=DA 5/10/077010   Do not remove. This document
-r M'O^rU/ y-//"UiO   .  • • •   .  •  ..  -•  T-.TI A
                 should be retained in the EPA

                 Region 5 Library Collection.
    RECOGNITION AND MANAGEMENT


         OF PESTICIDE POISONINGS
                 Second Edition
         U. S. ENVIRONMENTAL PROTECTION AGENCY



            OFFICE OF PESTICIDE PROGRAMS


               WASHINGTON, D.C. 20460




                   AUGUST 1977

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RECOGNITION AND MANAGEMENT  OF
         PESTICIDE  POISONINGS
         Donald  P. Morgan,  M.D.,  Ph.D.*
Support for this publication was provided by the Epidemiologic
Studies Program, Human Effects Monitoring Branch, Technical
Services Division, Office of Pesticide Programs, U.S. Environ-
mental Protection Agency, Washington, D.C. 20460.

* Director, Iowa Epidemiologic Studies Program, located at University of
  Iowa Medical School, Iowa City, Iowa 52240.

                       U.S. Envlrorai'sr^ v." "         '  '  '
                       Region 5, !•-'.'. .-"
                       250  S. U'--' " - -
                       Chicago, IL
               Second  Edition
          For sale by the Superintendent of Documents, U.S. Government
                Printing Office, Washington, D.C. 20402

                 Stock number 055-004-00013-7

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                   CONTENTS

                                              Page
INTRODUCTION	   i
SOLID ORGANOCHLORINE PESTICIDES 	   1
ORGANOPHOSPHATE CHOLINESTERASE-
  INHIBITING PESTICIDES	   4
CARBAMATE CHOLINESTERASE-INHIBITING PESTICIDES ....   9
PARAQUAT, DIQUAT, AND MORFAMQUAT(Dipyridyls) 	  13
CHLOROPHENOXY COMPOUNDS 	  18
NITROPHENOLIC HERBICIDES	  21
PENTACHLOROPHENOL OR SODIUM
  PENTACHLOROPHENATE	  24
ORGANONITROGEN  HERBICIDES	  27
DIMETHYLDITHIOCARBAMATE COMPOUNDS	  31
ANTICOAGULANT RODENTICIDES	  35
ARSENICAL PESTICIDES 	  39
VACOR 8 and DLP-787	  44
HALOCARBON and SULFURYL FUMIGANTS	  47
MISCELLANEOUS FUMIGANTS	  53
PESTICIDES INDEX	  64

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                       INTRODUCTION

  Sound judgment is as important as ever in the management of poisonings.
But emergency personnel cannot be expected to know instantly the properties
of dozens of modern pesticides and the mechanisms by which  they produce
toxic effects. It  is equally unrealistic to suppose that professionals who only
occasionally encounter pesticide poisonings can  bring together quickly the
accumulated clinical and laboratory experience needed for the best possible
treatment of each  case. These  considerations  inspired preparation  of an
excellent manual, Clinical Memoranda  of  Economic  Poisons,  in 1956 by
Wayland J. Hayes,  Jr., M.D., Ph.D., U.S. Public Health Service. Dr.  Hayes
revised the manual  in  1963 under  the title Clinical Handbook on Economic
Poisons—Emergency Information for Treating Poisoning. The present  pub-
lication further  updates  both these useful handbooks.

  Pesticides with similar chemical structures and toxic properties are grouped
into major classes,  such as  chlorinated hydrocarbons, chlorophenoxy  com-
pounds, and arsenicals.  Under these major classes  are listed chemical struc-
tures, examples  of  commonly  used pesticides, pertinent  toxicology and fre-
quent symptoms  of poisoning,  methods to confirm diagnoses  of poisoning,
and the latest information on  clinical management of poisonings caused by
the respective classes of chemicals.

  A deliberate  effort has been made to suggest  treatment measures that can
be  implemented (or at  least initiated)  in  small hospitals and clinics, where
victims of pesticide poisonings are likely to be  received.  At the expense of
some repetition,  treatment  procedures  are spelled out sequentially  for the
several classes of chemical poisonings included.
  The  author  assumes  full responsibility  for judgments when alternative
interpretations and  recommendations have appeared in the published litera-
ture. Generous  assistance has  been extended by colleagues  and other pro-
fessionals interested in the treatment of poisonings: Dr. Albert L. Picchioni,
Professor of Pharmacology,  College of Pharmacy;  and Dr. Elmer S. Light-
ner, Professor  of Pediatrics, College of Medicine, University  of Arizona;
Dr. Robert  J. Roberts,  Professor  of Pediatrics; Dr. John J. Ambre, Asso-
ciate  Professor  of  Internal  Medicine;  Dr. Raymond F.  Sheets, Professor
of Medicine; and Dr.  Henry E. Hamilton, Professor of Medicine, University
of  Iowa College of  Medicine.  Dr.  Maynard  B.  Chenoweth,  Biomedical
Research, Dow  Chemical, U.S.A.;  Dr. Jon E.  Ford, Chevron Environmental
Health Center; and Dr. Robert H. Lang, Corporate Medical Director of Rohm
and Haas Co. Members  of the staff of the Human Effects Monitoring Branch
and Technical Services Division, Office of Pesticide  Programs, U.S. Environ-
mental Protection Agency,  have  patiently edited the  manuscript, prepared
the index and attended to the details of publication.

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 SOLID  ORGANOCHLORINE  PESTICIDES
CHEMICAL STRUCTURES
                       ci
                      CHLORDANE
                                        CI
                S=0
  CI
                                         CH30
                                                              OCH,
                                                METHOXYCHLOR

COMMON COMMERCIAL  PESTICIDE  PRODUCTS (approximately in
  order of toxicity)
  Highly toxic: endrin (Hexadrin), a stereoisomer of dieldrin.
  Moderately toxic: aldrin (Aldrite, Drinox), endosulfan (Thiodan), dieldrin
(Dieldrite), toxaphene (Toxakil, Strobane-T), lindane (Isotox, Gammexane),
benzene hexachloride  (BHC, HCH), DDT  (Chlorophenothane), heptachlor,
kepone, terpene polychlorinates  (Strobane), chlordane  (Chlordan),  dicofol
(kelthane), chlorobenzilate (Acaraben),  mirex, methoxychlor (Marlate).

TOXICOLOGY
  In adequate dosage, these chemicals interfere with axonic  transmission of
nerve impulses and therefore disrupt the function  of  the nervous system,
principally that  of the brain.  This results  in behavioral  changes, sensory
and equilibrium  disturbances, involuntary muscle  activity, and depression of
vital centers, particularly that controlling respiration.  Adequate  doses in-
crease the irritability of the myocardium and  cause degenerative changes in
the liver.

FREQUENT SYMPTOMS AND SIGNS OF POISONING
  APPREHENSION, excitability, dizziness, HEADACHE, DISORIENTA-
TION, weakness, PARESTHESIAE,  muscle  twitching, tremor,  tonic  and
clonic CONVULSIONS (often  epileptiform),  coma. Soon  after  ingestion,
nausea and vomiting  are often prominent. When  chemicals are  absorbed
by parenteral routes, apprehension, twitching,  tremors, and convulsions may
be the first symptoms. Respiratory depression is caused by the pesticide and
by the petroleum solvents in which these pesticides are usually  dissolved.
Pallor occurs in moderate to severe poisoning. Cyanosis may result as con-
vulsive activity interferes with respiration.
                                  1

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CONFIRMATION OF DIAGNOSIS
  Pesticide and/or metabolites can usually be identified in blood or urine
by gas-liquid chromatographic examination  of samples taken within 72 hours
of poisoning.  Some chlorinated hydrocarbon pesticides persist in  the  serum
for weeks or months  after absorption.  DO NOT DELAY TREATMENT
of acute poisoning pending confirmatory blood analysis. Presence of chlori-
nated hydrocarbon residues in blood or tissues does not, of itself, indicate
poisoning; actual concentrations are critical to a diagnosis  of poisoning.

TREATMENT
  1.  Establish CLEAR AIRWAY and TISSUE OXYGENATION by aspira-
     tion of secretions,  and if necessary, by assisted pulmonary  ventilation
     with oxygen.
  2.  CONTROL  CONVULSIONS.  The  anticonvulsant  of  choice is  DI-
     AZEPAM (VALIUM). Adult dosage, including children  over 6 years
     of age or 23 kg in weight: inject 5-10  mgm (1-2  ml)  slowly intra-
     venously (no faster than one ml per  minute), or give total  dose intra-
     muscularly (deep). Repeat in 2-4  hours if needed.
     Dosage  for children under  6 years or 23 kg in  weight: inject 0.1-0.2
     mgm/kg (0.02-0.04  ml/kg) slowly intravenously (no faster than  one-
     half total dose/minute), or give total dose intramuscularly (deep). Re-
     peat in 2-4 hours if needed.
     CAUTION:  Administer intravenous  injection  slowly to  avoid  irrita-
                 tion of the vein, occasional  hypotension, and  respiratory
                 depression.
     Because of a greater tendency  to cause respiratory  depression,  BAR-
     BITURATES are probably of less value  than DIAZEPAM. One used
     successfully in the past is  PENTOBARBITAL (NEMBUTAL). Maxi-
     mum safe dose:  5  mgm/kg body  weight, or 0.20 ml/kg  body weight,
     using the usual 2.5% solution.
     If possible, inject solution  intravenously,  at  a rate not exceeding one
     ml/minute until  convulsions are controlled. If intravenous  administra-
     tion is  not possible, give total dose rectally, not exceeding  5 mgtn/kg
     body weight (0.2 ml/kg of 2.5%  solution).
     CAUTION:  Be prepared  to assist pulmonary ventilation mechanically
                 if respiration is depressed.
  3.  If pesticide has been INGESTED in quantity sufficient to cause poison-
     ing, the stomach must be emptied.
     If victim is ALERT and respiration is not depressed, give SYRUIP OF
     IPECAC to induce vomiting (adults  and  children 12 years  and older:
     30 ml; children under 12 years: 15 ml).
     CAUTION: OBSERVE THE  VICTIM closely  after  administering
                 IPECAC.  If consciousness  level declines, or  if vomiting
                 has not occurred  in 15 minutes, proceed  immediately to
                  INTUBATE the stomach.

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   Following emesis,  have  victim drink a  suspension of 30  gm  ACTI-
   VATED CHARCOAL in 3-4 ounces of water  to limit  absorption of
   toxicant remaining in the gut.
   If the victim is NOT FULLY ALERT, empty the stomach immediately
   by  INTUBATION,  ASPIRATION,  and LAVAGE, using  isotonic
   saline or 5%  sodium bicarbonate. Because  many  pesticides are  dis-
   solved in petroleum distillates, emesis and intubation  of the stomach
   involve a serious risk that solvent will be aspirated, leading  to chemical
   pneumonitis.
   For this reason:
   A.  If the victim is unconscious  or obtunded,  and if  facilities are at
       hand, insert  an ENDOTRACHEAL  TUBE (cuffed, if available)
       prior to gastric intubation.
   B.  Keep the victim's HEAD BELOW THE LEVEL OF  THE STOM-
       ACH during intubation and lavage (Trendelenburg,  or left lateral
       decubitus, with head of table tipped  downward). Keep  the victim's
       head turned to the left.
   C.  ASPIRATE PHARYNX as regularly  as possible to remove gagged
       or vomited stomach contents.
   After aspiration of gastric contents and washing of stomach,  instill 30
   gm of ACTIVATED CHARCOAL  in  3-4  ounces of water through
   stomach tube to limit absorption of remaining toxicant. Do  NOT instill
   milk, cream, or  other substances  containing vegetable or  animal  fats
   which enhance absorption of chlorinated hydrocarbons.
   If bowel movement has  not occurred in 4 hours and if patient  is fully
   conscious, give SODIUM  SULFATE  (Glauber's Salts) as  a  cathartic.
   (Adults, 12  years and older: 15  gm  in 6-8 ounces of water;  children
   under 12: 0.2  gm/kg body weight in 1-6  ounces of water).
4.  BATHE and SHAMPOO the victim vigorously with  soap and water
   if SKIN and HAIR are contaminated.
5.  DO NOT give epinephrine or other adrenergic amines, because of the
   myocardial irritability produced by chlorinated  hydrocarbons.
6.  During convalescence,  enhance CARBOHYDRATE, PROTEIN,  and
   VITAMIN intake by diet or parenteral  therapy to minimize toxic in-
   jury to the liver.
7.  The chemical ENDRIN is much more HEPATOTOXIC  than are other
   chlorinated hydrocarbons in common use. Bilirubinemia and elevated
   blood enzyme  activities occur commonly  in poisoning. Special measures
   should be taken to minimize injury by supplying ample nutrients.
8.  With the exception of endrin poisoning, the likelihood of  recovery from
   poisoning by most chlorinated hydrocarbon pesticides is generally good,
   even when convulsions  occur. Fatalities  occur as a result of massive
   doses. The prognosis in endrin poisoning is more guarded.

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               ORGANOPHOSPHATE
         CHOLINESTERASE-INHIBITING
                       PESTICIDES

GENERAL CHEMICAL  STRUCTURE
         C2H5O  or  CH3O^       ^S  (or  O)
         C2H5O or CH30

COMMON COMMERCIAL PESTICIDE PRODUCTS (approximately in
  order of decreasing toxicity)

  Highly  toxic:  TEPP, phorate  (Thimet),  mevinphos (Phosdrin), fensul-
fothion (Dasanit),  demetonf  (Systox),  disulfotonf  (Disyston), sulfotepp
(Bladafume, Dithione),  Counter,  ethyl  parathion (Parathion,  Thiophos),
fonofos (Dyfonate), EPN, azinphosmethyl (Guthion), methyl parathion (Dalf),
monocrotophos (Azodrin), dicrotophos (Bidrin),  methamidophos (Monitor),
carbophenothion (Trithion), phosphamidon (Dimecron).
  Moderately toxic: famphur (Warbex, Bo-Ana, Famfos), ethoprop (mocap),
coumaphos  (Co-Ral), demeton-methylt  (Metasystox),  dichlorvos (DDVP,
Vapona),dioxathion (Delnav), crotoxyphos (Ciodrin), chlorpyrifos (Dursban),
ethion, fenthion (Baytex, Entex), diazinon (Spectracide), dimethoate (Cygon),
naled (Dibrom), trichlorfon  (Dylox, Dipterex,  Neguvon), crufomate  (Rue-
lene), ronnel (Korlan), malathion  (Cythion).
  t  Certain of  the organophosphates are systemic,  i.e., they are taken up
by the plant and translocated into foliage and sometimes into the fruit.

TOXICOLOGY
  Toxicants of this class phosphorylate almost irreversibly varying amounts
of the acetylcholinesterase  enzyme of  tissues, allowing accumulation of
acetylcholine at cholinergic neuro-effector junctions (muscarinic effects), and
at skeletal muscle  myoneural junctions and in autonomic ganglia (nicotinic
effects). Poison also impairs CNS function. Toxicants can be absorbed by
inhalation, ingestion, and skin penetration. Some  are converted to more toxic
intermediates (-oxons) before they are metabolized. All undergo hydrolytic
degradation in liver and other tissues, usually  within hours of absorption.
Degradation products are of low toxicity, and are excreted in urine and feces.

FREQUENT  SYMPTOMS  AND SIGNS OF POISONING

   Symptoms of acute poisoning develop during exposure or within 12 hours
of   contact.  HEADACHE,  DIZZINESS,   EXTREME   WEAKNESS
ATAXIA, TINY  PUPILS,  blurred or  dark vision, muscle TWITCHING,
                                                                ,

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TREMOR, sometimes convulsions, mental confusion, incontinence,  uncon-
sciousness. NAUSEA, vomiting, abdominal cramps,  diarrhea.  Tightness in
chest, SLOW HEARTBEAT, wheezing, productive cough, sometimes PUL-
MONARY EDEMA (up to 12 hours after poisoning).  SWEATING,  rhi-
norrhea,  tearing,  salivation.  Severe poisoning  may  cause sudden  uncon-
sciousness or TOXIC PSYCHOSIS resembling acute alcoholism. Extreme
BRADYCARDIA and heart  block have  been  observed.  RESPIRATORY
DEPRESSION is caused by toxicant and also by hydrocarbon solvent. Con-
tinuing absorption at intermediate dosage may cause an INFLUENZA-LIKE
ILLNESS characterized by weakness,  anorexia,  and malaise.
CONFIRMATION OF DIAGNOSIS

  Depression of plasma  and/or RBC  cholinesterase activity  is  the most
satisfactory and generally available evidence of  excessive  absorption of  this
class of toxicants. Depression of plasma cholinesterase often persists from
1 to 3  weeks;  depression of RBC acetylcholinesterase  persists up to  12
weeks. Organophosphates yield metabolites that  are commonly  detectable in
the urine of  poisoning victims 12 to 48  hours after absorption  of significant
quantities. The  table below lists approximate LOWER LIMITS OF NOR-
MAL of plasma and red cell CHOLINESTERASE ACTIVITIES of human
blood, measured by  generally available methods. Test values  BELOW these
levels usually  indicate excessive  absorption  of a cholinesterase-inhibiting
chemical.  (About 3% of individuals have a  genetically determined  low
plasma cholinesterase  activity due to  generation of  an atypical enzyme by
the liver.) Whenever possible, comparison of the test  sample with a pre-
exposure value  offers  the best confirmation of organophosphate absorption:
a depression of 25% or more is strong evidence of excessive absorption.
CAUTION:   If diagnosis is probable, do  not delay treatment pending con-
             firmation of diagnosis by blood analysis.
      TABLE  1.  Approximate Lower Limits of Normal Plasma and
              Red Cell Cholinesterase Activities in Humans *
METHOD                PLASMA   RBC
ApH (Michel)                 0.4       0.5
pH STAT (Nabb-Whitfield)    2.3       8.0
ChE-tel (Pfizer)                40
A ChE-tel (Pfizer)                      210
1-Test Cholinesterase
   (EM  Diagnostics)           3.6
ACHOLEST Test Paper     >20
Dupont ACA                 <8
Garry-Routh     Male             7.8
   (Micro)        Female           5.8
Merckotest                         3.0
* Because measurement technique varies among
  estimates of  minimum normal  values are  usu
  laboratories.
          UNITS
ApH per ml per hour
/jM per ml per  minute
ChE-tel units
A ChE-tel units

Units per ml
Minutes
Units per ml

/iM-SH per ml  per  3  min
Units per ml
laboratories, more accurate
ally provided by  individual

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TREATMENT
      CAUTION:  Persons attending the victim must  avoid contamination
                   with vomitus and other sources  of toxicant. Wear rubber
                   gloves while decontaminating the victim.
   1.  Establish CLEAR AIRWAY and TISSUE OXYGENATION by aspira-
      tion of secretions, and  if necessary, by assisted pulmonary  ventilation
      with oxygen. Do  not administer atropine until a  satisfactory level  of
      oxygenation has been achieved. Atropine may induce ventricular fibril-
      lation if victim is severely asphyxic.
   2.  Administer  ATROPINE  SULFATE intravenously, or intramuscularly
      if IV injection is  not possible.  Atropine protects  the  end-organs from
      excessive  concentrations  of acetylcholine. It  does not reactivate  cho-
      linesterase,  and the effects of unmetabolized  toxicant may appear  as
      atropinization wears off.
      In MODERATELY SEVERE poisoning:
      Adult  dosage, including children over 12 years: 0.4-2.0 mgm (1.0 to 5.0
      ml of  usual 0.4 mgm/ml solution) repeated every 15-30 minutes  until
      atropinization is achieved (tachycardia, flushing, dry mouth, mydriasis).
      Maintain  atropinization by repeated doses for 2-12 hours, depending
      on severity  of poisoning. Watch the patient closely for relapse as  atro-
      pinization wears off.
      Dosage for children under 12 years: 0.05 mgm/kg body weight (0.125
      ml/kg  of  usual  0.4  mgm/ml solution) repeated every 15-30 minutes
      until atropinization is  achieved. Maintain atropinization with repeated
      dosage of 0.02-0.05  mgm/kg.
      Severely  poisoned  individuals may exhibit  remarkable tolerance to
      atropine: twice the doses  suggested above may sometimes be  needed.
      Signs  of  over-atropinization are: muscle twitching, FEVER anddelirium.
  3.  Administer PRALIDOXIME   (Protopam-Ayerst,   2-PAM)  in  those
      cases of severe poisoning by  organophosphate (specifically)  pesticides
      in which muscle weakness and twitchings  persist despite atropine ther-
      apy. When  administered  early  (less  than 36 hours after  poisoning)
      protopam is  of value in  relieving the nicotinic effects of severe poison-
      ing  that are not reversed by atropine.
      Note:  Protopam is of no  value in poisonings  by cholinesterase-inhibit-
             ing carbamate compounds.
      Adult dose (including children over 12 years): give 1.0 gm intravenously,
      at  no more  than  0.5  gm per minute, repeating dose in one  hour if
      muscle  weakness has not been relieved.
      Child's dose (under 12 years):  give 20-50 mgm per kg (depending on
      severity) intravenously, injecting no more than half the total  dose  per
      minute. This dosage  amounts  to 0.4 ml-1.0 ml per kg of the recom-
      mended 5% solution. Repeat  every 10-12 hours  as  needed, up to  3
      times.
      In very severe poisonings, dosage rates may be doubled.  Slow adminis-
      tration may be achieved by administering pralidoxime in 250 ml normal
      saline over  a  30-60  minute  interval.  If intravenous  injection is  not

                                   6

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   possible, pralidoxime may be given by deep intramuscular injection.
   CAUTION:  Be prepared to assist pulmonary ventilation if respiration
                is depressed.
4. Observe patient closely  at  least 24  hours to  insure  that  symptoms
   (sometimes pulmonary edema) do not occur as atropinization wears off.
   In very severe poisonings, metabolic disposition of toxicant may require
   as long as 5-10 days.
5. BATHE and SHAMPOO victim with soap and water  if there is  any
   chance that SKIN and HAIR are contaminated.
6. If pesticide has been INGESTED in quantity sufficient to cause poison-
   ing,  the stomach must be emptied. If  victim is  alert  and respiration is
   not depressed, give SYRUP OF IPECAC to induce  vomiting:
   Adults (12 years and over):  30 ml; children under 12 years:  15 ml.
   CAUTION:  OBSERVE  the   victim   closely  after   administering
                IPECAC.  If consciousness  level declines, or if vomiting
                has  not occurred  in 15 minutes, proceed  immediately to
                INTUBATE the stomach.
   Following  emesis,  have victim drink  a suspension  of  30 gm ACTI-
   VATED CHARCOAL  in 3-4  ounces of water to limit absorption of
   toxicant remaining in the gut.
   If victim  is obtunded or  respiration is depressed, empty the stomach
   by INTUBATION,  ASPIRATION,  and  LAVAGE,  using  isotonic
   saline  or  5% sodium bicarbonate.  Because many pesticides are dis-
   solved in petroleum distillates, emesis  and intubation of the stomach
   involve a  serious risk that solvent will be  aspirated, leading to chemical
   pneumonitis. For this reason:
   A.  If  the victim  is unconscious or obtunded,  and  if facilities  are at
       hand,  insert an ENDOTRACHEAL  TUBE (cuffed, if  available)
       prior to gastric intubation.
   B.  Keep the victim's HEAD BELOW THE LEVEL  OF THE STOM-
       ACH  during intubation  and lavage (Trendelenburg,  or left lateral
       decubitus,  with head of table tipped downward).  Keep the victim's
       head turned to the left.
   C.  ASPIRATE PHARYNX as regularly  as possible  to remove gagged
       or vomited stomach contents.
   After aspiration of gastric contents and washing of stomach, instill 30
   gm of  ACTIVATED CHARCOAL in  3-4  ounces of water  through a
   stomach tube to limit absorption of remaining toxicant.
   If bowel movement has  not occurred in 4 hours, and if patient is fully
   conscious,  give SODIUM SULFATE  (Glauber's Salts)  as a cathartic:
   Adults (12 years and older): 15 gm in 6-8  ounces of water.
   Children under 12: 0.2 gm/kg  body  weight in  1-6  ounces  of water.
7. DO  NOT give morphine, aminophylline,  phenothiazines,  or  reserpine.

