Organophosphate and pesticide poisoning

• Organophosphates (OPs) are insecticides and herbicides that block acetylcholinesterase, so acetylcholine builds up and overstimulates muscarinic, nicotinic and central cholinergic receptors (the cholinergic crisis). Untreated respiratory failure from bronchorrhoea and bronchospasm is the usual cause of death.^[2]
• A single large ingestion can kill within hours; fatsoluble OPs such as fenthion can leach from stores and cause repeated crises over days. About one in five patients develop an intermediate syndrome 24 to 96 hours later, with proximal weakness and respiratory failure.^[5]
• The antidote pairing is atropine (for muscarinic effects) plus an oxime such as pralidoxime (to reactivate the enzyme). Atropine is given in repeated doubling boluses until the chest is clear, then as an infusion of 10 to 20 percent of the loading dose per hour.^[1][6]
• For every other add-on (hemoperfusion, plasma exchange, lipid emulsion, magnesium, alkalinisation, penehyclidine, rhubarb, xuebijing) the evidence is very weak, and current reviews recommend against routine use.^[1]
• Paraquat deserves separate attention: it is not a cholinesterase inhibitor, has no antidote, and kills mainly through lung fibrosis. Its case fatality remains high even after formulation changes.^[4]

By the end of this page you should be able to:

1. Explain why an organophosphate produces a cholinergic crisis and trace each clinical sign to its receptor.
2. Distinguish acute cholinergic crisis, intermediate syndrome and delayed neuropathy by timing and mechanism.
3. Atropinise a patient safely, including end-points, doubling, infusion rate and signs of atropine toxicity.
4. Give the standard oxime regimen, state when it helps and when it does not, and manage benzodiazepine use.
5. Outline an evidence-based approach to decontamination and airway care in a poisoned, vomiting patient.
6. Recognise paraquat and other pesticide classes that masquerade as organophosphate poisoning, and explain why some (amitraz, fipronil, 2,4-D) look similar.
7. Counsel a reader on the global burden of pesticide poisoning and on prevention at the population level.

Organophosphates are a broad group. Clinically relevant subtypes include:

• Insecticides such as chlorpyrifos, diazinon, parathion, malathion, monocrotophos and dimethoate. These cause most human poisonings.
• Nerve agents such as sarin, soman, tabun, VX and the Novichok agents. These follow the same biochemistry but are far more potent and act within minutes.^[2]
• Carbamate insecticides (for example aldicarb, carbofuran) also block AChE but bind reversibly, so oximes are not used.
• Other pesticides that produce a similar picture without touching AChE: amitraz, fipronil and 2,4-dichlorophenoxyacetic acid (2,4-D) are common mimics.^[1]

A note on pronouns and units: doses below are adult doses from published review sources. Paediatric and renal or hepatic adjustments are flagged where a source gives them; otherwise check your local formulary before use.

Pesticide poisoning is one of the world's most frequent and most lethal poisonings, and it falls hardest on people who farm.

• Global annual burden. One 2020 synthesis estimated about 385 million cases of unintentional acute pesticide poisoning including 11,000 fatalities per year. An updated systematic review covering 2006 to 2023 across 139 countries now estimates about 402 to 433 million cases of unintentional acute pesticide poisoning annually, including around 11,000 deaths. About 46 percent of the roughly 934 million people in farming occupations are estimated to be poisoned by pesticides each year, with the highest estimated numbers of non-fatal cases in southern Asia, then south-eastern Asia and east Africa.^[3]
• Intentional self-poisoning. Pesticides account for an estimated 14 to 20 percent of global suicides, with 110,000 to 168,000 deaths a year in 2010 to 2014 (down from an estimated 258,234 in 2002, credited to pesticide regulation and rural-urban shift). Some 14 million people have died by suicide using pesticides since the Green Revolution began in the 1960s.^[3]
• Occupational burden. Jeyaratnam's earlier estimate was 25 million cases of occupational acute pesticide poisoning a year, most unrecorded because the person never seeks care.^[3]
• Organophosphates specifically. OP poisoning is estimated to cause around 200,000 deaths per year, concentrated in agricultural regions where these compounds are widely available.^[5] The case fatality for pesticide self-poisoning in general is commonly 10 to 20 percent, but for particular compounds it can be as high as 50 to 70 percent.^[6] Mortality from deliberate OP poisoning exceeds that from accidental exposure.^[2]
• Trend. Global pesticide use has doubled since 1990 to about 3.8 million tonnes per year in 2023, even though developed nations have cut their poisoning burden through stricter regulation.^[2][3]

