www.PharmaDost.info 28 Pesticides Pesticides are compounds that are used to kill pests which may Chlorfenvinphos, Chlorpyriphos, Demeton, Diazinon, be insects, rodents, fungi, nematodes, mites, ticks, molluscs, Dichlorvos, Dimethoate, Disulfoton, Ediphenphos, Ethion, and unwanted weeds or herbs. Fenitrothion, Fensulfothion, Fenthion, Fonophos, Formothion, 1. Insecticides Methyl Parathion, Mevinphos, Monocrotophos, Oxydemeton 2. Rodenticides Methyl, Phenthoate, Phorate, Phosphamidon, Quinalphos, 3. Fungicides TEPP, and Thiometon. 4. Nematicides The following compounds are moderately toxic (LD50: 5. Acaricides 501 to 5000 mg/kg), or slightly toxic (LD50: more than 5000 6. Molluscicides mg/kg)— 7. Herbicides Abate, Acephate, Coumaphos, Crufomate, Famphur, 8. Miscellaneous Pesticides. Glyphosate, Malathion, Phenthoate, Primiphos Methyl, Ronnel, Temephos, Triazophos, and Trichlorphon. Even in cases where treatment was begun early with atropine INSECTICIDES and oximes, mortality in organophosphate poisoning is gener- These are compounds which kill or repel insects and related ally to the extent of 7 to 12%. species. For example, organophosphates, carbamates, organo- chlorines, pyrethrum and its derivatives (pyrethroids). Mode of Action ■■ Organophosphates are powerful inhibitors of acetylcho- Organophosphates (Organophosphorus linesterase which is responsible for hydrolysing acetyl- Compounds) choline to choline and acetic acid after its release and completion of function (i.e. propagation of action poten- It is true that calling these compounds “organophosphates” tial). As a result, there is accumulation of acetylcholine is not correct, and they should be referred to as “organophos- with continued stimulation of local receptors and eventual phorus compounds”. But, “organophosphates” is such an irre- paralysis of nerve or muscle. sistibly compact expression. So, with apologies to the purists, ■■ Although organophosphates differ structurally from this term will be used for the sake of convenience in this book, acetylcholine, they can bind to the acetylcholinesterase even if it raises some hackles. molecule at the active site and phosphorylate the serine Organophosphates are among the most popular and most moiety. When this occurs, the resultant conjugate is widely used insecticides in India. Table 28.1 lists common infinitely more stable than the acetylcholine-acetylcho- varieties along with respective brand names. linesterase conjugate, although endogenous hydrolysis does occur. Depending on the amount of stability and Physical Appearance charge distribution, the time to hydrolysis is increased. These compounds are available as dusts, granules, or liquids. Phosphorylated enzymes degrade very slowly over days Some products need to be diluted with water before use, and to weeks, making the acetylcholinesterase essentially some are burnt to make smoke that kills insects. inactive. ■■ Once the acetylcholinesterase is phosphorylated, over the Usual Fatal Dose next 24 to 48 hours an alkyl group is eventually lost from Toxicity Rating*: the conjugate, further exacerbating the situation. As this The following compounds are extremely toxic (LD50: 1 to occurs, the enzyme can no longer spontaneously hydrolyse 50 mg/kg), or highly toxic (LD50: 51 to 500 mg/kg)— and becomes permanently inactivated. * Partly as per the Insecticide Rules, 1971. www.PharmaDost.info Table 28.1: Common Organophosphate Pesticides 387 Generic Name Brand Name Acephate Acemil, Acet, Acetaf, Agrophate, Asataf, Dhanraj, Hilfate, Hythane, Orthene, Ortran, Sicothene, Starthene, Torpedo Anilofos Aniloguard, Arozin, Dhanudan Chlorfenvinphos Birlane, Chlorfenvinphos Chlorpyriphos Agrofas 20, Calban, Chlorofos 20, Classic, Coroban 20, Cyfos, Daspan, Dermite, Dermot, Dhanuchlor, Dhanvan, Dursban, Force, Gilphos, Hildan, Hyban 20, Lasso, Lethal, Nuchlor, Phors 20, Primaban, Radar, Roban, Ruban 20, Sicobon, Strike, Suchlor, Tafaban, Tefaban, Tricel Cyclopyriphos Duramet Demeton methyl Metasostox Diazinon Agroziron, Basudin, Bazanon, Ditaf, Suzinon, Tik 20, Zionosul 50 Dichlorvos Agrovan 76, Agro 76 EC, Bangvas, Cockroach killer, Dash, DDVP, Divap, Divisol, Madhuvun, Nuvan, Nuvasul 76, Paradeep, Savious,Vapona, Vapox, Vegfru Dimethoate Agrodimet 30, Agromet 30EC, Bangor 30EC, Corothate, Cropgor 30, Cycothate, Cygon, Devigor, Dimethoate, Dimex, Entogor, Hexagor, Hygro 30, Klex Dimethoate, Krogar, Methovip, Milgor, NB Dimethoate, Paragor, Parrydimate, Primogor, Ramgor, Rogor, Tagor, Tara 909, Tara Dimex Sulgor, Tka 30, Unigor, Vijaygor, Vikagor Chapter 28 Pesticides Ediphenphos Hinosan, Nukil Ethion Challenge, Demite, Dhanumit, Dhan-unit, Ethion, Ethione, Ethiosul 50, Fosmit, Mit 505, Mitex, Miticil, Mitvip, Phostech, RP-thion, Tafethion, VegFru Fosmite, Volathin Fenitrothion Accothion, Agrothion, Danathion, Fenicol, Fenitrosul 50, Folithion, Sicothoin, Sumithion, Vikathion Fenthion Agrocidin, Baytex, Fenthiosul, Labaycid, Lebaycid, Lebazate Formothion Anthio Iprobenfos Tagkite Malathion Agromal, Bharat, Celthion, Cythion, Dhuthione, Finit, Himalaya, Kathion, Licel, Madhuthione, Maladan, Maladol, Malafil, Malathione, Malazene, Primothion, Sulmathion, VegFru Malatox Methyl Parathion Ant repellant,* Agropara, Agrotex, Ekatox, Folidol, Folidol-M, Harvest Kempar, Kilex-M, Metacid, Metapar, Metpar, Milphor, Paracrop, Paradol, Parahit, Parataf, VegFru Paratox Monocrotophos Atom, Azodrin, Balwan, Corophos, Entophos, Hilcrone, Luphos, Macrophos, Microphos, Monocil, Monochrovin, Monocrome, Monocron, Monocrown, Monocyl, Monodhan, Monokem, Monostar, Monovip, Nuvacron, Sicocil, Sufos, Unicron Oxydemeton Dhanuciytax, Hexasystox, Hymox, Knock Out, Metaciyta, Metasystox Methyl Phenthoate Agrofen, Delsan, Elsan, Guard, Phentox Phorate Anuphorate, Croton, Dhan, Dhang, Dragnet, Fortan, Glorat, Luphate, Phorachem, Phoratox, Phrotax, Thimate 10G, Thimet, VegFru Foratox, Vijayphor, Volphor Phosalone Zolone Phosmet Phosmite Phosphamidon Agromidon 85, Bangdon 85, Bilcran 85, Cildon, Delphamidon, Demacron, Demecron, Dimecron, Directon, Eagle, Entecron 85, Hildon, JK Midon, Midon, Phamidon, Phosul, Rilon, Sudon, Sumidon, Vimidon Phoxim Phoxin Primiphos Methyl Acetellic Profenfos Carina, Curacrone, Polytrine, Profex Quinalphos Agroquin, Agroquinol, Bayrusil, Chemlox, Coroqueen, Dhanulux, Dyalux, Ekalux, Fact, Flash, Kilex, Quenguard, Quick, Quinal, Quinaltof, Quinseed 25, Silofos, Solux, Vazara, Vikalux Temephos Abate 50EC, Farmico’s Thiometon Agrothimeton, Ekatin (Morphothion) Triazophos Hostathion, Sutathion, Triphos, Truso Trichlorphon Dipterex * Caution : The same brand name may refer to lindane fatiguability. and –– Exposure to organophosphate vapours rapidly have been reported even following the cutaneous produces symptoms of mucous membrane and absorption of organophosphate. plasma and hepatic carboxyles. Tachycardia is also common. Death usually hydrolases such as chymotrypsin. PVCs. respiratory muscles. tremor. other causes may contribute including hypertension. of death. –– Miosis while being a characteristic feature. Neuropathy caused by inhibition of NTE secretions. nausea. Acute Poisoning: muscle fasciculations. increased salivation. Acute respiratory insufficiency. and GU mucosa. Hypertension can occur in up to 20 –– Patients with OP poisoning and QTc prolongation per cent of patients. as well as depression of central terases.g.or brady- manifestations): Common manifestations include cardia. and urinary incontinence. tachycardia. ST-T wave changes. may not cough. inhalational. bradycardia. are more likely to develop respiratory failure and tricular conduction delays. organophosphates exert cases of paediatric organophosphate poisoning. such to any combination of CNS depression. and sweating. transconjunctival. –– Nicotinic Effects (autonomic ganglionic and –– While respiratory failure is the commonest cause somatic motor effects): Fasciculations. are more likely to develop respiratory failure and Cardiac arrhythmias and conduction defects have have a worse prognosis than patients with normal been reported in severely poisoned patients. respiratory as neurotoxic esterase. butyrlcholinesterase results from respiratory failure due to weakness of (pseudocholinesterase). c. It is more . can be remembered by the acronym SLUDGE –– Ocular exposure can result in systemic toxicity. and convulsions. abdominal cramps. ECG QTc intervals. and/or QT solvents may cause potentially fatal lipoid pneu- intervals. Acute lung injury (non-cardiogenic ■■ It has been proposed that delayed peripheral neuropathy pulmonary oedema) is a common manifestation of caused by organophosphates is due to phosphorylation severe poisoning. weakness. there may be either tachy. Excessive systemic therapy. significant concentrations. necessity for of certain compounds (e. paraoxonases. Some of these tion. drowsi. 1. vomiting. Cholinergic Excess— level of consciousness. ataxia. bronchoconstriction with wheezing and dyspnoea. and atrial fibrillation. hypo. Bradycardia and upper airway irritation and bronchospasm. Blurred vision may persist for several months. phosphate poisonings. and paralysis. bronchospasm. Muscle hypoxia due to seizures. prolongation of the PR. due of some esterase(s) other than acetylcholinesterase. hypotension. also known as neuropathy target paralysis. Other points of importance— ■■ Manifestations usually begin within a few minutes to few –– The Peradeniya Organophosphorus Poisoning hours. renal failure. all 16 388 powerful inhibitory action over other carboxylic ester children developed stupor and/or coma. –– Musscarinic Effects (hollow organ parasympathetic –– In a given case. or increased bronchial esterase (NTE). CNS Effects—Restlessness. and diarrhoea are common muscarinic effects. slurred speech. can cause persistent miosis in spite of appropriate Gastrointestinal distress and Emesis. very often present. Diarrhoea. headache. It —Salivation. bradycardia. mechanical ventilation.PharmaDost. Patients with OP poisoning who abnormalities may include sinus bradycardia or develop PVCs (premature ventricular contractions) tachycardia. pine (or scopolamine) instillation. fenthion. ARDS. QRS. respiratory drive. and a. each on a 0 to 2 scale: miosis. pulmonary oedema.or hypertension. idioventricular rhythm. Lacrimation. parathion). followed hypotension occur following moderate to severe by systemic symptoms if patients are exposed to poisoning. www. and hence treatment should not tion. weakness. ventricular tachycardia or fibrillations. lacrima. monitis. and the required total atro- pine dose over the first 24 hours. but may be delayed upto 12 hours or more in the case (POP) Scale is predictive of death. hyperthermia. atrioventricular and/or intraven.info ■■ Apart from acetylcholinesterase. diarrhoea. is the main cause of death in acute organo- may develop 2 to 5 weeks after an acute poisoning. be apparent in the early stages.Metabolic acidosis has occurred in severe poisonings. have a higher mortality rate than patients without multiform premature ventricular extrasystoles. be delayed if there is absence of pupillary constric- miosis. In a review of 16 esterase inhibition and muscle necrosis. A characteristic kerosene-like Toxicokinetics odour is often perceptible in the vicinity of the patient ■■ Organophosphates can be absorbed by any route including since the solvent used in many organophosphate insec- Section 8 Hydrocarbons and Pesticides transdermal. vomiting. and fasciculations are and hepatic failure. and through direct injection. torsades de –– Aspiration of preparations containing hydrocarbon pointes. and other non-specific proteases. respirations. across the GI ticides is some petroleum derivative such as aromax. –– An Intermediate Syndrome sometimes occurs one to ness. Urination. delirium. and may necessitate topical atro- salivation. very common. b. This scale rates Clinical (Toxic) Features 5 clinical variables. four days after poisoning due to long-lasting cholin- Coma supervenes in the later stages. In fact mydriasis is abdominal cramps. the pulmonary oedema is an infrequent. atrophy of distal limb muscles. Other classical signs of organophosphate Paralytic signs include inability to lift the neck or sit poisoning such as miosis. coma. respiratory paralysis. logical. gait disorders. Some it sets in. and proximal limb muscles. but severe. fenitrothion. causing burning or tingling. and noted that the standard hen neurotoxic esterase thion. It may be due to inadequate treatment of less than 8/minute are not unusual. dimethoate. significant hypoxia. –– A Delayed Syndrome sometimes occurs 1 to 4 2. Chapter 28 Pesticides dose and route of exposure. . dichlorvos. merphos. Gurgling may occur due to accumulation that intermediate syndrome may develop as a result of pulmonary oedema