of
 particular herbicide formulations whose active ingredients do not have
 this property.
  Safeners are substances added to mixtures of fertilizers  with pesti-
 cides (commonly herbicides) to limit the formation of undesirable reac-
 tion products. Some substances used are: alcohol sulfates, sodium alkyl
 butane diamate,  polyesters of sodium thiobutane dioate, and benzene
 acetonitrile derivatives. Some are moderately irritating to the skin and
 eyes. Systemic toxicities are generally low.
  Anticaking agents are added to granular and dust  "formulations to
 facilitate application by preventing cakes and clumps. Among several
 products used are the sodium salt of mono- and di-methyl naphthalene
 sulfonate, and diatomaceous earth. Diatomaceous earth has little  ad-
 verse effect except a drying action  on the skin. Methyl naphthalenes
 are said to be skin irritants and photosensitizers; whether their deriva-
 tives have this effect is  not known.

 TREATMENT CONSIDERATIONS

  Petroleum distillates  are mineral hydrocarbons which undergo limit-
 ed absorption across the gut.  In general, clinical toxicologists do  not
 recommend induced emesis or gastric lavage in treating ingestions of
these materials, because of the serious risk of hydrocarbon  pneumoni-
tis  if even tiny  amounts of the liquid  are  aspirated  into the  lung.

                                157

-------
However, this injunction against emptying the stomach must be  set
aside when the petroleum distillate is a vehicle for toxic pesticides in
significant  concentration.  Preferably,  a cuffed endotracheal  tube
should be put in place before the stomach is aspirated and lavaged
with a slurry of activated charcoal (Chapter 1, TREATMENT, Section
6, p.  8). If this protection  is not available,  all possible precautions
should be taken (head down position, frequent aspiration of pharynx)
to minimize the likelihood of aspiration of hydrocarbon into the respi-
ratory tract. Rapid  respiration, cyanosis;  tachycardia, and low-grade
fever are the usual  indications of frank hydrocarbon pneumonitis. If
these occur within 6-8 hours of gastric lavage, hospitalization is usual-
ly indicated. Within a few hours following gastric evacuation, a chest
x-ray should be taken to detect or confirm signs of pneumonitis,  the
urine should be examined for protein, sugar,  acetone, casts, and cells,
and an EGG should be examined for arrhythmias and conduction  de-
fects. Mechanically assisted pulmonary ventilation  with pure  oxygen
may be required. Hydrocarbon pneumonitis is sometimes fatal; survi-
vors usually require  several weeks for full recovery.
  The presence of chlorinated solvents  in  some formulations may add
significantly to the toxic hazard, particularly if the product is ingested.
Certain adjuvants are irritants to skin, eyes,  and mucous membranes,
and may account for irritancy of some products  whose active ingredi-
ents do not have this effect. With these exceptions,  however, the pres-
ence of adjuvants in most finished pesticide products probably does  not
enhance or reduce systemic mammalian toxicity to any great extent.
                                 158

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                        CHAPTER 16

   INDEX TO PESTICIDE  POISONINGS
         BY SYMPTOMS AND SIGNS
  Presented in this chapter are lists  of pesticides reported to have
caused particular symptoms and signs,  or combinations  thereof,  in
poisoned individuals. The lists may on  occasion direct the attention of
health professionals to possible  toxic  causes  of  the various disease
manifestations, prompting inquiry into likelihood of exposure to the
listed chemicals. If certain agents appear suspect, inquiry can then  be
made into the presence of additional manifestations typical of poison-
ing by those substances.
  The limitations of this approach to  diagnosis must be understood.
First, all manifestations of illness have multiple causes, pesticidal and
nonpesticidal. Second, there are no specific symptoms or signs that are
invariably present in poisonings by particular  pesticides. Third, many
poisonings are characterized by unexpected manifestations.
  Finally,  it is evident that neither route  of  exposure nor dosage  of
pesticide is taken into account in this  listing.  For example, effects of
high-dose ingestion are not distinguished from  effects of relatively low-
dose dermal absorption, nor are topical effects distinguished from sys-
temic dermal manifestations. Clearly, the lists of pesticides can only  be
regarded as clues to prompt further inquiry by  the interviewing profes-
sional.
  The term manifestation means either  symptom or sign. The word
"poisoning" is used loosely in these headings to include topical as well
as systemic effects. Pesticides which are relatively consistent in caus-
ing particular manifestations are listed in the middle column, headed
"Characteristic of These Poisonings." Agents that have caused various
conditions  with less consistency, or are less prominent  features  of
poisoning,  are  listed in  the right-hand  column, headed  "Occurs  in
These Poisonings." Obviously, the distinction is not clear-cut.
  Some symptoms (malaise,  fatigue, dizziness) occur so commonly  in
poisoned individuals that they have little  or  no value in  differential
diagnosis, and are therefore not included in  these tables.
     SYSTEM
                   MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
                               159
OCCURS IN THESE
  POISONINGS
General






Breath odor of:
Garlic



Bitter almonds
Rotten cabbage

Arsenic
Phosphorus
Phosphides
Phosphine
Cyanide
Carbon disulfide

Thiram






-------
                                              —Continued
        SYSTEM
                              MANIFESTATION
                              CHARACTERISTIC OF
                              THESE POISONINGS
                               OCCURS IN THESE
                                  POISONINGS
Skin
                          Rotten egg
                          Peanuts

                          Hypothermia
                          Hyperthermia
                            (fever,
                            pyrexia)
                          Chills


                          Hot sensations


                          Myalgia



                          Thirst
                         Anorexia
Alcohol
  intolerance

Sweet taste in
  the mouth

Metallic taste
  in the mouth

Salty, soapy
  taste in the
  mouth

Irritation,
  rash,
  blistering,
  or erosion
  (without
  sensitization)
                            Sulfur
                            Pyriminyl

                            Creosote
                            Norbormide

                            Nitrophenols
                            Pentachlorophenol
 Phosphine
 Arsine

 Nitrophenols
 Chlordimeform

 Paraquat
 Chlorophenoxy
  compounds

 Pentachlorophenol
 Nitrophenols
 Inorganic arsenicals
 Phosphorus
 Phosphides
 Phosphine
 Sodium fluoride
 Cholecalciferol
 Aminopyridine

 Organophosphates
 Carbamate
  insecticides
 Nicotine
 Pentachlorophenol
 Hexachlorobenzene
Chlordimeform
Cholecalciferol

Thiram
Calcium cyanamide

Chlordimeform
                                                   Inorganic arsenicals
                                                   Organic mercury

                                                   Sodium fluoride
                                                   Copper, organotin,
                                                     cadmium compounds
                                                   Metam sodium
                                                   Paraquat
                                                   Diquat
                                                   Sodium chlorate
                                                   Phosphorus
                                                   Sulfur
                                                   Thiram
                           Borate
                           Thallium
                           Metaldehyde
                           Inorganic arsenicals
                           Chlorophenoxy compounds
                           Cadmium dusts
                           Naphthalene
                                                      Pentachlorophenol
                                                                              Borate
                                                                              Endothall
                                                                              Halocarbon fumigants
                                                                              Nitrophenols
                                                                              Inorganic arsenicals
                                                                              Aminopyridine
                                                                              Pyriminil
                          Pentachlorophenol
                          Picloram
                          Chlorophenoxy compounds
                          Captan
                          Rotenone
                          Diethyltoluamide
                          Creosote
                          Fungicides and herbicides
                            with irritant properties
                                                160

-------
SYSTEM
                                      —Continued

                      MANIFESTATION
   CHARACTERISTIC OF
   THESE POISONINGS
    OCCURS IN THESE
       POISONINGS
                  Flushing
                  Dermal sensi-
                    tization
                  Beefy red palms,
 Ethylene oxide
 Formaldehyde
 Acrolein
 Methyl bromide
 Eththylene dibromide
 Ethylene oxide
 Dibromochloropropane
 Dichloropropane
 EndothaU
 Aliphatic acids

 Cyanamide
 Nitrophenols

 Propachlor
 Propargite
 Ethylene oxide
                                            Borate
                                                                       Petroleum distillate
                                                                       Thiram plus alcohol
Anilazine
Chlorothalonil
Barban
Captafol
Formaldehyde
                  Urticaria

                  Bullae

                  Paresthesia
                    (chiefly
                    facial,
                    transitory)

                  Pallor
                  Cyanosis
                  Yellow stain

                  Keratoses, brown
                   discoloration
Liquid fumigants

Fenvalerate
Fluvalinate
Cypermethrin
Flucythrinate

Organochlorines
Fumigants
Sodium fluoride
Creosote

Sodium chlorate
Paraquat
Cadmium dusts
Sodium fluoroacetate
Strychnine
Crimidine
Nicotine
Chlorinated
  hydrocarbons