• Exposure routes. Ingestion (most fatal self-poisonings), dermal absorption (especially during spraying without protection) and inhalation of spray mist.
• Compounds. Lipophilic OPs such as fenthion and dimethoate are metabolised slowly and carry a higher risk of intermediate syndrome.^[5]
• Occupation. Farmers, agricultural workers and applicators.
• Other risk factors. Malnutrition lowers muscle reserve, elderly patients have reduced reserve, and genetic variation in the detoxifying enzyme paraoxonase-1 may modulate susceptibility (evidence is preliminary).^[5]
• Exposure clustering. Family members of spray workers are exposed secondarily. A large Sri Lankan randomised trial showed that encouraging locked household storage of pesticides did not reduce poisoning.^[4]
• Intent. Self-poisoning has a higher case fatality than accidental exposure, and is the dominant driver of OP deaths worldwide.^[2]

Acetylcholine is the neurotransmitter at every autonomic ganglion, every parasympathetic post-ganglionic ending, the sympathetic sweat glands and all skeletal neuromuscular junctions. AChE sits in the synaptic cleft and hydrolyses acetylcholine within milliseconds, ending each signal.

An OP molecule binds to the serine in the active site of AChE and phosphorylates it. The enzyme is inactivated. Acetylcholine accumulates and overstimulates nicotinic (Nm, Nn) and muscarinic (M1 to M5) receptors, as well as central cholinergic pathways. Three clinical pictures follow, each with its own timing.^[2]

1. Acute cholinergic crisis. Starts within minutes to a few hours of exposure and dominates the first 48 hours. Muscarinic excess produces bronchorrhoea, bronchospasm, miosis, sweating, salivation, vomiting, diarrhoea, bradycardia and hypotension. Nicotinic excess produces fasciculations, skeletal muscle weakness, tachycardia and paralysis. Central effects are agitation, confusion, seizures and coma.
2. Intermediate syndrome (IMS). A separate nicotinic problem that appears after the cholinergic crisis has been controlled: 24 to 96 hours after exposure, often as atropine is being withdrawn. It is driven by sustained inhibition of AChE at the neuromuscular junction (especially by lipophilic compounds), nicotinic receptor desensitisation, oxidative stress and direct myotoxicity. The result is proximal limb and neck-flexor weakness, cranial nerve palsies and respiratory muscle weakness.^[5]
3. Delayed neuropathy. A polyneuropathy that can follow weeks after exposure to particular OPs, caused by inhibition of neuropathy target esterase rather than AChE. It is not prevented by atropine and recovery is slow.

Acute cholinergic crisis: a farm worker was spraying in the field when he suddenly felt sick, his eyes watered, he could not see properly, he was drooling, his stomach cramped and he vomited, and he could not breathe. Poisoning often announces itself by a smell of garlic, solvents or rubber in the breath, or a fainting spell.

• Screening signs that demand action: pinpoint pupils, profuse sweating, air entry reduced by bronchorrhoea or bronchospasm, bradycardia, hypotension. These are the five signs used by the treatment protocol referred to throughout this page.^[6]
• Muscle twitching, cramps and weakness.
• Headache, dizziness, confusion, agitation, seizures, coma.
• Late cranial nerve weakness (ptosis, diplopia, nasal voice) signals intermediate syndrome, not persistent poisoning.