8. Give adrenergic amines ONLY if there is a specific indication.

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 9.  If intractable  CONVULSIONS (unresponsive to  antidotes)  occur in
    severe poisoning, causes unrelated to direct organophosphate action may
    be responsible: head trauma, cerebral anoxia,  mixed poisoning.
    Although not thoroughly tested  in these  circumstances, DIAZEPAM
    (Valium) (5-10  mgm for  adults, 0.1-0.2 mgm/kg for  children under 6
    years or 23 kg) is probably the safest and most reliable anticonvulsant.
    CAUTION:  Be prepared to assist pulmonary ventilation mechanically
                 if  respiration is depressed, and to counteract hypotensive
                 reactions.
10.  Persons  who have been clinically poisoned by organophosphate  pesti-
    cides should not  be re-exposed  to cholinesterase-inhibiting  chemicals
    until symptoms  and signs have resolved completely and blood cholines-
    terase activities  have returned to at least  80% of pre-poisoning values.
    If blood cholinesterase  was not  measured  prior  to  poisoning,  blood
    enzyme  activities should reach at  least minimum normal levels (Table 1)
    before the victim  is returned to  a pesticide-contaminated environment.
11.  DO NOT administer atropine or pralidoxime prophylactically to  work-
    ers  exposed  to  organophosphate pesticides.  It  is neither practical  nor
    medically sound to do so.

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                      CARBAMATE

         CHOLINESTERASE-INHIBITING
                       PESTICIDES

GENERAL CHEMICAL STRUCTURE

                           O

                     .N	C	O—
              H3C^


COMMON COMMERCIAL PESTICIDE  PRODUCTS  (approximately in
  order of decreasing toxicity)
  Highly toxic: aldicarbf (Temik), oxamyl  (Vydate), carbofuran (Furadan),
methomyl  (Lannate, Nudrin), Zectran, methiocarb (Mesurol).
  Moderately toxic: propoxur (Baygon), Landrin, carbaryl (Sevin),  metal-
kamate (Bux).
  f  Some chemicals of this class are systemic,  i.e., they are taken up by
the plant and translocated into foliage and sometimes  into the  fruit.

TOXICOLOGY

  Toxicants of this class cause  reversible  carbamylation of the acetylcho-
linesterase enzyme  of tissues,  allowing  accumulation  of acetylcholine at
cholinergic neuroeffector junctions (muscarinic effects), and at skeletal  muscle
myoneural junctions and in autonomic  ganglia  (nicotinic  effects).  Poison
also  impairs CNS  function.  The  carbamyl-enzyme combination  dissociates
more readily than the phosphorylated enzyme produced by organophosphate
insecticides. The lability tends to mitigate  the toxicity of carbamates, but
also  limits the usefulness of blood enzyme measurements  in diagnosis of
poisoning.  Carbamates are absorbed by inhalation,  ingestion,  and  dermal
penetration. They are actively metabolized by the liver, and the  degradation
products are excreted by  the liver and kidneys.
  A  few of the carbamate insecticides are formulated in methyl (wood) alco-
hol. In cases of ingestion of these formulations, the toxicology of the  metha-
nol  must be taken  fully into  consideration: severe gastroenteric irritation,
acidosis, and CNS injury.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

  Symptoms of acute poisoning develop during exposure or within 12 hours
of contact. HEADACHE,  DIZZINESS, WEAKNESS,  ATAXIA,  TINY
PUPILS, blurred or "dark" vision, muscle TWITCHING, TREMOR, some-
times  convulsions,  mental  confusion,  incontinence,   unconsciousness.

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NAUSEA, vomiting, abdominal cramps, diarrhea. Tightness in chest, SLOW
HEARTBEAT, wheezing, productive cough, occasionally pulmonary edema.
Sweating, rhinorrhea, tearing, SALIVATION. Severe poisoning may  cause
sudden unconsciousness, or a toxic psychosis.  RESPIRATORY DEPRES-
SION may  result from  actions of the toxicant  and solvent.  Continuing  ab-
sorption at intermediate dosage  may cause protracted  weakness,  anorexia,
and malaise.

CONFIRMATION OF  DIAGNOSIS
  Depression of plasma and/or RBC  cholinesterase activity is sometimes
useful in detecting excessive absorption of carbamates. However, enzyme activ-
ities commonly revert to normal within a few hours. They are not, therefore,
reliable detectors of carbamate poisoning; i.e.,  intoxication may exist when
blood cholinesterase activities are normal. The rapid methods for  cholines-
terase estimation (ACHOLEST, ChE-TEL, MERCKOTEST) are more likely
to detect depressions. Some  carbamates yield metabolites  that are  meas-
urable in the urine of poisoning  victims up  to 48 hours after absorption of
significant quantities.
   The table below lists the  approximate LOWER LIMITS OF NORMAL
plasma and red cell  CHOLINESTERASE  ACTIVITIES of human blood,
measured by generally  available  methods.  When test  values are  BELOW
these levels,  excessive  absorption of  a cholinesterase-inhibiting carbamate
may be suspected. Whenever possible,  comparison of the "test" sample with
a "pre-exposure" value  offers the best  confirmation of excessive carbamate
absorption: a  depression of 25%  or more  is strong evidence of  excessive
exposure. (About 3%  of  individuals  have a  genetically  determined  low
plasma cholinesterase  activity, due to  generation of an atypical enzyme by
the liver. The red cell  acetylcholinesterase  is normal in these cases.)
       TABLE 1. Approximate Lower Limits of Normal Plasma and
              Red Cell Cholinesterase Activities in Humans *
 METHOD                 PLASMA   RBC
 ApH (Michel)                 0.4       0.5
 pH  STAT (Nabb-Whitfield)    2.3       8.0
 ChE-tel  (Pfizer)                40
 A ChE-tel (Pfizer)                       210
 1-Test Cholinesterase
   (EM Diagnostics)           3.6
 ACHOLEST Test Paper      >20
 Dupont ACA                 <8
 Garry-Routh      Male             7.8
   (Micro)        Female           5.8
 Merckotest                        3.0
         UNITS
ApH per ml per hour
iuM per ml per minute
ChE-tel units
A ChE-tel  units

Units per ml
Minutes
Units per ml

/xM-SH per ml per 3  min
Units per ml
 * Because measurement technique varies  among laboratories, more accurate
  estimates  of minimum normal values are usually provided by  individual
  laboratories.
                                  10

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CAUTION:  If diagnosis is probable, do not delay treatment  pending con-
             firmation of diagnosis by blood analysis.
TREATMENT
     CAUTION:  Persons  attending the victim must  avoid contamination
                 with vomitus and  other sources  of toxicant. Wear rubber
                 gloves while decontaminating the victim.
  1.  Establish CLEAR AIRWAY and TISSUE  OXYGENATION by aspira-
     tion of secretions,  and if necessary, by  assisted pulmonary ventilation
     with  oxygen. Do not  administer  atropine until a  satisfactory level of
     oxygenation  has  been  achieved.  Atropine may induce ventricular fibril-
     lation if the victim is severely asphyxic.
  2.  Administer ATROPINE  SULFATE  intravenously, or  intramuscularly
     if IV  injection is not  possible.  Atropine protects  the end-organs from
     excessive concentrations of acetylcholine. It does not reactivate cholin-
     esterase, and effects of unmetabolized toxicant may appear as atropiniza-
     tion wears off.
     In MODERATELY SEVERE poisoning.
     Adult dose  (including children  over  12 years): 0.4-2.0 mg/kg  body
     weight (1.0-5.0 ml of usual 0.4  mgm/ml solution) repeated every 15-30
     minutes  until  atropinization  is  achieved  (tachycardia,  flushing,  dry
     mouth, mydriasis). Maintain atropinization by repeated doses for 2-12
     hours, depending on severity of poisoning.
     Child's dose: 0.05 mgm/kg body weight  (0.125  ml/kg  of  usual  0.4
     mgm/ml solution) repeated every 15-30  minutes until atropinization is
     achieved. Maintain  atropinization  with repeated dosage  of  0.02-0.05
     mgm/kg.
     Severely poisoned individuals may exhibit remarkable tolerance to atropine:
     twice the doses suggested  above  may sometimes be  needed. Signs of over-
     atropinization are: muscle twitching, FEVER,  delirium.
 3.  Do NOT give pralidoxime (Protopam-Ayerst, 2-PAM).  It  is  of no
     value in carbamate poisonings.
 4.  OBSERVE patient closely  at least 24 HOURS to insure that symp-
     toms  (possibly pulmonary edema)  do not occur as atropinization  wears
     off.
 5.  BATHE and SHAMPOO victim with soap and water  if there  is  any
     chance that SKIN and HAIR are  contaminated.
 6.  If pesticide  has  been  INGESTED, the stomach must  be emptied. If
     victim is alert  and respiration  is not  depressed,  give  SYRUP  OF
     IPECAC  to  induce vomiting: adults  (including children  over  12), 30
     ml; children under 12, 15 ml.
     CAUTION:  OBSERVE   the   victim   closely  after    administering
                 IPECAC. If consciousness  level  declines,  or if  vomiting
                 has not occurred in 15  minutes, proceed  immediately to
                 INTUBATE the stomach.
     Following emesis,  have victim  drink  a  suspension of  30 gm  ACTI-
     VATED CHARCOAL in 3-4 ounces of water to bind toxicant remain-
     ing in the gastrointestinal tract.
     If victim is obtunded or respiration is depressed, empty  the stomach by

                                   11

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    INTUBATION,  ASPIRATION, and LAV AGE,  using isotonic  saline
    or 5% sodium bicarbonate.  Because many pesticides  are  dissolved in
    petroleum distillates, emesis and intubation  of  the  stomach involve  a
    serious risk that solvent will be aspirated, leading  to chemical  pneu-
    monitis. For this reason:
    A. If the victim is unconscious or obtunded,  and  if facilities are at
       hand,  insert  an ENDOTRACHEAL TUBE  (cuffed,  if available)
       prior to gastric intubation.
    B. Keep  the  victim's  HEAD  BELOW  THE  LEVEL OF  THE
       STOMACH  during intubation  and lavage (Trendelenburg,  or  left
       lateral decubitus, with head of table tipped downward). Keep  the
       victim's head turned to the left.
    C. ASPIRATE PHARYNX as regularly as  possible to remove gagged
       or vomited stomach contents.
    After aspiration  of gastric contents and  washing of  stomach,  instill 30
    gm of ACTIVATED CHARCOAL in 3-4 ounces of  water through  a
    tube  to limit absorption of remaining toxicant.
    If bowel movement has not occurred in  4 hours, and if patient is fully
    conscious, give SODIUM SULFATE as a cathartic. Adult dose, includ-
    ing children over 12: 15 gm in 6-8  ounces of water.  For children under
    12, give 0.2 gm/kg body weight in 1-6 ounces of water.
 7.  DO NOT give morphine,  aminophylline, phenothiazines,  or reserpine.
 8.  Give  adrenergic amines ONLY if there is a specific indication.
 9.  CONVULSIONS are uncommon manifestations of  poisoning  by car-
    bamates.  If they  occur,  causes other  than direct carbamate  action
    should be considered: cerebral  anoxia, head trauma, mixed poisoning.
    Although not tested in these circumstances, DIAZEPAM  (Valium)  is
    probably the  anticonvulsant of  choice. Dosage  for adults  and children
    over 6 years  or  23 kg body weight is 5-10  mgm given  slowly IV (no
    more than half total dose per minute),  or intramuscularly (deep). Dosage
    for children under 6 years, or 23 kg body weight, is 0.1-0.2 mgnn/kg.
    Repeat  this dosage every  2-4 hours if needed  to control  convulsions.
    Be prepared  to  intubate  and to assist pulmonary ventilation mechani-
    cally if  respiration is depressed. Hypotensive reactions may also  occur.
10.  Persons  who have been  clinically  poisoned by  carbamate  pesticides
    should  not be  re-exposed to cholinesterase-inhibiting chemicals until
    symptoms and signs have  resolved completely and blood  cholinesterase
    activities have returned to at least 80% of pre-poisoned values. If blood
    cholinesterase was not measured  prior to poisoning,  blood  enzyme
    activities should reach at least minimum normal levels (Table 1) before
    the victim is  returned to a pesticide-contaminated environment.
11.  Do NOT administer atropine prophylactically  to workers exposed to
    carbamate insecticides.  It  is neither practical nor  medically sound  to
    do so.
                                  12

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            PARAQUAT,   DIQUAT,  AND
            MORFAMQUAT  (Dipyridyls)
CHEMICAL STRUCTURES
           PARAQUAT
                        2cr
                                            DIQUAT
                                                           -CH
                                                              2\
      CH
            CH
                             MORFAMQUAT
                                                           -CH.,
                                                            2CP
COMMON COMMERCIAL  PESTICIDE PRODUCTS
  The  highly polar  dipyridyl compounds are available  commercially as
halide and dimethyl sulfate salt solutions. Both are used as contact herbi-
cides; diquat  is particularly effective against water weeds. Plant  tissues and
soil particles  adsorb dipyridyl compounds strongly. Concentrates are  more
likely to cause poisoning than are  the more  dilute agents sold over the
counter.
  Paraquat products: Paraquat Cl, Dual Paraquat, EM-7217, Gramoxone S,
Weedol and Dextrone X are all concentrates containing 20% paraquat ion.
Preeglone extra and Gramonol are concentrate mixtures with other herbi-
cides. Ortho Spot Weed and Grass Killer contains 0.2% paraquat ion.
  Diquat products: Aquakill,  Aquacide, Heavy Duty Weed Control, Aqua-
tate, Aquatic Weed Killer, Reglone, Vegetrole, Watrol, and Di-Kill  Vegeta-
tion Killer are all packaged as concentrates. Preeglone extra is a  concentrate
mixture with paraquat.
  Morfamquat products: Morfoxone, PP-745.

TOXICOLOGY

  The dipyridyl compounds bind to, and injure, the epithelial tissues of the
skin, nails, eyes, nose,  mouth, and respiratory and gastrointestinal tracts.
Concentrated  solutions  cause inflammation and  sometimes necrosis  and
ulceration of mucosal linings.
  The toxicology of paraquat has been more  thoroughly  investigated  than
                                13

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that  of  the  other dipyridyls. Diquat  appears  to  be substantially  less toxic
than paraquat. Little is  known  of the effects of morfamquat.
  The consequences of ingestion of  paraquat concentrate  (which accounts
for nearly all of the mortality and serious morbidity from these  compounds)
are  unique.  Because  dosages  necessary to produce poisoning in  hurnans
vary widely, all  cases of ingestion  should  be  treated vigorously,  regardless
of estimated intake.
  For 24-72 hours, there is often very little indication  of systemic  toxicity.
Evidence of poisoning may be  limited to pain, vomiting,  and diarrhea from
irritation of the  gastrointestinal linings. At 48 to  72 hours, kidney damage
may be apparent from proteinuria, hematuria, and rising BUN and creatinine
levels. Liver damage is reflected in  hyperbilirubinemia, often associated with
increased serum GOT, OPT, alkaline phosphatase,  and  LDH enzyme activi-
ties.  From  72 hours to  as long as  14 days after ingestion, indications of a
diffuse toxic pneumonitis often appear.
  Histopathology of  the  pulmonary  lesion is complex,  commencing  with
intra-alveolar  edema and  hemorrhage,  then  rapid  proliferation  of  bron-
chiolar  epithelium  and  fibrous connective tissue.  Focal  atelectasis occurs,
possibly as a result  of impaired synthesis of pulmonary surfactant. The func-
tional consequence  is impaired gas exchange, due to patchy consolidation,
alveolar collapse and increased  airway resistance. The proliferation of fibrous
connective tissue is often progressive, and so  generalized as to cause death
in 1-3 weeks. Surviving patients should be  examined for evidence of residual
fibrosis  up  to 6 months  after  poisoning.  Injuries to liver  and kidnev are
commonly  reversible, ameliorating  even as the pulmonary lesion  worsens.
  Electrocardiographic  evidence of toxic myocarditis is commonly observed,
and  cranial nerve palsies have been  reported as toxic  manifestations.
  Lens cataracts have  been  reported in  laboratory  animals  given diquat
by mouth.

FREQUENT SYMPTOMS AND  SIGNS OF POISONING

  Skin  IRRITATION,  drying, and cracking  follow untreated  skin contact
with  paraquat.  DISCOLORATION  and  IRREGULARITY  of  FINGER-
NAILS commonly  occur  in workers  regularly exposed to  paraquat concen-
trates. Delayed  CONJUNCTIVITIS and KERATITIS  develop 12-48 hours
after contact with  the  eye. Inhalation of spray droplets irritates the nose
and throat,  and sometimes causes NOSEBLEED.
   FOLLOWING INGESTION of  paraquat concentrate, the earliest  symp-
toms and signs are due to mucosal  irritation and ulceration of the gastro-
intestinal  tract.  PAIN (oral,  substernal, abdominal),  VOMITING,  and
DIARRHEA (sometimes melena)  occur.  Generalized  MUSCLE  ACHING
is reported. Early symptoms are sometimes so mild  that vigorous treatment
is improperly delayed.
   From 48-72  hours, indications  of  renal and  hepatic insult appear. Albu-
 minuria, hematuria, pyuria, and elevated  BUN and creatinine occur.  OLI-
GURIA may develop,  and this signals severe  poisoning.  JAUNDICE and

                                  14

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elevations of  serum GOT,  GPT,  alkaline phosphatase  and LDH reflect
hepatocellular injury. The effects on liver and kidney are generally reversible.
Indications of lung injury usually appear  72-96 hours after exposure, but
may be delayed as long as 14 days. COUGH, DYSPNEA, and TACHYPNEA
often progress in the manner of a diffuse pneumonitis. In some cases, severe
PULMONARY EDEMA occurs and  persists for several days. The lung dis-
ease usually progresses to death.

CONFIRMATION OF  DIAGNOSIS
   Qualitative  and quantitative methods for paraquat  and diquat in  urine
are available at some toxicology laboratories  and at the Chevron Environ-
mental Health  Center,  225  Bush Street,  San Francisco,  California  94104,
telephone (415) 233-3737.

