RECOGNITION AND MANAGEMENT
        OF PESTICIDE POISONINGS
U. S. ENVIRONMENTAL PROTECTION AGENCY
     OFFICE OF PESTICIDE PROGRAMS
            WASHINGTON, D.C. 20460
                AUGUST 1976

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EPA-540/9-011
     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.

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               CONTENTS
                                       Page
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
UREA-, URACIL- AND TRIAZINE- BASED
  HERBICIDES	  27
ACETANILIDE-, ACETAMIDE-, CARBANILATE-,
  AND ANILIDE-,  BASED HERBICIDES	  30
DIMETHYLDITHIOCARBAMATE COMPOUNDS	  33
ANTICOAGULANT RODENTICIDES	  37
ARSENICAL PESTICIDES	  41
PESTICIDES INDEX	  46

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 SOLID ORGANOCHLORINE  PESTICIDES
CHEMICAL STRUCTURES
                                       ci
     Cl
   LINDANE
 Cl
CHLORDANE
Cl
 DIELDRIN
                S=O
  Cl
                                       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 hi  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 and occasional hypotension.

     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 mgm/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 SYRUP  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,  emes,is 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 CH3O
LEAVING
 GROUP
COMMON COMMERCIAL PESTICIDE  PRODUCTS (approximately  in
  order of decreasing toxicity)
  Highly toxic: TEPP, phorate  (Thimet), mevinphos (Phosdrin),  fensul-
fothion (Dasanit), demeton (Systox), disulfoton (Disyston), sulfotepp (Blada-
fume,  Dithione), Counter, ethyl parathion (Parathion, Thiophos), fonofos
(Dyfonate), EPN, azinphosmethyl (Guthion), methyl parathion (Dalf), mono-
crotophos (Azodrin), dicrotophos  (Bidrin),  methamidophos  (Monitor), car-
bophenothion (Trithion), phosphamidon (Dimecron).
  Moderately toxic: famphur (Warbex, Bo-Ana, Famfos), ethoprop (mocap),
coumaphos  (Co-Ral),  demeton-methyl (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).  Certain  of the organophos-
phates 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
acetylchloline 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 before they are metabolized.  All undergo hydrolytic degrada-
tion in liver and other tissues, usually within hours of absorption. Degrada-
tion 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-
	nrmation of diagnosis by  blood analysis.	
      TABLE  1.   Approximate Lower Limits of Normal Plasma and
             Red Cell Cholinesterase Activities in Humans *
METHOD
ApH (Michel)
pH STAT (Nabb-Whitfield)
ChE-tel (Pfizer)
A ChE-tel (Pfizer)
1-Test Cholinesterase
   (EM Diagnostics)
ACHOLEST Test Paper
Dupont ACA
Garry-Routh      Male
   (Micro)        Female
Merckotest
PLASMA   RBC
   0.4
   2.3
    40
   3.6
  >20
   <8
 0.5
 8.0

210
        7.8
        5.8
        3.0
         UNITS
ApH per ml per hour
fjM per ml per hour
ChE-tel units
A ChE-tel  units

Units per ml
Minutes
Units per ml

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

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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 TV injection is not possible. Atropine protects  the  end-organs  from
     excessive concentrations of acetylcholine. It  does not reactivate cho-
     linesterase, arid  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: 0.02 mgm/kg body weight  (0.05
     ml/kg of usual  0.4  mgm/ml  solution)  repeated  every  15-30 minutes
     until atropinization is achieved.
     In SEVERE poisoning, use  TWICE the dosage of  atropine  recom-
     mended above.
  3.  Administer  PRALBDOXIME (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

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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 3 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 watei^.
    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.  If 'intractable CONVULSIONS  (unresponsive  to  antidotes)  occur in
    severe poisoning, causes unrelated to direct organophosphate action may

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    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.
 9.  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.
10.  DO NOT administer atropine or pralidoxime prophylactically to work-
    ers exposed  to organophosphate pesticides.  It is neither practical  nor
    medically sound to do so.
                                   8

