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             Environmental Protec  EPA-540/9-80-005 1982
             Agencv
vvEPA        Recognition and

             Management of

 I <          Pesticide Poisonings
             Third Edition

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   RECOGNITION AND MANAGEMENT OF
            PESTICIDE POISONINGS

            Donald P. Morgan, M.D., Ph.D.*
   Support for this publication was provided by the National
   Pesticide Hazard Assessment Program, Health Effects
   Branch, Hazard  Evaluation Division,  Office of Pesticide
   Programs,  U.S. Environmental Protection Agency, Wash-
   ington, D.C. 20460.

   *lowa Pesticide Hazard Assessment Project, located at University of
    Iowa Medical School, Iowa City, Iowa 52240.
                 Third  Edition
US  [iV.vi-onrf.pntcil Promotion Agency
Re-p..on V, Lici'.'.y
2'0 ^'.•,:!-, 0 V'ibo.'r; ociCGt.   -_ .,-•
Chicago, iiiinois  60604.
     For sale by the Superintendent of Documents, U.S Government Printing Office, Washington, D.C. 20402

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U,S. Environmental Protection  Agency

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                 Contents
                                       Page
INTRODUCTION	   v
CHAPTER  1—ORGANOPHOSPHATE
           CHOLINESTERASE-INHIBITING
           PESTICIDES	   1
CHAPTER  2—CARBAMATE CHOLINESTERASE-
           INHIBITING PESTICIDES	   9
CHAPTER  3—SOLID ORGANOCHLORINE
           PESTICIDES	  14
CHAPTER  4—PENTACHLOROPHENOL	  19
CHAPTER  5—NITROPHENOLIC AND
           NITROCRESOLIC HERBICIDES ....  23
CHAPTER  6—CHLOROPHENOXYCOMPOUNDS..  27
CHAPTER  7—PARAQUAT AND DIQUAT	  31
CHAPTER  8—DITHIOCARBAMATES AND
           THIOCARBAMATES	  36
CHAPTER  9—PYRETHRUM, PYRETHRINS,
           PYRETHROIDS AND PIPERONYL
           BUTOXIDE	  42
CHAPTER 10—ARSENICAL PESTICIDES  	  46
CHAPTER 11—RODENTICIDES 	  54
CHAPTER 12—FUMIGANTS	  68
CHAPTER 13—MISCELLANEOUS PESTICIDES OF
           HIGHTOXICITY	  77
CHAPTER 14—MISCELLANEOUS PESTICIDES OF
           LOW OR MODERATE TOXICITY ....  82
INDEX TO PESTICIDE POISONINGS BY
SYMPTOMS AND SIGNS	  88
PESTICIDE INDEX	  94

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                       INTRODUCTION
   This manual is designed to help professionals responsible for the health of
 persons exposed to pesticides to recognize and treat properly poisonings by
 these substances.  This third edition discusses many more compounds than
 were dealt with in previous  editions, and it updates particular management
 methods according to recently published clinical literature.
   No text or manual on so complex a topic can presume to take the place of
 good clinical judgment. But it is unrealistic to expect health professionals con-
 fronted with a pesticide poisoning emergency  to assemble quickly the many
 details of toxicology,  diagnosis, and treatment that are essential to optimal
 management.  This manual provides such information in a concise format.
   A deliberate effort has been made to suggest treatment that can be imple-
 mented (or at least initiated) in small hospitals and clinics where victims of
 pesticide poisonings are likely to be received. At the expense of some repeti-
 tion, details of treatment have been spelled out sequentially for the common
 classes of chemical poisonings.
   The author is deeply indebted to the following reviewers who have con-
 tributed generously to this edition:

 S. H. Sandifer, M.D., Professor            J. R. Reigart, M.D., Assoc. Professor
 Director, Division of Preventive Medicine     Department of Pediatrics
 Department of Family Practice             College of Medicine
 College of Medicine                     Medical University of South Carolina
 Medical University of South Carolina        Charleston, South Carolina 29403
 Charleston, South Carolina 29403

 Harold E. Trammel, Pharm.D., Assoc. Prof.   John E. Davies, M.D., M.P.H.
 Director of Poison Information Center        Professor and Chairman
 College of Pharmacy                     Department of Epidemiology
 Medical University of South Carolina          and Public Health
 Charleston, South Carolina                University of Miami School of Medicine

 Arthur D. Nelson, M.D.                   Jon E. Ford, Ph.D.
 Director                               Environmental Toxicologist
 Scottsdale Memorial Hospital              Chevron Environmental Health Center
 Scottsdale, Arizona                       Standard Oil Company of California

   Victor B. Beat, D.V.M., of the Iowa Pesticide Hazard Assessment Project
 compiled the many proprietary  names of the products  listed in the manual.
 Mrs. Pamela Mason and Ms. Diane Cornwall of the Iowa Project have pa-
tiently typed the manuscript drafts.
   Ms. Martha Finan of the Information Support Services Branch, Manage-
ment Support Division, Office of Pesticides and  Toxic Substances of the
United States Environmental Protection Agency  has  skillfully  edited  the
manuscript. Staff of the Health Effects Branch, Hazard Evaluation Division
of the Office of Pesticides and Toxic Substances, United States Environmental
Protection Agency, have prepared the index and attended to  the details of
publication.

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                          Chapter 1

              ORGANOPHOSPHATE
        CHOLINESTERASE-INHIBITING
                      PESTICIDES

 GENERAL CHEMICAL STRUCTURE

 C2H5O or CH3O \  ^ S (or O)
                   . P
 C2H5OorCH3O
COMMON COMMERCIAL PESTICIDE PRODUCTS*

  Highly toxic:  tetraethyl pyrophosphate (TEPP), phorate (Thimet), disulfo-
tonf (Di-Syston), fensulfothion (Dasanit),  demetont  (Systox), terbufos
(Counter),  mevinphos (Phosdrin), methidathion (Supracide),  chlormephos
(Dotan, MC2188),  sulfotepp (Bladafum,  Dithione),  chlorthiophos
(Celathion), monocrotophos (Azodrin), fonofos (Dyfonate), prothoate (Fac),
fenamiphos  (Nemacur),  phosfolan  (Cyolane),  methyl  parathion  (Dalf,
Penncap-M), schradan (OMPA), chlorfenvinphos (Birlane), ethyl parathion
(Parathion,  thiophos),  azinphos-methyl  (Guthion),  phosphamidon
(Dimecron), methamidophos  (Monitor),  dicrotophos (Bidrin), isofenphos
(Amaze, Oftanol), bomyl (Swat), carbophenothion (Trithion), EPN, fam-
phur, (Warbex,  Bo-Ana, Famfos), fenophosphon (Agritox, trichloronate),
dialifor (Torak), cyanofenphos (Surecide).
  Moderately  toxic: bromophos-ethyl  (Nexagan),  leptophos  (Phosvel),
dichlorvos  (DDVP,  Vapona),  coumaphos  (Co-Ral),  ethoprop (Mocap),
quinalphos (Bayrusil),  triazophos (Hostathion),  demeton-methylt
(Metasystox), propetamphos  (Safrotin),  chlorpyrifos  (Lorsban, Dursban),
sulprofos (Bolstar), dioxathion (Delnav), isoxathion (Karphos), phosalone
(Zolone),  thiometon  (Ekatin),  heptenophos (Hostaquick),  crotoxyphos
(Ciodrin), cythioate (Proban), phencapton (G28029), DBF (De-Green, E-Z-
off  D), ethion, dimethoate (Cygon,  De-Fend), fenthion (Baytex,  Entex,
Tiguvon, Spotton, Lysoff), dichlofenthion (Mobilawn),  EPBP (S-Seven),
   These are listed approximately in order of descending toxicity. "Highly
   toxic" organophosphates have listed oral LD50 values (rat) less than 50
   mg/kg; "moderately toxic" agents have LD50 values in excess of 50 mg/kg.
   These organophosphates are systemic; i.e., they are taken up by the plant
   and translocated into foliage and sometimes into the fruit.

                               1

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diazinon (Spectracide), phosmet (Imidan, Prolate), formothion (Anthio), pro-
fenofos (Curacron), naled (Dibrom), phenthoate, trichlorfon (Dylox, Dipterex,
Neguvon),  pyrazophos  (Afugan,  Curamil),  fenitrothion  (Agrothion,
Sumithion), cyanophos (Cyanox), pyridaphenthion (Ofunack), propylthio-
pyrophosphate (Aspon), acephate (Orthene), merphos (Folex), malathion
(Cythion), etrimfos (Ekamet), phoxim (Baythion), pirimiphosmethyl (Actellic),
iodofenphos (Nuvanol-N), bromophos (Nexion), tetrachlorvinphos (Gardona,
Rabon), temephos (Abate, Abathion).

TOXICOLOGY

  Organophosphates poison insects and mammals primarily by phosphoryla-
tion of the acetylcholinesterase enzyme at nerve endings. The enzyme is critical
to normal  transmission of nerve impulses from nerve fibers to innervated
tissues. Some critical proportion of the tissue enzyme mass must be inactivated
by phosphorylation before symptoms and signs of poisoning are manifest. At
sufficient   dosage,  loss  of enzyme  function  allows  accumulation  of
acetylcholine (the impulse-transmitter substance) at cholinergic neuroeffector
junctions (muscarinic effects), and  at skeletal myoneural junctions and in
autonomic ganglia (nicotinic effects). Organophosphates also impair nerve im-
pulse transmission in the  brain, causing  disturbances in sensorium,  motor
function, behavior, and respiratory drive. Depression  of respiration is the
usual cause of death in organophosphate poisoning. Recovery depends ulti-
mately on generation of new enzyme.
  Organophosphates are efficiently absorbed by inhalation, ingestion, and
skin penetration. To a degree, toxicity depends on  the rate at which specific
Organophosphates are metabolized in the body (principally by hydrolysis in the
liver),  thus   limiting  the   amount of  pesticide  available   to  attack
acetylcholinesterase enzyme in other tissues.
  Many Organophosphates readily undergo conversion from -thions to -oxons
(replacement  of sulfur by  oxygen). In general, -oxons are much more toxic
than -thions. This conversion occurs in the environment under the influence of
sunlight and in the body, mainly by the action of liver microsomes. Ultimate-
ly, both -oxons and -thions are inactivated by hydrolysis at the ester linkage,
yielding alkyl phosphates  and  phenols  which  are  readily excreted.  The
hydrolysis products present little  toxic hazard.
  One to two days  after organophosphate  absorption,  depending on the
specific organophosphate,  some phosphorylated acetylcholinesterase enzyme
can be de-phosphorylated (reactivated) by certain oxime antidotes. After this
interval, the nature of the enzyme-phosphoryl bond changes, rendering the
enzyme inactivation irreversible. New enzyme must then be generated.
  Very rarely, organophosphate pesticides have produced a different type of
neurotoxicity, consisting of damage to the myelin substance of peripheral
nerves. This leads to a protracted peripheral neuropathy, characterized by
numbness, pain, and weakness in the extremities, which persists for months or
years. Organophosphates associated with these chronic illnesses have included

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some whose acute toxic potential is low; i.e., there appears to be no relation-
ship between acute toxicity and the likelihood of a chronic neuropathic effect.
Particularly suspect as neurotoxic agents of this type are the phenylphospho-
nothioate series, cyanofenphos, EPN, leptophos,  and EPBP.
  Other unusual properties  of  specific organophosphates may render them
more hazardous than basic toxicity data suggest. By-products can develop in
long-stored malathion which strongly inhibit the hepatic enzymes operative in
malathion catabolism, thus enhancing its toxicity. Certain organophosphates
are exceptionally prone to storage in fat tissue, prolonging the need for an-
tidote when stored pesticide is released back into the circulation. It is possible
that other unrecognized factors modify the toxicity of organophosphates.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

  Symptoms of acute poisoning develop during exposure or within 12 hours
(usually within four hours) of contact. HEADACHE, DIZZINESS, WEAK-
NESS, INCOORDINATION, MUSCLE TWITCHING, TREMOR, NAUSEA,
ABDOMINAL CRAMPS, DIARRHEA, and SWEATING are common early
symptoms. Blurred or dark vision, confusion, tightness in the chest, wheezing,
productive cough, and PULMONARY EDEMA may occur. Incontinence, un-
consciousness  and  convulsions  indicate  very   severe  poisoning.  SLOW
HEARTBEAT, salivation, and tearing are common. TOXIC PSYCHOSIS,
with manic or bizarre behavior, has led to misdiagnosis of acute alcoholism.
Slowing of the heartbeat may rarely progress to complete sinus arrest. RESPI-
RATORY  DEPRESSION may be fatal.  Continuing daily absorption of
organophosphate at  intermediate  dosage may cause an INFLUENZA-LIKE
ILLNESS characterized by weakness, anorexia, and malaise.
  The very few individuals who have suffered peripheral neuropathy follow-
ing organophosphate exposure exhibited diverse clinical courses. Onset of
symptoms was generally  slow, sometimes after an asymptomatic interval of
several days following exposure.  Principal symptoms have been numbness,
tingling, pain and weakness  of the arms  and legs. Some recovered fully in a
few weeks; a few others experienced  muscle  atrophy, leaving  a degree of
paresis and sensory loss.

CONFIRMATION OF DIAGNOSIS

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

  Depressions of plasma  pseudocholinesterase and/or RBC acetylcholinester-
ase enzyme activities are the most satisfactory and generally available bio-
chemical indices of  excessive  organophosphate absorption. A minimum
amount of organophosphate must be absorbed to depress blood cholinesterase
activities, but activities are lowered by dosage considerably less  than are  re-
quired to cause symptomatic poisoning. The enzyme depression is usually ap-
parent immediately after, or within 12-24 hours of, significant absorption of

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organophosphate. Depression of the plasma enzyme generally persists several
days to a few  weeks; the RBC enzyme activity usually remains depressed
longer,  sometimes  1-3 months. Table  1  lists  APPROXIMATE LOWER
LIMITS OF NORMAL FOR PLASMA and RBC CHOHNESTERASE AC-
TIVITIES  of  human  blood, measured by  generally available methods.
LOWER LEVELS usually indicate excessive absorption of a cholinesterase-
inhibiting chemical. Whenever possible, comparison of the test sample with a
pre-exposure value offers the best confirmation of organophosphate absorp-
tion: a depression of 25% or more is strong evidence of excessive absorption.
  In certain conditions, the activities of plasma and RBC cholinesterase are
depressed in the absence of chemical inhibition. About 3% of individuals have
a genetically determined low level of plasma cholinesterase. These persons are
particularly vulnerable to the action of cholinesterase-inhibiting pesticides and
to the drug succinylcholine, often administered to surgical patients. Patients
with advanced  liver disease,  malnutrition,  chronic alcoholism and dermato-
myositis exhibit low plasma cholinesterase activities. A number of toxicants,
notably carbon disulfide, benzalkonium salts, organic mercury compounds,
ciguatoxins, and solanines may reduce plasma pseudocholinesterase activity.
The RBC acetylcholinesterase is less likely than the plasma enzyme to be af-
fected by factors other than organophosphates. It is reduced, however, in cer-
tain conditions that damage the  red  cell membrane, such as hemolytic
anemias.
  The alkyl phosphates and  phenols to which organophosphates are hydro-
lyzed in the body can often be detected in the urine during pesticide absorption
and up to 48 hours thereafter. These analyses are useful in identifying the ac-
tual pesticide to which workers have been exposed.  Alkyl phosphate and
phenol  analyses can  demonstrate  organophosphate absorption at lower
dosages than those required to depress cholinesterase activities.
  Detection of intact organophosphates in the blood is usually not possible ex-
cept after extreme exposures, such as ingestions of pesticide. Few organophos-
phates remain unhydrolyzed in the blood more than a few minutes or hours,
unless the quantity absorbed is extraordinary or the hydrolyzing liver enzymes
are inhibited.

TREATMENT

     CAUTION:  Persons attending the victim should avoid direct contact
                  with heavily contaminated clothing and vomitus. Wear
                  rubber gloves while washing pesticide from skin and hair.
 1.   Establish  CLEAR AIRWAY  by aspiration of secretions.  Administer
     OXYGEN  by  mechanically assisted  pulmonary ventilation. Improve
     tissue oxygenation as much as possible before administering atropine to
     minimize the risk of ventricular fibrillation.
 2.   Administer ATROPINE SULFATE intravenously, or intramuscularly, if
     IV injection is not possible. Atropine protects the muscarinic end-organs
     from excessive concentrations of acetylcholine. It does not reactivate the

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  TABLE 1.  Approximate Lower Limits of Normal Plasma and Red Cell
             Cholinesterase Activities in Humans*
METHOD
A pH (Michel)
pH Stat (Nabb-
  Whitfield)
ChE-tel (Pfizer)
A ChE-tel (Pfizer)
BMC Reagent Set
 (Ellman-Boehringer)
1-Test Cholinesterase
 (EM Diagnostics)
Acholest Test Paper
Dupont ACA
Garry-Routh (Micro)

Merckotest
GLC Method
 (Cranmer)
Technicon
PLASMA RBC
   0.45    0.55
    2.3
     40
   1875
    3.6

   >20
   < 8
    2.1
    2.0
     WHOLE
     BLOOD
8.0
           210
                  Male 7.8
                Female 5.8
                       3.0
8.2
8.0
      UNITS
      A pH per hr per ml
          per min per ml
      ChE-tel units
      A ChE-tel units

3000  mU per min per ml
      Units per ml
                Minutes
                Units per ml
                /xM-SH per 3 min
                  per ml
                Units per ml
          per min per ml
          per min per ml
*  Because measurement technique varies among laboratories, more accurate
   estimates of minimum normal values are usually provided by individual
   laboratories.
    Cholinesterase enzyme. Recrudescence of poisoning may occur if tissue
    concentrations  of organophosphate remain  high when the  effect  of
    atropine wears off. Atropine is the ideal antidote for muscarinic manifes-
    tations; it is ineffective against nicotinic actions: muscle weakness and
    twitching, and respiratory depression.
    In MODERATELY SEVERE poisoning:
    Adult dosage, including children over 12 years: 0.4-2.0 mg repeated every
    15 minutes until atropinization is achieved: tachycardia (pulse of 140 per
    minute), flushing, dry mouth, dilated pupils. Maintain atropinization by
    repeated doses for 2-12 hours or longer depending on severity of poison-
    ing. Rales in  the lung bases indicate inadequate atropinization. Miosis,
    nausea, bradycardia, and other cholinergic manifestations are also in-
    dicative.
    Dosage for children under 12 years: 0.05 mg/kg body  weight, repeated
    every 15 minutes until atropinization is achieved. Maintain atropinization
    with repeated dosage of 0.02-0.05 mg/kg.
    SEVERELY POISONED individuals may exhibit remarkable tolerance
    to atropine; two  or more times the dosages suggested above may be

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    needed.  Persons not poisoned or only slightly poisoned, however, may
    develop  signs of atropine toxicity from  such large dosages: FEVER,
    muscle fibrillations, and delirium are the main signs of atropine toxicity.
    If these signs appear  while the patient  is fully atropinized,  atropine
    administration should be discontinued, at least temporarily.
3.   Draw a BLOOD SAMPLE for PLASMA and RBC CHOLINESTERASE
    analysis.
4.   Administer PRALIDOXIME (Protopam®-Ayerst, 2-PAM) in cases of
    severe poisoning by organophosphate pesticides in which respiratory
    depression, muscle weakness and twitchings are severe.  When adminis-
    tered early (usually less than 36 hours  after poisoning)  pralidoxime
    relieves the nicotinic effects of poisoning.
    Note:  Pralidoxime is of questionable value in poisonings by the cholin-
           esterase-inhibiting carbamate compounds. (See Chapter 2).
    Adult dosage (including children over 12 years): 1.0 gm intravenously at
    no more than 0.5 gm per minute.
    Child's dose (under 12 years): 20-50 mg/kg (depending on severity of
    poisoning) intravenously, injecting no more than half the total dose per
    minute.
    Dosage of pralidoxime may be repeated in 1-2 hours, then at 10-12 hour
    intervals if needed. In very  severe poisonings, dosage rates may be
    doubled.
    Note:  slow administration of pralidoxime is strongly recommended,
           and may be achieved by administering the total dose in 250 ml
           5% glucose solution over 30-60 minutes.
    If intravenous injection is not possible,  pralidoxime may be  given by
    deep intramuscular injection.
    CAUTION:  Be prepared to assist pulmonary ventilation mechanically
                 if respiration is depressed during and after pralidoxime in-
                jection.

5.   OBSERVE PATIENT CLOSELY for at least 24  hours to insure that
    symptoms (sweating, visual disturbances,  vomiting, diarrhea, chest and
    abdominal  distress and sometimes  PULMONARY EDEMA) do not
    recur as atropinization wears off. In very severe poisonings by ingested
    organophosphates, particularly the  more lipophilic and slowly hydro-
    lyzed compounds,  metabolic disposition of toxicant may require as many
    as 5-10 days, during which atropinization must be maintained.  Rising
    levels of blood cholinesterase activity are a useful signal that  atropine
    dosage can be tapered off by lengthening the intervals between doses. As
    dosage is reduced,  the lung bases should be checked frequently for rales.
    If rales are heard,  or if there is a  return of miosis, bradycardia, sweating
    or other cholinergic signs, atropinization must be re-established promptly.
6.   BATHE and SHAMPOO victim with soap and water if there is any
    chance that SKIN  and HAIR are contaminated.

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7.  IF PESTICIDE HAS BEEN INGESTED in quantity sufficient to cause
    poisoning, empty the stomach and intestine.

    A.  IF victim is ALERT and respiration is not depressed, give SYRUP
        OF IPECAC, followed by 1-2 glasses of water to induce vomiting.
        Adults (12 years and over): 30 ml; children under 12 years:  15 ml.

        CAUTION:   OBSERVE  victim  closely  AFTER administering
                     IPECAC. If consciousness level declines, or if vomit-
                     ing has not occurred in 15 minutes, proceed immedi-
                     ately to INTUBATE the stomach.

        Following emesis, have  victim  drink a suspension of  30-50 gm
        ACTIVATED CHARCOAL in 3-4 ounces of water to limit absorp-
        tion of toxicant remaining in the gut.
    B.  IF victim is OBTUNDED or respiration is depressed, empty stomach
        by INTUBATION,  ASPIRATION, and LAV AGE, using isotonic
        saline or 5% sodium bicarbonate. Because many pesticides are
        dissolved in  petroleum distillates,  emesis and intubation  of the
        stomach involve a serious risk that solvent will be aspirated, leading
        to chemical pneumonitis.  For this reason:

        (a).  If victim is unconscious or obtunded and facilities are at hand,
             insert ENDOTRACHEAL TUBE (cuffed, if available) prior
             to gastric intubation.
        (b).  Keep victim's HEAD BELOW LEVEL OF STOMACH dur-
             ing intubation and  lavage (Trendelenburg, or left  lateral
             decubitus,  with  head  of table  tipped  downward). Keep
             victim's head turned to left.
        (c).  ASPIRATE PHARYNX as regularly as possible to remove
             gagged or vomited  stomach contents.
             After aspiration of gastric  contents and washing of stomach,
             instill 30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces
             of water through stomach tube to limit absorption of remain-
             ing toxicant.

    C.  SAVE A SAMPLE of emesis, or the initial gastric washings, for
        chemical analysis.
    D.  If bowel movement  has not occurred in 4 hours, and if patient is
        fully conscious,  give SODIUM SULFATE, 0.25  gm/kg,  in 1-6
        ounces water, as a  cathartic. Magnesium sulfate  and  citrate are
        equally suitable at similar dosage if renal function is adequate. Re-
        tained magnesium may depress CNS function.

8.  DO  NOT  give morphine, aminophylline,  phenothiazines,  reserpine,
    furosemide, or ethacrynic acid in poisonings by organophosphates.
9.  Give adrenergic amines ONLY if  there is a specific indication, such as
    marked hypotension.

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10.   Rarely, in severe organophosphate poisonings, CONVULSIONS occur
     which are unresponsive to atropine and pralidoxime. Insure that causes
     unrelated to pesticide toxicity are not responsible: head trauma, cerebral
     anoxia, or mixed poisoning. DIAZEPAM (Valium), 5-10 mg for adults,
     0.1 mg/kg for children under 6 years or 23 kg is probably the safest and
     most reliable anticonvulsant  to use under these  circumstances.  Give
     SLOWLY (no more than half the total dose per minute) intravenously.
     Se-vere protracted convulsions may require additional medication, as sug-
     gested in the chapter on Solid Organochlorine Pesticides.

     CAUTION:   Be prepared to assist pulmonary ventilation mechanically
                  if respiration is depressed;  to  intubate  the trachea,  if
                  laryngospasm occurs; and to counteract hypotensive reac-
                  tions.

11.   Persons  who  have  been  clinically  poisoned by organophosphate
     pesticides should not be re-exposed to cholinesterase-inhibiting chemicals
     until symptoms and signs have resolved completely and  blood cholines-
     terase activities  have returned to  at least 80 percent of pre-poisoning
     levels. If blood cholinesterase was not  measured prior to  poisoning,
     blood enzyme activities should  reach at least minimum normal levels
     (Table 1) before the patient is returned to a pesticide-contaminated envi-
     ronment.
12.   DO NOT administer atropine or pralidoxime prophylactically to workers
     exposed  to  organophosphate pesticides.  It  is neither practical  nor
     medically sound to do so.

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                         Chapter 2

                     CARBAMATE
       CHOLINESTERASE-INHIBITING
                      PESTICIDES

GENERAL CHEMICAL STRUCTURE

             o
   H

H3C
           -C—O—
LEAVING
GROUP
COMMON COMMERCIAL PESTICIDE PRODUCTS*

  Highly  toxic**: aldicarbf  (Temik),  oxamyl  (Vydate),  carbofuran
(Furadan), methomyl (Lannate, Nudrin), formetanate HC1 (Carzol, Dicarzol),
aminocarb (Matacil), dimetilan (Snip Fly Bands).
  Moderately  toxic***: promecarb  (Carbamult),  methiocarb (Mesurol,
Draza), propoxur (Baygon), pirimicarb (Pirimor, Aphox, Rapid), bufencarb
(Bux), carbaryl (Sevin).

TOXICOLOGY

  Insecticides of this class cause reversible carbamylation of acetylcholinester-
ase enzyme, allowing accumulation of acetylcholine at cholinergic neuroeffec-
tor junctions (muscarinic effects), and at skeletal muscle myoneural junctions
and in autonomic ganglia (nicotinic  effects). Poison also  impairs CNS func-
tion. The carbamyl-enzyme combination dissociates more readily  than the
phosphorylated enzyme produced  by organophosphate insecticides. This
lability tends to mitigate the toxicity of carbamates, but also limits the useful-
ness of blood enzyme  measurements in diagnosis of poisoning. Carbamates
are absorbed by inhalation, ingestion, and dermal penetration. They are ac-
tively metabolized by the liver,  and the degradation products are excreted by
the liver and kidneys.
*   Listed approximately in order of decreasing toxicity.
**  Acute oral LD5o in the rat less than 50 mg/kg.
*** Acute oral LD50 in the rat above 50 mg/kg.
t   This carbamate is a systemic, i.e., it is taken up by the plant and trans-
    located into foliage and sometimes into the fruit.

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  A few carbamate insecticides are formulated in methyl (wood) alcohol. In
cases of ingestion of these formulations, the toxicology of the methanol must
be taken fully into consideration: severe gastroenteric irritation, acidosis, CNS
injury, and neuropathy.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

  DIARRHEA, NAUSEA, VOMITING, ABDOMINAL PAIN, PROFUSE
SWEATING,  SALIVATION,  and  BLURRED  VISION  are  frequently
reported.  Other  common  symptoms  have been dyspnea, tremor, muscle
twitching, ataxia, and headache. Temporary paralysis of the extremities has
also occurred. Most reported illnesses have not exceeded a few hours, and the
prognosis is generally better than in organophosphate intoxications. However,
in severe poisonings, one should anticipate the possibility of RESPIRATORY
DEPRESSION, pulmonary edema, and convulsions. Continuing absorption
of intermediate quantities may cause protracted MALAISE, weakness, and
anorexia, resembling influenza.

CONFIRMATION OF DIAGNOSIS

     CAUTION:  If there is strong clinical evidence of poisoning, treat pa-
                 tient immediately. DO NOT WAIT for laboratory confir-
                 mation.

Depressions of plasma and/or RBC cholinesterase activities may be observed
following  absorption of extraordinary amounts  of  carbamate insecticide.
However, enzyme activities commonly revert to normal within a few minutes
or hours. They are not, therefore, reliable detectors of carbamate poisoning;
i.e.,  intoxication  may exist when blood cholinesterase activities are normal.
The  rapid methods for  cholinesterase  estimation (ACHOLTEST, ChE-tel,
MERCKOTEST) are  more likely to detect depressions  than the longer test
methods.
  Table 1 in the chapter on ORGANOPHOSPHATE PESTICIDES lists the
approximate lower limits of normal  plasma and red  cell cholinesterase-
inhibiting carbamates. A normal value does not preclude carbamate insecticide
poisoning. Whenever possible, comparison of the test sample  with pre-
exposure values offers the best confirmation of excessive carbamate absorp-
tion: a depression of 25% or more is strong evidence of excessive absorption.
  Consult the chapter on ORGANOPHOSPHATE PESTICIDES for detailed
interpretation of the blood cholinesterase tests.
  Measurement of carbamate metabolites in urine within 48 hours of exposure
represents a specific and sensitive method for confirming absorption of several
pesticides of this class. A number of government and university laboratories in
contact with poison control centers can  perform these  tests. Specimens for
such analysis should be collected as promptly as possible after exposure.
                                 10

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TREATMENT

     CAUTION:  Persons attending the victim should avoid direct contact
                  with heavily contaminated clothing and vomitus. Wear
                  rubber gloves while decontaminating skin and hair.

