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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... --------------------- Forwarded message: From: [log in to unmask] (Tebay, Wendy) To: [log in to unmask] (athome) Date: 95-06-26 16:55:26 EDT --PART.BOUNDARY.claven.06aa.2fef1e69.0001 Content-Type: text/plain; charset=us-ascii 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 --PART.BOUNDARY.claven.06aa.2fef1e69.0001 Content-Type: text/plain; charset=us-ascii 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. --PART.BOUNDARY.claven.06aa.2fef1e69.0001 Content-Type: text/plain; charset=us-ascii 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. --PART.BOUNDARY.claven.06aa.2fef1e69.0001 Content-Type: text/plain; charset=us-ascii 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. --PART.BOUNDARY.claven.06aa.2fef1e69.0001 Content-Type: text/plain; charset=us-ascii 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. --PART.BOUNDARY.claven.06aa.2fef1e69.0001 Content-Type: text/plain; charset=us-ascii 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. --PART.BOUNDARY.claven.06aa.2fef1e69.0001 Content-Type: text/plain; charset=us-ascii 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). --PART.BOUNDARY.claven.06aa.2fef1e69.0001--