Nitrophenols

Inorganic arsenicals
                           Fluoride

                           Hexachlorobenzene
                                                                       Coumarins
                                                                       Indandiones
                                                                       Organophosphates
                                                                       Carbamate insecticides
                                                                       Agents that cause shock,
                                                                        myocardiopathy, severe
                                                                        arrhythmias or
                                                                        convulsions.
                  Ecchymoses


                  Jaundice
                 Excessive hair
                   growth
Coumarins
Indandiones

Carbon tetrachloride
Chloroform
Phosphorus
Phosphides
Phosphine
Paraquat
Sodium chlorate
Phosphorus
Phosphides

Inorganic arsenicals
Diquat
Copper compounds
                          He'xachlorobenzene
                                         161

-------
       SYSTEM
                                            —Continued

                            MANIFESTATION
   CHARACTERISTIC OF
   THESE POISONINGS
    OCCUHS IN THESE
       POISONINGS
                         Loss of hair

                         Loss of
                          fingernails

                         Brittle nails,
                          white
                          striations

                         Sweating,
                          diaphoresis
                                                  Thallium
Eye
                        Conjunctivitis
                          (irritation of
                          mucous mem-
                          branes,
                          tearing)
                        Tearing





                        Yellow sclerae



                        Keratitis

                        Ptoeis

                        Diplopia




                        Photophobia

                        Constricted
                          visual fields

                        Optic atrophy

                        Miosis
Organophosphates
Carbamato
  insecticides
Nicotine
Nitrophenols
Pentachlorophenol
Naphthalene
Aminopyridine

Copper compounds
Organotin compounds
Cadmium compounds
Metam sodium
Paraquat
Diquat
Acrolein
Chloropicrin
Sulfur dioxide
Naphthalene
Formaldehyde
Methyl bromide
Ethylene oxide
Endothall
Toluene
Xylene

Organophosphates
Carbamate
  insecticides
Chloropicrin
Acrolein

Nitrophenols
Paraquat

Thallium

Organophosphates
Carbamate
  insecticides
Nicotine
Organic mercury
                                                  Organophosphates
                                                  Carbamate
                                                    insecticides
                           Inorganic arsenicals

                           Paraquat
                           Inorganic arsenicals

                           Inorganic arsenicals
                           Thallium
Copper compounds
Thiophthalimides
Thiram
Thiocarbamates
Pentachlorophenol
Chlorophenoxy compounds
Chlorothalonil
Picloram
Creosote
Aliphatic acids
Pentachlorophenol
Pyrethrins
                          Agents that cause
                            jaundice (see above
                            under Skin)
Organotin compounds




Thallium

Nicotine (early)
                                               162

-------
                                            —Continued
      SYSTEM
                            MANIFESTATION
  CHARACTERISTIC OF
  THESE POISONINGS
   OCCURS IN THESE
      POISONINGS
Nervous
  system
                         Dilated pupils
                         Unreactive
                          pupils

                         Headache
                         Behavioral-mood
                          disturbances
                          (confusion,
                          excitement,
                          mania,
                          disorien-
                          tation,
                          emotional
                          lability)
                         Nervous system
                          depression,
                          stupor, coma,
                          respiratory
                          failure, often
                          without
                          convulsions.
                         Convulsions
                          (clonic-tonic),
                          sometimes
                          leading to coma.
Cyanide
Fluoride

Cyanide
Organophosphates
Carbamate
  insecticides
Nicotine
Inorganic arsenicals
Organic mercury
Cadmium compounds
Organotin compounds
Copper compounds
Thallium
Fluoride
Borates
Naphthalene
Phosphine
Halocarbon fumigants
Creosote
Diquat
Cholecalciferol
Cyanamide

Organic mercury
Inorganic arsenicals
Organotin compounds
Thallium
Nicotine
Sodium fluoroacetate
Diquat
Cyanide
Nitrophenols
Pyriminil
Aminopyridine
Carbon disulfide
Methyl bromide

Organophosphates
Carbamate
  insecticides
Sodium fluoride
Borate
Diquat
Organochlorines
Strychnine
Crimidine
Sodium fluoroacetate
Nicotine
Cyanide
Acrylonitrile
Metaldehyde
                                                                             Nicotine (late)
Organochlorines
Nitrophenols
Thiram
Pentachlorophenol
Paraquat
Diethyltoluamide
Organophosphates
Carbamate insecticides
Pentachlorophenol
Sodium fluoride
Diethyltoluamide
Organochlorines
Inorganic arsenicals
Metaldehyde
Sulfuryl fluoride
Halocarbon fumigants
Phosphorus
Phosphides
Phosphine
Paraquat
Chlorophenoxy compounds
Diethyltoluamide
Alkyl phthalates

Nitrophenols
Pentachlorophenol
Inorganic arsenicals
Organotin compounds
Diquat
Borate
Sulfuryl fluoride
Methyl bromide
Chlorophenoxy compounds
Organophosphates
Carbamate insecticides
Aminopyridine
                                                163

-------
                                             —Continued
       SYSTEM
                              MANIFESTATION
                              CHAEACTERISTIC OF
                              THESE POISONINGS
                               OCCURS IN THESE
                                  POISONINGS
                          Muscle twitching
                         Myotonia

                         Tetany,
                           carpopedal
                         Tremor
Cardio-
  vas-
  cular
  system
                         Incoordination
                           (including
                           ataxia)
                         Paralysis,
                           paresis,
                           muscle
                           weakness
                         Paresthesia of
                           extremities
Hearing loss

Hypotension,
  shock
                         Hypertension
                        Cardiac
                          arrhythmias
                                                    Organophosphates
                                                    Carbamate
                                                      insecticides
                                                    Nicotine
                                                    Sulfuryl fluoride
 Fluoride
 Phosphides
 Phosphorus

 Organic mercury
 Thallium
 Organophosphates
 Carhamate
   insecticides
 Nicotine
 Metaldehyde
 Berates

 Halocarbon fumigants
 Organophosphates
 Carbamate
   insecticides
 Carbon disulfide
 Nicotine
 Thallium

 Inorganic arsenicals
 Organophosphates
 Carbamate
   insecticides
 Nicotine

 Inorganic arsenicals
 Organic mercury
 Sodium fluoroacetate
 Carbon disulfide
 Pyriminil
 Thallium

 Organic mercury

 Phosphorus
 Phosphides
 Phosphine
 Sodium fluoride
 Sodium chlorate
 Borate
 Thallium
 Copper compounds
 Endothall
 Cyanamide

 Thallium (early)
 Nicotine (early)

 Sodium fluoroacetate
 Halocarbon fumigants.
 Nicotine
 Sodium fluoride
 Ethylene oxide
JSodium chlorate    »
 Pyriminil   .
                                                      Organic mercury
                                                      Chlorophenoxy compounds
                                                      Chlorophenoxy compounds
                                                                              Pentachlorophenol
                                                                              Nitrophenols
                                                                              Thiram
                                                      Organic mercury
                                                      Organochlorines
                                                     Organic mercury
                                                     Diethyltoluamide
                                                     Pyrethroids (transitory)
Inorganic arsenicals
Nicotine (late)
Creosote
Alkyl phthalate
Cycloheximide
Formaldehyde
Norbormide
                                                                              Organophosphates
                                                     Inorganic arsenicals
                                                     Phosphorus
                                                     Phosphides
                                                     Phosphine
                                                     Organochlorines
                                                     Cyanide
                                                     Acrylonitrile
                                                164

-------
       SYSTEM
                                            —Continued

                             MANIFESTATION
                             CHARACTERISTIC OF
                             THESE POISONINGS
                              OCCURS IN THESE
                                 POISONINGS
Respira-
  tory
  system
                         Bradycardia
                          (sometimes to
                          asystole)
                         Tachycardia
Upper
  respiratory
  tract
  irritation:
  rhinitis,
  scratchy
  throat, cough
Cyanide
Organophosphates
Carbamate
  insecticides

Nitrophenols
Pentachlorophenol
Cyanamide

Naphthalene
Paraquat
Chloropicrin
Acrolein
Dichloropropene
Ethylene dibromide
Sulfur dioxide
Sulfuryl fluoride
Acrylonitrile
Formaldehyde
Cadmium dusts
ANTU
                                                                              Nicotine
                                                     Metaldehyde
                                                     Organophosphates
Dry formulations of
  copper, tin, zinc
  compounds.
Dusts of thiocarbamate
  and other organic
  pesticides.
Chlorophenoxy compounds
Aliphatic acids
Rotenone
                         Runny nose
                           Sabadilla

                           Pyrethrins
                           Inorganic arsenicals
                           Organophosphates
                           Carbamate
                            insecticides
                                                                              (Irritants listed above)
                         Pulmonary edema
                         Pulmonary
                           consolidation
                         Dyspnea
Gastro-
  intes-
  tinal
  tract
  and
  liver
Nausea, vomiting
  commonly
  followed by
  diarrhea
Methyl bromide
Phosphine
Phosphorus
Phosphides
Ethylene oxide
Ethylene dibromide
Acrolein