TREATMENT

  1.  Contaminated  SKIN must  be  FLUSHED  with  copious  amounts of
     water.  Material splashed in the EYES must be removed by PRO-
     LONGED IRRIGATION with clean  water. Eye contamination should
     thereafter be treated by an ophthalmologist.
  2.  INGESTION of ANY  DIPYRIDYL should be  treated promptly and
     vigorously to  LIMIT ABSORPTION from the  gastrointestinal  tract
     and ACCELERATE EXCRETION  of material already absorbed. Be-
     cause the absorption  of dipyridyls  from  the gut  is  relatively  slow,
     measures to  MINIMIZE  ABSORPTION offer the most promising op-
     portunity to  save the victim. These measures must be undertaken  even
     though the patient  is essentially  free of signs of systemic toxicity, and
     even when, by all accounts, the  ingested dose was probably small and
     was taken as long as 72 hours before treatment.
     A. LAVAGE THE STOMACH with at least 2 liters normal saline or
        5% sodium bicarbonate solution.  With st'" ,ach tube still in place,
        introduce a slurry of 8-10  ounces of  ADSORBENT,  allowing as
        much time as necessary for the material to be accommodated  with-
        out overdistension of the stomach. Suitable adsorbents are, in  order
        of  effectiveness: Fuller's  Earth *,  30% suspension, and bentonite
        (or Montmorillonite),  7% suspension. These agents effectively bind
* Optimal mesh 100-200. Sources of adsorbents are as follows:
    Sigma Chemical Company,  3500  Dekalb Street, St.  Louis,  Missouri
       63178
    Robinson's Bentonite U.S.P., Cat. No.  1138, Robinson  Laboratories,
       Inc., San Francisco, California 94104
    Robinson's Fuller's Earth U.S.P.,  Cat.  No.  1343,  Robinson Labora-
       tories, Inc., San Francisco, California 94104
    U.S.P. Volclay Bentonite, American Colloid Company, Skokie, Illinois
    Emathlite VMP 600, Mid-Florida  Mining Co., Lowell, Florida 32663

                                  15

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      dipyridyls with which they come in contact in the gut. Activated char-
      coal is less effective, but  should be used if other agents are not
      immediately available. Allow about one hour  for  the adsorbent to
      contact the toxicant before  administering  SODIUM SULFATE as
      a cathartic (adults,  12 years and older: 15 gm in  6-8  ounces of
      water; children under 12: 0.2 gm/kg body weight  in 1-6 ounces of
      water). Repeat  dosage  of  Fuller's Earth  (or other adsorbent  if
      Fuller's Earth is not available) by mouth every 4 hours for at least
      12 complete  doses.  Repeat  saline catharsis  if continuing  bowel
      movements do not occur.
   B. Institute a regimen of FORCED DIURESIS. Put  a  retention  cath-
      eter in place to insure accurate monitoring of  urine output. Inquire
      into possible  medical limitations  to the victim's ability to tolerate
      high fluid  loads.  Examine the urine sediment  to  assess  likelihood
      that dipyridyl injury to  the  kidneys has  already reduced  tolerance
      to fluid infusion by severe tubular injury.
      In  the absence  of contraindications,  INFUSE  intravenously, in
      rotation,  solutions of either  glucose,  electrolyte or mannitol. As
      time progresses, particular electrolyte  solutions will  be required to
      maintain normal extracellular fluid composition.
      Give parenteral  FUROSEMIDE  (Lasix) by slow intravenous injec-
      tion to sustain diuresis.  Adult dose: 20-40 mgm every 2-6 hours.
      MONITOR FLUID BALANCE  AND  BLOOD ELECTROLYTE
      CONCENTRATIONS regularly,  and look for signs of fluid overload
      (basilar rales, venous distension, high  central venous pressure) that
      would warn of excessive fluid accumulation.
       If circumstances do not permit  vigorous forced diuresis undertake
       PERITONEAL  DIALYSIS or  EXTRACORPOREAL  HEMO-
      DIALYSIS.  These measures appear to offer  little advantage  over
      forced diuresis in victims able to tolerate  high rates of intravenous
      fluid infusion. Hemodialysis with ultrafiltration is  reported to offer
       effective removal  of paraquat from the circulating  blood.
       Measure  dipyridyl in urine to estimate levels of remaining toxicant.
3.  DO  NOT ADMINISTER SUPPLEMENTAL OXYGEN, unless arterial
   pO2 drops below 60-70 mm Hg. Increased levels of alveolar oxygen
   accelerate the pathologic process caused by dipyridyls.
4.  SUPEROXIDE DISMUTASE (Truett Laboratories) is an enzyme from
   bovine erythrocytes which, by virtue of its free radical scavenging prop-
   erty, represents a rational  antidote  for dipyridyl poisoning.  Tests  of
   antidotal  power in rats have yielded very promising results.  The value of
   the  material  in treating human poisonings has not  yet  been reported. It
   can  be given both by aerosol  and  intravenously,  and appears  to  be
   nontoxic.
5.  Corticosteroids  have  usually been  administered   in  human  poisoning
   cases. While  they have not influenced the outcome  adversely,  neither
   have they proven definitely beneficial. Immunosuppressive drugs  have
   been tried in a few cases without apparent  benefit. In one case, a regimen

                                  16

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   of AZATHIOPRINE and POTASSIUM AMINOBENZOATE appears
   to have been effective. Laithwaite, J.A., Brit. J. Clin. Pract. 30(3): 71-73
   March 1976)
6.  There is some evidence that expectorants (especially ammonium chloride
   and potassium iodide) may  be of therapeutic value  in minimizing  the
   reduction  in lung surfactant  activity that is characteristic  of  paraquat
   poisoning.
                                 17

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       CHLOROPHENOXY  COMPOUNDS

GENERAL CHEMICAL  STRUCTURE
                         H
                         C
                         H
OH
                             N
                                               or
COMMON COMMERCIAL PESTICIDE PRODUCTS

  2,4-D (Weedone), 2,4,5-T  2,4,5-TP, Silvex  (Kuron), 2,4-DB (Butyrac,
Butoxone),  erbon, Fenac, 2,4-DEP,  MCPA, MCPB, MCPP (Mecoprop),
Weedestron, Esteron,  Estone,  Dacamine,  Weed-B-Gon,  Weed-No-More,
Weed-Out, Ded-Weed, Weed or Brush-Rhap, Broadleaf Weed Killer, Dande-
lion Killer, Vegetation Killer, Chickweed and Clover Killer. Several hundred
herbicide preparations include one or more chlorophenoxy compounds. They
can usually be identified in the active ingredient description  on the product
label.

TOXICOLOGY
  The chlorophenoxy acids, salts, and esters are mildly to severely irritating
to skin, eyes, and respiratory and gastrointestinal linings. They are  absorbed
across  the gut wall,  the lung,  and  the skin. They are not  significantly  fat
storable: excretion occurs within hours, or  at most days, primarily in  the
urine.
  These compounds  apparently have very  low toxic potential for most indi-
viduals. Human  subjects have tolerated 0.5 gm ingested doses daily for 2-4
weeks  without adverse  effects. Paradoxically, several cases of peripheral
neuropathy have been reported in workers after  seemingly minor exposures
to 2,4-D.  Whether these  individuals  were peculiarly predisposed, or were
exposed concurrently to other unidentified neurotoxic materials, is  not known.
In a few individuals, local depigmentation  has apparently resulted from pro-
longed and repeated  dermal contact with chlorophenoxy materials.
  Given  in large  doses  to experimental  animals,  2,4-D causes  vomiting,
diarrhea, anorexia, weight loss, ulcers of the mouth and pharynx, and toxic
injury  to the liver, kidneys, and central nervous  system. Myotonia (stiffness
and incoordination of hind extremities) develops in some species and is  ap-
parently 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. A single victim of acci-

                                 18

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 dental ingestion of over 7 gm of  2,4-D exhibited direct toxic  damage  to
 skeletal muscle, manifest as myoglobinuria and creatinuria. Other chemicals
 in the ingested formulation may have  contributed  to the unusual pathology
 in this  case. In another isolated instance of extreme  dosage, convulsions
 apparently occurred before death.

 FREQUENT  SYMPTOMS AND SIGNS OF INJURY AND  POISONING

   IRRITATION of the skin  follows  excessive  contact with many chloro-
 phenoxy compounds. Protracted inhalation of spray is likely to  irritate the
 nose, eyes, throat and bronchi, causing disagreeable local  BURNING  SEN-
 SATIONS and COUGH. Prolonged inhalation has  also caused DIZZINESS
and ATAXIA, usually of a transient nature.
  WHEN INGESTED,  these  compounds IRRITATE the MOUTH  and
THROAT, and usually  cause  enough gastrointestinal  irritation  to induce
prompt EMESIS. CHEST PAIN from esophagitis  is  common. ABDOMINAL
PAIN and TENDERNESS and DIARRHEA usually ensue. Absorption of
large  quantities of  chlorophenoxy  herbicide  may  produce FIBRILLARY
MUSCLJE TWITCHING, SKELETAL  MUSCLE TENDERNESS,   and
MYOTONIA (stiffness of muscles of extremities).  Respiratory insufficiency
from muscle  weakness apparently occurred in one  victim  of accidental poison-
ing, although poisoning in this  case may  have involved  additional  toxicants.

 CONFIRMATION OF  DIAGNOSIS
   Gas-liquid chromatographic methods are available for detecting  and meas-
 uring many  of the  chlorophenoxy compounds in urine. These analyses are
 useful in confirming and assessing the  magnitude of  toxicant  absofption.
 Urine samples should be collected as soon as possible after exposure because
 the herbicides  may be almost completely excreted in 24-72 hours,  depending
 on the dose. Analyses can be performed at special  laboratories operated by
 state  health  departments,  universities,  agricultural  research facilities,  com-
 mercial chemical companies, and the U.S. Environmental Protection Agency.
   Treatment should not be delayed pending confirmation of the  causative
 agent, if there is a strong circumstantial basis for the diagnosis.

 TREATMENT

  1.  BATHE  and SHAMPOO with soap and  water to remove chemicals
     from the  skin and hair. Individuals with chronic skin  disease or known
     sensitivity to  chemicals should either avoid using these herbicides or
     should  take extraordinary  measures to avoid direct contact.
  2.  FLUSH contaminating chemicals from the eyes with copious amounts of
     clean water for 10-15 minutes.
  3.  If  symptoms of illness occur during or following inhalation of  spray,
     REMOVE the victim FROM CONTACT with the material for at  least
     2 days. Allow  subsequent  use of  chlorophenoxy  compounds only if
     effective respiratory protection is practiced.

                                19

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4.  When chemicals of  this class  have  been INGESTED,  spontaneous
   emesis usually occurs,  and may empty the stomach  as  effectively as
   intubation and lavage.  If  vigorous  emesis has not occurred, and  IF
   VICTIM IS FULLY ALERT, induce EMESIS with SYRUP of IPECAC
   (adults 12 years and older, 30 ml; children under 12 years, 15 ml).
   A. If consciousness level is depressed, an effect of the solvent petroleum
       distillates and/or other pesticides should be suspected. In this case,
       empty the  stomach  by  INTUBATION,  ASPIRATION,  AND
       LAVAGE, using all available means to avoid aspiration of vomitus:
       Trendelenberg or left lateral decubitus position,  frequent aspiration
       of the pharynx, and, in  unconscious  victims,  trachea!  intubation
       (using a cuffed tube), prior to gastric intubation.
    B. After emesis or aspiration of the stomach and washing with isotonic
       saline or sodium bicarbonate, administer or instill  30  gm  of ACTI-
       VATED CHARCOAL in 3-4 ounces  of water  to limit  absorption
       of remaining toxicant.
    C. If the irritant properties  of the toxicant  fail  to produce  a  bowel
       movement  in  4  hours, and if the patient is fully conscious,  give
       SODIUM SULFATE  (Glauber's  Salts)  as a cathartic  (adults 12
       years and older, 15 gm in 6-8 ounces  of water; children under  ]2,
       0.2 gm/kg of body weight in 1-6 ounces of water).
    D. If absorption of as  much  as 0.5  gm may have occurred in an adult
       (or about 0.02 gm/kg in  children  under 12 years), administer glu-
       cose  and  electrolyte solution intravenously to  accelerate excretion
       of toxicant. Observe  the  patient for renal irritation  (albuminuria,
       hematuria); liver  injury  (serum  bilirubin,  alkaline   phosphatase,
       serum LDH, GOT and GPT);  gastrointestinal  ulceration (melena);
       leukopenia (WBC and differential); myalgia and myotonia (manifest
       as stiffness  and incoordination); and  peripheral neuropathy (par-
       esthesiae, pain, hypesthesia and  paresis of  the extremities).
                                 20

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         NITROPHENOLIC  HERBICIDES
GENERAL  CHEMICAL STRUCTURE

                          NO,
                               O—H(or ESTER)
              (ALKYL)    (ALKYL)

COMMON COMMERCIAL  PESTICIDE PRODUCTS

  Dinitrophenol (Chemox PE), dinitroorthocresol  (DNOC, DNC,  Sinox),
Dinoseb (DNBP, DN-289), dinosam (DNAP), DN-111 (DNOCHP), dinoprop,
dinoterbon, dinoterb,  dinosulfon, binapacryl (Morocide,  Endosan, Ambox,
Mildex), dinobuton, dinopenton.

TOXICOLOGY

  These materials should be  regarded as highly toxic to humans and  ani-
mals.  Most nitrophenols and  nitrocresols are well  absorbed from the  gas-
trointestinal tract,  across the skin, and by the lung when very fine droplets
are inhaled. Except in a few sensitive individuals, they are only moderately
irritating to the skin. They usually produce a yellow stain wherever  contact
occurs. Like other phenols, they are  toxic to the liver, kidney, and nervous
system. Basic mechanism of toxicity is a stimulation of oxidative metabolism
in cell mitochondria,  by  interference with  the  normal  coupling  of carbo-
hydrate  oxidation  to phosphorylation reactions.  Increased oxidative  metab-
olism  depletes body  carbohydrate and  fat stores and  leads  to pyrexia,
tachycardia,  and  dehydration. Most severe poisonings from  absorption of
these  compounds have occurred in workers who were concurrently exposed
to hot environments. Direct action on the brain causes  cerebral edema, mani-
fest clinically as a toxic  psychosis  and sometimes  as  convulsions. Liver
parenchyma  and renal tubules show degenerative changes. Albuminuria,
pyuria, hematuria, and increased BUN are often prominent signs of renal
injury. Agranulocytosis has occurred following large doses of dinitrophenol.
  Cataracts have occurred in some chronically poisoned  laboratory  species.
This is a possible, but as  yet unconfirmed, hazard in humans.
  Death in  nitrophenol poisoning is  followed  promptly by intense rigor
mortis.

FREQUENT SYMPTOMS AND  SIGNS OF POISONING

  YELLOW STAINING of skin and hair signify contact with a nitrophenolic
chemical. Staining of the sclerae and urine indicate  absorption of potentially
                               21

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toxic  amounts. PROFUSE SWEATING,  HEADACHE,  THIRST, MAL-
AISE, and LASSITUDE are the  common  early symptoms of poisoning.
WARM,  FLUSHED, SKIN,  TACHYCARDIA,  and FEVER  characterize
a serious degree of poisoning.  APPREHENSION, restlessness, anxiety, manic
behavior, or unconsciousness  reflect severe cerebral injury. Cyanosis, tachy-
pnea  and dyspnea occur  as a consequence of extreme stimulation of metab-
olism, pyrexia, and tissue anoxia. Weight loss occurs in persons chronically
poisoned at low dosages.

CONFIRMATION OF DIAGNOSIS

  Unmetabolized nitrophenols  and nitrocresols can be  identified spectro-
photometrically in the serum and urine  at concentrations well  below those
necessary to cause poisoning. Many laboratories can also analyze for these
compounds by gas-liquid chromatography. If poisoning is probable, do not
await confirmation before commencing treatment.

TREATMENT
  1. WASH contaminated SKIN and HAIR promptly with soap and water.
 2. FLUSH chemical from EYES with  copious amounts of clean water.
 3. IN EVENT OF SYSTEMIC POISONING:
     A.  REDUCE  BODY TEMPERATURE BY PHYSICAL  MEANS.
        Sponge baths and low-temperature blankets probably offer the best
        opportunity for survival of poisonings by these agents. In  fully con-
        scious patients, administer cold, sugar-containing liquids by mouth,
        as tolerated.
    B.  Administer  OXYGEN  continuously  by  mask  to minimize tissue
        anoxia.
    C.  Administer INTRAVENOUS FLUIDS at maximum tolerated rates
        to enhance urinary excretion of  toxicant and to support physiologic
        mechanisms for heat loss. Monitor blood electrolytes and  sugar, ad-
        justing IV infusions  to  stabilize  electrolyte concentrations.
     D. Administer  SEDATIVES if necessary to control  apprehension and
        excitement. Amobarbital or PENTOBARBITAL, 100-200 mgm IM
        or slowly IV, every 4-6 hours, may be needed in adults (child's dose:
        up  5  mgm/kg body weight). Although not previously  used in this
        type of poisoning, DIAZEPAM (Valium) should be of value: adult
        dose 5-10 mgm  intramuscularly (deep), or slowly TV. Dosage  for
        children under 6 years or 23 kg: 0.1-0.2 mgm/kg. Repeat every 2-4
        hours as needed.
        CAUTION:  Be prepared to counteract  respiratory depression and
                    hypotension,  which may occur following administra-
                    tion of anticonvulsants.
     E. If toxicant has  been INGESTED, the stomach  must  be emptied.
        If victim is alert and respiration is not depressed, give SYRUP  OF
        IPECAC to induce  vomiting (adults  12 years  and older: 30  ml;

                                22

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   children under 12: 15 ml).
   CAUTION:  OBSERVE the victim closely AFTER  administering
                IPECAC. If consciousness level declines, or if vomit-
                ing has  not occurred in 15 minutes, proceed immedi-
                ately to INTUBATE and LAV AGE the stomach.
   Following emesis, have victim drink a suspension of 30 gm ACTI-
   VATED  CHARCOAL in 3-4 ounces of water to bind toxicant re-
   maining in the gastrointestinal tract.
   IF VICTIM IS NOT FULLY ALERT, empty the stomach immedi-
   ately  by  INTUBATION,  ASPIRATION,  and  LAVAGE, using
   isotonic saline or 5%  sodium bicarbonate.  Because these pesticides
   are usually dissolved in petroleum distillates, emesis and intubation
   of the stomach involve a serious risk that solvent will be aspirated,
   leading to chemical pneumonitis. For this reason:
   (1) If the victim is unconscious or obtunded, and if facilities are
       at hand, insert an ENDOTRACHEAL TUBE (cuffed, if avail-
       able) prior to gastric intubation.
   (2) Keep the victim's HEAD BELOW THE  LEVEL OF THE
       STOMACH during intubation and lavage (Trendelenburg, or
       left  lateral  decubitus, with head of table  tipped  downward).
       Keep the victim's head turned to the left.
   (3) ASPIRATE  PHARYNX  as  regularly as possible to  remove
       gagged or vomited stomach contents.
   After  aspiration  of gastric  contents and washing  of stomach, instill
   30 gm of  ACTIVATED  CHARCOAL  in 3-4 ounces  of water
   through the  stomach tube to  limit  absorption of remaining toxicant.
   Do NOT instill milk,  cream or other materials containing vegetable
   or animal fats, as these are likely  to enhance  absorption.
   If bowel  movement has not  occurred in 4 hours, and if patient is
   fully conscious,  give  SODIUM SULFATE (Glauber's  Salts)  as  a
   cathartic  (adults  12 years and older: 15 gm in 6-8 ounces of water;
   children under 12: 0.2 gm/kg body weight in 1-6 ounces of water).
F. DO NOT administer  atropine, aspirin or other antipyretics to con-
   trol fever. Animal tests indicate that aspirin  enhances, rather than
   reduces,  the toxicity of nitrophenolic and nitrocresolic compounds.
G. During  convalescence,  administer  high-calorie,  high-vitamin  diet
   to facilitate  repletion  of body fat and carbohydrate stores.
H. Discourage  subsequent  contact with  the  toxicant for at  least  4
   weeks, to allow full restoration of  normal metabolic processes.
                            23

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   PENTACHLOROPHENOL  OR  SODIUM
             PENTACHLOROPHENATE
CHEMICAL STRUCTURE

                        Cl   Cl
\    //
  \ _ /J
                    °
                                       (or Na)
                       Cl    Cl
COMMON COMMERCIAL PESTICIDE PRODUCTS

  PCP, Dowicide-7, Penchlorol,  Pentacon,  Penwar, Weedone,  Veg-I-Kill,
Wood Preserver, Wood Tox 140, Purina Insect Oil Concentrate, Gordon
Termi Tox,  Usol Cabin Oil, Certified Kiltrol-74 Weed Killer, Ciba-Geigy
Ontrack OS 3,  4 or 5, Ortho Triox Liquid Vegetation Killer, Black Leaf
Grass Weed and Vegetation Killer Spray.
  Pentachlorophenol has many uses as a weed killer, defoliant, wood pre-
servative, germicide, fungicide, and molluscicide. It is an ingredient of many
other formulated mixtures sold for one or more of these purposes.