fluid. diazinon. Depression of cholinesterase activity: with haemorrhagic pancreatitis which can termi. ethyl para. www. flaccidity. and is characterised by flaccid weakness and especially those who are engaged in pesticide spraying of crops. trichloronate. fasciculations. ophthalmoparesis.Normal cholinesterase level is based on popula- cog-wheel rigidity. and choreoathetosis. and TOCP (tri-ortho- cresyl phosphate). –– It is important to note that children may have tophos. poisoning than adults. Respiratory rates of and death. CNS Effects : drowsiness. (primarily proximal). trichlorofon. methamidophos. it indicates organophosphate toxicity. and weakness. difficulty swallowing. methyl parathion. mala. A mixed sensory-motor neuropathy usually skin. isofenphos. –– Bradypnoea sometimes occurs. The following are the main features— begins in the legs. fenthion. mipafox. Resolution managed by supportive measures. or psychiatric syndromes. a. weak- weakness. Snoring prior to the acute episode especially involving subtherapeutic fatal overdose has been reported and is likely due administration of oximes or inadequate assisted to a failure to maintain the patency of the upper ventilation. confusion. Organophosphates that have been associated with One author has termed these “chronic organophos- delayed neuropathy in humans include chlorophos. Main features include muscle poisoned by organophosphate or carbamate weakness and paralysis characterised by motor compounds. -.info common with chlorpyrifos. pink frothy sputum. Diagnosis –– Parathion ingestion is sometimes associated 1. the intermediate syndrome will have to be patients require mechanical ventilation. since it does not of symptoms usually occurs rapidly with supportive respond to oximes or atropine. Severe cases progress to b. (COPND) chlorpyrifos. stupor. RBC Haemoperfusion is said to be beneficial if this occurs. Sheep Farmer’s Disease : psychiatric manifestations The nerve damage of organophosphate-induced encountered in sheep farmers involved in long-term delayed neuropathy is frequently permanent. Once bilateral fluffy infiltrates on chest X-ray. monocro. the major signs and symptoms were cranial nerve palsies. either oximes or atropine. muscle cramps. These tion estimates and there is a wide distribution in effects began 4 to 40 days after acute OP poisoning the definition of normal. anxiety. dipterex. irritability. malathion. –– Disadvantages— ramidal effects including dystonia. phate-induced neuropsychiatric disorder. dyspnoea. the chemical structure complication of overdose and is generally abrupt in of the organophosphates. Polyneuropathy: paraesthesias. different predominant signs of organophosphate 389 ethyl parathion. mechanism appears to involve phosphorylation of d. In one study of children thion. such as fenthion have rarely developed extrapy. within hours to 1 to 2 days. parathion. then a. or spasticity and Route of exposure is usually inhalation or contamination of ataxia. and enhance elimination of the organophosphates. fenthion. and trichlorfon.PharmaDost. Manifestations include therapy. areflexia. It usually occurs as an occupational hazard in agriculturists. limb weakness gastrointestinal symptoms were infrequent. Organophosphate poisoning has been associated with esterases in peripheral nervous tissue and results a variety of subacute or delayed onset chronic neuro- in a “dying back” pattern of axonal degeneration. This syndrome also does not respond to ness. A person with a “high and spontaneously resolved over 1 to 4 weeks in normal” level may become symptomatic with survivors. test is not sufficient to detect which OPs can cause this mecarbam. complete paralysis. excessive salivation and lacrimation. impaired respiration and death. Non-cardiogenic of several factors: inadequate oxime therapy. weakness of neck flexor and CNS depression. and acute respiratory paresis. condition. Diazinon has also been implicated. a “low normal” activity. leptophos. slow eye movements. c. and possibly efforts to decrease absorption or rales. the time to initiation of onset (immediate-2 hours). care alone. cholinesterase levels are more reliable in diagnosing –– Patients poisoned with highly lipid soluble OPs organophosphate poisoning than serum cholinesterase. neurobehavioural. If the RBC cholinesterase level is less than 50% of nate fatally. Several investigators have proposed airway. resting tremor. facial cardia. normal. Chronic Poisoning: weeks after poisoning due to nerve demyelination. The sheep-dip operations. sumithion. brady- up. parathion.Repeat the wash and rinse procedure with hot distillate. If pancreatitis is b. toxicity. some anaemias.PharmaDost. It is then dried in steam solution. silica gel-coated TLC plate along with the standard and run –– In the case of ingestion. hyperglycaemia. Add sodium hydroxide (2 pellets) and heat on water. Many organophosphate compounds are found in Section 8 Hydrocarbons and Pesticides poisonings. and the extract tion should be done with normal saline or Ringer’s is washed with distilled water. and blood collected in poisoning. ethion). esterase usually recovers in a few days or weeks. neoplasia. in a chair. 2. Decontamination: may selectively inhibit plasma pseudocholines. myocardial develop as a complication of organophosphate-induced infarction.Wash with cold water for 5 minutes from head blood cell cholinesterase recovers in several days to 4 to toe using non-germicidal soap. solution with a variety of hydrocarbon-based solvents. Latex and vinyl 3. pulmonary oedema. and is usually associated with mortality. Thin Layer Chromatography (TLC): The presence of an gloves provide inadequate protection. Steam distill 10 ml of urine and collect the -. ficiency and have a worse prognosis. while plasma Determine plasma or red blood cell cholinesterase activities. in the urine. Activated charcoal with that of the standard. Depression of plasma cholinesterase level (to less than suspected. a water bath for 10 minutes. or or PVCs are more likely to develop respiratory insuf- treatment of megaloblastic or pernicious anaemias. or gastric aspirate double pair is used. weeks postpartum. thiamine. haemorrhage. or vomit. –– Studies have demonstrated that RBC cholinesterase levels may be significantly higher in pregnant Treatment women than in nonpregnant controls. Acute Poisoning: –– The organophosphates phosdrin and chlorpyrifos a. tap compressed air. in a mixture of petroleum ether and methanol (25 : 1). masks with be done on vomitus or stomach contents. -. soap and water. and morphine. Ancillary Investigations: 390 known baseline level. pancreatic isoamylase levels in patients with significant anti-malarial treatment. For the purpose of estimation of cholinesterase level. or seated Alternatively. Bronchopneumonia may trition. plasma cholinesterase Aspiration pneumonitis may occur if these products activity is depressed in cirrhosis. –– Because it is a liver protein. and is excreted water. Make the patient stand blood should be collected only in heparinised tubes. In every case. phate compounds in human serum. a. and spotted on water can be used. acidosis. Patients who have increased serum amylase oxalate tubes. and infections. (if he is able to) under the shower. 1. High performance thin layer chromatography (HPLC) codeine. eye shields.g. The RF is compared time he is brought to hospital. samples can be frozen. The sample is –– If ocular exposure has occurred. the plate would have usually vomited several times by the is dried and exposed to iodine vapour. If respiratory tract irritation is present. These levels revert to normal by six associated with severe symptoms (vide supra). Plasma cholin. red -. c. monitor chest done. Rinse hair months depending on severity of depression. it is imperative that terase. sample can also be determined by TLC. cholinesterase levels are generally lower during Depression in excess of 50 per cent of baseline is generally pregnancy. but is easier to assay and more commonly c. can be administered in the usual way. –– If skin spillage has occurred. and chlo. malnu.Repeat the wash and rinse procedure with warm organophosphates (e. -. After though this is often unnecessary because the patient the solvent has travelled a considerable distance. stomach wash can be done. lignocaine. and shoe covers. . technique can be used to identify several organophos- roquine can also depress its activity. Production of yellow colour -. and chronic debilitating conditions. monitor electrolytes.Several individuals do not seem to possess a 4. high haematocrit.Treating personnel should protect themselves indicates the presence of p-nitrophenol. There may be evidence of leukocytosis (with relatively -. are aspirated into the lungs. Elevated levels may be seen with levels and those who develop a prolonged QTc interval reticulocytosis due to anaemias. an abdominal CT-scan can be performed to 50%) is a less reliable indicator of organophosphate evaluate diffuse pancreatic swelling.A very low cholinesterase level does not always normal differential count).Shower is preferable. while phosmet and dimethoate may selec. Depressions in excess of 90% may occur in severe X-ray. haemoglobinopathies. www.False depression of RBC cholinesterase level is b. anion gap correlate with clinical illness. ether. well. ECG and serum seen in pernicious anaemia. If these are not immediately available. the patient be stripped and washed thoroughly with tively inhibit red blood cell cholinesterase. P-Nitrophenol Test: P-nitrophenol is a metabolite of some -. unless a organophosphate in a lavage. –– Certain drugs such as sucinyl choline. d. The test can also with water-impermeable gowns.info -. copious eye irriga- extracted twice with 5 ml of petroleum ether. reconstituted in methanol. and delirium Pralidoxime (Pyridine-2-aldoxime methiodide. rapid pulse. Suction and in the CNS. it can be administered even much later with beneficial effects Till recently. www. and should be used if large doses are required • The half-life of atropine is significantly longer in children under 2 years and adults over 60.) If these findings occur following a diagnostic atropine dose. –– Administer IV fluids to replace losses. etc.2. raised intraocular pressure. nicotinic. drying up of tracheobronchial secretions. at a rate of 0. Preservative-free atropine preparations are available. However. while maintaining adequate oxygenation. ventilation may be necessary. 391 choline at the muscarinic postsynaptic membrane –– Maintain airway patency and oxygenation. Once the endpoint has been reached. Child—0.05 mg/kg IV (child). and CNS sites.PharmaDost.2: Antidotes for Organophosphates Atropine Mode of action : Blocks the muscarinic manifestations of organophosphates. tion: To minimise barotrauma and other compli- human studies have not conclusively substantiated cations.000 milligrams of atropine over several hours to weeks Atropine therapy must be withdrawn slowly to prevent recurrence or rebounding of symptoms. thereby liberating the latter and reactivating it While it is advisable to begin pralidoxime therapy within 48 hours of poisoning.9% sodium chloride. Supportive Measures: –– Atropine—It is a competitive antagonist of acetyl. given IV over 30 minutes This can be repeated after 1 hour. 0. and dilated and unresponsive pupils Adverse effects : Atrial arrhythmias. Antidotes: c. However. i. pathomimetics. and subsequently every 6 to 12 hours. irritability. phenothiazines. High-dose therapy with these preparations may result in benzyl alcohol or chlorobutanol toxicity. pralidoxime is 2-hydroxyiminomethyl-1-methyl pyridinium chloride Mode of action: It is usually given along with atropine. pralidoxime was said to be contraindicated in carbamate poisoning because experiments with carbaryl (Sevin) suggested a worsening of symptoms when it was administered. Pupillary dilatation and tachycardia are not reliable indicators of the endpoint Atropine can also be administered as an IV infusion after the initial bolus dose. it may be beneficial in some cases Dose: For adults—1 to 2 gm in 100 to 150 ml of 0. and blocks the muscarinic mani. dilated pupils. hyperpy- rexia. etry or arterial blood gases to determine need for 2-aldoxime methiodide). use the lowest amount of PEEP possible the benefit of oxime therapy in acute organophos. Actually.info b. Monitor pulse oxim- –– Oximes—The commonest is pralidoxime (pyridine. Pralidoxime competes for the phosphate moiety of the organophosphorus compound and releases it from the acetylcholinesterase enzyme. inspiratory stridor. warm dry skin. Endotracheal intubation and mechanical festations of organophosphate poisoning. often in the form of pulmonary oedema. AV dissociation.. The antidotes for organophosphates have been –– The following drugs are contraindicated: parasym- discussed together in detail in Table 28. from mechanical ventilation in patients with ARDS. for 24 to 48 hours Contd. secretions. the rate of administration in these patients should be adjusted accordingly • Effects of overdosing with atropine include fever.25 mg (about 0. the patient is probably not seriously poisoned Diagnostic dose—Adult: 1 mg intravenously or intramuscularly. multiple ventricular ectopics.. antihistamines.01 mg/kg) intravenously or intramuscularly Therapeutic dose: 1 to 2 mg IV or IM (adult). . since atropine affects only the postsynaptic muscarinic receptors. it has no effect on muscle weakness or paralysis Diagnostic dose: Organophosphate-poisoned patients are generally tolerant to the toxic effects of atropine (dry mouth.e.02 to 0. Chapter 28 Pesticides Table 28. Use of phate poisoning. recent studies have pointed out that while pralidoxime is not a neces- sary adjunct to atropine in carbamate overdose. but they are widely used. Most smaller tidal volumes (6 ml/kg) and lower plateau authors advocate the continued use of pralidoxime pressures (30 cm water or less) has been associated in the clinical setting of severe organophosphate with decreased mortality and more rapid weaning poisoning. which is a nucleophilic supplemental oxygen. photophobia. This is especially true of poisonings from lipophilic organophosphates such as fenthion Precautions: • Many parenteral atropine preparations contain benzyl alcohol or chlorobutanol as preservatives. This may require administration of 2 to 2. every 15 minutes until the endpoint is reached. the dose should be adjusted to maintain the effect for at least 24 hours Atropinisation must be maintained until all of the absorbed organophosphate has been metabolised. 