Off-Target Stoichiometric Binding Identified from Toxicogenomics Explains Why Some Species Are More Sensitive than Others to a Widely Used Neonicotinoid

Abstract

Neonicotinoids are currently licensed for use in 120 countries, making accurate nontarget species sensitivity predictions critical. Unfortunately, such predictions are fraught with uncertainty, as sensitivity is extrapolated from only a few test species and neonicotinoid sensitivities can differ greatly between closely related taxa. Combining classical toxicology with de novo toxicogenomics could greatly improve sensitivity predictions and identify unexpectedly susceptible species. We show that there is a >30-fold differential species sensitivity (DSS) for the neonicotinoid imidacloprid between five earthworm species, a critical nontarget taxon. This variation could not be explained by differential toxicokinetics. Furthermore, comparing key motif expression in subunit genes of the classical nicotinic acetylcholine receptor (nAChR) target predicts only minor differences in the ligand binding domains (LBDs). In contrast, predicted dissimilarities in LBDs do occur in the highly expressed but nonclassical targets, acetylcholine binding proteins (AChBPs). Critically, the predicted AChBP divergence is capable of explaining DSS. We propose that high expression levels of putative nonsynaptic AChBPs with high imidacloprid affinities reduce imidacloprid binding to critical nAChRs involved in vital synaptic neurotransmission. This study provides a clear example of how pragmatic interrogation of key motif expression in complex multisubunit receptors can predict observed DSS, thereby informing sensitivity predictions for essential nontarget species.

Long-Term Exposure to Neonicotinoid Insecticide Acetamiprid at Environmentally Relevant Concentrations Impairs Endocrine Functions in Zebrafish: Bioaccumulation, Feminization, and Transgenerational Effects

“…1 Neonicotinoid insecticides have been registered in over 120 countries, sharing one-fourth of the global insecticidal market. 2 Because of their widespread use and moderate persistence, neonicotinoids are ubiquitous in the environment. 3 Designed to target the post-synaptic nicotinic acetylcholine receptor (nAChR) in invertebrates, neonicotinoids exhibit low acute lethality to vertebrates.…”

“…Agrochemicals are one of the main drivers for degradation of freshwater diversity at a global scale, raising emerging concerns of aquatic risks from current-use insecticides, including neonicotinoids . Neonicotinoid insecticides have been registered in over 120 countries, sharing one-fourth of the global insecticidal market . Because of their widespread use and moderate persistence, neonicotinoids are ubiquitous in the environment .…”

Variation in the Chemical Sensitivity of Earthworms from Field Populations to Imidacloprid and Copper

“…Still, the species tested in our study, including E. fetida , were very sensitive to copper and imidacloprid, which are known to be toxic compounds for earthworms (see Streit, 1984; Wang et al, 2012). Short et al (2021) exposed different earthworm species to imidacloprid and found that the safety factor proposed by the EFSA did not cover the most sensitive species tested, Amynthas gracilis (KINBERG, 1866). In addition, Frampton et al (2006) performed a pesticide analysis using SSDs and soil invertebrates.…”

“…For example, a reduced sensitivity to copper in earthworms from highly acidic soil may be an adaptation to low pH values (<5.5), in which toxic metals such as copper are mobilized (Fernández-Calviño et al, 2008). Moreover, recent studies have used toxicogenomic analysis to investigate and explain why some species are more sensitive to a certain compound (cf., Short et al, 2021). Pesticide uptake in earthworms is mainly through direct contact and oral ingestion (see Short et al, 2021;Streit, 1984).…”

“…Moreover, recent studies have used toxicogenomic analysis to investigate and explain why some species are more sensitive to a certain compound (cf., Short et al, 2021). Pesticide uptake in earthworms is mainly through direct contact and oral ingestion (see Short et al, 2021;Streit, 1984). Uptake varies among different species, as do their toxicokinetic and toxicodynamic traits; and these dynamics mainly determine organism sensitivity to pesticides (Ashauer & Jager, 2018).…”