TOXICOLOGY

  Pentachlorophenol irritates the skin, eyes, and upper respiratory mucous
membranes.  It is efficiently absorbed across the skin, the lung, and the gastro-
intestinal lining. Like the nitrophenolic compounds, it stimulates oxidative
metabolism of tissue cells by uncoupling oxidative processes from the normal
stepwise phosphorylation reactions. In common with other phenols, it is toxic
to the liver,  kidney, and central  nervous system. Impurities in the technical
formulation may well be responsible for chloracne.
  The majority of  severe poisonings have occurred in workers  exposed to
hot environments.  However, a  major  epidemic of poisoning occurred in
newborn infants who absorbed PCP from treated diapers. Dehydration and
metabolic acidosis  are  important features of poisoning in children.
  Albuminuria, glycosuria, and  elevated BUN reflect  renal  injury. Liver
enlargement has been observed in some cases.  Anemia and leukopenia have
been found  in chronically exposed workers, but leucocytosis  is  more com-
monly found in acute poisoning.

FREQUENT SYMPTOMS AND SIGNS OF  POISONING

  IRRITATION of nose, throat, eyes, and skin is the most common symp-
tom of exposure to PCP. Severe or protracted exposure may  result in a
CONTACT DERMATITIS. Intensive occupational exposure has resulted in
chloracne.

                               24

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  PROFUSE SWEATING, HEADACHE, WEAKNESS, and NAUSEA are
the most consistent presenting symptoms of systemic poisoning by absorbed
PCP. FEVER is usually present but may be minimal or absent. TACHY-
CARDIA, TACHYPNEA, and  PAIN in the CHEST and ABDOMEN are
often prominent. THIRST is usually intense, but may be masked by nausea
and vomiting. DECLINING MENTAL ALERTNESS may progress to stupor
and/or convulsions. Protracted  exposure  results  in  WEIGHT LOSS  from
increased basal metabolic rate.

CONFIRMATION OF DIAGNOSIS
  PCP can be measured in blood,  urine, and  adipose tissue by gas-liquid
chromatography. A few parts per billion can usually be found in the blood
and urine of persons having no known exposure. Based on studies of persons
occupationally exposed to PCP, symptoms of systemic toxicity probably do
not appear in adults until blood and urine concentrations  reach at least one
part per million (0.1 mgm %, or 1,000 parts per billion).
  If poisoning is strongly suspected on grounds of exposure history, symptoms
and signs, do not postpone treatment until diagnosis is confirmed.

TREATMENT

 1. BATHE and  SHAMPOO contaminated SKIN and  HAIR promptly
    with soap and water.
 2. FLUSH chemical from EYES with copious amounts of clean water.
 3. IN EVENT OF SYSTEMIC POISONINGS:
    A. REDUCE BODY  TEMPERATURE  BY  PHYSICAL  MEANS.
        Sponge baths and low-temperature blankets  probably offer the best
        opportunity for survival of poisonings by these  agents.  In fully
        conscious  patients, administer cold,  sugar-containing  liquids  by
        mouth, as tolerated.
    B. Administer OXYGEN continuously by mask  to  minimize  tissue
        anoxia.
    C. Administer INTRAVENOUS FLUIDS at maximum tolerated rates
        to enhance urinary excretion of toxicant and to support physiologic
        mechanisms for heat  loss.  Monitor blood  electrolytes  and sugar,
        adjusting IV infusions  to stabilize electrolyte concentrations.
    D. Administer SEDATIVES if necessary  to control apprehension and
        excitement. Amobarbital or  pentobarbital,  100-200 mgm IM  or
        slowly  IV,  every 4-6 hours may be needed. (Children's dosage: 5
        mgm/kg.) Diazepam,  10 mgm intramuscularly, should be valuable,
        although its use has not been reported  in  this type of poisoning.
        (Children's dosage: 0.1-0.2 mgm/kg.)
        CAUTION:  Be prepared to assist pulmonary ventilation mechani-
                    cally in event of respiratory depression, and  to  coun-
                    teract any hypotensive reaction.
                                25

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E. If toxicant has been INGESTED, the stomach must be emptied. If
   victim is  alert and respiration is not  depressed, give SYRUP  OF
   IPECAC  to induce vomiting. (Adults, 12  years and older: 30  ml;
   children under 12: 15 ml.)
   CAUTION:  OBSERVE the  victim closely AFTER administering
                IPECAC. If consciousness  level  declines, or if vomit-
                ing has  not occurred in 15 minutes,  proceed immedi-
                ately to INTUBATE the stomach.
   Following emesis, have victim drink a suspension of  30 gm ACTI-
   VATED CHARCOAL in 3-4 ounces of water to bind toxicant re-
   maining in the gastrointestinal tract.
   If victim  is  not fully  alert,  empty  the stomach  immediately by
   INTUBATION,  ASPIRATION,  and  LAVAGE,  using   isotonic
   saline or 5% sodium  bicarbonate. Because these pesticides are usu-
   ally  dissolved  in  petroleum distillates, emesis and intubation of the
   stomach involve a serious risk that solvent will  be aspirated, leading
   to chemical pneumonitis. For this reason:
   (1)  If  the victim is  unconscious or obtunded, and if facilities  are
        at  hand,  insert an ENDOTRACHEAL TUBE  (cuffed, if  avail-
        able) prior to gastric intubation.
    (2)  Keep the victim's HEAD  BELOW THE LEVEL OF  THE
        STOMACH during intubation  and lavage (Trendelenburg,  or
        left lateral decubitus, with head of table tipped  downward).
        Keep the victim's head turned to the left.
    (3)  ASPIRATE PHARYNX as  regularly as possible  to remove
        gagged or vomited stomach contents.
   After aspiration of gastric  contents and  washing of stomach,  instill
   30  gm of ACTIVATED  CHARCOAL in 3-4  ounces of  water
   through a stomach tube to limit absorption of remaining  toxicant.
   Do  NOT instill milk, cream, or other materials containing vegetable
   or animal fats which are likely to enhance  absorption.
   If bowel  movement has not  occurred  in 4  hours,  and if patient is
   fully conscious,  give SODIUM SULFATE (Glauber's Salts)  as  a
    cathartic  (adults  12 years and older: 15  gm in 6-8  ounces of water;
   children under 12: 0.2 gm/kg body weight in 1-6  ounces of water).
F. DO NOT administer  atropine, aspirin or  other antipyretics to control
    fever.
G. During  convalescence, administer  high-calorie,  high-vitamin diet
   to facilitate repletion of body fat and carbohydrate stores.
H. Discourage subsequent contact with the toxicant for at least 4 weeks,
   to allow full restoration of normal metabolic processes.

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        ORGANONITROGEN  HERBICIDES
       CLASSES OF ORGANONITROGEN HERBICIDES AND
              COMMON COMMERCIAL PRODUCTS
      X = HALOGEN

UREA DERIVITIVES
                                        R = ALKYL
         o = c
                 monuron (Monurex, Telvar)
                 diuron (Di-on,  diurex,  Karmex,  Von-
                  duron)
                 linuron (HOE-2810, Afalon, Lorox. Sarc-
                  lex)
URACIL DERIVITIVES

               H
       H,C — C
         X — C
             \
               C
               II
               0
 C = 0
 I    /CH3
 N-C^-H
'    \C2H5
                bromacil (Borea, Hyvar X, Hyvar X-L,
                  Borocil IV, Urox HX or B, Isocil)
                terbacil (Sinbar)
ACETANILIDE DERIVITIVES
   '	MR)
   Isopropyl or
   Methoxymethyl

\    "
 NC —C—Cl
  II   H
                                propachlor (Ramrod),
                                alachlor (Lasso)
                                propanil (DPA, Propanex, Stam F-34)
ACETAMIDE COMPOUNDS
         Allyl —N
/

\
                   Allyl
                      H
                   C —C—Cl
                   II   H
                   0
               alhdochlor (Randox, CDAA)
                               27

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 s-TRIAZINE COMPOUNDS
^
N
H I
N— C
fOR
X or ISR
1
>\
N
II H
C — N
 PICOLINIC ACID DERIVITIVES
                                       atrazine (Aatrex. Atranex, Gesaprim, Pri-
                                         matol A)
                                       simazine (Princep, Primatol S,  Simanex,
                                         Gesatop)
                                       propazine  (Milogard, Gesamil,  Primatol
                                         P)
                                       prometone (Pramitol, Gesafram, prome-
                                         ton)
                                       atraton (Atratone)
                                       prometryn (Caparol, Gesagard,  Primatol
                                         Q, Prometrex)
                                       ametryn (Evik, Ametrex, Gesapax)
                                       desmetrjn (Semeron)
                                       terbutryn (Igran, Shortstop E)
                                       cyanazine (Bladex, Scogal)
                                       cyprazine (Outfox)
     Cl
 —OH
               U Cl
          NH,
                                       picloram (Tordon, Borolin)
 CARBAMATE COMPOUNDS
     o
— N—C —0-
 CH,
  r
-CH
  I
 CH,
chlorpropham (Chloro IPC, CIPC, Fur-
loe)
 Liquid technical  formulations  of these products  are usually dissolved
 in   petroleum distillates.

TOXICOLOGY

  Adverse effects have occurred only rarely as a result of human or animal
contact with these  herbicides. LD50  values  for most compounds are in the
thousands  of mgm per kg. A few  are  in the range of several hundred mgm
per kg; the lowest  LDM value listed  is 180  mgm per kg for cyanazine.
                                      28

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   Certain of these chemicals, however, irritate the skin  and mucous mem-
 branes (uracil,  acetanilide,  acetamide  and picolinic  acid compounds),  and
 particular classes can cause  sensitization (acetanilides and acetamides).

   When  administered to experimental animals  at  extreme dosage  levels
 some of these chemicals can  injure the nervous  system, liver,  kidney,  and
 capillary  membranes.  Large  doses  of triazines  have caused  anemia  and
 impaired  adrenal  function.  No such effects have been observed in persons
 exposed to the herbicides occupationally, or by accidental ingestion. Absorbed
 herbicide is not stored in the  body; the native chemical and metabolites are
 excreted primarily through  the urine.  Ingestion of large  quantities  of  any
 of these materials is likely to  cause gastrointestinal irritation. In such cases,
 the hazard of the petroleum distillate  solvent may equal or exceed hazards
 presented by the active herbicidal ingredients.

 SYMPTOMS AND SIGNS OF UNDUE EXPOSURE

   IRRITANT  EFFECTS on skin and mucous  membranes are the most
 common reactions  to these  chemicals. Large  ingestions  can cause nausea,
 vomiting,  abdominal distress, and diarrhea. SENSITIZATION to acetanilides
 or acetamides can result in protracted DERMATITIS.

 CONFIRMATION OF ABSORPTION

  Particular industrial, university,  and government laboratories  can detect
 some  compounds or metabolites in the  urine of persons who have absorbed
significant amounts. The laboratories can be reached  through health depart-
ments or poison  control centers.

TREATMENT

  1.  FLUSH the  chemical  from the eyes with copious  amounts of  clean
      water. Severe contamination  may require specialized ophthalmologic
      attention.

  2.  WASH contaminating  herbicide from the skin  with soap  and water.
      Severe irritation may require medical attention.  Persons who become
      sensitized  may  require  specialized  medical  management  with  anti-
      inflammatory agents. Thereafter they will need to take  stringent pre-
     cautions to avoid contact with the chemical.

  3. Considering the low inherent toxicities of these herbicides,  and the
      risk  of hydrocarbon pneumonitis when the stomach  is intubated  or
      emesis is induced, INGESTIONS  of these chemicals KNOWN TO IN-
     VOLVE LESS THAN 10 MGM PER KG body weight are probably
      treated best by administering 30-60  gm of activated charcoal in 5-10
     ounces of  water. If diarrhea  has not already  developed,  follow the
     charcoal administration in 4 hours with SODIUM SULFATE catharsis:
      adult dose  (over 12 years of age), 15 gm  in 6-8 ounces of water; for
     children under 12, 0.2  gm per kg in  1-6 ounces of water.
                                  29

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4.  Ingestions of more than 10 mgm per kg body weight, especially when
   ingestion  occurred  less  than  an hour before treatment,  should  be
   managed by EVACUATING the STOMACH:
   A. If victim is alert and respiration is not depressed give SYRUP of
      IPECAC: 30 ml for adults;  15 ml for children under 12 years.

      CAUTION:  OBSERVE the victim closely after administering ipecac.
                  If consciousness level  declines, or if  vomiting has not
                  occurred  in 15 minutes,  proceed immediately to  IN-
                  TUBATE, ASPIRATE and LAVAGE the stomach with
                  isotonic saline or sodium bicarbonate solution.
     Following emesis, have victim drink a  suspension of 30 gm ACTI-
     VATED CHARCOAL in  3-4 ounces  of water to  limit  toxicant
     absorption.

   B. If victim is not fully alert, or if  respiration is depressed, empty the
      stomach  immediately  by  INTUBATION,  ASPIRATION,  and
      LAVAGE, using  isotonic  saline or 5%  sodium  bicarbonate.  Be-
     cause these herbicides  are usually dissolved in petroleum distillates,
      emesis and  intubation of the stomach involve  a serious  risk of
      chemical  pneumonitis  if solvent  is  aspirated. For this reason:
      (1) If the victim is unconscious or obtunded, and if facilities are at
         hand, insert an ENDOTRACHEAL TUBE (cuffed,  if available)
         prior to gastric intubation.
      (2) Keep  the victim's HEAD BELOW  THE LEVEL OF THE
         STOMACH during intubation and lavage (Trendelenburg, or left
         lateral decubitus,  with  head end  of table tipped  downward).
         Keep  the head turned to the left.
      (3) ASPIRATE  PHARYNX as  regularly as possible  to  remove
         gagged or  vomited stomach contents.

      After aspiration of gastric contents and washing of stomach, instill
      30 gm of ACTIVATED CHARCOAL in 3-4 ounces  of water by
      way  of stomach tube to limit absorption of remaining toxicant.  Do
      NOT instill  milk, cream or other substances containing  vegetable or
      animal fats, as they  may  enhance toxicant  absorption. If bowel
      movement has not occurred in 4 hours, and if patient  is fully
      conscious,  give  SODIUM SULFATE  as a cathartic.
                               30

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         DIMETHYLDITHIOCARBAMATE
                      COMPOUNDS*
GENERAL CHEMICAL  STRUCTURE
          (CH,)2-N-C-S
                       II
COMMON COMMERCIAL PESTICIDE  PRODUCTS

  Tetramethyl thiuram disulfide:
Thiram  (Arasan,  Thiramad,  Thirasan, Thylate,  Tirampa,  Pomasol forte,
TMTDS, Thiotex, Fernasan, Nomersan, Tersan, TUADS)
  Metallodimethyldithiocarbamates:
Ziram, Pomasol Z forte (zinc), Ferbatn (iron), Vapam (sodium).

TOXICOLOGY

  Many  compounds of this class are irritants and  sensitizers.  They may
exacerbate  allergic skin  and respiratory  disease, and  sensitize  otherwise
normal individuals to subsequent contact with similar chemicals.
  The two types of  fungicide  listed above are  metabolized  in  a  manner
similar to disulfiram (tetraethyl  thiuram disulfide) that is  used to condition
individuals against beverage alcohol. The  molecule is first cleaved to yield
two of alkyl  dithiocarbamate, then further degraded to dialkyl  amine  and
carbon disulfide. The metabolites are  powerful inhibitors of multiple sulf-
hydryl enzymes in the liver and  CNS. CS2  is neurotoxic in its own right.  To
this extent, the  toxicology of these fungicides  probably  resembles  that of
disulfiram,  whose effects  have been  most  thoroughly explored. Animal  ex-
periments indicate that thiram is more toxic than the medicinal disulfiram.
Even  so, systemic reactions (excluding irritation and sensitization)  to  the
fungicides themselves have been rare.
  The systemic toxicologic effects of these compounds  fall into  two cate-
gories: those  following absorption of toxicant alone,  and  those resulting
from  ingestion of alcohol following absorption of a dithiocarbamate com-
pound.
  Given  to laboratory animals in extreme doses, disulfiram itself  causes
gastrointestinal irritation,  demyelinization  of  the central  nervous  system,
and necrosis  of the  liver, spleen, and kidney  parenchyma.  Functional  and
anatomical CNS  damage  has been  demonstrated in rats on  high  chronic
dietary intakes of the iron and zinc  dimethyldithiocarbamates. Peripheral

* The ethylene  bisdithiocarbamate  fungicidal  compounds  are  chemically
  similar to those considered here,  but are metabolized in different ways
  and have somewhat different toxicologic properties.
                                 31

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neuropathy and psychotic reactions have occurred  in  alcohol-abstinent in-
dividuals on disulfiram regimens (ingestion of several hundred mgm daily).
A possible role of the metabolite carbon disulfide has been suspected in these
neurotoxic reactions.
  Illness following combined intake of  disulfiram and  alcohol is due  pri-
marily to inhibition of liver enzymes necessary for oxidation of acetaldehyde
to acetic acid.  Peripheral vasodilation is the main pathophysiologic  feature
of the disulfiram-alcohol reaction,  presumably  due  to  high tissue levels of
acetaldehyde. This  may occasionally lead to shock,  and even more rarely,
to myocardial ischemia, cardiac arrhythmias, circulatory failure, and death.
Animal experimentation has supported certain other biochemical mechanisms
of toxicity involving reaction products of ethanol and disulfiram.

FREQUENT SYMPTOMS AND SIGNS OF INJURY AND POISONING
BY DIALKYLDITHIOCARBAMATES
  ITCHING, REDNESS, and ECZEMATOID  DERMATITIS have resulted
when sensitive or predisposed  individuals come in contact with these com-
pounds.  Persons excessively exposed to air-borne fungicides have suffered
UPPER RESPIRATORY  CONGESTION,  HOARSENESS,  COUGH,  and
even PNEUMONITIS. When large amounts have been ingested,  NAUSEA,
EMESIS,  and DIARRHEA  ensue.  HYPOTHERMIA and  ATAXIA are
characteristic.  MUSCLE   WEAKNESS, progressing  to a   condition  of
ASCENDING PARALYSIS,  and  finally RESPIRATORY  PARALYSIS,
can be anticipated from animal  toxicologic studies based on extreme  dosage.
   The reaction to  ethanol which follows absorption of  disulfiram is char-
acterized by FLUSHING,  SWEATING, POUNDING  HEADACHE, SEN-
SATION OF WARMTH, WEAKNESS, CONGESTION OF  UPPER RES-
PIRATORY and CONJUNCTIVAL MEMBRANES, DYSPNEA, HYPER-
PNEA,  CHEST PAIN,  TACHYCARDIA,  PALPITATION, and HYPO-
TENSION.
   Respiratory distress may resemble ASTHMA, and, in some  instances,
RESPIRATORY DEPRESSION has been life-threatening.  EMESIS  com-
monly occurs. Severe reactions may  result  in SHOCK, UNCONSCIOUS-
NESS and/or CONVULSIONS, and, therefore,  threaten coronary insuf-
ficiency in predisposed individuals. Only under exceptional occupational cir-
cumstances  can  a person absorb enough of these fungicidal  compounds to
suffer a  severe reaction to ethanol.

CONFIRMATION  OF DIAGNOSIS

   The native pesticides are so rapidly metabolized in the body  that detec-
tion in blood or urine is rarely possible. There are  biochemical methods for
measuring blood acetaldehyde to  confirm an ethanol-dithiocarbamate re-
action.
                                32

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TREATMENT

 1.  WASH contaminating fungicide from the skin  and hair with soap and
    water. Atopic individuals and persons  specifically sensitive to thiuram
    disulfide  compounds  (individuals  recognized  as "rubber-sensitive")
    should be permanently REMOVED FROM CONTACT with chemi-
    cals of this nature.
 2.  FLUSH contaminant from the eyes with fresh water for 10-15 minutes.
 3.  Treatment for INGESTION OF  DIMETHYLDITHIOCARBAMATE
    COMPOUNDS, NOT COMPLICATED BY ALCOHOL INGESTION:
    A. If fungicidal  compounds of this type have  been INGESTED, it  is
       first essential that  the individual NOT TAKE ANY FORM OF
       ALCOHOLIC BEVERAGE for at least 3  weeks.  (Gastrointestinal
       absorption of dialkyldithiocarbamates is protracted, and effects on
       critical enzymes are slowly reversible.)
    B. If vigorous emesis  has not already  occurred, and if victim is fully
       alert and respiration is normal, give SYRUP OF  IPECAC to in-
       duce vomiting (adults, 12 years and  older: 30 ml; children under 12:
       15ml).
       CAUTION:  OBSERVE the victim closely AFTER administering
                    IPECAC. If consciousness level declines, or if vomit-
                    ing has not occurred in 15 minutes, proceed to empty
                    the stomach  by INTUBATION,  ASPIRATION and
                    LAVAGE.
       Following emesis,  administer  30 gm ACTIVATED CHARCOAL
       in 3-4 ounces of water to bind toxicant remaining in the  gut.
    C. If consciousness  level or respiration is depressed, empty the stomach
       by INTUBATION,  ASPIRATION, and LAVAGE, using  all  avail-
       able means to avoid aspiration of vomitus: left lateral Trendelenburg
       position, frequent aspiration of the pharynx,  and, in unconscious
       victims,  tracheal intubation (using  a cuffed tube)  prior to gastric
       intubation.
       After aspiration of the stomach and washing  with isotonic saline
       or sodium bicarbonate, instill 30 gm of ACTIVATED CHARCOAL
       in 3-4 ounces of water through the stomach tube to limit absorption
       of remaining toxicant.
    D. If the irritant properties of  the toxicant fail  to produce  a bowel
       movement in 4  hours, and if the  patient  is  fully conscious, give
        SODIUM SULFATE (Glauber's Salts) as  a  cathartic (adults,  12
       years and older: 15 gm in 6-8 ounces of water; children under 12:
        0.2 gm/kg of body weight in 1-6 ounces of water).
 4. Treatment for a reaction to ETHANOL INGESTION following absorp-
    tion  of a DIALKYLDITHIOCARBAMATE COMPOUND:
    A. Administer  100% OXYGEN  as  long  as  the reaction continues.
        Oxygen  usually  gives substantial relief  from the  distressing symp-
       toms and hypotension.