• Airway and breathing: count the respiratory rate; listen for wheeze and crepitations; watch for accessory muscle use and nasal flaring. Suction and auscultation are the practical monitors.
• Pupils: symmetric miosis from systemic absorption. If only one eye is constricted, that eye was splashed and may not dilate with atropine.
• Skin: profuse sweating; in a hot ward diaphoresis plus fasciculation produces dangerous hyperthermia.
• Heart: pulse may be slow, normal or even fast; do not exclude poisoning because the rate is fast.
• Muscles: fasciculations, proximal weakness, neck-flexor weakness. Test neck flexion specifically: ask the patient to lift the head off the pillow.
• Abdomen: diarrhoea, hyperactive bowel sounds early; ileus later (especially with atropine).

A vignette: a 24-year-old farm labourer is brought in two hours after drinking a colourless liquid with a strong smell. He is sweating heavily, has pinpoint pupils, audible wheeze and a respiratory rate of 32. His heart rate is 48 per minute. There are fasciculations in the arms. The diagnosis is OP poisoning until proven otherwise; the immediate question is not the bottle label but whether he needs atropine now.

The diagnosis is clinical. Laboratory tests support it and measure its course, but treatment must not wait for them.

• Red cell (erythrocyte) AChE activity. The specific test for OP effect at the synapse. It falls in OP poisoning and a value under 10 to 20 percent of normal is a strong predictor of intermediate syndrome.^[5]
• Plasma or serum butyrylcholinesterase ("pseudocholinesterase"). Cheaper and easier, but less specific and less closely linked to clinical severity. Useful in resource-limited settings.^[5]
• Electrolytes, renal and liver function, arterial blood gases, creatine kinase. Hypokalaemia and hypomagnesaemia worsen muscle weakness; a raised creatine kinase reflects myotoxicity in intermediate syndrome.^[5]
• Chest radiograph and ECG. Often nonspecific; may show aspiration or tachyarrhythmia.
• Electrophysiology (nerve conduction, repetitive nerve stimulation, single-fibre EMG). A decremental response at low frequencies or repetitive compound muscle action potentials can appear before clinical weakness. Rarely available where most poisonings occur; clinical vigilance then carries the case.^[5]
• Identification of the product. Keep the bottle and its label. Blood and urine toxicology confirms the agent when results are available, but the clinical syndrome decides treatment.

There is no single validated score that safely grades initial severity: patients change quickly and any mild label can falsely reassure.^[6] Clinically, most presentations are described as mild, moderate or severe by features:

• Mild: localized muscarinic signs (miosis, salivation, vomiting, diarrhoea) without respiratory distress or weakness.
• Moderate: bronchorrhoea or bronchospasm, fasciculations, marked sweating, but protected airway.
• Severe: respiratory failure, coma, seizures or cardiovascular collapse; these patients need immediate atropine, airway control and ventilation.

Because the World Health Organization classifies OP products by acute toxicity, exposure to a WHO class I compound (for example parathion or monocrotophos) carries the higher risk of intermediate syndrome.^[5]

The first minutes are airway, breathing and circulation. Then antidotes. Decontamination follows only once the patient is stable.

The protocol above is distilled from Eddleston et al. and the umbrella review; always defer to your local poison centre and hospital protocol.^[1][6]

• Protect yourself and others first: gloves, gown and eye protection; remove contaminated clothing and wash skin with soap and water. Personnel have developed symptoms from splashes.
• Skin and eye. Irrigate copiously.
• Gastric lavage is considered only after the patient is stable, and only if a highly toxic pesticide was taken and arrival is within 1 to 2 hours. Perform it in a calm, consented patient or in an intubated unconscious one; manage uncooperative, drowsy or un-intubated patients by airway control first. Use 300 mL aliquots of water or normal saline through a nasogastric tube and measure what is returned.^[6]
• Activated charcoal. 50 g without cathartic, orally or via nasogastric tube, in cooperative or intubated patients, particularly with early presentation or severe toxicity.^[1]
• Current reviews recommend against gastric lavage beyond about one hour of OP self-poisoning, because benefit is uncertain and harm is possible (aspiration, arrhythmia).^[1]
• Do not induce vomiting (ipecac is harmful) and do not give cathartics. Gastric lavage is not used routinely for carbamate poisoning.

