Chiral Pesticides Research Articles

Enantioselective inhibition of human CYP2C19 by the chiral pesticide ethofumesate: Prediction of pesticide-drug interactions in humans

Ethofumesate is a chiral herbicide that may display enantioselective behavior in humans. For this reason, the enantioselective potential of ethofumesate and its main metabolite ethofumesate-2-hydroxy to cause pesticide-drug interactions on cytochrome P450 forms (CYPs) has been evaluated by using human liver microsomes. Among the evaluated CYPs, CYP2C19 had its activity decreased by the ethofumesate racemic mixture (rac-ETO), (+)-ethofumesate ((+)-ETO), and (−)-ethofumesate ((−)-ETO). CYP2C19 inhibition was not time-dependent, but a strong inhibition potential was observed for rac-ETO (IC50 = 5 ± 1 μmol L−1), (+)-ETO (IC50 = 1.6 ± 0.4 μmol L−1), and (−)-ETO (IC50 = 1.8 ± 0.4 μmol L−1). The reversible inhibition mechanism was competitive, and the inhibition constant (Ki) values for rac-ETO (2.6 ± 0.4 μmol L−1), (+)-ETO (1.5 ± 0.2 μmol L−1), and (−)-ETO (0.7 ± 0.1 μmol L−1) were comparable to the Ki values of strong CYP2C19 inhibitors. Inhibition of CYP2C19 by ethofumesate was enantioselective, being almost twice higher for (−)-ETO than for (+)-ETO, which indicates that this enantiomer may be a more potent inhibitor of this CYP form. For an in vitro-in vivo correlation, the Food and Drug Administration's (FDA) guideline on the assessment of drug-drug interactions used in the early stages of drug development was used. The FDA's R1 values were estimated on the basis of the obtained ethofumesate Ki and distribution volume, metabolism, unbound plasma fraction, gastrointestinal and dermal absorption data available in the literature. The correlation revealed that ethofumesate probably inhibits CYP2C19 in vivo for both chronic (oral) and occupational (dermal) exposure scenarios.

Biochar decreased enantioselective uptake of chiral pesticide metalaxyl by lettuce and shifted bacterial community in agricultural soil

A 35-day microcosmic experiment was conducted with lettuce (Lactuca sativa L.) and two metalaxyl (MET) enantiomers (R-MET and S-MET) to understand the roles of biochar in the enantioselective fate of chiral pesticides in soil-plant ecosystems. Wood waste-derived biochar (WBC) amendment effectively decreased the shoot concentrations of R-MET/S-MET and their metabolites R-MET/S-MET acid by 57.7–86.3% and 13.3–32.5%, respectively. The reduced uptake was mainly attributed to the decreased bioavailability of R-MET and S-MET. A lower fraction of R-MET was accumulated by the lettuce in the WBC-amended soils relative to the control, suggesting a decrease in the enantioselective uptake of the chiral pesticide MET in the presence of biochar. Regardless of the WBC amendment, no enantiomerization of MET or MET acid occurred. The application of WBC stimulated soil bacterial diversity, shifted the bacterial community, and enhanced the abundance of pesticide degrading bacteria (e.g., Luteimonas, Methylophilus, and Hydrogenophaga), which were responsible for the enantioselective degradation of MET in the soil. This work expands our understanding of the enantioselective fate of chiral pesticides in the biochar-amended soil ecosystems. These findings can be used to develop biochar-based technologies to remediate soils contaminated with these chiral pesticides to ensure food safety.

Complexation and enantioselectivity of novel bridge-like uranyl- 2-((1Z,9Z)-9-(2-Hydroxyphenyl)-3,5,6,8-tetrahydrobenzo[h][1,4,7,10] dioxadiazacyclododecin-2-yl)-5-methoxyphenol with chiral organophosphorus pesticide enantiomers of R/S-malathions