Paraquat
Cadmium dusts
Methyl bromide

Organophosphates
Carbamate
  insecticides
Nicotine
Paraquat
ANTU
Cadmium dusts
Cyanamide
Sulfuryl fluoride
Pentachlorophenol
Methyl bromide
Sulfur dioxide
Chloropicrin

Organophosphates
Carbamate
  insecticides
Nicotine
Arsenicals
Fluoride
Cadmium compounds
                                                     Organophosphates
                                                     Carbamate Insecticides
                                                     Paraquat
                                                     Phosphides
                                                                              Diquat
                                                     Nitrophenols
                                                     Cyanide
                                                     Creosote
                                                     Pyrethrins
Pentachlorophenol
B. thuringiensis
Cholecalciferol
Thiram
Many pesticides having
  some irritant property.
                                                165

-------
       SYSTEM
                                            —Continued

                             MANIFESTATION
                             CHARACTERISTIC OF
                             THESE POISONINGS
                              OCCURS IN THESE
                                 POISONINGS
                        Bloody diarrhea
                        Abdominal pain
                        Stomatitis
                        Salivation
Liver
Ileus


Constipation

Enlargement
Organotin compounds
Copper compounds
Sodium chlorate
Borate
Cyanide
Chlorophenoxy
  compounds
Phosphorus
Phosphides
Phosphine
Carbon disulfide
Chloropicrin
Halocarbon fumigants
Endothall

Fluoride
Paraquat
Diquat
Thallium
Coumarins
Indandiones
Endothall
Arsenicals

Organophosphates
Carbamate insecticides
Paraquat
Diquat
Nicotine
Metaldehyde
Fluoride
Borate
Phosphorous
Phosphides
Inorganic arsenicals
Cadmium compounds
Copper compounds
Thallium
Organotin compounds

Inorganic aresenicals
Paraquat
Diquat
Copper compounds

Organophosphates
Carbamate
  insecticides
Nicotine
Aminopyridine
Sodium fluoride
Cyanide
Cadmium compounds

Thallium
Diquat

Pyriminil

Copper compounds
Sodium chlorate
Phosphine
Carbon tetrachloride
Cholorform
                                                                             Phosphorus
                                                                             Phosphides
                                                                             Cycloheximide
                                                                             Chlorophenoxy compounds
                                                                             Aliphatic acids
                                                                             Sodium chlorate
                                                                             Creosote
                                                                             Endothall
                                                                             Aminopyridine
                                                                             Coumarins
                                                                             Indandiones
                                                                             Fumigants (ingested)
                                                                             Cycloheximide
                                                                            Thallium
                                                                            Inorganic arsenicals
                                                                            Hexachlorobenzene
                                                                            Other organochlorines
                                               166

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      SYSTEM
                                           —Continued

                            MANIFESTATION
                            CHARACTERISTIC OF
                            THESE POISONINGS
                             OCCURS IN THESE
                                POISONINGS
Kidney
Blood
Jaundice—see
  section on
  "Skin"

Proteinuria,
  hematuria,
  sometimes
  leading to
  oliguria,
  acute renal
  failure with
                        Dysuria,
                          hematuria,
                          pyuria

                        Urinary
                          retention

                        Polyuria

                        Hemoglobinuria
                        Wine-red urine
                          (porphyrinuria)
                        Smoky urine

                        Glycosuria

                        Ketonuria

                        Hemolysis
                        Methemoglo-
                          binemia

                        Hypopro-
                          thrombinemia
                         Hyperkalemia
Inorganic arsenicals
Copper compounds
Sodium fluoride
Naphthalene
Borate
Nitrophenols
Pentachlorophenol
Sodium chlorate
Sulfuryl fluoride
Paraquat
Diquat
Arsine
Ethylene dibromide

Chlordimeform
                          Pyriminil
                          Cholecalciferol

                          Naphthalene
                          Sodium chlorate
                          Arsine

                          Hexachlorobenzene

                          Creosote

                          Pyriminil

                          Pyriminil

                          Naphthalene
                          Sodium chlorate
                          Arsine

                          Sodium chlorate
                          Creosote

                          Coumarins
                          Indandiones
                          Sodium chlorate
                          Naphthalene
                          Arsine
Cadmium compounds
Phosphorus
Phosphides
Phosphine
Chlorophenoxy compounds
Creosote
Organotin compounds
                                                    Fluoride
                          Organotin compounds

                          Borate

                          Copper compounds
                          Phosphorus
                          Phosphides
                          Carbon tetrachloridc

                          Sodium fluoride
                                               167

-------
SYSTEM
              —Continued


MANIFESTATION
CHARACTERISTIC OF
THESE POISONINGS
                                                                OCCURS IN THESE
                                                                   POISONINGS
                Hypocalcemia
                Hypercalcemia
                                       Fluoride
                                      Cholecalciferol
                                                             Thallium

                                                             Phosphorus

                                                             Phosphides








Repro-
ductive
system
Carboxyhemo-
globinemia
Hyperglycemia
Ketoacidosis
Anemia
Leukopenia,
thrombocyt-
openia
Elevated LDH,
GOT, OPT,
alkaline
phosphatase,
ALT, AST
enzymes
Depressed RBC
acetylcholin-
plasma pseudo-
cholinesterase
Low sperm count

Pyriminil
Pyriminil
Naphthalene
Sodium chlorate
Arsine
Inorganic arsenicals
Inorganic arsenicals
Carbon tetrachloride
Chloroform
Phosphine
Organophosphates

Dibromochloropropane
Methylene chloride
Organotin compounds



Inorganic arsenicals
Phosphorus
Phosphides
Phosphine
Sodium chlorate
Nitrophenols
Pentachlorophenol
Thallium
Organochlorines
Chlorophenoxy compounds
Carbamate insecticides

Kepone
                                  168

-------
Index of Chemical and Product Names

                                               Page
1080	  116
2,3,6-TBA	   84
2,4,5 trichlorophenoxyacetic acid	   63
2,4,5-T	   63
2,4-D	   63
2,4-DB	   63
2,4-dichlorophenoxyacetic acid	   63
2,4-dichlorophenoxybutyric acid	   63
2,4-dichIorophenoxypropionic acid	   63
2,4-DP	.„   63
2-methyl-3,6 dichlorobenzoic acid	  64, 84
2-methyl-4-chlorophenoxy aliphatic acids and
  esters	   64
4-Aminopyridine	  148
4-Ap	  148
A7 Vapam	   98
AASTAR	  1,34
AAtack	......*...   96
Aaterra...	  113
AAtrex	   86
Abate	    2
Abathion	    2
Abol	„   12
Acaraben 51	   46
Acaricides	   34
Accelerate	,	  154
Accotab	   85
Accothion	    2
acephate	,	    2
Acetamides	   84
Acme Amine 4	   63
Acme Butyl Ester 4	   63
Acme LV 4	....:	   63
Acme LV 6	.^..	   63
Acrex.,	   68
Acricid	   68
Acritet	  132
acrolein	  132, 135
acrylaldehyde	  132, 135
Acrylofume	132
acrylonitrile	  132
Actellic	:	    2
Acti-dione	:...;	  112
Actispray	,	  112
                        169

-------
Activol	  33
Actor	  76
Adjuvants	 156
Afalon	  87
Afesin	  87
Aficida	  12
Afugan	   2
Agritox	   1
Agrosan	 105
Agrotect	  63
Agrothion	   2
Agroxone	  64
Akar	  46
Akzo Chemie Mancozeb	 101
Akzo Chemie Maneb	 101
alachlor	  84
Alanox	  84
alcohol sulfates	:.	 157
aldicarb	  12
aldrin	  17
Aldrite	  17
Aliphatic  acids	  84
alkyl amine acetate	 157
alkyl aryl sulfonates	 157
alkyl phosphates	 157
alkyl phthalates	  52
alkyl sulfonates	 157
Allethrin	  34
allidochlor	  84
Allisan	  94
Alon	  87
AIP	 132
alpha-naphthyl thiourea	  116, 126
alphametrin	  34
Altosid CP-10	  48
Altosid SR-10	  48
aluminum phosphide	 132
Amaze..	    1
Ambox	  68
Ambush	  34
Amerol	  86
Ametrex	:	  85
ametryn	  85
Amex	  85
Amiben	   84
Amine 2,4,5-T for rice	  63
aminocarb	   12
                        170