Atropine is an antimuscarinic. It reverses bronchorrhoea, bronchospasm, bradycardia and excessive secretions, but it does not reactivate AChE and does not help nicotinic paralysis.

Loading. For an unconscious patient, give 1.8 to 3 mg IV (three to five 0.6 mg vials) rapidly into a fast-flowing drip. Do not delay atropine for oxygen if oxygen is unavailable, because atropine itself improves oxygenation by drying secretions.^[6]

Atropinisation. Three to five minutes later, check five parameters: clear chest on auscultation with no wheeze, heart rate above 80 per minute, pupils no longer pinpoint, dry axillae, systolic blood pressure above 80 mmHg. A uniform improvement in most parameters is required; the most important are air entry, heart rate and blood pressure.^[6]

Pupil dilatation is sometimes delayed and is the least reliable of the five. Do not chase a fast heart rate: 120 to 140 per minute suggests atropine toxicity rather than adequate treatment. Conversely, tachycardia from hypoxia, agitation, alcohol withdrawal or fast oxime administration is not a reason to withhold atropine.^[6]

Continuation. If 3 to 5 minutes pass without a uniform improvement, double the dose, and keep doubling each time there is no response. Do not simply repeat 3 mg: some patients need tens or hundreds of milligrams, and using small repeated doses can let the patient die before atropinisation. Severely poisoned patients need rapid atropinisation, not gradual escalation.^[6]

Infusion. Once atropinised, give 10 to 20 percent of the total loading dose every hour through a separate infusion. If the initial requirement was over 30 mg, use a lower percentage. Rates above 3 to 5 mg per hour require especially frequent review.^[6]

Observation. Recheck the five parameters every 15 minutes at first, then hourly for the first 6 hours, then every 2 to 3 hours once stable. If cholinergic signs return (bronchorrhoea, bradycardia, wheeze), give further boluses and raise the infusion rate.^[6]

Atropine toxicity. Excess atropine causes agitation, confusion, urinary retention, hyperthermia and ileus (loss of bowel sounds) with tachycardia.^[6] If confusion plus pyrexia plus absent bowel sounds occur together, stop the infusion, review every 30 minutes, and restart at 70 to 80 percent of the previous rate when settled. Delirium in a poisoned patient may also be alcohol withdrawal, which needs benzodiazepines rather than more atropine.^[6]

Endotracheal intubation. Unconscious patients should be intubated early to protect the airway, even if a Guedel airway is working. Diazepam keeps the patient tolerant of the tube.^[6]

Temperature control. Hyperthermia is lethal in hot, humid wards. Use the minimum atropine that controls muscarinic signs, sedation for agitation, and active cooling (water-soaked towel with fan airflow).^[6]

Oximes reactivate phosphorylated AChE and thus can address nicotinic paralysis and prevent intermediate syndrome, but only if given before the enzyme "ages" (the phosphate-enzyme bond becomes irreversible, within hours to days depending on the OP).^[1][6]

• Regimen (WHO guideline, as cited in the review sources). Pralidoxime chloride: 30 mg/kg IV loading dose over 10 to 20 minutes, then a continuous infusion of 8 to 10 mg/kg per hour until clinical recovery, for example 12 to 24 hours after atropine is no longer required or the patient is extubated, or up to 7 days, whichever is later. In adults this is often expressed as a 2 g loading dose followed by 500 mg per hour. Obidoxime: 250 mg IV loading dose, then 750 mg every 24 hours (or an infusion of 0.5 mg/kg per hour).^[5][6]
• Evidence. The most recent umbrella review of 19 systematic reviews found no clear evidence of benefit or harm from oximes, with a pooled relative risk of mortality of 1.53 (95 percent confidence interval 0.97 to 2.41) and a very low-quality signal for intermediate syndrome (relative risk 1.63, 1.01 to 2.62). Methodological flaws, small samples and inconsistent dosing limit confidence. The reviewers therefore say it is not possible to definitively recommend or reject oximes, but WHO recommends supplementing atropine with an oxime, and that is the position followed at the bedside.^[1][6]
• One point of honesty. WHO recommends adding oximes to atropine; the umbrella review finds neither benefit nor harm. Both statements stand; an individual patient's management should follow local protocol and toxicology advice. It is not appropriate to quote either as a proven mortality benefit.

