Neonicotinoids represent 25% of the insecticidal market and are essential for crop production, yet traditional neonicotinoids are toxic to most pollinators, which are also essential for food production. This issue may be addressed by the use of some chiral neonicotinoid isomers, which are much less toxic. Here, we review the chiral neonicotinoids dinotefuran, sulfoxaflor, cycloxaprid, and paichongding, with focus on their chiral characteristics, configuration stability, biological activity, ecological toxicology, and environmental fate. Isomeric separation of chiral neonicotinoids can be achieved by chromatography. The dinotefuran R isomer is less toxic than the S isomer to honeybees and earthworms by a factor of 2.7-145.9, with similar control efficiency of common agricultural pests. The insecticidal activity of (5R,7S)-paichongding are up to 20.1 times higher than that of other isomers, and it is absorbed fastest by crop roots and tends to be preferentially degraded and mineralized in soils. Therefore, formulations containing R-dinotefuran or (5R,7S)-paichongding could decrease ecological damage without compromising food production. On the other hand, it has not been possible to synthesize chiral isomers of sulfoxaflor and cycloxaprid, owing to the instability of their monomers in polar solvents.

Neonicotinoids (NEOs) are currently the fastest-growing and most widely used insecticide class worldwide. Increasing evidence suggests that long-term NEO residues in the environment have toxic effects on non-target soil animals. However, few studies have conducted surveys on the effects of NEOs on soil animals, and only few have focused on global systematic reviews or meta-analysis to quantify the effects of NEOs on soil animals. Here, we present a meta-analysis of 2940 observations from 113 field and laboratory studies that investigated the effects of NEOs (at concentrations of 0.001-78,600.000 mg/kg) on different soil animals across five indicators (i.e., survival, growth, behavior, reproduction, and biochemical biomarkers). Furthermore, we quantify the effects of NEOs on different species of soil animals. Results show that NEOs inhibit the survival, growth rate, behavior, and reproduction of soil animals, and alter biochemical biomarkers. Both the survival rate and longevity of individuals decreased by 100 % with NEO residues. The mean values of juvenile survival, cocoon number, and egg hatchability were reduced by 97 %, 100 %, and 84 %, respectively. Both individual and cocoon weights were reduced by 82 %, while the growth rate decreased by 88 % with NEO residues. Our meta-analysis confirms that NEOs pose significant negative impacts on soil animals.

Pesticides are substances used for controlling, preventing, and repelling pests in agriculture. Among them, neonicotinoids have become the fastest -growing class of insecticides because of their efficiency in targeting pests. They work by strongly binding to nicotinic acetylcholine receptors (nAChRs) in the central nervous system of insects, leading to receptor blockage, paralysis, and death. Despite their selectivity for insects, these substances may be hazardous to non -target creatures, including earthworms. Although earthworms may be invasive in some regions like north America, they contribute to the development of soil structure, water management, nutrient cycling, pollution remediation, and cultural services, positively impacting the environment, particularly in the soil ecosystem. Thus, this study aimed to develop a novel earthworm behavior assay since behavior is a sensitive marker for toxicity assay, and demonstrated its application in evaluating the toxicity of various neonicotinoids. Here, we exposed Eisenia fetida to 1 and 10 ppb of eight neonicotinoids (acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram pestanal, thiacloprid, thiametoxam, and sulfoxaflor) for 3 days to observe their behavior toxicities. Overall, all of the neonicotinoids decreased their locomotion, showed by a reduction of average speed by 24.94 -68.63% and increment in freezing time movement ratio by 1.51 -4.25 times, and altered their movement orientation and complexity, indicated by the decrement in the fractal dimension value by 24 -70%. Moreover, some of the neonicotinoids, which were acetamiprid, dinotefuran, imidacloprid, nitenpyram, and sulfoxaflor, could even alter their exploratory behaviors, which was shown by the increment in the time spent in the center area value by 6.94 -12.99 times. Furthermore, based on the PCA and heatmap clustering results, thiametoxam was found as the neonicotinoid that possessed the least pronounced behavior toxicity effects among the tested pesticides since these neonicotinoid-treated groups in both concentrations were grouped in the same major cluster with the control group. Finally, molecular docking was also conducted to examine neonicotinoids ' possible binding mechanism to Acetylcholine Binding Protein (AChBP), which is responsible for neurotransmission. The molecular docking result confirmed that each of the neonicotinoids has a relatively high binding energy with AChBP, with the lowest binding energy was possessed by thiametoxam, which consistent with its relatively low behavior toxicities. Thus, these molecular docking results might hint at the possible mechanism behind the observed behavior alterations. To sum up, the present study demonstrated that all of the neonicotinoids altered the earthworm behaviors which might be due to their ability to bind with some specific neurotransmitters and the current findings give insights into the toxicities of neonicotinoids to the environment, especially animals in a soil ecosystem.

