A Critical Evaluation of the Use of Neonicotinoid Insecticides on Human Health
Insecticides are universally used, not just by farmers, but by household gardener’s as a way to prevent, mitigate or repel pests. Due to outbreaks of infectious disease in honey bees and amphibians, the use of systematic insecticides has significantly increased over the last 20 years (Mason et al., 2012). And is now thought to be the preferred choice; because of their toxicity and mechanistic action. One type, in particular, seen to show a usage increase is – neonicotinoids - a class of agrochemicals derived from nicotine (a substance found in cigarettes). It is thought this derivative form is solely based on the chemical similarity of the two (Calderon-Segura et al., 2012). First introduced within the 1990’s, neonicotinoids were principally used for their systematic nature. While most insecticides are placed on the surfaces of yielding crops, neonicotinoids are taken up by the roots and translocated to separate areas. This, therefore, makes the plant toxic to certain insect species (Pisa et al., 2014). It is this mechanism of action that has now simultaneously been linked to the adverse impacts on several other invertebrate and vertebrate species (Sluijs et al., 2014).
There are currently, five authorised neonicotinoid insecticides available for use in the UK, including (1) acetamiprid, (2) clothianidin, (3) imidacloprid, (4) thiacloprid, and (5) thiamethoxam (Kimura-Kuroda et al, 2012); these are continually divided into separate categories, known as N-nitroguanidines and N-cyano-aminides (Kanne et al., 2005). Two of these insecticides, in particular, acetamiprid (ACE) and imidacloprid (IMI), are known for their cytotoxic and genotoxic effects on the human genome (Stocker et al., 2004) and are currently the basis of clinical investigations among the mammalian population. Both ACE and IMI are thus, seen to have the highest adverse effects on the complete family of neonicotinoids (Stocker et al., 2004).
ACE is an odourless neonicotinoid insecticide, composed of a synthetic organic compound. In insects, ACE targets the nervous system, causing paralysis and extermination, by binding to the nicotine acetylcholine receptors (nAChRs) in the neuronal pathways (Imamura et al., 2010). The Environmental Protection Agency (EPA) has established that ACE is of low risk to both the environment and to human health. Risk to health can only be attributed to an adverse effect if directly contacted through consumption. ACE is, however, also a recognised irritant to human skin, which should always be handled with care in large quantities (Environmental Protection Agency, 2002). Overall, it should be noted, that ACE has been classified as an unlikely carcinogen to human health (Environmental Protection Agency, 2002).
IMI, on the other hand, is a neonicotinoid in the chloronicotinyl nitroguanidine chemical family (Horowitz et al., 1998). Similar to ACE, it is widely recognised as a neurotoxin. Acting on the central nervous system (CNS), IMI blocks the nicotinergic neuronal pathway, preventing the release of the neurotransmitter acetylcholine; causing paralysis in insects (Horowitz et al., 1998). Again, IMI has a low toxicity to animals and humans and has been classified as an unlikely carcinogen by EPA. IMI is, however, weakly mutagenic and must be tested for under the Endocrine Disruptor Screening Program (EDSP) (Environmental Protection Agency U.S., 2009). There is currently no published studies involving humans being chronically exposed to IMI, which has questioned as to whether IMI is toxic at all to human health. Adverse effects to IMI are completely dependent on length and level of exposure, as well as previous health records; both ACE and IMI are therefore selectively more toxic to insects than any other mammal species (Horowitz et al., 1998).
In the past, both ACE and IMI have been disregarded due to their impacts on environmental ecosystems and populations. For example, the increase in neonicotinoids was found to be linked with honey bee colony collapse disorder (CCD) and a population decrease of both birds and insects (co-dependent of one another) (Gill et al., 2012). It should however, be noted that the existent use for these was focused on rats and fruit flies (Yamamoto et al., 1999), before there now known common use on aphids (Pesticide Action Network, 2013). Previous animal studies have indicated a low toxicity to neonicotinoids, due to the resistance of their nicotinic receptors against chemical substances. When compared to insects, however, this toxicity was increased, as protection from the blood brain barrier and central nervous system is limited (open-circulatory present) (Wu et al., 2001); thus providing easy access to chemical and physical influences.
Despite the pre-misconception of neonicotinoids having a limited effect on human health, it could be argued that this class of insecticides is now thought to even play a role in the neurotoxicity of the central nervous system (CNS). Thus, the fundamental effector to adverse health effects is the human exposure to these neonicotinoids. While it may be limited, human exposure is thought to be mainly due to food and water intake. As neonicotinoids are widely used in the UK, this treatment is given to crops, during growth and before consumption; consequently increasing the attributable risk by more than 30 % (Eriksson, 1997). It is therefore thought most human exposure is self-inflicted by personal agricultural routines at home or by acquiring the produce grown in pesticide-based conditions (Mohamed et al., 2009). Neonicotinoids are, however, also found in treatment creams for animals, and used to prevent or kill infestations. The residue of these neonicotinoid creams is thought to remain for up to 3-4 weeks post-usage; thus, increasing the likelihood of human contact during activities such as petting or playing (Mohamed et al., 2009).
According to Kimura-Kuroda et al., (2012), the reasoning behind the adverse effects from human exposure, is due to the chemical similarity of neonicotinoids and nicotine. Neonicotinoids, therefore, have the ability to share agonist (ligand-induced responses) activity at nicotinic acetylcholine receptors (nAChRs). nAChRs are the functional neuron receptor proteins that play a role in muscular contraction, upon the presence of a chemical stimulus (Purves et al., 2008). It is this mechanism of action that is the key to changes within the central nervous system (CNS). As these nAChRs are cholinergic receptors, they have to ability to form ligand-gated ion channels within the plasma membrane of neurons and at the neuromuscular junction (Hibbs et al., 2009). Upon the binding of acetylcholine, the ion channels open, allowing for the influx of cations, such as sodium, potassium or calcium (Gotti et al., 2004); which in neuroscience is important for the regulation of signalling pathways (Stocker et al., 2004). Upon the binding of a neonicotinoid, such as acetamiprid (ACE) however, it is believed this is the cause behind adverse functioning known as, developmental neurotoxicity (DNT).