2-PAM) Structurally. hallucinations. oxime that helps to regenerate acetylcholinesterase –– Oxygenation/intubation/positive pressure ventila- at muscarinic.08 mg/kg/hr. and is the only oxime available in Portugal A few investigators suggest that oximes have only a limited role in organophosphate poisoning. Supportive and symptomatic measures. Prolonged neuromuscular blockade may such as stage of gestation. evidence of infection. he should not be re-exposed to organophos. Many workers feel that this high dose therapy minimises the incidence of complications such as the Intermediate Syndrome Maximum dose should not exceed 12 gm in a 24 hour period. laryngospasm. phenytoin or phenobarbitone can be used instead and opiates. www. and muscle weakness It is generally not advised for the treatment of carbamate overdose. Treatment of Pregnant Victim: Therapeutic choices (suxamethonium) or other cholinergic medica. be a candidate for emergency Caesarean section. and repeated every 6 to 12 hours for 24 to 48 hours Alternatively. . every 5 to 10 minutes. patients should be precluded b. during pregnancy depend upon specific circumstances tions. haemodialysis. Prevention of Further Exposure: After the patient has foetus may be best served by treating the mother to recovered. retain good respiratory function and foetal oxygen- phates for at least a few weeks since he is likely to ation. A severely –– Treat convulsions with benzodiazepines or barbi. poisoned patient with a late gestation viable foetus may turates. usually does not readily cross the placenta and would phosphate poisoning. and even cardiac or respiratory arrest Section 8 Hydrocarbons and Pesticides Other adverse effects include drowsiness.5% concentration of pralidoxime can be given as a loading dose followed by a maintenance dose Serious intoxication may require continuous infusion of 500 mg/hr in adults..25 to 0. 392 Alternatively. Characteristic odour (garlicky or kerosene-like). upto a maximum of 30 mg For children—0. Chronic Poisoning: be harmless. Do not administer succinylcholine e. Scandinavia. and exchange pregnant patient to counteract muscle weakness. Infusion over a period of several days may be necessary and is gener- ally well tolerated The WHO currently recommends an initial bolus of at least 30 mg/kg. and Germany. 1. be treated adequately to treat the foetus. iv infusion can be resorted to. severity of poisoning. headache. not directly affect foetal poisoning. vertigo. This may take 3 to 4 a. Plateau has been obtained when sequential determina. upto a maximum of 10 mg If diazepam is ineffective.PharmaDost.info Contd.. b. the d. External— tions differ by no more than 10%. pralidoxime can be given intramuscularly as an initial dose of 1 gram or up to 2 grams in cases of very severe poisoning In some countries obidoxime is used instead of pralidoxime.4 mg/kg IV slowly. transfusion have not been shown to affect outcome –– Glycopyrrolate: Unlike atropine. and result when succinylcholine is administered after clinical signs of mother and foetus. However. The Netherlands. –– Pralidoxime chloride is recommended for use in the –– Haemoperfusion. Israel. glycopyrrolate or duration of toxicity in controlled trials of organo. at a rate of 9 to 19 mg/kg/hr Adverse effects: Rapid administration can cause tachycardia. though it does not appear to be superior to the latter It is apparently favoured over pralidoxime in clinical practice in Belgium. The –– Antibiotics are indicated only when there is foetus may require intensive care after birth. Following acute poisoning. though this view is not shared by most other workers in the field Diazepam Some studies indicate that the addition of diazepam to atropine and 2-PAM improves survival. Removal of the patient from the source of exposure. owing to alteration of body chemistry. suffer serious harm from a dose that normally would 2. especially carbaryl In cases where intravenous administration is not possible. and successful management is possible without employing them at all. followed by an infusion of more than 8 mg/kg /hr It is estimated that a plasma concentration of at least 4 mg/L may be necessary for pralidoxime to be effective For children—20 to 40 mg/kg to a maximum of 1 gm/dose given IV. Frothing at mouth and nose. it reduces the risk of seizure-induced brain and cardiac damage Dose: For adults—5 to 10 mg IV slowly. from further organophosphate exposure until sequential RBC cholinesterase (AChE) levels have been obtained Autopsy Features and confirm that AChE activity has reached a plateau. a. months following severe poisoning. The mother must organophosphate exposure. every 15 minutes. a 2. PharmaDost. With propoxur. variety of low toxicity phenolic substances. VegFru Diafuran Carbosulfan Marshal Fenobucarb Merlino Methomyl Astra. but carbamylate the serine moiety at the active intoxicated with carbamate insecticides. Usual Fatal Dose Acute lung injury (pulmonary oedema) is a potential clinical Toxicity Rating*: manifestation of severe carbamate poisoning and is attributed The following are extremely toxic (LD50: 1 to 50 mg/kg). 393 2. This is a reversible type of a cardiac arrhythmia or respiratory failure is associated with a binding and hence symptoms are less severe and of shorter higher incidence of fatal poisoning. is characteristic of severe and Forensic Issues moderately severe poisonings. The following are moderately toxic (LD50: 501 to 5000 Headache. Pupil dila- Discussed at the end of the chapter. Constricted pupils. Carburan. Internal— Carbamates are rapidly metabolised. Dyspnoea is a common manifestation of carbamate expo- ties. classic muscarinic effects has been reported in several children cholinesterase. blurred vision. Sevidal. Generalised visceral congestion. Sinus tachycardia with ST segment depression may occur Carbamates early in the course of poisoning. Dimetan. may sometimes be measured in urine as long as 2 to 3 days c. increased pulmonary secre- Chapter 28 Pesticides tions. dystonias. and convulsions have Pirimicarb. Propoxur. and Mode of Action and Clinical Features hypotonia than the typical cholinergic syndrome. Furadan 3G. 1971. Acute pancreatitis has been reported with organophosphates. They are rapidly a. Pulmonary and cerebral oedema. MPMC. CNS toxicity is likewise much less. Bufencarb. together with all the other tion may occur as a nicotinic effect and may be present in up pesticides. mg/kg). brands are listed in Table 28. Only the differentiating features will be discussed. all been reported with carbamate poisoning. Protox Bait Thiodicarb Larvin * Partly as per the Insecticide Rules. similarity between carbamates and organophosphates. Mathoyl MPMC (Xylylcarb) Bipuin MTMC (Metolcarb) Emisan Propoxur Baygon. Lannet. Oxamyl. since carbamate use. Table 28. The symptoms are similar to those seen with carbamates do not penetrate the CNS to the same extent as organophosphates. Carbaryl. These metabolites b.3: Common Carbamates Generic Name Brand Name Aldicarb Aldrin. duration. Bangvin 50. to the muscarinic action of the insecticide. Dimetilan. Also. respect to all other clinical manifestations. Crane. there is general d. Benfuracarb. Kevin 50. Carbocil 3. and weakened cardiac contraction from an accumulation of Carbofuran. or slightly toxic (LD50: more than 5000 mg/kg)— mental depression.info c. a muscarinic effect. Sevin 50. Hypoxia may Methiocarb. Kilex Carbaryl. Agroyl. Isocarb. Congestion of GI tract. Dunet. convulsions. garlicky or kerosene-like odour hydrolysed by liver enzymes to methyl carbamic acid and a of contents. Miosis. Sujacarb. Cyanosis of extremities. weakness. Repolarisation abnormalities Carbamates are as popular as organophosphates in their role as may occur and are generally transient. various Aldicarb. Temik Carbaryl Agrovin. Children may be more likely to develop CNS depression. acetylcholine on the cardiovascular system. Contributing factors or highly toxic (LD50: 51 to 500 mg/kg)— to the development of pulmonary oedema include bradycardia Aminocarb. The presence of either site instead of phosphorylation. Absence of Carbamates (like organophosphates) are inhibitors of acetyl. bronchospasm. . Methomyl. Sulfarl 50 Carbaryl + Gamma BHC Sevidol Carbofuran Agrofuron 3G. after significant pesticide absorption. www. delayed neuropathies. Formetanate. MTMC. As a result both morbidity and mortality are limited Various peripheral neuropathies have been reported after when compared to organophosphate poisoning. paresis.3. insecticides (and fungicides) and share a number of similari. muscle twitching. Isoprocarb. coma. Corovin. Lannate. Bendiocarb. Caravet. Chest tightness. Hexavin. Dioxacarb. and rales may develop secondary to muscarinic effects. to 10% of patients. but may appear late. Hexafuran. tremor. Indian sure. dizziness. develop due to increasing capillary permeability. heptachlor. chlordane. Endosol. Scaboma. VegFru Heptex Lindane Agrodane. Table 28. administer In the case of carbamate poisoning. Termex. Aldrin 30. Unidhan Heptachlor Agrochlor D5. Soltax. Kenrilfan. Mitox 20EC. Bexarid. isobenzan. Gab. In vitro decarbamylation Organochlorines has been found to be promoted by dilution of the sample. Agro BHC. Alcrop.05 mg/kg IV every 10 to 15 aldrin. Chlordane. carbaryl (alpha-naphthol).4: Common Organochlorine Pesticides Generic Name Brand Name Aldrin Agroaldrin. Heptachlor. oxime therapy ■■ Insecticide. while DDT. effort. Emscab. measurement of cholinest. The Organochlorine pesticides are one variety of chlorinated hydro- carbamylated sample should be stored undiluted and refriger. pulmonary secretions). Benzene hexachloride group—for example. whereas phosphorylated nyltrichloroethane). or lotion. Sudarshan. Especially in carbaryl poisoning. Carbamylated cholinesterase activity follows a 1. Section 8 Hydrocarbons and Pesticides carbofuran (carbofuranphenol) propoxur (isopropoxyphenol). Hildane. There are 4 distinct categories of these pesticides: ated or frozen. aldrin. Hexidole Hilbleach 50WP. Gamazene. Gamaric (Euphonic). dieldrin. benzene hexachlo- non-linear pattern characteristic of carbamates is easily mapped. Tarmahit 30 BHC Agrobenz D10. Heptox. a Some Indian brand names include Bexarid (Shalaks). or decreased respiratory ■■ DDT. Agrodono. An important differentiating point from organophosphates is that oximes are generally not recommended. heptachlor. Scaboma (Glenmark). Ranodit. Canodane. Starbrand Lindane. mirex (dechlorane). endosulfan (thiodan). can lead to the production of a carbamylated oxime which may ■■ Gamma benzene hexachloride is used as a scabicide (treat- be a more potent acetylcholinesterase inhibitor than carbaryl ment of scabies). endrin. Paediatric dose—0. and can be used in conjunction with atropine for specific indica. Sunbrand Chlordane Agrodane 20EC. Sudarshan 5EC. Chemusulfan. Usual Fatal Dose ness. Premodole 10EC. Didinex 25EC. kepone. www. VegFru Chlortox DDT DDT Sudarshan 50. Heptaf 50. enzyme activity is linear. These compounds are available as dusting powders. Hexasulfan. and gamma-hexachlorocyclohexane (lindane). Endoseed. tions as follows: ■■ Life-threatening symptoms such as severe muscle weak. At inhibition of greater than 40%. erase activity in blood may be misleading due to in vitro reac- tivation of carbamylated enzyme. Scabex. Alditon.4 lists Indian brand names of organochlorine The major cause of morbidity and mortality in carbamate pesticides. One technique for assessing absorption of the principal 3. Adult dose—2 to 4 mg IV every 10 to In addition. endrin : 2 to 6 grams. Sunbrand. and In all cases. lindane: 15 to 30 grams. Ethsulfan. Tafidex Dicofol Kelthane. Kesulfan. In 1986. ■■ Continued excessive requirements of atropine. and toxaphene. Aldrex. Endotaf. Endoxin.info Convulsions can be controlled with a benzodiazepine 394 Diagnosis (diazepam or lorazepam). 