Diazepam is the preferred sedative in severe OP poisoning: it controls seizures, reduces agitation (avoiding hyperthermia from struggling against restraints), and may reduce central respiratory depression and cerebral injury.^[6] Atropine does not control nicotinic seizures.

• Diazepam 5 to 10 mg (0.05 to 0.3 mg/kg per dose) IV, lorazepam 2 to 4 mg (0.05 to 0.1 mg/kg per dose) or midazolam 5 to 10 mg (0.15 to 0.2 mg/kg per dose).^[1]
• For intubated patients, sedate to tolerance of the tube. Diazepam 10 mg by slow IV push, repeated up to 30 to 40 mg per 24 hours, is one commonly used regimen.^[6]
• Avoid haloperidol (non-sedating, thermoregulatory disturbance, QT prolongation, pro-convulsant effect).^[6]

• Airway. Left lateral, head-down position, Guedel airway, suction, then endotracheal intubation if unconscious. Aspiration of pesticide and gastric contents causes chemical pneumonitis, not pneumonia; steroids and early antibiotics have not been shown to help pneumonitis. Pneumonia is diagnosed if fever persists beyond 48 hours or focal consolidation appears.^[6]
• Breathing. High-flow oxygen; endotracheal intubation for unconsciousness; mechanical ventilation for respiratory failure or exhaustion. Non-invasive ventilation can delay intubation in early respiratory compromise. Succinylcholine must be avoided for intubation (unpredictable effect with low cholinesterase activity); short- or intermediate-acting non-depolarising agents such as vecuronium or atracurium are preferred, in the lowest effective dose with train-of-four monitoring.^[5]
• Circulation. Give 500 to 1000 mL (10 to 20 mL/kg) of normal saline over 10 to 20 minutes. Hypotension from cholinergic excess usually responds to atropine; vasopressors rarely needed. Catheterise for urine output and for toxicity monitoring.^[6]

The onset is typically 24 to 96 hours after exposure, after cholinergic signs are controlled. About 20 percent of orally exposed patients develop it; rates up to 65 percent are reported from South Asia against 15 to 20 percent in developed regions, and mortality is 10 to 20 percent.^[5]

• Monitor every severely poisoned patient in an intensive care unit for 72 to 96 hours for neck-flexor weakness, cranial nerve palsies and respiratory distress.^[5]
• Serial red cell AChE and creatine kinase, plus electrolytes, help risk stratification. A red cell AChE under 10 to 20 percent of normal at presentation is a strong predictor.^[5]
• Atropine offers little protection against IMS but is used for any recurrent muscarinic signs; the loading dose of 1.8 to 3.6 mg IV and the infusion at 10 to 20 percent of the loading dose per hour are standard.^[5]
• Once IMS has developed, oximes have not been shown to improve survival, and continued oxime use can prolong neuromuscular weakness. Atropine is not required unless cholinergic symptoms recur.^[5]
• Respiratory failure is the leading cause of death. Non-invasive ventilation may delay intubation; severe cases need intubation and mechanical ventilation, with weaning guided by clinical and electrophysiological recovery. Avoid succinylcholine. Correct hypokalaemia and hypomagnesaemia. Magnesium sulphate 4 g IV over 24 hours has shown promise in trials for stabilising the neuromuscular junction, though evidence is very weak.^[5]

The most recent umbrella review concluded that, beyond atropine (and possibly oximes), routine use is not recommended for:^[1]

• Gastric lavage beyond about one hour (doubtful efficacy, possible harm)
• Hemoperfusion with hemofiltration or plasma exchange
• Intravenous lipid emulsion
• Magnesium sulphate
• Alkalinisation (sodium bicarbonate)
• Penehyclidine
• Crude rhubarb
• Xuebijing

These recommendations rest on very low-certainty evidence, heavily biased by single-country (mostly Chinese) trials and methodological flaws. Some individual trials reported lower mortality with several of these agents, but the reviewers considered the evidence too weak to adopt them. Where sources disagree (heavy self-poisoning protocols versus minimalist ones), be honest: the consensus is that atropine is the mainstay, oximes are standard but contested, and the rest are experimental.

