Here's the beginnings of  some info on pesticides.  The first subgroup is
those which have a neurotoxic effect of twitching.  These particular
pesticides are grouped under Carbamate Pesticides.  The descriptions speak
for themselves.  I also can't help but wonder  at the terror of the animals
on whom these chemicals  were surely first tested...
 
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Forwarded message:
From:   [log in to unmask] (Tebay, Wendy)
To:     [log in to unmask] (athome)
Date: 95-06-26 16:55:26 EDT
 
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From: Tebay, Wendy on Mon, Jun 26, 1995 3:08 PM
Subject: twitching - carbamate pesticides
To: meme
File(s): Commercial Products; Confirmation of N-Methyl Carbam;
Symptoms and Signs of Poisoning; Toxicology; Treatment of EXTERNAL
N-Methyl ; Treatment of N-Methyl Carbamate
 
From: Tebay, Wendy on Mon, Jun 26, 1995 2:40 PM
Subject: twitching - carbamate pesticides
To: myself
File(s): Commercial Products; Confirmation of N-Methyl Carbam;
Symptoms and Signs of Poisoning; Toxicology; Treatment of EXTERNAL
N-Methyl ; Treatment of N-Methyl Carbamate
 
 
 
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Commercial Products
 
Highly toxic*: aldicarb+ (Temik), oxamyl (Vydate L, DPX 1410), methiocarb
(Mesurol, Draza), carbofuran (Furadan, Curaterr, Crisfuran), isolan
(Primin), methomyl (Lannate, Nudrin, Lanox), formetanate (Carzol),
aminocarb (Matacil), cloethocarb (Lance), bendiocarb (Ficam, Dycarb,
Multamat, Niomil, Tattoo, Turcam).
 
Moderately toxic*: dioxacarb (Elocron, Famid), promecarb (Carbamult),
bufencarb (metalkamate, Bux), propoxur (aprocarb, Baygon), trimethacarb
(Landrin, Broot), pirimicarb (Pirimor, Abol, Aficida, Aphox, Fernos,
Rapid), dimetan (Dimethan), carbaryl (Sevin, Dicarbam), isoprocarb
(Etrofolan, MIPC).
 
*Compounds 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
50mg/kg.
 
+These organophosphates are systemic; they are taken up by the plant and
translocated into foliage and sometimes into the fruit.
 
 
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Confirmation of N-Methyl Carbamate Absorption
 
Unless a substantial amount of N-methyl carbamate has been absorbed and a
blood sample is taken within an hour or two, it is unlikely that blood
cholinesterase activities will be found depressed. Even under the above
circumstances, a rapid test for enzyme activity must be used to detect an
effect, because enzyme reactivation occurs in vitro as well as in viro. See
  Table 1 in the Organophosphate Insecticides section for methods of
measurement of blood cholinesterase activities, if circumstances appear to
warrant performance of the test.
 
Absorption of some N-methyl carbamates can be confirmed by analysis of
urine for unique metabolites: alphanaphthol from carbaryl, isopropoxyphenol
from propoxur, carbofuran phenol from carbofuran, aldicarb sulfone and
nitrile from aldicarb. Unfortunately, analyses for these excretion
end-products are complex and not generally available.
 
 
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Symptoms and Signs of Poisoning
 
MALAISE, MUSCLE WEAKNESS, DIZZINESS, and SWEATING are commonly reported
early symptoms of poisoning. Headache, diarrhea, nausea, vomiting,
abdominal pain, and salivation are often prominent. Miosis, incoordination,
and slurred speech are reported. Dyspnea, bronchospasm, and chest tightness
may eventuate in PULMONARY EDEMA. Blurred vision, muscle twitching, and
spasms characterize some cases. Severe neurologic manifestations, including
convulsions, are less common than in organophosphate poisonings.
Bradycardia occurs infrequently. Poison-ings by N-methyl carbamates tend to
be of shorter duration than poisonings by organophosphates, but they are
not easily differentiated from organophosphate poisoning in the acute phase
in the absence of an accurate exposure history.
 