Incorrect use of neonicotinoid pesticides poses a serious threat to human and pollinator health, as these substances are commonly present in bee products and even drinking water. To combat this threat, the study developed a new method of degrading the pesticide imidacloprid using surface discharge cold plasma oxidation technology. The study showed that this method achieved a very high efficiency of imidacloprid degradation of 91.4%. The main reactive oxygen species (H2O2, O3, & sdot;OH, O2- , 1O2) effectively participated in the decomposition reaction of imidacloprid. Reactive oxygen species were more sensitive to the structure of the nitroimine group. Density functional theory (DFT) further explored the sites of reactive oxygen species attack on imidacloprid and revealed the process of energy change of attacking imidacloprid. In addition, a degradation pathway for imidacloprid was proposed, mainly involving reactive oxygen species chemisorption, a ring-opening intermediate, and complete cleavage of the nitroimine group structure. Model predictions indicated that acute oral and developmental toxicity were significantly reduced after cold plasma treatment, as confirmed by insect experiments. Animal experiments have shown that plasma treatment reduces imidacloprid damage to mice hippocampal tissue structure and inhibits the reduction of brain-derived neurotrophic factor content, thus revealing the detoxification mechanism of the body.

The increasing popularity of seed treatment applications in agriculture may leave unintended hazards to soil biota, such as earthworms. The objective of this study was to explore mitochondrial DNA toxicity resulting from sublethal exposures to systemic pesticides, including four neonicotinoid insecticides (neonics), as well as coexposure to difenoconazole (DIF), a triazole fungicide, in earthworms (Eisenia fetida) in vivo. Earthworms were exposed under dose regimes resembling label recommendation and levels left in soil post seed treatment application for 30 days in an earthworm breeding facility. Mitochondrial DNA copy numbers (mtDNAcn) in earthworms were determined by using the 2(-Delta Ct) algorithm. Earthworms' body weights were recorded before and after the exposure period. We found a highly significant increase of mtDNAcn in earthworms across all exposure groups (ANOVA, p < 0.001), either under a single neonic or combined with DIF exposure. Coupled with mtDNA toxicity, earthworms in the treatment groups gained significantly less weight than control earthworms (ANOVA, p < 0.001). We concluded that systemic pesticides, both neonics and DIF, posed mtDNA toxicity as measured by mtDNAcn, in earthworms.

Imidacloprid (IMI), a neonicotinoid insecticide, has a wide variety of applications in both agriculture and horticulture. As a result of it massive and repeated use, its traces remained in soil pose severe damage to soil invertebrates, particularly earthworms. Limited information is available regarding the underlying mechanisms of IMI toxicity toward earthworms at the molecular, transcriptional, and cellular levels. Here, Eisenia fetida coelomocytes and key defensive proteins were selected as targeted receptors to explore the toxic mechanisms of oxidative stress-mediated cytotoxicity, genotoxicity, and antioxidant responses induced by IMI stress and the molecular mechanisms underlying the binding of IMI and superoxide dismutase (SOD)/catalase (CAT). Results showed that IMI exposure destroyed the cell membrane integrity of earthworm cells, causing cell damage and cytotoxicity. The intracellular levels of ROS, including center dot O-2(-) and H2O2 were induced by IMI exposure, thereby triggering oxidative stress and damage. Moreover, IMI exposure attenuated the antioxidative stress responses (reduced antioxidant capacity and CAT/SOD activities) and caused deleterious effects (enhanced DNA damage, lipid peroxidation (LPO), and protein carbonylation (PCO)) through ROS-mediated oxidative stress pathway. Aberrant gene expression associated with oxidative stress and defense regulation, including CAT, CRT, MT, SOD, GST, and Hsp70 were induced after IMI exposure. Concentration-dependent conformational and structural alterations of CAT/SOD were observed when IMI binding. Also, direct binding of IMI resulted in significant inhibition of CAT/SOD activities in vitro. Molecular simulation showed that IMI preferred to bind to CAT active center through its direct binding with the key residue Tyr 357, while IMI bound more easily to the connecting cavity of two subunits away from SOD active center. In addition, hydrogen bonds and hydrophobic force are the main driving force of IMI binding with CAT/SOD. These findings have implications for comprehensive evaluation of IMI toxicity to soil eco-safety and offer novel strategies to elucidate the toxic mechanisms and pathways of IMI stress.