A critical review on the potential impacts of neonicotinoid insecticide use: current knowledge of environmental fate, toxicity, and implications for human health

Abstract

Neonicotinoid insecticides are widely used in both urban and agricultural settings around the world. Historically, neonicotinoid insecticides have been viewed as ideal replacements for more toxic compounds, like organophosphates, due in part to their perceived limited potential to affect the environment and human health. This critical review investigates the environmental fate and toxicity of neonicotinoids and their metabolites and the potential risks associated with exposure. Neonicotinoids are found to be ubiquitous in the environment, drinking water, and food, with low-level exposure commonly documented below acceptable daily intake standards. Available toxicological data from animal studies indicate possible genotoxicity, cytotoxicity, impaired immune function, and reduced growth and reproductive success at low concentrations, while limited data from ecological or cross-sectional epidemiological studies have identified acute and chronic health effects ranging from acute respiratory, cardiovascular, and neurological symptoms to oxidative genetic damage and birth defects. Due to the heavy use of neonicotinoids and potential for cumulative chronic exposure, these insecticides represent novel risks and necessitate further study to fully understand their risks to humans.

Figure 1:

Chemical structures of common neonicotinoids and related compounds. Figure adapted from C. Giorio, et al. Environmental Science and Pollution Research, 2017, 1–33.

Figure 2:

The electronegative pharmacophore (either nitro- or cyano-group) of the neonicotinoid confers selective binding to the insect nicotinic acetylcholine receptor (nAChR). Insecticidal target specificity is lost when the metabolite desnitro-imidacloprid without the nitro-group binds to the the vertebrate nAChR. Republished with permission of Annual Reviews, Inc, from Neonicotinoid Insecticide Toxicology: Mechanisms of Selective Action, Motohiro Tomizawa, John E. Casida, vol 45, 2005; permission conveyed through Copyright Clearance Center, Inc.

Figure 3:

Chlorination of the hydrolysis products of thiamethoxam (THX-H 237 and THX-H 248) to form novel chlorinated product CLO-THX-H 270. Figure 3 taken with permission from Klarich-Wong, et al., Environmental Science & Technology Letters, 2019. 6(2): p. 98–105. Copyright 2019 American Chemical Society.

Figure 4:

Chlorination of desnitro-imidacloprid and imidacloprid-urea to form chlorinated products desnitro-IMI 245, desnitro-IMI 279, and IMI-urea 246. Figure 4 taken with permission from Klarich-Wong, et al., Environmental Science & Technology Letters, 2019. 6(2): p. 98–105. Copyright 2019 American Chemical Society.

Figure 5:

Main transformation of the nitro-functional group neonicotinoids from the electronegative functional group to the positive guanidine (blue) metabolites of enhanced vertebrate toxicity. Image created by LeFevre; Data and information adapted from Dai et al., Appl. Microbiol. Biotechnol., 2006, 71, 927–934; Pandey et al., Biochem. Biophys. Res. Commun., 2009, 380, 710–714.; and Zhou et al., Appl. Microbiol. Biotechnol., 2013, 97, 4065–4074.

Figure 6:

Microbial transformation of neonicotinoids containing a cyano functional group. The electronegative cyano pharmacophore can be transformed via nitrile hydratase enzymes to amide metabolites, with subsequent decomposition to guanidine metabolites. Various products are also formed via the demethylation pathway. Image created by LeFevre; Data and information adapted from Chen et al., Biodegradation, 2008, 19, 651–658.; Dai et al., J. Agric. Food Chem., 2010, 58, 2419–2425.; Tang et al., Process Biochem., 2012, 47, 1820–1825.; Wang et al., Bioresour. Technol., 2013, 138, 359–368.; Yang et al., Int. Biodeterior. Biodegrad. 85, 2013, 95–102.; Zhang et al., J. Agric. Food Chem., 2012, 60, 153–159.; and Zhou et al., Int. Biodeterior. Biodegrad., 2014, 93, 10–17.