                                 33

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   CAUTION:  If respiration is  depressed, administer  oxygen by  an
                intermittent  positive pressure breathing device and
                observe the victim closely to maintain pulmonary ven-
                tilation artificially in case of apnea.
B.  If the fungicide was INGESTED no more than 4 hours prior to
   treatment  and vigorous  emesis  has not  occurred,  evacuate  the
   stomach by  INTUBATION,  ASPIRATION,  and LAV AGE,  ob-
   serving precautions cited in 3C, above.
C.  Regardless of time  interval since ingestion of fungicide, ADMIN-
   ISTER 30 gm ACTIVATED  CHARCOAL in 3-4 ounces of water
   to limit absorption of toxicant remaining in the gut. Absorption of
   the dithiocarbamate compounds is slow.
D.  For adults and children over  12 years,  inject  1.0 gm ASCORBIC
   ACID (Vitamin C) intravenously at  a rate not exceeding 0.2 gm/
   minute. For children under 12, give 10-20 mgm per kg body weight.
   As a hydrogen-donor,  ascorbic acid  may have significant antidotal
   action against absorbed, but unreacted,  dithiocarbamate compound.
E. For  severe or protracted reactions, INFUSE 5% GLUCOSE in
   D/W,  or  alternative glucose-containing fluids, to  accelerate  dis-
   position of absorbed  toxicants and metabolites.
F.  Use sodium sulfate catharsis (3D  above) only if no bowel movement
    occurs within 4 hours of the beginning of the reaction.
G. If the victim has  suffered from  arteriosclerosis, myocardial  insuffi-
    ciency, diabetes, neuropathy, cirrhosis, or other severe chronic dis-
    ease, OBSERVE  him  CAREFULLY  for  48  hours to insure  that
    complications  (especially  myocardial  infarction,  toxic  psychosis,
    and neuropathy) are  treated promptly.
                             34

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      ANTICOAGULANT  RODENTICIDES
STRUCTURES OF PRINCIPAL CLASSES
         OH
                                                    ALKYL, PHENYL.
                                                   DIPHENYLACETYLor
                                                 CHLORODIPHENYLACETYL
    WARFARIN (COUMARIN TYPE)
                                       1,3 INDANDIONE TYPE
COMMON COMMERCIAL PESTICIDE PRODUCTS

  Coumarin type: warfarin  (Kypfarin, Warf-42, D-Con, Warficide, Prolin),
coumafuryl (Fumarin), Dethmor, Rax.
  1,3-indandione type: diphacinone, or diphenadione (Ramik), chlorophaci-
none (Drat, Caid, Liphadione, Microzul, Ramucide, Rotomet, Raviac, Topi-
tox), pindone (Pivalyn, Pivacin, Tri-ban, Pival), valone, (PMP).
  These materials are commonly added to baits or dissolved in small amounts
of water for pest rodents to drink. One hundred grams of the prepared com-
mercial baits  must be ingested  to yield 25 mgm  of anticoagulant.  Rodenti-
cide "drinks" are made  by  adding dry concentrate (0.54  gm of active  in-
gredient per 100 gm of powder) to specified volumes of water. The poison in
the concentrate is coated on sugar or  sand  to facilitate measurement  and
handling.

TOXICOLOGY
  Gastrointestinal absorption of these toxicants is efficient, beginning with-
in minutes of ingestion and continuing for 2-3 days. Apparently, warfarin can
also be absorbed across  the skin,  although the circumstances under which
this has occurred are extraordinary.
  Both types of anticoagulant  depress the  hepatic synthesis of substances
essential to normal blood clotting: prothrombin (factor II), and factors VII,
IX, and X. The anti-prothrombin effect  is best known and provides  the basis
for  detection  and assessment of clinical poisoning. Direct  damage  to capil-
lary permeability occurs  concurrently. In  rare instances,  coumarin-type anti-
coagulants  have caused  ecchymosis and  extensive skin  necrosis in humans
for reasons not related to  excessive dosage.
  Unlike the coumarin anticoagulants, the indandiones cause  symptoms  and
signs of neurologic  and  cardiopulmonary injury  in laboratory  rats; these
often lead to death before hemorrhage occurs. These actions may account for
the somewhat greater toxicity of this class of anticoagulants. Cardiopulmo-
nary and neurologic symptoms  and signs have not been reported in human
poisonings.
  Lengthened prothrombin time from a toxic dose usually appears within 24
                                35

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hours of toxicant ingestion and reaches a maximum in 36 to 72 hours. With-
out intervention, hypoprothrombinemia may persist  10-15 days,  depending
on the agent and dosage. Prothrombin depression will occur  in response to
doses that are much lower than those necessary to cause hemorrhage.

FREQUENT SYMPTOMS  AND  SIGNS OF  POISONING
  In most instances of accidental ingestion of anticoagulant baits,  victims
have remained asymptomatic, due to the  small dosage taken. Even in cases
involving ingestion of substantial doses,  hypoprothrombinemia occurs with-
out symptoms  of  poisoning. Hemorrhage appears only when extraordinary
amounts have been absorbed. In these cases, the anticoagulants were either
taken deliberately,  were absorbed  over long periods  out  of neglect  of  ele-
mentary hygienic  standards, or were ingested by starving  indigents  who
used quantities of rodent bait for food.
  Victims of large doses exhibit HEMATURIA, NOSEBLEED, HEMATO-
MATA, BLEEDING GUMS,  and MELENA. ABDOMINAL  PAIN  and
BACK PAIN probably reflect hemorrhage in the abdominal and  retroperi-
toneal tissues. WEAKNESS occurs as a result of ANEMIA. RENAL COLIC
often complicates  severe hematuria. Nasal and gastrointestinal hemorrhages
have caused death from exsanguination.

CONFIRMATION OF DIAGNOSIS
   Increase of  the prothrombin time (Quick) reflects a reduction in serum
prothrombin concentration,  and occurs  in response  to physiologically  sig-
nificant absorption of these toxicants. This widely available clinical test offers
a sensitive and reliable diagnostic method for detecting a toxic effect of these
compounds.  Readily detectable change in prothrombin time  appears within
24-48 hours of ingesting the anticoagulant.
   A few laboratories can  measure warfarin and its  metabolites in human
urine,  but it is rarely practical to use  these determinations for diagnostic
purposes.

TREATMENT
  1.  If it is  known or suspected that  anticoagulant rodenticide has  been
     ingested recently, but that the total  amount ingested was LESS THAN
     0.25 MGM/KG body weight, administer a  single dose of the specific
     antidote,  PHYTONADIONE, INTRAMUSCULARLY:  adults 12  years
     and older: 25 mgm IM; children under 12: 0.6 mgm/kg body weight
     IM.
     Note:  PHYTONADIONE  (Vitamin K,, Mephyton, Aquamephyton,
            Konakion) specifically  is  required-  Vitamin K.,  (menadione,
            Hykinone) and vitamin K,  (menadiol)  have little  or no  anti-
            dotal effect.
     This treatment is adequate when the total amount  of toxicant  ingested
     is known not to have exceeded the limits stated above, and in which no

                                 36

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    pre-existing liver injury or blood clotting disease is present.
2.  If the victim ingested anticoagulant rodenticide WITHIN the PRECED-
    ING 2-3 HOURS in a quantity that may have exceeded 0.25 mgm/kg,
    INDUCE VOMITING with SYRUP of IPECAC  (adults  12 years and
    older:  30 ml; children under 12: 15 ml). After  emesis, give 30 gm
    ACTIVATED CHARCOAL in 4-6 ounces of water to  limit  absorp-
    tion of rodenticide still in the gut.
3.  If the victim  may  have ingested anticoagulant rodenticide  any time
    within the preceding 15 days IN AMOUNTS EXCEEDING 0.25 mgm/
    kg, or if the  victim may have a  pre-existing  liver or bleeding  disease,
    determine  the  PROTHROMBIN TIME.  Then  administer  PHYTO-
    NADIONE INTRAMUSCULARLY  (adults,  12  years and older:  25
    mgm; children under 12: 0.6 mgm/kg). Subsequent  treatment  will de-
   pend on the degree  of prothrombin time lengthening, and on the esti-
   mated dosage and time of toxicant ingestion. High dosage or lengthen-
   ing of the prothrombin time by more than 10 seconds over the control
   may dictate administration of a second dose of phytonadione (as above)
   and another  measurement of prothrombin  time  24 hours after the
   first. Reversal of prothrombin time usually occurs  in 12-24 hours, but
   may require as long as three days.
    CAUTION: Doses  of phytonadione in excess  of 25 mgm are some-
               times hepatotoxic, and should be given only when lower
               doses have not been effective. Doses in excess of 50 mgm
               involve significant hazard and are of doubtful benefit.
4.  If the victim shows SYMPTOMS  or SIGNS of POISONING (bleeding,
    anemia, hematomata)  in addition to hypoprothrombinemia,  it may be
   necessary  to give PHYTONADIONE INTRAVENOUSLY. Aquame-
   phyton may be administered by this route in doses of 25 mgm for adults,
    12 years  and older; or 0.6 mgm/kg for children  under 12, repeating
    this amount once in 24 hours if bleeding continues.  Inject at rates not
    exceeding  1  mgm/minute for adults,  but proportionately slower in
    children.  To achieve slow intravenous injection, dilute the  phytonadione
   in either  0.9% saline or 5%  glucose solution. Bleeding is usually con-
    trolled within 3-6 hours of intravenous infusion.
       CAUTION:  Adverse reactions,  some fatal,  have occurred from
                    intravenous phytonadione injections, even when rec-
                    ommended 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, dy-
                    spnea and cyanosis  have characterized adverse re-
                    actions.
5.  A.  Antidotal  therapy  in  cases  of severe poisoning  should be  supple-
       mented with TRANSFUSIONS  of  FRESH BLOOD or  FRESH
       FROZEN PLASMA. Use of  fresh blood or plasma represents the
       most rapidly effective method for stopping hemorrhage due to these

                              37

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      anticoagulants.
   B. Determine  PROTHROMBIN  TIMES  (and hemoglobin  concentra-
      tions,  if appropriate) every 6-12 hours to assess effectiveness of
      antidotal and antihemorrhagic measures.
   C. When  normal blood coagulability is restored, it may be advisable to
      drain large hematomata.
   D. Ferrous  sulfate therapy may be appropriate  in  the recuperative
      period to rebuild lost erythrocyte mass.
6.  Give ASCORBIC ACID (vitamin C) orally or intramuscularly in  mild
   and severe poisoning to limit capillary injury caused by the anticoagu-
   lants (adults, 12 years and  older:  100 mgm; children under 12: 50-100
   mgm).
                                38

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           ARSENICAL PESTICIDES


CHEMICAL STRUCTURES

EXTREMELY TOXIC: (TRIVALENT INORGANIC ARSENICALS)

  O^As — O—As^O                       K—O—As = O

  ARSENIC TRIOXIDE                     POTASSIUM ARSENITE

         O
         II                                H
  Cu—(O—C—CH3)2
                                             As—H
   Cu3—
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COMMON  COMMERCIAL PESTICIDE PRODUCTS
  Inorganic  arsenicals: arsenic trioxide  (white  arsenic), sodium  arsenite
(Acme Weed Killer, Atlas A, Penite, As-655 Weed Killer, Kill All), copper
arsenite  (Paris Green), copper ammonium  arsenite  (Chemonite), arsenic
acid (Zotox Crabgrass Killer, Dessicant L-10, Lincks Liquid Di-met, Pax
Total, Purina Top Grass and Weed Killer).
  Organic arsenicals: MSMA (Ansar 170, Bueno, Weed-E-Rad,  Ansar 529,
Broadside, Crabgrass  Dallis Grass Killer, Daconate, Fertilome Nutgrass and
Weed Killer, Mad, Nutgrass Spray, Selector #1, Spot Grassy Weed Killer);
DSMA  (Ansar  8100, Biochecks,  Burpee Crabgrass  Killer, Chipco  Crab
Kleen, Clout,  D Krab R + Prills, DMA,  E Krab R, Greenfield Crabgrass
and Dandelion Killer, Sears Liquid Crabgrass Killer, Lawn Weed Killer, Pro-
turf Monocot  Weed Control);  cacodylic acid (Silvisar  510); sodium cacody-
late (sodium dimethyl arsinate,  Phytar 560, Acme Weed Killer);  ammonium
methane arsenate (AMA, Ansar 157,  Super Crab E-Rad, C-4000, Antrol
Crabgrass Killer, Crabgrass Broadleaf Killer,  Systemic  Crabgrass and Broad-
leaf Killer);  methane  arsonic acid (MAA,  Ortho Crabgrass Killer).

TOXICOLOGY

  Although the  pentavalent arsenicals are generally less  toxic than the in-
organic trivalent chemicals, all  poisonings by  arsenic-containing  substances
should be regarded as serious threats to life and health. To some  degree, the
pentavalent  compounds undergo reduction  in the gut and/or body tissues to
trivalent forms.  Some absorption  of solid arsenical compounds  may  occur
by dermal or pulmonary routes, but the great  majority of poisonings  result
from  ingestion.  Intestinal  absorption is generally  efficient.  Most absorbed
arsenic  is excreted by way  of the kidneys;  a lesser proportion is excreted by
the liver  and gut. Arsine gas in absorbed rapidly by the lung;   an arsenic
metabolite is excreted in the urine.
  Toxicology of arsine gas  (absorbed  by inhalation) is unique in  that  it
causes hemolysis and secondary acute renal tubular necrosis. Arsine  is not
used as a pesticide, but is involved in the manufacture of organic arsenicals.
  Trivalent arsenicals bind critical sulfhydryl-containing enzymes in tissues.
When taken up from the gut, they  injure the splanchnic vasculature, causing
colic  and diarrhea. Once absorbed, they produce toxic injury to the liver,
kidney, bone  marrow, brain and peripheral nerves. Liver  injury  is manifest
as  hepatomegaly,  jaundice,  and  an increase  in circulating hepatocellular
enzymes LDH and GOT.  Renal damage is reflected  in albuminuria,  hema-
turia, pyuria, cylindruria, then azotemia.  Acute tubular necrosis  may occur
in severe poisoning.  Injury to blood-forming tissues  can  take the form  of
agranulocytosis, aplastic anemia, thrombocytopenia, or pancytopenia. Toxic
encephalopathy  may  become  manifest as  speech and  behavioral  distur-
bances. Peripheral neuropathy occurs in both  acute and  chronic forms.  In-
halation of arsenic dusts may cause bronchitis or pneumonitis.
   Sequelae of arsenic poisoning include cirrhosis, hypoplastic bone marrow,
renal insufficiency, and peripheral neuropathy. Excessive exposures to  arseni-
cals have caused cancers of skin and various epithelial tissues.

                                   40

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FREQUENT SYMPTOMS AND SIGNS OF POISONING

ACUTE arsenic poisoning (solid compounds):
  COLIC, BURNING ABDOMINAL PAIN, VOMITING, and WATERY
or BLOODY DIARRHEA are the  primary manifestations of ingestion  of
solid arsenical poisons. Symptoms following ingestion of inorganic arsenicals
are more severe than those resulting from ingestion of pentavalent organic
arsenicals. Symptoms sometimes  do  not  appear for minutes  or even  hours
after ingestion. HEADACHE, DIZZINESS,  MUSCLE SPASMS, DELIR-
IUM, and sometimes CONVULSIONS reflect direct  injury  to the central
nervous system, as  well as extracellular electrolyte disturbances and shock.
A GARLIC  ODOR to the breath and feces helps  to identify the responsible
toxicant.  SHOCK, TOXIC NEPHROSIS, HEPATITIS (hepatomegaly and
jaundice), and NEUROLOGIC INJURY (delirium, paralysis,  respiratory de-
pression) may progress to a fatal outcome.

SUBACUTE arsenic poisoning (solid  compounds):
   Dosages less than those necessary to produce severe acute symptoms are
known to cause CHRONIC HEADACHE,  ABDOMINAL  DISTRESS,
SALIVATION, LOW-GRADE FEVER, AND PERSISTENT symptoms  of
UPPER RESPIRATORY  IRRITATION. Stomatitis and garlicky breath are
characteristic.

CHRONIC arsenic poisoning (solid compounds):
  Prolonged low intakes of arsenic  cause PERIPHERAL  NEUROPATHY
(paresthesiae,  pain,  anesthesia,  paresis,  ataxia);  ENCEPHALOPATHY
(apathy); varied DERMATOLOGIC DISORDERS (keratoses, pigmentation,
eczemas,  brittle nails,  loss of hair); and TOXIC HEPATITIS (hepatomegaly,
sometimes progressing to  cirrhosis  with  ascites).  WEAKNESS and vulner-
ability to infections may result from bone marrow depression. Local EDEMA,
frequently of the eyelids, characterizes some chronic poisoning cases.

ACUTE arsine poisoning (gas):
   The gas causes HEMOLYSIS  of red blood cells in addition  to inhibition
of cellular sulfhydryl respiratory enzymes. Hemolysis causes HEMOGLO-
BINEMIA  AND  HEMOGLOBINURIA.  This  in  turn,  causes  ACUTE
TUBULAR NECROSIS. Early symptoms of poisoning (chills, weakness, burn-
ing sensations) are followed by abdominal cramps,  vomiting, and prostration,
as renal function deteriorates to ANURIA.

CONFIRMATION OF DIAGNOSIS
   Measurement of 24-hour urinary excretion of arsenic is probably the best
way to confirm excessive  arsenic absorption,  although methods for  blood
arsenic concentration are  available.  Persons  on ordinary  diets usually ex-
crete less than 20 /tgm/day, but diets rich in seafood may generate as much
as 200 jugm/day.  Excretions above 100 /tgm/day should be viewed with sus-
picion  and tests should be  repeated. Excretions above 200 jugm/day reflect

                               41

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a potentially toxic intake.
  The  qualitative  Gutzeit test for arsenic in the urine is  available in most
hospital laboratories, and is useful  in identifying acute poisonings promptly.
  Chronic storage of arsenic can be detected by analysis  of hair or  finger-
nails.
  The  hemoglobinuria caused by arsine is identified by finding the pigment
in fresh urine from which  intact red cells are absent.

TREATMENT FOR POISONING BY SOLID  ARSENICALS

 1. Flush contaminated  EYES, HAIR and SKIN with copious  amounts of
    fresh water.
 2. In cases of poisoning  by RECENTLY  INGESTED  (up  to 6  hours)
    ARSENICALS:
    A. INTUBATE the stomach,  ASPIRATE, and LAVAGE with  3 liters
        of isotonic saline or 5% sodium bicarbonate. Use  all available pre-
        cautions to avoid aspiration of vomitus:
        (1) If the victim is unconscious or obtunded, it is helpful to insert
            an ENDOTRACHEAL TUBE  (cuffed, if available) prior to
            intubation.
        (2) Keep the victim's  HEAD BELOW THE LEVEL OF THE
            STOMACH during intubation (Trendelenburg, or left lateral
            decubitus, with head  of table tipped downward). Keep the  vic-
            tim's head turned toward the left.
        (3) ASPIRATE the pharynx as regularly as possible to  remove
            gagged or vomited stomach contents.
    B. After  lavage, INSTILL  60 gm ACTIVATED   CHARCOAL in
        water:  6-8 ounces,  or the  smallest amount necessary to deliver the
        charcoal.
    C. If diarrhea or colic have not ensued within an hour of gastric lavage
        and charcoal administration, give SODIUM SULFATE as a  cathar-
        tic (adults, 12  years and  older:  15  gm in 6-8  ounces of water;
        children under 12:  0.2 gm/kg body weight  in 1-6 ounces of water.
    D. Administer INTRAVENOUS ELECTROLYTE  and  GLUCOSE
        solutions  to maintain hydration and to accelerate toxicant excretion.
        COMBAT SHOCK with  TRANSFUSIONS of WHOLE BLOOD,
        and by inhalation of 100% OXYGEN.
        CAUTION:  Monitor urine flow via catheter. Monitor fluid balance,
                    body  weight,  and/or central venous pressure to guard
                     against fluid overload  resulting  from  acute  tubular
                     necrosis (anuria).
     E. PROMPTLY administer  DIMERCAPROL (BAL, British antile-
        wisite, dimercaptopropanol) INTRAMUSCULARLY,  as the  10%
        solution in vegetable oil, to neutralize the toxic action of arsenicals.
        Recommended dosage schedule is:
                                42

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            Mild Poisoning                       Severe Poisoning
Days 1&2  2.5 mgm/kg q6h X 8 doses      3.0 mgm/kg q4h  X 12 doses
Day 3      2.5 mgm/kg q!2h X 2 doses     3.0 mgm/kg q6h  X 4 doses
Succeeding
  10 days   2.5 mgm/kg q24h X  10 doses    3.0 mgm/kg q!2h X 20 doses
        CAUTION:  DIMERCAPROL can cause troublesome side effects
                    (hypertension,  tachycardia,  nausea,  headache,  pares-
                    thesiae and pain, lachrymation,  sweating, anxiety, and
                    restlessness). Although usually  not so  severe as to
                    handicap treatment,  these manifestations may require
                    antihistaminic therapy for adequate control.
     F.  Intense abdominal pain may require morphine (adults,  12 years and
        older: 4-15 mgm; children under 12: 0.1-0-2 mgm/kg.)
     G.  Severe poisoning (especially when  renal function is  impaired) may
        require hemodialysis to remove arsenic combined with dimercaprol
        from the blood.
 3.   If arsenical was  ingested more than 48 hours prior to treatment, or if
     excessive  absorption has occurred over an  extended period, treatment
     should probably be limited to  administration  of  dimercaprol  as pre-
     scribed  in 2E plus  nutritional supplements  to  restore metabolic func-
     tions as promptly as possible.

