Environmental toxicology of neonicotinoid pesticides: effects on central nervous system function in small mammals

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Over the last two decades the neonicotinoids have become the most important and fastest growing of the five major chemical classes of insecticides worldwide. As the name suggests, these compounds act as agonists at the nicotinic subclass of acetylcholine receptors (nAchRs) resulting in “over-stimulation” that leads to neuromuscular paralysis. Commonly used as seed treatments they are also applied directly to plants and are used as “flea powders” for domestic animals including dogs and cats. Although nAChRs are fundamental to the physiology of all vertebrate species (as well as invertebrates) the neonicotinoids have been approved and used widely based on toxicological data indicating that they bind with substantially higher affinity to insect nAChRs than mammalian nAChRs; conferring a larger “margin of safety” than other classes of insecticides such as organophosphates or methylcarbamates. This conclusion, however, is based almost exclusively on comparisons of the relative potency to produce lethality (LD50 ) in the target species. Comparisons of sublethal toxicity of these compounds in mammals, however, are comparatively sparse. There is some limited data of effects on reproduction and immunosuppression in vertebrates but almost no available data on either the neurodevelopmental toxicity of these compounds in mammals or the long-term effects of low dose exposure. This lack of knowledge in species such as rats and mice that would consume treated seed and in turn become prey for higher-order mammals (e.g. foxes) or avian species such as raptors (owls, hawks, etc.) is a major gap in our current understanding of the environmental consequences of neonicotinoid use, and was highlighted in a recent review by Gibbons et al. (2015) that raises serious questions about the effects of these compounds on vertebrate wildlife.***Based on both existing data reports and obvious data gaps, there is an urgent need to further investigate the sublethal and neurodevelopmental toxicity of neonicotinoids in non-target mammalian species. This proposal will investigate the effects of low concentrations of the neonicotinoid pesticides imidacloprid and thiamethoxam on nAChR-mediated behaviour and CNS neuropathology in both adult and juvenile rats; representing both a susceptible non-target population and a surrogate species for other vertebrate wildlife. Further we will determine if pre-gestational exposure to these compounds produces deficits in the resulting offspring.******The studies proposed will provide much needed data on the effects of neonicotinoid pesticides on small mammals and form a foundation for future field studies if warranted.**