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                      CARBAMATE
         CHOLINESTERASE-INHIBITING
                       PESTICIDES
GENERAL CHEMICAL STRUCTURE
                           O
                           n
                     N - C - O
              H3C
LEAVING
 GROUP
COMMON  COMMERCIAL  PESTICIDE PRODUCTS (approximately  in
  order of toxicity)
  Highly toxic: aldicarb (Temik), oxamyl (Vydate), carbofuran (Furadan),
methyomyl (lannate, Nudrin),  Zectran, methiocarb (Mesurol).
  Moderately toxic: propoxur (Baygon), Landrin,  carbaryl  (Sevin), metal-
kamate (Dux).
  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
 ApH (Michel)
 pH STAT (Nabb-Whitfield)
 ChE-tel  (Pfizer)
 A ChE-tel (Pfizer)
 1-Test Cholinesterase
   (EM Diagnostics)
 ACHOLEST Test Paper
 Dupont ACA
 Garry-Routh      Male
   (Micro)        Female
 Merckotest
PLASMA   RBC
               UNITS
   0.4
   2.3
    40
   3.6
  >20
   <8
 0.5   ApH per ml per hour
 8.0   pM per ml per  hour
      ChE-tel units
210   A ChE-tel units

      Units per ml
      Minutes
      Units per ml
        7.8
        5.8
        3.0
             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: 0.01 mgm/kg body weight (0.05 ml/kg of usual 0.4 mgm/
    ml solution) repeated every  15-30  minutes  until  atropinization  is
    achieved. In SEVERE poisoning: use TWICE the dosage of atropine rec-
    ommended above.
 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 emesjis, 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 LAVAGE, using isotonic saline
    of  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.  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 mgm/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.
 9.  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.
10.  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
CH3-N
                        2cr
           PARAQUAT
                                                       2Br
            CH.
            I  *
            •CH

               N —
       C — CH2—N
      CH.
•CH
 I
 CH.
             CH.
             I  *
            .CH
J—CH0—C—N
                                                     \
                             MORFAMQUAT
             CH
             I
             CH.
                                                •CH.
-CH.
                                                              !\
                                                 2CI
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  humans
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, GPT, 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 kidney 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
                                              i
                                 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 toricity,  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 stomach 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 vivo. 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,  hi
       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.

                                 16

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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
H
                                                        ESTER
                                                        GROUP
                                              or
    N
                                                       METAL
                                                         ION
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 KiUer, Dande-
lion Killer, Vegetation Killer, Chickweed and Clover Killer. Several hundred
herbicide preparations include  one  or  more CHLOROPHENOXY COM-
POUND. 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 hi 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  MUSCLE TWITCHING, SKELE-
TAL MUSCLE TENDERNESS,  and MYOTONIA (stiffness  of muscles of
extremities). Respiratory insufficiency from  muscle weakness  apparently oc-
curred  in one victim of accidental poisoning, 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 absorption.
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
States,  agricultural research facilities, commercial 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,  tracheal  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 12,
       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
                               O—H(or  ESTER)
              (ALKYL)     (ALKYL)

COMMON COMMERICIAL  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, or  slowly IV, 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 LAVAGE 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 hi 6-8 ounces of water;
   children under 12: 0.2 gm/kg body weight in 1-6 ounces of water).
F. DO NOT administer aspirin  or other antipyretics to control 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
                            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  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
        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 hi  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 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.
                           26

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  UREA-,  URACIL-  AND  TRIAZJNE-  BASED
                       HERBICIDES
 GENERAL CHEMICAL STRUCTURES
                                  H
                                 ,N
                          H,C — C
                               II     I     CH.
II
o
                                         C2H5
       UREA                    URACIL               s-TRIAZINE
    DERIVATIVES               DERIVATIVES            DERIVATIVES
  X=HALOGEN      R=ALKYL

COMMON COMMERCIAL PESTICIDE  PRODUCTS
  Urea derivatives: monuron (Monurex, Telvar), diuron (Di-on, Diurex, Kar-
mex, Vonduron), linuron (HOE 2810, Afalon, Lorox, Sarclex).
  Uracil derivatives:  bromacil (Borea, Hyvar  X,  Hyvar X-L, Borocil  IV,
Urox HX or B, Isocil), terbacil (Sinbar).
  Triazine derivatives:  atrazine (Aatrex, Atranex, Gesaprin, Primatol  A),
simazine (Princep, Primatol  S, Simanex,  Gesatop),  propazine  (Milogard,
Gesamil, Primatol  P), prometone  (Pramitol, Gesafram, prometon), atraton
(Atratone), prometryn (Caparol, Gesagard, Primatol Q, Prometrex), ametryn
(Evik, Ametrex, Gesapax), desmetryne (Semeron), terbutryn  (Igran, Short-
stop E), cyanazine (Bladex, Scogal), cyprazine (Outfox).

