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The Basics
Neonicotinoids are a newer class of insecticides with a favorable toxicological profile. They have been a popular choice with increasing usage in recent decades due to their safety in mammals. Neonicotinoids include: acetamiprid, imidacloprid, dinotefuran, thiacloprid, clothianidin, nitenpyram, and thiamethoxam.
While neonicotinoids may be safe to some degree for mammals, it is lethal in insects. While this is ideal for an insecticide, some studies have shown that neonicotinoids are a contributor to the honey bee decline and may also contribute to a decline in monarch butterflies.
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Biotransformation
Information on the biotransformation of neonicotinoid insecticides is limited. Pandey et al. found that imidacloprid and thiamethoxam were transformed into nitrosoguanidine, desnitro, and urea metabolites which are toxic to vertebrates. Their proposed transformation pathway can be seen below.
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Toxicokinetics
Neonicotinoids were originally thought to have low mammalian toxicity due to being selective to insects. However, studies in the last few years have shown that there is a variety of toxic effects in humans and animals. However, they are considered to have a high margin of safety for humans because of their specificity to insects, the wider distribution of receptors in the neuromuscular junction of humans than insects, rapid metabolism, and poor penetration of the blood brain barrier.
Severe intoxication can occur in oral ingestion. Dermal exposure is not quantified in humans and inhalation absorption is minimal due to the compounds being nonvolatile.
A clinical study found that imidacloprid had prolonged absorption and/or saturable elimination after patients ingested. A graph of patients’ blood concentrations post-ingestion can be seen below.
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Mechanism of Action
Neonicotinoids act similar to nicotine by acting as agonists and binding to the postsynaptic nicotinic acetylcholine receptors in the CNS. Acetylcholinesterase is unable to break down the neonicotinoids and acetylcholine begins to accumulate. This causes the excitation of the nerves which leads to paralysis and eventually death in insects.
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Target organ(s)
- Central Nervous System
- Neonicotinoids act on CNS receptors
Signs and symptoms of toxicity
Texas Poison Center reported neonicotinoid symptomatology from 1,142 exposures from 2000 to 2012 which can be found here.
Symptoms included: dizziness, hypertension, tachycardia, nausea, vomiting, eye irritation, dermatitis, and oral mucosal lesions.
- Fatigue (as well as headaches, seizures, and coma) are due to neonicotinoids continuous stimulation of the nicotinic receptors and blockade of nerve transmission.
- Autonomic nerve receptor stimulation leads to hypertension, tachycardia, diaphoresis (sweating), and mydriasis (pupil dilation).
- Gastrointestinal symptoms are also common and include nausea, vomiting and abdominal pain.
- Severe clinical features that have been reported include: respiratory failure, ventricular fibrillation, myocardial ischemia due to coronary vasospasm, acute renal failure, and rhabdomyolysis.
Treatments
There is no antidote for neonicotinoid toxicty.
- Due to clinical features of neonicotinoid toxicty atropine and oximes have been administered inadvertently.
- Atopine can be justified if the patient has life-threatening clinical features.
- Oximes can cause tachycardia, hypertension, and other nicotinic symptoms due to its weak acetylcholinesterase inhibiting activity.
Biomarkers
Six neonicotinoid biomarkers were evaluated in this article: Ospina, M., Wong, L.-Y., Baker, S. E., et al. (2019). Exposure to neonicotinoid insecticides in the U.S. general population: Data from the 2015–2016 national health and nutrition examination survey. Environmental Research, 176, 108555. https://doi.org/10.1016/j.envres.2019.108555
- Four parent compounds: acetamiprid, clothianidin, imidacloprid, thiacloprid
- Two metabolites: N-desmethyl-acetamiprid, 5-hydroxy-imidacloprid
Abstract found here