Much of the success in the agricultural fields in our country is due to the knowledge and use of agricultural insecticides. There are other uses of these insecticidal agents e.g. domestic and commercial uses. As has already been mentioned earlier, some of them are non-toxic to human being, some are mildly toxic, some moderately and some deadly. Organophosphorus compounds are deadly toxic to human beings, as they are also most effective as insecticidal agents. Hence, these preparations are most popular on one side and also takes many lives every year, though mostly in the rural areas but also to a considerable extent in the urban areas.

These are dangerous to factory and agricultural workers. They polute air and water in the rural side. They disturb eco-system by killing harmless insects and helpful animals. They create resistance in disease carrying vector insects. Prolonged use causes direct effect on human body and indirect effect on economic condition of the society.

Mode of use of organophosphorus compounds – In the agricultural fields these are either used as aerial spray, mixed with suitable liquid or dust as their vehicle, or they are mixed with soil. When sprayed in air, absorption in the plants occurs through leaves and stems. When used by mixing with the soil, absorption occurs through the roots of the plant. In case of herbicidal agents, undesirable herbs or weeds die. In case of insecticidal agents like organophosphorus agents no harm is caused to the plant. When the insect sits on the plant, the poison is absorbed through their exoskeleton or when it eats the leaves of the plant, it consumes the poison alongwith. In human being no harm is caused by consuming the grain, fruits or other parts of the plants, if used with recommended cautions.

ORGANOPHOSPHORUS COMPOUNDSAbsorption, fate and excretion – Organophosphorus compounds are well absorbed through the mucus membrane of the G.I. tract, respiratory tract and through the skin. Parathion is stored in the body fat and is slowly released in the circulation, prolonging the duration of its toxic action. It is first metabolised to paraoxon which is the active toxic agent of the preparation and then to paranitrophenol to be excreted through urine. Malathion is metabolised in the liver by the esterases. A part of the metabolised product is excreted in urine as phosphate. The rate of excretion varies. Some of the preparations remain in the body longer than others. Parathion may be retained for a period of about a week and malathion for a period of more than a week.

Fatal dose – According to the fatal dose, organophosphorus compounds can be classified as:

Mildly toxic – Fatal dose more than 25 gm and up to 60 gm. e.g. chlorothion, malathion, dipterex.

Moderately toxic – Fatal dose – 10 gm. to 25 gm. e.g. diazinon.

Highly toxic – Fatal dose – 15 mg. to 5 gm. e.g. parathion (15 mg. to 30 mg.), methyl parathion (15 mg.), Systox (20 mg.), pestox (200 mg.), trithion (600 mg.), phosdrine (150 mg.), TEPP (5 gm), delnav (5 gm).

Action and mode of action – Organic polyphosphates, though cause some degree of irritation to the mucus membrane, they are primarily nerve poisons. They have action both on the autonomic nervous system as well as central nervous system. On autonomic nervous system, they have parasympathomimetic action by inactivating cholinesterase and thereby prolonging the action of acetylcholine. The actions are both muscarinic and nicotinic. On the C.N.S., the action is depression.

Acetylcholine as a chemical transmitter plays the vital role to propagate cholinergic nerve impulse across the synapses of the peripheral and central nervous system. In the blood and nervous tissue cholinesterase inactivates acetylcholine after its liberation and action which prevents its sustained action. Cells of the blood and nervous tissue contains true or specific cholinesterase, while plasma and white matter of brain contains pseudocholinesterase. Ordinarily, true cholinesterase present in the cells is at work to inactivate the acetylcholine after its liberation. When excess of esters of choline escapes in blood, plasma esterase becomes important and acts as a safeguard against the unrestricted action of acetylcholine. Most of the parasympathomimetic drugs and the organophosphorus compounds inactivate the cholinesterase to facilitate the action of acetylcholine. This occurs first at the plasma level and then at the cellular and brain level. Inactivation of the esterase by neostigmine and similar drugs is reversible. Organophosphorus compounds inactivate the polypeptide enzyme by phosphorylation of one of its constituent aminoacids. This inactivation is reversible for a few hours only. Then it becomes irreversible. Hence, a sustained action of acetylcholine continues so long the drug is not inactivated or removed or fresh esterase is synthesized to resume function.

Some of the polyphosphates like T.E.P.P. are active in vitro and start acting rapidly after absorption in the body. But their action is for a short period. On the other hand, others like parathion are inactive in vitro. To start their action, after absorption in the body, they first have to change to some intermediate state (e.g. parathion changes to paraxon). But their action is more persistent, insiduous and proves more fatal.

Fruits and vegetables contaminated due to spraying becomes free from danger after a few days of use.

Signs and symptoms – Depending on the action, the signs – symptoms are parasym-pathomimetic (muscarine like and nicotinic) and those of C.N.S. depression.

Parasympathomimetic signs-symptoms – Nausea, excessive salivation, vomiting, pallor, colic, slow pulse, low B.P., cold sweating, diarrhoea, constriction of pupils, bronchospasm, muscular weakness.