TOXICOLOGY

  Adverse effects have  occurred only rarely as a result of human contact
with these  herbicides. Most injuries reported have been skin irritation after
prolonged  contact.  Improbability of severe systemic poisoning is indicated
by LD50 values over 180 for all of the compounds listed under COMMON
COMMERCIAL PESTICIDE PRODUCTS. In fact, LD50's for all but  one
herbicide are over 1,000; that for cyanazine is  182 mgm/kg.
  Administered at very high dosage levels to laboratory animals and to sheep
and cattle, some of these chemicals have been found to  injure the nervous
system, liver, and kidneys, and to cause increased permeability of  capillaries.
Anemia  and altered adrenal  function have also been detected in animals
given extreme doses of  certain triazine compounds. These effects have  not
been observed in persons exposed  occupationally or by accidental ingestion.

                               27

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In varying degree these herbicides are likely to produce irritation of the gut
if  ingested in substantial  quantity. They are  efficiently absorbed from the
intestine, and presumably  there is some absorption across the skin and lung.
Following absorption,  they are partially metabolized:  native chemicals  and
metabolities  are  promptly excreted by  the kidney  and liver.  In cases of
accidental ingestion in humans, the hazards of petroleum distillate  solvents
may equal or exceed hazards presented by  the active herbicidal ingredients.

POSSIBLE PRESENTING SYMPTOMS AND SIGNS OF  INJURY

   Some compounds of these classes cause IRRITATION of the eyes  and
mucous membranes, particularly if direct contact is protracted. NAUSEA,
VOMITING, and DIARRHEA can be expected to  result from ingestion
of large quantities.

CONFIRMATION OF ABSORPTION

   Certain industrial, university, and government laboratories can detect these
compounds or their metabolites in the  urine of persons who have absorbed
significant amounts. These laboratories  can be reached through health de-
partments, poison  control centers, or  the U.S. Environmental Protection
Agency.

TREATMENT
  1.  FLUSH contaminant from the eyes  with  copious  amounts of clean
     water.
  2.  WASH chemical from the skin and hair with soap and  water.
  3.  If one of these compounds has been INGESTED, optimal treatment will
     depend on dosage:
     A. Ingestions known to involve less than 10 mgm/kg body weight of
        the compounds having LD50 values over  1,000 (all except cyanazine)
        are probably  managed best without induced  emesis or gastric lav-
        age, particularly  if the ingestion occurred more than an hour  prior
        to  treatment.  In these  cases,  administer  30  gm ACTIVATED
        CHARCOAL in 3-4 ounces of water to  limit absorption. If a bowel
        movement does not occur in 4 hours, give  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).
     B. In all other cases (unknown dosage,  dosage over 10 mgm/kg  body
        weight,  and all  cyanazine ingestions), EMPTY  THE  STOMACH
        either by induced EMESIS or  by gastric LAVAGE:
         (1)  If victim is  alert and respiration is  not depressed, give SYRUP
             OF IPECAC (adults, 12 years and older: 30  ml; children un-
             der 12: 15 ml).
                                 28

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    CAUTION:  OBSERVE the victim closely after administering
                IPECAC.  If consciousness  level  declines,  or  if
                vomiting has not occurred in 15 minutes, proceed
                immediately to EVTUBATE,  ASPIRATE,  and
                LAV AGE  the stomach  with  isotonic  saline or
                sodium bicarbonate solution.
    Following emesis, have victim  drink a suspension of  30 gm
    ACTIVATED  CHARCOAL in 3-4 ounces of water to limit
    toxicant absorption.
(2)  If victim is not fully alert or if  respiration is depressed,  empty
    the stomach immediately by INTUBATION,  ASPIRATION,
    and LAV AGE, using isotonic saline or 5% sodium bicarbon-
    ate. Because 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:
    (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  (Tren-
        delenburg,  or left lateral  decubitus, with head end of
        table tipped downward). Keep the victim's head turned
        to the left.
    (c)  ASPIRATE PHARYNX  as  regularly  as  possible  to re-
        move 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 substances con-
    taining vegetable or animal fats which may enhance toxicant
    absorption.
(3)  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).
                        29