 1.   Establish CLEAR AIRWAY and TISSUE OXYGENATION by aspira-
     tion of secretions,  and if necessary, by assisted pulmonary ventilation
     with oxygen. Improve tissue oxygenation as much as possible before ad-
     ministering atropine to minimize the risk of ventricular fibrillation.
 2.   Administer ATROPINE SULFATE intravenously, or intramuscularly if
     IV injection is not  possible. Atropine protects the end-organs from ex-
     cessive concentrations of acetylcholine. It does not reactivate the cholin-
     esterase enzyme. Recrudescence of poisoning may occur if tissue concen-
     trations of carbamate remain high when the effect of atropine wears off.
     Atropine is the ideal antidote for muscarinic symptoms; it is ineffective
     against nicotinic  actions such as muscle weakness and twitching, and
     respiratory depression.
     In MODERATELY SEVERE poisoning: Adult  dosage, including
     children over 12 years: 0.4-2.0 mg repeated every 15  minutes until
     atropinization is achieved (tachycardia, flushing, dry mouth, mydriasis).
     Maintain atropinization by repeated doses for 2-12 hours, or longer,
     depending on severity of poisoning. The appearance of rales in the lung
     bases, miosis, salivation, nausea, bradycardia, are all indications of in-
     adequate atropinization.
     Dosage for children under 12 years: 0.05 mg/kg body weight repeated
     every  15 minutes until atropinization is achieved. Maintain atropiniza-
     tion with repeated dosage of 0.02-0.05  mg/kg.
     SEVERELY POISONED  individuals may exhibit remarkable tolerance
     to atropine; twice the doses suggested above may be needed.  Persons not
     poisoned, or only slightly poisoned, may develop signs of atropine toxici-
     ty if large doses are given: FEVER, muscle fibrillations, and delirium. If
     these appear while the patient is fully atropinized, atropine should be dis-
     continued, at least temporarily.
 3.   Pralidoxime (Protopam®-Ayerst,  2-PAM) is  of  doubtful  value  in
     poisonings by carbamate inhibitors of cholinesterase. Atropine alone is
     almost always an adequate antidote. Pralidoxime is probably contrain-
     dicated in poisonings by carbaryl, specifically.  If victim of carbamate
     poisoning exhibits  severe  muscle weakness and/or  respiratory depres-
     sion, or if poisoning involves a combination of carbamate and organo-
     phosphate,  a dilute solution of pralidoxime (total dose in  250 ml 5°/o
     glucose solution) may be given cautiously IV. The infusion should be ter-
     minated if patient's condition worsens. Pralidoxime dosage: adults, 1.0
     gm; for children under 12 years, 20-50 mg/kg.
 4.   OBSERVE  treated  patients closely  at  least 24 HOURS to  insure that
     symptoms (possibly pulmonary edema) do not recur as atropinization
     wears  off. In very severe poisonings, metabolic disposition  of toxicant

                                   11

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    may require several hours or days during which atropinization must be
    maintained. Markedly lower levels of urinary metabolites indicate that
    atropine dosage can be tapered off. As dosage is reduced, check the lung
    bases frequently for rales. If rales are heard, or if nausea, salivation, or
    bradycardia returns, RE-ESTABLISH ATROPINIZATION promptly.
5.   BATHE and SHAMPOO victim with soap and water if there is any
    chance that SKIN and HAIR are contaminated.
6.   If pesticide has been INGESTED in quantity sufficient to cause poison-
    ing, empty the stomach and intestine.

    A.  If victim is alert and respiration is not depressed, give SYRUP OF
        IPECAC, followed by 1-2 glasses  of water to induce vomiting;
        adults (including children over 12), 30 ml; children (under 12 years),
        15ml.

        CAUTION:  OBSERVE  victim closely AFTER  administering
                    IPECAC. If consciousness level declines, or if vomit-
                    ing has not occurred in 15 minutes, proceed immedi-
                    ately to INTUBATE the stomach.

        Following emesis, have victim drink a suspension of 30-50 gm
        ACTIVATED CHARCOAL in 3-4 ounces of water to bind toxicant
        remaining in the gastrointestinal  tract.
    B.   If victim is OBTUNDED or respiration is depressed, empty stomach
        by INTUBATION, ASPIRATION,  and LAV AGE, using isotonic
        saline or  5%  sodium bicarbonate.  Because many pesticides are
       dissolved  in petroleum distillates,  emesis and intubation of the
        stomach involve a serious risk that solvent will be aspirated, leading
       to chemical pneumonitis. For this reason:

       (a).  If victim is unconscious or obtunded and facilities are at hand,
             insert ENDOTRACHEAL  TUBE (cuffed, if available) prior
             to gastric intubation.
       (b).  Keep victim's HEAD BELOW LEVEL OF STOMACH dur-
             ing  intubation and  lavage (Trendelenburg,  or left lateral
             decubitus,  with  head  of  table tipped  downward).  Keep
             victim's head turned to left.
       (c).   ASPIRATE PHARYNX as regularly as possible to  remove
             gagged or vomited stomach contents.

       After aspiration of gastric contents and washing of stomach, instill
       30-50 gm  of ACTIVATED CHARCOAL in 3-4 ounces of water
       through the tube to limit absorption of remaining toxicant.
    C.  SAVE A SAMPLE of emesis or initial gastric washings for chemical
       analysis.
    D.  If bowel movement has not occurred in 4 hours and patient is fully
       conscious, give SODIUM SULFATE, 0.25 gm/kg in 1-6 ounces of
       water, as a cathartic. Magnesium sulfate or citrate is equally suitable
       if renal function is satisfactory.
                                 12

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 7.  DO NOT give morphine,  aminophylline,  phenothiazines,  reserpine,
     furosemide, or ethacrynic acid.
 8.  Give adrenergic amines ONLY if there is a specific indication, such as
     severe hypotension.
 9.  CONVULSIONS are RARE manifestations of poisoning by carbamates.
     If they occur, causes other than direct carbamate action should be con-
     sidered: cerebral anoxia, head trauma, mixed poisoning. Although not
     tested in these circumstances, DIAZEPAM (Valium) is probably the an-
     ticonvulsant of choice. Dosage for adults and children over 6 years or 23
     kg body weight is 5-10 mg given slowly intravenously (no more than half
     total dose per minute), or intramuscularly (deep).  Dosage for children
     under  6 years or 23 kg body weight is 0.1 mg/kg. Repeat this dosage
     every 2-4 hours if needed to control convulsions. Be prepared to intubate
     and to assist pulmonary ventilaton mechanically if respiration is depressed.
     Hypotensive reactions may also occur.
10.  Persons who  have  been clinically  poisoned by carbamate pesticides
     should  not be re-exposed to  cholinesterase-inhibiting chemicals until
     symptoms and signs  have resolved completely, and normal blood cholin-
     esterase activities have been demonstrated.
11.  DO NOT administer  atropine prophylactically to workers exposed to car-
     bamate insecticides.  It is neither practical nor medically sound to do so.
                                  13

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                           Chapters

SOLID  ORGANOCHLORINE PESTICIDES
CHEMICAL STRUCTURES
                                HEXACHLOROBENZENE
    ENDOSULFAN   HEPTACHLOR

                           METHOXYCHLOR
                                                *
COMMON COMMERCIAL PESTICIDE PRODUCTS

  Highly toxic: endrin (Hexadrin), a stereoisomer of dieldrin.
  Moderately toxic: aldrin (Aldrite, Drinox), endosulfan (Thiodan), dieldrin
(Dieldrite), toxaphene (Toxakil, Strobane-T), lindane (Gammexane), benzene
hexachloride (BHC, HCH), DDT (chlorophenothane), heptachlor, kepone,
terpene polychlorinates (Strobane), chlordane (Chlordan), dicofol (Kelthane),
chlorobenzilate (Acaraben), mirex, methoxychlor (Marlate), dienochlor (Pen-
tac), hexachlorobenzene (HCB), ethylan (Perthane). All except HCB are insec-
ticides or acaricides; HCB is a fungicide.
  The  U.S.  Environmental Protection  Agency has sharply  curtailed the
availability of many organochlorines, particularly DDT, dieldrin, and chlor-
dane. Others, however, are still the active ingredients of various home and
garden products and some agricultural and structural pest control agents. Hex-
achlorobenzene is used as a seed protectant. Lindane may no longer be used in
continuous vaporizers, but it is the active ingredient of many products for pest
control in the home and on  the farm. It is the active ingredient of the scabicide
Kwell®.

TOXICOLOGY

  Most organochlorines are efficiently absorbed from the gut and across the
skin. In adequate dosage, they interfere with axonic transmission of nerve im-
pulses and, therefore, disrupt the function of the nervous system, principally
that of the brain. This results in behavioral changes, sensory and equilibrium
disturbances, involuntary muscle activity, and depression of vital centers, par-
ticularly those  controlling  respiration.  Adequate doses  of some organo-
chlorines increase myocardial  irritability, and stimulate synthesis of hepatic
drug-metabolizing enzymes.
   Listed approximately in order of decreasing toxicity.

                                 14

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   Chlordane has apparently induced a few cases of self-limited megaloblastic
 anemia after protracted low-level exposures. The  condition  has resolved
 following termination of exposure.
   Kepone has caused nervousness, tremor, incoordination, weakness and in-
 fertility in excessively exposed workers. Clinical improvement has occurred as
 the pesticide  was excreted.
   Endrin is more toxic to the liver and kidneys than the other organochlorines
 at comparable dosages.
   Prolonged  ingestion of HCB-treated grain produced porphyria cutanea tar-
 da in several thousand Turkish citizens  who  mistakenly ate the seed grain.
 Disease was  manifest as excretion of red urine, bullous dermatitis, hyper-
 pigmentation, generalized hair growth, muscle wasting and liver enlargement.
 Slow improvement occurred when HCB ingestion was stopped.
   A series of anecdotal reports of bone marrow injury has tended to indict lin-
 dane as a hematotoxic agent in certain predisposed individuals, but no rela-
 tionship has been proved.
   Lindane, methoxychlor, terpene poly chlorinates, chlorobenzilate, dicofol,
 and  the constituents of chlordane, except heptachlor and oxychlordane, are
 excreted rapidly by humans, usually  within 3-4 days of ingestion. Dieldrin,
 aldrin, endrin, hexachlorobenzene, heptachlor, and oxychlordane are excreted
 within weeks to several months of absorption by humans. DDT, kepone,
 mirex, and the beta isomer of benzene hexachloride are excreted very slowly,
 requiring months or years for elimination. The excretion kinetics of perthane,
 kelthane, and dienochlor are not known.  Because of  their lipophilicity,  all
 organochlorines are likely to be excreted in the milk  of lactating women.

 FREQUENT SYMPTOMS AND SIGNS OF POISONING

   APPREHENSION, EXCITABILITY, DIZZINESS, HEADACHE,  DIS-
 ORIENTATION,   WEAKNESS,  PARESTHESIAE, muscle  twitching,
tremor, tonic and clonic CONVULSIONS (often epileptiform), and uncon-
sciousness are the  major manifestations. Soon  after ingestion, nausea and
vomiting commonly occur. When chemicals are absorbed dermally, apprehen-
sion, twitching, tremors, confusion, and convulsions may be the first symp-
toms. Respiratory depression is caused by the pesticide  and by the petroleum
solvents in which  these pesticides are  usually  dissolved.  Pallor occurs in
moderate to severe poisoning. Cyanosis may result as convulsive activity in-
terferes with respiration.
  Even though convulsive activity may be severe, the prognosis in poisonings
by these agents is far from hopeless. Although fatalities  have occurred follow-
ing absorption of large amounts of some organochlorines, there is a substan-
tial likelihood of complete recovery if convulsions can be controlled, and vital
functions sustained.
                                  15

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CONFIRMATION OF DIAGNOSIS

  Pesticide and/or metabolites can usually be identified in blood or urine by
gas-liquid chromatographic examination of samples taken within 72 hours of
poisoning. These tests can be performed by some private laboratories, and by
state health department and university laboratories supported by the U.S. En-
vironmental Protection Agency.  Such laboratories can be reached through
poison control centers.  Some chlorinated hydrocarbon pesticides (notably
DDT) persist in the serum for weeks or months after absorption, but most are
excreted in a few days. DO NOT DELAY TREATMENT of acute  poisoning
pending confirmatory blood analysis. Detection of chlorinated hydrocarbon
residues in blood or tissues does not, of itself, indicate poisoning; actual con-
centrations are critical to a diagnosis of poisoning.

TREATMENT

 1.   Establish CLEAR AIRWAY and TISSUE OXYGENATION by aspira-
     tion of secretions, and, if necessary, by assisted pulmonary ventilation
     with oxygen.
 2.   CONTROL CONVULSIONS. DIAZEPAM  (VALIUM®) is a valuable
     anticonvulsant.
     Adult dosage, including children over 6 years of age or 23 kg in weight:
     5-10 mg (1-2 ml)  slowly, intravenously (no faster than one ml per
     minute), or give total dose intramuscularly (deep). Repeat in 2-4 hours if
     needed.
     Dosage for children under  6 years or 23  kg  in weight:  0.1  mg/kg
     (0.02 ml/kg)  intravenously, no  faster  than half the total  dose per
     minute, or give total dose intramuscularly (deep). Repeat in 2-4 hours if
     needed.
     CAUTION:   Administer intravenous diazepam slowly to avoid irrita-
                  tion of the vein, hypotension, and respiratory depression.

     A.  Persons suffering SEVERE PROTRACTED CONVULSIONS may
         require additional anticonvulsant  medication. Agents that  have
         been used successfully in the past are pentobarbital (Numbutal®),
         phenytoin (Dilantin®), thiopental (Pentothal®),  and  succinyl-
         choline (Anectine®).

         CAUTION:  Be prepared to maintain pulmonary ventilation me-
                     chanically if respiration is depressed during adminis-
                     tration of anticonvulsants. Laryngospasm sometimes
                     occurs during anticonvulsant therapy, and may neces-
                     sitate tracheostomy.

         (a).   PENTOBARBITAL: 5 mg/kg body weight,  or  0.20 ml/kg
              body weight, using the usual 2.5%  solution. If possible, inject
              solution intravenously, at a rate not exceeding 25 mg (one ml)
                                 16

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             per minute until convulsions are controlled. If intravenous ad-
             ministration is not possible,  give total dose  rectally, not ex-
             ceeding 5 mg/kg body weight (0.20 ml/kg of 2.5% solution).
        (b).  PHENYTOIN: loading dose 15-18 mg/kg. Maintenance dose
             4-8 mg/kg q 4-24 hours as needed. Intramuscular administra-
             tion is not recommended. Give IV slowly at no more than 20%
             total dose per minute.
        (c).  THIOPENTAL (PENTOTHAL): a solution of one gm in 500
             ml of 5% glucose in water is given by intravenous drip at a
             rate just sufficient to suppress convulsions.
        (d).  SUCCINYLCHOLINE: occasionally, curarization may be re-
             quired to stop seizures. Prior to curarization, the trachea must
             be intubated, and pulmonary ventilation maintained mechani-
             cally. Blood gases and pH must be monitored. A person expe-
             rienced in general anesthesia should conduct these procedures.
3.   BATHE and SHAMPOO the victim vigorously with soap and water if
    skin and hair have been  contaminated.
4.   IF PESTICIDE HAS BEEN INGESTED  in quantity sufficient to cause
    poisoning, the stomach and intestine must be emptied.

    A.  IF victim is ALERT and gag reflex is not depressed, give SYRUP
        OF IPECAC to induce vomiting (adults and children 12 years and
        older: 30 ml; children under 12: 15 ml), followed by 1-2 glasses of
        water.

        CAUTION:  OBSERVE the VICTIM closely  after administering
                    IPECAC.  If consciousness level   declines,  or  if
                    vomiting has not occurred in 15 minutes, proceed im-
                    mediately to INTUBATE stomach.
        Following emesis, have victim drink a suspension of 30-50 gm AC-
        TIVATED CHARCOAL in 3-4 ounces of water to limit absorption
        of toxicant remaining in the gut.
    B.  If the victim is  NOT FULLY ALERT, empty the stomach immedi-
        ately by INTUBATION,  ASPIRATION, and LAV AGE, using
        isotonic saline or 5% sodium bicarbonate.  Because many pesticides
        are dissolved in petroleum  distillates, emesis and intubation of the
        stomach involve a serious risk that solvent will be aspirated, leading
        to chemical pneumonitis. For this reason:
        (a).  If victim  is unconscious or obtunded and if facilities are at
             hand, insert an ENDOTRACHEAL TUBE (cuffed, if avail-
             able) prior to gastric  intubation.
        (b).  Keep victim's  HEAD BELOW LEVEL OF STOMACH and
             turned to left  during  intubation and  lavage. (Trendelenburg,
             or left lateral decubitus, with head of table tipped downward).
        (c).  ASPIRATE PHARYNX as regularly as  possible to remove
             gagged or vomited stomach contents.

                                 17

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    C.   After aspiration of gastric contents and washing of stomach, instill
        30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces of water
        through stomach tube to limit absorption of remaining toxicant.
        DO NOT instill milk, cream,  or  other substances  containing
        vegetable or animal fats, which enhance absorption of chlorinated
        hydrocarbons.
    D.   -SAVE  A SAMPLE of emesis or gastric washings  for chemical
        analysis.
    E.   If bowel movement has not occurred in 4 hours and if patient is fully
        conscious, give SODIUM SULFATE, 0.25 gm/kg in  1-6 ounces of
        water, as a cathartic. Magnesium sulfate and  citrate are as suitable
        as sodium sulfate if renal function is adequate. Retained magnesium
        may depress CNS function.

5.   DO NOT give epinephrine or other adrenergic amines, because of the
    enhanced myocardial irritability induced by chlorinated hydrocarbons.
6.   CHOLESTYRAMINE resin may accelerate the biliary-gastrointestinal
    excretion of the more slowly eliminated organochlorine compounds. This
    is usually administered in 3-8 gm doses, 4 times a day, before meals and
    at bedtime. Dose should be mixed with a pulpy fruit or liquid. Prolonged
    treatment (several weeks or months) may be necessary.
7.   During convalescence, enhance CARBOHYDRATE, PROTEIN,  and
    VITAMIN intake by diet or parenteral therapy to minimize injury to the
    liver.
                                  18

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                            Chapter 4

             PENTACHLOROPHENOL
CHEMICAL STRUCTURE

                Cl   Cl
                Cl   Cl

COMMON COMMERCIAL PESTICIDE PRODUCTS
  Pentachlorophenol or Sodium Pentachlorophenate, PCP, Dow Pentachlo-
rophenol, Dowicide EC-7, Penchlorol, Pentacon, Penwar, Veg-I-Kill, penta,
Wood Preserver, Wood Tox 140, Purina Insect Oil Concentrate, Garden Ter-
mi Tox, Usol Cabin Oil, Certified KiltroI-74 Weed Killer, Ciba-Geigy On-
track OSS, 4 or 5, Ortho Triox Liquid Vegetation Killer, Black Leaf Grass
Weed and Vegetation Killer Spray, DP-2 Antimicrobial, Priltox, Sinituho.
  Pentachlorophenol is  used as an herbicide, defoliant, wood  preservative,
germicide, fungicide, and molluscicide. It is an ingredient of many formulated
mixtures sold for one or more of these purposes.
  Pentachlorophenol volatilizes from treated wood and fabric. Excessively
treated interior surfaces  may represent a source of intensive PCP exposure.

TOXICOLOGY

  Pentachlorophenol irritates the skin,  eyes, and upper respiratory mucous
membranes. It is efficiently absorbed across the skin, the lung, and the gastro-
intestinal lining. Like the nitrophenolic compounds, it stimulates cellular ox-
idative metabolism by uncoupling phosphorylation. In common with other
phenols, it is toxic to the liver, kidney, and central nervous system. Impurities
in the technical formulation may be responsible for chloracne in workers
regularly exposed.
  Most severe poisonings have  occurred in workers exposed to  hot environ-
ments.  However, a  major epidemic of poisoning occurred in an American
hospital among newborn infants who absorbed PCP from treated diapers.
Dehydration and  metabolic acidosis are important features of poisoning in
children.
  Albuminuria, glycosuria, and elevated BUN reflect renal injury. Liver
enlargement has been observed  in some cases. Anemia and leukopenia have
occurred in some chronically exposed workers, but leukocytosis is more com-
monly found in acute poisoning.
                                 19

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FREQUENT SYMPTOMS AND SIGNS OF POISONING

  IRRITATION of nose, throat, eyes, and skin is the most common symptom
of exposure to PCP. Severe or protracted exposure may result in CONTACT
DERMATITIS. Intensive occupational exposure has resulted in chloracne.
  PROFUSE SWEATING, HEADACHE, WEAKNESS, and NAUSEA are
the most consistent presenting symptoms of systemic poisoning by absorbed
PCP. FEVER is usually present but may be minimal or absent. TACHYCAR-
DIA, TACHYPNEA, and PAIN in the CHEST and ABDOMEN are often
prominent. THIRST is usually intense, but may be masked by nausea and
vomiting. DECLINING MENTAL ALERTNESS may  progress to stupor
and/or convulsions. Protracted exposure may result in WEIGHT LOSS from
increased basal metabolic rate.

CONFIRMATION OF DIAGNOSIS

  PCP can be measured in  blood, urine,  and adipose tissue by gas-liquid
chromatography. Up to about 100 parts per billion may be found in the blood
and urine of persons having no recognized exposure. Based on studies of per-
sons occupationally exposed to PCP, manifestations of systemic toxicity prob-
ably do not appear in adults until blood and urine concentrations reach at least
one part per million (0.1 mg%, or 1,000 parts per billion).
  If poisoning is strongly suspected on grounds of exposure, symptoms, and
signs, DO NOT POSTPONE TREATMENT until diagnosis is confirmed.

TREATMENT

 1.   BATHE and SHAMPOO contaminated SKIN and HAIR promptly with
     soap and water, or water alone if soap is not available.
 2.   FLUSH chemical from  EYES with copious amounts of clean water.
 3.   IN EVENT OF SYSTEMIC POISONING:

     A.  REDUCE ELEVATED BODY TEMPERATURE BY PHYSICAL
        MEANS. Administer  sponge baths and cover victim with low-
        temperature blankets. In fully conscious patients, administer cold,
        sugar-containing liquids by mouth as tolerated.
     B.  Administer  OXYGEN continuously by mask  to minimize tissue
        anoxia.
     C.  Unless there are manifestations of cerebral edema, administer IN-
        TRAVENOUS FLUIDS at maximum tolerated rates to  enhance
        urinary excretion of toxicant and to support physiologic mechan-
        isms for heat  loss. Monitor fluid balance, blood electrolytes and
        sugar,  adjusting IV infusions to stabilize electrolyte concentra-
        tions, Follow urine contents of albumin and cells. In the presence of
        CEREBRAL EDEMA, intravenous FLUIDS  must be administered
        very CAUTIOUSLY to avoid increasing the cerebral injury.
                                20

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    D.  Administer SEDATIVES, if necessary, to control apprehension and
        excitement. DIAZEPAM® (Valium) should be valuable, although
        its use has not been reported in this type of poisoning. Give slowly,
        intravenously,  5-10  mg  in  the  adult, 0.1  mg/kg in children.
        Amobarbital or pentobarbital,  100-200 mg IM or slowly IV, every
        4-6 hours may be needed. (Children's dose: up to 5 mg/kg.)

        CAUTION:  Be prepared to assist pulmonary ventilation mechani-
                    cally in  event of  respiratory depression, and to
                    counteract hypotensive reactions.

4.   If toxicant has been INGESTED, evacuate the stomach and intestine.
    A.  If victim is alert and  respiration is not depressed, give SYRUP OF
        IPECAC,  followed by 1-2 glasses of water, to induce vomiting.
        (Adults, 12 years and older: 30 ml; children under 12: 15 ml).

        CAUTION:  OBSERVE the victim closely AFTER administering
                    IPECAC. If consciousness level declines, or if vomit-
                    ing  has not occurred in  15 minutes, proceed  im-
                    mediately to INTUBATE the stomach.

        Following emesis, have the victim drink a suspension of 30-50 gm
        ACTIVATED CHARCOAL in 3-4 ounces of water to bind toxicant
        remaining in the gastrointestinal tract.
    B.   If victim is not  fully alert, empty the stomach immediately by  IN-
        TUBATION, ASPIRATION, and LAV AGE, using isotonic saline
        or 5% sodium bicarbonate. Because PCP is commonly dissolved in
        petroleum distillates, emesis and intubation of the stomach involve
        a serious risk that solvent will be aspirated, leading to chemical
        pneumonitis. For this reason:
        (a).   If victim is unconscious or obtunded and facilities are at hand,
             insert an  ENDOTRACHEAL TUBE (cuffed, if available)
             prior to gastric intubation.
        (b).   Keep victim's HEAD BELOW LEVEL OF THE STOMACH,
             turned to left, during intubation and lavage. (Trendelenburg,
             or left lateral decubitus, with head of table tipped downward).
        (c).   ASPIRATE  PHARYNX as  regularly as possible  to remove
             gagged or  vomited stomach contents.
        (d).   After aspiration of gastric contents and washing of stomach,
             instill 30 gm of ACTIVATED CHARCOAL in 3-4 ounces of
             water through a stomach tube to limit absorption of remain-
             ing toxicant. Do NOT instill milk, cream, or other materials
            containing vegetable or  animal  fats, which  are likely to
            enhance absorption.

   C.   If bowel movement has not occurred in 4 hours and patient is fully
        conscious, give  SODIUM SULFATE as a cathartic: 0.25 gm/kg
        body weight in 1-6 ounces of water. Magnesium sulfate and citrate

                               21

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        are equally suitable unless renal function is impaired; retention of
        magnesium may depress CNS function and alter myocardial irrita-
        bility.

5.   DO NOT administer atropine,  aspirin, or other antipyretics to control
    fever. These are likely to enhance the toxicity of phenolic compounds.
6.   During  convalescence, administer  high-calorie,  high-vitamin  diet to
    restore body fat and carbohydrate.
7.   Discourage  subsequent contact  with the toxicant for at least 4 weeks to
    allow full restoration of normal metabolic processes.
8.   HEMODIALYSIS and HEMOPERFUSION may be considered in PCP
    poisoning, although phenols are extensively bound to plasma protein.
    EXCHANGE TRANSFUSION was used to rescue the infants inadver-
    tently poisoned by PCP in a hospital. Unless renal and liver functions are
    impaired, PCP is rapidly eliminated from the blood  and tissues.
                                 22

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                          Chapter 5

               NITROPHENOLIC AND
        NITROCRESOLIC HERBICIDES

 GENERAL CHEMICAL STRUCTURE
            NO2

 O2N V    ^O—H (or ESTER)
 (ALKYL)   (ALKYL)

 COMMON COMMERCIAL PESTICIDE PRODUCTS

  Dinitrophenol (Chemox PE), dinitrocresol (DNOC, DNC, Sinox, Chemsect
 DNOC, Elgetol 30, Nitrador, Selinon, Trifocide), dinoseb (DNBP, Dinitro,
 Basanite,  Caldon,  Chemox  General,  Chemox  PE, Chemsect  DNBP,
 Dinitro-3, Dinitro General,  Dow General Weed Killer, Dow Selective Weed
 Killer, Dynamyte, Elgetol 318, Gebutox, Kiloseb, Nitropone  C, Premerge 3,
 Sinox General,  Subitex, Unicrop DNBP, Vertac Dinitro Weed  Killer),
 dinosam (DNAP), dinoprop, dinoterbon, dinoterb, dinosulfon, bmapacryl
 (Morocide, Endosan, Ambox, Dapacryl), dinobuton (Acrex, Dessin, Dinofen,
 Drawinol, Talan), dinopenton, dinocap (Crotothane, Karathane).  Several
 combinations are widely used: Dyanap and Klean Krop = dinoseb  + nap-
 talam;  Ancrack  =  sodium salts of dinoseb  + naptalam;  Naptro  =
 dinitrophenol +  naptalam.


 TOXICOLOGY

  These materials should be regarded as highly toxic to humans and animals.
 Most nitrophenols and nitrocresols are well absorbed from the gastrointestinal
 tract, across the skin, and by the lung when fine droplets are inhaled. Except in
 a few sensitive individuals,  aromatic nitro-compounds are only moderately
 irritating to the skin. Like other phenols, they are toxic to the liver,  kidney,
 and nervous system. The basic mechanism of toxicity is a stimulation of oxida-
 tive metabolism in cell mitochondria, by interference with the normal coupling
 of carbohydrate oxidation to phosphorylation (ADP to ATP). Increased oxi-
 dative metabolism leads to pyrexia, tachycardia, and dehydration, and ulti-
 mately depletes carbohydrate and fat stores. Most severe poisonings from
absorption of these compounds have occurred in workers who were  concur-
rently exposed to hot environments. Pyrexia and direct action on the brain
cause cerebral edema, manifest clinically as a toxic psychosis and sometimes

                              23

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convulsions. Liver parenchyma and renal tubules show degenerative changes.
Albuminuria,  pyuria, hematuria, and increased BUN  are often prominent
signs of renal  injury.
  Agranulocytosis  has  occurred  in humans  following  large  doses  of
dinitrophenol. Cataracts  have occurred  in  some  chronically  poisoned
laboratory species, but this effect has not been observed in humans.
  Nitrophenols and nitrocresols are efficiently excreted by the kidneys, and
there is some hepatic excretion into the bile. Unless the absorbed dose was ex-
tremely high,  or kidney function  is impaired, nearly  complete elimination
from the body can be expected within 3-4 days.
  Death in nitrophenol poisoning is followed promptly by intense rigor mortis.

FREQUENT  SYMPTOMS AND SIGNS OF POISONING

  YELLOW STAINING of skin and hair  often signify contact with a nitro-
phenolic chemical. Staining of the sclerae and urine indicate absorption of
potentially toxic amounts. PROFUSE SWEATING, HEADACHE, THIRST,
MALAISE, and LASSITUDE are the common early symptoms of poisoning.
WARM, FLUSHED SKIN, TACHYCARDIA, and FEVER characterize a
serious degree of poisoning. APPREHENSION, restlessness, anxiety, manic
behavior, or unconsciousness reflect severe cerebral injury. CONVULSIONS
occur in the most severe poisonings. Cyanosis, tachypnea and dyspnea result
from stimulation of metabolism, pyrexia, and tissue anoxia.  Weight loss oc-
curs in persons chronically poisoned at low dosages.

CONFIRMATION OF DIAGNOSIS

  Unmetabolized nitrophenols and nitrocresols can be  identified spectro-
photometrically, or by gas-liquid chromatography, in the  serum and urine at
concentrations well below those necessary to cause poisoning. If poisoning is
probable, DO NOT  AWAIT  CONFIRMATION before  commencing treat-
ment.