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                                               Page
4-Aminopyridine	 148
amino-triazole	  86
Amiral	 113
AmitroI-T	  86
amitrole	  86
Ammo	  34
Amoxone	  63
Anilazine	:	 111
Anilides	  84
anisic acid derivatives	  84
Ansar 170	  56
Ansar8100	  56
Anthio	   2
Anticaking agents	 157
Anticarie	  90
Antimilace	 146
ANTU	   116, 126
4-Ap	 148
Apachlor	   1
Apex 5E	  48
Aphox	  12
Apl-Luster	 113
Appex	...   2
aprocarb	  12
Apron 25 WP	 113
Aquacide	  76
Aqua-Kleen	  63
Aqualin	 132
Aquathol	   85, 154
Aquatin	 108
Aquazine	  86
Aquinite	 132
Arbotect,	 113
Arelon	  87
Aresin	  87
Aretit.....	  68
Arresin	  87
Arrhenal	  56
Arsenal	  85
Arsenic acid	  55
Arsenic Compounds	  54
Arsenic Trioxide	  54
Arsenical Pesticides	  54
arsenous oxide	  54
Arsine	;	  54
Arsinyl	  56
Arsonate Liquid	  56
                        171

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                                              Page
aryl alkyl polyoxyethylene glycols	 157
Asana	  34
Aspon	   2
Aspor	 101
asulam	  84
Asulox	  84
Asuntol	   1
AT-90	  86
Atranex	  86
Atratol	 150
atraton	  85
Atratone	  85
Atrazine	  86
Aules	  96
Avadex	  84
AvadexBW	  84
Avicol	  93
Avitrol	 148
Azac	  84
Azar	  84
azinphos-methyl	   1
Azodrin	   1
Azolan	  86
Azole	  86

bacillus thuringiensis	  32
Bactimos	  32
Bactospeine	  32
Bactur	  32
Balan	  85
Balfin	  85
Banamite	 161
Ban-Hoe	  86
Banvel	   64, 84
barban	  84
Barricade	  34
Barrier.	  84
barthrin	  34
Basagran	  84
Basalin	  85
Basanite	  68
Basfapon	  84
BASF-Maneb Spritzpulver	 101
Bash	   1
Batasan	 108
Baygon	  12
Bayleton	 113
                       172

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                                                 Page
Bayrusil	    1
Baytex	    2
Baythion	    2
Baythion-C	    2
Baythroid	   34
Beet-Kleen	   84
Belgran..	   87
Belmark	   34
bendiocarb	   12
Benefin	   85
Benex	  112
benfluralin	   85
Benlate	  112
Benomyl	  112
bensulide	    2
bentazon	   84
Benzac	   84
Benzamide	   84
benzene acetonitrile derivatives	  157
Benzilan	   46
Benzofuroline	   34
Benzoic, anisic acid derivatives	   84
Benzonitriles	   84
benzothiadiazinone dioxide	   84
Benzyl Benzoate	   53
Berelex	   33
Bermat	   42
Betasan	    2
Bexton	          84
BH 2,4-D	",["''",   63
BH2.4-DP	   63
BHC	   17
Bicep	   84
Bidrin	    1
binapacryl	   68
Biological Insecticides	   25
biopermethrin	   34
bioresmethrin....	   34
Birlane	    1
Black Leaf 40	   27
Bladafum	    •)
Bladex	   86
Bo-Ana	    1
Bolate	""   56
Bolero	,	   84
Bolls-Eye	  ,55
Bolstar	    1
                        173

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                                            Page
bomyl	   1
Bophy	  56
borates	  39
borax	  39
Bordeaux Mixture	 103
Borea	  86
Boric acid	  39
boron trioxide	  39
Botran	  94
Botrilex	  93
Bravo	  95
Brestan	 108
Brimstone	  48
Brodan	    1
brodifacoum	 116
bromacil	  86
bromadiolone	 116
Bromax	  86
Bromofume	 132
Brom-O-Gas	 132
Brom-O-Gaz	 132
bromomethane	 132
Bromone	 116
bromophos	    2
bromophos-ethyl	    1
Brom-O-Sol	 132
Broot	  12
Bud-Nip	  84
Bueno 6	  56
bufencarb..;	  1.2
Bug-Geta	  146
Busan 1020	  98
Butoxon	  63
Butoxone	  63
butralin	  85
butylate	  84
Butyrac	  63
Bux	  12
BW-21-Z	  34

Cacodylic acid	  56
Caddy	  109
Cadminate	  109
Cadmium chloride	  109
Cadmium Compounds	  109
Cadmium sebacate	  109
Cadmium succinate	  109
                       174

-------
  Cadmium sulfate ..... ........... . .............................         •( QQ
  Cad-Trete...: .................................. ZZZZZ""96,  109
                                                    ! 16
                            . ...................... . ................  56
  Calcium acid  methane arsonate .................................  55
  Calcium arsenate ............................................. .".".".".....  55
  Calcium Arsenite ............................................ .".......".".   54
  Calcium Cyanamide ...................................... .""........". 149
  Caldon ................................................         .............  gg
  Caliber 90 ................    ............................... ' ...............  86
  CAMA ......................................... ZZi:::::ZZi::  56
  Canadien 2000 [[[ 1 16
  Can-Trol [[[ ............. ......  64
  Caparol [[[ "".....".... .........  86
  Captaf .................................................. !!"!!"™"""ZZ 102
  Captafol [[[ ...... 102
  Captan [[[ !....""."."........... 102
  Captanex [[[ '"""" 1Q2
  Carbacryl .................................................. ["."'".'.'.'.'. .......... 132
 Carbamate (ferbam) ............................. ."."".'."."I""."!!!""  99
 Carbamate Herbicides .............................. "."."."".".......  84
 Carbamate Insecticides ................................................  -\ 2
 Carbamult [[[  ................  12
 Carbanilates ....................... ................... ..."!!...".".......     84
 carbaryl.. ............................................... ......."...."...       12
 Carbazinc ............................................. ....."."........"... ......   99
 carbofuran ............ . .............................. !."....."...."... .........   12
 carbon disulfide .......................................... ".".".'"."."."!.".' 1 32
 carbon tetrachloride .................... . .......................... """ -132
 carbophenothion .............................. . ......... "' .......... .....   -j
 Carbyne ...................................... ""!!!"•!."".'.'.".'.".'."".".'.'.'.".'"  84
 Carpene [[[  " 1 12
 Carzol [[[  ..................  _I2
 Casoron ............................................... I!."."."!.".".".".'.' ........  84
 Castrix ...............                              ....... 116
 CCN52 ....................... [[[  34
 CDAA .................................... izzz:::::::::::::::::::::  84
 Cekiuron [[[              gg
 CekuC.B ............................ .•...".'.'."!.'."."!!.'.'."".'.'.'.'.'.".'.'.'.'."! .......  90

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                                              Page
Celmer	  105
Celmide	  132
Ceresan	  105
Certan	   32
Chem Bam	  101
Chem Fish	-	   30
Chem Pels C	-   54
Chem Rice	   84
ChemZineb	  101
Chemox General	   68
ChemoxPE	   68
ChemsectDNBP	   68
Chemsect DNOC	   68
Chem-Sen 56	   54
Chipco Thiram 75	   96
Chipco Turf Herbicide "D"	   63
chloramben	   84
Chlordan	   -17
chlordane	   17
chlordecone	••   17
chlordimeform	   42
chlorfenvinphos	     1
chlorimuron ethyl	   86
chlorinated hydrocarbons	   17
chlorinated solvents	  158
chlormephos	•	    1
chlorobenzilate	  46
chloroform	.	 132
Chloro-IPC	  84
chloroneb	  95
chlorophacinone	 116
Chlorophen	•  73
chlorophenothane	  17
Chlorophenoxy Herbicides	  63
Chlor-O-Pic	,	 132
chloropicrin	 132
chloropyridinyl	  85
Chlorothalonil	  95
chlorotoluron	- 86
Chloroxone	  63
chloroxuron	  86
chlorphoxim	    2
chlorpropham	  84
chlorpyrifos	•	    1
chlorthal-dimethyl	  85
chlorthiophos	    1
cholecalciferol	  116, 127
                        176

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                                               Page
 Chrysron	  34
 cinerins	  25
 Ciodrin....	   2
 cismethrin	  34
 Classic	  86
 Clifton Sulfur.	"."."."".'.  48
 cloethocarb	  12
 ClortoCaffaro	  95
 Clortosip	  95
 Cobex	  85
 Codal	  84
 Comite	..  44
 Command	  85
 Compound 1080	  116, 123
 Contrac	 1 is
 Contraven	   •)
 Copper acetate	 103
 Copper acetoarsenite	  54
 copper ammonium carbonate	 103
 Copper Arsenite	  54
 Copper carbonate	 103
 Copper Compounds	 102
 copper hydroxide	 102
 Copper lime dust	 103
 Copper linoleate	 103
 Copper naphthenate	 103
 Copper oleate	 1Q3
 copper oxychloride	 103
 Copper phenyl salicylate	 103
 copper potassium sulfide	 103
 copper quinolinolate	 103
 copper resinate	 1Q3
 copper silicate	 103
 copper sulfate	  103
 copper sulfate, tribasic	  103
 Co-Ral	    1
 Co-Rax	  11 e
 Corozate	  99
 Corry's Slug and Snail Death	  146
 Cosan	  48
 Cotoran	  87
 Cottonex	  87
 coumachlor	  -\-\Q
 coumafene	  -\-\Q
 coumafuryl	,	  -\-\Q
 coumaphos.....	    -\
Coumarins	  -\-\Q
                       177