4. Speed. and methoxychlor. Endosulfan. The following are least toxic: Table 28. Lintaf. With other carbamate insecticides (particularly aldicarb). Klin Endosulfan Agrosulfan. Toxicity Rating: Dieldrin is placed in the “extremely toxic” ■■ Concomitant organophosphate and carbamate exposure. 15 minutes.PharmaDost. emulsions. oximes may be a useful adjunct to atropine therapy. DDT and analogues—for example. Heptar. the 2. Solchlor. Endohit. Ultrascab (Perch). nously until atropinisation is achieved (indicated by drying of as per the Insecticide Rules. lice). chlordane. Tafarol. insecticide poisonings is respiratory failure and associated Physical Appearance pulmonary oedema. category (LD50: 1 to 50 mg/kg). Gab consensus of international experts concluded that pralidoxime (Gufic). wettable Treatment powders. Mildrin 30. If they persist or recur. fasciculations. Endovip. Sevidol (with carbaryl). lindane are considered “highly toxic”(LD50: 51 to 500 mg/kg). Suldit 50. Kargo BHC. Linsuline. ■■ Aldrin. endosulfan. toxaphene. N-methyl carbamate compounds is measurement of specific dieldrin. 1971. the following are extremely toxic: endrin. Haxaman. Chest X-ray should be obtained in all symptomatic patients. It is available as topical ointment. mirex. while atropine Uses can be given. phenolic metabolites in urine. Gamaric. Rasayan Lindane. paralysis. Hildon. e. Thiodon. Sulbenz 50. while these are highly toxic: minutes.g. granules and solutions. Toxaphene and related compounds—for example. Cyclodienes and related compounds—for example. Lindane 20. Thiodan. Gammexane. Ramdit. and a pediculocide (eradication of head itself. Lindex. cream. ride (BHC). Kenodan. chlordecone (kepone). Marvel. DDT (dichlorodiphe- non-linear kinetic pattern over time. administer atropine in repeated doses intrave. Scarab. phenobarbitone. Ultrascab . Gamascab. carbons. info methoxychlor. For YY mirex. aldrin. confusion. useful following acute exposure. perthane. and hexa. role of benzoquinones in the hepatotoxicity of chlorin- dermally. tion of the calmodulin-dependant Ca2+ -ATPase activity. with an average level in the newborn blood YY endrin reaching around a third of that in maternal blood. kelthane. aplastic anaemia. www. wherein different bound rines. 2. aspiration pneumonitis. All the organochlorines can be absorbed trans. carcinogenicity has been demon- strated in animal studies. Severe metabolic acidosis has YY chlordane (except the heptachlor component) been reported. YY methoxychlor 2. Gastrointestinal absorption ated hydrocarbons as opposed to traditional epoxides. hypotension. in fatty tissues of humans. oligospermia. agitation. least well absorbed transdermally. nervousness. aldrin). ataxia. weakness. ■■ An important property of the chlorinated hydrocarbons. chlordane. abdominal pain. and inhibition of approximately as: endrin. rine pesticides. the half-life for and convulsions. ■■ The neurotoxic mechanism of endosulfan involves inhibi- chlorobenzene. and sinus the rapidity of excretion from storage levels that represent an tachycardia may occur following exposure. although it also categorises them as being YY kepone inadequately assessed for human carcinogenic potential. Many of these compounds are metabolised slowly Clinical Features and persist in tissues (especially fat) for prolonged periods. but insufficient data has accrued from Mode of Action human studies. the axon. Occasional reports have associated the remaining store increases dramatically. while dieldrin is very well absorbed. 1. hyperaesthesia Chapter 28 Pesticides are found in adipose tissue. dieldrin. chlordane. of these agents is generally efficient. vertigo. (chlordecone. ■■ Excreted only over several months or years: The International Agency for Research on Cancer (IARC) YY beta isomer of benzene hexachloride has listed some of these agents (e. Coronary spasm. and by inhalation. DDT is the protein binding of reactive metabolites. Other systems: fever. pseudotumour cerebri. YY chlorobenzilate d. myoclonus. Dieldrin. methoxychlor does not substantially accumulate b. noradrenaline and acetylcholine. 3. amnesia. chlordane. mydriasis.g. weak- YY aldrin ness. tremor. They YY kelthane can also be found in breast milk. DDT) as “possibly carci- YY DDT nogenic to humans”.PharmaDost. They also alter the metabolism of serotonin. heptachlor. hepatomegaly. and urine by gas chromatography. orally. unlike other organochlo. 395 Acute hazard potential may be ranked (highest to lowest) alterations in the serotoninergic system. chlorobenzilate. CNS: headache. tremor. toxa. particularly in the pres.g. It is still c. kepone. adipose tissue. Organochlorines can be detected in serum. Evidence suggests an important added to water. rapid and dysrhythmic eye Excretion of organochlorine compounds does not follow movements. thrombocytopenic purpura. These compounds act by various other mechanisms. Organochlorines do not depress cholinesterase enzymes. This is probably peripheral neuropathy with exposure to organochlo- due to complex lipoprotein binding. DDT. acute toxic threat: endrin. chlordane. vomiting. Most of these agents cause liver necrosis and they are dissolved in petroleum distillates which form emulsions when potent enzyme inducers. toxaphene. abnormal YY dieldrin mental changes. As body stores get lower. heptachlor) results in cumulative ■■ Excreted within several weeks to a few months: toxicity with manifestations such as weight loss. renal possible to classify the organochlorines roughly in terms of failure. Organochlorine pesticides such as DDT pass through YY endosulfan the placenta. GABA receptors. Acute Poisoning: High residue levels from organochlorine insecticide poisonings a. Diagnosis ■■ DDT and analogues affect the sodium channel and sodium 1. other agents (e. ataxia. opsoclonus. and increased tendency to YY heptachlor leukaemias. and lindane is their Toxicokinetics capacity to induce the drug-metabolising enzymes of the Commercial preparations of organochlorines are commonly liver. GIT: nausea. However. forms exhibit different dissociation characteristics. centrilobular hepatic necrosis and liver cancer. first order kinetics. For most compounds . YY hexachlorobenzene. or paraesthesia of the mouth and face. ■■ The cyclodienes and lindane appear to inhibit the GABA. Cytochrome P450 appears to be associated with covalent ence of absorbable lipid (animal or vegetable) fat. particularly toxaphene. and DDT are direct ■■ Excreted or metabolised within hours to a few days: respiratory depressants. Abdominal radiograph may reveal the presence of certain conductance across the neuronal membrane especially of organochlorines which are radiopaque. Blood chlorinated hydrocarbon levels are not clinically mediated chloride channels in the CNS. Chronic Poisoning: YY perthane Long-term exposure to some of these compounds YY toxaphene. phene. DDT and methoxychlor. sprays. and hypoglycaemia (if Type I pyrethroids do not contain a cyano group. principally pyrethrosin (minor . and also act by inhibiting can be mixed with fruit juice and given orally (4 gm. etc. fenvalerate. the minimal 3. 2. The following are contraindicated—oil-based cathartics. and atropine. perform mentioned in Table 28. lethal dose of pyrethrum is not clearly established. exchange resin is effective in enhancing the faecal excretion Like DDT. Low toxicity in hourly). www. Decontamination—the same measures as detailed under two of the most insecticidally potent pyrethric and chrysan- organophosphate poisoning must be undertaken. Hyperthermia should be managed aggressively with side chain of the alcohol moiety with ester hydrolysis playing cooling. or 2 ml/kg (child) of 25% dextrose). treat with intravenous dextrose: 50 ml IV (adult). Leather absorbs pesticides. and the need for endotracheal intubation. amounts of water. Rescue ■■ Pyrethrum extract is effective for treating pediculosis of personnel and bystanders should avoid direct contact the head. and adequate circulation should be detoxification of pyrethrins via ester hydrolysis. and include pyrethrum as 1 mcg of organic halogen per 100 ml of urine. Section 8 Hydrocarbons and Pesticides endotracheal intubation and provide assisted ventilation as required. pyrethroids are of 2 types— hypoxia. Pyrethrin I and pyrethrin II are 1. Move patient from the toxic environment to fresh air. It agents are more potent in this regard. Pyrethroids are synthetic analogues and number a. They are esters of pyrethric and chry- santhemic acids formed by the keto alcohols pyrethrolone. which further increase myocardial irritability and Two types of allergens present in crude pyrethrum oleoresin produce refractory ventricular arrhythmias.PharmaDost. present. a role. over 1000 varieties which are used as insecticides to incapaci- b. If cough or difficulty tate or “knock out” insects. evaluate for hypoxia. Measurement of organic halogen compounds in urine is Pyrethrins are active extracts of the chrysanthemum plant suggested as an indicator of exposure. sodium thiopentone can be adminis. though it is phenytoin. Type II is administered at a dose of 16 gm/day for several days. Administer pyrethrins and pyrethroids available commercially in India are 100% humidified supplemental oxygen. have been identified: glycoproteins or glycopeptides ranging 9. dusts. Cholestyramine. Administer inhaled beta adrenergic agonists Uses if bronchospasm develops. mats. Supportive measures—special attention must be paid to the due to competition for carboxyesterases responsible for rapid airway and breathing. They are sold as liquids. amines. and piperonyl butoxide. Very young maintained. all contaminated leather should be discarded. jewelry. 4. Treatment cinerolone. They tend to increase intestinal Usual Fatal Dose absorption of these lipophilic toxicants. Monitor for respiratory depression. Evaluate for Structurally. and coils. deltame- 5. with contaminated skin. body and pubic area. particularly chlordecone.info they reflect cumulative exposure over a period of months Pyrethrins and Pyrethroids 396 or years rather than recent exposure. repeated soap washings. throids because they may not hydrolyse the pyrethrum esters adrenaline. If they are probably in the range of 10 to 100 grams. Type II pyrethroids contain a cyano group. Mode of Action mias. tered IV. e. isobutenyl side chain of the acid moiety and of the unsaturated 6. Seizures should be controlled with benzodiazepines. However. ■■ These compounds are used as household insect repellants c. or 4 hours after each dose of cholestyramine. Exposed skin and eyes should be flushed with copious and insecticides. Remove contaminated clothing and powders.g. or phenobarbitone in the usual way.5. It sodium channel by binding to it in the open state. Do NOT administer adrenergic efficiently. Haemodialysis and haemoperfusion have not been proven in molecular weight from 60. Common tract irritation. e. Sensitivity is as low (Chrysanthemum cinerariaefolium). clothing. or other objects. arrhyth. fenpropathrin. hair and nails vigorously with ■■ They are also used to prevent pest infestation in granaries.000 (most important) effective. hypotension. cypermethrin. Monitor for respiratory distress. Pyrethrum has an LD50 of over 1 gm/kg. Most cases of toxicity not effective enough. and the sesquiterpene lactones. 4. children are perhaps more susceptible to poisoning by pyre- 8. bronchitis. themic esters. and in agriculture as pesticides. permethrin. or neuromuscular blockade is done. It can interfere with absorption of other therapeutic mammals is probably due to rapid metabolic breakdown in the drugs which must therefore be administered either 1 hour liver: pyrethrum is broken down mainly by oxidation of the before.g. or pneumonitis. and jasmololone. electrolyte disturbances. wash skin.000 to 200. Some organophosphates may enhance pyrethrin toxicity 7. Do NOT give oils by mouth. pyrethroids prolong the inactivation of the of organochlorine compounds. a non-absorbable bile acid binding anion thrin. Most mammals are resistant since in breathing develops. 