TREATMENT

 1.   WASH contaminated SKIN and HAIR promptly with soap and water, or
     with water alone if soap is not available.
 2.   FLUSH  chemical from EYES with  copious amounts of clean water.
 3.   IN EVENT OF SYSTEMIC POISONING:
     A.  REDUCE ELEVATED BODY TEMPERATURE BY PHYSICAL
         MEANS.  Administer  sponge  baths and cover victim with Idw-
         temperature blankets.  In fully  conscious patients, administer  cold,
         sugar-containing liquids by mouth as tolerated.
     B.   Administer OXYGEN continuously by  mask  to minimize tissue
         anoxia.
                                 24

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    C.  Unless there are manifestations of cerebral edema, administer IN-
        TRAVENOUS FLUIDS at maximum tolerated rates to enhance uri-
        nary excretion of toxicant and to support physiologic mechanisms
        for heat loss. IN the presence of CEREBRAL EDEMA, intravenous
        FLUIDS must be administered very CAUTIOUSLY to avoid increas-
        ing the cerebral injury. Monitor fluid balance, blood electrolytes and
        sugar, adjusting IV infusions to stabilize electrolyte concentrations.
        Follow urine contents of albumin and cells. Follow serum alkaline
        phosphatase, GOT, and LDH to evaluate liver injury.
    D.  Administer SEDATIVES, if necessary, to control apprehension, ex-
        citement, and/or convulsions. Although not previously used in this
        type of  poisoning, DIAZEPAM (Valium® ) should help:  adult
        dose, 5-10 mg slowly IV, or IM (deep); child's dose, 0.1  mg/kg.
        Repeat every 2-4 hours as needed. Amobarbital or  pentobarbital
        may be needed. Dose in adults: 200 mg, IM or slowly IV, every 4-6
        hours; child's dose: up to 5  mg/kg.

        CAUTION:  Be prepared to counteract respiratory depression and
                    hypotension which may follow administration of
                    anticonvulsants and sedatives.

4.   If toxicant has been INGESTED, evacuate the stomach and intestine.

    A.  If victim  is alert and respiration is not depressed, give SYRUP of
        IPECAC, followed by 1-2  glasses of water,  to induce vomiting
        (adults 12 years and older: 30 ml; children under 12:  15 ml).

        CAUTION:  OBSERVE  victim closely AFTER administering IP-
                    ECAC. If consciousness level declines, or if vomiting
                    has not occurred  in 15 minutes,  immediately IN-
                    TUBATE, ASPIRATE, and LAV AGE the stomach.

        Following emesis, have victim drink a suspension of 30-50 gm AC-
        TIVATED CHARCOAL  in 3-4 ounces of water to bind toxicant
        remaining in the gastrointestinal tract.
    B.   IF VICTIM IS NOT FULLY ALERT, empty the stomach immedi-
        ately by  INTUBATION, ASPIRATION, and  LAV AGE,  using
        isotonic saline or 5% sodium bicarbonate. Because these pesticides
        are usually dissolved in petroleum distillates, emesis and intubation
        of the stomach involve serious risk that solvent will  be aspirated,
        leading to chemical pneumonitis. For this reason:

        (a).  If victim is unconscious or obtunded and facilities are at hand,
             insert an  ENDOTRACHEAL  TUBE (cuffed,  if available)
             prior to gastric intubation.
        (b).  Keep victim's HEAD BELOW LEVEL OF THE STOMACH
             and  turned  to the  left,  during  intubation   and lavage
             (Trendelenburg, or left lateral decubitus, with head of table
             tipped downward).
                               25

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        (c).  ASPIRATE PHARYNX as regularly as possible to  remove
             gagged or vomited stomach contents.
        (d).  After aspiration of gastric contents and washing of stomach,
             instill 30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces
             of water through the stomach tube to limit absorption of re-
             maining  toxicant.  Do  NOT  instill  cream, milk, or other
             materials containing vegetable or animal fats, as these are like-
             ly to enhance absorption.

    C.  If bowel movement has not occurred in 4 hours, and if patient is fully
        conscious, give SODIUM SULFATE as a cathartic: 0.25 gm/kg
        body weight in 1-6 ounces of water. Magnesium sulfate and citrate
        are equally suitable unless renal function is impaired; retention of
        magnesium may depress CNS function and alter myocardial irrita-
        bility.

5.   DO NOT administer atropine, aspirin, or other antipyretics to  control
    fever. Animal tests indicate that aspirin enhances, rather than reduces,
    the toxicity of nitrophenolic and nitrocresolic compounds.
6.   During convalescence, administer high-calorie, high-vitamin diet to facil-
    itate repletion of body fat and carbohydrate.
7.   Discourage subsequent contact with the toxicant for at least 4 weeks, to
    allow full restoration of normal metabolic processes.
8.   HEMODIALYSIS  and HEMOPERFUSION  may  be  considered in
    severe poisonings by aromatic nitro-compounds, although most phenols
    are extensively bound to plasma  proteins. EXCHANGE TRANSFU-
    SION is another option in poisonings characterized by impaired renal
    function. So long as renal and liver functions are intact,  these com-
    pounds are efficiently excreted.
                                26

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                          Chapter 6

     CHLOROPHENOXY COMPOUNDS
GENERAL CHEMICAL STRUCTURE
      (or CH3)
       Cl
Cl
— O —
       (Cl)
   O
   II
_ C — O — H or
n
COMMON COMMERCIAL PESTICIDE PRODUCTS

  Several hundred commercial products contain chlorophenoxy herbicides in
various concentrations and combinations. Following are names  of widely
advertised formulations. In some cases, the same name is used for products
with different ingredients. Exact composition must therefore be determined
from product label.
  2,4-D, or 2,4-dichlorophenoxyacetic acid (Weedonef, Agrotec, Amoxone,
Aqua-Kleen,  BH 2,4-D,  Chipco Turf Herbicide  "D", Chloroxone, Crop
Rider, D50, Dacamine 4D, Ded-Weed, Desormone,  Dinoxol, DMA4, Dor-
mone, Emulsamine BK, Emulsamine E-3, Envert DT or 171, Esteron 99 Con-
centrate, Esteron Four, Esteron Brush Killer, Estone, Fernoxone, Fernimine,
Ferxone, Fernesta, Formula 40, Hedonal, Herbidal, Lawn-Keep, Macondray,
Miracle, Netagrone 600, Pennamine D, Planotox, Plantgard, Rhodia, Salvof,
Spritz-Hormin/2,4-D, Spritz-Hormit/2,4-D, Superormone Concentre, Super
D Weedone, Transamine, U46, Verton 2D, Visko-Rhap,  Weed-B-Gon,
Weedar, Weed-Rhap, Weed Tox, Weedtrol, De broussaillant 600, Lithate,
Dicotox, Field Clean Weed Killer). 2,4-DB is the butyric acid homologue of
2,4-D. Dichlorprop is the propionic acid homologue.
  2,4,5-T or 2,4,5-trichlorophenoxyacetic acid (Brush-Rhap,  Dacamine  4T,
Debroussaillant Concentre, Ded-Weed Brush Killer, Esteron 245, Fence Rider,
Forron, Inverton 245, Line Rider, Spontox, Super D Weedone, Tormona,
Transamine,  Trinoxol, Trioxone,  U46, Veon 245,  Verton  2T, Weedar,
Weedone Envert T).
  Common mixtures of 2,4-D  and 2,4,5-T are: Dacamine 2D/2T, Esteron
Brush Killer, Rhodia Low Volatile Brush Killer No. 2, U46 Special, Tributon,
Visko-Rhap LV2D-2T, and Transamine.
f  A product of identical name containing pentachlorophenol (Chapter 4) as
   the active ingredient has been discontinued by Amchem Products Co.
t  A product of identical name marketed by the Crystal Chemical Company
   contains cacodylic acid as the active ingredient (Chapter 10).
                               27

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  2,4,5-TP (Silvex) is the propionic acid homologue of 2,4,5-T. Kuron is a low
volatile ester of 2,4,5-TP. 2,4,5-TB is the butyric acid homologue of 2,4,5-T.
Fenac or chlorfenac is 2,3,6-trichlorophenylacetic acid. Dicamba (Banvel) is
dichloroanisic acid.  MCPA, MCPB,  MCPB-Ethyl, MCPCA  and MCPP
(Mecoprop) are 2-methyl, 4-chlorophenoxy aliphatic acids and esters.

TOXICOLOGY

  Some of the chlorophenoxy acids, salts, and esters are moderately irritating
to skin, eyes, and respiratory and gastrointestinal linings. In a few individuals,
local depigmentation  has apparently resulted from prolonged and repeated
dermal contact with chlorophenoxy materials.
  The chlorophenoxy compounds  are absorbed across the gut wall, lung, and
skin. They are not significantly fat storable. Excretion occurs within hours, or
at most, days, primarily in the urine.
  Given in large doses to experimental animals, 2,4-D causes vomiting, diar-
rhea, anorexia, weight loss, ulcers of the mouth and pharynx, and toxic injury
to the liver, kidneys, and central nervous system. Myotonia (stiffness and in-
coordination of hind extremities) develops in some species and is apparently
due to CNS damage: demyelination has been observed in the dorsal columns
of the  cord, and EEC changes have indicated functional disturbances in the
brains  of heavily dosed experimental animals.
  Ingestion of large  amounts of chlorophenoxy acids has resulted in severe
metabolic acidosis in humans. Such cases have been associated with electro-
cardiographic  changes, myotonia, muscle weakness, myoglobinuria, and ele-
vated serum creatine phosphokinase, all reflecting injury to striated muscle.
Because chlorophenoxy acids are weak  uncouplers of oxidative phosphoryla-
tion, extraordinary doses may produce  hyperthermia from increased produc-
tion of body heat.
  PolyChlorinated DibenzoDioxin (CDD) compounds  are generated in the
synthesis of 2,4,5-T. The 2,3,7,8-Tetra  CDD form is extraordinarily toxic to
multiple mammalian tissues. Hexa- hepta-, and octa-compounds exhibit less
systemic toxicity, but are the likely cause of chloracne (a chronic, disfiguring
skin condition) seen  in workers engaged in the manufacture of 2,4,5-T, and
certain other chlorinated organic compounds. Although toxic effects, notably
chloracne, have been observed in manufacturing plant workers, they have not
been observed in formulators or applicators  regularly exposed to 2,4,5-T.
  The medical literature contains several reports of peripheral  neuropathy
following what seemed to be minor dermal exposures to 2,4-D. It is not cer-
tain that exposures to other neurotoxicants  were entirely excluded in these
cases. Single doses of 5 mg/kg body weight of 2,4-D and 2,4,5-T have been ad-
ministered to  human  subjects without any adverse effects. One  subject con-
sumed 500 mg of 2,4-D per day for 3 weeks without experiencing symptoms or
signs of illness.
                                   28

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FREQUENT SYMPTOMS AND SIGNS OF POISONING

  Chlorophenoxy compounds are moderately IRRITATING to skin and
mucous membranes. Inhalation of sprays may cause burning sensations in the
nasopharynx and chest, and coughing may result. Prolonged inhalation some-
times causes dizziness.
  When INGESTED, high concentrations of chlorophenoxy compounds may
irritate the mouth, throat, and  gastrointestinal tract. Prompt EMESIS,
CHEST PAIN (from esophagitis), ABDOMINAL PAIN, and DIARRHEA
commonly ensue. Injury to the GI tract does not usually progress to ulceration
or  perforation.  Absorbed chlorophenoxy  compounds  have  caused
FIBRILLARY MUSCLE TWITCHING, skeletal  muscle tenderness,  and
MYOTONIA (stiffness of muscles of the extremities). Ingestion of very large
amounts has produced METABOLIC ACIDOSIS, fever, tachycardia, hyper-
ventilation, vasodilatation and sweating. Particular cases have been charac-
terized by coma and convulsions.

CONFIRMATION OF DIAGNOSIS

  Gas-liquid chromatographic methods are available for detecting and mea-
suring the chlorophenoxy compounds in blood and urine. These analyses are
useful in confirming and assessing the magnitude of chlorophenoxy absorp-
tion. Urine samples should be collected as soon as possible after exposure
because the herbicides may be almost completely excreted in 24-72 hours,
depending on the extent of toxicant absorption. Analyses can be performed at
special laboratories  operated by  state health departments,  chemical com-
panies, universities, and government facilities. If circumstances  indicate
strongly that excessive exposure to any of these compounds has occurred, ini-
tiate appropriate treatment measures immediately, not waiting for chemical
confirmation of toxicant absorption.

TREATMENT

 1.   BATHE and SHAMPOO with soap and water to remove chemicals from
     skin and hair. Individuals with chronic skin disease or known sensitivity
     to chemicals should either avoid using these herbicides or take extraordi-
     nary measures to avoid contact.
 2.   FLUSH contaminating chemicals from eyes with copious amounts of
     clean water for 10-15 minutes.
 3.   If symptoms of illness  occur during or following inhalation of spray,
     REMOVE victim FROM CONTACT with the  material for at least two
     days. Allow subsequent contact with chlorophenoxy compounds only if
     effective respiratory protection is practiced.
 4.   IF substantial amounts of chlorophenoxy compounds have been  IN-
     GESTED, spontaneous emesis usually occurs.  Ordinarily, this empties
     the stomach as effectively as  intubation and lavage. If vigorous emesis
                                 29

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    has not occurred and IF VICTIM IS FULLY ALERT, induce EMESIS
    with SYRUP OF IPECAC (adults 12 years and older,  30 ml; children
    under  12 years,  15  ml), followed by 1-2 glasses of water.  Following
    emesis, administer 30-50 gm of ACTIVATED CHARCOAL in a slurry
    of 6-8 ounces tap water, to limit absorption of herbicide remaining in the
    gut.
5.   IF CONSCIOUSNESS LEVEL IS DEPRESSED  or  other signs of
    NEUROTOXICITY appear, SUSPECT additional or alternative in-
    gested toxicants. Evacuate the stomach by INTUBATION,  ASPIRA-
    TION,  and LAV AGE.  Because petroleum distillates are commonly in-
    cluded in chlorophenoxy formulations, gastric intubation incurs a risk of
    hydrocarbon  pneumonitis from aspiration. For this reason:

    A.  If victim is unconscious or obtunded and facilities are at hand, in-
        sert an ENDOTRACHEAL TUBE (cuffed, if available) prior to
        gastric intubation.
    B.  Keep victim's HEAD BELOW LEVEL OF THE STOMACH  dur-
        ing intubation and  lavage (Trendelenburg, or left lateral decubitus,
        with head of table tipped downward). Keep victim's head turned to
        left.
    C.  ASPIRATE PHARYNX as regularly as possible to remove gagged
        or vomited stomach contents.

    After aspiration of gastric contents and washing of stomach, instill 30-50
    gm of ACTIVATED CHARCOAL in 3-4 ounces of water through the
    stomach tube to limit absorption of remaining toxicant. Do NOT instill
    milk, cream,  or other materials containing vegetable or animal fats, as
    these are likely to enhance absorption.
6.   If bowel movement has  not occurred in 4 hours and patient is fully con-
    scious, give SODIUM SULFATE,  0.25 gm/kg, as a cathartic. Magne-
    sium sulfate and citrate, in comparable dosages, are equally suitable if
    renal function is adequate. Retained magnesium may depress CNS func-
    tion.
7.   In SEVERE POISONINGS by very large amounts of ingested chloro-
    phenoxy acids,  forced ALKALINE DIURESIS  may save the victim's
    life. Assess serum electrolyte concentrations, and serum and urine pH. If
    a metabolic acidosis is present, infuse solutions of sodium bicarbonate at
    rates sufficient  to keep the urine  distinctly alkaline, continuing  until
    plasma concentrations of chlorophenoxy compounds are less than about
    10Mg/ml. [Prescott, L F. et al., Br. J. Clin. Pharmacol. 7:11 (1979)]
                               30

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^\ II   iki'\y\-^-              f     \     f     \
   \5
                           Chapter 7


             PARAQUAT  AND  DIQUAT


CHEMICAL STRUCTURES


                           'CHs         v_rv
                             2Cr           ™      **

                                              CH2—CH2   2 Br~

          PARAQUAT                       DIQUAT
COMMON COMMERCIAL PESTICIDE PRODUCTS

  Paraquat  products: paraquat dichloride (usually as a 21% concentrate).
Other  names:  Ortho paraquat-CL,  Crisquat, Dextrone X, Esgram.  Mix-
tures: Priglone, Preeglone, Weedol—with diquat; Simpar,  Terraklene—with
simazine; Gramonol, Mofisal—with monolinuron; Pathclear—with diquat
and simazine; TotaCol, Dexuron—with diuron.
  Diquat products:  diquat (Reglone, Reglox, Aquacide,  Dextrone, Weed-
trine-D). Mixtures: Priglone, Preeglone, Weedol—with paraquat; Pathclear—
with paraquat and simazine.

TOXICOLOGY

  These dipyridyls injure the epithelial tissues: skin, nails, cornea, liver, kid-
ney, and the linings of the GI and respiratory tracts. In addition to direct irri-
tant effects, injury may involve peroxidation of intracellular and extracellular
phospholipids and inhibition of surfactant synthesis by lung tissue. These toxic
properties may derive from the capacity of dipyridyls to generate free radicals
in tissues. The injury is usually reversible; however, the  pulmonary reaction
which follows ingestion of paraquat is often fatal.
  Certain injuries have followed  occupational contact with paraquat. Contact
with  the concentrate may cause irritation and fissuring of the skin of the
hands,  and cracking, discoloration, and  sometimes loss of the fingernails.
Splashed in the eye,  paraquat concentrate causes conjunctivitis and, if not
promptly removed, may result in protracted opacification of the cornea.
  Although nearly all systemic intoxications by paraquat have followed inges-
tion of the chemical, occasional poisonings have resulted from excessive dermal
contact. Absorption of toxic amounts is much more likely to occur if the skin
is abraded. Persons who have experienced extraordinary dermal contact with
paraquat (especially  the concentrate) should  be examined, and  tested for
hazardous concentrations of the  agent in the blood and urine (see  section on
Confirmation of Diagnosis).

                                 31

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  Inhalation of dilute spray mist may irritate the upper respiratory passages,
causing a scratchy throat and nosebleed. Effects induced by dilute paraquat
sprays ordinarily resolve promptly following withdrawal from exposure.
  If ingested, paraquat produces inflammation of the mouth and GI tract,
sometimes progressing  to  ulceration within  1-4 days.  Once  absorbed,  it
damages the parenchymal cells of the liver and tubule cells of the kidney. In
most instances, the victim survives these injuries. Paraquat is actively concen-
trated in the pneumocytes of lung tissue. Several days after ingestion these cells
die, after which there is rapid proliferation of connective tissue cells which fill
the alveolar spaces. Although some victims have survived, death from asphyxia
usually occurs once  this  degree of lung damage has been sustained.  In sur-
vivors, recovery of normal lung function requires weeks or months. In a few
instances, ingestion  of large quantities of paraquat has induced protracted
pulmonary edema. Myocardial injury has also been noted in some poisonings.
  Diquat appears less likely than paraquat to cause death. Information from
suicidal ingestions and from orally dosed monkeys indicates that the principal
target organs in diquat toxicity are the gastrointestinal tract, kidney, and liver.
Diquat produces intense congestion and ulceration of the stomach and bowel.
Fatty liver and acute renal tubular necrosis  are produced by adequate doses.
Smaller doses administered chronically have caused lens cataracts in animals.
Diquat is not concentrated in lung tissue as paraquat is, and pulmonary lesions
are limited to punctate hemorrhages. Hemorrhages in brain tissue have been
reported after diquat ingestion.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

  The irritant effects of paraquat on skin, eye, and upper respiratory tract
have been described  under TOXICOLOGY.
  The earliest (1-4 days) symptoms of injury and signs following ingestion of a
toxic dose of PARAQUAT are burning PAIN (oral, substernal, abdominal),
NAUSEA, VOMITING, DIARRHEA, and sometimes melena. Early symp-
toms are sometimes  so mild that vigorous treatment is improperly delayed.
  From 24-72 hours, indications of renal and hepatic insult appear. Albumin-
uria, hematuria, pyuria, and ELEVATED BUN and CREATININE may occur.
OLIGURIA may develop, and this signals severe poisoning. JAUNDICE and
elevations  of serum GOT,  GPT, LDH, and alkaline phosphatase reflect
hepatocellular injury. These injuries are usually reversible, although severe
renal tubular damage may require extracorporeal hemodialysis.
  A progressive decline in arterial oxygen tension and CO diffusion capacity
commonly precedes the appearance of pulmonary symptomatology. COUGH,
DYSPNEA, and TACHYPNEA usually appear 72-96 hours after paraquat in-
gestion, but  may be delayed as long as 14 days. Progressive CYANOSIS
reflects deteriorating gas exchange caused by the fibrogenic reaction in the
alveolar sacs. In a few cases, the production of COPIOUS WATERY SPUTUM
(pulmonary edema) has followed ingestions of large amounts (200 ml) of para-
quat or diquat concentrate.
                                  32

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  DIQUAT  INGESTION results in intense NAUSEA, VOMITING, and
DIARRHEA,  with  accompanying  dehydration,  and  in  melena  and
hematemesis from gastrointestinal ulceration. INCREASED serum BUN and
CREATININE, and ANURIA result from acute tubular necrosis.  Serum
GOT, GPT, and LDH and alkaline phosphatase elevations reflect liver injury.
Early COMA has sometimes occurred following suicidal ingestion of large
amounts and has also been noted in experimentally poisoned monkeys. This
could be a consequence of  profound dehydration, with electrolyte  distur-
bances, or of diffuse hemorrhages in the central nervous system,  as noted in
one human poisoning.

CONFIRMATION OF DIAGNOSIS

  Qualitative and quantitative methods for paraquat and diquat in blood and
urine are available at some local, private, and government toxicology labora-
tories, and at the Chevron Environmental  Health Center, Box 1272, Rich-
mond, California 94802. The Chevron Chemical  Company maintains a
24-hour toxicology consultation service through an emergency telephone
number: (415) 233-3737. Sales representatives are prepared to deliver bentonite
to virtually any location in the United States, and to arrange for  the prompt
delivery of biologic specimens for  dipyridyl analysis to the Environmental
Health Center.  Company toxicologists are available 24 hours a day for assis-
tance in management of poisonings by Chevron products.

TREATMENT

 1.  Contaminated SKIN must be FLUSHED with copious amounts of water.
    Material splashed  in the EYES must be removed by  PROLONGED
    IRRIGATION with clean water. Eye contamination should thereafter be
    treated by an ophthalmologist. Mild skin reactions usually  respond to
    simple avoidance of further contact, but the irritation may take several
    weeks to resolve. Severe injuries, with cracking, secondary infection, or
    nail injury, should be treated by a dermatologist.
 2.  After a DIPYRIDYL compound has been INGESTED,
       EVACUATE the STOMACH, then LOAD the gastrointestinal tract
    with an effective ADSORBENT, to minimize toxicant absorption. These
     measures  must be  undertaken immediately,  even though  the patient is
    free of signs of systemic toxicity, and even when, by all accounts, the in-
    gested dose  was probably small and was taken as  long as several days
    prior to treatment.
       INTUBATE the STOMACH, ASPIRATE contents,  then LAV AGE
    with at least two liters  of a slurry of ADSORBENT in normal  saline.
    Then, slowly instill several hundred additional ml  of adsorbent  slurry,
    allowing the stomach and intestine to accommodate this  volume without
    overdistension and vomiting.
                                 33

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    A.  The ideal adsorbent is BENTONITE, administered as a 7 gm per
        100 ml suspension. If not immediately available, use ACTIVATED
        CHARCOAL, 30-50 gm in 300-400 ml of water, or any concentra-
        tion that will flow through the tube. As soon as bentonite has been
        obtained, administer it as rapidly as the patient will tolerate it. If pa-
        tient cannot swallow bentonite, administer it by stomach tube at the
        highest concentration that will flow through the tube.
    B.  Initiate  SALINE CATHARSIS. Give SODIUM SULFATE, 0.25
        gm/kg,  and repeat in two hours if no bowel movement has oc-
        curred. Magnesium salts are probably contraindicated, because of
        the risk of magnesium retention in the presence of impaired renal
        function.
    C.  Continue administering bentonite suspension and sodium sulfate
        until the gut has been thoroughly flushed. This may require several
        days.

3.  Secure samples of blood and urine for dipyridyl analysis. (See Confirma-
    tion of Diagnosis.)
4.  Commence INTRAVENOUS INFUSIONS of glucose and electrolyte to
    minimize toxicant concentrations in the tissues, and expedite excretion of
    the dipyridyl. Attempt to establish a diuresis of 10-15 liters per day.

    CAUTION:   Monitor fluid balance and electrolytes continuously to in-
                 sure  against fluid  overload if  acute  tubular necrosis
                 supervenes.

5.  Although cases of paraquat poisoning have been successfully managed
    by forced diuresis regimens alone, it is more effective to use extracorporeal
    HEMODIALYSIS and/or HEMOPERFUSION over specially coated
    charcoal. This procedure for toxicant removal is best executed in tertiary
    care centers where blood levels of paraquat can be monitored regularly,
    and various complications of hemoperfusion can be detected and fore-
    stalled. The prognosis is generally good when blood levels do not exceed
    0.05 to 0.10 ppm by 24-48 hours  after paraquat ingestion.
6.  DO NOT ADMINISTER SUPPLEMENTAL  OXYGEN  in paraquat
    poisoning. Increased levels of alveolar oxygen accelerate the pathologic
    process in the lung caused by paraquat. Some clinicians recommend
    maintaining the patient in an atmosphere of 15-16%  oxygen as soon as
    possible, to retard the fibrogenic  process.
7.  The tubular necrosis produced by large doses of DIQUAT may require
    protracted EXTRACORPOREAL HEMODIALYSIS.
8.  The topical  injuries  to mucous  membranes  produced  by ingested
    dipyridyls are painful  and may require topical local anesthetic.
9.  The effectiveness of  various medicines and  procedures  in paraquat
    poisoning remains  uncertain. The free-radical scavenger super oxide
    dismutase is  theoretically appropriate as an antidote, but is unproved.
    Corticosteroids are  often given,  and may be helpful. There is limited
                                 34

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laboratory evidence supporting the use of propranolol and expectorants:
glyceryl guaicolate, anise oil, terpin hydrate,  ammonium chloride and
potassium iodide. One victim is thought to have benefited from a com-
bination of azathioprine and potassium aminobenzoate. Lung transplant
in one case of paraquat poisoning was not successful.
                             35

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                       Chapters

          DITHIOCARBAMATES AND
               THIOCARBAMATES
CHEMICAL STRUCTURES AND
COMMON COMMERCIAL PRODUCTS

  These functional classes include many fungicides and herbicides. There are
several subclasses:

BIS DITHIOCARBAMATES

           s         s
CH3       ||         II       CH3
     ^ N-C-S-S-C-N

          THIRAM

COMMERCIAL PRODUCTS

  thiram (Arasan,  Thiramad, Thirasan, Thylate, Tirampa, Pomarsol forte,
TMTDS, Thiotex, Fernasan,  Nomersan,  Tersan,  Thiuramin,  Tuads,
AAtack, Aules, Chipco Thiram 75, Fermide 850, Trametan, Hexathir, Mer-
curam,  Polyram-Ultra,  Spotrete,  Tripomol, Tersan  75,  Tetrapom,
Thioknock). Thiram is a fungicide.

METALLO  BIS DITHIOCARBAMATES
-CH3
\
/
II
N -C-S

— Zn, Na, or Fe

COMMERCIAL PRODUCTS

  ziram (Z-C Spray, Carbazinc, Corozate, Cuman, Drupina 90, Fuclasin
Ultra, Fuklasin, Fungostop, Hexazir, Mezene, Pomarsol Z Forte, Prodaram,
Tricarbamix Z, Triscabol,  Zerlate,  Vancide  MZ-96,  Zincmate,  Ziram
Technical, Ziramvis, Zirasan 90, Zirberk, Zirex 90, Ziride); nabam (Dithane
D14, Chem Bam, DSE, Nabasan, Parzate, Spring-Bak); ferbam (Ferberk,
Hexaferb, Knockmate,  Trifungol,  Vancide  FE-95). These  chemicals are
fungicides.

                            36

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ETHYLENE BIS DITHIOCARBAMATES
  H     H      S
   I       I       II
HC-N-C-S,
   I                          Mn or Zn
   H      H     S
COMMERCIAL PRODUCTS

  maneb (Dithane M22, Griffin Manex, Kypman 80, Manebgan, Manesan,
Manzate, Nespor,  Manzeb, Polyram M, Manzin, Tersan LSR, Trimangol,
Tubothane, Vancide  Maneb 80);  zineb  (Aspor,  Dipher,  Dithane Z-78,
Hexathane, Kypzin, Lonacol, Parzate, Polyram Z, Tiezene, Tritoftorol, Zeb-
tox, Zinosan).
  These fungicides are often combined with thiram and with various inorganic
salts of copper, manganese, and zinc in commercial preparations. Mancozeb
(Dithane M45) is essentially a combination of maneb and zineb.
(MONO) THIOCARBAMATES
     R           o
        x       II
            N - C  -  S - R"
 Aror R'

COMMERCIAL PRODUCTS

  butylate (Sutan), cycloate (Ro-Neet), pebulate (Tillam), vernolate (Veraam,
Surpass), EPTC (Eptam), diallate (Avadex), triallate (Far-Go, Avadex-BW).
These chemicals are selective herbicides.

TOXICOLOGY

  Although these agents have chemical similarities, the separate classes are
metabolized differently by mammals, and effects on human health are also
different.
  In general,  mammalian toxicity, as  measured by oral  dosing studies in
laboratory rodents, is low. Occupational exposures have, however, caused
acute adverse effects, and laboratory investigations have suggested potential
chronic effects from some agents.