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                                              Page
coumatetralyl	 116
Counter	    1
Cov-R-Tox	 116
Crab-E-Rad	   56
Crag Turf Fungicide 531	 109
Creosote	 152
crimidine	  116, 124
Crisalamina	   63
Crisamina	   63
Crisazina	   86
Crisfolatan	  102
Crisfuran	   12
Crisquat	   76
Crisuron	   86
Crop Rider	   63
Crossbow	   85
Crotothane	   68
crotoxyphos	    2
crufomate	    2
cryolite	   37
Cuman	   99
cupric  oxide	  102
Cuprous oxide	  102
Curacron	    2
Curamil	    2
Curaterr	   12
Curitan	  112
Cyanamide	  149
cyanazine	   86
Cyanide	  136
cyanofenphos	    1
cyanophos	   2
Cyanox	   2
cyclethrin	  34
cycloate	  84
Cyclohexenone derivative	  85
Cycloheximide	 112
Cyclon	 132
Cyflee	    2
cyfluthrin	  34
Cygon	    2
cyhexatin	  47
Cyian	    1
Cymbush	  34
Cymperator	  34
Cyolane	    1
Cyperkill	  34
                        178

-------
 cypermethrin	   34
 Cypona	    2
 Cyprex	  -J •) 2
 Cyrux	   34
 cythioate	    2
 Cythion	    2
 Cytrol	,	...!Z""™""i   86
 Cytrolane	    -)

 2,4-D	  63
 2,4-DB	  63
 D50	  63
 Dacamine	  63
 Daconate 6	.	  55
 Daconil 2787	  95
 Dacthal	  35
 Dailon	  36
 dal-apon	  34
 Dal-E-Rad	;.	""."!!"""".'."  56
 Dalapon	  34
 Danitol	]]"  34
 Dapacryl	...""!!!!!!..".   68
 Dart	  45
 Dasanit	              -)
 DBCP	         	 132
 DCNA		  94
 DCPA	IZZZI  85
 D-D	 132
 D-D92	 132
 ODD	                             17
 DDT	:::::::::::::::::::::::::::::  ^ 7
 DDVP	   1
 Debroussaillant 600	'."'."".'.".  63
 Decabane	"_"""  34
 decamethrin	.".."."  34
 Dechlorane	".""".".  17
 Decis	      34
 Ded-Weed	;...Z"Z""ZZZ"   63, 84
 Ded-Weed SULV	                        63
 DEET	ilZZI   49
 DEF	    2
 DeFend	....[      "'"    2
 De-Fol-Ate	""!!""!Z!""!!Z"!!Z! 150
 Dettor	!."!""!!.'""!!!!   37
DeGreen	    2
Deiquat	"    75
Delnav	"...".'".'"!!""!!!!    1
                       179

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                                               Page
deltamethrin	   34
demeton	    "I
demeton-S-methyl	    1
Denarin	  113
Dervan	,	  15°
Des-i-cate	  154
desmetryn	   86
Desormone	—   63
Dessicant L-10	   55
Dessin	•	   68
Detamide	   50
Dethdiet	   116, 126
Devizeb	  101
Dextrone	•	   ^6
Dexuron	   76
di-methyl naphthalene sulfonate	 157
Di-on	  87
Di-Tac	  56
Diacon	••	  48
dialifor	-	    1
diallate	  84
Dianex	•	  48
Diaract	•	   45
Diater..	•	   87
diatomaceous earth	  157
diazinon	•	    2
Dibrom	    2
dibromochloropropane	  132
dibromoethane	•  132
dibutylphthalate	   52
 Dicamba	  64, 84
 Dicarbam	   12
 dichlobenil	   84
 dichlofenthion	    2
 Dichloran	•	   94
 dichloroethane	  132
 2,4-dichlorophenoxyacetic acid	   63
 2,4-dichlorophenoxybutyric acid	   63
 2,4-dichlorophenoxypropionic acid	   63
 dichloropropane	  132
 dichloropropene	  132
 dichloropropene plus dichloropropane	  132
 dichloropropionic acid	  84
 dichlorvos	   1
 dicofol	•	  17
 dicrotophos	   1
 Dicuran	.••  86
                          180

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                                                  Page
 dieldrin	.   17
 Dieldrite	   17
 dienochlor	.	   17
 diethyltoluamide	   49
 difenacoum	  116
 difenoxuron	.	   86
 Diflubenzuron	   45
 Difolatan	                102
 Dine	;;;   56
 Dimecron	    1
 dimefox	    -)
 dimephenthoate	    2
 dimetan	   12
 Dimethan	   12
 dimethoate	    2
 dimethrin	   34
 Dimethyl Phthalate	!.""""""   52
 Dimilin	;	.   45
 dinitramine	   35
 Dinitro.,	.	   @8
 Dinitro General	   68
 Dinitro-3	   68
 Dinitro-amino-benzene derivatives	   85
 Dinitro Weed Killer 5	   68
 dinitrocresol	.	   68
 Dinitrophenol	   68
 dinobuton	   68
 dinocap	   68
 Dinofen	   68
 dinopenton	.   68
 dinoprop	   68
 dinosam	   68
 dinoseb	      68
 dinoseb acetate	   68
 dinoseb methacrylate	   68
 dinosulfon	   68
dinoterb	   68
dinoterb acetate	   68
dinoterb salts	   68
dinoterbon	   68
Dinoxol	   63
Di-on	   86
dioxacarb	   12
dioxathion	   f
Dipel	""m""'m  32
diphacin	
diphacinone
                         181

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                                                 Page
    Cipher	 101
    Dipterex	   2
    Dipyridyls	  76
    Diquat	  76
    Direx	  87
    Dirimal...	  85
    Disodium arsenate	  55
    Disodium methane arsonate	  56
    disulfoton	   1
    Disyston	   1
    Di-Tac	  56
    DithaneM-22	 101
    DithaneM-45	 101
    Dithane 2-78	 101
    Dithione	   1
    ditranil	  94
    Diurex	  87
    Diurol	  87
    diuron	  87
    DLP-87	  116, 126
    DMA	  56
    DMA 4	  63
    DMP	  52
    DNAP	  68
    DNBP	  68
    DNC	  68
    DNOC	  68
    Dodine	 112
    Dojyopicrin	 132
    Dolochlor	 132
    Dormone	  63
    Dosaflo	  87
    Dosanex	  87
    Dotan	   1
    Dowpon	 84
    2,4-DP	 63
    DPA	»	 84
    DPX 1410	  12
    Drat	 116
    Drawinol	  68
    Draza	  12
    Drexar530	  56
    Drexel Defol	 150
     Drinox	  17
     Drop-Leaf	 150
v    Drupina 90	,	  99
     DSE	 101
                            182

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 Du-Ter	 108
 Dual	  34
 Duraphos	,	   -\
 Duratox	   1
 Dursban	   -\
 Outer	""'." 108
 Dwell	 113
 Dycarb	  12
 Dyclomec	  84
 Dyfonate	   1
 Dylox	   2
 Dynamyte	  68
 Dyrene	 111

 E-48	            1
 E-601	       	   1
 E-S05	.'."!".'.'."!!!".'."!!"   1
 Earthcide	  93
 Easy off-D	   2
 EBDC compounds	 100
 Ectiban	                   34
 EDB	Z!!!Z!!""!Z""™.'.""" 132
 E-D-Bee	                       132
 EDO	.""I"!!!"";!.'""™";™;"";; ^ 32
 edifenphos	   1
 Ekamet	   2
 Ekatin	   2
 Eksmin	  34
 Elgetol 30	'    68
 Elgetol 318	'      68
 Elocron	  12
 Embutox	  63
 emerald green	  54
 Emisan 6	 105
 Emulsamine BK	 63
 Emulsamine E-3	 63
 Emulsifiers	 157
 Endosan	 68
endosulfan	  17
endothall	 35, 154
Endothall Turf Herbicide	        154
Endothall Weed Killer	!"....""...."  154
endothion	   1
Endrin	     17
Entex	   2
Envert 171	.    63
                       183