ABSTRACT Designing new uranyl complexes with enantioselectivity is of great significance for the identification and separation of enantiomers of chiral pesticides. In this paper, a new asymmetric rigid uranyl-2-((1Z,9Z)-9-(2-Hydroxyphenyl)-3,5,6,8-tetrahydrobenzo[h][1,4,7,10] dioxadiaza-cyclododecin-2-yl)-5-methoxyphenol(Uranyl-HTDM) was designed, we used Uranyl-HTDM as a receptor to selectively coordinate with the guests of the chiral organophosphorus pesticide R/S-malathions(R/S-MLTs) to explore the receptor's enatioselectivity recognition of the chiral guests of R/S-MLTs. Density functional theory (DFT) method was used to comprehensively study the complexation mode of the receptor with enantiomers. The results showed that the U of Uranyl-HTDM could coordinate with both the thiophosphoryl sulfur and carbonyl oxygens of R/S-MLTs in different environments, respectively. The thermodynamics calculations further indicated that the receptor could selectively recognize the thiophosphoryl sulfur and carbonyl oxygen atoms of R/S-malathions, and the complexation abilities of Uranyl-HTDM to the R/S-malathions under different solvents were not the same. The smaller the polarity of solvents, the stronger the complexation ability of Uranyl-HTDM with R-malathion, toluene was an ideal solvent with large △G change and enatioselectivity coefficient of 99.55%. The study provides useful references for the design of new uranyl-salophens and for the experimental study on the molecular recognition of chiral organophosphorus pesticides.

Enantioselective metabolism of phenylpyrazole insecticides by rat liver microsomal CYP3A1, CYP2E1 and CYP2D2

The stereoselective difference of chiral pesticide enantiomers is an important factor of risk evaluation and the subject has received wide attention. In the present work, enantioselective metabolism of chiral phenylpyrazole insecticides including fipronil, ethiprole and flufiprole in rat liver microsomes was investigated in vitro. The result showed remarkable enantioselectivity for fipronil and ethiprole with the EF values of 0.11–0.58. The metabolite fipronil-sulfone was formed with the degradation of fipronil. R-Ethiprole to S-ethiprole transformation was observed, but not S-ethiprole to R-ethiprole. No enantioselective metabolism was observed for flufiprole with the EF values of 0.49–0.51. The enzymatic assays showed that the inhibition ratio of R-fipronil and S-ethiprole was 1.5–2.1times that of the corresponding enantiomers on CYP2E1 and CYP2D2 activity, leading to the enantioselective metabolism. The result of the homology modeling and molecular docking further revealed that S-fipronil (−7.56 kcal mol−1) and R-ethiprole (−6.45 kcal mol−1) performed better binding with CYP2E1 and CYP2D2, respectively. The results provided useful data for the risk evaluation of chiral phenylpyrazole insecticides on ecological safety and human health.

Enantioselective degradation of the organophosphorus insecticide isocarbophos in Cupriavidus nantongensis X1T: Characteristics, enantioselective regulation, degradation pathways, and toxicity assessment

The chiral pesticide enantiomers often show selective efficacy and non-target toxicity. In this study, the enantioselective degradation characteristics of the chiral organophosphorus insecticide isocarbophos (ICP) by Cupriavidus nantongensis X1T were investigated systematically. Strain X1T preferentially degraded the ICP R isomer (R-ICP) over the S isomer (S-ICP). The degradation rate constant of R-ICP was 42-fold greater than S-ICP, while the former is less bioactive against pest insects but more toxic to humans than the latter. The concentration ratio of S-ICP to R-ICP determines whether S-ICP can be degraded by strain X1T. S-ICP started to degrade only when the ratio (CS-ICP/CR-ICP) was greater than 62. Divalent metal cations could improve the degradation ability of strain X1T. The detected metabolites that were identified suggested a novel hydrolysis pathway, while the hydrolytic metabolites were less toxic to fish and green algae than those from P-O bond breakage. The crude enzyme degraded both R-ICP and S-ICP in a similar rate, indicating that enantioselective degradation was due to the transportation of strain X1T. The strain X1T also enantioselectively degraded the chiral organophosphorus insecticides isofenphos-methyl and profenofos. The enantioselective degradation characteristics of strain X1T make it suitable for remediation of chiral organophosphorus insecticide contaminated soil and water.

The stereoselectivity of metconazole on wheat grain filling and harvested seeds germination: Implication for the application of triazole chiral pesticides

Plant growth can be influenced by the application of triazole pesticides as these regulate physiological processes such as plant hormonal levels and enzyme activity. Homology modeling and molecular docking studies suggested that inhibition of ADP-glucose pyrophosphorylase activity in two trans-stereoisomers treatments hinders starch accumulation during the grain filling stage. A field experiment investigated the effects of metconazole racemate, cis-1R,5S-stereostereoisomer, and cis-1S,5R-stereoisomer application at the flowering stage on wheat grain ripening and yield. The concentrations of racemate and both cis-stereoisomers were detected in wheat plant and grain samples. Compared with the racemate, both cis-stereoisomers were more persistent in the matrices. Treatment with cis-1R,5S-stereoisomer decreased grain weight and yield of wheat by delaying chlorophyll degradation, increasing the ethylene content, and decreasing the level of abscisic acid. The germination of harvested seeds was adversely affected by racemate treatment as a result of gibberellin and abscisic acid metabolism regulation and the transcription of signaling-related genes. Therefore, cis-1S,5R-stereoisomer was recommended to be used as metconazole pesticide at the flowering stage.