                                 37

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  None of these agents is a cholinesterase inhibitor.
  Thiram is irritating to skin and mucous membranes. It has sensitized some
individuals,  generally after contact with rubber products containing residues
of thiram used as a curing agent.
  The metallo dithiocarbamates and ethylene dithiocarbamates are moderately
irritating to skin and the respiratory mucous membranes following contact
with sprays or dusts.
  Thiram is the  methyl analogue of disulfiram (Antabuse), an agent used to
condition alcoholics against beverage alcohol. Much more is known of the tox-
ic effects-of disulfiram than of thiram, although the acute toxicity of thiram in
laboratory animals is substantially greater. Given to animals in extreme doses,
disulfiram has  caused gastrointestinal  irritation,  demyelinization of CNS
tissues, and necrosis of liver, splenic, and kidney tissues. Peripheral neuropa-
thy and psychotic reactions  have occurred  in humans taking large doses of
disulfiram regularly.
  Functional and anatomic CNS damage has been demonstrated in rats on
high chronic dosage regimens of  iron  and zinc  dimethyldithiocarbamates.
Because all of these agents are degraded partly to carbon disulfide in  the body,
a role of this metabolite in neurotoxic effects is suspected.
  Both thiram and disulfiram inhibit aldehyde dehydrogenase, and are there-
fore capable of inducing "Antabuse" reactions in  persons who  consume
beverage alcohol following substantial absorption of dithiocarbamates. Reac-
tions may have occurred rarely in workers who imbibed after extraordinary oc-
cupational exposure to thiram. Theoretically, the metallo dithiocarbamates
may also predispose to an "Antabuse" reaction. Peripheral vasodilation is the
main pathophysiologic feature of  the disulfiram-alcohol reaction,  probably
due to high tissue levels of acetaldehyde. This may occasionally lead  to shock,
and  even more rarely, to myocardial ischemia, cardiac arrhythmias, circula-
tory failure, and death.  Animal experimentation has  suggested certain other
biochemical mechanisms of toxicity involving reaction products of ethanol
and  disulfiram.
  The ethylene bis dithiocarbamates do not inhibit aldehyde dehydrogenase,
and  there is no evidence of neurotoxicity  from  them. They do,  however,
degrade in the environment, and in  mammalian tissues, to ethylene thiourea, a
compound known as a goitrogen and carcinogen in laboratory animals. This
feature mandates extra care in the protection of harvesters, and in removal of
residues from harvested  crops.
  Except  for some moderate irritant effects on  skin, respiratory tract,  and
eyes, the (mono) thiocarbamate herbicides do not appear to be highly toxic.
Extreme doses in laboratory animals  do produce paralysis.  There is a very
remote possibility of "Antabuse"  reactions from ethanol following extraor-
dinary exposure to these (mono) thiocarbamates. They  do not form ethylene
thiourea on degradation.
                                   38

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 SYMPTOMS AND SIGNS OF POISONING

 Thiram and metallo bis dithiocarbamates

   Itching, redness, and eczematoid DERMATITIS have resulted when predis-
 posed individuals have come into contact with these agents. Inhaled sprays and
 dusts have caused NASAL STUFFINESS,  hoarseness, cough, and, rarely,
 pneumonitis. Repeated contact may produce sensitization. Ingestion of large
 amounts may produce  nausea,  VOMITING, and  DIARRHEA. HYPO-
 THERMIA and ataxia are characteristic of  poisoning.  Muscle WEAKNESS
 and/or ascending  paralysis may progress to  respiratory paralysis if absorbed
 dosages are equivalent to those tested in experimental animals.
   The reaction to  beverage alcohol that may  follow exceptional absorption of
 thiram and  metallo  bis  dithiocarbamates is characterized by FLUSHING,
 HEADACHE, SWEATING, warm  sensations, weakness, nasal congestion,
 labored breathing, tightness in the chest, tachycardia, palpitation, and hypo-
 tension. Extreme dosages may result in shock, convulsions, respiratory depres-
 sion, and/or unconsciousness.  Reactions are not likely to occur unless the
 absorbed dose is extraordinary.
 Ethylene bis dithiocarbamates and (mono) thiocarbamates

   Some of these agents are irritating to skin and respiratory mucous  mem-
 branes,  causing  ITCHING,  SCRATCHY  THROAT,  SNEEZING, and
 COUGH, if excessive amounts of  spray or dust are inhaled. Apart from this
 effect, toxic potential is low. Neurotoxic and post-ethanol "Antabuse" reac-
 tions are not known to occur as a result of contact with these particular com-
 pounds.

 CONFIRMATION OF DIAGNOSIS

   Skin testing may be useful in identifying sensitization to these agents.
   In general, these compounds are so rapidly metabolized in the body and ex-
creted, that detection in blood is rarely possible. There are methods for detec-
tion of ethylene thiourea (from the ethylene bis dithiocarbamates) in urine.

TREATMENT

 1. WASH contaminating chemical from SKIN and HAIR with soap and
    water. Persons sensitive  to  thiram (rubber-sensitive) should be per-
    manently REMOVED  FROM  CONTACT with  compounds of this
    nature.
 2. FLUSH contaminant from EYES with fresh water for 10-15 minutes.
 3. If THIRAM  or METALLO  DITHIOCARBAMATE compounds have
    been INGESTED:
                                 39

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    A.  If vigorous emesis has not already occurred and victim is fully alert,
        give SYRUP OF IPECAC, followed by 1-2 glasses of water to in-
        duce vomiting (adults, 12 years and older: 30 ml; children under 12:
        15 ml).

        CAUTION:  OBSERVE  victim closely  AFTER  administering
                    IPECAC. If  CONSCIOUSNESS  level declines or
                    vomiting has not occurred in 15 minutes, empty the
                    stomach  by INTUBATION, ASPIRATION,  and
                    LAVAGE.

    B.  IF consciousness level or respiration is DEPRESSED, empty the
        stomach by INTUBATION, ASPIRATION, and LAVAGE, using
        all available  means to avoid aspiration  of vomitus: left lateral
        Trendelenburg position, frequent aspiration of the pharynx and, in
        unconscious victims, tracheal intubation (using a cuffed tube) prior
        to gastric intubation.
        After aspiration of the stomach and washing with isotonic saline or
        sodium bicarbonate, instill 30-50  gm of ACTIVATED CHAR-
        COAL in 3-4 ounces of water  through the stomach tube to limit
        absorption of remaining toxicant.
    C.  If the irritant properties of the toxicant fail to  produce a bowel
        movement in 4  hours, administer SODIUM or MAGNESIUM
        SULFATE as a cathartic: 0.25 gm/kg body weight in 1-6 ounces of
        water.
    D.  Administer glucose-containing fluids intravenously to accelerate ex-
        cretion of toxicant.
    E.  For adults and children over 12 years, inject 1.0 gm ASCORBIC
        ACID (Vitamin  C)  intravenously  at a  rate  not exceeding  0.2
        gm/minute. For children under 12, give 10-20 mg/kg body weight.
        As a hydrogen-donor, ascorbic  acid may have significant antidotal
        action against absorbed, but  unreacted,  dithiocarbamate com-
        pounds.
    F.  The victim must AVOID consumption of any ALCOHOLIC bever-
        age for 3 weeks. Gastrointestinal absorption of these substances is
        slow, and the enzyme inhibition which they cause is slowly reversed.

4.   Management of a reaction to  ETHANOL, following absorption of a
    DITHIOCARBAMATE:

    A.  Administer 100% OXYGEN as long as the reaction continues. Ox-
        ygen usually gives substantial relief from the distressing symptoms
        of vasodilation and hypotension.

        CAUTION:  If respiration is depressed, administer oxygen by an
                    intermittent positive pressure breathing device  and
                    observe the victim closely  to maintain pulmonary
                    ventilation mechanically in case of apnea.
                               40

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    B.   Gastric evacuation, charcoal administration, catharsis, intravenous
        fluids, and ascorbic acid administration (3 A,B,C,D, and E) may be
        appropriate, depending on the amount of dithiocarbamate absorbed,
        the time interval between exposure and treatment, and the severity
        of symptoms.
    C.   If the victim has suffered from arteriosclerosis, myocardial insuffi-
        ciency, diabetes, neuropathy,  cirrhosis,  or other severe chronic
        disease, OBSERVE him CAREFULLY for 48 hours to insure that
        complications (especially myocardial infarction, toxic psychosis,
        and neuropathy) are treated promptly.

5.   If an ETHYLENE BIS DITHIOCARBAMATE, or (mono) THIOCAR-
    BAM ATE have been ingested:

    A.   Give SYRUP OF IPECAC, followed by 1-2 glasses of water, to in-
        duce vomiting (adults: 30 ml; children under 12 years: 15 ml). Fol-
        lowing emesis, administer 30-50 gm ACTIVATED CHARCOAL
        to bind toxicant remaining in the gut.
    B.   Follow charcoal with SODIUM or MAGNESIUM SULFATE, 0.25
        gm/kg, to remove toxicant from the gut by catharsis.
                              41

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                          Chapters

          PYRETHRUM,  PYRETHRINS,
      PYRETHROIDS, AND  PIPERONYL
                       BUTOXIDE
  Pyrethrum is the partly refined extract of the chrysanthemum flower which
has been used as an insecticide for more than 60 years. Pyrethrins are the insec-
ticidally active ingredients of pyrethrum, now  known to consist of keto-
alcohol esters of pyrethric and chrysanthemic acids. The alcohols are pyrethro-
lone, cinerolone, and jasmololone, whose respective esters are known as
pyrethrins, cinerins, and jasmolins. Pyrethroids are synthetic compounds
based structurally on the pyrethrin molecule but modified to improve stability
in the natural environment (light, heat, etc.)

GENERAL CHEMICAL STRUCTURE

R   H    H                CH3
 11    I    H  O    H    '
C = C  -  C    I   II      \ /<%
 I        |^C-C-0-C    C-R'
CH3  CHa-C^            |    |
         I             H C — C = O
         CH3            H

COMMON COMMERCIAL PESTICIDE PRODUCTS

  Pyrethrins: There are several hundred commercial products containing
pyrethrins and pyrethroids. Commonly, these products combine pyrethrins or
pyrethroids with a synergist, such as piperonyl butoxide, and an additional
pesticide, for increased killing power. Many of these combinations are pack-
aged  with a propellant in a spray can or bug-bomb.

  Pyrethroids: Allethrin (Pynamin), barthrin, bioresmethrin, cypermethrin
(Ripcord), decamethrin,  fenothrin,  fenpropanate,  fenvalerate  (Belmark,
Pydrin), permethrin (Ambush, Ectiban, Pounce), phthalthrin or tetramethrin
(Neo-Pynamin), resmethrin (Synthrin, Chrysron).

TOXICOLOGY

  These esters rapidly  paralyze the insect nervous  system,  making them
famous for their quick "knockdown" effect. Mammalian toxicity, however, is
extraordinarily low for pyrethrins and pyrethroids. Oral LD5o values for these
compounds in rats are several hundred or thousand mg/kg body weight. There
is apparently less  efficient absorption of pyrethrins across the GI lining and

                              42

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skin  than  across insect  chitin,  and much  more  rapid  biodegradation
(hydrolysis and oxidation) by the mammalian liver than by insect tissues.
  Some of the less purified pyrethrum extracts contain allergenic substances
that induce attacks of allergic rhinitis and asthma in humans. Rarely, hyper-
sensitivity pneumonitis has followed pyrethrum inhalation.
  Administered orally  to  rodents  in extraordinary dosage,  pyrethrins  and
pyrethroids cause nervous irritability, tremors, and motor ataxia. Bloody tears
and urinary incontinence have also been observed. Manifestations of toxicity
occur at much lower dosage following intravenous administration than after
oral dosing. Chronic feeding of these chemicals induces an increase in liver size
and bile duct hyperplasia. To date, neither pyrethrins nor pyrethroids have
been identified as mutagenic, carcinogenic, or teratogenic.
  Piperonyl butoxide inhibits the mixed function oxidase enzymes of the liver
which catabolize pyrethrins and pyrethroids. The amount absorbed by humans
during ordinary exposure is not  likely to affect liver function measurably.

FREQUENT  SYMPTOMS AND SIGNS OF UNDUE EXPOSURE

  A STUFFY, RUNNY NOSE and scratchy throat from inhalation of partly
purified pyrethrum extract is the most common adverse effect of these agents.
Asthmatic WHEEZING may be  precipitated by exposure of predisposed indi-
viduals.
  Sudden bronchospasm, swelling of oral and laryngeal mucous membranes,
and shock (anaphylaxis)  have  been reported  after pyrethrum inhalation.
Delayed appearance of dyspnea, cough and fever, with patchy lung infiltrates
on x-ray, suggest hypersensitivity pneumonitis.
  Nervous  irritability, tremors,  and ataxia have occurred  rarely in persons
who have had massive inhalation exposure to pyrethrins.
  Halocarbon propellents in bug-bomb products present a risk of CARDIAC
ARRHYTHMIA and possibly fibrillation if inhaled to excess. Hydrocarbons
used as solvents in spray products are likely to result in COUGH, FEVER, and
CHEST PAIN (hydrocarbon pneumonitis) if these  liquids  are inadvertently
aspirated.

CONFIRMATION OF DIAGNOSIS

  Skin tests sometimes identify  sensitivity  to pyrethrum. Neither pyrethrins
nor pyrethroids inhibit cholinesterase enzymes. There  are gas-chromato-
graphic methods for  identifying some of these insecticides  in environmental
samples, but they are not likely to be useful in diagnosing poisoning because of
the rapid metabolism of the esters following absorption. There are no methods
for identifying urinary metabolites.
                                  43

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TREATMENT

 1.   WASH contaminating pesticide from the EYE with copious amounts of
     water. Wash contaminated SKIN with soap and water.
 2.   For life-threatening allergic reaction to pyrethrum (severe ASTHMA or
     ANAPHYLAXIS), give 0.1 to 0.5 ml of 1:1000 ADRENALIN intramus-
     cularly, or slowly intravenously. Repeat if necessary to relieve respiratory
     distress and maintain blood pressure. Intravenous AMINOPHYLLINE
     (10 ml, slowly) may be indicated. Give HYDROCORTISONE (50-100
     mg), or equivalent steroid, intravenously.
      Less severe allergic  reactions (rhinitis) can be managed with ANTI-
     HISTAMINES and DECONGESTANTS, given orally.
      HYPERSENSITIVITY PNEUMONITIS  may require oxygen,  ste-
     roids, antibiotics and several days bedrest, depending on severity.
 3.   INGESTION of a SMALL AMOUNT of a pyrethrin or pyrethroid for-
     mulation is not likely to cause poisoning. EXAMINE THE LABEL to
     identify additional insecticides, which may  be  more toxic.  BASE
     TREATMENT ON THE MOST TOXIC ingredients.

     A.  If a formulation  contains  ONLY pyrethrins, or  pyrethroids,  and
        synergists, ingestion of a small amount (up to about 5 mg/kg) is
        probably best treated by  large doses of ACTIVATED CHAR-
        COAL, 30-50 gm in 3-4 ounces of water, followed by cathartic doses
        of SODIUM  or  MAGNESIUM  SULFATE, 0.25 gm/kg body
        weight in 1-6 ounces of water.
 4.   If LARGE AMOUNTS of pyrethrin or pyrethroid formulation have
     been INGESTED, the  stomach and intestine  must be evacuated:

     A.  IF victim is ALERT and respiration is not depressed, give SYRUP
        OF IPECAC,  followed by 1-2 glasses of water, to induce vomiting
        (adults and children 12 years and  older: 30 ml; children under 12
        years: 15 ml).
        CAUTION:  OBSERVE VICTIM closely AFTER administering
                    IPECAC. If consciousness level declines or vomiting
                    has not occurred in 15 minutes,  INTUBATE the
                    stomach immediately.

        Following emesis, have victim drink a suspension  of 30-50 gm AC-
        TIVATED CHARCOAL in 3-4 ounces of water to limit absorption
        of toxicant remaining in the gut.
    B.  IF victim is NOT FULLY ALERT, empty stomach immediately by
        INTUBATION,  ASPIRATION, and LAVAGE, using  isotonic
        saline or 5% sodium bicarbonate. Because  many pesticides are dis-
        solved in petroleum distillates, emesis and intubation of the stomach
        involve a risk  that solvent will be aspirated, leading to chemical
        pneumonitis. For this reason:
                               44

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        (a).  If victim is unconscious or obtunded and facilities are at hand,
             insert an ENDOTRACHEAL TUBE (cuffed, if available) prior
             to gastric intubation.
        (b).  Keep victim's HEAD BELOW LEVEL OF THE STOMACH
             during intubation and lavage (Trendelenburg, or left lateral
             decubitus,  with  head of  table  tipped  downward).  Keep
             victim's head turned to left.
        (c).  ASPIRATE PHARYNX as regularly as possible to remove
             gagged or vomited stomach contents.
        (d).  After aspiration of gastric contents and washing of stomach,
             instill 30-50 gm of ACTIVATED CHARCOAL in 3-4 ounces
             of water through stomach tube to limit absorption of remain-
             ing toxicant.
        (e).  If bowel movement has not  occurred in 4 hours and patient is
             fully conscious, give  SODIUM or MAGNESIUM SULFATE
             as a cathartic: 0.25 gm/kg body weight in 1-6 ounces of water.

5.   Do NOT administer or instill milk, cream, or other substances containing
    vegetable or animal fats, which enhance absorption of lipophilic sub-
    stances, such as pyrethrins and  pyrethroids.
6.   DIAZEPAM (Valium®), 5-10 mg in adults, 0.1 mg/kg in children, given
    orally or slowly IV, should control nervousness and tremors in rare cases
    having these symptoms after extraordinary exposure to pyrethrins and
    pyrethroids.
                               45

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                   Chapter 10

         ARSENICAL PESTICIDES
CHEMICAL STRUCTURES

INORGANIC ARSENICALS

 Extremely Toxic
      As - O - As
Na - O - As = O
K - O - As = O
      ARSENIC
      TRIOXIDE
  SODIUM
  ARSENITE
 POTASSIUM
 ARSENITE
  Cu - (O - C - CH3) 2
        n
  •      0

  3Cu - (As O2)2


  COPPER
  ACETOARSENITE
  Highly Toxic

     Ca3(As 04) 2

  CALCIUM ARSENATE

  Moderately Toxic
        Ca (As O2) 2

     CALCIUM ARSENITE
       Cu - (AsO2)
       I
       O
       H
    COPPER ARSENITE
                (HO)3 AS = O


                ARSENIC ACID
  Pb      As = O


          O
          H

    LEAD ARSENATE
                        46

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ORGANIC ARSENICALS

 Moderately Toxic
CH3 ^     CH3

   / AS\
  O^     OH


CACODYLIC ACID
                                   As
                           METHANE ARSONIC ACID
                           (MAA)
       . As
     <>   \
    O       OH

MONOSODIUM
METHYL ARSONATE
(MSMA)
                            CH3x    ^ONa

                                s- As
                              °       ONa

                           DISODIUM
                           METHYL ARSONATE
                           (DSMA)
    ,\   /ONH4
       As

   O^     OH
MONOAMMONIUM
METHANE ARSONATE
                     47

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COMMON COMMERCIAL ARSENIC PRODUCTS
 1.   Arsenic trioxide
 2.   Sodium arsenite:

 3.   Calcium arsenite:
 4.   Copper arsenite:
 5.   Copper acetoarsenite:
 6.   Arsenic acid:

 7.   Sodium arsenate:
 8.   Calcium arsenate:
 9.   Lead arsenate:

10.   Methane arsonic acid:
11.   Monosodium methyl arsonate:
12.   Disodium methyl arsonate:
13.  Monoammonium methyl arsonate:

14.  Calcium acid methanearsonate:

15.  Cacodylic acid:
"White arsenic," arsenious oxide
(registered  only  for  ant pastes,
veterinary medicinals, and marine
antifouling preparations).
Chem Pels C, Chem-Sen 56, Kill-
All, Penite, Prodalumnol Double.
Mono-calcium arsenite.
Chemonite.
Paris  green,  Schweinfurt green,
emerald green, French green, mitis
green.
Desiccant  L-10,  Hi-Yield Desic-
cant H-10.
Jones Ant Killer, Terro Ant Killer.
Pencal, Spra-cal, Security.
Gypsine,   Security,   Soprabel,
Talbot.
MAA.
MSMA, Ansar 17OHC,  methane
arsonate, Ansar 529HC, Arsonate
liquid, Bueno 6, Daconate 6, Dal-
E-Rad,  Herb-All,  Merge  823,
Mesamate, Target MSMA, Trans-
Vert, Weed-E-Rad,  Weed-Hoe.
DSMA, Ansar 8100, methane ar-
sonate, Ansar DSMA liquid, Ar-
rhenal,  Arsinyl,  Chipco  Crab
Kleen,   Crab-E-Rad,  Dal-E-Rad
100,  Di-Tac,  DMA,  DMA 100,
Methar, Namate, Sodar,  Weed-E-
Rad, Weed-E-Rad  360,  Weed-E-
Rad DMA Powder, Weed-Hoe.
MAMA, monoammonium  meth-
anearsonate.
CAMA, Super Crab-E-Rad-Calar,
Super Dal-E-Rad "Calar".
Dilic, Phytar 560, Rad-E-Cate 25,
Salvo, f  [Crystal Chemical  Com-
pany)
     A product of identical name marketed by Crystal Chemical Company
     contains 2,4-D as the active ingredient (Chapter 6).
                                 48

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 TOXICOLOGY

   Although there may be some degree of dermal and pulmonary absorption of
 arsenical liquids and sprays, ingestion is the route of intake involved in virtual-
 ly all acute poisonings by the solid arsenicals.
   Inhalation of arsine gas (sometimes generated inadvertently in pesticide
 manufacturing plants) has caused serious illness and death by hemolytic action.
   Generally, the organic  (methylated) pentavalent arsenicals are considerably
 less  toxic than  the trivalent inorganic arsenicals. In fact, methylation is the
 principal mechanism of  detoxification  of inorganic arsenicals in mammals.
 The less soluble inorganic forms (notably lead arsenate, and even arsenic triox-
 ide) present less hazard than the highly soluble salts such as sodium arsenite
 and copper acetoarsenite. But because gastric pH, gastrointestinal motility,
 and gut bacterial action can enhance the  absorption and toxicity of ingested
 compounds,  it  is safest to manage cases of arsenic ingestion as though all
 forms of arsenic are highly toxic.
   Trivalent arsenicals (or, more likely, an arsenious acid metabolite) bind effi-
 ciently to the functional thiol groups of many tissue components, including en-
 zymes. The affinity for thiol groups in keratin accounts for the accumulation
 of arsenic in skin, nails, and hair in cases of chronic poisoning. When absorbed
 across the gut wall, these arsenicals injure the splanchnic vasculature, causing
 abdominal pain, colic, and diarrhea. Once absorbed into the blood, they cause
 toxic damage to the liver,  kidneys, brain, bone marrow, and peripheral nerves.
 Liver injury is manifest as hepatomegaly, jaundice, and increase in circulating
 hepatocellular enzymes LDH and GOT. Renal damage is reflected in albumin-
 uria, hematuria, pyuria,  cylindruria, then azotemia. Acute tubular necrosis
 may occur in severe poisoning. Injury to  blood-forming  tissues can take the
 form of agranulocytosis, aplastic anemia, thrombocytopenia, or pancytopenia.
 Toxic encephalopathy may be manifest as speech and behavioral disturbances.
 Peripheral neuropathy occurs in both acute and chronic forms.
   Sequelae of arsenic poisoning include cirrhosis, hypoplastic bone marrow,
renal insufficiency, and peripheral neuropathy. Excessive exposures to arseni-
cals have caused hyperkeratosis and skin cancers. Excessive inhalation of dusts
may cause  bronchitis and pneumonia; protracted inhalation has been asso-
ciated epidemiologically with increased occurrence of lung cancer.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

ACUTE arsenic poisoning

  COLIC, BURNING ABDOMINAL PAIN, VOMITING, and WATERY or
BLOODY DIARRHEA are the primary manifestations of ingestion of solid
arsenical poisons. Symptoms following ingestion  of inorganic  arsenicals are
much more severe than those resulting from ingestion of pentavalent organic
arsenicals. Symptoms are sometimes delayed for minutes  or even hours after
ingestion.  HEADACHE, DIZZINESS, MUSCLE  SPASMS,  DELIRIUM,
                                  49

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and sometimes CONVULSIONS reflect direct injury to the central nervous
system, as well as extracellular electrolyte disturbances and shock. A GARLIC
ODOR to the breath and feces helps to identify  the responsible toxicant.
SHOCK, TOXIC NEPHROSIS, HEPATITIS (hepatomegaly and jaundice),
and NEUROLOGIC INJURY  (delirium, paralysis, respiratory depression)
may progress to a fatal outcome.

SUBACUTE arsenic poisoning

  Repeated intakes less than those necessary to produce severe acute symp-
toms are known to cause CHRONIC HEADACHE, ABDOMINAL DIS-
TRESS, SALIVATION, LOW-GRADE FEVER, and  PERSISTENT symp-
toms of UPPER RESPIRATORY IRRITATION. Stomatitis and  garlicky
breath are characteristic.

CHRONIC arsenic  poisoning

  Prolonged low intakes of arsenic cause peripheral  neuropathy (PARES-
THESIAE, PAIN,  anesthesia, paresis, ataxia), encephalopathy (APATHY,
disorientation),   dermatologic  disorders  (KERATOSES,  pigmentation,
eczema, brittle nails, loss of hair), toxic hepatitis (HEPATOMEGALY, some-
times  progressing  to  cirrhosis  with  ascites),  and bone  marrow injury
(ANEMIA, leukopenia, WEAKNESS). Local EDEMA, frequently of the eye-
lids, characterizes some poisonings.

ACUTE arsine gas  poisoning

  The gas causes hemolysis of  red blood cells, in  addition  to inhibition of
cellular sulfhydryl respiratory  enzymes. Hemolysis causes HEMOGLOBINE-
MIA and HEMOGLOBINURIA. This in turn, causes acute tubular necrosis.
Early symptoms  of poisoning (CHILLS, weakness, burning sensations) are
followed by abdominal  CRAMPS, vomiting, and prostration. Failing renal
function deteriorates to ANURIA.

CONFIRMATION  OF DIAGNOSIS

  Measurement of  24-hour urinary excretion of arsenic is probably the best
way to confirm excessive arsenic absorption, although  methods for blood
arsenic concentration are available. Persons on ordinary diets usually excrete
less than 20 Mg/day but diets rich in seafood may generate  as much as  200
Mg/day. Excretions  above 100 Mg/day should be viewed with suspicion and
tests should be repeated. Excretions above 200 Mg/day  reflect a toxic intake,
unless seafood was ingested. (The arsenic in seafood is apparently bound firm-
ly to an organic moiety that renders the arsenic essentially nontoxic and highly
excretable.)
  The qualitative Gutzeit test for arsenic in the urine is available  in most
hospital laboratories, and is useful in identifying acute  poisonings promptly.

                                 50

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  Chronic storage of arsenic can be detected by analysis of hair or fingernails.
  The hemoglobinuria caused by arsine is identified by finding free hemoglo-
bin in fresh urine.

TREATMENT OF POISONING BY SOLID ARSENICALS

 1.   Flush contaminated EYES, HAIR and SKIN with copious amounts of
     fresh water. WASH SKIN and HAIR with soap and water.
 2.   In poisonings by INGESTED ARSENICALS
     A.   INTUBATE the stomach, ASPIRATE, and LAV AGE with 3 liters
         of isotonic saline  or 5% sodium bicarbonate. Use all possible pre-
         cautions to avoid  aspiration of vomitus:

         (1)   If victim is unconscious or  obtunded,  insert an ENDO-
              TRACHEAL TUBE (cuffed, if available) prior to gastric intu-
              bation.
         (2)   Keep victim's HEAD BELOW LEVEL OF THE STOMACH
              during intubation (Trendelenburg, or  left lateral  decubitus,
              with  head of  table  tipped downward). Keep victim's head
              turned to the left.
         (3)   ASPIRATE pharynx as regularly as possible to remove gagged
              or vomited stomach contents.

     B.   After lavage, INSTILL 30-50 gm ACTIVATED CHARCOAL in
         the  smallest amount of water  necessary to deliver  the charcoal
         through the tube.
     C.   If diarrhea or colic has not ensued within an hour of gastric lavage
         and charcoal administration, give SODIUM SULFATE as a cathar-
         tic 0.25 gm/kg body weight in 1-6 ounces of water.
 3.   An ABDOMINAL X-RAY film is useful in detecting concretions of the
     less  soluble arsenicals  (As2O3 and lead arsenate) in  the gut. If not re-
     moved these may become a repository of slowly absorbed toxicant.
 4.   Administer INTRAVENOUS ELECTROLYTE  and GLUCOSE solu-
     tions to maintain hydration and to accelerate  toxicant excretion. COM-
     BAT SHOCK with TRANSFUSIONS of WHOLE BLOOD,  and by in-
     halation  of 100% OXYGEN.
     CAUTION:  Monitor urine flow via catheter. Monitor fluid balance,
                 body  weight, and/or  central venous  pressure to guard
                 against fluid  overload that may result if  tubular necrosis
                 (anuria)  supervenes.

 5.   Administer DIMERCAPROL (BAL) and PENICILLAMINE to acceler-
     ate arsenic excretion.

     A.   Give dimercaprol, 3-5 mg/kg q4h intramuscularly  until abdominal
         pain and diarrhea subside and patient is regularly  passing  admin-
         istered  charcoal  in the   feces.  IF victim is ALLERGIC  to

                                 51

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         PENICILLIN, continue dimercaprol therapy at 3-5 mg/kg q6h x 4
         doses, then q!2h  x 2 doses, then q24h  x 10 doses, monitoring
         urine arsenic excretion periodically to judge effectiveness.

         CAUTION:   DIMERCAPROL can cause troublesome side effects
                      (hypertension, tachycardia, nausea, headache, pares-
                      thesiae and pain, lacrimation, sweating, anxiety, and
                      restlessness).  Although usually not so severe  as to
                      preclude treatment, they may require antihistaminic
                      therapy.
     B.   IF victim is NOT ALLERGIC to PENICILLIN, oral d-PENICIL-
         LAMINE is the therapy of choice and should REPLACE dimer-
         caprol treatment as soon as the feces are laden with charcoal, limiting
         gut absorption of arsenic. Adult dosage is 0.5 gm four times daily (2
         gm/day), given before meals, for 5 days. Dosage for children is
         0.025 gm/kg four times daily, not to exceed 2 gm/day for 5 days.

         CAUTION:   Although oral d-penicillamine therapy is usually better
                      tolerated  than  intramuscular dimercaprol,  serious
                      reactions to it have occurred: the most common has
                      been maculopapular rash,  with fever,  leukopenia,
                      thrombocytopenia, eosinophilia, arthralgia and lym-
                      phadenopathy. It has also induced the nephrotic syn-
                      drome on occasion, and has  caused thrombophlebitis,
                      cheilosis, angioneurotic edema, and even fatal agran-
                      ulocytosis in  particular patients given the drug over
                      long periods for conditions  unrelated to arsenic poi-
                      soning.  Penicillin sensitive individuals are likely to be
                      sensitive to d-penicillamine.

         (a).  A single 5 day course of d-penicillamine therapy is usually suf-
              ficient. However,  if symptoms recur after  treatment,  addi-
              tional d-penicillamine should be given at a dosage just  suffi-
              cient to abolish symptoms.
 6.  Intense abdominal pain may require morphine (adults, 12 years and
     older: 4-15 mg; children under 12 years: 0.1-0.2 mg/kg).
 7.  Severe poisoning (especially when renal function is impaired) may re-
     quire HEMODIALYSIS to remove arsenic combined with dimercaprol
     from the blood, and to control extracellular fluid composition. HEMO-
     PERFUSION may be useful, but its effectiveness has not been reported.