TREATMENT FOR POISONING BY ARSINE GAS

 1.   REMOVE the victim to FRESH AIR.
 2.   MAINTAIN  RESPIRATION and  CIRCULATION by  resuscitation
     and cardiac massage, if necessary.
 3.   Administer INTRAVENOUS FLUIDS as promptly as possible to dilute
     hemoglobin in the  glomerular filtrate  and  minimize tubular injury.  Use
     enough sodium bicarbonate to keep the urine alkaline.
     CAUTION:   Monitor  urine flow via catheter.  Monitor fluid balance,
                 body  weight, and/or central  venous pressure to guard
                 against fluid overload resulting from acute tubular necrosis.
 4.   Administer DIMERCAPROL as recommended in 2E even  though  it
     has only limited effect in arsine poisoning.
 5.   EXCHANGE BLOOD TRANSFUSIONS and  PERITONEAL DIAL-
     YSIS have saved the lives  of victims of arsine poisoning suffering acute
     tubular necrosis.
                                 43

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               VACOR®  and  DLP-787
CHEMICAL STRUCTURE
                         H                 	

                       -C-N-C-N-//      YV
                         i    i    n    i    \        /
N02
                             I    II    I
                         H   H   O   H
                          RH-787
COMMON COMMERCIAL PESTICIDE PRODUCTS

  Vacor® Rat Killer (2% RH-787 in vehicle resembling corn meal); DLP-
787 Bait (2% RH-787 in vehicle resembling corn meal);  DLP-787 House
Mouse Tracking Powder  (10%  RH-787  in  a light green  powder vehicle).
Compound RH-787  is the  active ingredient  of both formulations.

 TOXICOLOGY

  Acute oral LD50 values for RH-787 in the dog and Rhesus monkey are
2000-4000 mgm/kg. LD50  ratings of the diluted formulations ingested by
rodents are quoted as follows:
                                        Rats            Mice
    Vacor® Rat Killer or Bait          580 mgm/kg  4,120 mgm/kg
    DLP-787, 10% Tracking Powder     	      1,050 mgm/kg
  The minimum lethal dose in humans is not known.

  The  exact  mechanism of  RH-787  toxicity is not known. It has no anti-
coagulant action, and is therefore  entirely  different from  the  coumarin-
indandione rodenticides.  One established  effect in rats is  interference with
nicotinamide  metabolism. Symptoms  and  signs in poisoned animals suggest
toxic actions on the brain,  the peripheral nerves, myoneural junctions, the
pancreas (including islet  tissues), the autonomic nervous  system, and the
conducting tissues of the heart. Abnormalities of renal and  vascular function
may be due to direct toxic  effects, or may reflect metabolic and  autonomic
nervous system disturbances  (hypotension).

  If absorbed in adequate dosage by rats or  by humans, RH-787 can induce
persistent diabetes  mellitus, manifest  as hyperglycemia,  glycosuria,  and
ketoacidosis.  This has occurred in humans following ingestion of one 30 gm
package of Vacor®.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

  Human poisonings  of a  significant nature have occurred only after de-
liberate ingestions of RH-787. Symptoms  vary, depending on dose and indi-
vidual susceptibility.

  Symptoms may not appear until 4-48 hours after ingestion of the formu-
lated rodenticide. EARLY  symptoms include NAUSEA, VOMITING, AB-
DOMINAL CRAMPS, CHILLS, and MENTAL CONFUSION.
                               44

-------
   LATER clinical  manifestations  have included:  ACHING  and FINE
 TREMORS of the extremities, DILATED PUPILS, PERIPHERAL NEU-
 ROPATHY (plantar hyperesthesia),  MUSCLE WEAKNESS, DYSPHAGIA,
 CHEST  PAIN,  POSTURAL  HYPOTENSION,  ANOREXIA, CONSTI-
 PATION or  DIARRHEA, URINARY BLADDER DYSTONIA  (urinary
 retention),  HYPOTHERMIA  and  the consequences of  diabetes mellitus:
 GLYCOSURIA, POLYURIA, KETOACIDOSIS, and DEHYDRATION.

   Abnormal  laboratory findings include hyperglycemia, glycosuria, ketosis
 (acidosis and electrolyte disturbances), and elevation of serum amylase and
 lipase activities.
   Temporary blindness has occurred in dogs.

   Death may result from respiratory failure, cardiovascular collapse,  or keto-
 acidosis.

  LATE and PERSISTENT manifestations of poisoning  are  POSTURAL
HYPOTENSION and DIABETES MELLITUS.

CONFIRMATION OF DIAGNOSIS

  Analysis of blood, urine, and tissues for RH-787 is difficult, and cannot
yet be done on a routine basis. In particular cases of poisoning that require
chemical  confirmation, contact the Office of Pesticide Programs, U.S.  En-
vironmental Protection Agency.

TREATMENT

  1. If  no more  than 12  hours  have elapsed  since toxicant  ingestion,
     EVACUATE THE  STOMACH by  INDUCED EMESIS and LAV-
     AGE.

     A.  INDUCE EMESIS with SYRUP OF IPECAC (30 ml for adults and
       children over  12  years; 15 ml  for children under 12) ONLY if
       copious vomiting has not already occurred and if the victim is fully
       alert.  If consciousness  declines after ipecac  administration, proceed
       immediately with gastric intubation.

    B. Following  emesis,  INTUBATE the STOMACH, ASPIRATE CON-
       TENTS, and LAVAGE with  2-3  liters of isotonic saline  or  5%
       sodium  bicarbonate solution. To avoid aspiration of stomach con-
       tents, put  the victim in left  lateral  Trendelenburg position, aspirate
       the pharynx frequently, and, in  unconscious patients, intubate the
       trachea with a cuffed tube prior to gastric intubation.

    C. After  gastric lavage, instill 30 gm  of ACTIVATED  CHARCOAL
       in 3-4 ounces of water through the stomach tube to limit absorption
       of the toxicant.
                                 45

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2. Administer NIACINAMIDE (nicotinamide) intravenously  (slowly)  or
   intramuscularly. In adults and in children over 12 years or 30 kg body
   weight, give 500 mg immediately, then repeat injections of 200-400 mgm
   every 4 hours for 10-12 doses. Select the proper dosage on the basis
   of body  weight and estimated quantity  of  Vacor®  or  DLP  787 in-
   gested. If symptoms and signs of  rodenticide toxicity appear, adminis-
   ter nicotinamide by continuous IV infusion at  a rate of  400 mgm every
   4 hours.  Avoid total dosage of nicotinamide above 3000 mgm/day.

   Dosage for children under  12 years, or less than 30 kg body weighl,
   is approximately half that  needed for adults.

   When the  patient is  able  to take medication  by  mouth, give  100
   mgm nicotinamide orally four times daily for two weeks.

3. MONITOR blood  and urine  sugar  concentrations, serum  alkaline
   phosphatase, amylase, LDH, and GOT activities, urine ketone  concen-
   trations, blood  electrolytes  and BUN. Examine  the electrocardiogram
   for arrhythmias.

4. Unless the  patient is able to void easily, put in place a RETENTION
   CATHETER to monitor urine flow and urinary glucose  excretion.

5. Infuse ELECTROLYTE SOLUTIONS intravenously to accelerate toxi-
   cant excretion and correct errors  in specific ion concentrations.  If keto-
   acidosis appears, use bicarbonate or Ringer's-lactate to control acidosis.
6. If DIABETIC KETOACIDOSIS  appears (ketonuria, metabolic acidosis,
   hyperglycemia)  administer enough regular insulin to control the acido-
   sis and hyperglycemia, as in naturally occurring diabetic ketosis. The
   diabetes resulting from RH-787 tends to be brittle and correspondingly
   difficult to control.
7. In all cases of ingestion of Vacor® or DLP-787  (whether or not acute
   poisoning occurs), follow  the patient's clinical status carefully for at
   least 6 months. Look for indications of diabetes  mellitus, and for con-
   sequences of autonomic  nervous system  disorders:  orthostatic hypo-
   tension,  urinary  retention,  constipation,  diarrhea,  or  abdominal
   cramping.
                                  46

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             HALOCARBON and SULFURYL
                       FUMIGAIMTS
COMMON COMMERCIAL PESTICIDE PRODUCTS
         H
         I
     Cl — C —Cl
         I
         H

      METHYLENE
      CHLORIDE
         Cl
         I
     Cl— C — H
         I
         Cl

     CHLOROFORM
    Cl  Cl
    I   I
H — C — C — H
    I   I
    H  H
   ETHYLENE
   DICHLORIDE
    Br  Br
    I   I
 H — C — C — H
    I   I
    H   H


   ETHYLENE
   DIBROMIDE
 J   Cl   H   Cl
    I   I    '
 H— C — C s= C
    I       I
    H       H

    1.3.DICHLORO-
    PROPENE
                                                   Cl
                                                   I
H— C— C — C — H
   I   I   I
   H   H   H

   1,2-DICHLORO-
      PROPANE
         Cl
         I
     Cl — c —Cl
         I
         Cl


     CARBON
     TETRACHLORIDE
        BR
         I
     H — C— H
       METHYL
       BROMIDE
        Cl
         I
     Cl — C — N02

        Cl

     CHLOROPICRIN
    Cl  H
    I   I
 Cl- C — C — H
    I   I
    Cl  H


 1.1.1 -TRICHLORO
     ETHANE
                                                PARADICHLOROBENZENE
                                         SULFURYL
                                         FLUORIDE
  ALIPHATIC
  Chloroform, carbon  tetrachloride, methyl bromide  (Brom-O-Gas, Fumi-
gant-1, Kayafume, Me  Br, Meth-O-Gas, Pestmaster, Profume); chloropicrin
(Acquinite, Chlor-O-Pic, Pic-Clor, Picfume; Trichlor); ethylene dichloride
(EDC); ethylene dibromide (EDB, Bromofume, Celmide, Dowfume W-85,
Kop-Fume, Nephis,  Pestmaster EDB-85,  Soilbrom); dichloroprop-ene and
-ane (Telone,  D-D). The Dowfume fumigants manufactured by  the Dow
Chemical Company are mixtures of halocarbons, mainly EDC, EDB, carbon
tetrachloride, Me Br, and chloropicrin, formulated to meet specific needs.
                              4/

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  AROMATIC
  Paradichlorobenzene (PDB, Paracide, Paradow)
  SULFURYL
  Sulfuryl fluoride (Vikane)

TOXICOLOGY

  Except for the solid paradichlorobenzene moth  crystals, these chemicals
are gases or highly  volatile liquids at room temperature. As fumigants, they
have  a  remarkable capacity  for  penetration.  Some, especially the bromine
compounds, pass readily  through human  skin  and rubber protective  gear,
thus complicating the protection of exposed workers. In varying degrees they
irritate the skin, eyes, and respiratory tract. When held on the  skin by  an
occluding cover,  such  as  contaminated  gloves, these chemicals  not  only
irritate,  but cause  acute dermatitis and vesiculation. Repeated contact with
the liquid halocarbons defats the  skin, leading to chronic dermatitis. All are
capable  of  producing  pulmonary  edema  and/or hemorrhage  in persons
heavily exposed by  inhalation, ingestion, or dermal absorption. Death follow-
ing exposure to the halocarbon fumigants is usually due either to pulmonary
edema or to respiratory depression.

  Inhalation of pyrolysis products of these fumigants has caused massive
necrosis  of respiratory tract linings in exposed firemen.

  Toxic  action on the central  nervous  system  is  generally  depressant,
causing  unconsciousness,  seizures, and general  muscle weakness,  including
weakened respiratory effort.  The neurotoxic action of methyl bromide ap-
parently  includes the basal ganglia as well as the cerebrum, causing not only
sensory   and motor impairments  but also behavioral and  emotional dis-
turbances. These may or may not progress to epileptiform seizures and coma.
In some  cases,  behavioral and neurologic manifestations have first  appeared
several hours or even days after exposure, then  they have  persisted for days
to months.
   The  chlorocarbons,  notably chloroform,  increase  myocardial irritability
and impair contractile  strength. Large  inhalation dosages may cause death
by  inducing ventricular fibrillation.

   In varying  degree,  these  fumigants damage the  liver and kidneys.  In
laboratory animals, and in autopsy specimens from fatal  human cases, this
is commonly manifest as fatty degeneration.  More severe poisoning causes
centrilobular necrosis  of the liver and acute tubular necrosis of the kidney.
Fatty degeneration of the myocardium  and corneal opacities have  been
observed in dogs  following systemic  absorption  of ethylene dichloride.

   Methyl bromide  and ethylene  dichloride (and possibly other chemicals of
this series, by analogy) are alkylating agents in  mammalian tissues; they can
inhibit multiple enzyme systems,  including the sulfhydryl enzymes and hexo-
kinases  in multiple tissues. This  may be a major mechanism of toxicity of
this series of chemicals.

                                   48

-------
  Paradichlorobenzene is  substantially less toxic  to  humans than are the
gaseous and liquid fumigants. It has neither the hemolytic nor the cataracto-
genic  properties of naphthalene fumigant, which it  has largely displaced.
Given at extreme  dosage  to laboratory animals, it causes  liver injury  and
neurologic disturbances.

FREQUENT SYMPTOMS AND SIGNS OF POISONING
  HEADACHE, DIZZINESS, NAUSEA,  and  VOMITING  are prominent
early  symptoms of the  poisonings  produced  by these fumigants. Irritants,
especially  METHYL  BROMIDE and the 3-carbon  CHLOROCARBONS
often produce TEARING,  RHINORRHEA, PHARYNGITIS, COUGH, and
DYSPNEA.  These symptoms  may progress  to PULMONARY EDEMA,
with coughing of frothy sputum.
  DROWSINESS, TREMORS, ATAXIA, DIPLOPIA, MUSCLE TWITCH-
INGS and WEAKNESS,  and JACKSONIAN  SEIZURES are  the  major
early manifestations of central nervous system injury. Twitching and regional
myoclonic movements may progress to general and severe EPILEPTIFORM
SEIZURES, coma, and death in respiratory failure.
  DELAYED MANIFESTATIONS have characterized some poisonings by
METHYL BROMIDE.  Convulsions and/or pulmonary edema may appear
up  to 48  hours after exposure. Bizarre  myotonic  states, behavioral  and
emotional  disturbances, impaired speech, and awkward gait have developed
after repeated,  relatively low-level occupational  exposures,  persisting  there-
after for weeks or months.
  Following heavy accidental exposures  to  the  CHLOROPROPANES -
ENES, a  few victims have complained of protracted  neurologic  sympto-
matology:  headache, irritability, poor memory and personality changes.
  INGESTION of acutely toxic amounts of liquid HALOCARBONS is
likely  to be followed by PULMONARY EDEMA, SEIZURES, and SHOCK.
Because toxic dosages and individual susceptibilities  vary  widely, cases of
ingestion should be treated vigorously, regardless of estimated  dosage.
  PARADICHLOROBENZENE has occasionally caused  dermal sensitiza-
tion.  Tremors  and liver injury  produced by extreme doses in laboratory
animals  have occurred rarely, if ever, in humans.
  SULFURYL  FLUORIDE may  cause MUSCLE  TWITCHINGS, then
CONVULSIONS,  on  acute exposure. Because pulmonary and renal damage
may develop on repeated contact, every attempt  should be made to minimize
exposure.

CONFIRMATION OF POISONING

  Although there  are methods available for measuring gaseous halocarbons
in expired air, these facilities are found only in anesthesiology research units
or industrial plants. Paradichlorobenzene concentrations can be  measured
in the blood.

                                49

-------
  Blood bromide concentrations* have some value in identifying poisonings
by methyl bromide, and possibly ethylene dibromide, provided it can be es-
tablished that  the  person exposed  to the fumigant has not  recently taken
inorganic bromide medication.  A level of organic bromide of more than 5
mgm/100  ml  indicates excessive  absorption of fumigant.  A blood  con-
centration  of more than 10 mgm/100 ml of organic bromide represents a
serious  threat  to health. A blood level of more  than 15  mgm/100 ml
endangers life.

TREATMENT

  1.  FLUSH  contaminating  fumigant  FROM  the  EYES  with copious
      amounts of water, for at least 10 minutes.

  2.  WASH liquid fumigant FROM  the SKIN with soap and water.  Severe
      inflammation and vesiculation will require continuing medical manage-
      ment.

  3.  REMOVE VICTIMS of FUMIGANT INHALATION to FRESH AIR.
      Even though initial  symptoms  and signs  are  mild, put victim  in a
      comfortable sitting or reclining position so as to REDUCE PHYSICAL
      ACTIVITY  to  an absolute  minimum. If respiration is  depressed,
      RESUSCITATE  by mechanical intermittent positive pressure breath-
      ing (IPPB),  if available.  Use whatever concentrations  of oxygen are
      necessary to overcome hypoxemia. Mouth-to-mouth  or  mouth-to-nose
      resuscitation may be necessary.

  4.  PULMONARY  EDEMA must be treated initially by vigorous inter-
      mittent  (sometimes  continuous)  positive   pressure  breathing, using
      sufficient oxygen  to overcome hypoxemia.  Administer with the  victim
      in a sitting  or semi-reclining position.

      CAUTION:  Whenever possible, avoid prolonged use of high concen-
                  trations of oxygen  (80%-100%), as these  may aggravate
                  existing injury to lung tissue.
  5.  CONTROL  CONVULSIONS.  Although  there  is no  published ex-
      perience to document its value in these poisonings, DIAZEPAM is
      probably the drug of choice  to control seizures caused by the halo-
      carbon fumigants. Give 5-10 mgm by  slow intravenous injection, stop-
      ping with the lowest effective dose. Deep intramuscular injection can be
      used if seizures preclude intravenous administration.

      CAUTION: Inject diazepam slowly IV to avoid irritation of the  vein,
                  hypotension, and respiratory depression.

        Severe seizures caused by methyl bromide have been controlled with
      barbiturates.  A  maximum dosage of PENTOBARBITAL (NEM-
      BUTAL)  of 5 mgm/kg body  weight  may be  given slowly IV  until
      convulsions are  controlled, and repeated  in 4-6 hours if necessary. If
      t Conway, E. J. Microdiffusion Analysis and Volumetric Error. 3rd Edition.
      Crosby Lockwood, London  1950.

                                 50

-------
    IV administration is  not  possible, the total 5 mgm/kg dose can be
    administered rectally.
    CAUTION: Be prepared to assist pulmonary ventilation mechanically,
               if  respiration  is depressed.

      In methyl bromide poisoning, it may be necessary to give diazepam
    or pentobarbital orally for  some time after the acute convulsive episode
    to control involuntary  motor activity.

6.  INGESTED FUMIGANT liquids MUST BE REMOVED from the gut.
    Because of the  strong likelihood of  respiratory  depression shortly
    after ingestion, it is probably best to AVOID use of IPECAC, and to
    undertake  GASTRIC INTUBATION, ASPIRATION, and LAVAGE
    immediately. To avoid aspiration of  gastric  contents:  a)  place  the
    victim in left lateral  Trendelenburg; b) if  the victim  is unconscious,
    insert a cuffed endotracheal tube prior to gastric intubation; c) if
    victim is conscious, or if it is not  possible to accomplish  tracheal
    intubation for other  reasons,  aspirate  the pharynx as regularly  as
    possible during gastric intubation.

     ASPIRATE the stomach as completely as possible. Then LAVAGE
    with  2-3 liters  of 0.9% sodium  chloride, or 5% sodium bicarbonate,
    containing a  slurry  of 60-90 gms ACTIVATED CHARCOAL.  After
    lavage,  instill 30  gnr activated charcoal into the stomach before with-
    drawing the tube, to adsorb remaining toxicant.