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         ACETANILIDE-,  ACETAMIDE-,
       CAR BAN I LATE-,  AND  ANILIDE-,
               BASED  HERBICIDES
CHEMICAL STRUCTURES
     PROPACHLOR
                                          H
                                     H2C=C— H2C
                                          H
                                                \      H
                                                 N—C—C—Cl
                                                    N  Cl
   ALLIDOCHLOR
             O —CH.
           ALACHLOR
         0
         o

    PROPANIL
                                  — O —
                           CHLORPROPHAM
CH.
I  '
CH
I
CH-
COMMON COMMERCIAL PESTICIDE PRODUCTS
  Propachlor  (Ramrod),  allidochlor (Randox, CDAA),  alachlor (Lasso),
chlorpropham (Chloro IPC, CIPC, Furloe), propanil (DPA, Stam,Propanex).
  Most technical formulations of these materials are in petroleum distillates.

TOXICOLOGY

  These newer herbicides exhibit low systemic toxicity in laboratory  rats
(lowest oral LD50 of those listed is 700 mgm/kg). They are, however,  irri-
tating to skin, eyes, and mucous membranes. Propachlor and alachlor appear
to have sensitizing properties. Severe skin reactions have occurred in  sen-
sitive individuals.
  Any systemic toxicity of these compounds appears only at high dosage
levels. Adverse effects from accidental ingestion by humans have not been
reported. In all likelihood, substantial doses would  cause gastrointestinal
irritation.
                            30

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SYMPTOMS AND SIGNS  OF  UNDUE EXPOSURE
  IRRITATION of the skin and membranes of the upper respiratory tract
is the principal adverse effect of  contact with these compounds. Exaggerated
reactions on repeated  contact (SENSITIZATION) occur in some individuals.
Propachlor has been the  principal offender.  Sensitization  can  result  in
ACUTE and CHRONIC SKIN INJURY, and in protracted irritation of the
nose, eyes, and throat.
  Nausea, abdominal distress, and diarrhea may be expected to result from
ingestion of these compounds.

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 and hair  with  soap and
    water. Severe  irritation may require medical attention.  Persons who
    become  sensitized  may need to take stringent precautions  to  avoid
    subsequent contact with these chemicals.
 3.  Ingestions known to involve less  than 10 mgm/kg body weight are
    probably managed best without induced emesis or lavage,  particularly
    if the ingestion occurred more than an hour before treatment. Admin-
    ister 30 gm ACTIVATED CHARCOAL in 3-4 ounces of water to limit
    absorption. If  a  bowel movement  has not occurred in 4  hours, give
    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).
 4.  Ingestions of  more than 10 mgm/kg  body weight, especially when
    ingestion occurred less  than an hour before treatment, should be man-
     aged by prompt EVACUATION of the STOMACH:
    A. If victim is alert and respiration is not depressed, give SYRUP of
        IPECAC (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 vomiting
                    has not occurred  in  15 minutes,  immediately  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

                                31

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    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 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 remain-
        ing  toxicant. Do not instill  milk, cream,  or other substances
        containing vegetable or animal fats which may enhance toxi-
        cant absorption.
C.  If bowel movement has not  occurred in  4 hours, and if patient is
    fully conscious, give SODIUM SULFATE (Glauber's Salts) as a
    cathartic (adult, 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).
Severe sensitization reactions may require specialized medical manage-
ment to control inflammatory responses that threaten to impair breath-
ing or compromise circulation to the distal  extremities. Reactions of
this severity are rare.
                            32

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         DIMETHYLDITHIOCARBAMATE
                      COMPOUNDS*
GENERAL CHEMICAL STRUCTURE
                      C-S-—--	-S-C-N-(CH3)2
COMMON COMMERCIAL  PESTICIDE  PRODUCTS

  Tetramethyl thiuram disulfide:
Thiram  (Arasan, Thiramad, Thirasan,  Thylate,  Tirampa, Pomasol  forte,
TMTDS, Thiotex, Feraasan, Nomersan, Tersan, TUADS)
  Metallodimethyldithiocarbamates:
Ziram, Pomasol Z forte (zinc), Ferbam (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,  demyelmization 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.

                                 33

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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, 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
   	                                     i
   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.
                               34

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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:
       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 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.