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                                              Page
Envert DT [[[  63
EPBP [[[   2
EPN ....................... . [[[   1
epoxyethane ....................... . .......................................... ^32
Eptam [[[  84
EPTC [[[  84
Eradicane [[[  84
Eraze [[[ 116
Erban [[[  84
esfenvalerate [[[  34
Esgram [[[  76
Estone [[[  63
ethalfluralin ................... . ................................................  85
Ethanox ........................ .'. ................................................    1
Bhazol .......................... : ................................................  1 13
ethion [[[    1
ethoprop [[[    1
ethyl  parathion [[[    1
ethylan [[[   17
Ethylene Bis Dithiocarbamates ...................................  100
ethylene dibromide [[[  1 32
ethylene dichloride [[[  132
ethylene oxide [[[  "I32
                                               H OO
ETO [[[  132
etrimfos [[[    2
Etrofolan [[[   1 2
Evik [[[  85

-------
                                               Page'
Fentin acetate	 108
Fentin chloride	 108
Fentin hydroxide	 108
fenvalerate	  34
Ferbam	  99
Fermide 850	  96
Fernasan	  96
Fernesta	  63
Fernimine	  63
Fernos	  12
Fernoxone	  63
Ferxone	  63
Ream	  12
film extenders	 156
Final	 116
Flectron	  34
Florocid	  37
fluchloralin	,	  85
flucythrinate	  34
fluometuron	,	  87
fluorides	  37
Fluorodinitrotoluidine compounds	  85
fluvalinate	  34
FMC9044	  68
Folbex	  46
Folcord	  34
Folex	   2
Foliafume	  30
Folosan	  93
Folpan	 102
Folpet	 102
Foltaf	 102
fonofos	   1
formaldehyde	 132
formalin	 132
formetanate	  12
formothion	   2
Formula 40	  63
Forron	  63
Fortrol	  86
fosamine ammonium	  85
fosthietan	   1
Fratol	   116, 123
French green	  54
Fumarin	 116
Fumigants	 131
Fumitoxin	 132
                       185

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                                            Page
Fundal	  42
Fungicides	•	  89
Funginex	 "I "13
Fungitrolll	 102
Fungostop	  "
Furadan	  12
furethrin	  34
Furloe	  84
furmarin	 116
Futura	  32

G 28029	   2
GAs	  33
Galecron	  42
Gallotox	 105
gamma BHC	   17
gamma HCH	   17
Gardona	   2
Gardoprim	   86
Garlon	   85
Gebutox	   68
Gesafram 50	   86
Gesagard	   86
Gesamil	   86
Gesapax	   85
Gesatamin	   85
Gesatop	r	   86
gibberellic acid	   33
Gibberellin	   33
Gibrel	   33
Glifonox	   85
Glycophene	  112
glyphosate	   85
Go-Go-San	  85
Golden Dew	  48
Goidquat276	  76
Gordon's Amine 400	  63
Gordon's Butyl Ester 600	v.  63
 Gordon's Dymec Turf Herbicide Amine 2,4-D	  63
 Gordon's LV 400 2,4-D	,	  63
 Gordon's Mecomec	  64
 Gordon's Phenaban 801	  63
 Graminon	  87
 Gramocil	  76
 Gramonol	  76
 Gramoxone	  76
 Gramuron	  76
                        186

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                                              Page
Qranurex	  87
Graslan	  87
Grazon	  85
Griffex	  86
Grocel	  33
Gusathion	   1
Guthion	   1
Gypsine	  55

Haipen	 102
Haitin	 108
Halizan	 146
Halocarbon Fumigants	 132
Hanane	   1
Harvest-Aid	 150
Havoc	     116
HCB	  90
Hedonal	  63
Hedonal DP	  63
Hel-Fire	  68
Helothion	   1
heptachlor	  17
Heptagran	  17
heptenophos	   2
Herald	    34
Herb-All	  56
Herbalt	  87
Herbaxon	  76
Herbicide 273	 154
Herbidal	  63
Herbizole	  86
Herbodox	  85
Herboxone	  76
hexachlorobenzene	  90
Hexachlorocyclohexane	  17
Hexadrin	  17
Hexaferb	  99
Hexathane	 101
Hexathir	  96
Hexazir	  99
Hi-Yield Dessicant H-10	  55
Hoe 002784	  68
Hong Nien	 105
Hostaquick	  2
Hostathion	  1
hydrocyanic acid	 132
Hydrogen Cyanamide	 149
                       187

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                                              Page
hydrogen cyanide	 132
Hydrothol	 154
Hyvar	  86

IBP	    2
Igran	  86
Imidan	    2
Indandiones	 116
indothrin	  34
Inverton 245	  63
iodofenphos	    2
IP50	  87
Iprodione	 112
isofenphos	    1
isolan	   12
isomethiozin	  86
Isopestox	    1
isoprocarb	   12
isopropalin	   85
isopropanol	  156
isoproturon	   87
Isotox	   17
isoxathior)	    1
Isoxazolidinone	   85

jasmolins	   25
Jones Ant Killer	   55

Kabat	   48
Kack	   56
Kafil	   34
KafilSuper	   34
Karathane	   68
Karbation	   98
Karmex	'.	-   87
Karphos	     1
Kayafume	  132
Kelthane	   17
Kemate	 111
Kepone	?	  17
Kerb	  84
Kildip	  63
 Kill-All	  54
 Kill-Ko Rat Killer	 116
 Kiloseb	  68
 Kitazin	    2
 Kiwi Lustr 277	  94
                        188

-------
                   ;                            Page
 Klerat	  116
 Klorex	  150
 KM	  ! so
 Knockmate	   99
 Koban	,	  113
 Kobu	   93
 Kobutol	   93
 Kopfume	  132
 Kprlan	    2
 Krenite	   85
 Kromad	   96,109
 Kryocide	   37
 Krysid	   116,123
 Kumulus S	   48
 Kusatol	  150
 Kypfarin	  ne
 Kypman 80	  101
 Kypzin	  101

 Lacco Sulfur	   48
 Lance	   12
 Landrin	   12
 Lannate	   12
 Lanox.	   12
 Larvacide	  132
 Lasso	  84
 Lawn-Keep	  63
 Lazb	  84
 Lead arsenate	  55
 lenacil	  86
 leptophos	    1
 Lexone	  QQ
 lindane	  17
 Line Rider	  63
 Linex  4L	  87
 Linorox	.....  87
 Linurex	  87
 linuron	  Q-J
 Liphadione	 116
 Liqua-Tox	 116
 Liquid Sulfur	  48
 Liquiphene	 105
 Lironion	                   86
L.M91	"~I~2 116
Lonacol	 101
Lorox	„.	  87
Lorsban	',.	.„.
                       189

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                                          Page
MM [[[ • ............  56
Macondray [[[  63
Magnetics [[[  48
Maki [[[ 1 1 6
malathion [[[   2
MAMA.... [[[  56
Mancoze'b [[[ ^0
Mancozin [[[ 101
Maneb [[[ 10°
Maneba .............................. . ........................................... 101
Manesan [[[ 101
Manex [[[ • ...................... 101
ManexSO [[[ 101
Manzate [[[ 101
Manzate 200 [[[ 101
Manzate D [[[ 101
manzeb [[[ 1 01
Manzin [[[  101
Maposol [[[   98
Marlate [[[   17
Matacil [[[   12
Mavrik ....................................... : .....................................   34
Mavrik Aquaflow ..................... '. .....................................   34
MCPA [[[   64
MCPB ........................... '. .................................................   64
MCPP [[[   64
M-Diphar [[[ 101

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                                              Page
 Metalaxyl	 113
 Metaldehyde	 145
 metalkamate	  12
 Metam-Fluid BASF	  98
 Metam-Sodium	  93
 Metason	 146
 Metasystox	  * 1
 Metasystox (i)	   1
 Metasystox-R	   1
 Metasystox-S	   1
 metaxon	  64
 methabenzthiazuron	  87
 methamidophos	   1
 Metham-Sodium	  98
 Methane arsonic acid	  56
 methanol	 155
 Methar 30	  56
 methidathion	   1
 methiocarb	  12
 Meth-O-Gas	 132
 methomyl	  12
 methoprene	  48
 Methoxone M	  64
 methoxychlor	,	  17
 Methoxyethyl mercury acetate	 105
 Methoxyethyl mercury chloride	 105
 Methoxyethyl Mercury Compounds.	 105
 methyl bromide	 132
 methyl carbamate insecticides	  12
 2-methyl-3,6 dichlorobenzoic acid	  64
 Methyl mercury acetate	 105
 Methyl mercury benzoate	 105
 Methyl Mercury Compounds	 105
 Methyl mercury hydroxide	 105
 Methyl mercury nitrile	 105
 Methyl mercury pentachlorophenate	 105
 Methyl mercury propionate..	 105
 Methyl mercury quinolinolate	 105
 Methyl naphthalenes	 157
 methyl parathion	   1
 methyl trithion	   2
 methylene chloride	 132
 metobromuron	  87
 metolachlor	  84
metoxuron	  87
metribuzin	  86
mevinphos	   1
                       191