Signs-symptoms related to C.N.S. – Malaise, headache, dizziness, restlessness, fibrillatory twitching in the face and tongue, general weakness, ataxia, convulsion.

Severe signs and symptoms consist of both parasympathomimetic and C.N.S. depression.

These are – bronchospasm complicated by excessive secretion in the respiratory tract (parasympathetic) and weakening of diaphragm (relaxant action of acetylcholine). These two actions along with the interference of normal activity of central nervous system cause anoxia leading to death. At the terminal phase anoxia cause dilatation of the pupils when the patient is cyanosed and collapsed with periphery circulatory failure, acute pulmonary oedema and respiratory failure.

Repeated exposure causes toxic demyelination resulting neurological disorder, manifested as various forms of muscular weakness, paralysis of limbs and flexor spasms.

Diagnosis – History of exposure, signs and symptoms, estimation of cell and plasma cholinesterase (less than 30% of normal) are diagnostic of poisoning with organophosphorus compound. In some cases however, gastro-intestinal and pulmonary symptoms may cause confusion in diagnosis.

Treatment –

1. Avoiding the risk of further exposure –
(a) Removal of the patient from the place of exposure (e.g. from the field when spraying of the poison in the field is the cause of poisoning).
(b) Removal of the clothings – If the contact is through the skin, then the contaminated clothes should be removed to prevent further absorption.
(c) If the skin is contaminated then washing of the contaminated part or bathing will be necessary.

2. Stomach wash with strong KMnO4 solution.

3. Atropine sulphate, I.V. in 2 mg/hr. doses till atropinisation i.e. dilatation of pupils. Apart from stimulating respiration and relieving bronchospasm, atropine also helps by reducing secretion. In case of poisoning with parathion, atropine in lower doses should be continued for a few days.

4. Oximes are considered proper antidotes of organophosphorus poisons. They release cholinesterase from the esterase-phosphate combination by removing phosphate radical. The time factor is important for this reaction to occur, because, the esterase-phosphate combination loses alkyl group with passage of time. This makes other phosphorylated esterase ineffective to oximes. Different preparations of oximes are available, namely, Diacetyl monoxime (D.A.M.), Pralidoxime or pyridine aldoxime methiodide (P2AM), Pyridine aldoxime methane sulphonate (P2S). Dose is 1 gm in 1 – 2.5% isotonic solution (40 – 100 ml) given intravenously. A second- dose may be repeated after 1 to 6 hours according to necessity. Alternatively, a separate regimen may be followed in which the dose is calculated as 30 mg/kg body weight given intravenously in similar dilution, 0.5 gm dose at the start, repeated after 1/2 hour with a similar dose, followed by 125 mg dose intramuscularly, half hourly for 4 – 5 injections. If pralidoxime therapy is started, then the dose of atropine should be cautiously calculated to avoid subsequent atropine toxicity.

5. The respiratory tract lumen should be made free from mucus secretion by way of suction.

6. Oxygen inhalation.

7. Artificial respiration if necessary.

8. Absolute rest is given, if necessary by giving suitable sedative.

9. Diuretics may be given to prevent pulmonary oedema.

Prophylaxis – To prevent accidental exposure .and poisoning, certain precautionary steps are recommended during its manufacture, storage, distribution and while using the insecticide in the agricultural field and elsewhere. These are –

1. Use of protective clothes (apron, gloves, boots, mask).
2. Washing of head and face with soap after use.
3. Spraying in the field should not be done for more than 2 hours a day and more than 6 days in a week.
4. Diseases of lungs, liver and kidneys are contraindications for spraying.
5. No smoking, drinking or eating should be allowed during spraying.
6. There should be proper instruction to the sprayers and supervision of the spraying work.
7. While spraying, the sprayer should move backward and against the current of the wind.
8. Appliances should be thoroughly washed after use.
9. Workers (sprayers and others) should be subjected to intermittent neurological test.

Postmortem appearance –

Externally, there are 1. cyanosis, 2. deep postmortem staining, 3. congested face, 4. frothy discharge, often blood stained, from the nose and mouth, and 5. kerosene-like smell due to the diluent of the poison (may or may not be appreciated near the mouth).

Internally, 1. the mucosa of the stomach and intestine is congested, 2. the stomach content may give a kerosene-like smell due to the vehicle or diluent used for the poison, petechial haemorrhagic spots may be present at the sub-pleural level and sub-mucosal level of other viscera, 3. gross congestion and oedema of lungs, 4. congestion of other organs, 5. oedema of brain, 6. blood stained froth in the respiratory tract.

Cholinesterase level of cells and plasma is low.

Medicolegal aspects –

Accidental poisoning occurs in manufacturers, packers, sprayers and other users, children of the users, and due to contamination of food grains by seeds preserved by the insecticide for seedling purposes.

Suicidal poisoning is common in our country, both in rural and in urban areas, but more commonly in rural areas.

Homicidal poisoning does not occur due to detectable smell of the substance used as diluent of the poison and due to alarming signs and symptoms which appear rather early.