TREATMENT OF POISONING BY  ARSINE GAS

 1.  REMOVE victim to FRESH AIR.
 2.  MAINTAIN  RESPIRATION and CIRCULATION by resuscitation and
     cardiac massage, if necessary.
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3.   Administer INTRAVENOUS FLUIDS promptly to dilute free hemoglo-
    bin and minimize tubular injury. Include enough sodium bicarbonate to
    keep the urine alkaline.

    CAUTION:  Monitor urine flow via catheter. Monitor  fluid balance,
                body weight, and/or central venous  pressure to guard
                against fluid  overload  resulting   from  acute  tubular
                necrosis.

4.   Administer DIMERCAPROL as recommended in 5A even though it has
    only limited effect in arsine poisoning.
5.   EXCHANGE BLOOD TRANSFUSIONS and PERITONEAL DIALY-
    SIS have saved the lives of victims of arsine poisoning suffering acute
    tubular necrosis.
                               53

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                     Chapter 11

                RODENTICIDES
STRUCTURES OF PRINCIPAL COMPOUNDS
                                      ALKYL, PHENYL,   i
                                    DIPHENYLACETYL or
                                  CHLORODIPHENYLACETYL
  WARFARIN
                           1,3 INDANDIONE
         C = S
 a-NAPHTHYL
 THIOUREA
        H O
        I  H
      F - C - C-ONa
        I
        H

     SODIUM
     FLUOROACETATE
      Zn
     /  \
    P - Zn - P
     \  /
      Zn

    ZINC
    PHOSPHIDE
  \  /
   P

YELLOW
PHOSPHORUS
                         54

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SCILLIROSIDE
(Active principle of Red Squill)
                  = O
                                             STRYCHNINE
                                       ,— C-N-C-N—V    \
              -NO,
                                          H  H  II  H
                                                O
                                       RH- 787 (Active
                                       ingredient of VACOR and
                                       DLP-787)
                                      CH3-C
                                           II
                                        H -C
'C-CI
 I
 N
                                              I
                                              N
      NORBORMIDE
                                          CRIMIDINE
                               55

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COMMON COMMERCIAL RODENTICIDE PRODUCTS

  Coumarins: warfarin, coumafene, zoocoumarin (Kypfarin,  Ratox, RAX,
Rodex,  Tox-Hid,  Warfarin  Plus);  coumafuryl   (Tomarin,  Fumarin);
bromadiolone (Bromone, Super-Caid, Ratimus), coumachlor (Tomorin).
  Indandiones:  diphacinone  (Diphacin, Promar,  Ramik); chlorophacinone
(Caid,  Drat,  Liphadione,  Microzul,  Ramucide, Ratomet, Raviac,  Rozol,
Topitox); pindone or pivaldione (Pival, Pivacin, Pivalyn, Tri-ban).
  Other  anticoagulant  rodenticides  of  different  structure: difenacoum
(Ratak); brodifacoum (Talon).
  Sodium fluoroacetate: 1080,  Fratol, Yasoknock.
  Zinc phosphide: Phosvin, Zinc-Tox.
  Yellow phosphorus and strychnine have limited use and are generally identi-
fied by these long established common names.
  Crimidine: Castrix.
  RH-787: This product is no  longer available for sale, but existing stocks
present a continuing threat of poisoning. Commercial products are: Vacor Rat
Killer (2% RH-787  in  vehicle  resembling corn meal); DLP-787 Bait  (2%
RH-787 in vehicle resembling corn meal);  DLP-787 House Mouse Tracking
Powder (10% RH-787 in a light green powder).
  Red squill: Dethdiet, Rodine.
  Antu: Krysid.
  Norbormide:  Shoxin, Raticate.

TOXICOLOGY

  Rodent poisons are generally  added to baits, i.e., grain or paste designed to
encourage consumption. Safety for pets,  domestic  animals,  and  humans
depends on the toxicity of the agents, concentration of active ingredients in the
baits, and the likelihood that a toxic dose will be consumed by nontarget
species. The coumarins are reasonably effective against pest rodents and have
a good safety record. This is due mainly to the low concentration of active in-
gredient in the bait: about 100 gm of the commercial bait must be ingested to
yield 25 mg of anticoagulant. This is important in evaluating suspected poison-
ings by anticoagulants,  which are the most widely available rodenticides for
public use.
  Very small amounts of the extremely toxic rodenticides—sodium fluoro-
acetate, zinc phosphide, crimidine, strychnine, and yellow phosphorus—can
cause fatal poisoning.
  Vacor should  be considered highly toxic. Ingestion of less than 1 gm by an
adult has caused severe poisoning.
  Antu, red squill, and norbormide present considerably less toxic hazard to
humans and to domestic animals.
 t  A rodenticide of identical trade name is still available in some areas which
   contains thallium sulfate as the active ingredient. Use of thallium in the
   United States is now restricted.

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   Coumarins, indandiones, and other anticoagulants: Gastrointestinal absorp-
tion of these toxicants is efficient, beginning within minutes of ingestion and
continuing for 2 to 3 days. Apparently warfarin can also be absorbed across
the skin, although the circumstances under which this occurred were extraordi-
nary.
   These agents depress the hepatic synthesis of substances essential to blood
clotting: prothrombin (factor II) and factors VII, IX, and X. The antipro-
thrombin effect is best known, and provides the basis for detection and assess-
ment of clinical poisoning.  Direct damage to capillary permeability occurs
concurrently. The ultimate effect of these actions is to induce widespread in-
ternal hemorrhage. This generally occurs in the rodent after several days of
bait ingestion, although the modern products (diphacinone, chlorophacinone,
pindone, difenacoum, and brodifacoum) may be lethal after fewer feedings.
These modern agents should be considered more toxic than warfarin.
   In rare instances, coumarin-type anticoagulants have caused ecchymosis and
extensive skin necrosis in humans for reasons not related to excessive dosage.
   Unlike the coumarin anticoagulants, the indandiones cause symptoms and
signs of neurologic and cardiopulmonary injury in laboratory rats; these often
lead to death before hemorrhage occurs. These actions may account for the
somewhat greater toxicity of this class of anticoagulants. Neither cardiopul-
monary  nor neurologic  symptoms  or signs  have been reported in  human
poisonings.
   Lengthened prothrombin time from a toxic dose is usually evident within 24
hours of ingestion and reaches a maximum in 36 to 72 hours. Without inter-
vention,  hypoprothrombinemia may persist 10 to 15 days, depending on the
agent and dosage. Prothrombin depression occurs in response to  doses much
lower than those necessary to cause hemorrhage.
   Sodium fluoroacetate: the fluorocitrate metabolite of this poison blocks
energy production in mammalian cells at the level of the tricarboxylic acid cy-
cle. The critical sites of toxic effect in humans are the myocardium (where ven-
tricular fibrillation is the usual cause of death) and the brain, where seizures
are induced and respiration is depressed. Seizures, respiratory depression, and
ventricular fibrillation are all causes of death.
   Zinc phosphide: this inorganic compound produces severe gastrointestinal
irritation. It degrades in the gut to phosphine gas which, when absorbed,
causes pulmonary edema and severe liver, kidney, CNS, and  myocardial
injury.
   Yellow phosphorus: this agent causes severe gastrointestinal irritation result-
ing in vomiting, diarrhea, and melena. Circulatory collapse may occur  and
prove irreversible. Liver necrosis and acute renal tubular necrosis are equally
ominous threats to  life. Hemorrhage, from hypoprothrombinemia, and  car-
diac arrest or fibrillation, account for some deaths.
   Strychnine: this natural poison acts directly on the cells of the brain  and
spinal cord to cause convulsions. Death is caused by convulsive interference
with pulmonary gas exchange, by depression of respiratory center activity, or
both.
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  Crimidine: this is a synthetic pesticide which, although unrelated chemically
to strychnine, exerts toxic effects similar to those of strychnine, producing
violent convulsions and secondary tissue anoxia by its action on the CNS.
  Vacor, DLP-787: the exact mechanism of RH-787 toxicity is not  known
although one established effect in rats is  interference  with  nicotinamide
metabolism. RH-787 has  no anticoagulant action. Symptoms and signs in
poisoned animals suggest toxic actions on the brain,  peripheral nerves,
myoneural junctions, pancreatic islet tissues, autonomic nervous system, and
the conducting tissues of the heart. Abnormalities of renal and vascular func-
tion may be direct effects of poisoning, or they may reflect metabolic and
autonomic nervous system disturbances, impaired vascular reactivity in par-
ticular.
  Red squill: this biological agent is unlikely to present a serious toxic hazard
to humans  or other vomiting species, because 1) it usually induces prompt
emesis, 2) it is poorly absorbed from the gut, and 3) the active principles are in
low concentration, and are rapidly excreted. Natural squill contains digitalis-
like glycosides, which might, theoretically, produce manifestations of digitali-
zation in humans. The glycoside known as scilliroside is the probable cause of
convulsive death in the rat; convulsions have  not been observed in human
poisonings.
  Antu: this agent exhibits selective toxicity for the rat,  causing pulmonary
edema and pleural effusion. Only one human poisoning is recorded, and it was
induced by a large suicidal dose. Vomiting was followed by dyspnea,  cyanosis,
and pulmonary  rales, presumably reflecting pulmonary edema. The patient
recovered.
  Norbormide: this is selectively toxic to Norway and roof rats, which it kills
by inducing a generalized, sudden, and intense vasoconstriction. Other vari-
eties of rats are resistant,  and the chemical is only moderately toxic to other
mammals, including humans. Oral doses of 300 mg cause transient lowering of
blood pressure and body temperature in humans.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

  Coumarins, indandiones, and other anticoagulants: In most cases of inges-
tion of anticoagulants, victims have remained asymptomatic, due to  the small
dosage taken. Even in cases involving ingestion of substantial amounts of anti-
coagulant compound (more  often medication than rodenticide),  hypopro-
thrombinemia has occurred without symptoms of poisoning. Hemorrhage ap-
pears only  when  extraordinary amounts have been absorbed. In reported
cases, the anticoagulants were either taken deliberately, were absorbed over
long periods out of neglect of elementary hygienic standards, or were ingested
by starving  indigents who  used  quantities of rodent bait as food.
  Victims of large doses exhibit HEMATURIA, NOSEBLEED, HEMATO-
MATA, BLEEDING GUMS,  and MELENA. ABDOMINAL PAIN and
BACK PAIN probably reflect hemorrhage in the abdominal and retroperito-
neal tissues. WEAKNESS occurs as a result of ANEMIA. RENAL COLIC
                                 58

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 often complicates severe hematuria. Nasal and gastrointestinal hemorrhages
 have occasionally caused death from exsanguination.
   Sodium fluoroacetate: A delay of several minutes or even hours may be ex-
 pected before symptoms appear. Epigastric distress and vomiting often occur.
 Apprehension,  PARESTHESIAE  and  hallucinations  are  the usual
 premonitory symptoms, leading to epileptiform CONVULSIONS. CARDIAC
 IRREGULARITIES (ectopic beats, pulsus alternans, ventricular tachycardia
 and fibrillation) appear after seizures commence. These are frequently fatal.
   Zinc phosphide: Intense NAUSEA, abdominal pain, excitement, and chills
 are early symptoms. Tightness in the chest, DYSPNEA and COUGH, produc-
 tive of FROTHY SPUTUM, reflect pulmonary edema.  SHOCK from toxic
 myocarditis is common. If these conditions are survived, JAUNDICE from
 liver necrosis, and ANURIA  from renal tubular injury are later complications.
 Hypocalcemic TETANY and PURPURA have occurred in some poisonings.
   Yellow phosphorus: BURNING PAIN in the throat, chest, and abdomen
 reflect severe mucosal irritation. Vomiting and diarrhea ensue. Breath has
 garlicky odor. Feces may luminesce and "smoke"  from phosphorus fumes.
 SHOCK often progresses to  death in 1 to 2 days. The patient who survives
 may then  be  relatively  symptom-free for several hours or even days, after
 which the  delayed manifestations appear due to liver, CNS, myocardial and
 renal injury. Nausea and VOMITING persist. HEMORRHAGE at various
 sites reflects  mainly  depression  of clotting-factor synthesis  in the liver.
 SHOCK may be due to hemorrhage and/or  toxic myocarditis. CONVUL-
 SIONS, delirium, and coma are common. ANURIA usually ensues as a result
 of direct nephrotoxic effect  of phosphorus, enhanced by biliary nephrosis
 (hepatorenal syndrome).
   Strychnine: Within 10 to 60 minutes of ingestion of an adequate dose (as lit-
 tle as 16 mg), the victim suffers VIOLENT CONVULSIONS caused by clonic,
 then tonic  contraction  of all the skeletal muscles of the body.  Cyanosis
 develops promptly. Brief periods  of relaxation may occur, followed by even
 more severe seizures. Opisthotonus is common, and the muscles of the face are
 drawn into a grimace. Death  is usually due to ASPHYXIA, a consequence of
 convulsive spasm of the respiratory muscles.
   Crimidine: Ingestion is followed promptly by VIOLENT CONVULSIONS,
 essentially  like those caused by strychnine (see preceding paragraph).
  Vacor,  DLP-787: Minimum toxic  and lethal doses in humans  are  not
known. Ingested amounts less than one gram have proved severely toxic.
   Symptoms may not appear for 4 to 48 hours after ingestion.  Earliest symp-
 toms are usually  NAUSEA, vomiting, abdominal cramps, CHILLS,  and
 CONFUSION. Later manifestations are aching and fine tremors of the ex-
 tremities,  dilated  pupils, plantar  hyperesthesia,  MUSCLE  WEAKNESS,
 dysphagia,  chest pain,  postural  hypotension, anorexia, diarrhea,  urinary
retention,  and HYPOTHERMIA.  Subsequently,  DIABETES MELLITUS
commonly  develops,  manifest as glycosuria, polyuria,  ketoacidosis,  and
dehydration. Death may result from respiratory failure, cardiovascular  col-
lapse, or ketoacidosis. Survivors of the acute phase of the poisoning are often
                                59

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left with permanent sequelae: postural hypotension, diabetes mellitus, bladder
dystonia (retention or frequency), bowel dystonia (constipation or diarrhea),
and peripheral neuropathy.
  Abnormal  laboratory findings include hyperglycemia, glycosuria, ketosis
(acidosis and electrolyte disturbances),  and elevation of serum amylase and
lipase activities.
  Red squill: Nausea and VOMITING are the predominant effects. In the
unlikely event that significant amounts of glycosides are absorbed, cardiac ar-
rhythmias and slowing might be expected. Convulsions have not been observed
in humans as they have in rats.
  Antu: Pulmonary rales, DYSPNEA and cyanosis may be expected follow-
ing ingestion  of large amounts.
  Norbormide:  No human poisonings have been reported. Ingestion of 300
mg by an individual  caused a slight  fall in body temperature and blood
pressure.

CONFIRMATION OF DIAGNOSIS

  Coumarins, indandiones, and  other anticoagulants: Increase of the pro-
thrombin time (Quick) reflects a reduction in serum prothrombin concentra-
tion, and occurs in response to physiologically significant absorption of these
toxicants. This  widely available  clinical test offers a sensitive and reliable
diagnostic method for detecting a toxic effect of these compounds. Readily
detectable change in prothrombin time appears within 24 to 48 hours of inges-
tion of anticoagulant.
  Zinc phosphide and phosphorus: Zinc phosphide smells like rotten fish and
imparts a  garlicky odor to the breath. Luminescence of vomitus or feces in-
dicates yellow phosphorus ingestion.
  Other rodenticides: There are analytical methods  available for identifying
some remaining rodenticides in food or liquids suspected of contamination, in
gastric contents, and sometimes in blood and urine. (See Sunshine, I., Hand-
book  of Analytical Toxicology (1969)  published by the Chemical Rubber
Company,  18901  Cranwood  Parkway,  Cleveland,  Ohio 44128.) These
methods are generally complex and must be performed by a toxicology labora-
tory experienced in these tests. Analysis is often time-consuming, limiting the
usefulness of the results in clinical management. Analyses may be important,
however, for legal reasons.

TREATMENT

  Coumarins, indandiones, and other anticoagulants
 1.   If only a few grains of anticoagulant bait have been ingested by an adult
     or child having no antecedent liver or blood clotting disease, treatment is
     probably unnecessary.
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    A.  If there is uncertainty about the amount of bait ingested or the
        general  health of the patient,  PHYTONADIONE (vitamin K,,
        Mephyton®) given orally protects against the anticoagulant effect
        of these rodenticides. For adults, give 15-25 mg; for children under
        12, give 5-10 mg. Alternatively, a  colloidal solution of phytona-
        dione, Aquamephyton®, may be given intramuscularly. For adults,
        give 5-10 mg; for children under 12, give 1-5 mg.

        CAUTION:   PHYTONADIONE, specifically, is required. Neither
                     vitamin K3  (menadione, Hykinone®) nor vitamin K4
                     (menadiol)  is an antidote for these anticoagulants.

    B.  Whatever the doage, insure that patients (especially children) will be
        CAREFULLY OBSERVED for 4-5 days after ingestion. The indan-
        diones and the more recently introduced anticoagulants have toxic
        effects apart from anticoagulation that are not yet well defined.
2.  If LARGE AMOUNTS of anticoagulant were ingested  in the preceding
    2-3 hours, INDUCE VOMITING with SYRUP OF IPECAC, followed
    by 1-2 glasses of water. For adults, give 30 ml; for children under 12, 15
    ml. Following emesis,  give 30-50 gm ACTIVATED CHARCOAL in 4-6
    ounces of water to limit absorption  of anticoagulant remaining  in the
    gut.
3.  If anticoagulant has been  ingested any time in the preceding 15 days,
    determination of PROTHROMBIN TIME provides a basis for judging
    the severity of poisoning.

    A.  If the prothrombin time  is lengthened, give Aquamephyton®, in-
        tramuscularly: adult dose, 5-10 mg; child's dose:  1-5 mg.  Decide
        dose according to the degree of prothrombin time lengthening and,
        in children, the age and weight of the child.
    B.  Repeat prothrombin time in 24 hours. If it has not decreased from
        the original value, repeat  Aquamephyton® dosage.

4.  If victim shows SYMPTOMS  or SIGNS of ANTICOAGULANT POI-
    SONING (bleeding) in addition to hypoprothrombinemia, administer
    Aquamephyton®  intramuscularly, up to  25 mg in the adult,  and up to
    0.6 mg/kg in children under 12 years. Phytonadione administration may
    be repeated in 24 hours if bleeding continues.

    A.  In cases of  SEVERE  BLEEDING, it may be necessary to give
        Aquamephyton® intravenously.  This  is  especially true  if  the
        bleeding tendency is so severe that intramuscular injection is likely
        to cause hematoma formation. Dosage is up to 25 mg in the adult,
        up to 0.6 mg/kg in children under 12 years. Repeat this  dose in 24
        hours if bleeding continues. Inject at rates not exceeding 5% of the
        total dose  per  minute.   INTRAVENOUS INFUSION  of  the
        Aquamephyton® DILUTED IN SALINE  OR GLUCOSE SOLU-
        TION is recommended. Bleeding is usually controlled in  3-6 hours.
                               61

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        CAUTION:  Adverse reactions, some fatal, have occurred from
                    INTRAVENOUS  phytonadione   injections,   even
                    when recommended dosage limits and injection rates
                    were observed. For this reason, the INTRAVENOUS
                    route should be  used ONLY IN cases of SEVERE
                    POISONING.  Flushing,  dizziness,  hypotension,
                    dyspnea, and cyanosis have characterized  adverse
                    reactions.

    B.   Antidotal therapy IN cases of SEVERE BLEEDING should be sup-
        plemented with TRANSFUSIONS of FRESH BLOOD or  FRESH
        FROZEN PLASMA. Use  of fresh blood or plasma represents the
        most rapidly effective method of stopping hemorrhage due to these
        anticoagulants.
    C.   Determine PROTHROMBIN TIMES (and hemoglobin  concentra-
        tions, if appropriate) every 6-12 hours to assess effectiveness of anti-
        hemorrhagic measures.
    D.   When normal blood coagulation is restored, it may be advisable to
        drain large hematomata.
    E.   Ferrous sulfate therapy may be appropriate in the recuperative
        period to rebuild lost erythrocyte mass.

 Sodium fluoroacetate

1.   If this substance has been INGESTED, empty the stomach immediately
    by  INTUBATION, ASPIRATION, and LAV AGE,  using 5% sodium
    bicarbonate. Before withdrawing the lavage tube, instill a slurry  of 30-50
    gm ACTIVATED CHARCOAL.
2.   MONITOR cardiac  rhythm   by  continuous  ELECTROCARDIOG-
    RAPHY.
3.   MONOACETIN (glyceryl monoacetate) has antidotal properties  in ex-
    perimental animals. The liberated  acetate competes  successfully with
    fluorocitrate in the tricarboxylic acid cycle. However,  there is no  sterile
    pharmaceutical  preparation  of  this compound: high-quality,  fresh
    laboratory grade material must be used.

    A.   If victim is fully conscious and not convulsing, administer 100 ml of
        monoacetin in 500  ml of  water, by mouth. Repeat in  one  hour.
        (Arena, J. M. Poisoning, 1970.)
    B.   If victim is obtunded, unconscious,  or convulsing, give 0.1-0.5
        ml/kg  of undiluted monoacetin by deep intramuscular injection
        every half  hour  for  4-6  hours,  rotating  the  injection  sites  to
        minimize pain and  swelling. Monoacetin can also be given  intra-
        venously on the same schedule, using a 1:5 dilution in sterile isotonic
        saline.
                                62

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        CAUTION:  The use of parenteral monoacetin is hazardous. Tech-
                     nical grade material contains glycerin which, in ade-
                     quate dosage, may cause hemolysis,  hypotension,
                     convulsions, and paralysis. If a nonsterile solution is
                     injected, the monoacetin should be cultured to guide
                     the administration of antibiotics if sepsis develops.

4.  CONTROL CONVULSIONS

    A.  Administer 100%  OXYGEN by positive pressure to provide as
        much pulmonary gas exchange as possible, despite seizures.
    B.  ANTICONVULSANT DRUGS

        CAUTION:  It may be difficult  or impossible to stop the seizure
                     activity without stopping respiration. Be prepared to
                     maintain  pulmonary  ventilation  mechanically.
                     Tracheostomy may be necessary if seizures are pro-
                     longed.

        (a).  Diazepam  (VALIUM®) usually  controls  mild  convulsions.
             For adults, give 5-10 mg, slowly, intravenously; for children
             under 6 years or 23 kg body weight, give 0.1  mg/kg body
             weight, slowly, IV. Repeat in 4-6 hours  if necessary.
        (b).  Pentobarbital  may be needed in addition to control severe
             convulsions. Dosage:  5 mg/kg body weight, or 0.20 ml/kg
             body weight, using the usual 2.5% solution. If possible, inject
             solution intravenously, at a rate not exceeding 25 mg (one ml)
             per minute until convulsions are controlled. If intravenous ad-
             ministration is not possible, give total dose by deep intramus-
             cular  injection, not exceeding 5  mg/kg body  weight (0.20
             ml/kg of 2.5% solution).
        (c).  Phenytoin (DILANTIN®) has prolonged anticonvulsant ac-
             tion. Dosage: loading dose  15-18 mg/kg.  Maintenance dose
             4-8 mg/kg  q  4-24 hours as needed. Intramuscular adminis-
             tration is not  recommended. Give IV slowly at no more than
             20% total dose per minute.
        (d).  Thiopental  (PENTOTHAL®), by continuous intravenous in-
             fusion, may help to control severe seizures. Dissolve one gram
             in  500 ml of glucose solution, and infuse at a rate just suffi-
             cient to stop seizures.

             CAUTION:  Laryngospasm is a complication of anticonvul-
                          sant therapy and may require tracheostomy.

        (e).  In  some  instances,  curari/ation  with succinylcholine or  a
             similar agent  is required to stop  convulsions. This requires
             tracheal  intubation or tracheostomy and mechanical  pulmo-
             nary ventilation, with regular monitoring of blood gases and
             pH.
                                63

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5.   Many other agents tested in fluoroacetate poisoning are NOT EFFEC-
    TIVE: sodium acetate,  calcium  chloride, ethanol, propylene  glycol,
    digitalis glycosides, di- and tri-acetates of glycerol.
6.   Administer IV electrolyte solutions cautiously to avoid fluid overload in
    presence of a weak and irritable myocardium.

 Zinc phosphide and yellow phosphorus

1.   WASH SKIN  BURNS due to yellow phosphorus with water and a 1%
    copper sulfate solution. Make sure all particles of phosphorus have been
    removed. Cover burned area with ointment.
2.   Poisonings by INGESTED yellow phosphorus or zinc phosphide are ex-
    tremely difficult to manage. The mortality rate of 50% is the result of
    either shock or pulmonary edema in the first few hours or days, or coma,
    seizures, and/or liver, kidney and myocardial damage in the ensuing days
    or weeks.

    CAUTION:   Highly toxic  phosphine gas may evolve  from emesis,
                lavage fluid, and feces of victims of these poisons. The pa-
                tient's room should be well ventilated.

    A.  INTUBATE and ASPIRATE the stomach.  LAVAGE with several
        quarts of 1:5000 potassium permanganate solution.

        CAUTION:  Persons attending  victim must avoid contact  with
                    yellow phosphorus, which causes skin burns.

    B.  Combat shock and acidosis with TRANSFUSIONS of whole blood
        and INFUSIONS of glucose and electrolyte solutions. Monitor fluid
        balance  and  central venous  pressure  to  avoid fluid overload.
        Monitor blood electrolytes and pH  to guide choice of intravenous
        solutions.
    C.  Administer 100% OXYGEN by mask or nasal tube.
    D.  Combat pulmonary  edema with  intermittent or continuous POSI-
        TIVE PRESSURE OXYGEN.
    E.   MONITOR URINE  albumin, glucose, and sediment to detect early
        renal injury. Monitor EKG to detect  myocardial impairment. Moni-
        tor serum alkaline  phosphatase, LDH, prothrombin time,  and
        bilirubin to evaluate liver damage.
    F.   Include Aquamephyton®  (vitamin  K]) in intravenous infusions if
        prothrombin level declines. Dosage of 10-50 mg per day may be re-
        quired.  Administer Aquamephyton®  slowly, intravenously;  stop
        infusion if Mushing, cyanosis, paresthesiae, hypotension, or dyspnea
        occurs.
    G.  MORPHINE SULFATE, 8-16 mg every few hours may be necessary
        to control pain. Child's dose: 0.1-0.2 mg/kg.
    H.  CONTROL CONVULSIONS with diazepam, barbiturates, and/or
        phenytoin as  suggested under treatment of sodium fluoroacetate
        poisoning.
    I.   CORTICOSTEROIDS at high dosages may  be beneficial.

                               64

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 Strychnine and crimidine

1.  Administer 100% OXYGEN by positive pressure.
2.  CONTROL CONVULSIONS. This may be attempted with intravenous
    diazepam, barbiturates, and/or phenytoin, as described under manage-
    ment of sodium fluoroacetate poisoning.

    A.  CURARIZATION is  often  required,  using  succinylcholine  or
        similar agent. Tracheal intubation or tracheostomy and continuous
        mechanical pulmonary ventilation are necessary. Blood gases and
        pH must be monitored.
3.  FORCED DIURESIS  with  mannitol  accelerates  the  excretion  of
    strychnine. Infusion of SODIUM BICARBONATE relieves metabolic
    acidosis.  There may  be  some  benefit  from  peritoneal dialysis,
    hemodialysis, and hemoperfusion.
4.  Once seizures have been controlled, remove unabsorbed toxicant  from
    the stomach by gastric INTUBATION, ASPIRATION, and LAV AGE.
    Leave a slurry of 30-50 gm ACTIVATED CHARCOAL in the stomach.
    Follow  charcoal with  SODIUM or MAGNESIUM SULFATE,  0.25
    gm/kg, in 1-6 ounces of tap water, to induce catharsis. Repeat cathartic
    dosage as needed.

 Vacor, DLP-787 (Active ingredient RH-787)

1.  If toxicant was ingested recently, EVACUATE the STOMACH by IN-
    TUBATION, ASPIRATION, and LAVAGE with 2-3 liters isotonic
    saline.
    A.  Before withdrawing stomach tube, instill 30-50 gm of ACTIVATED
        CHARCOAL as a slurry in 3-4 ounces of water, to limit absorption
        of remaining toxicant.
    B.   As soon as patient can  tolerate oral fluids after withdrawal  of
        stomach tube, give SODIUM or  MAGNESIUM SULFATE, 0.25
        gm/kg body weight in 1-6 ounces of water to induce catharsis.
        Repeat dose in 4 hours if patient has had no bowel movement.
2.  Administer NICOTINAMIDE (niacinamide) intravenously, slowly,  or
    intramuscularly. For adults and children over 12 years, give 500 mg im-
    mediately, then repeat injections of 200-400 mg every 4 hours  for 10-12
    doses. Within this range, select the dose on the basis of body weight and
    the estimated quantity of RH-787 ingested. If manifestations of RH-787
    toxicity appear, give nicotinamide by  continuous IV infusion at about
    100 mg per hour. There is probably no advantage in giving more  than
    3000 mg per day of nicotinamide.

    A.   Dosage  of nicotinamide for children under 12  years, or  23 kg, is
        about half the dosage suggested for adults.
    B.   After 2-3 days of parenteral therapy, give nicotinamide by mouth,
        100 mg  four times daily, for 2 weeks.

                              65

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3.  MONITOR blood  and urine sugar concentrations,  serum alkaline
    phosphatase, amylase, LDH, and GOT activities, urine ketone concentra-
    tions, blood electrolytes and BUN. Examine the electrocardiogram for
    arrhythmias.
4.  Unless the patient is able to void easily, put in place a RETENTION
    CATHETER to monitor urine flow and urinary glucose excretion.
5.  Infuse ELECTROLYTE SOLUTIONS intravenously to accelerate toxi-
    cant excretion and  correct errors in specific ion concentrations. If
    ketoacidosis appears,  use  bicarbonate  or Ringer's-lactate to control
    acidosis.
6.  If DIABETIC KETOACIDOSIS appears (ketonuria, metabolic acidosis,
    hyperglycemia) administer enough regular insulin to control the acidosis
    and hyperglycemia, as  in  naturally  occurring  diabetic ketosis.  The
    diabetes resulting from RH-787 tends to be brittle and correspondingly
    difficult to control.
7.  In  all cases of ingestion of Vacor or DLP-787  (whether or not acute
    poisoning occurs), follow the patient's clinical status carefully for at least
    6 months. Look  for indications of diabetes mellitus (glycosuria,  hyper-
    glycemia), and for consequences of autonomic nervous system damage:
    orthostatic hypotension, urinary retention, constipation, diarrhea, ab-
    dominal cramping, pain and weakness in the limbs'.