7.  In  poisonings  by  METHYL  BROMIDE and  ETHYLENE  DI-
    CHLORIDE (and possibly by other chemicals of this series, by  infer-
    ence) there may  be some therapeutic  value in  the administration of
    DIMERCAPROL (BAL, dimercaptopropanol), especially if it can be
    given within a few minutes of absorption of  the  toxicant. Administered
    in vegetable oil intramuscularly, the usually recommended dosage is 3
    mgm/kg body weight  q 6h for 8 doses in first 2 days; then 3 mgm/kg
    q 12h for 2 doses during day 3; then  3 mgm/kg q 24h for 10  doses
    during succeeding 10 days.
    CAUTION: DIMERCAPROL  may  cause troublesome side effects
              (hypertension, tachycardia, nausea, headache, paresthesiae,
               pain, lachrymation, sweating,  anxiety and restlessness).
               Although usually not so severe as  to handicap treatment,
               these manifestations may  require antihistamine  therapy
               for adequate control.
8. MONITOR poisoning victims closely FOR RECURRENT PULMO-
    NARY  EDEMA and secondary  BRONCHOPNEUMONIA.  Fluid
    balance should be  charted, and the  urine  sediment examined  regu-
    larly, to detect incipient  TUBULAR  NECROSIS. Measure serum
    alkaline phosphatase, GOT, GPT, LDH and bilirubin to assess LIVER
   INJURY. Administer intravenous fluids cautiously to avoid  exacerbat-
    ing the  pulmonary edema.

                                  51

-------
  Protracted neurologic manifestations of poisoning may require sever-
al days or weeks of sedative therapy.  Pulmonary function tests should
be done after resolution of acute symptoms to evaluate the degree of
permanent lung damage, if any.
                            52

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         MISCELLANEOUS FUMIGANTS
CHEMICAL FORMULAE OF COMMON FUMIGANTS:
ORGANIC OXIDES
      CH,
       ETHYLENE
        OXIDE
ALDEHYDES
                        CH,
          CH2"

       PROPYLENE
          OXIDE
                                 ' CH,
JC»
H

C= O
1
H

FORMALDEHYDE



H
1
C =O
•
O
1
H— C — H

H

METHYL
FORMATE
H
1
C =0
1
1

H — C — H
1
H-C — H
1
H

H
C= 0
I
H-C
1
H-C — H

ACROLEIN



                                FORMATE
SULFUR-CONTAINING
          O =  S = O

          SULFUR DIOXIDE
CYANIDE AND NITRILE
          H —  C  H N

         HYDROGEN CYANIDE
             S = C =  S

            CARBON DISULFIDE
                   H
             H2C = C — C s. N

              ACRYLONITRILE
PHOSPHINE
          V
             H
          PHOSPHINE
FROM
                         H2O
                                       AROMATIC HYDROCARBON
       AL = P

    METAL PHOSPHIDE
COMMON COMMERCIAL PESTICIDE PRODUCTS
  Many fumigants are identified by generic chemical names.
  Published common and commercial names are identified below:

  Ethylene oxide: ETO, oxirane
  Propylene oxide: epoxy propane
  Formaldehyde: Formalin (40% soln); Paraformaldehyde (solid
  polymer) Methyl and ethyl formates: Areginal
                           53

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  Propenal: Acrolein,  Aqualin,  Acrylaldehyde
  Carbon disulfide (carbon  bisulfide): an ingredient of many grain fumigant
     mixtures
  Hydrogen cyanide: hydrocyanic acid, prussic acid (Cyclon)
  Acrylonitrile:  ingredient  of  Acrylofume,  Acritet, Carbacryl. These  are
  fumigant  mixtures with halocarbons
  Phosphine:  generated  by contact of moisture  in  air  with  aluminum
     phosphide; Phostoxin
  Naphthalene: ingredient of many domestic moth repellent balls and flakes

TOXICOLOGY

  The primary toxic actions  of the  organic oxides, aldehydes, and  sulfur
dioxide are irritant effects on the skin, mucous membranes, and lung. Dermal
contact with the oxide and aldehyde gases may cause reactions varying from
mild irritation to vesiculation and deep necrosis of the skin. Inhaled fumigant
may induce edema of the larynx or lung.

  Like other fumigants, these substances are rapidly absorbed  by  the lung.
Also, the oxides and aldehydes may penetrate the skin in sufficient dosage to
cause poisoning by this route of absorption alone.
  Deep dermal necrosis  has resulted from severe skin exposures to ethylene
oxide. Liquid  forms of ethylene  and propylene oxide are the most damaging
on  contact.  Material splashed in the eyes may result in permanent corneal
scarring.  Propylene oxide is somewhat  less  tissue-damaging than ethylene
oxide. Excessive  absorption  of  these oxides  results  in systemic illness  due
mainly to toxic effects on the central nervous  system. The oxides also damage
the liver and  kidneys. They are usually formulated with carbon dioxide to
reduce explosion hazard.
  The aldehydes also produce systemic illness when absorbed. This is mani-
fest primarily  as CNS depression. Systemic toxicity  may result from degrada-
tion products  in the cases of ethyl formate (formic  acid) and methyl formate
(methyl  alcohol).  Although  pulmonary  edema  can result  from  excessive
exposure, formaldehyde and acrolein are more likely to embarrass respiration
by  inducing laryngeal edema.
  The primary toxic actions of carbon disulfide, hydrogen cyanide,  acrylonit-
rile, phosphine, and naphthalene are systemic rather than irritative.
   Carbon  disulfide (CSu),  or  thiocarbamates formed  metabolically from
CSL>, impair the activities of multiple enzymes essential to normal  function
of  the brain and  the  peripheral nerves.  In  acute  exposure, this neurotoxic
action is much more prominent than are effects on the liver and  kidneys. The
ability of thiocarbamates to chelate the copper components of certain cerebral
enzymes has been cited as  a major mechanism of  neurotoxicity. Protracted
occupational  exposure to carbon  disulfide  has caused  a great variety  of
disabling neuropsychiatric disorders, due, apparently, to irreversible  effects
of  the toxicant on brain tissue itself, or on the cerebral vasculature. Peripheral

                                   54

-------
neuropathy is another common sequel of long-term carbon disulfide exposure.
   Hydrogen cyanide (HCN)  and its salts poison by inactivating the cyto-
chrome oxidase of cells  in critical  tissues, primarily the heart and brain.
Acrylonitrile  degrades  slowly to HCN in the body, and  therefore acts by
the same  mechanism, although the  slow  release of free cyanide renders it
less toxic than  HCN  itself.  Both  HCN  and acrylonitrile are sufficiently
absorbable across  the skin to cause poisoning in the absence of inhalation
exposure.  Manifestations  of poisoning  are due mainly to intracellular anoxia
of brain tissue (leading  to respiratory failure),  and to the circulatory in-
sufficiency that results from myocardial weakness. The liver has substantial
capacity for conversion of cyanide to the  less toxic thiocyanate, a metabolic
conversion that is  accelerated by therapeutically administered  thiosulfate.
   Inhaled phosphine gas  (PH3)  and ingested metal  phosphides cause  pul-
monary edema, CNS depression,  toxic myocarditis, and circulatory collapse.
Victims who  survive these immediate actions suffer liver injury (fatty de-
generation and necrosis),  and  acute renal  tubular necrosis. Phosphine is not
hemolytic, like its analogue  arsine.  Enzymatic mechanisms of toxicity are
not known. Ingested metal phosphide causes  intense gastrointestinal irrita-
tion, followed by degenerative and  necroti/ing lesions of the liver, kidney
and  heart. Death  is often due either to  cardiogenic shock  or pulmonary
edema.

   Naphthalene is metabolized to naphthols, which are chemical hemolysins.
Some  members  of dark-skinned races are genetically  more  vulnerable  to
these metabolites because of red cell deficiency of glucose-6-phosphate dehy-
drogenase. Severe  anemia and/or acute renal tubular  necrosis result from
the hemolysis. A few individuals develop dermal  hypersensitivity to naphtha-
lene. Corneal ulcers and  cataracts have occurred in laboratory animals, and
rarely in humans as a result of occupational exposure to vapor and dust.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

   The  ORGANIC OXIDES, ALDEHYDES,  and SULFUR  DIOXIDE
irritate  skin and mucous membranes,  causing BURNING, REDNESS and
SWELLING  on contact.  LARGE  BLISTERS,  and  sometimes deep tissue
BURNS, result when an area of contact has been occluded by gloves or other
clothing. CONJUNCTIVAL REDNESS and LACHRYMATION result from
eye exposure.  HOARSENESS reflects  laryngeal irritation,  and may  portend
life-threatening laryngeal  edema.  DYSPNEA,  SUBSTERNAL PRESSURE,
HACKING COUGH,  and FROTHY SPUTUM  are  signs  of pulmonary
edema,  which may progress  to  cause CYANOSIS  and UNCONSCIOUS-
NESS. Although irritant effects are usually severe enough that  exposed indi-
viduals leave contaminated atmospheres promptly, rapid absorption of oxides
and  aldehydes has  resulted  in severe  systemic toxicity:  HEADACHE,
NAUSEA, VOMITING, DIARRHEA, PAIN IN  CHEST AND ABDOMEN,
and DEPRESSED RESPIRATION.
  CARBON  DISULFIDE has moderate  irritative effects  on  the skin  and
mucous membranes,  but  the major  symptoms of poisoning  are  those of a
                                  55

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toxic encephalopathy: HEADACHE, NAUSEA, DIZZINESS, WEAKNESS,
DELIRIUM, PARESTHESIAE, HALLUCINATIONS of hearing, vision,
and smell, CONVULSIONS and RESPIRATORY DEPRESSION.
  Excessive absorption of HCN or ACRYLONITRILE may produce sud-
den UNCONSCIOUSNESS and RESPIRATORY ARREST, without warn-
ing  symptoms.  Lesser exposures  cause HEADACHE,  NAUSEA, and a
sense of CONSTRICTION in the THROAT, followed by APPREHENSION,
DIZZINESS, and HYPERPNEA. Deepening toxicosis is manifest as IR-
REGULAR RESPIRATION, BRADYCARDIA, THREADY PULSE and
UNCONSCIOUSNESS.  CONVULSIONS may be either EPILEPTIFORM
or TONIC,  with OPISTHOTONUS, TRISMUS,  and loss of sphincter con-
trol. RESPIRATORY PARALYSIS follows the seizures. Heart action often
continues  after  breathing  has  stopped:  vigorous  treatment at this  critical
stage has  saved some victims of  cyanide  poisoning.  The SKIN  generally
remains PINK  in  color,  rather than  becoming cyanotic, due  to failure
of poisoned tissue cells to remove  oxygen from the capillary blood.
  PHOSPHINE GAS  poisoning is  usually heralded  by  WEAKNESS,
TREMORS, VOMITING, SENSE OF PRESSURE in the CHEST, COUGH
and DYSPNEA, the latter sometimes progressing to PULMONARY EDEMA.
INTENSE THIRST is probably a result of HYPOTENSION and dehydrating
DIARRHEA.  Severe poisonings produce  CONVULSIONS,  COMA, and
RESPIRATORY  DEPRESSION,  leading  to death. Liver injury  in those
who survive the initial phases  is indicated  by elevations of serum activities
of alkaline phosphatase, GOT, GPT and LDH,  and sometimes by reduced
prothrombin concentration, hemorrhage,  and jaundice.  Renal toxicity causes
ALBUMINURIA,  HEMATURIA  and, in  the  most severe  poisonings,
ANURIA.  Chronic  exposures  to  lesser concentrations of phosphine  have
caused  PAIN  in the EYES  and NOSE,  NOSEBLEEDS',  and chronic
ABDOMINAL  DISTRESS.
  INGESTED  METAL  PHOSPHIDE produces intense NAUSEA and
(usually) VOMITING, followed  by manifestations  of liver,  kidney, lung,
heart and CNS injury that are characteristic of phosphine poisoning. Hypo-
calcemic TETANY (probably from hyperphosphatemia), and METABOLIC
ACIDOSIS typically develop several hours  after metal  phosphide ingestion.
  Most poisonings by NAPHTHALENE  have resulted from occupational
exposures in the petrochemical industry, although one infant victim absorbed
the  agent  from mothball-treated  diapers. Extreme exposures  by inhalation
cause HEADACHE, NAUSEA,  VOMITING, CONFUSION  and TREM-
ORS. Ingestion  causes ABDOMINAL PAIN and  DIARRHEA. Poisoning by
either route may progress to CONVULSIONS, COMA, and death by RES-
PIRATORY FAILURE. Acute  hemolytic  action  may cause  ANURIA
from the tubular  damage induced by HEMOGLOBINEMIA  and HEMO-
GLOBINURIA. Slow hemolysis may be tolerated by  the kidney, but WEAK-
NESS and  INANITION  result from the ANEMIA.  Hemolytic JAUNDICE
may  develop from normal degradation  of the heavy  load of  unconjugated
                               56

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hemoglobin.  DERMATITIS  has  appeared where skin was  covered  by
naphthalene-impregnated  fabric.   Photosensitization  has  also   occurred.
BLINDNESS from lens cataracts and optic neuritis have resulted from pro-
tracted industrial exposures to naphthalene.
CONFIRMATION OF DIAGNOSIS
  Methods for  detecting the organic oxides, aldehydes,  and sulfur dioxide
are not generally available, but they are rarely  needed. A simple method is
available for detecting carbon disulfide in urine  (Djuric et al. Brit. J. Indust.
Med. 22:321-323.  1965).  Cyanide can be detected and measured in  blood
and tissues, as can the thiocyanate  metabolite in urine and saliva. There are
no practical analytical methods for phosphine. Exposure to naphthalene can
be  assessed by  measuring urinary naphthols  (although  some other  toxic
substances yield the same  metabolite), and should be suspected in all cases
exhibiting hemoglobinuria. Odor of gases on the victim's breath  are  some-
times helpful diagnostic clues: cyanide  smells  like  bitter almonds, carbon
disulfide  like  rotten cabbage, and phosphine somewhat like  garlic or  acety-
lene.

TREATMENT

   1.  The  following measures are appropriate  in  treating all  injuries  and
      illnesses caused by FUMIGANTS:
      A.  REMOVE  VICTIM  from  contaminated atmosphere to FRESH
         AIR.

      B.  If respiration is depressed, RESUSCITATE with intermittent posi-
         tive pressure breathing  (IPPB) apparatus, if available; if not  avail-
         able, administer artificial respiration  by periodic mouth-to-mouth
         or mouth-to-nose inflation of the chest.
      C.  If SKIN or EYES have been contaminated, FLUSH COPIOUSLY
         with water. Leave skin  exposed to air until victim can be delivered
         to a hospital. EYE INJURIES should always receive  PROMPT
         MEDICAL  ATTENTION.
  2.  The  following  treatment  measures  apply  to  poisonings by  the
      ORGANIC OXIDES, ALDEHYDES, and SULFUR DIOXIDE:
      A.  Insist that the recently  exposed individual REDUCE PHYSICAL
         ACTIVITY to an absolute  minimum.  Transport victim  to an
         emergency  vehicle with minimum disturbance  and then on  to a
         hospital, even though early symptoms  may not seem serious.  Keep
         patient comfortably warm. Place him  in a comfortable sitting or
         semireclining position.
      B.  COMBAT PULMONARY EDEMA by having the victim sit up-
         right,  and  by  administering  OXYGEN by  IPPB  in  sufficient
         concentration to  overcome hypoxemia. Avoid unnecessary use  of
         high (50-100%) oxygen concentrations, as this may exaggerate the
         injury to  lung tissue. A  slight positive expiratory mask pressure

                                  57

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      (4 cm) may be advantageous. Once IPPB has been instituted suc-
      cessfully, small  doses  of  morphine (8-10 mgm) may be given to
      allay  anxiety, reduce  physical  exertion, and promote  deeper
      respiratory excursions.  ROTATING  TOURNIQUETS  on the
      extremities may be of some value; venoclysis  should be considered
      only if  blood pressure is well maintained.  AMINOPHYLLINE
      (0.25-0.50 gm, slowly IV) may be beneficial, and, occasionally,
      rapid digitalization by intravenous  digoxin  may  be considered,
      even  though  the pulmonary edema  is  not  basically cardiac in
      origin.
      CAUTION: serious arrhythmias can result when the myocardium
                 is anoxic.
      Intravenous 50%  glucose or  sucrose  has only transient benefit.
      Epinephrine,  atropine, and expectorants  are generally not helpful,
      and may have harmful side effects: arrhythmias from  adreiiergic
      agents, thickened sputum  from atropine, nausea from expectorants.
      ASPIRATE sputum from the upper respiratory passages regularly.
      TRACHEOSTOMY may be necessary in some cases to cope with
      large flows of edema fluid, and to rescue victims from  respiratory
      obstruction due to laryngeal edema.

   C. COMBAT SHOCK by placing victim in Trendelenburg position.
      Administer electrolyte and sugar solutions intravenously with great
      care, to avoid precipitating or aggravating pulmonary edema. Use
      vasopressor amines with caution, in view  of the irritable state of the
      myocardium.
   D. LIMIT INFLAMMATORY REACTION by  administering steroids
      on a tapered dosage schedule.
   E. CONTROL SECONDARY INFECTION with antibiotics.
   F. WATCH for  RECURRENT PULMONARY EDEMA,  even up to
      2 weeks after the initial episode, particularly  if the victim becomes
      active too soon. Severe  physical weakness usually  indicates per-
      sistent pulmonary injury.

   G. Observe the  clinical  progress  of the  victim  for at least 6 weeks.
      Serial pulmonary  function testing may  be important in assessing
      degree of recovery.
3.  The  following treatment  measures apply to poisonings  by  CARBON
   DISULFIDE (CS2):
   A. Mild poisonings  from brief  respiratory and dermal exposure to
      CS2 are managed best by CAREFUL OBSERVATION to forestall
      serious consequences: respiratory depression,  delirium, convulsions,
      coma.
                                58

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B. CAFFEINE and  sodium benzoate (0.5 gm subcutaneously) may
   help to relieve CNS depression.
C. Do NOT use catecholamine-releasing agents such as reserpine and
   amphetamines.
D. CONVULSIONS  may  be due to  anoxia  from respiratory  depres-
   sion.  Administer   100% OXYGEN by  face  mask  or  IPPB,  if
   available. If not effective, continue oxygen and  administer DIAZE-
   PAM (Valium) slowly IV in dose sufficient to control convulsions,
   but no more  than  10  mgm.  Although not tested in this  type of
   poisoning, diazepam has proven to be a satisfactory anticonvulsant
   in many other circumstances.

    CAUTION:  diazepam may cause hypotension, or may exaggerate
               respiratory depression.  Extravasation  at site  of  in-
               jection may cause severe local irritation.
E. Delirium may  require only careful observation  and restraint of the
   victim until it resolves. If  activity threatens safety of the victim,
   cautious use of diazepam or another  tranquilizer as in (D)  may be
   necessary.
F. An intravenous  infusion containing  0.5-1.5  gm/kg  UREA has
   been used with apparent benefit. Urea, which must  be  added to
   5 % glucose or normal saline to avoid osmotic hemolysis, inactivates
   free CS2 in the tissues.
G. If CARBON BISULFIDE  has been INGESTED, empty the stom-
   ach by INTUBATION, ASPIRATION and LAV AGE. Do NOT
   use IPECAC, because  of probable CNS depression by €82.
      If  victim   is  already unconscious, insert  a cuffed  ENDO-
   TRACHEAL  TUBE prior  to gastric intubation.
      If conscious, place the victim in Trendelenburg position, or left
   lateral  decubitus,  and  prepare   to  aspirate  material from  the
   pharynx promptly  if  vomiting occurs during  INTUBATION of
   the stomach. When tube is in place,  ASPIRATE as thoroughly as
   possible before LAV AGING  the  stomach with 2-3 liters of saline
   or  5% sodium bicarbonate.  Before removing the tube,  instill a
   slurry  of  30 gm  ACTIVATED CHARCOAL  to limit absorption
   of remaining toxicant.
      If  bowel movement has  not  occurred  within  one  hour  of
   ingestion, administer 15 gm SODIUM SULFATE in 6-8 ounces of
   water by ingestion (if victim conscious) or by gastric tube (if victim
   unconscious) to speed elimination of CS2.
      Do NOT give vegetables  oils, which may enhance gut absorption
   of CS2.
                             59

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H. Parenteral  pyridoxine  injections  have been  recommended  for
   chronic CS2 poisoning.
I.  OBSERVE victims of CS2 poisoning for several weeks or months
   for evidence of neurologic disease, psychiatric  illness, peripheral
   neuropathy, hypertension, and chronic gastrointestinal symptoms.
   Every  effort should be made to eliminate, or at least minimize,
   subsequent exposure to CS2.
The following treatment measures apply to poisoning by HYDROGEN
CYANIDE gas.
A. RESUSCITATE unconscious, apneic individuals. Clear secretions
   from airway. Administer  100%  OXYGEN by IPPB, if available.
   Otherwise use mouth-to-mouth  or mouth-to-nose resuscitation.