6th GABA-mediated inhibitory chloride channels. respiratory they can rapidly metabolise and detoxify these agents. are actually the result of allergic reactions. Cypermil. intravenously. Sicerin. Java. Lee. Cyrux. Serum cholinesterase levels are normal. Pest-seal. diphenhydramine 50 mg orally. Arjun. 1. Fencidin. Challenger. Gilcyp Tech. Silofen. Pounce Pyrethrum Tortoise mosquito coil importance). Cyperin. Systemic poisoning— reaction. corticosteroids (e. the eyes. corneal damage that generally resolves with conservative and ventricular premature beats. may occur. Super-D Chlorpyriphos Chapter 28 Pesticides Cypermethrin + Prasanth Quinalphos Decamethrin Decathrin Deltamethrin Butox. a bulbous dermatitis may also occur. Raksha. Stop Alphamethrin + Anuphan. Skin contact: dermatitis. Severe poisoning may result in marked 1. Inhalation: rhinorrhoea. coma. dyspnoea and bron.5: Pyrethrins and Pyrethroids 397 Generic Name Brand Name Allethrin Baygon mats. Hycper. altered mental mg orally every 4 to 6 hours for 24 to 72 hours) with status. Farward. Shekari. Hypowder. Nausea. Permethrin. Ingestion (large doses): paraesthesias. Nurelle-D. Riptan. Ripcord. Triumpheard. Cymber. A colour test with 2-2 (2-aminoethylamine) ethanol been reported following ocular contact exposure during produces red to violet colour in the presence of pyre- normal use of pediculicide shampoos containing pyrethrin. Skin contact—decontaminate with soap and water. Sumitox. Ralo. The usual lesion is a adrenal activation. Sicorin. 15 minutes. Starcyprin. seizures. Suraksha. K-Othrine Deltamethrin + Crove. It is however not suitable for analysis Chemical conjunctivitis was diagnosed in a patient after a of pyrethrins in body fluids. Hilten. Reeva Cypermethrin Agrocyper. Dhanusan. blistering. Treatment Asthma or reactive airways disease syndrome can occur 1. Anchor. Colt. Bilsif. Cymperm. hyperthermia. Cymper. throidal substances. 2. Shakti. or intramuscularly initially. Cypermethrin-Sandoz. Gilfen. 4. Fenit-20. Starfen. chospasm. Deltex. Trumpcard. ECG may demonstrate ST-T changes. except. Decis. Parafen.g. Anusan.PharmaDost.info Table 28. Capvalerate. Hit insect repellant Barthrin Basothrin Cyfluthrin Bulldock Cyhalothrin Karate. wheezing. then 25 to 50 vertigo. Corneal denudation and decreased visual acuity have 3. Motal. cough. Mild to moderate allergic reactions may be treated with following exposure to pesticide mists. Cypersul. Cybil. Hexit (with allethrin). fasciculations. Fenvip. Tackle. sore throat. care. Cymbush. Hilcyperin. Fury. . Cilcord. and intense pruritus. Bilcyp. Retolin. Fenfen. Decaguard. Spark Triazophos Fenvalerate Agrofen. possibly at very high pyrethrin-containing mist was inadvertently sprayed into concentrations. Ramceper. associated with anaphy- Clinical Features laxis. antihistamines (e. Fenval. Eye contact—irrigate with normal saline or water for 10 to pneumonitis with chest pain. Fighter. or without inhaled beta agonists. Eye contact: Eye exposures may result in mild to severe 2. as also hypersensitivity 2. Cyper. 3. Megathrine. Baygon Power mats. moist areas. Basathrin. Sumicidin. Fenvil. Megacypher. following inhalation exposures. Vegfrucott. Refined pyrethrins and synthetic pyrethroids are vomiting and abdominal pain commonly occur and said to have little or no allergenic effect. Unicyper. Ralothrin. Fenny. Cyperguard. Cymet. Parathrin. dyspnoea. Cannon. Fenhit. Primovel. pulmonary oedema. Skin contamination with pyrethrins can cause Diagnosis localised paraesthesia. with increases in adrenaline and mild erythematous dermatitis with vesicles. Shelter. nausea. develop within 10 to 60 minutes following ingestion. Cyperhit. Ustad Cypermethrin + Anaconda. Vijayfen Fluvalinate Marvik Permethrin Ambush. Ralathin. Cypervip. Dizziness and headache have been reported a. sinus tachycardia.g. Fenkill. Superkiller. Eosinophilia may accompany an acute allergic 3. Neurocombi. papules in noradrenaline accompanying motor signs. vomiting. Fenlid. Cypertech. Twister Chlorpyriphos D-allethrin Baygon Knock-out aerosol. www. Good Knight mats. Good Knight. Permasect. Pynamin Forte Alphamethrin Alfaguard. Farsa. Hypotension and tachycardia. ml diluted in 10 ml 0. charcoal is unlikely to be of benefit. arsenic. mice. paraquat also investigators recommend the former for drying up accumulates in muscle tissue. prednisone 60 mg/day Gramoxone and Uniquat.9% saline slow intravenous push Some of these are very commonly involved in human over 5 to 10 minutes). ECG monitoring and diolone). secretions.* Paraquat is 1. activated dalaphon. Consider is less commonly used than paraquat. Examples. These are compounds which kill weeds.1-ethylene-2. e. The Administer beta2 adrenergic agonists. trate which is an odourless brown liquid (100–200 gm/L). If the pyrethrin is simazine. It has the same indica- phenobarbitone if seizures recur after diazepam 30 mg tions and mode of action as paraquat but produces much less (adults) or 10 mg (children > 5 years). . Mode of Action ■■ Paraquat is a rapidly-acting herbicide. and g. significant bronchospasm. Consider use granular form is available as colourless crystals (dichloride of inhaled ipratropium and systemic corticosteroids. and therefore 10 ml of a 20% solution can contain about sary. Oils and fats (including milk) promote the intestinal to the bipyridyl group. Consider systemic corticosteroids in patients with 2 grams of paraquat. skin contact. atrazine. Treatment of severe anaphylaxis poisoning.2 to 1. After absorption it tends to accumu- sion. However.000 solution.6 L/kg). applications of vitamin E. paraquat.4-bipyridy- absorption of pyrethroids and should be avoided. adrenaline. Bronchospasm is treated with standard bronchodilators. than the granular form.2-dipyridylium dibromide. Gastric decontamination is therefore. Paraquat and diquat are widely used herbicides which belong d. More than 90% of an absorbed adrenaline. (adult). It is available either as indicated. etc. mentation. b. Vasopressors such as dopamine should be used late in the lungs and kidneys.info methyl prednisolone 1 to 2 mg/kg intravenously every fluoroacetamide. Activated charcoal is beneficial. and after vigorous intravenous crystalloid dose is excreted by the kidneys as the parent compound within rehydration 12 to 24 hours. rodents. Seizures can be controlled with diazepam. red squill. moles. and chlorophenoxy formulated in a petroleum base. vacor.g. though prolonged contact can be hazardous. Examples acrolein. may result following eye exposure to paraquat. nitrofen. Absorption through inhalation. and was first synthesized in 1882. severe pulmonary lesions. urine output). anticoagulants. Diquat is 1. paraquat solution is much more rapidly absorbed recommended in patients with persistent hypoten. barium carbonate. if the pyre. ■■ Corneal injury and protracted opacification of the cornea zinc and aluminium phosphide. which may represent a reservoir. monitor for hypoxia of the concentrates of paraquat are available as 10–20% solu- and respiratory failure. In India. explaining prolonged detection of plasma or urine paraquat j. phosphorus. propazine. and other amount of translocation to the xylem. Oxygen and ventilatory asistance must be administered be used as a herbicide only since the 1960s. lium dichloride. difenzoquat and morfamquat. Paraquat has a large volume of in refractory cases unresponsive to repeated doses of distribution (1. Section 8 Hydrocarbons and Pesticides pneumonitis may exceed the toxic hazard of the insec- ticide. phosphorus. In massive ingestions. Extensive cholecalciferol. diquat. Highest i. 398 6 to 8 hours) or adrenaline (1:10. (consult Index). alpha-naphthyl-thiourea. c. loss of superficial areas of the corneal and conjunctival * Other bipyridyl herbicides which are rarely encountered include chlormequat. but some concentrations are found in kidney and lung. e. but began to e. salt) or a yellow solid (bis(methyl sulfate) salt). Cutaneous paraesthesias are said to respond to topical weeks or months following ingestion. bromethalin. aggressive phide.PharmaDost. Common brand names include Weedol. thrin is formulated in an organic solvent. the risk of hydrocarbon compounds.. and administer oxygen as neces. or eye contact adults may require up to 6 to 10 litres/24 hours. h. long acting anticoagulants (especially broma- airway management. It kills the tissues RODENTICIDES of green plants by contact action with foliage and by some These are compounds which kill rats. Atropine and oximes are contraindicated. or 1 to 2 mg/kg/day (child). generally Paraquat and Diquat not recommended. sodium monofluoroacetamide. 3 to 5 strychnine.g. Paraquat is distributed into all organs. most Monitor peak expiratory flow rate. glyphosate. Central is minimal. If hypotensive give 500 to 2000 ml crystalloid initially (20 ml/kg in children) and titrate to desired effect Toxicokinetics (stabilisation of vital signs. www. On venous or pulmonary artery pressure monitoring is ingestion. thallium.1-dimethyl-4. in granular form (25–80 gm/kg) or as water soluble concen- f. trichloroacetic acid. zinc and aluminium phos- also includes oxygen supplementation. stomach wash can be done after making sure that there are no petroleum distillate addi- HERBICIDES (WEEDICIDES) tives. but they have been discussed elsewhere IV fluids. tions. Monitor renal and liver function tests carefully. ingestion be treated as potentially fatal poisonings. and diarrhoea may occur immediately Mortality in paraquat poisoning can be high and is related following ingestion.2 mcg/ml at 24 hours.e. The hydroxyl presentation. no abnormalities may be noted on the chest radical causes degradation of cell membranes through lipid X-ray. 2. tions. vomiting. death in 3 to 4 days. Obtain GI haemorrhage. Plasma paraquat level can be assayed by spectroscopy. vomiting. 4. Pneumothorax. nausea. baseline urinalysis and monitor urine output. and paraquat enhances the toxicity of oxygen. Hyperacute Form: (ingestion of more than 50 mg/kg of of ingestion. 399 ■■ Irritation of the skin and mucous membranes may be severe 3. Tachycardia. pneumopericardium ■■ The maximum damage is seen in the lungs where cellular and subcutaneous emphysema may develop in patients with injury is initiated by the NADPH-dependant reduction of paraquat induced lung injury. Obtain baseline pulmonary function tests. if death is due to the hyperacute form of thought to be the ultimate toxic element. Concentrated solutions of paraquat to two factors—concentration and quantity. i.PharmaDost. c. the toxicity of paraquat. Estimated lethal dose is 10 to 15 ml of the concentrate. Serum levels greater than Usual Fatal Dose 0. Healing. since paraquat stomach due to corrosion. Superoxide 1. Two superoxide species form hydrogen peroxide Diagnosis in a reaction catalysed by superoxide dismutase. Renal and hepatic lesions are also common. Perform upper gastrointestinal endoscopy to identify the by pulmonary fibrosis which leads to progressive extent and severity of corrosion. paraquat) Activated charcoal is of doubtful value. death may be delayed upto 70 days and is usually severe abdominal pain. Prudence requires that all cases of paraquat colour is a positive test.0 ml of 20% (w/v) paraquat concentrate) results in adding a few mg of sodium dithionite. then (7. peroxidation resulting in cellular death. Second Phase—begins after 2 to 5 days and is char. There may be gastric perforation/ 6. clinical outcome is generally not All cases of paraquat ingestions should be considered as determined by hepatotoxic effects. diarrhoea.1mcg/ml at 48 hours are associated with high mortality. 7. and 0. respiratory failure. Third Phase—begins after 5 days and is characterised 1. hypotension. X-ray of the chest may reveal patchy infiltration in the early and hydrogen peroxide undergo a series of iron-catalysed stages. due to pulmonary fibrosis. chest X-ray. If it is less than a in some cases of acute paraquat poisoning. aphonia. and ensured that only plastic containers are used. ABGs and monitor serially for several days. lopathy and centrilobular hepatic necrosis respectively. Stomach wash may be beneficial only if done within 1 hour 2. Continued survival is dependant on the extent This process known as redox cycling is sustained by the of lung involvement. 2. www. medical emergencies even if the patient is asymptomatic. Ingestion of 20% corrode the GI mucosa. or HPLC.5–15. renal tubu.info epithelium may occur. Although hepatic injury from exposure to paraquat Treatment may be quite severe. Reaction with Survivors of severe paraquat poisoning often develop molecular oxygen yields the superoxide radical (O2-) and progressive pulmonary fibrosis within 5 to 10 days or longer Chapter 28 Pesticides reforms the paraquat dication. and can cause mouthful. paraquat) ■■ After ingestion. Survival is usually associated with levels less than 1mcg/ Clinical Features ml. while mortality is high when the level exceeds 10 mcg/ ml. paraquat to the monocation radical (PQ+). 