                                 35

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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 artifically 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  LAVAGE, 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.
                            36

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      ANTICOAGULANT  RODENTICIDES
STRUCTURES OF PRINCIPAL CLASSES
                                                    ALKYL. PHENYL.
                                                   DIPHENYLACETYL or
                                                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,
DC,  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
                               37

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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: 0.4 mgm/kg body weight
     IM.
     Note:  PHYTONADIONE  (Vitamin  Kv  Mephyton,  Aquamephyton,
           Konakion)  specifically is  required.  Vitamin K3  (menadione,
           Hykinone)  and vitamin  K4 (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

                                38

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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: 0.4 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 hi 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 0.4 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

                             39

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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).
                                40

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           ARSENICAL  PESTICIDES
CHEMICAL STRUCTURES
EXTREMELY TOXIC: (TRIVALENT INORGANIC ARSENICALS)
  O=A$— O— As s=O

  ARSENIC TRIOXIDE

         O
         II
  Cu— (O— C—
   K—O—As=O
POTASSIUMARSENITE
   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-fonnhig 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.
                                   42

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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  NE^HROSIS, HEPATITIS (hepatomegaly  and
jaundice), and NEUROLOGIC INJURY (delirium, paralysis, respiratory de-
pression) may progress to a fatal outcome.

SUB ACUTE 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 /Agm/day, but diets rich in seafood may generate as much
as 200 /igm/day. Excretions above 100 /xgm/day should be viewed with sus-
picion  and tests should be repeated.  Excretions above 200 /Agm/day reflect

                               43

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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:
                               44

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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, lachrimation, 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.
                               45

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              PESTICIDES INDEX

                                            Page
                     —A—

 Aatrex  	  27
 Acaraben  	    1
 Acetamide based herbicides 	  30
 Acetanilide based herbicides	  30
 Acme Weed Killer  	  42
 Afalon  	  27
 alachlor  	  30
 aldicarb  	   9
 aldrin	   1
 Aldrite  	   1
 allidochlor  	  30
 AMA  	  42
 Ambox  	  21
 Ametrex  	  27
 ametryn  	  27
 ammonium methane  arsenate 	  42
 Anilide based herbicides	  30
 Ansar 157 	  42
 Ansar 170	  42
 Ansar 529 	  42
 Ansar 8100  	  42
 Anticoagulant Rodenticides  	  37
 Antrol Crabgrass Killer  	   42
 Aquacide  	  13
 Aquakill 	   13
Aquatate   	   13
Aquatic Weed Killer	   13
Arasan 	   33
Arsanilic Acid  	   42
Arsenical Pesticides  	   42
 arsenic  acid  	   42
 arsenic  trioxide  	   42
Arsine gas 	   42
As-655 Weed Killer  	   42
Atlas A 	   42
Atranex  	   27
atraton 	   27
Atratone	   27
atrazine  	   27
azinphos-methyl	   4
Azodrin  	   4
                       46

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 Baygon  	    9
 Baytex  	    4
 benzene hexachloride	    1
 BHC	    1
 Bidrin	    4
 binapacryl  	   21
 Biochecks	   42
 Black  Leaf Grass  Weed  and Vegetation
   Killer Spray	   24
 Bladafume  	    4
 Bladex  	   27
 Bo-Ana  	    4
 Borea  	   27
 Borocil IV	   27
 Broadleaf  Weed Killer  	   18
 Broadside  	   42
 bromacil  	   27
 Bueno	   42
 Burpee Crabgrass  Killer  	   42
 Butoxone  	   18
 Butyrac   	   18
 Bux  	    9
cacodylic  acid  	  42
Caid  	  37
Caparol	  27
Carbanilate based herbicides  	  30
Carbamates   	    9
carbaryl  	    9
carbofuran 	    9
carbophenothion  	    4
CDAA  	  30
Certified Kiltrol-74 Weed Killer	  24
C-4000	  42
Chemonite  	  42
Chemox PE	  21
Chickweed and Clover Killer	  18
Chipco Crab  Kleen	  42
Chlordan  	    1
chlordane  	    1
chlorobenzilate	    1
Chloro IPC 	  30
chlorophacinone	  37
Chlorophenothane  	    1
                      47