 
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Toxicology
 
The N-methyl carbamate esters cause reversible carbamylation of
acetylcholinesterase enzyme, allowing accumulation of acetylcholine, the
neuromediator substance, at parasympathetic neuroeffector junc-tions
(muscarinic effects), at skeletal muscle myoneural junctions and autonomic
ganglia (nicotinic effects), and in the brain (CNS effects). The
carbamyl-acetylcholinesterase combination dissociates more readily than the
phosphoryl-acetylcholinesterase complex produced by organo-phosphate
compounds. This liability has several important consequenc-es: 1) it tends
to limit the duration of N-methyl carbamate poison-ings, 2) it accounts for
the greater span between symptom-producing and lethal doses than exists in
the case of most organophosphate compounds, and 3) it frequently
invalidates the measurement of blood cholinesterase activity as a
diagnostic index of poisoning (see
  Confirmation of Absorption). N-methyl carbamates are absorbed by
inhalation, ingestion, and some by skin penetration. Dermal absorption of
particular compounds (notably carbofuran) is very slight. N-methyl
carbamates are hydrolyzed enzymatically by the liver and the degradation
products are excreted by the liver and kidneys.
 
At cholinergic nerve junctions with smooth muscle and gland cells, high
acetylcholine concentration causes muscle contraction and secretion,
respectively. At skeletal muscle junctions, excess acetylcholine may be
excitatory (cause muscle twitching), but may also weaken or paralyze the
cell by depolarizing the end-plate. In the brain, elevated acetylcholine
concentrations may cause sensory and behavioral disturbances,
incoordination, and depressed motor function (rarely seizures), even though
N-methyl carbamates do not penetrate the central nervous system very
efficiently. Depression of respiration combined with pulmonary edema is the
usual cause of death from poisoning by N-methyl carbamate compounds.
 
 
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Treatment of EXTERNAL N-Methyl Carbamate Insecticide Poisoning
 
CAUTION: Persons attending the victim should avoid direct contact with
heavily contaminated clothing and vomitus. Wear rubber gloves while washing
pesticide from skin and hair.
 
1. Insure that a CLEAR AIRWAY exists by aspiration of secretions, if
necessary. Administer OXYGEN by mechanically assisted pulmonary ventilation
as needed. Improve tissue oxygenation as much as possible before
administering atropine, so as to minimize the risk of ventricular
fibrillation. Support pulmonary ventilation mechanically as long as
respiratory drive is depressed.
 
2. Administer ATROPINE SULFATE intravenously, or intramuscularly, if
intravenous injection is not possible. The objective of atropine antidotal
therapy is to antagonize the effects of excessive concentrations of
acetylcholine at end-organs having muscarinic receptors. Depending on the
severity of poisoning, doses of atropine ranging from small to very large
may be required. Atropine does not reactivate the cholinesterase enzyme or
accelerate excretion or breakdown of pesticide. Recrudescence of poisoning
may occur if tissue concentrations of toxicant remain high when the effect
of atropine wears off. Atropine is effective against muscarinic
manifestations, but it is ineffective against nicotinic actions,
specifically muscle weakness and twitching, and respiratory depression.
Despite these limitations, atropine is often a lifesaving agent in N-methyl
carbamate poisonings. Favorable response to a test dose of atropine (1 mg
in adults, 0.01 mg/kg in children under 12 years) given intravenously can
help differentiate poisoning by anticholinesterase agents from other
conditions. In MODERATELY SEVERE poisoning (hypersecretion and other
end-organ manifestations without central nervous system depression) the
following dosage schedules have proven effective:
 
Dosage of ATROPINE: Adults and children over 12 years: 0.4 - 2.0 mg
repeated every 15 minutes until atropinization is achieved: tachycardia
(pulse of 140 per minute), flushing, dry mouth, dilated pupils. Maintain
atropinization by repeated doses for 2-12 hours or longer depending on
severity of poisoning. Rales in the lung bases nearly always indicate
inadequate atropinization. Miosis, nausea, bradycardia, and other
cholinergic manifestations also signal the need for more atropine.
 
Children under 12 years: 0.05 mg/kg body weight, repeated every 15 minutes
until atropinization is achieved. Maintain atropinization with repeated
doses of 0.02-0.05 mg/kg body weight.
 