 Red squill

1.  Significant toxicity is not expected from this agent. If, for some reason, a
    significant amount is retained  in the  stomach, remove it by gastric IN-
    TUBATION, ASPIRATION,  and LAV AGE, followed by 0.25 gm/kg
    SODIUM or MAGNESIUM SULFATE in 1-6 ounces water.
2.  Monitor ELECTROCARDIOGRAM for arrhythmias and conduction
    disturbances characteristic of digitalis.

 Antu
1.  Significant toxicity is not expected from this  agent. If an extraordinary
    amount has been ingested, empty the gut. Administer  SYRUP OF
    IPECAC, then 1-2 glasses of water, to induce vomiting. Adult dose: 30
    ml; dose for children under 12 years:  15 ml. Follow with 30-50 gm ac-
    tivated charcoal in 3-4 ounces of water, then 0.25 gm/kg SODIUM or
    MAGNESIUM SULFATE in 1-6 ounces water.
2.  If dyspnea  appears, administer  OXYGEN by continuous  flow or by
    intermittent POSITIVE PRESSURE.

 Norbormide
1.  Significant toxicity is not expected from this  agent. If an extraordinary
    amount has been ingested, empty the gut. Administer  SYRUP OF
                                66

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   IPECAC, then 1-2 glasses of water, to induce vomiting. Adult dose: 30
   ml; dose for children under 12 years: 15 ml. Follow with 30-50 gm AC-
   TIVATED CHARCOAL in 3-4 ounces of water, then 0.25  gm/kg
   SODIUM or MAGNESIUM SULFATE in 1-6 ounces water.
2.  Monitor BLOOD PRESSURE and BODY TEMPERATURE for several
   hours, if a large amount has been absorbed.
                             67

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                Chapter 12



              FUMIGANTS
CHEMICAL STRUCTURES
HALOCARBONS

Cl
1
CI-C-CI
1
Cl
Carbon
Tetrachloride

Cl
1
CI-C-H
1
Cl
Chloroform


Cl
1
Cl - C - NO2

Cl
Chloropicrm

H
I
1
H - C - Br
1
H
Methyl Bromide






Br Br
1 1
H -C— C-H
1 1
H H
Ethylene
Dibromide

Cl H Cl
1 1 1
H -C - C = C
1 1
H H
1,3-Dichloro-
propene

Br Br Cl
Ii i
1 1
H - C -C - C - H
1 1 1
H H H
Dibromo-
chloropropane

Cl Cl
i i
1 1
H - C -C - H
| |
H H
Ethylene
Dichloride




OXIDES AND
H
ALDEHYDES



O
' ^
CH2- CH2
Ethylene Oxide


O
/ \
GH2 - CH • CHg

Propylene Oxide

H
C= 0
H

Formaldehyde

O
[•f]
L. — 1

Paraformaldehyde

H H H
1 1 1
C = C-C = O
1
H
Acrolein
SULFUR AND
PHOSPHORUS
COMPOUNDS


O = S = O

Sulfur Dioxide

S = C = S
Carbon Disulfide
_
\
S = O
F
Sulfuryl Fluoride

ii ii
p
I
I
H
Phosphme (from
MZP+ H20)

CYANIDES

H-C = N
Hydrogen Cyanide

H H
1 1
C = C-C = N
1
H
                                  Acrylonitrile
                    68

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 COMMON COMMERCIAL FUMIGANT PRODUCTS

   Chloroform, carbon  tetrachloride, methyl  bromide (Brom-O-Gas,  Fumi-
 gant-1, Kayafume, Me Br, Meth-O-Gas, Pestmaster, Profume); chloropicrin
 (Acquinite, Chlor-O-Pic,  Pic-Clor, Picfume, Tri-Clor); ethylene dichloride
 (EDC), ethylene  dibromide (EDB, Bromofume, Celmide, Dowfume  W-85,
 Kop-Fume, Nephis, Pestmaster EDB-85, Soilbrom); dichloroprop-ene and
 -ane  (Telone,  D-D),  sulfuryl  fluoride  (Vikane),  dibromochloropropane
 (DBCP).
   The Dowfume fumigants manufactured by the Dow Chemical Company are
 mixtures of halocarbons,  mainly EDC, EDB, carbon tetrachloride, Me Br,
 and chloropicrin, formulated to meet specific  needs.
   Ethylene oxide (ETO, oxirane); propylene oxide (epoxypropane); formalde-
 hyde (Formalin is a 40%  aqueous solution), propenal (Acrolein, Aqualin,
 Acrylaldehyde); carbon di- (or bi-) sulfide; hydrogen cyanide (prussic acid,
 Cyclon); acrylonitrile (ingredient of fumigant mixtures Acrylofume, Acritet,
 Carbacryl); aluminum phosphide  (Phostoxin).

 TOXICOLOGY

   Fumigants have extraordinary power to penetrate the lining membranes of
 the respiratory and gastrointestinal tracts, and the skin. They also penetrate
 the rubber and plastics  used in protective garb and they  are not efficiently
 taken up by conventional adsorbents used in ordinary respirators. These prop-
 erties make the protection  of applicator personnel very difficult, essentially
 mandating methods of use that do not require on-site operator handling.
   Because these chemicals are either gases or volatile liquids at room tempera-
 ture, inhalation is the most common route of absorption. Dermal injury does
 follow contact with some fumigants, ranging in severity from a mild chemical
 burn to vesiculation and ulceration. Fumigant gases irritate the eyes;  liquid
 fumigant may cause blindness from corneal ulceration.
   Respiratory tract irritation is the most common and serious injury caused by
 fumigants. Some  agents such as sulfur dioxide, chloropicrin, formaldehyde
 and acrolein cause so much irritation of the upper respiratory tract that the ex-
 posed individual is unlikely to inhale a quantity of fumigant capable of damag-
 ing the lung. Rarely, laryngeal edema or bronchospasm results from inhalation
 of high concentrations.
  Other gases, such as methyl bromide, phosphine, and ethylene oxide, are
 not so irritating to the nose, eyes, throat, and bronchi, but cause serious injury
 to the cells lining the fine air sacs of the lung. Thus, they are more likely than
 other fumigants to induce pulmonary edema,  a major cause of death from
 fumigant exposure.
  In varying degrees, these fumigants depress the central nervous system. As
 in the case of the anesthetic chloroform, adequate dosage may lead to uncon-
sciousness.  Depression or cessation of respiration is a major hazard of acute
inhalation exposure to fumigants. Acute exposures to methyl bromide have in-
duced convulsions. Absorbed in lower concentrations over several consecutive
                                  69

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days, methyl bromide has impaired basal ganglion function in humans, caus-
ing ataxia for weeks or months after exposure. Protracted exposure to carbon
disulfide has caused  peripheral  neuropathy and  changes  in CNS function
(chronic encephalopathy) of chronically  exposed workers.
  The halocarbon fumigants increase the irritability of the heart muscle. In-
tensive exposures may lead  to sudden death as a result of ventricular fibrilla-
tion.
  Liver and kidney damage occurs commonly following excessive exposure to
fumigants. Liver injury may  take the  form  of fatty  infiltration, diffuse
necrosis or massive necrosis. Elevated serum levels of GOT, LDH,  alkaline
phosphatase, and bilirubin  reflect hepatocellular injury.  The fumigants may
inflict direct injury on glomerular and tubular elements of the kidney, leading
to functional proteinuria and glycosuria, or to acute renal failure, depending
on  severity of toxicant  exposure. In addition, hyperbilirubinemia resulting
from liver damage may compound the tubular injury (hepatorenal syndrome).
  Inhaled  phosphine gas   (PH3)  and  ingested  metal  phosphides  cause
pulmonary edema, CNS depression, toxic myocarditis, and circulatory col-
lapse. Victims who survive  these immediate actions suffer liver injury  (fatty
degeneration and necrosis) and acute  renal  tubular necrosis.  Unlike  its
analogue arsine,  phosphine is not hemolytic. Enzymatic mechanisms of toxici-
ty are not known. Ingested metal phosphide (from which phosphine is gener-
ated) causes intense gastrointestinal irritation,  followed by degenerative and
necrotizing lesions of the liver,  kidney, and heart. Death is often due either to
cardiogenic shock or pulmonary  edema.
  Hydrogen  cyanide (HCN)  and its  salts  poison by  inactivating  the
cytochrome oxidase of cells  in critical tissues, primarily the heart and brain.
Acrylonitrile degrades slowly to HCN in the body, and therefore acts primarily
by the same mechanism, although the slow release of free cyanide renders it
somewhat less toxic than HCN itself. Both HCN and acrylonitrile are  suffi-
ciently absorbable across the skin to cause poisoning in the absence of inhala-
tion exposure. Manifestations  of poisoning are due mainly  to intracellular
anoxia of brain tissue (leading to respiratory failure), and to the circulatory in-
sufficiency that results from myocardial weakness. The liver has substantial
capacity for converting cyanide to the less toxic thiocyanate, a metabolic con-
version that is accelerated by therapeutically administered thiosulfate.
  Dibromochloropropane has  reportedly caused  sterility in manufacturing
plant workers and reduced sperm counts in highly exposed applicators.

FREQUENT SYMPTOMS AND SIGNS OF POISONING

  HEADACHE, DIZZINESS, NAUSEA, and vomiting are prominent early
symptoms of excessive exposure to these gases. Sulfur dioxide, formaldehyde,
chloropicrin,  and acrolein are  strong irritants,  causing BURNING SENSA-
TIONS in the nose and throat,  TEARING, COUGH, and sometimes hoarse-
ness and wheezing. Exposures to methyl bromide, phosphine and ethylene ox-
ide  are more likely to produce prompt pulmonary edema: COUGHING  of
                                   70

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copious amounts of FROTHY FLUID, associated with severe SHORTNESS
OF BREATH and cyanosis. The remaining fumigants are less likely to cause
respiratory tract injury.
  DROWSINESS, TREMORS, double vision, and weakness are the common
early  manifestations of central nervous system impairment. Tremors may
progress to myoclonic movements, then to generalized SEIZURES, UNCON-
SCIOUSNESS, and death.  Protracted low level exposure to methyl bromide
causes ATAXIA and impairment of manual coordination.
  Injuries to the skin by liquid fumigants may be manifest as areas of redness
or as BLISTERS which rupture, leaving raw skin or deep ulcers.
  If ingested, the LIQUID forms of HALOCARBONS often cause pulmonary
edema and SHOCK within  a few moments. If victim survives, injuries to the
brain, liver and kidney are  life-threatening.
  Longer-term low level inhalation of CHLOROCARBONS may cause liver
damage, first manifest  as ANOREXIA, then as JAUNDICE. Biochemical
studies confirm hepatocellular injury.
  Poisoning by excessive inhalation of CARBON DISULFIDE is character-
ized by DIZZINESS, headache, nausea, and sometimes disorientation, pares-
thesiae, hallucinations, and,  rarely, convulsions. Protracted low level exposures
produce PAIN, tingling, WEAKNESS of the extremities, and deterioration of
mental functions.
  Poisoning by  PHOSPHINE gas  is  usually  heralded  by weakness,
TREMORS, vomiting, a sense of pressure in the chest, COUGH, and dyspnea,
sometimes progressing to PULMONARY EDEMA. Intense thirst results from
hypotension and diarrhea. Severe poisonings lead to CONVULSIONS, coma,
and death. Those who survive the acute  phase suffer LIVER INJURY (eleva-
tion of serum GOT, LDH, and alkaline phosphatase, and sometimes, reduced
prothrombin concentration, hemorrhage, and jaundice) and kidney damage
(hematuria and sometimes anuria). Chronic exposures to lesser amounts have
caused pain in the eyes and nose, nosebleeds, and abdominal  pain.
  Ingestion of METAL PHOSPHIDES leads  promptly to  NAUSEA and
VOMITING, followed  by injury to the lung, liver, kidney, heart and central
nervous system. Hypocalcemic tetany (from hyperphosphatemia) and metabolic
acidosis  develop several hours after ingestion of solid phosphides.
  Excessive inhalation of SULFURYL FLUORIDE may induce muscle twitch-
ing and  convulsions. Persons repeatedly exposed risk injury to the lung (im-
paired pulmonary function) and kidney  (proteinuria and azotemia).
  Poisoning  by HYDROGEN CYANIDE or ACRYLONITRILE may pro-
duce sudden UNCONSCIOUSNESS and respiratory arrest without warning
symptoms. Lesser exposures cause HEADACHE, nausea, and  a sense of con-
striction in the throat,  followed by hyperpnea, dizziness, and apprehension.
Pulse and respiratory movements then become weak, slow, and irregular as
consciousness is lost. CONVULSIONS, either tonic or epileptiform,  may
supervene. Opisthotonus and trismus commonly appear, and sphincter control
is usually lost. The heart often continues to beat after respiration has stopped.
The skin generally remains pink.
                                 71

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CONFIRMATION OF DIAGNOSIS

  Large industrial concerns monitor  human absorption of halocarbons by
analysis of expired air. Similar technology is available in many departments of
anesthesiology. Such analyses  are not  often needed to identify the offending
toxicant, because  this is known from the exposure history. In managing dif-
ficult cases of poisoning, however, it may help to monitor breath concentra-
tions of toxic gas.
  Blood bromide  concentrations t have some value in identifying poisonings
by methyl bromide, and possibly ethylene dibromide, provided it can be estab-
lished that the person exposed to the fumigant has not recently taken inorganic
bromide medication. A level of organic bromide higher than 5 mg/100 ml in-
dicates excessive absorption of fumigant. A blood concentration of more than
10 mg/100 ml of organic bromide represents a  serious threat  to health. A
blood level of more than 15 mg/100 ml indicates an  immediate threat to life.
  Methods for detecting the organic oxides, aldehydes, sulfur dioxide, and
phosphine are not generally available, but they are  rarely needed. A simple
method is available for detecting carbon disulfide in urine (Djuric et al. Brit. J.
Indust. Med. 22:321-323. 1965). Cyanide can be detected and measured in
blood and tissues, as can the thiocyanate metabolite in urine and saliva. Odors
of gases on the victim's breath are sometimes helpful  diagnostic clues: cyanide
smells like bitter almonds, carbon disulfide like rotten cabbage, and phosphine
somewhat  like garlic or acetylene.

TREATMENT

 1.  FLUSH contaminating fumigant  from the SKIN and EYES with copious
     amounts of water for  at least  15  minutes.  Contact with LIQUID
     fumigant can cause  BLINDNESS or DEATH. Treat  injuries IM-
     MEDIATELY.
 2.  REMOVE victims of fumigant inhalation TO FRESH AIR. Even though
     initial symptoms and signs are mild, keep victim quiet, in a semireclining
     position. Reduction in physical activity reduces  the likelihood of pulmo-
     nary  edema.
 3.  If victim is not breathing, RESUSCITATE with positive pressure oxygen
     breathing apparatus,  if  available. If apparatus is not available,  use
     mouth-to-mouth or mouth-to-nose methods. If  victim is pulseless,use
     cardiac resuscitation.
 4.  If PULMONARY EDEMA is evident,  there are several measures  avail-
     able to sustain life. Medical judgment  must be  relied upon, however, in
     the management of each case. The following procedures  are generally
     recommended:
     A.  Put the victim in a SITTING position with a backrest.
   Conway, E. J. Microdiffusion Analysis and Volumetric Error, 3rd edition.
   Crosby Lockwood, London 1950.

                                  72

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    B.  Use intermittent and/or continuous positive pressure OXYGEN to
        relieve hypoxemia. (Do not give oxygen at greater concentrations or
        longer periods than necessary, because it may exaggerate the fumi-
        gant injury to lung tissue. Monitor arterial p O2).
    C.  Apply TOURNIQUETS in rotation to arms and legs to limit venous
        return.
    D.  Administer AMINOPHYLLINE (0.25-0.50 gm) slowly, intraven-
        ously.
    E.  Administer MORPHINE in small doses (5-10 mg), slowly, intra-
        venously, to allay anxiety and promote deeper respiratory excur-
        sions. Children's dose, 0.1-0.2 mg/kg.
    F.  Digitalization may be considered, but be alert to the serious risk of
        arrhythmias in an anoxic mycardium.
    G.  Slowly  administer  FUROSEMIDE,  40  mg,  or  SODIUM
        ETHACRYNATE, 50 mg,  to  reduce  venous load  by inducing
        diuresis.
    H.  TRACHEOSTOMY may be necessary in  some cases to facilitate
        aspiration of large amounts of edema fluid.
    I.   Epinephrine,  atropine,  and expectorants are generally NOT
        HELPFUL and may complicate treatment.
    J.   STEROIDS at high dosage are usually recommended, although
        their effectiveness is unproved.
    K.  If secondary pneumonitis occurs, administer ANTIBIOTICS.
    L.  Watch for RECURRENT PULMONARY EDEMA, even up to 2
        weeks after the initial episode. Limit victim's physical activity for at
        least 4 weeks. Severe physical weakness usually indicates persistent
        pulmonary injury.  Serial pulmonary function testing may be useful
        in assessing recovery.
5.  Combat SHOCK by placing victim in the Trendelenburg position and ad-
    ministering blood plasma and/or electrolyte and glucose solutions intra-
    venously, with great care,  to avoid pulmonary edema. Central  venous
    pressure should be monitored continuously. Vasopressor amines must be
    given with great caution, because of the irritability of the myocardium.
6.  Control CONVULSIONS. Seizures are most likely to occur in poisonings
    by methyl bromide, carbon  disulfide, phosphine,  metal phosphide,
    cyanide, and acrylonitrile.

    A.  Establish pulmonary gas exchange at the best  possible level by ad-
        ministering 100% OXYGEN by IPPB.
    B.   In poisoning by CYANIDE and acrylonitrile, proceed directly with
        ANTIDOTAL therapy (see below, paragraph IOC).
    C.   Control convulsions caused by other agents with careful IV injec-
        tion of DIAZEPAM, 5-10 mg in the adult, 0.1 mg/kg in children
        under 12 years. Repeat dosage in 4-6 hours if necessary.

        CAUTION:   Be  prepared to  maintain  pulmonary  ventilation
                    mechanically, and to manage hypotension and car-
                    diac arrhythmias.

                                73

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

 7.   If FUMIGANT LIQUIDS have been INGESTED, quantities remaining
     in the gut must be removed as effectively as possible by gastric INTUBA-
     TION, ASPIRATION, and LAVAGE.

     A.  IF victim is UNCONSCIOUS, put in place a cuffed endotracheal
         tube prior to gastric intubation.
     B.   Place conscious victim in a left lateral Trendelenburg position for
         intubation, and aspirate the pharynx as effectively as possible to
         minimize likelihood of tracheal aspiration.
     C.   After aspirating stomach contents, LAVAGE the stomach with 2-3
         liters 0.9% saline or 5% sodium bicarbonate, containing 30-50 gm
         ACTIVATED CHARCOAL. After lavage, leave 30-50 gm activated
         charcoal in stomach before withdrawing tube.
     D.  If  diarrhea does not  develop  spontaneously, give  SODIUM
         SULFATE orally, 0.25 mg/kg, to induce catharsis.

 8.   Intravenous INFUSIONS of GLUCOSE are  valuable in limiting the
     hepatotoxicity of fumigants. Monitor central venous pressure to avoid
     precipitating, or aggravating, pulmonary edema by fluid overload.
 9.   MONITOR fumigant poisoning victims closely for recurrent pulmonary
     edema and bronchopneumonia. Chart  fluid balance and check urine
     sediment regularly  to detect incipient tubular necrosis. Measure serum
     alkaline phosphatase, LDH, and bilirubin to assess liver injury.
10.   Certain SPECIFIC  MEASURES are recommended in poisonings by par-
     ticular fumigants:
     A.  If given very soon after exposure to METHYL BROMIDE, there
         may be  some  value in administering DIMERCAPROL (BAL) in
         vegetable oil intramuscularly. For adults, give 3-5 mg/kg q6h for 4
         doses.
         CAUTION:  DIMERCAPROL  may cause troublesome side ef-
                     fects (hypertension, tachycardia, nausea, headache,
                     paresthesiae, pain,  lacrimation,  sweating, anxiety,
                     and restlessness). Although usually not so severe as to
                     preclude treatment, these manifestation may require
                     antihistamine therapy for adequate control.

     B.   Mild poisonings by CARBON DISULFIDE inhalation may be man-
         aged best by no more than careful observation, even though sensory
         hallucinations, delirium, and behavioral aberrations can be alarm-
         ing. Severe poisonings may require specific measures:

         1.   CAFFEINE and sodium benzoate (0.5  gm subcutaneously)
             may help to relieve CNS depression.
                                 74

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    2.   If  manic behavior  threatens  the safety  of  the  victim,
         DIAZEPAM, 5-10 mg,  0.1  mg/kg in children, adminis-
         tered cautiously, intravenously,  may be helpful as  a  tran-
         quilizer. Do not give catecholamine-releasing agents  such as
         reserpine and amphetamines.

C.  Poisonings by HYDROGEN CYANIDE and ACRYLONITRILE
    gases are treated in essentially the same way as poisoning by  cyanide
    salts. In addition to the general treatment described earlier,  specific
    ANTIDOTES are  required. (See line 6 for pediatric regimen).

    1.   Administer AMYL NITRITE (perles) by inhalation for  15-30
         seconds of every minute, while a fresh solution of 3 %  sodium
         nitrite is being prepared.
    2.   As soon as solution is available, inject intravenously 10 ml of
         3% SODIUM NITRITE solution over a 2-4 minute interval,
         keeping the NEEDLE IN PLACE.

         CAUTION:   Monitor PULSE and BLOOD PRESSURE dur-
                      ing administration of amyl nitrite  and  sodium
                      nitrite. If systolic blood pressure falls below 80
                      mm Hg, slow or stop nitrite administration un-
                      til blood pressure recovers.

    3.   Follow sodium nitrite injection with an infusion  of 50 ml of
         25% aqueous solution of SODIUM THIOSULFATE  admin-
         istered over 10-minute period.  Initial adult dose should not ex-
         ceed 12.5 gm.
    4.   If symptoms persist or recur, treatment by sodium nitrite and
         sodium thiosulfate  should be REPEATED AT HALF  THE
         DOSAGES listed in paragraphs 2 and 3.
    5.   Measure hemoglobin and methemoglobin in blood. If more
         than 50% of total hemoglobin has been converted to  methe-
         moglobin, BLOOD TRANSFUSION or exchange transfusion
         should be considered, because conversion back to normal
         hemoglobin proceeds slowly.
    6.   Dosage of ANTIDOTES in CHILDREN:
            C. M. Berlin (Pediatrics  46:793-796, 1970)  has  recom-
            mended the following procedures in case of cyanide poi-
            soning in children:

         (a) Children  over  25  kg body weight should receive adult
            dosages of sodium nitrite and sodium thiosulfate.
         (b) Children less than 25 kg body weight should first have two
            3-4 ml samples of blood  drawn and then, through the
            same needle, receive 10 mg/kg (0.33 ml/kg of 3% solu-
            tion) of SODIUM NITRITE injected over a 2-4 minute in-
            terval. Following sodium nitrite, administer an infusion of
                            75

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                  1.65 ml/kg of 25% SODIUM THIOSULFATE at rate of
                  3-5 ml per minute.
              (c)  At this point, determine the hemoglobin content of the
                  original blood sample. If symptoms and signs of poison-
                  ing  persist or return,  give  supplemental  infusions  of
                  sodium nitrite and sodium thiosulfate based on hemoglo-
                  bin level, as presented in TABLE 2. (These recommended
                  quantities are calculated to avoid life-threatening methe-
                  moglobinemia in anemic children).
  TABLE 2.
   Initial
 Hemoglobin
Concentration,
 gm/100 ml

   14.0
   13.0
   12.0
   11.0
   10.0
    9.0
    8.0
    7.0
Recommended dosages of supplemental sodium nitrite and
sodium thiosulfate based on hemoglobin level.
              Supplemental
              Volume of 3%
             Sodium Nitrite,
                 ml/kg

                 0.26
                 0.21
                 0.17
                 0.12
                 0.07
                 0.04
                    0
                    0
   Supplemental
  Volume of 25%
Sodium Thiosulfate,
     ml/kg

     1.28
     1.05
     0.83
     0.60
     0.38
     0.23
        0
        0
              (d) When possible, monitor BLOOD LEVELS of METHE-
                  MOGLOBIN  to achieve approximately 40%  conversion
                  of hemoglobin to methemoglobin.
                                  76

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                           Chapter  13

      MISCELLANEOUS  PESTICIDES OF
                      HIGH  TOXICITY
   Pesticides included in this chapter are not similar in chemical structure or
 toxicologic actions to the major classes of pesticidal toxicants (organophos-
 phates, arsenicals, etc.) In general, they are not widely used and opportunities
 for serious human exposure are rare. However, those included here are charac-
 terized by either high toxicity or an important unique mechanism of toxic ac-
 tion. Occasional poisonings by these chemicals have occurred in humans and
 domestic animals.

 4-aminopyridine (Avitrol, 4-AP)
   This chemical, now used as a bird repellant, has caused severe poisoning in
 adult humans at dosages no greater than about 60 mg. This is only 2-3 times
 the dosage employed clinically in managing certain rare neuromuscular dis-
 orders. The principal pharmacologic action of 4-aminopyridine is to facilitate
 release of transmitter substances at neuroeffector junctions and at synapses
 throughout the nervous system.
   Human poisonings have been characterized by thirst, nausea, dizziness,
 weakness,  and  intense diaphoresis,  followed by toxic psychosis,  ataxia,
 tremors, dyspnea, and tonic-clonic convulsions. Metabolic acidosis, leukocy-
 tosis, and elevations of serum GOT, LDH, and alkaline phosphatase  were
 notable laboratory findings. EKG may show nonspecific ST-T wave changes.
 Treatment
   Promptly evacuate gut by intubation, lavage, activated charcoal administra-
 tion, and saline catharsis. Control convulsions with diazepam. Initiate diuresis
 with intravenous infusions, including mannitol. To date, poisoning victims
 have recovered in 24-48 hours without severe sequelae.
   Pancuronium is an antagonist of 4-aminopyridine, and can control seizures.
 It must be administered under the supervision of an anesthesiologist because
 of the likelihood of generalized paralysis. Propranolol may help to limit car-
 diac toxicity. Atropine controls the gastrointestinal symptoms.

Chlordimeform (Acaron,  Fundal, Fundex, Galecron, Spanone)
  Although the acute toxicity of this ovicidal agent is low (oral LDJO in the rat
about 200 mg/kg), it is now known from an incident of excessive respiratory
and dermal exposure to chlordimeform powder that it can cause acute illness
and urinary bladder irritation. In all likelihood, the offending metabolite is
2-methyl-4-chloroaniline.  Principal symptoms are  dysuria, gross hematuria,
urethral discharge, abdominal and back pain, and a hot sensation  all over.
Sleepiness, skin rash, anorexia, and a sweet taste in the mouth have also been
                                 77

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reported.  Cystoscopic  examination   of  victims  of  excessive  exposure
demonstrated acute hemorrhagic cystitis.
  Methods are available for detecting the 2-methyl-4-chloroaniline metabolite
in the urine.

Treatment
  Flush contaminant from eyes and wash from skin. Symptoms resulting from
undue occupational exposure resolve in a few days if exposure is terminated. If
chlordimeform has been recently ingested, it should be removed from the gut
either by administering Syrup of Ipecac, or by gastric intubation, aspiration,
and lavage with 0.9%  sodium chloride, followed by activated charcoal and
sodium sulfate catharsis. Serial urinanalyses should be performed to assess in-
jury to the urinary tract.

Copper salts and organic  complexes (oxide, hydroxide, arsenite, carbonate,
chloride,  oxalate,  phosphate,   silicate,  sulfate,  zinc  chromate,  acetate,
naphthenate, oleate, quinolinolate, and resinate).
  These are commonly used as fungicides, either alone or in combination with
other agents. There are several dozen proprietary products.
  LDi0 values vary from 6 to 1000 mg/kg, depending mainly on the solubility
and degree of ionization of the copper  compound.
  Toxicity of copper-arsenite salts is due mainly to the arsenic content.
  All of these salts irritate the skin and  eyes and damage mucous membranes.
When  ingested,  they are  powerfully emetic:  the  stomach usually empties
promptly and automatically in fully conscious individuals. When retained and
absorbed, toxic  injury affects the gastrointestinal lining, capillaries,  brain,
liver, kidney, and formed  elements of the blood. Copper salts are hemolytic.
  Manifestations of poisoning include burning pain in the chest and abdomen,
intense nausea, vomiting, diarrhea, headache, sweating and shock. Later, the
liver is enlarged. Jaundice may  reflect hemolysis or liver damage or both.
Anuria indicates kidney injury by copper and/or free hemoglobin. Death may
occur from convulsions, coma, or hepatorenal failure. Elevated serum copper
levels (maximum normal level is 125 jug per 100 ml) indicate severity of poison-
ing.

Treatment
  Wash contaminated skin and flush eyes with copious amounts of water. If
copper salts have  been ingested, lavage the stomach with 0.1% potassium
ferrocyanide, then  instill  a suspension of egg white.  Intravenous fluids  ac-
celerate excretion. If signs of systemic poisoning develop, give dimercaprol
(see Arsenical Pesticides for dosage) or penicillamine, 0.5 gm orally four times
daily, if patient  can retain oral medication. Shock may require blood trans-
fusions and pain may require morphine. Exchange transfusions may be consid-
ered in severe poisonings.  Renal  failure may require protracted hemodialysis.

Cycloheximide (naramycin, Acti-dione, Actispray, Hizarocin)
  This is an antibiotic fungicide of high toxicity: oral LD,0 in rats is 2 mg/kg.
                                   78

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    Dermal absorption is probably not efficient.  When ingested, the agent
 causes excitement, tremors, salivation, diarrhea, and melena. Mechanisms of
 toxicity are not well defined,  but probably include irritation  of  the  gut,
 stimulation  of sympathetic and parasympathetic  nervous systems, renal in-
 jury, and damage to the adrenal cortex.
    There are no chemical tests to confirm cycloheximide poisoning.

 Treatment
   Remove toxicant  from  gut by lavage. Instill activated charcoal,  then a
 cathartic dose  of sodium sulfate. Intravenous fluids accelerate excretion.
   Hydrocortisone appears to be antidotal, particularly in combination with
 the adrenergic  agent methoxyphenamine (Orthoxine®). Atropine  relieves the
 cholinergic symptoms.