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                                           Page
Mezene	  99
MGK	  50
MGK 264	 155
Micromite	  45
Microzul	 116
Miller 531	 109
Milogard	  86
Milo-Pro	  86
Minex	  48
mipafox	   1
MIPC	  12
Miracle	  63
mirex	  17
mitis green	  54
Mocap	   1
Monitor	•	   1
Monoammonium methane arsonate	  56
Mono-calcium arsenite	  54
monocrotophos	•—•   1
monolinuron	  87
mono-methyl naphthalene sulfonate	 157
Monosodium methane arsonate	  56
Monuron	•	  87
Morocide	  68
Morrocid	  68
MSMA	  56
Multamat	  12
Mycodifol	 102

N-2790	    1
Nabam	 100
Nabasan	 101
naled	.»    2
Namekil	 146
naphthalene	 132
naphthene	 132
naramycin	 112
NaTA	  84
Neburex	  87
neburon	  87
Neguvon	    2
Nemacur	    1
Nemafume	  132
Nemanax	•	  132
Nemaset	  132
Nemasol	   98
Nem-A-Tak	    1
                       192

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                                              Page
Nematocide	 132
Nemispor	 101
Neopynamin	  34
Neosorexa PP580	 116
Nephis	 132
Netagrone 600	  63
Nexagan	   1
Nexion	   2
NIA9044	  68
nicotine	  27
nicotine sulfate	  27
nicotinic acid-isopropylamine derivative	  85
Niomil	  12
Nitrador....	  68
nitrochloroform	 132
Nitrocresolic Herbicides	  68
Nitrolime	 149
Nitrophenolic Herbicides	  68
Nitropone  C	  68
Nix	  35
N-Methyl Carbamate Insecticides	  12
N-Octyl  Bicycloheptene Dicarboximide	 155
No Bunt	  90
Nomersam	  96
Nomolt	  45
norbormide	  116, 126
Noxfire	  30
Noxfish	  30
NRDC 149	  34
Nudrin	  12
Nusyn-Noxfish	  30
Nuvanol-N	   2

Octyl bicycloheptene dicarboximide	 155
OFF	  50
Oftanol	   1
Ofunack	   2
Omite	  44
OMPA...	   1
OntracicSOO	  86
Organochlorine Insecticides	  17
Organomercury Compounds	 105
Organophosphate Insecticides	   1
Organotin Compounds	 108
Orthene	   2
Ortho Danitol	  34
Ortho Diquat....	,	  76
                        193

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                                             Page
Ortho Paraquat CL	  76
Ortho Paraquat Plus	  76
Orthocide	 102
oryzalin	  85
Osaquat Super	  76
Oust	  87
Outflank	  34
Ovatoxin	  42
Oxadiazolinone	  85
oxadiazon	  85
oxamyl	  12
oxirane	 132
oxydemeton-methyl	   1
oxydeprofos	   1

Paarlan	  85
Pamisan	 105
Panogen	 105
Panogen M	 105
Pansoil	 113
Paracide	 132
Para-col	  76
paradichlorobenzene	 132
paraformaldehyde	 132
Paraquat	  76
parathion	   1
Paris Green	  54
Parzate	 101
Parzate C	 101
Pathclear	  76
Patoran	  87
Pattonex	  87
Pay-off	  34
PB-Nox	  30
PCNB	  93
PGP	  73
P.C.Q	 116
PDB	 132
PDQ	  64
PEBC	  84
pebulate	  84
Pencal	  55
Penchlorol	  73
pendimethalin	  85
Penetrants	 157
Penite	  54
Pennamine D	  63
                       194

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                                              Page
Pennant	   84
Penncap-M	    1
Penncozeb	  101
Penta	   73
Pentac	   17
Pentachloronitrobenzene	   93
Pentachlorophenate	   73
PentachlorophenoL.	   73
Pentacon	;	   73
Pentagen	   93
Penwar	   73
Permasect	   34
permethrin	   34
Perthane	   17
Perthrine	   34
PestoxXIV	    1
PestoxXV	    1
Petroleum distillates	  157
Petroleum oils	  157
petroleum sulfonates	  157
Phalton	  102
Pharorid	   48
phencapton	    2
Phenostat-A	  108
Phenostat-C	  108
Phenostat-H	  108
phenthoate	    2
Phentinoacetate	  108
Phenyl mercuric acetate	  105
phenyl mercury ammonium acetate	  105
Phix	  105
phorate	    1
phosalone	    2
Phosdrin	    1
phosfolan	    1
phosmet	    2
phosphamidon	    1
phosphides	  121
phosphine	  132
Phosphonates	   85
phosphorus compounds	  121
phostoxin	  132
Phosvel	    1
Phosvin	  116,  120
phoxim	    2
phthalates	   85
phthalthrin	   34
                       195

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                                               Page
Phytar 560	  56
Pic-CIor	 132
picloram	  85
picolinic acid compound	  85
Pillarquat	  76
Pillarxone	  76
pindone	 116
Piperonyl Butoxide	 155
pirimicarb	  12
pirimiphos-ethyl	   2
pirimiphos-methyl	   2
Pirimor	  12
Pivacin	 116
pival	 116
pivaldione	 116
Pivalyn	 116
Place-Pax	 116
Planotox	  63
Plantgard	  63
Plictran	  47
PMAA	 105
PMAS	 105
PMP Tracking Powder	 116
Poast	  85
Policar MZ	 101
Policar S	 101
Polybor	  39
polyesters of sodium thiobutane dioate	 157
polyethoxylated fatty acid esters	 157
polyethylene glycol	 157
polyhydric alcohols	 157
Polymone	  63
polyol fatty acid esters	 157
polyoxyethylene oleate	 157
Polyram M	 101
Polyram-Ultra	  96
Polyram Z	 101
Polytrin	  34
Pomarsol forte	  96
Pounce	  34
PP581	 116
Pramex	  34
Pramitol25E	  86
Prebane	  86
Precor	!	  48
Preeglone	  76
Prefar	   2
                        196

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                                               Page
Preglone	  76
Premerge 3	  68
Prentox	  30
Priglone	,	  76
Primagram	  84
Primatol M	  86
Primatol P	  86
Primatol Q	  86
Primatol S	  86
Primextra	,	  84
Primicid	   2
Primin	  12
Princep	  86
Proban	   2
Prodalumnol Double	  54
Prodan	  37
Prodaram	  99
profenofos	,   2
profluralin	  85
Pro-Gibb	  33
Pro-Gibb Plus	  33
Prolate	   2
prolin	 116
promecarb	  12
prometon.	  86
Prometrex	  86
prometryn	  86
pronamide	  84
propachlor	  84
Propanex	  84
propanil	  84
propargite	  44
propazine	  86
propenal	 132
propetamphos	   1
propoxur	  12
propylene oxide	 132
propyl thiopyrophosphate	   2
prothoate	   1
Prowl	  85
Proxol	   2
prussic acid	 132
Purivel...,	  87
Pydrin	  34
Pynamin	  34
Pynosect	  34
Pyradex	  84
                        197

-------
pyrazophos	   2
pyrethrins	  25
pyrethroids	  34
pyrethrum	  25
pyridaphenthion	   2
pyriminil	   116, 126
Pyrobor	  39

Quilan.:	  85
quinalphos	   1
Quintox	   116, 127
quintozene	  93

Racumin	 116
Rad-E-Cate 25	  56
radione	 116
Rampage	   116, 127
Rampart	   1
Ramrod	  84
Ramucide	 116
Randox	  84
Rapid	  12
Ratak	 116
Ratak Plus	 116
Raticate	   116, 126
Ratilan	 116
Ratimus	 116
Ratomet	 116
Raviac	 116
RAX	 116
red squill	   116, 126
Reglone	  76
Reglox	  76
Regulex	  33
Remasan  Chloroble M...,	 101
Repellents	  34
Resisan	  94
resmethrin	  34
Revenge	  84
RH-787	   116, 126
Rhodianebe	"... 101
Rhothane	  17
Ridall-Zinc	   116, 120
Ridomil	  113
Ripcord	  34
Riselect	  84
Rodent Cake	  116
                       198

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                                              Page
 Roderrticides	 115
 Rodex	 116
 Rodex-Blox	 us
 Rodine	   116, 126
 Rody	,	  34
 Ro-Neet	  84
 ronnel	   2
 Ronstar	  85
 Rotacide	  30
 rotenone	  30
 Rotenone Solution FK-11	  30
 Roundup	  85
 Rout (bromacil and diuron)	  86, 87
 Rovral	 112
 Rozol	 11 e
 Ruelene	   2

 sabadilla	  31
 Safeners	 157
 Safrotin	   2
 Safsan	  37
 Salvo (contains either arsenic) p. 56, or 2, 4-D	  63
 Sanspor	 102
 Santophen	  73
 Saprol	 113
 Sarclex	  87
 Saturn	  84
 schradan	   1
 Schweinfurt green	  54
 Scilliroside	 115
 Scout	  34
 Seedtox	 105
 Selinon	  68
 Semeron	  86
 Sencor	  86
 Sencoral	  86
 Sencorex	  86
 Seritox 50	  63
 sethoxydim	  85
 Setrete	 105
 Sevin	  12
 Shimmer-ex	 105
 Shoxin	   116, 126
siduron	  87
simazine	  86
Simazol	  86
Sinbar	  86
                       199