SEVERELY POISONED individuals may exhibit remarkable tolerance to atropine;
two or more times the dosages suggested above may be needed. Reversal of
muscarinic manifestations, rather than a specific dosage, is the object of
atropine therapy. However, prolonged intensive intravenous administration
of atropine sometimes required in organophosphate poisonings is rarely
needed in treating carbamate poisoning.
 
Note: Persons not poisoned or only slightly poisoned by N-methyl carbamates
may develop signs of atropine toxicity from such large doses. FEVER, muscle
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, while the
severity of poisoning is reevaluated.
 
3. Save a URINE SAMPLE for metabolite analysis if there is need to identify
the agent responsible for poisoning. Also, urine metabolite measurement can
be used to follow the progress of carbamate disposition.
 
4. Pralidoxime is probably of little value in N-methyl carbamate
poisonings. Its use is usually unnecessary because atropine alone is
effective, and in some cases of carbamate poisoning, pralidoxime
administration has been followed by severe reactions, even sudden death.
Both animal studies and experience in human poisonings CONTRA-INDICATE USE
OF PRALIDOXIME IN CARBARYL POISONINGS. In mixed poisonings involving
organophosphates, or in poisonings by unidentified anticholinesterase
agents which produce significant nicotinic effects, cautious administration
of pralidoxime may have to be considered (see
  Organophosphate Insecticides, Treatment, Section 4).
 
5. In patients who have been poisoned by carbamate pesticide contamination
of skin, clothing, hair, and/or eyes, DECONTAMINATION MUST PROCEED
CONCURRENTLY with whatever resuscitative and antidotal mea-sures are needed
to preserve life. Contamination of the eyes should be removed by flushing
with copious amounts of clean water. For asymptomatic individuals who are
alert and physically able, a prompt shower and shampoo may be appropriate,
provided the patient is carefully observed to insure against sudden
appearance of poisoning. If there are any indications of weakness, ataxia,
or other neurologic impairment, clothing should be removed and a complete
bath and shampoo given while the victim is recumbent, using copious amounts
of soap and water. Attendants should wear rubber gloves. Surgical green
soap is excellent for this purpose, but ordinary soap is about as good. The
possibility of pesticide sequestered under fingernails or in skin folds
should not be overlooked. CONTAMINATED CLOTHING should be promptly removed,
bagged, and not returned until it has been thoroughly laundered.
Contaminated leather shoes should be discarded. The possibility that
pesticide has contaminated the inside surfaces of gloves, boots, and head
gear should be kept in mind.
 
 
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Treatment of N-Methyl Carbamate Poisoning by INGESTION
 
CAUTION: Persons attending the victim should avoid direct contact with
heavily contaminated clothing and vomitus. Wear rubber gloves while washing
pesticide from skin and hair.
 
1. Insure that a CLEAR AIRWAY exists by aspiration of secretions, if
necessary. Administer OXYGEN by mechanically assisted pulmonary ventilation
as needed. Improve tissue oxygenation as much as possible before
administering atropine, so as to minimize the risk of ventricular
fibrillation. Support pulmonary ventilation mechanically as long as
respiratory drive is depressed.
 
2. Administer ATROPINE SULFATE intravenously, or intramuscularly, if
intravenous injection is not possible. The objective of atropine antidotal
therapy is to antagonize the effects of excessive concentra-tions of
acetylcholine at end-organs having muscarinic receptors. Depending on the
severity of poisoning, doses of atropine ranging from small to very large
may be required. Atropine does not reactivate the cholinesterase enzyme or
accelerate excretion or breakdown of pesticide. Recrudescence of poisoning
may occur if tissue concentrations of toxicant remain high when the effect
of atropine wears off. Atropine is effective against muscarinic
manifestations, but it is ineffective against nicotinic actions,
specifically muscle weakness and twitching, and respiratory depression.
Despite these limitations, atropine is often a lifesaving agent in N-methyl
carbamate poisonings. Favorable response to a test dose of atropine (1 mg
in adults, 0.01 mg/kg in children under 12 years) given intravenously can
help differentiate poisoning by anticholinesterase agents from other
conditions. In MODERATELY SEVERE poisoning (hypersecretion and other
end-organ manifestations without central nervous system depression) the
following dosage schedules have proven effective:
 
Dosage of ATROPINE: Adults and children over 12 years: 0.4 - 2.0 mg
repeated every 15 minutes until atropinization is achieved: tachycardia
(pulse of 140 per minute), flushing, dry mouth, dilated pupils. Maintain
atropinization by repeated doses for 2-12 hours or longer depending on
severity of poisoning. Rales in the lung bases nearly always indicate
inadequate atropinization. Miosis, nausea, bradycardia, and other
cholinergic manifestations also signal the need for more atropine.
 