 Endothall (Accelerate, Aquathol, Des-i-cate,  Hydout, Hydrothol)
   Acute oral LD50 of this  herbicide is 51 mg/kg.  Dermal absorption of the
 commonly used salts is probably slight. It is irritating to eyes, mucous mem-
 branes and skin, but it is not sensitizing. Mechanisms of systemic  toxicity are
 not clear, but the central  nervous system, heart, blood vessels, and gastrointes-
 tinal lining appear to be primary targets. Poisoned animals exhibit ataxia, con-
 vulsions, shock, and respiratory depression. Erosions and ulcers of the gastro-
 intestinal tract  follow ingestion.
   There are no standard analytical methods for  confirming poisoning.

 Treatment
   Wash contaminated skin and flush eyes with copious amounts of water. In-
 stead of gastric evacuation  following ingestion,  administer  cold milk  or
 aluminum hydroxide gel. This may be followed by saline catharsis.  There is no
 specific antidote. Shock  may require blood transfusions.  Use of adrenergic
 amines is probably hazardous in view of myocardial irritability.

Nicotine sulfate (Black Leaf 40)
  This time-honored natural insecticide is still used in horticulture.  Lethal
dose  in  humans is about  60 mg. Nicotine preparations, especially those
using the free alkaloid, are  well absorbed across the gut wall, lung, and skin.
Poisoning symptoms from excessive doses appear promptly. They are due to
transient stimulation,  then prolonged depression, of the central nervous
system,  autonomic ganglia, and motor end-plates of skeletal muscle. Central
nervous  system injury is manifest as headache, dizziness, incoordination,
tremors, then clonic convulsions leading to tonic-extensor convulsions which
are often fatal.  In some instances, convulsive activity is minimal and death by
respiratory arrest occurs  within a few minutes. Effects on autonomic ganglia
give rise to sweating, salivation, nausea, abdominal pain, diarrhea,  and hyper-
tension. The  heart is usually slow, and often arrhythmic. Block  of skeletal
muscle motor end-plates causes  profound  weakness, then paralysis.  Death
may occur from respiratory depression or from shock.
  Nicotine can  be measured in blood and urine to confirm poisoning.

                                   79

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Treatment
  Promptly wash contaminated skin and flush eyes with water. Ingestion of
nicotine requires immediate gastric intubation, aspiration, and lavage, the lat-
ter preferably with 1.5% tannic acid solution,  or 1:5000 potassium perman-
ganate solution. Before withdrawing the lavage tube, instill 3-4 ounces of ac-
tivated charcoal in a slurry of water. Diazepam and/or barbiturates may be re-
quired to  control convulsions.  Atropine and phenoxybenzamine (Diben-
zaline®) may help to control the autonomic manifestations. Positive pressure
ventilation of the lungs with  oxygen may be necessary to sustain life when
respiration is arrested.

Phenylmercuric salts. Most  commonly used is phenylmercuric acetate (PMA,
Agrosan, Cekusil, Gallotox, Hong Nien, Luquiphene, Mersolite, Phenmad,
Phix, PMAS, Shimmer-ex)
  Phenylmercuric acetate is a widely used fungicide. Acute oral LDSO in the rat
is 22 mg/kg.  Other salts are also highly toxic.  They probably undergo some
dermal absorption.  Because of lower volatility and less penetration  of the
brain, they are somewhat less toxic than alkyl mercury compounds.
  Early manifestations reflect injury  to the central nervous system: ataxia,
muscle weakness, visual impairment, and delirium. After a single moderate ex-
posure, these symptoms usually resolve  promptly. Repeated intensive exposures
cause symptoms and  signs resembling amyotrophic lateral sclerosis: weakness
and incoordination of the arms, difficulty in swallowing and talking, weakness
and spasticity of the legs. Concurrent or later manifestations of excessive ab-
sorption reflect renal injury:  albuminuria, hematuria, azotemia, and some-
times acute tubular  necrosis. Induction of nephrotic syndrome has been
reported. This is characterized by massive albuminuria, generalized edema,
and hypercholesterolemia.
  Methods are available at  specialized toxicology laboratories for measuring
phenylmercuric compounds in urine.

Treatment
  Wash contaminated skin and flush eyes with water.  If ingested, remove the
chemical from the gut by prompt gastric intubation, aspiration, and lavage
with 5%  sodium bicarbonate solution and instillation of activated charcoal,
followed by catharsis with  sodium or magnesium sulfate. Intravenous infu-
sions of fluids accelerate excretion of mercurials and limit kidney damage.
There is no specific antidote; dimercaprol is not very effective in limiting tox-
icity.

Sodium chlorate (De-Fol-Ate, Drexel Defol, Drop-Leaf, Fall, Grain Sorghum
Harvest-Aid, Klorex, Kusatol, Tumbleaf)
  Although the oral LD30 in the rat is high (1200 mg/kg), there have been sev-
eral deaths from this herbicide-defoliant in  the past decade. The principal
mechanisms of toxicity are irritation of the gastrointestinal lining, central ner-
vous system depression, hemolysis, oxidation  of free hemoglobin to methemo-
globin, and renal tubular injury. Dermal absorption is minimal. If ingested,

                                  80

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chlorate causes swelling of the oral and pharyngeal membranes and pain in the
chest and abdomen. The victim is first restless, then apathetic. On the third or
fourth day after ingestion, lumbar pain, albuminuria, hematuria, then anuria
with azotemia, reflect renal injury. Death may be due  to hyperkalemia
(hemolysis), tissue anoxia (methemoglobinemia), or renal failure.
  Although chlorate  itself  is  not readily  measured  in  the blood,  free
hemoglobin and methemoglobin in the plasma point to poisoning by an oxidiz-
ing agent.

Treatment
  Remove from gut by prompt gastric intubation, aspiration, and lavage using
3 gm sodium thiosulfate in 300 ml 5% sodium bicarbonate. Instill 30-50 gm ac-
tivated charcoal in a slurry. Pain may require narcotics. Both hemodialysis
and exchange transfusions have been used successfully in treating poisonings.
Methylene blue is of no value in reducing the extracellular methemoglobin. In-
travenous infusions of 1% sodium thiosulfate (100-500 ml) limit the concen-
tration of circulating chlorate. Monitor serum electrolytes. Hemodialysis may
be needed to sustain life in the event of extensive renal tubular necrosis.

Sodium cyanide (Cymag)
  Occasionally, this is used as a rodenticide. Toxicity is extreme, similar to
that of hydrogen cyanide gas used as a fumigant. CONSULT Chapter 12 on
FUMIGANTS (hydrogen cyanide) for toxicology, poisoning manifestations,
diagnosis, and management. Cyanide salts are not adsorbed on activated char-
coal.
                                 81

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                          Chapter 14

     MISCELLANEOUS  PESTICIDES  OF
        LOW  OR MODERATE  TOXICITY
  These compounds are included in the manual  because their wide use
generates inquiries as to their potential for causing adverse effects.
  Description of the toxic potential of these chemicals as low or moderate does
not preclude the need for cautious handling. Many agents have irritant prop-
erties,  and individuals  vary  widely in their  reactions  to them.  Certain
predisposed persons may suffer dermal and respiratory illness from substances
that have no effect on other persons or experimental animals.  It is also true
that the sum total of potential effects of a chemical,  and by-products formed
in synthesis and storage, plus the metabolites formed into vivo is never fully
known. Reasonable precautions to avoid contact with pesticides are always
recommended regardless of the reported toxicity of the principal active ingre-
dient.
  Lowest reported acute oral LD50 in the rat is cited in this listing as an indica-
tion of overall toxicity, manifest  as killing power. The LD50  rating says
nothing of dosages necessary to produce symptoms or signs, disease conditions
characterized by long latency, subclinical biochemical effects,  or other non-
lethal effects on health.  It is essential that high LD50 ratings not  be interpreted
as indications that the subject chemicals are innocuous.
  Knowledge of use is sometimes helpful in identifying chemicals. Agents on
this list are used as herbicides (H), fungicides (F), or insecticides (I).
  There are many proprietary MIXTURES of these chemicals and it is common
to tank mix many of them according to the grower's  requirements. Intelligent
management of exposures requires that the full list of  active ingredients in mix-
tures be ascertained from the producer or applicator.  In general, management
is aimed at the most toxic ingredient.
Chemical
Clan
Acetamldes
Acetanilides

Generic
Name
allidochlor
metolachlor
alachlor
propachlor
Use
H
H
H
H
"-DSO
750
2,780
1,800
710
Proprietary Known or Suspected
Name Advert* EHeet*
Randox, CDAA
Dual, Bleep, Primagram, ~
Primextra
Moderately Irritating
to skin and eyes.
Lasso, Lazo, Alanex Mild Irritant
Ramrod, Bexton Dermal irritant and
sensltlzer
            propanil
1,384 DPA, Propanex, Riselect, Ros-  |~~
    anil, Stam F34, Strel, Super-   I M
    nox, Surcopur, Surpur, Vertac H
                                                      Mild Irritant
                                 82

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Chemical
Cla»«
Aliphatic Acids
Alumlnofluorlde
salt
Benzenes


Benzole and
Benzlllc Acid
Derivatives

Benzonitrlles
Carbamates


Carbanllate
Dicarboxlmides


Dlnltrotoluldlne
Compounds




Generic
Name
dichloro-
propionic acid
trichloro-
acetic acid
sodium fluoro-
alumlnate
hexachloro-
benzene
(perchloroben-
zene)
paradichloro-
benzene
pentachloro-
nitrobenzene
benzyl benzoate
chlorobenzllate
trichloro-
benzole acid
chlorothalonll
dlchlobenil
asulam
benomyl
chlorpropham
terbucarb
barban
captafol
captan
folpet
(thlophal)
benefin
butralin
dinitroamine
fluchloralm
isopropalin
oryzalin
pendimethalin
profluralin

Use
H
H
1
F
1
F
1
1
H
F
H
H
F
H
H
H
F
F
F
H
H
H
H
H
H
H
H

LD50
970
5,000
>1 0,000
10,000
500
1,700
1,700
960
1,370
10,000
3,160
5,000
10,000
3,800
34,000
600
6,200
10,000
10,000
10,000
12,600
3,700
1,550
5,000
10,000
1,250
1,808
83
Proprietary Known or Suspected
Name Adverse Effects
Dalapon, Dowpon, Crisapon, |~~
Basfapon _] Skin and eye
~"| irritants
TCA L-
Cryolite, Kryocide Slight irritant
HCB, No Bunt, Anticarie I Chronic ingestlon
— causes porphyrla
cutanea tarda
PDB, Paracide [Mild respiratory
— irritant and
Ihepatotoxin
PCNB, Terrachlor Skin irritant
Benzyl benzoate
Acaraben, Akar, Benzllan, Kop~
Mite, Benz-0-Chlor
Benzac, TBA, TCBA, Tribac
Bravo, Daconil 2787
Casoron, Du-Sprex
Asulox 40, Asulox F
Benlate, Tersan 1991
Furloe, Chloro IPC, CIPC, ~~
Sprout Nip, Taterpex, Unicrop
CIPC
Azak, Azac, Azar
Irritating to skin and
eyes.
-
Moderately Irritating
to skin and
respiratory tract
Mild irritants.
These carbamates
do not Inhibit
chollnesterase
enzyme.
-
Carbyne, Neoban, Caryne Irritant and dermal sensltizer.
Oifolatan Skin irritant
Captan, Merpan, Orthocide Skin irritant
Phaltan, Folpan Skin irritant
Benfluralin, Bethrodine, Balfin,
Benefex, Quilan
Amex
Dinitramme, Cobex
Basalm 	
Paarlan
Surflan, Rycelan, Ryzelan
Prowl, Herbadox, Stomp
Tolban, Pregard

Slightly to
moderately irritating
to skin, eyes, and
mucous membranes.
These agents do not
uncouple oxidatlve
phosphorylation.

„_


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Chemical
Class







Oxadiazollnone

Phthalate

Picolinic acid
Derivative

Pyridazinone


Phosphonomethyl
glycine
Thladiazin (ol)









Triazines





















Generic
Name
trifluralin






oxadlazon

chlorthal-
dimethyl
picloram


maleic
hydrazide

glyphosate

bentazon






terrazole


ametryn
anilazlne
atraton
atrazine



cyanazine

desmetryn

isomethiozin

metribuzin

prometone

prometryn

propazine

Simazine
Use LD50
H >1 0,000






H 3,500

H 3,000

H 8,200


Growth 6,950
retardant

H 4,300

H 2,063






F 1,077


H 1,750
H 5,000
H 1,465
H 3,080



H 334

H 1,390

H 10,000

H 1,100

H 2,980

H 5,235

H >5,000

H >1 0,000
Proprietary Known or Suspected
Name Adverse Effects
Tteflan, Crisalma, Digermin,
Elancolan, Ipersan

-



Slightly to
to moderately irritating
to skin, eyes, and
mucous membranes.
These agents do not
uncouple oxldatlve
phosphorylation.
Ronstar Irritating to skin and
eyes
Dacthal, DCPA Mild irritant

Tordon, Amdon pTrrltating to skin,
-I eyes, and
Ljespiratory tract
Burtolm, Chemform, De-Cut,
De-Sprout, Regulox, KMH, Slightly Irritating
Maintain, Stunt-Man
Roundup Irritant to eyes and
respiratory tract
Basagran


_



Terrazole
_

Evik, Ametrex, Gesapax
Dyrene, Direz, Kemate, Triasyn
Atratone, Gesatamin
AAtrex, Atranex, Gesaprim,
Primatol A, Atred, Crisazine,
Vectal SC

Bladex, SO 15418

Semeron —

Tantizon

Sencor, Lexone, Sencorex,
Sencoral
Pramitol, Gesafram-50, Pro-
meton, Primatol 25E
Caparol, Gesagard, Primatol Q.
Prometrex
Milogard, Gesamil, Primatol P,
Prozinex
Prmcep, Gasatop, Simadex,
Moderately irritating
to skin, eyes,
respiratory tract. On
ingestion, has
caused vomiting,
diarrhea, dyspnea,
tremors, weakness.
"Moderately Irritating
to skin, eyes, and
respiratory tract.
-




Some triazines are
mildly irritating to
skin, eyes, and up-
per respiratory tract.
Systemic toxicity is
unlikely unless very
large amounts have
been ingested.









   Simanex
84

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Chemical
Class
Triazmes
Uracils

Urea Derivatives





'









Generic
Name
terbuthylazme
terbutryn
bromacil
lenacil
terbacil
chloroxuron
chlortoluron
difenoxuron
diflubenzuron
diuron
fluometuron
isoproturon
Imuron
methabenz-
thiazuron
metobromuron
metoxuron
monolmuron
monuron
neburon
siduron
tebuthiuron
tetrafluoron
Use
H
H
H
H
H
H
H
H
1
H
H
H
H
H
H
H
H
H
H
H
H
H
"-DSD
2,610
2,500
5,200
11,000
5,000
3,700
10,000
7,750
4,640
3,400
6,416
1,826
1,500
2,500
3,000
3,200
1,800
3,600
11,000
7,500
644
1,265
Proprietary Known or Suspected
Name Adverse Effects
Pnmatol-M, Gardoprim, GS
13529
Igran, Terbutrex
Some triazmes are
mildly irritating to
skin, eyes, and up-
per respiratory tract
Systemic toxicity is
unlikely unless very
large amounts have
been ingested
Hyvar X, Uragan, Urox B, Urox Irritant to skin, eyes,
HX and respiratory
tract
Venzar
Sinbar
Tenoran, Chloroxifemdim
Dicuran, Tolurex, Clortokem
Lironion
Dimilm
Cekiuron, Crisuron, Gallon,
Dialer, Di-on, Diurex, Dirurol
Dynex, Karmex, Unidron, Urox
D, Vonduron
Cotoran, Lanex, Cottonex
Arelon, Belgran, Grammon,
Tolkan
Atalon, Hoe 2810, Lmurex,
Lorox, Premalm, Sarclex
Tribunil
Patoran, Pattonex
Deftor, Dosanex, Dosaflo,
Punvel
Aresm, Afesm, Arresm,
Premalm
Monurex
Granurex, Kloben, Neburex
Tupersan
Spike
Tomilon
Moderately irritating






Many substituted
ureas are moderate-
ly irritating to skin,
eyes, and mucous
membranes.









85

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TOXICOLOGY

  Many of these compounds are primary irritants to skin, eyes, and respira-
tory tract. The ureas and uracils are perhaps the most common offenders,
although captafol and  chlorothalonil have apparently  caused  contact der-
matitis in some agricultural workers. Propachlor is  a  dermal  sensitizer in
predisposed individuals.
  Although hexachlorobenzene has low acute toxicity, long-term ingestion of
HCB-treated seed grain caused an epidemic of porphyria cutanea tarda among
Turkish farm families in the 1950's. No such effect has been found in HCB
handlers in the United States.
  Given to cattle in extreme dosage, some triazines have caused neuromuscu-
lar abnormalities and damage to internal organs. It is unlikely that domestic
animals would consume these amounts voluntarily, and still less likely that
humans would be exposed to such extreme dosage.

CONFIRMATION OF ABSORPTION

  The benzene derivatives and benzonitriles can be identified in plasma by gas-
liquid chromatography.  Methods for benzoic acid and triazine metabolites in
urine have been developed. Analytical methods used for agricultural residues
of the remaining compounds might be adapted to analysis of gastric contents
or skin wipings. Samples must be collected within hours of exposure, because
most of these chemicals are promptly excreted.
  It is unlikely that such analyses will be required in cases of human exposure
to these agents. In the event that workers experiencing protracted heavy ex-
posure develop suspicious manifestations of injury or toxicity, urine or blood
analyses may help to confirm chemical absorption. Tests may be conducted in
private or university laboratories, or laboratories supported by the state or
federal government, i.e., the United States Environmental Protection Agency
or Occupational Safety and Health Administration.

TREATMENT

 1.   WASH contaminated SKIN with soap and  water.
 2.   FLUSH contaminated EYES with copious amounts of fresh water for 15
     minutes.
 3.   INGESTIONS of SMALL amounts (less than 10 mg/kg body weight) oc-
     curring less than an hour before treatment, are probably best treated by:

     A.  SYRUP OF IPECAC, followed by 1-2 glasses of water. Dose for
         adults and children over 12 years: 30 ml. Dose for children under 12
         years: 15 ml.
     B.  ACTIVATED CHARCOAL
         Administer 30-50 gm as a slurry in tap water, after vomiting stops.
     C.  SODIUM OR MAGNESIUM SULFATE, 0.25 gm/kg in tap water,
         as a cathartic.

                                 86

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4.  INGESTIONS of LARGE amounts (more than 10 mg/kg) occurring less
    than an hour before treatment, should probably be treated by gastric
    lavage:

    A.  INTUBATE stomach and ASPIRATE contents.
    B.  LAVAGE  stomach with slurry of ACTIVATED CHARCOAL in
        0.9% saline. Leave 30-50 gm activated charcoal in the stomach be-
        fore withdrawing tube.
    C.  SODIUM SULFATE, 0.25 gm/kg in tap water, as a cathartic.

        CAUTION:  Hydrocarbons  (kerosene, petroleum distillates) are
                    included in some formulations of these chemicals. In-
                    gestion of very LARGE AMOUNTS may cause CNS
                    depression. In  this  case, IPECAC IS CONTRAIN-
                    DICATED. Also, gastric intubation incurs a risk of
                    HYDROCARBON PNEUMONITIS. For this reason
                    observe the following precautions:

                    (1)  If the victim is unconscious or obtunded and
                         facilities  are at  hand, insert an ENDOTRA-
                         CHEAL TUBE (cuffed, if available) prior to
                         gastric intubation.
                    (2)  Keep victim's  HEAD  BELOW LEVEL  OF
                         STOMACH during  intubation  and  lavage
                         (Trendelenburg, or left lateral decubitus,  with
                         head of table tipped downward). Keep victim's
                         head turned to the left.
                    (3)  ASPIRATE PHARYNX as regularly as possible
                         to remove gagged or vomited stomach contents.
5.   INGESTIONS occurring MORE THAN an HOUR before treatment are
    probably best treated only by ACTIVATED CHARCOAL, 30-50 gm,
    and SODIUM or MAGNESIUM SULFATE, 0.25 gm/kg, as described
    above.
6.   There are no specific antidotes for these chemicals. Because manifesta-
    tions of toxicity do occasionally occur in peculiarly predisposed individ-
    uals, MAINTAIN CONTACT with victim for at  least 72 hours so that
    unexpected adverse effects can be treated promptly.
                               87

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    INDEX TO PESTICIDE  POISONINGS
           BY SYMPTOMS AND SIGNS
  A listing of pesticides capable of causing specific symptoms and signs may
be of some help to professionals confronted with illnesses possibly caused by
pesticides. However, the limitations of this kind of index should be clearly
understood. Rarely are particular manifestations always present in poisonings
by a given chemical, and many poisonings  are characterized by unexpected
symptoms. Furthermore, there are usually many causes of particular symp-
toms and signs.
  The purpose of these lists is, therefore, only to direct the professional's at-
tention to a series of chemicals possibly responsible for various symptoms and
signs,  based  on past experience.  Starting from the major presenting feature
of the illness, the interviewer can inquire closely into possible exposures to the
principal causative toxicants, and then, if appropriate, assemble more substan-
tive evidence for or against a poisoning  diagnosis, e.g., concurrence of multi-
ple manifestations of specific poisonings, and laboratory test findings.
  Not all  manifestations  of illness are included. Some symptoms,  such as
dizziness and weakness, are caused by so many chemicals by either direct or in-
direct  mechanisms that they have little value diagnostically.
  This approach to clinical toxicology has been developed by Alan K. Done,
M.D., of Wayne State School of Medicine.  His general  format of classifica-
tion (Solving the Poison Puzzle, Emergency Medicine, February 1979) is used
in  the  following  tables.  Chemicals appearing   in  the  lists  headed
"Characteristic of These  Poisonings" have been substantially consistent in
producing the symptoms or signs identified in the left column. Agents listed in
the column headed "Occurs in These Poisonings" are found with sufficient
frequency to deserve mention, but  the association is not highly consistent.

                           CHARACTERISTIC OF             OCCURS IN
	MANIFESTATIONS	THESE POISONINGS	THESE POISONINGS
General
  Breath odor of.
   Garlic                  Arsenic
                        Phosphorus
                        Phosphides
                        Phosphine
   Bitter almonds            Cyanide
   Rotten cabbage            Carbon disulfide
  Fever                    Nitro-, chloro- phenols          Chlorophenoxy compounds
  Hypothermia               Vacor
  Myalgia                                         Chlorophenoxy compounds
  Chills                    Arsine
                        Vacor
                                 88

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         MANIFESTATIONS
        CHARACTERISTIC OF
        THESE POISONINGS
            OCCURS IN
        THESE POISONINGS
  Thirst
  Anorexia
  Hot sensations

Skin and Mucous Membranes
  Dry, cracked skin of hands
  Loss of nails

  Brittle nails

  Loss of hair


  Sweating
  Pallor

  Cyanosis
  Scratchy throat and Irritated
    eyes
  Blisters or burns
  Rash
 Yellow stain

 Eccrtymoses



 Keratoses
 Nitro-, chloro-, phenols
 Aminopyridine
 Phosphine

 Organophosphates
 Carbamate Insecticides
 Nicotine

 Chlordimeform
 Arslne

 Paraquat
 Petroleum distillates
 Weed oil

 Paraquat

 Inorganic arsenicals

 Thallium
 Inorganic arsenicals

 Organosphates
 Carbamate insecticides
 Nitro-, chloro- phenols
 Nicotine
 Aminopyridine

 Organchlorlnes

 Paraquat
 Strychnine
 Crimidine
 Nicotine
 Sodium fluoroacetate

 Sulfur dioxide
 Acrolein
 Chloropicrin
 Nitro-, chloro- phenols
 Formaldehyde
 Pyrethrins
 Copper compounds
 Endothall
 Sodium chlorate
 Methyl bromide

 Phosphorus
                                   Sulfur
                                   Thiram
                                   Propachlor
                                   Barban
Nitrophenols

Anticoagulant rodenticides
Phosphorus
Phosphides

Inorganic arsenicals
                                                                       Fumlgants
                                                                       Nitro-, chloro-, phenols
                                                                       Arsenicals
Anticoagulant rodenticides

Organophosphates
Carbamate insecticides
Organochlorlnes
Paraquat
Blsdlthlocarbamates
Ethylene bisdlthlocarbamates
Chloroallphatlc acids
                                    Liquid methyl bromide or ethylene
                                     oxide

                                    Plcloram
                                    Dlfolatan
                                    Captan
                                    Chlorothalonll
                                    Nitro-, chloro- phenols
                                    Many other herbicides and
                                     fungicides
                                                 89

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        MANIFESTATIONS
                                         CHARACTERISTIC OF
                                         THESE POISONINGS
                                             OCCURS IN
                                         THESE POISONINGS
  Jaundice
Central Nervous System
  Headache
  Ataxia
  Convulsions
  Muscle twitching
  Tremors
  Mental confusion
  Sudden unconsciousness
Central Nervous System
  Tingling and numbness in the
    extremities
  Tetany


  Myotonia
                                  Phosphorus
                                  Phosphides
                                  Phosphme
                                  Halocarbon fumigants
Organophosphates
Carbamate insecticides
Organochlorines
Fumigants
Nicotine
Inorganic arsenicals

Organophosphates
Carbamate insecticides
Endothall
Nicotine
Phenyl mercuric acetate

Organochlorines
Strychnine
Crimldine
Phosphorus
Cyanide
Sodium fluoroacetate
Nicotine
Aminopyridine
Endothall

Organophosphates
Carbamate insecticides
Sulfuryl fluoride

Organophosphates
Carbamates insecticides
Phosphine
Aminopyridine
Cycloheximide
Nicotine

Organophosphates
Carbamate insecticides
Nitrophenols
Chlorophenols
Cyanide
Organochlorines
Vacor
Sodium fluoroacetate
Carbon disulfide
Aminopyridine
Cycloheximide

Cyanide
Carbon disulfide
Vacor
Sodium fluoroacetate

Phosphorus
Phosphides
                                   Paraquat
                                   Inorganic arsenicals
                                                                     Nitrophenols
                                                                     Chlorophenols
                                                                     Fumigants
                                                                     Inorganic arsenicals
                                                                     Organochlorines
                                                                     Nitro-, chloro- phenols
                                                                     Organophosphates
                                                                     Carbamate  insecticides
                                                                     Sulfuryl fluoride
                                                                     Chlorophenoxy compounds
                                                                     Pyrethrins
                                                                     Nitro-, chloro- phenols
                                                                     Bentazon
                                                                     Sulfuryl fluoride
                                                                     Strychnine
                                                                     Crimidine
                                                                     Nicotine
                                                                     Inorganic arsenicals
Organophosphates
Diquat
Carbamate insecticides
Halocarbon fumigants

Inorganic arsenicals
                                   Chlorophenoxy compounds
                                                  90

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       MANIFESTATIONS
                                        CHARACTERISTIC OF
                                        THESE POISONINGS
                                             OCCURS IN
                                         THESE POISONINGS
  Mlosls
                                  Organophosphates
                                  Carbamate insecticides
Gastrointestinal Tract
  Nausea, vomiting, abdominal
    cramps, diarrhea
  Salivation
Respiratory System
  Stuffy nose, wheezing
  Nosebleed

  Coughing frothy sputum
    (pulmonary edema)
  Rhinorrhea



  Tachypnea

  Respiratory depression
  Labored breathing
 Chest pain
 Organophosphates
 Carbamate insecticides
 Diquat
 Phosphorus
 Phosphides
 Phosphine
 Inorganic arsenlcals
 Arslne
 Fumlgants
 Red squill
 Cyclohexlmide
 Endothall
 Nicotine
 Chlorates
 Copper Compounds

 Organophosphates
 Carbamate Insecticides
 Cycloheximlde
 Nicotine
 Pyrethrum
 Bisdithiocarbamates plus alcohol
 Methyl bromide
 Phosphine
 Phosphorus
 Phosphides
 Ethylene oxide

 Organophosphates
 Carbamate insecticides
 Fumigants

 Nitro-, chloro- phenols

 Organophosphates
 Carbamate insecticides
 Fumlgants
 Cyanide
 Acrylomtrile
 Nicotine
 Endothall
 Sodium chlorate

 Methyl bromide
 Organophosphates
 Carbamate Insecticides
 Phosphine
 Phosphides
 Phosphorus

 Fumlgants
Sodium chlorate
Organochlorines
Chloro-, nitro- phenols
Bisdithiocarbamates
Ethylene bisdithiocarbamates
Chlorophenoxy compounds
Organic arsenicals
Paraquat
Bentazon
Chloroaliphatic acids
Paraquat

Organophosphates
Carbamate insecticides
ANTU
                                                                    Organochlorines
                                                                    Sulfuryl fluoride
                                                                    Organophosphates
                                                                    Carbamate Insecticides
                                                                    Chlorophenoxy herbicides
                                                                    Nitro-, chloro- phenols
                                                                    Chloroaliphatic acids
                                                 91

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       MANIFESTATIONS
                                       CHARACTERISTIC OF
                                        THESE POISONINGS
                                            OCCURS IN
                                        THESE POISONINGS
Cardiovascular System
  Bradycardia
  Hypertension

Renal System
  Renal failure
  Urinary frequency, dysuria
  Renal colic
Blood
  Anemia
  Leukopenia


  Hypoprothrombmernia

  Depressed cholmesterase
  enzyme activities

  Methemoglobinemia

  Free hemoglobin in plasma
  Elevated alkaline phosphatase,
    GOT, LDH
  Elevated blood bromide

  Hyperbilirubmemia
                                  Organophosphates
                                  Carbamate insecticides
                                  Cyanide
Tachycardia
Hypotension, shock
Irregular heart beat
Nitrophenols
Chlorophenols
Phosphorus
Phosphides
Phosphine
Vacor
Endothall
Cyanide
Sodium fluoroacetate
Halocarbon fumigants
Endothall
Organochlorines
Bisdithiocarbam;
Inorganic arsenic
Anticoagulant ro<
Organochlorines
Red squill
                                  Nicotine
Arsine
Fumigants
Cycloheximide
Chlorates

Chlordimeform
Vacor

Anticoagulant rodenticides
Chlorates
                                  Naphthalene
                                  Anticoagulant rodenticides
Anticoagulant rodenticides