• Respiratory failure from bronchorrhoea, bronchospasm or intermediate syndrome. The leading cause of death.^[2]
• Aspiration pneumonia from vomit and secretions.
• Intermediate syndrome (about 20 percent of oral exposures; rates up to 65 percent in South Asia, 10 to 20 percent mortality), with respiratory failure as the main lethal mechanism.^[5]
• Atropine toxicity: delirium, hyperthermia, ileus, urinary retention, tachycardia.^[6]
• Recurrent cholinergic crisis days later with fatsoluble agents (fenthion) that leach from fat stores.
• Delayed neuropathy (peripheral, not central) weeks to months later in a minority.

Survival depends on the compound, dose, time to care and quality of airway management. Self-poisoning carries a higher case fatality than accidental exposure. Intensive supportive care in the first days and 72 to 96 hours of ICU observation for severe cases are what turn the curves. Long-term problems (weakness after IMS, delayed neuropathy) are uncommon but real; a minority need rehabilitation.

• Regulate the most toxic compounds out of routine sale; bans of paraquat and several highly hazardous organophosphorus insecticides have been followed by falls in pesticide suicide deaths without apparent loss of agricultural output.^[4]
• Restrict sale and professionalise application; restrictions alone, especially in low- and middle-income settings, have often failed to reduce deaths, and countries moved on to bans.^[4]
• Store high-risk products outside the home in lockable commercial storage; household locked-storage programmes have not shown benefit in a randomised trial.^[4]
• Protective equipment and farmer education, and reduced reliance on the highest-toxicity products as a matter of public health priority.
• Ninety-three thousand suicide deaths were estimated to have been prevented in Sri Lanka over 20 years through cumulative pesticide bans including paraquat.^[4]

• Children. Paediatric dosing is rarely standardised in the open literature. Treat as severe until proven otherwise; the protocol above gives 0.02 mg/kg IV for atropine in children where the source specifies it.^[1] Avoid self-medication and verify every dose against your local formulary.
• Pregnancy. No well-quantified fetal safety data are available in credible open sources; manage as for the adult, involve obstetrics and toxicology, and weigh lifesaving maternal treatment against any fetal risk. Do not withhold atropine or airway care from the mother.
• Older adults. Reduced physiological reserve and comorbid cardiac disease raise the risk of atropine-induced tachycardia and myocardial infarction. Use the minimum dose that achieves the end-points and be cautious with large cumulative doses.

• What is missing. AChE assays, electrophysiology, ventilators and intensive care may be absent. The diagnosis then rests entirely on the cholinergic syndrome.
• What still works. Atropine (cheap and on the essential medicines list), diazepam, oxygen, oral airway, positioning and manual ventilation, with frequent clinical observation. Titration by auscultation and heart rate requires no technology.^[6]
• Where to act. Treat in the largest available facility; evacuating unstable patients does them harm. District hospitals should hold atropine and pralidoxime if OP poisoning is common locally. If ICU is unavailable, transfer after stabilisation, not before.
• Paraquat specifically. No antidote exists; supportive care (airway, hydration, avoidance of oxygen unless hypoxic, because oxygen increases paraquat toxicity to the lung) and early referral are the main options.^[4]

Paraquat is a bipyridyl herbicide, not an acetylcholinesterase inhibitor, and it has no antidote. It is classed as moderately toxic (WHO hazard class II) based on rat oral data, but human toxicity is far greater than that classification suggests.^[4]