Children under 12 years: 0.05 mg/kg body weight, repeated every 15 minutes
until atropinization is achieved. Maintain atropinization with repeated
doses of 0.02-0.05 mg/kg body weight.
 
SEVERELY POISONED individuals may exhibit remarkable tolerance to atropine;
two or more times the dosages suggested above may be needed. Reversal of
muscarinic manifestations, rather than a specific dosage, is the object of
atropine therapy. However, prolonged intensive intravenous administration
of atropine sometimes required in organophosphate poisonings is rarely
needed in treating carbamate poisoning.
 
Note: Persons not poisoned or only slightly poisoned by N-methyl carbamates
may develop signs of atropine toxicity from such large doses. FEVER, muscle
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, while the
severity of poisoning is reevaluated.
 
3. Save a URINE SAMPLE for metabolite analysis if there is need to identify
the agent responsible for poisoning. Also, urine metabolite measurement can
be used to follow the progress of carbamate disposition.
 
4. Pralidoxime is probably of little value in N-methyl carbamate
poisonings. Its use is usually unnecessary because atropine alone is
effective, and in some cases of carbamate poisoning, pralidoxime
administration has been followed by severe reactions, even sudden death.
Both animal studies and experience in human poisonings CONTRA-INDICATE USE
OF PRALIDOXIME IN CARBARYL POISONINGS. In mixed poisonings involving
organophosphates, or in poisonings by unidentified anticholinesterase
agents which produce significant nicotinic effects, cautious administration
of pralidoxime may have to be considered (see
  Organophosphate Insecticides, Treatment, Section 4).
 
5. IF N-METHYL CARBAMATE HAS BEEN INGESTED in a quantity probably
sufficient to cause poisoning, the stomach and intestine must be emptied,
and measures taken to limit absorption from the gut. Procedures for
accomplishing this are essentially the same as those used in
organophosphate poisonings (see
  Organophosphate Insecticides, Treatment, Section 5).
 
6. OBSERVE PATIENT CLOSELY for at least 24 hours to insure that symptoms
(sweating, visual disturbances, vomiting, diarrhea, chest and abdominal
distress, and sometimes PULMONARY EDEMA) do not recur as atropinization is
withdrawn. As the dosage of atropine is reduced over time, check the lung
bases frequently for rales. If rales are heard, or if there is a return of
miosis, sweating or other signs of poisoning, atropinization must be
re-established promptly.
 
7. Furosemide may be considered for relief of pulmonary edema if rales
persist in the lungs even after full atropinization. It should not be
considered until the maximum effect of atropine has been achieved. Consult
package insert for dosage and administration.
 
8. Particularly in poisonings by large doses of N-methyl carbamates,
MONITOR PULMONARY VENTILATION carefully, even after recovery from
muscarinic symptomatology, to forestall respiratory failure.
 
9. In severely poisoned patients, MONITOR CARDIAC STATUS by continuous ECG
recording.
 
10. The following drugs are contraindicated in nearly all N-methyl
carbamate poisoning cases: morphine, theophylline, phenothiazines, and
reserpine. Adrenergic amines should be given only if there is a specific
indication, such as marked hypotension.
 
11. Persons who have been clinically poisoned by N-methyl carbamate
pesticides should not be re-exposed to cholinesterase-inhibiting chemicals
until symptoms and signs have resolved completely.
 
12. DO NOT ADMINISTER ATROPINE PROPHYLACTICALLY to workers exposed to
N-methyl carbamate pesticides. Prophylactic dosage may mask early symptoms
and signs of carbamate poisoning and thus allow the worker to continue
exposure and possible progression to more severe poisoning. Atropine itself
may enhance the health hazards of the agricultural work setting: impaired
heat loss due to reduced sweating and impaired ability to operate
mechanical equipment due to blurred vision (mydriasis).
 
 
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