1. However. is usually There is rapid development of cardiogenic shock ending in complete if given prompt medical care. after exposure. Typical Form: (ingestion of 30 to 50 mg/kg of paraquat) 5. binds to glass. oesophagus. b. than a mouthful can cause death in 72 hours because it corre- Cerebral oedema may occur. Urine paraquat level can be assayed by spectrophotometry. . sore throat and difficulty in swallowing This is characterised only by gastrointestinal manifesta- can occur. Initial Phase—pain in the mouth. This Occupational exposure to paraquat can cause a dry. Swallowing more cardiorespiratory arrest can occur with large ingestions. although slow. and opacification of one or both lung fields in later reactions to yield the hydroxyl radical (OH) which is stages. Pancreatitis may develop sponds to ingestion of more than 50 mg/kg. ready to be reduced again. radioimmunoassay. and acterised by renal and hepatic toxicity. Subacute Form: (ingestion of less than 30 mg/kg of following paraquat exposure. extensive supply of electrons and oxygen in the lungs. When submitting samples for chemical analysis it must be a. Urine can be tested for gross amounts of paraquat by alka- Ingestion of 20 to 40 mg of paraquat ion per kg body weight lising 3 to 5 ml with a few mg of sodium bicarbonate. Irritation of the gut including abdominal pain. Emesis and cathartics are contraindicated. 3. dysphagia. An intense blue-green death in most cases. and solution is associated with high mortality. cracking and the subsequent reactions explain why oxygen enhances dermatitis and nail atrophy. and the gastrointestinal tract. mouthwashes. from the GI tract has been reported. Cut surface reveals fusion sessions against activated charcoal. 4. www. Ulceration around lips and mouth. ice cream). a minor amount cases where it was attempted. miosis. Dermal absorption is 9. 4. or activated charcoal instillation. 6. two 8-hour haemoper. ECG abnormalities. Haemodialysis or haemoperfusion may be beneficial if undertaken within the first 10 to 12 hours. controlled clinical trials. hyperthermia. therapy because of lack of clinical evidence of efficacy. Opiates may be required in some cases. of severely poisoned patients must be performed to lakes. and peripheral nervous systems.4-dichlorophenoxypropionic acid) patient by a second pulse of methylprednisolone on ■■ 2. local anaesthetic sprays. oral and oesophageal mucosa (Fig 28. prevention or treament of renal failure. desferrioxamine. Allow additional oxygen only in victims considered beyond rescue to relieve air hunger and terminal disease. 7. Brands 8. fibrinous pleurisy. peripheral neuropathy. patients received gastric lavage followed by proliferative pulmonary fibrosis. centri- although efficacy has not been proven in prospective lobular necrosis. intravenous dexamethasone every 8 hours for 14 days. confirm or refute benefit of this approach before it can be recommended as a standard treatment. Non-steroidal anti-inflammatory agents. liver. 2.4-dichlorophenoxyacetic acid) day 30 when pulmonary inflammation and hypoxaemia ■■ 2. N-acetylcysteine may be of value. synthesis inhibitors. erosion and patchy muscle weakness. There may be evidence of study. fever. Chlorophenoxy Compounds venous methylprednisolone daily for days 1. Pain due to corrosion may be relieved by ice-cold fluids 400 (e. Supportive measures form the mainstay of treatment : protection of airway.4D (2. colchicine. The patients randomised into the treatment group also received at the end of haemoperfusion 1 gram of intra. Pulmonary damage may be ameliorated by radiotherapy. 5. reddened or desquamated pulmonary oedema. hypotension. and lozenges. 2. acidaemia and coma. randomised 3. muscle rigidity. haemorrhages in the stomach. The combination of corticosteroids and cyclophospha- mide has shown promise in reducing paraquat mortality. collagen 2. or total exclusion from external respiration may prevent lung fibrosis. maintenance of circulation. limited. and weeds in ponds. ■■ MCPP (2-methyl-4-chlorophenoxypropionic acid) recovery was achieved in a severely poisoned paraquat ■■ DCPP (2. Liver may show pallor or mottled fatty change.1: Oral corrosion—Paraquat ingestion (Pic: Dr N (within 4 hours of ingestion) are undertaken. Ingestion: a.4D: Fennoxone. Nitric oxide inhalation by the kidneys via the renal organic anion secretory system.g.info 3. Autopsy Features emesis. bradycardia. They are highly protein bound. central However the current consensus is NOT to undertake radio. More study of a larger number cereal crops. scanty blood-stained pleural effusion. and 10 mg oedema. survival rate Ganapathy) may improve. Weednash.1). rhabdomyolysis.4. tachycardia. In a single case reported separately. Clinical Features is recommended by some investigators. though some recent reports is conjugated. to maintain tissue oxygenation in anticipation of lung trans- plantation once all absorbed paraquat has been eliminated. 1. diarrhoea.5-trichlorophenoxyacetic acid) emerged despite steady daily therapy of dexamethasone These herbicides are used to kill broad-leaved weeds in after the first pulse therapy. treatment of secondary infection.5-T (2. Phenoxy acid esters and salts Lung transplantation has not met with success in most are primarily metabolised by acid hydrolysis. Kidneys may reveal evidence of tubular damage. and treatment of complications. Lungs often appear stiffened.4. and 3. . However. Chief organs of deposition are kidneys. grassland parks and gardens. In one prospective.PharmaDost. They are primarily eliminated unchanged (90%) indicate that it could be beneficial. Oxygen must not be administered as far as possible since it enhances lung damage. Chlorophenoxyacetate herbicides include the following: and cyclophosphamide 15 mg/kg daily for days 2 and ■■ MCPA (4-chloro-2-methylphenoxyacetic acid) 3 of pulse therapy. There are indications Section 8 Hydrocarbons and Pesticides that if intravenous n-acetylcysteine and early haemodialysis Fig 28. the Toxicokinetics efficacy of these treatments has yet to be established in the Rapid and complete absorption of chlorophenoxy compounds treatment of human paraquat poisonings. vomiting. Nausea. and irrigation canals. 1. and silica gel column chromatography for cardia is present. matography with mass selective detection (GC/MSD) e.4-D and/or selective method which does not differentiate between 2. Limited data suggest that urinary and electrolyte disturbances (particularly hypokalaemia. institute continuous cardiac monitoring b. HPLC. Evaluate for hypoxia. or pneumonitis. to partially quantify a variety of chlorophenoxy d. place in Trendelenburg position. 2. Ingestions involving high concentrations. and many other 2. etc. Lignocaine industrial and commercial exposure. some evidence chlorophenoxy and benzonitrile herbicides. administer dopamine or noradrenaline. These two from a report on Vietnam veteran’s children shows a limited herbicide types are often combined in commercial or suggestive level of evidence between exposure to 2. Move patient from the toxic environment to fresh air.8-tetrachlorodibenzodioxin or TCDD) 3. Assisted venti- illnesses in Vietnam veterans. Radiographic Studies: Monitor the chest X-ray in patients monomorphic ventricular tachycardia. The causal relationship between chlorophenoxy herbicides 2. respira- 1 ppb for urine samples. If cough or difficulty sation was successful in improving the detection limit to in breathing develops. Maintain adequate ventilation and oxygena- c. Unstable rhythms require a. Thrombocytopenia and leukopenia have also been with a lower limit of detection of 5 ppb. Monitor liver and kidney function tests. Some studies have suggested a relationship between chlorophenoxy herbicides Treatment Chapter 28 Pesticides and both soft tissue sarcoma and non-Hodgkin’s lymphoma. and cancer remains controversial. 1. evaluate for hypoxia. HPLC—Can be used by utilising methanolic hydro. and hypomagnesaemia). and blood and plasma and/or pulse oximetry. A major limitation of the dubious value. perform endotracheal intubation and provide assisted b. This method is designed for use tory tract irritation. e. patients with underlying impaired cardiac function.4-D levels may be useful in monitoring workers with hypocalcaemia. Allegations of human birth defects related to 2. while others have not. malaise and paraesthesias can occur. eluent. in large epidemiologic studies to document exposure to b.7. alleged to have caused cancer.. However.4. d. or severe a. and hypophosphataemia. acidosis. Decontamination: Activated charcoal. levels as low as 19 ppm and has been validated in 3. chloric acid extraction and resolution with a phenyls. Monitor urine for pH. www. headache. deproteinised with methanol. reported. diazoethane cardioversion. protein.4. The limit of detection is said to be 20 mg/L. If a high FIO2 is required to .5-T and spina bifida. hyperkalaemia. Administer inhaled beta adrenergic agonists if bron- ilyl-modified silica column/aqueous buffer acetonitrile chospasm develops. Onset of acute lung injury after toxic exposure may be compounds in biological samples of acutely poisoned delayed up to 24 to 72 hours after exposure in some patients. A direct enzyme immunoassay can detect urinary exposure in individual troops. Published values using this method are of and/or 2. as a confirmatory test. RBC’s. Manage hyperthermia with sponge baths.3. extraction with diethyl ether. Monitor for respiratory distress. Manage respiratory depression if present. and metabolic acidosis is present. 2. 2. 5. Monitor fluid and electrolyte b. Hypotension: Infuse 10 to 20 ml/kg of isotonic fluid and caused these effects. bronchitis. Laboratory Methods: Sotalol is a good alternative. Ultraviolet Spectrometry—This is an older and non- 2. Induce alkaline diuresis if myoglobinuria. balance and replace as required. sample preparation followed by combined capillary gas 8.4-D products. can be considered if no more than 4 hours have elapsed 4.4-D can be quantitated in human autopsy material. chlorophenoxy herbicides. birth defects. gastric lavage.4-D can be detected with gas chro- d. report was the inability to quantify levels of herbicide f. c. oesophagus and stomach. Monitor CPK levels and serum myoglobin levels. If hypotension persists. and analysis using 401 of long duration may produce burning in the mouth. ventilation as required.5-T have not been confirmed. cases. Urine: 6.info b. GC/MS—A method using acid hydrolysis. Serum/Blood: 4. Hypocalcaemia. 7. a contaminant (2. 1. A mixture of 2. For inhalation exposure: chromatography and mass spectrometry in the selective a. Vertigo. and amiodarone are generally first line agents for stable 3. Obtain an ECG. Consider central Diagnosis venous pressure monitoring to guide further fluid therapy. ionisation modes of positive and negative chemical ioni.PharmaDost. Administer 100% humidified supplemental oxygen. tion with frequent monitoring of arterial blood gases Visceral samples are acidified. Monitor CBC and platelet count. or exposures tion. urine output. Urinary levels of 2.4-D-exposed workers.4. the victim is dehydrated. myoglobin. c.4-D and 2. particularly in with significant exposure. 4. It is however more likely that lation may be required. coma. followed by acidifica- c.5-T (Agent Orange) has been since ingestion. Atropine may be used when severe brady- derivatisation. Maintain adequate urine flow with intravenous fluids if a. Chlorophenoxy compound urine analysis may be useful and administer oxygen. polyoxyethylenea- is preferred if ARDS develops. Monitor Glyphosate herbicides are commonly applied in spray form cardiovascular function. Section 8 Hydrocarbons and Pesticides reactions may require treatment with systemic or topical corticosteroids or antihistamines. alkaline diuresis may While instances of glyphosate poisoning have not been very be useful. If burns are found. may be responsible for many of the wedge pressure should be kept relatively low while still toxic effects of glyphosate. and severe alveolar oedema 4. mucosal erosion/ulceration. Obtain consultation concerning endoscopy as soon as on the type and concentration of the active ingredient and/or possible. Scintigraphy: Scans utilising radioisotope labelled sucral- herbicide additives include sulfuric and phosphoric acid and a fate (technetium 99m) may represent an alternative to variety of inert materials. and chest radiograph in symptomatic patients.PharmaDost. bradycardia. evidence of disseminated no full thickness injury. expressible from cut surfaces were described at autopsy in 5. repeat as indicated. 