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Chlorophenoxy compounds	   18
chlorpropham	   30
chlorpyrifos 	    4
Ciba-Geigy Ontrack OS 3, 4 or 5	   24
Ciodrin	    4
CIPC  	   30
Clout  	   42
Copper acetoarsenite 	   42
copper  arsenite  	   42
Co-Ral 	    4
coumafuryl 	   37
Coumarin  	   37
coumophos 	    4
Counter  	    4
Crabgrass Broadleaf Killer  	   42
Crabgrass Dallis Grass Killer	   42
crotoxyphos 	    4
cmfomate	    4
cyanazine  	   27
Cygon	    4
cyprazine  	   27
Cythion	    4
Dacamine 	   18
Daconate  	   42
Dalf  	    4
Dandelion Killer  	   18
Dasanit	    4
D-Con  	   37
DDT  	    1
DDVP  	    4
Ded-Weed  	   18
Delnav  	    4
demeton  	    4
demeton-methyl  	    4
desmetryne 	   27
Dessicant  L-10  	   42
Dethmor	   37
Dextrone X 	   13
diazinon  	    4
Dibrom	    4
dichlorvos  	    4
dicofol 	    1
dicrotophos  	    4
dieldrin  	    1
                       48

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Dieldrite	    1
Di-Kill Vegetation Killer	   13
Dimecron	    4
dimethoate  	    4
Dimethyldithiocarbamate compounds 	   33
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  	   37
diphenadione  	   37
Dipterex 	    4
Diquat  	   13
Di Sodium Methyl Arsonate	   42
disulfoton 	    4
Disyston 	    4
Dithione 	    4
Diurex  	   27
diuron  	   27
D Krab R + Prills	   42
DMA  	   42
DNAP  	   21
DNBP  	   21
DNC  	   21
DNOC  	   21
DNOCHP  	   21
DN-111  	   21
DN 289 	   21
Dowicide-7	   24
DPA	   30
Drat  	   37
Drinox	    1
DSMA	   42
Dual Paraquat 	   13
Dursban  	    4
Dyfonate"  	    4
Dylox  	    4
                      49

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E  Krab R  	  42
EM-7217  	  13
Endosan  	  21
endosulfan  	   1
endrin   	   1
Entex  	   4
EPN 	   4
erbon  	  18
Esteron  	  18
Estone	  18

                    —F—

Famfos ,	   4
famphur  	   4
Fenac  	  18
fensulfothion  	   4
fenthion  	   4
Ferbam	  33
Fernasan	  33
Fertilome Nutgrass and Weed Killer	  42
fonofos 	   4
forte  	  33
Fumarin 	  37
Furadan  	   9
Furloe	  30

                    —G—

Gammexane 	    1
Gesafram 	  27
Gesagard  	  27
Gesamil  	  27
Gesapax 	  27
Gesaprin	  27
Gesatop  	  27
Gordon Termi Tox  	  24
Gramonol	   13
Gramoxone S	   13
Greenfield Crabgrass and Dandelion Killer ...  42
Guthion  	   4

                    —H—

Heavy Duty Weed Control	   13
HCH  	    1
                      50

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heptachlor  	    1
Hexadrin  	    1
HOE 2810	   27
Hyvar X	   27
Hyvar X-L	   27

                    —I—

Igran  	   27
Isocil  	   27
Isotox	    1

                    —K—

Karmex  	   27
Kelthane	    1
Kepone	    1
Kill All  	   42
Korlan 	    4
Kuron	   18
Kypfarin	   37
Landrin  	   9
Lannate  	   9
Lasso  	  30
Lawn Weed Killer	  42
Lincks Liquid Di-met	  42
lindane  	   1
linuron  	  27
Liphadione	   37
Lorox  	  27

                   —M—
MAA  	  42
Mad  	  42
malathion	   4
Marlate  	   1
MCPA  	  18
MCPB  	  18
MCPP  	  18
Mecoprop  	  18
Mesurol  	   9
metalkamate	   9
Metallodimethyldithiocarbamates  	  33
Metasystox	   it
                      51

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methamidophos  	    4
methane arsonic  acid	   42
methiocarb 	    9
methomyl 	    9
methoxychlor  	    1
methyl parathion 	    4
mevinphos  	    4
Microzul	   37
Mildex  	   21
Milogard  	   27
mirex  	    1
Mocap  	    4
Monitor  	    4
monocrotophos  	    4
Mono Sodium Methyl Arsonate	   42
Monurex  	   27
monuron  	   27
Morfamquat  	   13
Morfoxone 	   13
Morocide 	   21
MSMA	   42

