Introduction
In some countries, purposeful self-poisoning is frequently caused by acute pesticide poisoning. In the Asia-Pacific region, the World Health Organization (WHO) estimates that 3,00,000 deaths occur yearly due to pesticide poisoning. Organophosphates are the leading cause of self-poisoning death among different pesticides in southern and central India. In addition, pesticides, including organochlorides, carbamates, and pyrethroids, are also reported to increase poisoning cases in the country. Therefore, there has been an ongoing search for novel insecticides with a favorable safety profile due to the high mortality of these substances.
Due to their favorable toxicological profile, neonicotinoids, a newer class of insecticides, have seen an increase in usage in recent years. Neonicotinoids have a considerable margin of safety due to the insecticides' affinity for nicotinic acetylcholine receptors (nAChRs) in insects as opposed to mammals, as well as their quick metabolism and poor blood-brain barrier penetration. Neonicotinoid poisoning has a mortality rate of 0 to 2.9 percent, significantly lower than other pesticides.
How Are Neonicotinoids Classified?
A more recent class of insecticides called neonicotinoids is used in agriculture for flea control, horticulture, and crop protection. The first neonicotinoid nithiazine was created in 1972. However, it was never put on the market. Chloronicotinyl neonicotinoid is the first member of the class to be applied as a commercial pesticide. Its use has been steadily growing over the years, and it is one of the insecticides with the highest global sales, as per recent reports. The classification table is below:
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First-Generation Neonicotinoids - Imidacloprid, Nitenpyram, Acetamiprid, and Thiacloprid.
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Second-Generation Neonicotinoids - Thiamethoxam and Clothianidin.
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Third-Generation Neonicotinoids - Dinotefuran, Sulfoxaflor, and Cycloxaprid.
What Is the Mechanism of Action of Neonicotinoid?
Neonicotinoids are neurotoxins that primarily affect the parasympathetic and some sympathetic nervous systems by acting as agonists in postsynaptic nAChRs (neuronal nicotinic acetylcholine receptors). They bind to the receptors irreversibly, first stimulating them and subsequently blocking Na+/K+ channels to prevent the transmission of neuronal influx. Neonicotinoids are selective for receptor subtypes in the vertebrate brain and have little to no effect on nAChRs in the peripheral nervous system. However, the agents' impact on insects' nAChRs causes insecticidal activity.
Due to their affinity for the insect-specific receptor subtype, absence of the blood-brain barrier, and prevalence of the receptors in the central nervous system, they have a more insect-toxic impact than humans. The more excellent distribution of receptors in the neuromuscular junction, where neonicotinoid affinity is low, and less penetration of these drugs through the blood-brain barrier account for the improved safety profile in humans. Due to their target site specificity, neonicotinoids and pyrethroids have higher selectivity factors for insects than for mammals compared to other pesticides.
What Are the Clinical Symptoms of Neonicotinoid Poisoning?
Because of their reduced affinity for human nicotinic receptors, fast metabolism by cytochrome enzymes, and restricted capacity to penetrate the blood-brain barrier, neonicotinoids have less severe clinical effects in humans. Imidacloprid's most widely used insecticide in the neonicotinoid family has clinical characteristics that are better described. The Texas Poison Center published one of the extensive reports on neonicotinoid symptomatology, which includes exposures from 2000 to 2012. Dizziness, hypertension, tachycardia, nausea, vomiting, eye irritation, dermatitis (skin inflammation), and oral mucosal lesions are the predominant after-exposure symptoms listed in the study. The neurological system's nicotinic receptors are first stimulated by neonicotinoid, which causes blockage of nerve transmission and weariness.
This effect causes a headache, agitation, fasciculations (brief contractions affecting the muscle fibers), and seizures as its initial symptoms, which are followed by disorientation, sleepiness, decreased muscular tone, and coma. Tachycardia, hypertension, diaphoresis (sweating to an unusual degree), and mydriasis (dilation of the eye pupil) are brought on by the stimulation of autonomic nervous system receptors. Abdominal pain, nausea, vomiting, and caustic injury to the orogastric (nasogastric) mucosa are frequent gastrointestinal symptoms. There have been reports of severe clinical characteristics such as rhabdomyolysis (destruction of muscle cells), ventricular fibrillation (a type of irregular heart rhythm), myocardial ischemia (blockage of heart arteries) brought on by coronary vasospasm, acute renal failure, and respiratory failure. A case report describes simultaneous alcohol and imidacloprid intoxication that resulted in multiorgan loss and death. Insecticide solvents also contribute to the symptoms of poisoning. N-methyl pyrrolidone is the solvent that is most frequently utilized with neonicotinoids. When used in significant doses, this solvent can cause nausea, mouth ulcers, and stomach pain.
How Is Neonicotinoid Poisoning Treated?
Acute neonicotinoid poisoning is mainly treated with symptomatic and supportive care. As the dermal and inhalational routes absorb these substances, rapid skin and mucosal decontaminating and removing contaminated clothing are required. After consuming a significant volume (more than 100 milliliters) and if the patient shows up within an hour, gastric cleaning should be considered. If it is thought that the solvent has caused corrosive damage to the orogastric mucosa, gastric lavage and activated charcoal should be avoided. When there is hypotension, a low Glasgow coma scale (used to describe the extent of impaired consciousness), hypoventilation, respiratory distress, assisted ventilation, and hemodynamic support (to maintain mean arterial pressure) should be taken into account. The airway should be secured as soon as possible in cases of voice or hoarseness (abnormal change in voice), and the vocal cords and airway mucosa should be examined endoscopically.
Neonicotinoid agents have no particular antidote. Similar to organophosphate poisoning, neonicotinoid poisoning occasionally exhibits muscarinic clinical signs such as profuse salivation, lacrimation (flow of tears), urine, bronchorrhea (a condition where more than 100 ml of sputum is produced within 24 hours), miosis (excessive constriction of the pupil of the eye), and bradycardia. Due to the clinical appearance, atropine and oximes (organic compounds) may be accidentally delivered. When given in neonicotinoid poisoning, oximes are ineffective or can have adverse effects. When taken without organophosphate chemicals, oximes have poor acetylcholine inhibitory action and can result in tachycardia, hypertension, and other nicotinic symptoms. However, if individuals exhibit significant life-threatening clinical characteristics, such as severe bronchorrhea that compromises the airway or severe bradycardia (slow heart action), judicious use of atropine may be recommended.
Conclusion
The usage of neonicotinoids, a more recent kind of insecticide, has grown in recent years. Due to their widespread use, there have been more poisonings in recent decades. Although neonicotinoids seem less hazardous than other insecticides, there have occasionally been reports of severe side effects such as respiratory failure, cardiac fibrillation, and death. Since there is currently no specific treatment, treatment is symptomatic and supportive.