Organophosphates


Chlorates

Naphthalene
Arsine
Copper compounds
Sodium chlorate

Halocarbon fumigants
Inorganic arsenicals
Diquat
Paraquat
Aminopyndine

Methyl bromide

Paraquat
Diquat
Phosphine
Phosphorus
Phosphides
Copper compounds
Inorganic arsenicals
                                                                    Paraquat
                                                                    Diquat
                                                                    Inorganic arsenicals
                                                                    Copper compounds
                                                                    Inorganic arsenicals
                                  Nitrophenols
                                  Inorganic arsenicals
Carbamate insecticides
  (targe dosage)
                                                                     Endnn
Halocarbon fumigants
                                                92

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      MANIFESTATIONS
                                       CHARACTERISTIC OF
                                       THESE POISONINGS
                                           OCCURS IN
                                       THESE POISONINGS
  Elevated BUN, creatinine
Hyperkalemia
Urine
  Proteinuria
  Hematuna




  Ketonuria


  Hemoglobinuria



  Myoglobinuria

  Porphyrinuria

  Bilirubinuria




  Glycosuna

Feces
  Blood present (melena)
  Luminescence

Semen
  Low sperm count
Paraquat
Diquat
Fumigants
Chlorates
Inorganic arsenicals

Naphthalene
Chlorates
Copper compounds
Diquat
Paraquat
Nitro-, chloro-, phenols
Fumigants
Cycloheximide
Copper compounds
Phenyl mercuric acetate
Sodium chlorate

Anticoagulant rodentlcldes
Sodium chlorate
Cycloheximide
Chlordlmeform

Vacor
Aminopyridine

Naphthalene
Arsine
Sodium chlorate
Hexachlorobenzene

Halocarbon fumigants
Phosphorus
Phosphides
Phosphine

Vacor
Diquat
Sodium chlorate
Anticoagulant rodentlcides
Phosphorus
Phosphides
Endothall
Cycloheximide

Phosphorus
Sulfuryl fluoride
Nitro-, chloro-, phenols
                                                                     Endothall
                                                                     Sulfuryl fluoride
Chlordimeform
Fumigants
Paraquat
Diquat

Phosphorus
Phosphides
                                  Chlorophenoxy compounds
Paraquat
                                                                    Dibromochloropropane
                                                                    Kepone
                                                93

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             PESTICIDES INDEX

                                           Pagef
1080 ....................................    54
AAtack .................................    36
AAtrex ..................................    82
Abate  ...................................     1
Abathion ................................     1
Acaraben ................................ 14, 82
Acaron ..................................    77
Accelerate ...............................    77
acephate .................................     1
Acquinite ................................    68
Acrex  ...................................    23
Acritet ..................................    68
Acrolein .................................    68
Acrylaldehyde ............................    68
Acrylofume ..............................    68
acrylonitrile ..............................    68
Actellic ..................................     1
Acti-dione ...............................    77
Actispray ................................    77
Afalon ..................................    82
Afesin ...................................    82
African ..................................     1
Agritox ..................................     1
Agrosan .................................    77
Agrotec .................................    27
Agrothion ...............................     1
Akar ....................................    82
alachlor .................................    82
Alanex ..................................    82
aldicarb .................................     9
aldrin  ...................................    14
Aldrite ..................................    14
allethrin .................................    42
allidochlor ...............................    82
alumino fluoride salt  ......................    82
aluminum phosphide  ......................    68
Amaze ..................................     1

tPage  number refers to the beginning page of the
chapter in which the pesticide is covered.
                       94

-------
Ambox	   23
Ambush	   42
Amdon	   82
Ametrex	   82
ametryn	   82
Amex	   82
aminocarb	    9
4-aminopyridine	   77
Amoxone	   27
Ancrack	   23
anilazine	   82
Ansar 170 HC	   46
Ansar 529 HC	   46
Ansar 8100	   46
Ansar DSMA liquid	   46
Anthio	    1
Anticarie	   82
Anticoagulent rodenticides	   54
antu	   54
4-AP	   77
Aphox	    9
Aquacide	   31
Aqua-Kleen	   27
Aqualin	   68
Aquathol	   77
Arasan	   36
Arelon	   82
Aresin	   82
Arresin	   82
Arrhenal	   46
arsenic	   46
arsenic acid	   46
arsenic trioxide	   46
arsenious oxide	   46
arsine	   46
Arsinyl	   46
Arsonate liquid	   46
Aspon	    1
Aspor	   36
asulam	   82
Asulox 40	   82
Asulox F 	   82
Atranex	   82
atraton	   82
                       95

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atrazine	    82
Atred	    82
Aules	    36
Avadex	    36
Avadex-BW	    36
Avitrol	    77
Azac	    82
Azak	    82
Azar	    82
azinphos-methyl	     1
Azodrin	     1

                     —B—

Balfin	    82
Banvel	    27
barban	    82
barthrin	    42
Basagran	    82
Basalin	    82
Basanite	    23
Basfapon	    82
Baygon	     9
Bayrusil	     1
Baytex	     1
Baythion	     1
Belgran	    82
Belmark	    42
Benefex	    82
benefin	    82
Benfluralin 	    82
Benlate	    82
benomyl	    82
bentazon	    82
Benzac	    82
benzene hexachloride	    14
Benzilan	    82
Benz-O-Chlor	    82
Benzyl benzoate	    82
bethrodine	    82
Bexton	    82
BH 2,4-D	    27
BHC	    14
Bicep  	    82
                      96

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 Bidrin	     1
 binapacryl	    23
 bioresmethrin	    42
 Birlane	     1
 Black Leaf 40 	    77
 Black Leaf Grass, Weed and Vegetation
  Killer Spray	    19
 Bladafum	     1
 Bladex	    82
 Bo-Ana  	     1
 Bolstar	     1
 bomyl	     1
 Bravo	    82
 brodifacoum	    54
 bromacil	    82
 bromadiolone	    54
 Bromofume	    68
 Brom-O-Gas	    68
 Bromone	    54
 bromophos	     1
 bromophos-ethyl 	     1
 Brush-Rhap	    27
 Bueno 6	    46
 bufencarb  	     9
 Burtolin	    82
 butralin	    82
 butylate	    36
 Bux	     9

                     	r<	

 cacodylic acid	    46
 Caid	    54
 calcium acid methanearsonate 	    46
 calcium arsenate	    46
 calcium arsenite 	    46
 Caldon	    23
 CAMA	    46
Caparol	    82
captafol	    82
captan 	    82
Carbacryl	    68
Carbamult	    9
Carbamates-cholinesterase-inhibiting	    9
                      97

-------
carbaryl	    9
Carbazinc 	   36
carbofuran	    9
carbon bisulfide	   68
carbon disulfide	   68
carbon tetrachloride	   68
carbophenothion 	    1
Carbyne	   82
Caryne	   82
Carzol 	    9
Casoron	   82
Castrix	   54
CDAA	   82
Cekiuron	   82
Cekusil	   77
Celathion	    1
Celmide	   68
Certified Kiltrol-74 Weed Killer	   19
Chem Bam	   36
Chemform	   82
Chemonite	   46
Chemox General	   23
Chemox PE	   23
Chem Pels C	   46
Chemsect DNBP	   23
Chemsect DNOC	   23
Chem-Sen 56	   46
Chipco Crab Kleen	   46
Chipco Thiram 75	   36
Chipco Turf Herbicide "D"	   27
Chlordan	   14
chlordane	   14
chlordimeform	   77
chlorfenac	   27
chlorfenvinphos	    1
chlormephos	    1
chlorobenzilate	   14
chloroform	   68
chloro IPC	   82
chlorophacinone	   54
chlorophenothane	   14
Chlorophenoxy compounds	   27
Chlor-O-Pic	   68
chloropicrin	   68
                     98

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chlorothalonil	    82
chloroxifenidim 	    82
Chloroxone	    27
chloroxuron	    82
chlorpropham	    82
chlorpyrifos	     1
chlorthaldimethyl	    82
chlorthiophos	     1
chlortoluron	    82
Chrysron	    42
Ciba-Geigy Ontrack (OS 3,4 or 5)	    19
cinerins	    42
Ciodrin	     1
CIPC	    82
Clortokem	    82
Cobex	    82
copper acetate	    77
copper acetoarsenite	    46
copper arsenite	46,77
copper carbonate	    77
copper chloride	    77
copper hydroxide	    77
copper naphthenate	    77
copper oleate	    77
copper oxalate	    77
copper oxide	    77
copper phosphate	    77
copper quinolinolate  	    77
copper resinate	    77
copper salts	    77
copper silicate	    77
copper sulfate	    77
copper zinc chromate	    77
Co-Ral	     1
Corozate	    36
Cotoran	    82
Cottonex	    82
coumachlor	    54
coumafene	    54
coumafuryl	    54
coumaphos	     1
counter	     1
Crab-E-Rad	    46
crimidine	    54
                      99

-------
Crisalina 	   82
Crisapon	   82
crisazine	   82
Crisquat	   31
Crisuron	   82
Crop Rider	   27
Crotothane	   23
crotoxyphos	     1
cryolite	   82
Cuman	   36
Curacron	     1
Curamil	     1
cyanazine	   82
cyanofenphos	     1
cyanophos	     1
Cyanox	     1
cycloate	   36
cycloheximide	   77
Cyclon	   68
Cygon	     1
Cymag	   77
Cyolane	     1
cypermethrin	   42
cythioate	     1
Cythion	     1

                    —D—

2,4-D	   27
D 50	   27
decamethrin	   42
Dacamine 2D/2T	   27
Dacamine 4D	   27
Dacamine4T	   27
Daconate 6	   46
Daconil 2787	   82
Dacthal  	   82
Dailon	   82
dalapon	   82
Dal-E-Rad	   46
Dalf	     1
Dapacryl	   23
Dasanit	     1
2,4-DB	   27
                    100

-------
DBCP	    68
DCPA	    82
D-D 	    68
DDT	    14
DDVP	     1
De broussaillant 600	    27
De broussaillant Concentre	    27
De-Cut	    82
Ded-Weed	    27
Ded-Weed Brush Killer	    27
DBF	     1
De-Fend	     1
De-Fol-Ate 	    77
Deftor  	    82
De-Green	     1
Delnav	     1
demeton	     1
demeton-methyl	     1
Des-I-Cate	    77
Desiccant L-10 	    46
desmetryn	    82
Desormone	    27
De-Sprout	    82
Dessin	    23
Dethdiet	    54
Dextrone	    31
Dextrone X	    31
Dexuron	    31
dialifor	     1
diallate	    36
Dialer	    82
diazinon	     1
Dibrom 	     1
dibromochloropropane	    68
dicamba	    27
dicarzol	     9
dichlobenil	    82
dichloroanisic acid	    27
2,4-dichlorophenoxyacetic acid  	    27
dichloropropene (ane)	   68
dichlofenthion	     1
dichloropropionic acid	    82
dichlorprop	    27
dichlorvos	     1
                      101

-------
dicofol	   14
Dicotox	   27
dicrotophos	    1
Dicuran	   82
dieldrin	   14
Dieldrite	   14
dienochlor	   14
difenacoum	   54
difenoxuron	   82
diflubenzuron	   82
Difolatan	   82
Digermin	   82
Dilic	   46
Dimecron	    1
dimethoate	    1
dimetilan	    9
Dimilin	   82
Dinitramine	   82
dinitro	   23
Dinitro-3	   23
dinitroamine	   82
dinitrocresol	   23
Dinitro General	   23
dinitrophenol  	   23
dinobuton	   23
dinocap	   23
Dinofen	   23
dinopenton	   23
dinoprop	   23
dinosam	   23
dinoseb	   23
dinosulfon	   23
dinoterb	   23
dinoterbon	   23
Dinoxol	   27
Di-on	   82
dioxathion	    1
Diphacin	   54
diphacinone	   54
Dipher	   36
Dipterex	    1
diquat	   31
Direz	   82
disodium methyl arsonate	   46
                      102

-------
disulfoton	    1
Di-Syston	    1
Di-Tac	   46
Dithane (D14, M22, M45, or Z78)	   36
Dithiocarbamates	   36
Dithione	    1
Diurex	   82
Diurol	   82
diuron 	   82
DLP-787	   54
DMA	   46
DMA 4	   27
DMA 100	   46
DNAP	   23
DNBP 	   23
DNC	   23
DNOC	   23
Dormone	   27
Dosaflo	   82
Dosanex	   82
Dotan	    1
Dow General Weed Killer	   23
Dow Pentachlorophenol	   19
Dow Selective Weed Killer	   23
Dowfume fumigants	   68
Dowicide EC-7	   19
Dowpon	   82
DP-2 Antimicrobial	   19
DPA	   82
Drat	   54
Drawinol	   23
Draza	    9
Drexel Defol	   77
Drinox	   14
Drop-Leaf	   77
Drupina 90	   36
DSE	   36
DSMA	   46
Dual	   82
Dursban	    1
Du-Sprex	   82
Dyanap  	   23
Dyfonate	    1
Dylox	    1
                     103

-------
Dynamyte	   23
Dynex	   82
Dyrene	   82

                    —E—

Ectiban	   42
EDB	   68
EDC	   68
Ekamet	    1
Ekatin 	    1
Elancolan	   82
Elgetol 30	   23
Elgetol318	   23
emerald green	   46
Emulsamine BK	   27
Emulsamine E-3	   27
Endosan	   23
endosulfan	   14
Endothall	   77
endrin	   14
Entex	    1
Envert DT, T or 171	   27
EPBP	    1
EPN	    1
epoxypropane	   68
Eptam 	   36
EPTC	   36
Esgram	   31
Esteron Brush Killer	   27
Esteron Four	   27
Esteron 99 Concentrate	   27
Esteron 245	   27
Estone	   27
ethion	    1
ethoprop	    1
Ethylan 	   14
ethyl parathion	    1
ethylene dibromide	   68
ethylene dichloride	   68
ethylene oxide	   68
ETO	   68
etrimfos	    1
Evik	   82
E-Z-OffD	    1
                    104

-------
                     —F—

Fac	     1
Fall	    77
Famfos	     1
famphur	     1
Far-Go	    36
fenac	    27
fenamiphos	     1
Fence Rider	    27
fenitrothion	     1
fenophosphon	     1
fenothrin	    42
fenpropanate	    42
fensulfothion	     1
fenthion	     1
f envalerate	    42
ferbam	    36
Ferberk 	    36
Fermide 850	    36
Fernasan	    36
Fernesta	    27
Fernimine 	    27
Fernoxone	    27
Ferxone	    27
Field Clean Weed Killer	    27
fluchloralin	    82
fluometuron	    82
Folex  	     1
Folpan	    82
folpet	    82
fonofos 	     1
formaldehyde	    68
Formalin	    68
formetanate HCI	     9
formothion	     1
Formula 40	    27
Forron	    27
Framed	    82
Fratol	    54
French green	    46
Fuclasin Ultra	    36
Fuklasin	    36
Fumarin	    54
Fumigant-1	    68
Fumigants	    68
                     105

-------
Fundal	    77
Fundex	    77
Fungostop	    36
Furadan	     9
Furloe	    82

                    —G—

G 28029	     1
Galecron	    77
Gallotox	    77
Gammexane 	    14
Garden Termi Tox	    19
Gardona	     1
Gardoprim	    82
Gebutox	    23
Gesafram 50	    82
Gesagard	    82
Gesamil	    82
Gesapax	    82
Gesaprim	    82
Gesatamin	    82
Gesatop	    82
glyphosate	    82
Grain Sorghum Harvest-Aid	    77
Graminon	    82
Gramonol	    31
Granurex	    82
Griffin Manex	    36
GS 13529	    82
Guthion	     1
Gypsine	    46

                    —H—

HCB	    82
HCH 	    14
Hedonal	    27
heptachlor	    14
heptenophos	     1
Herbadox	    82
Herb-All  	    46
Herbidal	    27
hexachlorobenzene	    82
                     106

-------
 Hexadrin	    14
 Hexaferb		    36
 Hexathane	    36
 Hexathir	    36
 Hexazir  	    36
 Hi-Yield Desiccant H-10	    46
 Hizarocin	    77
 Hoe 2810	    82
 Hong Nien	    77
 Hostaquick	     1
 Hostathion  	     1
 Hydout	    77
 hydrogen cyanide	    68
 Hydrothol	    77
 Hyvar X	    82

                     	I	

 Igran	    82
 Imidan	     1
 Inorganic arsenicals	    46
 Inverton 245 	    27
 iodofenphos 	     1
 Ipersan	    82
 isofenphos	     1
 isomethiozin	    82
 isopropalin 	    82
 isoproturon	    82
 isoxathion	     1

                     —J_

jasmolins	   42
 Jones Ant Killer	   46

                    —K—

Karathane	   23
Karmex  	   82
Karphos	     1
Kayafume	   68
Kelthane	    14
Kemate	   82
kepone	   14
                     107

-------
Kill-All	   46
Kiloseb	   23
Klean Krop	   23
Kloben	   82
Klorex 	   77
KMH	   82
Knockmate	   36
Kop-Fume	   68
Kop-Mite	   82
Kryocide 	   82
Krysid	   54
Kuron	   27
Kusatol	   77
Kwell	   14
Kypfarin 	   54
Kypman 80 	   36
Kypzin	   36

                    ' winjj^^—

Lanex	   82
Lannate	    9
Lasso	   82
Lawn-Keep	   27
Lazo	   82
lead arsenate	   46
lenacil	   82
leptophos	    1
Lexone	   82
lindane	   14
Line Rider	   27
Linurex  	   82
linuron	   82
Liphadione	   54
Liquiphene 	   77
Lironion	   82
Lithate	   27
Lonacol	   36
Lorox	   82
Lorsban	    1
Lysoff	    1
                     108

-------
                   —M—

MAA	   46
Macondray	   27
Maintain	   82
malathion 	     1
maleic hydrazide	   82
MAMA	   46
Mancozeb	   36
maneb 	   36
Manebgan	   36
Manesan 	   36
Manzate	   36
Manzeb	   36
Manzin	   36
Marlate 	   14
Matacil	     9
MC2188	     1
MCPA	   27
MCPB	   27
MCPB-Ethyl	   27
MCPCA	   27
MCPP	   27
MeBr	   68
Mecoprop	   27
Mercuram	   36
Merge 823	   46
Merpan	   82
merphos	     1
Mersolite	   77
Mesamate 	   46
Mesurol	     9
Metasystox 	     1
methabenzthiazuron	   82
methamidophos	     1
methane arsonate	   46
methane arsonic acid	   46
Methar	   46
methidathion	     1
methiocarb 	     9
Meth-O-Gas  	   68
methomyl	     9
methoxychlor	   14
methyl bromide	   68
methyl parathion  	     1
metobromuron	   82
                    109

-------
metolachlor	   82
metoxuron	   82
metribuzin	   82
mevinphos	    1
Mezene	   36
Microzul  	   54
Milogard	   82
Miracle	   27
mirex	   14
mitis green	   46
Mobilawn 	    1
Mocap	    1
Mofisal	   31
Monitor	    1
monoammonium methane arsonate	   46
monoammonium methyl arsonate	   46
mono-calcium arsenite	   46
monocrotophos	    1
monolinuron	   82
monosodium methyl arsonate	   46
Monurex	   82
monuron	   82
Morocide	   23
MSMA	   46

                   —N—

nabam	   36
Nabasan	   36
naled	    1
Namate 	   46
naptalam	   23
Naptro	   23
naramycin	   77
Neburex	   82
neburon	   82
Neguvon  	    1
Nemacur	    1
Neoban 	   82
Neo-Pynamin	   42
Nephis	   68
Nespor	   36
Netagrone 600	   27
Nexagan	    1
                     110

-------
Nexion	    1
nicotine sulf ate	   77
Nitrador	   23
Nitrophenolic and nitrocresolic herbicides	   23
Nitropone C  	   23
No Bunt	   82
Nomersan	   36
norbormide	   54
Nudrin	    9
Nuvanol-N	    1

                     —O—

Oftanol  	    1
Ofunack	    1
OMPA	    1
Organochlorines-solid	   14
Organophosphates-cholinesterase-inhibiting ..    1
Orthene	    1
Orthocide	   82
Ortho paraquat CL	   31
Ortho Triox Liquid Vegetation Killer	   19
oryzalin	   82
oxadiazon	   82
oxamyl	    9
oxirane	   68

                     —P—

Paarlan	   82
Paracide	   82
paradichlorobenzene	   82
paraquat 	   31
paraquat dichloride	   31
parathion	    1
paris green	   46
Parzate	   36
Pathclear	   31
Patoran	   82
Pattonex 	   82
PCNB	   82
PCP	   19
PDB	   82
pebulate	   36
                      111

-------
Pencal 	   46
Penchlorol	   19
pendimethalin	   82
Penite	   46
Pennamine D	   27
Penncap-M	    1
penta	   19
Pentac	   14
pentachloronitrobenzene	   82
pentachlorophenol	   19
Pentacon	   19
Penwar	   19
perchlorobenzene	   82
permethrin	   42
Perthane 	   14
Pestmaster (EDB-85)	   68
Phaltan 	   82
phencapton	    1
Phenmad	   77
phenthoate	    1
phenylmercuric acetate 	   77
Phix	   77
phorate	    1
phosalone 	    1
Phosdrin	    1
phosfolan	    1
phosmet	    1
phosphamidon	    1
phosphine	   68
phosphonomethyl glycine	   82
phosphorus	   54
Phostoxin 	   68
Phosvel 	    1
Phosvin	   54
phoxim	    1
phthalthrin 	   42
Phytar 560	   46
Pic-Clor	   68
Picfume	   68
picloram	   82
pindone	   54
pirimicarb	    9
Pirimor 	    9
piperonyl butoxide	   42
                      112

-------
pirimiphos-methyl	     1
Pivacin	    54
Rival	    54
pivaldione	    54
Pivalyn	    54
Planotox	    27
Plantgard	    27
PMA  	    77
PMAS	    77
Polyram M 	    36
Polyram Ultra	    36
Polyram Z	    36
Pomarsol forte	    36
Pomarsol Z Forte	    36
Pounce	    42
Pramitol	    82
Preeglone	    31
Pregard	    82
Premalin	    82
Premerge 3	    23
Priglone	    31
Priltox	    19
Primagram 	    82
Primatol (A, 25E, M, P, Q, or S)	    82
Primextra	    82
Princep	    82
Proban	     1
Prodalumnol Double	    46
Prodaram 	    36
profenofos	     1
profluralin	    82
Profume	    68
Prolate	     1
Promar	    54
promecarb	     9
Prometon	    82
Prometone	    82
Prometrex	    82
prometryn	    82
propachlor	    82
Propanex	    82
propanil	    82
propazine	    82
propenal	    68
propetamphos	     1
                     113

-------
prdpoxur	    9
propylene oxide	   68
propylthiopyrophosphate	    1
prothoate	    1
Prowl	   82
Prozinex	   82
prussic acid	   68
Purina Insect Oil Concentrate	   19
Purivel	   82
Pydrin	   42
Pynamin 	   42
pyrazophos	    1
pyrethrins  	   42
pyrethroids	   42
pyrethrum	   42
pyridaphenthion	    1

                    -Q-

Quilan	   82
quinalphos	    1

                    —R—

Rabon	    1
Rad-E-Cate25	   46
Ramik 	   54
Ramrod	   82
Ramucide	   54
Randox	   82
Rapid	    9
Ratak	   54
Raticate	   54
Ratimus	   54
Ratomet	   54
Ratox	   54
Raviac	   54
Rax	   54
Red Squill	   54
Reglone	   31
Reglox	   31
resmethrin	   42
RH-787 	   54
Rhodia	   27
Rhodia Low Volatile Brush Killer no. 2	   27
                     114

-------
Ripcord	    42
Riselect	    82
Rodenticides	    54
Rodex	    54
Rodine	    54
Ro-Neet	    36
Ronstar	    82
Rosanil	    82
Roundup	    82
Rozol	    54
Rycelan	    82
Ryzelan	    82

                     —S—

Safrotin	     1
Salvo 	27,46
Sarclex	    82
schradan  	     1
Schweinfurt green	    46
SD 15418	    82
Security	    46
Selinon	    23
Semeron	    82
Sencor	    82
Sencoral	    82
Sencorex  	    82
Sevin	     9
Shimmer-ex	    77
Shoxin	    54
siduron	    82
Silvex	    27
Simadex	    82
Simanex	    82
simazine	    82
Simpar	    31
Sinbar	    77
Sinituho	    19
Sinox General	    23
Snip Fly Bands	     9
Sodar	    46
sodium arsenate	    46
sodium arsenite	    46
sodium chlorate 	    77
sodium cyanide	    77
                     115

-------
sodium fluoroacetate	   54
sodium fluoroaluminate 	   82
sodium pentachlorophenate	   19
Soilbrom	   68
Soprabel	   46
Spanone	   77
Spectracide	    1
Spike 	   82
Spontox	   27
Spotrete	   36
Spotton	    1
Spra-cal	   46
Spring-Bak 	   36
Spritz-Hormin/2,4-D	   27
Spritz-Hormit/2,4-D	   27
Sprout Nip	   82
S-Seven 	    1
Stam F34	   82
Stomp	   82
Strel	   82
Strobane 	   14
Strobane-T 	   14
strychnine	   54
Stunt-Man	   82
Subitex	   23
sulfotepp	    1
sulfuryl  fluoride	   68
sulprofos	    1
Sumithion	    1
Super-Caid 	   54
Super Crab-E-Rad-Calar	   46
Super D Weedone	   27
Super Dal-E-Rad-Calar	   46
Supernox	   82
Superormone Concentre	   27
Supracide	    1
Surcopur	   82
Surecide	    1
Surflan	   82
Surpass	   36
Surpur	   82
Sutan	   36
Swat	    1
Synthrin	   42
Systox	    1
                      116

-------
                    —T—

2,4,5-T	   27
Talan	   23
Talbot 	   46
Talon	   54
Tantizon 	   82
Target MSMA	   46
Taterpex	   82
2,4,5-TB	   27
TEA	   82
TCA	   82
TCBA	   82
tebuthiuron	   82
Telone	   68
tempephos	    1
Temik	    9
Tenoran	   82
TEPP	    1
terbacil	   82
terbucarb	   82
terbufos	    1
terbuthylazine	   82
Terbutrex	   82
terbutryn	   82
terpene polychlorinates	   14
Terrachlor	   82
Terraklene	   31
Terrazole	   82
Tersan	   36
Tersan 75	   36
Tersan 1991	   82
Tersan LSR	   36
tetrachlorvinphos	    1
tetraethyl pyrophosphate	    1
tetrafluoron	   82
tetramethrin 	   42
Tetrapom	   36
Thimet	    1
Thiodan	   14
Thioknock	   36
thiometon	    1
Thiophal	   82
Thiophos	    1
Thiotex	   36
thiram 	   36
                     117

-------
Thiramad	   36
Thirasan	   36
Thiuramin	   36
Thylate	   36
Tiezene	   36
Tiguvon	    1
Tillam	   36
Tirampa	   36
TMTDS	   36
Tolban	   82
Tolkan	   82
Tolurex 	   82
Tomilon	   82
Tomorin	   54
Topitox	   54
Torak	    1
Tordon	   82
Tormona	   27
TotaCol	   31
Toxakil	   14
toxaphene	   14
Tox-Hid	   54
2,4,5-TP	   27
Trametan	   36
Transamine	   27
Trans-Vert	   46
Treflan	   82
triallate	   36
Triasyn	   82
triazophos	    1
Tribac	   82
Tri-ban	   54
Tribunil	   82
Tributon 	   27
Tricarbamix Z	   36
trichlorfon	    1
trichloroacetic acid	   82
trichloronate	    1
2,4,5-trichlorophenoxyacetic acid 	   27
2,3,6 trichlorophenylacetic acid	   27
Tri-Clor	   68
trifluralin	   82
Trifocide	   23
Trifungol	   36
                     118

-------
Trimangol ...............................   36
Trinoxol .................................   27
Trioxone ................................   27
Tripomol ................................   36
Triscabol ................................   36
Trithion .................................    1
Tritoftorol ...............................   36
Tuads ...................................   36
Tubothane ...............................   36
Tumbleaf ................................   77
Tupersan ................................   82

                    — U—

U 46 ....................................   27
U 46 Special ..............................   27
Unicrop CIPC ............................   82
Unicrop DNBP ...........................   23
Unidron .................................   82
Uragan ..................................   82
Urox (B, D, or Hx) ........................   82
Usol Cabin Oil  ...........................    4
Vacor Rat Killer ..........................   54
Vancide FE-95 ............................   36
Vancide Maneb 80 ........................   36
Vancide MZ-96 ...........................   36
Vapona .................................    1
Vectal SC ................................   82
Veg-I-Kill ................................   19
Venzar ..................................   82
Veon 245 ................................   27
Vernam .................................   36
vernolate ................................   36
Vertac Dinitro Weed Killer .................   23
Verton 2D ...............................   27
Verton2T ...............................   27
Vikane ..................................   68
Visko-Rhap ..............................   27
Visko-Rhap LV 2D-2T .....................   27
Vonduron ...............................   82
Vydate ..................................    9
                    119

-------
                      — w—

   Warbex .................................     1
   warfarin .................................    54
   Warfarin Plus ............................    54
   Weed-B-Gon .............................    27
   Weed-E-Rad .............................    46
   Weed-E-Rad 360 ..........................    46
   Weed-E-Rad DMA Powder .................    46
   Weed-Hoe ...............................    46
   Weed-Rhap ..............................    27
   Weed Tox  ...............................    27
   Weedar ..................................    27
   Weedol ..................................    31
   Weedone ................................    27
   Weedtrine-D .............................    31
   Weedtrol ................................    27
   white arsenic .............................    46
   Wood Preserver  ..........................    19
   Wood Tox 140 ............................    19
   Yasoknock ...............................    54
   yellow phosphorus ........................    54

                       — Z—

   Z-C Spray ...............................    36
   Zebtox ..................................    36
   Zerlate ..................................    36
   Zincmate ................................    36
   zinc phosphide  ...........................    54
   Zinc-Tox ................................    54
   zineb ....................................    36
   Zinosan .................................    36
   ziram ...................................    36
   Ziramvis .................................    36
   Zirasan 90 ...............................    36
   Zirberk ..................................    36
   Zirex90 .................................    36
   Ziride ...................................    36
   Zolone ..................................     1
   zoocoumarin .............................    54

JJ.U.S. GOVERNMENT PRINTING OFFICE. 1 98 2 -3 5 4 - 7 5 0 / 8 2 6 6
                       120

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U.O. fj^'i'-op.n'?:-,:.:-,!  ProlGction Agency
R .-7:0,5 V,  ! if-,-ary
230 S'y-th jea:born  Street     x
Chicago, ijlir.ois  .60604;  ^^^

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