                    —N—

naled  	    4
Neguvon	    4
Nitrophenolic  Herbicides  	   21
Nomersan	   33
Nudrin  	    9
Nutgrass Spray  	   42
Organochlorine Pesticides ................   1
Organophosphate Pesticides  ..............   4
Ortho Crabgrass  KiUer  ..................  42
Ortho Spot Weed and Grass  Killer  .........  13
Ortho Triox Liquid Vegetation Killer .......  24
Outfox  ...............................  27
oxamyl  ...............................   9
Paraquat Cl ...........................   13
Parathion  .............................   4
Paris  Green ...........................   41
Pax  Total  ............................   42
PCP  ......................... . .......   24
                      52

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Penchlorol  	  24
Penite	  42
Pentachlorophenol  	  24
Pentacon  	  24
Penwar	  24
phorate  	     4
Phosdrin  	   4
phosphamidon 	   4
Phytar 560	  42
pindone  	  37
Pivacin 	,	  37
Pival	  37
Pivalyn 	  37
PMP   	  37
Pomasol 	  33
Pomasol Z forte  	  33
Potassium Arsenite  	  41
PP-745	  13
Pramitol 	  27
Preeglone extra  	  13
Primatol A	  27
Primatol P 	  27
Primatol Q	  27
Primatol S 	  	  27
Princep		  27
Prolin  	  37
prometon 	  27
prometone	  27
Prometrex  	  27
prometryn  	  27
Propachlor 	  30
Propanex  	  30
propanil  	  30
propazine 	  27
propoxur  	   9
Proturf Monocot Weed Control	  42
Purina Insect Oil Concentrate	  24
Purina Top Grass and Weed Killer	  42

                   —R—

Ramik  	  37
Ramrod  	  30
Ramucide	  37
Randox  	  30
Raviac  	  37
Rax  	  37
                     53

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Reglone  	   13
ronnel	    4
Rotomet 	   37
Ruelene  	    4
Sarclex  	   27
Scogal  	   27
Sears Liquid Crabgrass Killer	   42
Selector #1 	   42
Semeron 	   27
Sevin  	    9
Shortstop  E 	   27
Silvex  	   18
Silvisar  510 	   42
Simanex 	   27
simazine 	   27
Sinbar	   27
Sinox	   21
sodium  arsenite  	   42
sodium  cacodylate	   42
sodium  dimethyl  arsinate 	   42
Sodium pentachlorophenate  	   24
Spectracide  	    4
Spot Grassy Weed Killer 	   42
Stam	   30
Strobane	    1
Storbane-T 	    1
sulfotepp  	    4
Super Crab E-Rad	   42
Systemic Crabgrass and Broadleaf Killer  ....   42
Systox  	    4

                     —X—

Telvar	   27
Temik	    9
TEPP	    4
terbacil 	   27
terbutryn  	   27
terpenepolychlorinates	    1
Tersan  	   33
Tetramethyl thiuram  disulfide	   33
Thimet  	    4
Thiodan 	    1
Thiophos  	    4
                      54

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 Thiotex   	   33
 Thiram   	   33
 Thiramad  	   30
 Thirasan	   30
 Thylate	   30
 Tirampa  	   30
 TMTDS	   30
 Topitox   	,   37
 Toxakil   	    1
 toxaphene  	    1
 Triazine based herbicides 	   27
 Tri-ban   	   37
 trichlorfon  	    4
 Trithion  	    4
 TUADS   	   33
 2,4-D 	   18
 2-4-DB	   18
 2,4-DEP	   18
 2,4,5-T	   18
 2,4,5-TP	   18

                    —U—

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

                      y

 valone  	   37
 vapam  	   33
 Vapona  	 	    4
 Vegetation Killer	   18
 Vegetrole   	   13
 Veg-I-Kill   	   24
 Vonduron   	   27
 Vydate	    9

                    —W—
 warfarin  	   37
 Warf-42  	•	   37
 Warficide  	   37
 Watrol  	   13
 Weed-B-Gon 	   18
 Weed-E-Rad 	   42
Weedestron  	   18
                      55

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Weed-No-More  	   18
Weedol   	   13
Weedone  	   18,24
Weed or Brush-Rhap	   18
Weed-Out  	   18
white arsenic  	   42
Wood Preserver	   24
Wood Tox  140 	   24
Zectran  	    9
Ziram  	   33
Zotox Crabgrass Killer	   42
                     56

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