• Mechanism. Redox cycling in the lung produces superoxide radicals, leading to pulmonary oedema and then progressive pulmonary fibrosis, the usual cause of death. Kidney and liver injury are common.
• First reports of human poisoning appeared in 1964, two years after the product launched. Hundreds of thousands of intentional and accidental poisonings have since occurred worldwide, many fatal.^[4]
• Clinical picture. Mucosal burns of mouth, oesophagus and stomach, vomiting, diarrhoea, acute renal failure, hepatic injury, multi-organ failure and delayed respiratory failure days to weeks later. The classic second-phase deterioration into pulmonary fibrosis often traps the patient in hospital.
• Management. No antidote. Supportive care: airway protection, antiemetics, adequate hydration, renal replacement where available, analgesia. Oxygen should be given only for hypoxia (hyperoxia may worsen lipid peroxidation in the lung). Avoid anything that increases systemic oxygen tension unnecessarily. Gastrointestinal decontamination (activated charcoal, possibly Fuller's earth) only early. Immunosuppressive or antioxidant cocktails (cyclophosphamide, methylprednisolone, vitamin C, vitamin E, N-acetylcysteine) have been studied with inconsistent results and no clear survival benefit; they are not part of standard care. The prognosis is poor once renal failure or pulmonary fibrosis develops.
• Formula changes. Adding emetic, dye and stenching agents and gelling the product failed to cut mortality usefully: in Sri Lanka case fatality fell only from 72.9 to 63.3 percent with Gramoxone Inteon, and reducing concentration from 20 percent to 6.5 percent dropped case fatality from 50 to 23 percent (still high). In Japan, diluting from 20 to 4.3 percent gave a modest benefit.^[4]
• Regulatory lesson. At least 74 countries have removed paraquat from domestic use. Restrictions (professional applicators, closed systems, ID checks) often failed to reduce deaths in low- and middle-income settings, while bans and phase-outs were followed by major falls. In South Korea, after the 2011/2012 ban, pesticide suicide mortality halved from 5.26 to 2.67 per 100,000 people, with an estimated 847 fewer pesticide suicides in 2013 (a 37 percent reduction). In Taiwan, the 2018 ban was followed by a 37 percent fall in the pesticide suicide rate in 2019. Cumulative bans in Sri Lanka, including paraquat, were estimated to have prevented 93,000 suicide deaths over 20 years. In Malaysia, a temporary relaxation of the ban led to a five-fold rise in paraquat deaths (annual deaths rose from 34 to 187 between 2006 and 2015), a rise that reversed when the ban was reinstated. None of these bans had an apparent adverse effect on agricultural output.^[4]

• Chlorophenoxy herbicides (2,4-D, MCPA). Dose-dependent gastrointestinal and muscular effects, metabolic acidosis, rhabdomyolysis; no cholinergic syndrome.
• Organochlorines (DDT, lindane, toxaphene). Excitatory neurotoxicity: tremor, seizures, paresthesia, without muscarinic signs; hepatic enzyme induction.
• Pyrethroids and pyrethrins. Paresthesia, tremor, seizures in severe cases; no miosis or bronchorrhoea. Type II pyrethroids cause choreoathetosis-salivation syndrome.
• Fipronil. Blocks GABA-gated chloride channels; seizures, with occasional fasciculations and little muscarinic picture.
• Amitraz. Alpha-2 agonist; miosis, bradycardia, hypotension, impaired consciousness, and hyperglycaemia; resembles OP but without bronchorrhoea or fasciculations. Atropine is sometimes used for bradycardia, but the mechanism is different.
• Carbamates (aldicarb, carbofuran). Reversible AChE inhibition; same clinical picture as OP but milder and shorter, and oximes are not indicated (they may worsen toxicity with carbaryl).
• Bipyridyl herbicides other than paraquat (diquat). Similar oxidative toxicity, less propensity for pulmonary fibrosis, more direct CNS and renal injury.

• Rapid sequence induction and airway management
• Seizures and status epilepticus
• Acute respiratory failure and mechanical ventilation
• Cholinergic and anticholinergic toxidromes
• Rural and occupational health in low-resource settings