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                                              Page
Sinituho	  73
Sinox	  68
Sinox General	  68
Siperin	  34
Skeetal	-...,	  32
Sodar	  56
Sodium alkyl butane diamate	 157
sodium aluminofluoride	  37
Sodium arsenate	  55
Sodium Arsenite	  54
sodium biborate	  39
sodium cacodylate	  56
Sodium Chlorate	 150
Sodium fluoaluminate	  37
Sodium fluoride	  37
sodium fluoroacetate	  116,123
Sodium fluosilicate	  37
sodium pentaborate	  39
sodium pentachlorophenate	  73
sodium silico fluoride	  37
sodium tetraborate decahydrate	  39
Sofril	  48
Sok-Bt	  32
Solasan 500	  98
Solvents	 156
Sometam	  98
Sonalan	  85
Soprabel	  55
Sopranebe	 101
Spectracide	    2
Spike	  87
Spotrete WP 75	  96
Spotrete-F	  96
Spra-cal	  55
spreaders	  156
Spring Bak	  101
Spritz-Hormin/2,4-D	  63
Spritz-Hormit/2,4-D	  63
Sprout-Nip	   84
Spur	  34
S-Seven	   2
Stam	  84
Stampede	  84
Stickers	 156
Stirofos	   2
Stomp	  85
Strobane	  17
                        200

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                                              NPage
Strobane-T.	  17
strychnine	   116, 123
Subdue 2E	 113
Subitex	  68
Substituted Benzenes	  90
Sul-Cide	  48
Sulerex	  87
Sulfated alcohols	 157
Sulfex	  48
sulfometuron methyl	  87
sulfotep	   1
sulfur	  48
sulfur dioxide	 132
sulfuryl fluoride	 132
sulprofos	   1
Sumicidin	  34
Sumithion	   2
Super Crab-E-Rad-Calar	  56
Super D Weedone	  63
Super Dal-E-Rad	  56
Supernox	  84
Superormone Concentre	  63
Supracide	..   1
Surecide	   1
Surflan	  85
Surpass	.  84
Surpur	  84
Sutan	  84
Suzu	 108
Suzu-H.	,	.	 108
Swat	   1
Sweep	  76
Syllit	 112
Synergists	 155
Synthrin	;	  34
Systox	   1

2,4,5-T	;	  63
Tag HL331	 105
Talan	  68
Talbot...,	,	  55
talc	 156
Talcord	;.	  34
Talon	 116
Tamex	  85
Tamogam	  ne
Tantizon	„....	   86
                       201

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Target MSMA	  56
Tattoo	  12
2,3,6-TBA	  84
TBZ	 113
TCA	  84
TCBA	  84
TDE	  17
tebuthiuron	  87
Tecto	 113
Teflubenzuron	  45
Teknar...	  32
Telone II Soil Fumigant	 132
temephos	   2
Temik	  12
1080	•• 116
Tenoran	  86
TEPP	•   1
terbacil	  86
terbucarb	  84
terbufos	   1
terbuthylazine	  86
Terbutrex	  86
terbutryn	  86
terpene polychlorinates	  17
Terraclor	  93
Terraklene	  76
Terraneb SP	  95
Terrazole	  113
Terra Ant Killer	  55
Terr-O-Gas	  132
Tersan	  112
tetrachlorvinphos	   2
tetraethyl pyrophosphate	   1
tetrafluoron	  87
tetramethrin	  34
Tetrapom	  96
Thallium	  116, 120
thallium sulfate	  116, 120
Thiabendazole	  113
Thibenzole	  113
Thimer	  96
Thimet	    1
thiobencarb	   84
Thiocarbamates	  84,96
Thiodan	.'	   17
Thioknock	   96
Thiolux	   48
                        202

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                                              Page
thiometon	   2
Thion	  48
Thiophal	 102
Thiophos	   1
Thiophthalimides	 102
Thiotepp	   1
Thiotex	  96
Thiovit	  48
Thiram	'.	  96
Thiramad	  96
Thirasan	  96
Thistrol	i	  64
Thiuramin	  96
Thuricide	  32
Tiezene	 101
Tiguvon	;..   2
Tilcarex	  93
Tillam	  84
Tinestan	 108
Tinmate	 108
Tirampa	  96
TMTD	  96
TMTDS	  96
T-Nox	•	  63
Tolban	  85
Tolkan	  87
toluene	 155
Tolurex	  86
Tomarin	 116
Tomilon	  87
Tomorin	 116
Topitox	 116
Torak	.,   1
Tordon	  85
Tota-col	  76
Toxakil	  17
toxaphene	.'.	  17
Toxer Total	  76
Tox-Hid	 116
TPTA	 108
TPTH	 108
TPTOH	 108
TR-10	  85
tralomethrin	;	  34
Trametan	  95
Transamine	  63
Trans-Vert	  56
                       203

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                                                Page
Treflan	  85
Triadimefon	 "I "13
triallate	  84
Triasyn	 111
Triazines	-  85
Triazole	  86
triazophos	   1
Tribac	  84
Tribactur	  32
Tri-ban	 116
Tribunil	  87
Tributon	  63
Tricalcium arsenate	  55
Tricarbamix Z	  99
trichlorfon	»	   2
trichloroacetic acid	  84
trichlorobenzoic acid	  84
trichloromethane	  132
trichloronate	   1
2,4,5 trichlorophenoxy acetic acid	  63
triclopyr	  85
Tri-Clor	  132
Tricyclohexyl tin hydroxide	  47
trifluralin	•	  85
Trifocide	  68
Triforine	  113
Trifungol	   99
Trimangol	  101
Trimaton	   98
trimethacarb	   12
Trinoxol	   63
Tri-PCNB	   93
TriphenylTin	  108
Triple Tin	  108
Tripomol	•	   96
Triscabol	   99
Trithion	    1
Tritoftorol	  101
Truban	  113
Tuads	   96
 Tuban	   63
 Tubothane	  101
 Tubotin	  108
 Tuffcide	   95
 Tupersan	.".	   87
 Turcam	   12
 Turf-Cal	   55
                         204

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                                             Page
Turflon	  85

U46.	.	  63
U 46 D-Ester	  63
U 46 D-Fluid	  63
U 46 DP-Fluid	  63
Ultracide	   1
Unicrop-CIPC	  84
Unicrop  DNBP	  68
Unicrop  Maneb	 101
Unidron	'.	  87
Uriiroyal DO14	  44
Unisan....	 105
Uracils	  86
Uragan	  86
Urea derivatives	  86
Urox B	;..-	  86
Ustaad	  34

Vacor	   116,126
valone	 116
VancideMZ-96	  99
Vancide TM	  96
Vapam	  98
Vapona	   1
Varitox	  84
VC-13 Nemacide	   2
VectaISC	  86
Vectobac	  32
Venturol	 112
Venzar	;	  86
Veratrin	  31
vernolate	  84
Vertac	  68
Vertac General Weed Killer	  68
Vertac Selective Weed Killer	  68
Vi-Cad	 109
Vikane	 132
Volid	 116
Vondcaptan	 102
Vondodine	 112
Vondozeb Plus	 101
Vonduron	,	  87
VPM	  98
VydateL	  12

warfarin	 116
                       205

-------
Warfarin Q	 116
Warfarin Q Concentrate	 116
Wax Up	  85
WBA 8107	 116
Weed Tox	  63
Weed-B-Gon	  63
Weed-E-Rad	  56
Weed-E-Rad 360	  56
Weed-Hoe	  56
Weed-Rhap	  63
Weedar	  63
Weedatul	  63
Weedazol	  86
Weedol	  76
Weedone	  63
Weedone DP	,  63
Weedone 170	  63, 64
Weedtrine-D	  76
Weedtrol	  63
White Arsenic	  54
white phosphorus	  119

xylene	  156

Yasoknock	  116,123
yellow phosphorus	  116,119

Zebtox	  101
Zerlate	  99
Ziman-Dithane	  101
Zinc arsenate	  55
zinc phosphide	  116,  120
Zinc-Tox	  1"16,  120
Zincmate	.-.	  99
Zineb	  100
Zineb 75 WP	  101
Zinosan	  101
Ziram	  99
Ziram F4	  99
Ziram Technical	  99
Ziram W76	  99
Ziramvis	  99
Zirasan 90	  99
Zirberk	  99
Zirex90	  99
Ziride	  99
Zitox	  99
                       206

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