B. Administer AMYL NITRITE  (perles) by inhalation for  15-30
   seconds of every minute, while  a fresh solution of 3% sodium
   nitrite  is being prepared.

C. As soon as solution is available, INJECT intravenously  10  ml of
   3% SODIUM NITRITE solution over 2-4 minute interval, keeping
   the NEEDLE IN PLACE.
   CAUTION: Monitor  PULSE and BLOOD  PRESSURE during
              administration of amyl nitrite and  sodium nitrite. If
              systolic blood pressure falls below  80 mm  Hg, slow
              or  stop  nitrite   administration until  blood  pressure
              recovers.
D. FOLLOW sodium nitrite injection with an infusion  of  50  ml of
   25% aqueous solution of SODIUM THIOSULFATE administered
   over 10-minute period.  Total adult  dose  should not exceed 12.5
   gm.
E. If symptoms  persist or recur,  treatment  by sodium nitrite  and
   sodium thiosulfate should be REPEATED at HALF THE  DOS-
   AGES listed in paragraphs C and D.
F. Measure HEMOGLOBIN and METHEMOGLOBIN in blood. If
   more than 50% of total hemoglobin has been converted  to methe-
   moglobin,  BLOOD TRANSFUSION  or  EXCHANGE  TRANS-
   FUSION should be considered, because conversion back  to normal
   hemoglobin proceeds  slowly.
G. Dosage of ANTIDOTES in CHILDREN:
      C. M. Berlin (Pediatrics 46:  793-796. 1970) has recommended
      the following procedures in case of cyanide poisoning in children.
   (1) Children over 25 kg body weight should receive adult dosages
       of  sodium nitrite and sodium  thiosulfate.
                            60

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         (2) Children less than 25 kg body weight should first have a 3-4 ml
            sample of blood drawn, then, through the same needle, receive
            10 mgm/kg (0.33 ml/kg of 3% solution) of SODIUM  NI-
            TRITE 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.
         (3) At this point, determine the hemoglobin content of the original
            blood sample.  If symptoms and signs of poisoning persist, or
            return,  give  supplemental  infusions  of  sodium nitrite   and
            sodium thiosulfate based  on hemoglobin  level, as presented in
            TABLE 2. (These recommended  quantities are calculated to
            avoid life-threatening methemoglobinemia in anemic children.)

TABLE  2.  Recommended  dosages of  supplemental  sodium nitrite   and
             sodium thiosulfate based on hemoglobin level.
          Initial               Supplemental             Supplemental
        Hemoglobin            Volume  of 3%          Volume of 25%
       Concentration,           Sodium Nitrite.         Sodium Thiosulfate,
        gm/100 ml               ml/kg                 ml/kg
          14.0                 0.26                  1.28
          13.0                 0.21                  1.05
          12.0                 0.17                  0.83
          11.0                 0.12                  0.60
          10.0                 0.07                  0.38
            9.0                 0.04                  0.23
            8.0                    0                     0
            7.0                    0                     0

         (4) When methodology is available, monitor  BLOOD levels of
         METHEMOGLOBIN  to  achieve  approximtely 40%   conver-
            sion of hemoglobin to methemoglobin.

      H.  Alternative antidoes, notably cobalt EDTA, are under investigation
         in Europe, but are not available for use in the U.S.
  5.  The following measures  apply to poisonings  by PHOSPHINE GAS
      and INGESTED METAL PHOSPHIDES:

     A. Advise person recently exposed to PHOSPHINE to LIMIT PHYSI-
        CAL ACTIVITY STRICTLY, even though early symptoms do  not
        seem  serious.  Put  victim in comfortable sitting or semi-reclining
        position during removal to a treatment facility. Provide comfortable
        warmth.  WATCH  closely for PULMONARY  EDEMA  and
        SHOCK,  also for  subsequent LIVER DAMAGE and ACUTE
        TUBULAR NECROSIS.

     B. Combat PULMONARY EDEMA and SHOCK as outlined under
        treatment for poisonings by ORGANIC OXIDES, section 2, para-
        graphs B and C.(p. 57-58).
                                 61

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   C. Treat CONVULSIONS as outlined under treatment for CARBON
      BISULFIDE poisonings, section 3, paragraph D. (pg. 59)
   D. Intravenous INFUSIONS of electrolyte and glucose solutions may
       accelerate  excretion  of toxicant and protect  the liver from to»cic
      injury. However, it is essential to MONITOR FLUID BALANCE
      and to take other precautions to avoid an excessive fluid load. Many
      factors—lung tissue injury, toxic myocarditis, renal tubular damage
      —predispose to pulmonary edema.

   E. MONITOR urine  albumin and  sediment  to assess renal injury.
      Observe serum bilirubin,  and serum  activities  of  alkaline phos-
      phatase, GOT, GPT and LDH to evaluate effects on liver. Examine
      EKG tracings for indications  of toxic myocarditis.

   F. For INGESTIONS of METAL PHOSPHIDES, promptly EVACU-
      ATE the stomach. If victim is fully alert and is not already vomit-
      ing copiously, INDUCE EMESIS with SYRUP of IPECAC: adult
       dose 30 ml; child's dose 15 ml.
         If victim is unconscious, evacuate stomach by INTUBATION,
      ASPIRATION  and LAVAGE while observing precautions cited
      in treatment  of poisonings by  CARBON DISULFIDE, paragraph
      G. Follow  by CATHARSIS as described in the same paragraph.
      (Pg- 59)
6.  The following measures apply to poisonings by NAPHTHALENE:

   A. Careful  OBSERVATION  and tranquilization  may be  the  only
      necessary treatment of mild poisoning when no  hemolytic reaction
      occurs.
   B. If  naphthalene  has  been INGESTED,  evacuate  stomach  by
      INTUBATION, ASPIRATION, and LAVAGE,  observing  pre-
      cautions cited in the treatment of poisonings by CARBON DISUL-
      FIDE, paragraph G. Follow by CATHARSIS, as described in the
      same paragraph. (Children's dosage of sodium sulfate is 0.2 gm per
      kg body weight.) Do NOT give vegetable oils, which may accelerate
      absorption  of naphthalene.

   C. For HEMOLYTIC REACTION, give intravenous INFUSIONS of
      electrolytes and glucose  to accelerate excretion of  unconjugated
      hemoglobin. Administer enough sodium bicarbonate to keep urine
      mildly alkaline.

      CAUTION: MONITOR fluid balance and  urine sediment regular-
                  ly to forestall excessive hydration should anuria occur
                  from acute tubular necrosis. In  this event, maintain
                  fluid and electrolyte balance by extracorporeal hemo-
                  dialysis.

      Corticosteroids  may limit  the  hemolytic reaction. Monitor serum
      BILIRUBIN. Severe hyperbilirubinemia may have to be treated

                                  62

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   by exchange transfusion or hemodialysis. ANEMIA may require
   multiple small TRANSFUSIONS of cells, preferably those  not
   deficient in glucose-6-phosphate dehydrogenase.

D. WARN sensitive individuals to avoid  all  future contact—domestic
   and occupational—with naphthalene.
                                 63

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               PESTICIDES  INDEX
                                             T.   *
                                             Page
  Aatrex  ...............................   27
  Acaraben  .............................    1
  Acetamide based  herbicides  ..............   27
  Acetanilide based  herbicides  ..............   27
  Acme Weed  Killer ......................   40
  Acquinite   ............................   48
  Acritet  ............................  48, 54
  Acrolein  ..............................   54
  Acrylaldehyde  .........................   54
  Acrylofume  .........................  48, 54
  Acrylonitrile   ..........................   54
  Af alon  .................... ...........   27
  alachlor  ..............................   27
  aldicarb  ..............................    9
  aldrin  ................................    I
  Aldrite  ...............................    1
  allidochlor  ............................   27
  AMA   ...............................   40
  Ambox   ..............................   21
  Ametrex   .............................   27
  ametryn   .............................   27
  ammonium methane  arsenate  ............   40
  Anilide  based  herbicides  ................   27
  Ansar 157  ............................   40
  Ansar  170  ..........................   40
  Ansar 529 ............................   40
  Ansar 8100  ...........................   40
  Anticoagulant Rodenticides  ..............   35
  Antrol Crabgrass Killer ..................   40
  Aquacide  .............................   13
  Aquakill  ..............................   13
  Aqualin  ..............................   54
  Aquatate  .............................   13
  Aquatic Weed Killer  ....................   13
  Arasan  ...............................   31
  Areginal   .............................   54
  Arsanilic Acid  .........................   40
  Arsenical Pesticides .....................   40
  arsenic acid  ...........................   40
  arsenic trioxide ........................   40
  Arsine  gas ............................   40
  As-655 Weed Killer .....................   40
*Page number refers to chapter in which pesticide is covered
 rather than the specific page number it appears on.

                          64

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Atlas A 	  40
Atranex  	  27
atraton 	  27
Atratone	  27
atrazine  	  27
azinphos-methyl  	    4
Azodrin  	    4
Baygon  	    9
Baytex  	    4
benzene  hexachloride 	    1
BHC  	    1
Bidrin	    4
binapacryl  	  21
Biochecks  	  40
Black Leaf Grass Weed and Vegetation
   Killer  Spray	  24
Bladafume  	    4
Bladex  	  27
Bo-Ana  	    4
Borea  	  27
Borocil IV 	  27
Borolin  	  27
Broadleaf Weed  Killer	  18
Broadside  	  40
bromacil	  27
Bromofume 	  48
Brom-O-Gas  	  48
Bueno  	  40
Burpee Crabgrass Killer 	  40
Butoxone  	  18
Butyrac  	  18
Bux   	    9
cacodylic acid 	  40
Caid  	  35
Caparol  	  27
Carbanilate based herbicides	  27
Carbamates  	   9
Carbacryl	48, 54
carbaryl  	   9
carbofuran  	   9
carbon bisulfide  	  54
                         65

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Carbon  disulfide  	   54
carbon tetrachloride	   48
carbophenothion  	    4
CDAA  	   27
Celmide  	   48
Certified Kiltrol-74 Weed Killer	   24
C-4000   	   40
Chemonite  	   40
Chemox PE 	   21

Chickweed  and Clover Killer	   18
Chipco Crab Kleen 	   40
Chlordan  	    1
chlordane  	    1
chlorobenzilate   	    1
Chloroform  	   48
Chloro IPC 	   27
chlorophacinone  	   35
Chlorophenothane  	    1
Chlorophenoxy compounds  	   18
Chlor-O-Pic 	   48
chloropicrin 	   48
chlorpropham   	   27
chlorpyrifos 	    4
Ciba-Geigy Ontrack OS 3, 4 or 5	   24
Ciodrin   	    4
CIPC 	   27
Clout 	   40
Copper  acetoarsenite  	   40
copper  arsenite  	   40
Co-Ral  	    4
coumafuryl  	   35
Coumarin  	   35
coumophos  	    4
Counter  	    4
Crabgrass Broadleaf Killer  	   40
Crabgrass Dallis Grass Killer	   40
crotoxyphos 	    4
crufomate  	    4
cyanazine 	   27
Cyanide  	   54
Cyclon  	   54
Cygon  	    4
cyprazine  	   27
Cythion  	    4
                     66

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                     —D—

 Dacamine  	   18
 Daconate  	   40
 Dalf  	    4
 Dandelion Killer  	   18
 Dasanit   	    4
 D-Con  	   35
 D-D  	   48
 DDT  	    1
 DDVP  	    4
 Ded-Weed  	   18
 Delnav  	    4
 demeton  	    4
 demeton-metnyl 	    4
 desmetryn  	   27
 Dessicant L-10 	   40
 Dethmor  	   35
 Dextrone X  	   13
 diazinon  	    4
 Dibrom   	    4
 dichloropropane   	  48
 dichloropropene 	  48
 dichlorvos  	   4
 dicofol  	    1
 dicrotophos  	   4
 dieldrin   	    1
 Dieldrite  	    1
 Di-Kill Vegetation Killer	  13
 Dimecron  	   4
 dimethoate  	   4
 Dimethyldithiocarbamate compounds 	  31
 dinitroorthocresol  	  21
 Dinitrophenol  	  21
 dinobuton  	  21
 dinopenton   	  21
 dinoprop  	  21
 dinosam  	   21
 Dinoseb  	   21
 dinosulfon  	   21
 dinoterb  	   21
dinoterbon 	   21
Di-on  	   27
dioxathion  	    4
diphacinone 	   35
diphenadione  	   35
Dipterex  	    4
                        67

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Diquat 	  13
Di Sodium Methyl Arsonate	  40
disulfoton   	   4
Disyston	   4
Dithione 	   4
Diurex 	  27
diuron 	  27
D Krab R +  Prills	  40
DLP-787  	  44
DMA  	  40
DNAP 	  21
DNBP 	  21
DNC   	  21
DNOC 	  21
DNOCHP   	  21
DN-111 	  21
DN 289 	  21
Dowfume W-85 	  48
Dowicide-7  	  24
DPA   	  27
Drat  	  35
Drinox 	   1

DSMA 	  40
Dual Paraquat 	  13
Dursban   	   4
Dyfonate   	   4
Dylox  	   4

                    —E—

EDB   	  48
EDC   	  48
E Krab R  	  40
EM-7217   	  13
Endosan	  21
endosulfan  	   1
endrin 	   1
Entex  	   4
EPN	   4
epoxy propane 	  54
erbon  	  18
Esteron  	  18
Estone 	  18
ethylene dibromide 	  48
ethylene dichloride 	  48
Ethylene  oxide 	  54
                       68

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ethyl  formate  	   54
ETO   	   54
Evik  	   27

                    —F—

Famfos  	    4
famphur  	    4
Fenac  	   18
fensulfothion  	    4
fenthion  	    4
Ferbam  	   31
Fernasan  	   31
Fertilome Nutgrass and Weed Killer	   40
fonofos  	    4
Formaldehyde	   54
Formalin  	   54
forte   	   31
Fumarin  	   35
Fumigant-1  	   48
Furadan  	    9
Furloe  	   27
Gammexane  	    1
Gesafram  	   27
Gesagard  	   27
Gesamil  	   27
Gesapax  	   27
Gesaprim  	   27
Gesatop  	   27
Gordon Termi Tox 	   24
Gramonol  	   13
Gramoxone S 	   13
Greenfield Crabgrass and Dandelion Killer ...   40
Guthion  	    4
                    —H—

Heavy  Duty Weed Control	   13
HCH  	    1
heptachlor  	    1
Hexadrin  	    1
HOE 2810  	   27
hydrocyanic  acid 	   54
Hydrogen  cyanide 	   54
                       69

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Hyvar X  .............................   27
Hyvar X-L  ...........................   27

                    —I—

Igran ................................   27
Isocil ................................   27
Isotox   ...............................    1
Karmex  ..............................   27
Kayafume  ............................   48
Kelthane   .............................    1
Kepone  ..............................    1
Kill All  ..............................   40
Kop-Fume  ............................   48
Korlan ...............................    4
Kuron ...............................   18
Kypfarin   .............................   35
Landrin  	    9
Lannate  	    9
Lasso  	   27
Lawn Weed Killer	   40
Lincks Liquid Di-met  	   40
lindane   	    1
linuron  	   27
Liphadione	   35
Lorox   	   27

                    —M—

MAA  	   40
Mad  	   40
malathion  	    4
Marlate  	    1
MCPA  	   18
MCPB  	   18
MCPP  	   18
Me Br  	   48
Mecoprop  	   18
Mesurol  	    9
metalkamate  	    9
Metallodimethyldithiocarbamates  	   31
Metasystox  	    4
                      70

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methamidophos 	    4
methane  arsonic acid  	   40
methiocarb  	    9
Meth-O-Gas  	   48
methomyl  	    9
methoxychlor 	    1
methyl bromide 	   48
methylene chloride  	   47
methyl formate 	   54
methyl parathion   	    4
mevinphos 	    4
Microzul   	   35
Mildex 	   21
Milogard  	   27
mirex  	    1
Mocap 	    4
Monitor  	    4
monocrotophos  	    4
Mono Sodium Methyl Arsonate	   40
Monurex   	   27
monuron   	   27
Morfamquat  	   13
Morfoxone 	   13
Morocide 	   21
MSMA  	   40

                    —N—

naled  	    4
Naphthalene  	   54
Neguvon   	    4
Nephis 	   48
Nitrophenolic Herbicides 	   21
Nomersan  	   31
Nudrin 	    9
Nutgrass  Spray 	   40
Organochlorine Pesticides 	    1
Organophosphate Pesticides 	    4
Ortho Crabgrass  Killer 	   40
Ortho Spot Weed and Grass Killer	   13
Ortho Triox Liquid Vegetation Killer 	   24
Outfox   	   27
oxamyl  	    9
oxirane   	   54
                        71

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                    —p—

Paracide   	  48
Paradichlorobenzene  	  48
Paradow   	  48
Paraformaldehyde  	  54
Paraquat  Cl 	  13
Parathion  	    4
Paris Green 	  39
Pax  Total  	  40
PCP 	  24
PDB   	  48
Penchlorol  	  24
Penite	  40
Pentachlorophenol   	  24
Pentacon   	  24
Penwar  	  24
Pestmaster  	  48
Pestmaster  EDB-85  	  48
phorate  	    4
Phosdrin   	    4
phosphamidon 	    4
Phosphine  	  54
Phostoxin  	  54
Phytar 560 	  40
Pic-Clor  	  48
Picfume  	  48
picloram   	  27
pindone  	  35
Pivacin 	  35
Pival   	  35
Pivalyn  	  35
PMP   	  35
Pomasol    	   31
Pomasol  Z forte	   31
Potassium  Arsenite 	   39
PP-745  	   13
Pramitol    	   27
Preeglone extra  	   13
Primatol A  	   27
Primatol  P 	   27
Primatol Q	   27
Primatol S 	   27
Princep  	   27
Profume  	   48
Prolin  	   35
prometon  	   27
prometone 	   27

                        72

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Prometrex  	   27
prometryn  	   27
Propachlor  	   27
Propanex  	   27
propanil  	   27
propazine   	   27
Propenal  	   54
propoxur  	    9
Propylene oxide  	   54
Proturf Monocot Weed Control	   40
prussic acid 	   54
Purina Insect Oil Concentrate 	   24
Purina Top Grass and Weed Killer	   40

                     —R—

Ramik  	   35
Ramrod  	   27
Ramucide   	   35
Randox  	   27
Raviac  	   35
Rax  	   35
Reglone  	   13
RH-787  	   44
ronnel  	    4
Rotomet  	   35
Ruelene  	    4
                     	§	

Sarclex  	  27
Scogal  	  27
Sears Liquid Crabgrass Killer	  40
Selector  #1  	  40
Semeron 	  27
Sevin  	    9
Shortstop E 	  27
Silvex  	  18
Silvisar  510 	  40
Simanex 	  27
simazine 	  27
Sinbar  	  27
Sinox  	  21
sodium  arsenite  	  40
sodium  cacodylate  	  40
sodium  dimethyl arsinate  	  40
Sodium pentachlorophenate  	  24

                        73

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Soilbrom  	   48
Spectracide  	    4
Spot Grassy Weed Killer	   40
Stam   	   27
Strobane  	    1
Strobane-T 	    1
sulfotepp  	    4
Sulfuryl fluoride  	   48
Super Crab E-Rad	   40
Systemic Crabgrass and Broadleaf Killer	   40
Systox  	    4

                     —T—

Telone  	   48
Telvar  	   27
Temik  	    9
TEPP  	    4
terbacil 	   27
terbutryn  	   27
terpenepolychlorinates  	    1
Tersan  	   31
Tetramethyl thiuram disulfide  	   31
Thimet 	    4
Thiodan 	    1
Thiophos  	    4
Thiotex  	   31
Thiram 	   31
Thiramad	   31
Thirasan  	   31
Thylate  	   31
Tirampa 	   31
TMTDS 	   31
Topitox  	   35
Tordon  	   27
Toxakil  	    1
toxaphene  	    1
Triazine based herbicides  	   27
Tri-ban  	   35
Trichlor 	   48
trichlorfon 	    4
Trithion 	    4
TUADS 	   31
2,4-D 	   18
2-4-DB  	   18
2,4-DEP   	   18
2,4,5-T  	   18
                         74

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2,4,5-TP  	   18

                    —U—

Uracil based herbicides	   27
Urea  based herbicides 	   27
Urox  HX or B	   27
Usol Cabin Oil	   24

                    —V—

Vacor® Rat Killer	   44
valone  	   35
vapam  	   31
Vapona  	   4
Vegetation Killer 	   18
Vegetrole  	   13
Veg-I-Kill  	   24
Vikane  	   48
Vonduron  	   27
Vydate  	   9

                    —W—

warfarin  	   35
Warf-42  	   35
Warficide  	   35
Watrol  	   13
Weed-B-Gon  	   18
Weed-E-Rad  	   40
Weedestron  	   18
Weed-No-More  	   18
Weedol   	   13
Weedone 	  18,  24
Weed  or Brush-Rhap  	   18
Weed-Out  	   18
white  arsenic  	   40
Wood Preserver	   24
Wood Tox  140 	   24
Zectran   	   9
Ziram 	  31
Zotox Crabgrass  Killer  	  40
                       75

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