2. Activated charcoal can be administered in the usual tablets. focal with reactive cellular infiltration. Less commonly. BUN. . all capillaries. The following preparations are and dilute with milk or water. Treatment itor-organophosphate compound). wash Results from animal studies indicate that essentially no toxic skin. Haemodialysis is not effective. Common features include pain in the mouth and throat. including ventricular arrhyth- There was in addition. and perform endoscopy within the first 24 hours the added surfactants. ingestion is controversial. Roundup. granules. follow 10 to 20 days polyoxyethylene amine or POEA) is a class of surfactants most later with barium swallow or oesophagram. Monitor CBC. Serum levels of glyphosate are not clinically useful in a low order of toxicity in mammals. ingestion. powders. an anionic surfactant. is used as a herbicide. the patient may suffer from diarrhoea. poisoning. mild hepatotoxicity. oliguria/anuria. Endoscopy in patients with ulceration Autopsy Features showed gastritis. pellets/ 4.info maintain adequate oxygenation. hyperthermia. massive haemostasis of the lungs in mias. and mucosal oedema. colourless to white crystalline tests. b. Sampoo. liver function toxic effects. minutes. arterial blood gases. is parent compound. nated leather should be discarded. a. mechanical ventilation Mode of Action 402 and positive-end-expiratory pressure (PEEP) may be required. It is an odourless. generalised oedema and and urine output. The polyoxyethylene tallowamines (e. components contained in many preparations may contribute to 2. Glyphosate formulations and their toxicity differ depending 5. Various cardiac arrhythmias. including blood pressure and primarily formulated as either a water-soluble liquid or frequently. blood pressure tory failure. It has 1. rinse the mouth powder and other ingredients. in one case of fatal abnormal mental status. oesophagitis. gastric erosion. urinalysis. In this case. when indicated. manner. endoscopy. respiratory failure. Fluid filled lungs with large quantities of oedema fluid nary oedema. an aminophosphonate (non-cholinesterase inhib. emulsions. cases are beginning to be reported. commonly used in glyphosate formulations. Apart from non-specific signs. Plasmapheresis may be effective for late treatment of 1. The man died within 12 hours of the ingestion. www. 3. Emesis is not recommended. Treat dermal irritation or burns with standard topical Usual Fatal Dose therapy.g. For dermal exposure: Glyphosate appears to undergo minimal metabolism. particularly in young children. serum creatinine. ventilation with small tidal volumes (6 ml/kg) The surfactant present in commercial solution. hair and nails vigorously with repeated soap metabolites are produced and nearly 100% of the body burden washings. The use of corticosteroids for the treatment of caustic Glycel. The pulmonary artery mine. serum electrolytes. particularly if begun soon (vide supra). Dermatitis resembling sunburn has been seen when the another fatal ingestion case. vomiting. Instead. 9. but the surfactant or other assessing the severity of exposure or poisoning. concentrate solution. Obtain baseline ECG. and leukocytosis. powder and is weakly acidic. as no sedation is required for this procedure. No systemic symptoms have been seen due to absorption via intact or abraded skin. or a solution made with a water-soluble 3. Surfactants alone may cause circula- maintaining adequate cardiac output. all contami. Glyphosate Glyphosate. Leather absorbs pesticides. seizures. Poor prognosis is associated with the combination of pulmo- 2. Significant erosion of the stomach lining was also observed. but 1. Patients developing dermal hypersensitivity Ingestion of > 200 ml is likely to produce severe toxicity. muscle cell necrosis was discovered in myocardial fibres. Remove contaminated clothing and jewellery. pulmonary oedema and shock. Brands 7. the abdominal and material has been in contact with skin for more than 30 thoracic cavities contained a thin reddish watery fluid. and cardiac arrest have been reported. acidosis and hyperkalaemia. Other glyphosate 6. common in India. Glyphos. Clinical Features 10. aerosols. also available: pressurised liquids. and microencapsulated products. metabolic acidosis. Repeat doses of no more than half the original colon cancer). zineb and ziram. They do not inhibit acetylcholinesterase (unlike 403 that cover anaerobes and oral flora such as penicillin. Some are found in suntan and antiseptic sprays.9 ml/min) was as good Clinical Features as by haemodialysis (52. FUNGICIDES and rarely renal failure. Fungi guard. embryonal lethality. Teratogenecity and carcinogenecity: Benomyl: Benlate. persists. hoarseness. extrapyramidal effects. Krilaxlyl. ampicillin. or if perforation or infection is suspected. Dithane M-45. Examples. textile. Other manifestations have included CNS depression. significant maternal toxicity. teratogenic effects. seizures. thiram. Absorption of these agents across the skin and GI lining is superior to haemoperfusion (6. and some required. Zinax. Indofil M-45.info 8. Paedistin 6. Ridomil. containing in particular. melanoma.PharmaDost. conjunctivitis. and thyroid carci- Mancozeb + Metalaxyl: Master. administer dopamine or noradrenaline. and retarded foetal development Dhanuka M-45. Zebatane down product of ethylene bisdithiocarbamate fungi- Carbendazim + Mancozeb: CM-75 cides (maneb. Hepatomas. which may be responsible for toxicity. 9. If a high FIO2 is required to Formulations are widely used for pest control in home maintain adequate oxygenation. captan. Carbendazim 11. robenzene and sodium azide. Zeb 75. abdominal pain. nabam. probably slower than absorption of the organochlorine and ester insecticides. thiocarbamates. and neuropathy. Usual Fatal Dose 12. Hilthane. no more often than every 10 minutes if required. Derosal. Benofit a.5 ml/min). maneb. hexachlo. plastic industry as an antioxidant. . Maintaining Ingestion of > 200 ml is likely to produce severe toxicity. ferbam. or clindamycin are to be preferred. Benfil. For hypotension. and positive-end-expiratory pressure (PEEP) may be 2. Glyphosate is excreted rapidly in the urine. Captaf. Ziram 2. Uthane. 5. fungicides. Kilex. usually Carbendazim: Bavistine. membranes. both of which were 1. Most of these compounds are used as fungicides. breast cancer. Captofol.4 ml/min). bavistin. Agents low toxicity. 3. Matca. Begin with 1 mEq/kg in adults and in with advanced malignancies (i. Thiocarbamates Some agricultural workers experience upper respiratory Examples include benomyl. Pestmil nomas have been described. and place in Trendelenburg position. Ziram: Cumun-L. Thiram is related to disulfiram and produces a mate or ethylenethiourea) compounds that are also used as similar reaction with ethanol. weakness. diallate. Exposure results in vomiting. congestion. the sulfur- Carbendazim (carbendazole).e. gases and/or pulse oximetry. Carbendazim is also used as a preservative in the paint. ventilation with small tidal volumes (6 ml/kg) medicated cleansing agents. Mancozeb: Bayleton. diarrhoea. papermaking and leather industries. all of these chemicals. molinate. mancozeb. Mancozeb + Thiophanate methyl: Roko Thiophanate methyl: Cover Treatment Zineb: Indofil 1 Activated charcoal can be administered. Gastric lavage is recommended if done early and cautiously. Zeb b. and as a rubber accel- 10. 2. Although detailed pharmacokinetic studies of these compounds are not available. Dhanustin. Chapter 28 Pesticides amount may be given. Sparsh. captafol. or dusts containing these compounds. If hypotension 3. Luzem. children. 4. To some degree. Ethylene thiourea (ETU): A contaminant and break- M. benthiocarb (or thiobenzcarb). were reported. trial. late. These are compounds which kill fungi and moulds. The use of antibiotics is suggested if corticosteroids are These compounds are used as fungicides and have relatively used. Vijay M-45. vitavax. For acute lung injury. Manzate. thiophanate. mechanical ventilation gardens and in commercial agriculture.1) with IV sodium is also currently undergoing clinical trials in adult patients bicarbonate. ETU. are irritating to the skin and mucous and vondozeb are benzimidazole (ethylenebisdithiocarba. vertigo. lymphomas. Kavach. infuse 10 to 20 ml/kg of isotonic fluid erator. Benguard. within hours or days of absorption. These agents are often compounded with hydrocarbon- based solvents. JK Stein. In female rats exposed to carbendazim during gesta- Benthiocarb: Saturn tion. Treat severe acidosis (less than pH 7. zineb) is a recognised carcinogen Carbendazim + Iprodione: Quindal in animals. an adequate urine output is important as the clearance of glyphosate by the kidney (52. www. Some are also used in the is preferred if ARDS develops. maintain adequate ventilation and Sources and Uses oxygenation with frequent monitoring of arterial blood 1. carbamates). there is indirect evidence Brands (minimal tissue storage after dosing) that these chemicals Propineb: Antracol are rapidly metabolised and/or excreted by humans. and cough if they breathe sprays cycloate. www. bromide levels do not accurately epine (diazepam or lorazepam). been suggested as antidotes based on the postulated 3. and they are not recommended for routine 4. results in progres. begin fluid administration.000 ml/hour intravenous saline Ethylene dibromide is a severe skin irritant in liquid form. coma and death. pests. Rinse thor- ropropane.PharmaDost. For convulsions: Attempt initial control with a benzodiaz. and grain crops. Place on a cardiac been used historically as fumigants. administer phenobarbitone. causing human poisoning not infrequently. ethylene dibromide. 3. Use caution to avoid hypothermia Ethylene dibromide was previously approved for use as when decontaminating patients.info 3 Intravenous fluids may be useful in restoring extracellular Diagnosis 404 fluid volume if this has been depleted by vomiting and diarrhoea. and nematodes the elderly. 6. chloroform. In cases of inhalation exposure.5% tetracaine. However. If seizures persist or recur predict the clinical course. These are compounds which kill nematodes (i. Higher inhaling or ingesting it can cause death. There is no proven antidote for ethylene dibromide rhoea. Treat patients who have bronchospasm with an aerosolised sive dysfunction. particularly children or a fumigant to protect against insects. worms). In 1984. Ethylene dibromide Treatment Fumigants are applied to control rodents. Dermal Exposure: Erythema. Inhalation/Ingestion: Burning sensation. 1. sion. Administer supplemental oxygen as required and grains. Ocular Exposure: Conjunctivitis has been reported after mechanism of ethylene dibromide’s toxicity. Activated charcoal is helpful in cases of ingestion. Dimercaprol (BAL) or N-acetylcysteine have 2. and or lactated Ringer’s solution may be appropriate. Manifestation of some of the effects of acute bronchodilator such as salbutamol. oughly with water. necrosis. and as a fumigant for tion as needed. hepatotoxicity with liver a 20 ml/kg bolus of normal saline over 10 to 20 minutes. 15 minutes. bolus perfusion of 1. . disruption and reduced glutathione levels. tissues and organs. pulse. and electrolyte determinations. chest radiography and example. pain. but only a few remain in monitor. acute renal failure. Flush exposed skin and hair with water for at least tetrachloride. Irrigate exposed or irritated eyes with tap water or Protection Agency (EPA) banned its use as a soil and grain saline for 15 to 20 minutes. Remove contact lenses if fumigant. and commodities. nematodes. rates. Chronic Exposure: There is inconclusive but suggestive use. For children with compromised perfusion administer dyspnoea. then infuse at 2 to 3 ml/kg/hour. bronchitis. glucose. high exposure may be delayed a few days. metabolic acidosis. insects. For 4. ensure adequate respiration and Section 8 Hydrocarbons and Pesticides weed seeds. time for late neuropsychiatric sequelae. particularly on golf courses. dibromochloropropane. Abdominal pain. evidence that ethylene dibromide may reduce fertility in 7.2-dichlo. Serum bromide levels can be used to document that expo- 4. such as 0. Cellular disruption in 3. 5. widely. Many different chemical classes have establish intravenous access if necessary. exposure to ethylene dibromide. Temporary loss of vision no adequate studies have tested the efficacy of these may occur. Additional studies for patients exposed to ethylene dibro- NEMATICIDES mide include liver-function tests and renal-function tests. the Environment b. may be necessary to alleviate blepharospasm. sure did occur. CNS depres. 2. and ethylene dichloride. men. blistering. such as liver and kidneys. and lid Mode of Action retractors may be required to allow adequate irrigation Ethylene dibromide alkylates macromolecules causing cellular under the eyelids. Establish a patent airway. therapies. it continues to be used easily removable without additional trauma to the eye. then wash twice with mild soap. Use blankets or warmers after decontamina- in citrus. pulmonary oedema. Supportive and symptomatic measures. Routine laboratory studies include CBC. many of which were halogenated solvents. 1. of discontinued halogenated hydrocarbons includes carbon a. in India. are common early manifestations in cases of ingestion.e. Irrigate exposed skin and eyes as appropriate. turf. use today. ethylene dibromide. structures. Remove toxicity. poisoning. crop. Antispermatogenic effects have been demonstrated 8. Unfortunately. vomiting. vegetable. The list contaminated clothing. Most fumigants were abandoned because of their 2. cough. For adults with systolic pressure less than 80 Clinical Features mmHg. arterial blood gas measurements may be helpful. Patients who survive should be monitored over a period of in various animal species. If evidence of shock or hypotension is observed. and diar. An ophthalmic anaesthetic. and fungi anywhere in the soil. 1. However. adult systolic pressures may necessitate lower perfusion 1. 4. Dialysis is ineffective. today instances of negligent storage of food grains. is so widespread in India. tedion. chlorfenson and chloralose. on the part of farmers who were preserving food grains with ciation with seizures. naphthalene.2: Subcutaneous injection of OP pesticide with accounting for an estimated 3 million cases of severe poisoning discolouration and myonecrosis (Pic: Dr S Senthilkumaran) . Over a thousand people were Instances of poisoning are however rare.PharmaDost. phosphide is making relentless inroads. and of offices sprayed with diazinon. such as India. hydrogen cyanide. though a few cases have involved It is a tetramer compound with an 8 member ring containing self-injection (Fig 28. nausea. Other effects have included renal spraying of BHC in concentrated form in a thickly populated tubular injury and liver necrosis. Health care professionals may be exposed to These include compounds of lead. revealed in many cases that surface concentrations were higher at 24 or 48 hours than at 1 hour after spraying. nico- tine. Among the MOLLUSCICIDES various pesticides. in 1958. and death. In the UK. with approximately 220. severe abdominal 1970s). and fruits along with toxic pesticides leading to large The probable lethal dose is in the range of 100 mg/kg for scale contamination are not uncommon. Mydriasis has been reported. in one study demonstrated residual insecticide levels in most of cial. and kelthane. or bendiocarb ascorbic acid. Respiratory failure may occur 24 Unfortunately. copper. methyl bromide. and is a cyclic polymer of acetaldehyde. More recently (late Metaldehyde overdosage results in lethargy. N-acetylcysteine. Pesticide contamination adults. which leaked into the Chapter 28 Pesticides the purpose of producing coloured flames used in entertaining. dinitrocresol. vegetables. None of these have been tested in humans. hyperthermia. sabadilla. Metaldehyde cides resulting from excessive crop spraying or improper storage sublimes to form copious “artificial snow”. metaldehyde. packages containing the former. For for most of the reported cases of poisoning. D-penicillamine. poisoned subsequently due to consumption of the contaminated tant on skin and mucous membrane and a systemic convulsant. dinitrobutylphenol. FORENSIC ISSUES (ALL PESTICIDES) Acute pesticide poisoning is a serious global problem Fig 28. seizures. hundred people in Uttar Pradesh due to shocking ignorance coma. In the paediatric age group domestic pesticides can account for a substantial number of poisoning cases. More than 90% of these cases are reported from developing countries 405 These are compounds which kill mites. A study for seizures. Suicidal exposure to these pesticides is Metaldehyde invariably via the oral route. aldehyde molecules. though aluminium example. Many of these compounds have been discussed in other sections elsewhere. rotenone. and the reader is advised to consult the Index for locating them. Inhalation of metaldehyde fumes may cause CNS depression. It is a tasteless substance with a mild charac. dinitro- phenol. In fact the contamination of food with pesti- the substance in a test tube and gently warming. pentachlorophenol. sugar. chlorobenzilate. Activated charcoal may be benefi. of vegetables is an even bigger problem in India as compared to Bait that contains metaldehyde can be detected by placing many other countries. secretions are prominent. www. It is a local irri. India indicate that the figures range from 20% to a staggering 70%. that blood samples and milk samples Treatment is mainly directed at decontamination and (from lactating mothers) collected randomly from several people management of convulsions. pesticides are responsible for only Examples. Increased tracheobronchial area leading to similar mass morbidity. organophosphates and carbamates account Compounds which kill molluscs such as snails and slugs. diarrhoea. Occupants should be warned of treatment times and steps taken to mini- MISCELLANEOUS PESTICIDES mise exposure. tetrachloroethylene. Unproved antidotes which have the samples. It is available in some countries in tablet form for in the same cabin on a ship as parathion. chlorpyrifos. Metabolic acidosis and respiratory BHC. trichloroethane. material and more than a hundred died. azobenzene. Dioxins which are present as contaminants of some herbicides also can produce toxicity. Wheat flour and sugar had been inadvertently stored teristic odour. ticks and spiders. vomiting. thiamine.info ACARICIDES worldwide each year.000 deaths. been tested in animals or suggested include: calcium gluconate Exposure to pesticides can occur in other ways. and mercury. lessons are not learnt from history and even to 40 hours after ingestion. a severe convulsive epidemic broke out among several pain.2). Another (even more recent) incident involved accidental alkalosis have been reported. The terrible potential for pesticides to cause mass poisoning Metaldehyde is a popular molluscicide being effective against was not realised in India till the Kerala food poisoning tragedy snails and slugs. Profound hyperthermia may occur in asso. about 1% of deaths from poisoning while various studies in They are infrequently encountered in human poisoning. especially in Northern and Central India. Srivastava SB. Marcel Dekker. Lin JL. Significant exceptions include thallium and 2003. abusers in an attempt to prolong cocaine effects by decreasing 10. Erratum: Cyclophosphamide in paraquat poisoning.39:109-11. Chen KW. Raji V. Poisoning due to other pesticides is relatively uncommon 16. 18. as ticide in blood and milk. have been developed as “nerve phorus pesticide poisoning: a systemiatic review. Pandya TP. Bawaskar HS.5:32-4. 2000.19:44-6.53:422-4. rather than herbicides. Med tions. Regional study of para- cholinesterase activity. toxic waste disposal. Pillay VV. Chandran MR. 2005.7:906-10. Srijithesh PR. (Abstract).51:1199. Q J Med gases” for chemical warfare. Paraquat: The underestimated lethal pesticide. Nair PMC. Somasundaram S. such as 7.000 people were affected by the attack with 12 deaths. Hall AH (Eds). Virendra Kumar.14:600-14. However. Determination of 2. . 5.39:266-9. phates and carbamates have always been extremely popular in 17. where sarin associated with emergency department treatment of organophos- was released in a subway system of Tokyo. Hospitals 3. Kaur H. J Med Toxicol Legal Med 2002. and individual ventila- 4. Balaji Pandian. many household insecticides consist of carbamates 15. Hall AH. groomers. and food stuff. 2. technicians. several 12. Acad Emerg Med 2000. Pseudochol Homicidal poisoning involving pesticides has always been inesterase levels. Carbendazim-induced 1. One case report documents two child syndromes. the incidence 14. 9. in some states. cases have been reported even 20. 13. pralidoxime or both (letter)? Owing to easy availability. 95-101. J has in fact edged out the other insecticides from the top spot Indian Soc Toxicol 2007. cases are still reported owing to surreptitious use. et al.36:755-64. FURTHER READING 22. Nosocomial poisoning Section 8 Hydrocarbons and Pesticides use by a terrorist group occurred in March. aluminium phosphide has begun to find increasing favour and (Abstract).95:275-83. 6. study of 350 patients suggested that viral and alcoholic complica.36:474-7. However. Human exposure secondary to 2002. Japan. Eyer P. Symptomatic organophosphate quat poisoning during 1997. A study of residual insec- resulting from occupational exposure. et al. Organophosphates found in veterinary products of organophosphorus compound poisoning. Daisley H.info cholinesterase inhibitors while caring for patients. Barlas N.51:1199. et al. Intermediate syndrome of poisoning involving these compounds has been declining. Chattopadhyay PK. In order to curb the incidence of accidental poisoning 11. soman. Simmons V. Ray DE. Badkur DS. Sanmuganathan PS. Oximes in acute organophos- tabun. J Assoc Physicians India tions complicating organophosphorous insecticide poisoning. well as contamination of water. Agrawal N.4-D) in human urine with mass selective Organophosphates may be deliberately ingested by cocaine detection. Geller RJ.3(2):11-4. Am Since several organochlorine pesticides have been banned J Respir Crit Care Med 2001. (including DDT and BHC) from 1997 onwards.22:814-5. synergies. In 406 need to plan for such emergencies by having access to large Bismuth C. pet owners. Senanayake N. Int rise. which most of these phosphorus poisoning.23:86-9. and domestic pets. Ritter DJ. Choudhary R. A review of 131 cases. Organophosphate except among individuals who are occupationally exposed. veterinary 1998. a Therapeut 1998. In recent times. Mass morbidity by BHC poisoning. Wong A. Today. Endosulfan poisoning in Vietnam veterans potentially exposed to chlorophenoxy herbi. stores of atropine. Clin Toxicol 2000. Paraquat Poisoning : Mechanisms – Prevention – Treatment. Food-borne outbreak tion systems. Saudi Med 2001.38: murders accomplished with paraquat. Job C. nostic factors of a glyphosate-surfactant herbicide intoxication: and the Insecticides Rules of 1971. www. J Assoc Physicians India chemicals possess. J Assoc Physicians India 2003. Organophosphate poisoning in 23. Songur S. Northern India: A report of 18 cases. Internatl J Clin Pharmacol cides were noted to have chronic liver abnormalities.4-dichlor- that 1. J Indian Acad Forensic Med 2001. New York. arsenical compounds. Javad H. RBC cholines- India for the purpose of committing suicide. Bismuth C. and VX.39:305.163:585. Pyrethroid insecticides: Poisoning with other pesticides. 1995. Forshaw PJ. Mishra G. Tarantino ML. clinical assessment and outcome in organo- rare owing to disagreeable odour/taste. phenoxyacetic acid (2. Human Exp Toxicol 1995. 1995. Lee HL. 2001. Bala S.20:625-30.23:15-6. Skin toxicity from haematological. Satpathy DK. Nagesh KR. Spiller HA. Al-Mandhiry ZA.317:268-9. Sharma VK. Hum Exp Toxicol 2004. Clin Toxicol 2001. J Toxicol . Toxicol Clin Toxicol 2001. Motta A. Mishra B.atropine. Sullivan JE. USA. 19. Mattingly JE. J Environ Sci Health B 2001. Chi CH. Revi NG. biochemical and histopathological changes glyphosate-surfactant formulation. Pradeep Kumar G. The most notable case of sarin 8.PharmaDost. particularly among children. Joshi SR. Estimates are phate toxicity-Georgia 2000. Hughes DL.42:317-9. et al. Wilson RD. Amerio P. Extrapyramidal manifesta- agricultural India – Status in 2005. Dhawan R. poisoning in children . J Ind Acad Forensic Med 1997. terase and serum cholinesterase in organophosphorus poisoning. Br Med J may be a source of poisoning for veterinarians. Paraquat ingestion exposure. Sci Law 1999. Toto P. Singleton KL. were the causative factors. J Indian Acad Forensic Med poisoning has been reported in this setting. terrorist activity has occurred. 21. Selmanoglu G. sarin. and therapy. and pyrethroids and hence poisoning involving them are on the Glyphosate poisoning – a rare case of herbicide poisoning. Szinicz L.Clin Toxicol to the liver and kidney of male rats. Clinical presentations and prog- clauses have been incorporated in the Insecticides Act of 1968. after exposure to chlorpyrifos in a 16-month-old female. Eddleston M. Organophosphates which are very rapid-acting. negligent handling. Homicide by paraquat poisoning. milk. pesticides such as organophos. et al. Chugh SN. J However.