Application of biochar: An approach to attenuate the pollution of the chiral pesticide fipronil and its metabolites in leachate from activated sludge

The present study investigated the bio-effects and fate of the chiral pesticide fipronil and its three primary metabolites, fipronil desulfinyl, fipronil sulfide and fipronil sulfone on Chlorella pyrenoidosa and Danio rerio in the absence and presence of biochar. The results revealed that fipronil and its metabolites exhibited high toxicity to algae and fish. Enantioselectivity was observed with regard to the toxicity and degradation of fipronil and its metabolites. For Chlorella pyrenoidosa, R-fipronil was more toxic than S-fipronil and degraded preferentially during the toxicity and degradation experiments. For Danio rerio, S-fipronil exhibited higher toxicity than R- and rac-fipronil. The toxicities of fipronil sulfide and sulfone were 3–6 and 5–6 times higher, respectively, than that of rac-fipronil, and the metabolites also exhibited longer persistence. The remediation capacity for water and leachate contaminated by fipronil with the application of biochar was investigated. Biochar significantly mitigated the toxicity of fipronil and its metabolites to nontarget organisms, and reduced residues by 90 % for fipronil, 72 % for sulfone, 65 % for sulfide and 60 % for desulfinyl, whereas mitigation of only 30 %-51 % was observed in the absence of biochar. This study demonstrates that biochar has strong potential as an ideal material for the removal of fipronil and its metabolites from contaminated aquatic environments.

Enantioselective environmental behavior of the chiral fungicide mandipropamid in four types of Chinese soil

AbstractEnantioselective degradation behavior of mandipropamid, and factors affecting its degradation and metabolites in four types of Chinese soil were investigated in this work. The results showed that the enantiomeric selectivity values ranged from 0.025 to 0.170, indicating that enantioselectivity was found in the degradation process of the racemate in all of the soil samples and that the R‐(−)‐enantiomer was preferentially degraded. The degradation compounds formed faster in native alkaline soils (half‐lives = 35.5–39.80 d) than in native acidic soils (half‐lives = 51.3–77.90 d). The half‐lives of the R‐(−)‐enantiomer and S‐(+)‐enantiomer were 35.5–73.7 and 37.5–77.9 d, 66.6–97.6 and 70.0–103.5 d, and 52.5–110.0 and 66.0–144.4 d in the four types of soil under native, sterilized, and organic matter‐removed conditions, respectively, which indicated that mandipropamid degradation can be attributed to microbial activity and the organic matter content in the soil. Furthermore, the half‐lives of the R‐(−)‐enantiomer and S‐(+)‐enantiomer decreased 1.07–1.95 and 1.08–1.79 times with each 10 °C increase in incubation temperature, and the half‐lives of the R‐(−)‐enantiomer and S‐(+)‐enantiomer decreased 1.09–1.43 and 1.06–1.50 times with increasing moisture content. However, the incubation temperature and soil moisture did not change the enantioselectivity. Mandipropamid enantiomers were observed to be configurationally stable in the selected soil, and no interconversion was found during the incubation of enantiopure R‐(−)‐mandipropamid or S‐(+)‐mandipropamid in native or sterilized soil. During the degradation process, four major metabolites were detected. In comprehensive consideration of the environmental behavior, the enantioselective degradation results should be considered to more accurately assess the risk of this chiral pesticide in a real environment.

Monitoring the hepatic residues of cis- and trans-diastereoisomers of second generation anticoagulant rodenticides reveals a different bioaccumulation of diastereoisomers in the food chain of the Réunion harrier (Circus maillardi).

The Réunion harrier is an endangered raptor and endemic species to the Réunion Island. Second generation anticoagulant rodenticides (SGARs) are widely used pesticides on the island in order to control rodent populations. The latter are responsible for the transmission of leptospirosis to humans, the damage of sugarcane crops, and the decline of endemic endangered birds. SGARs are very persistent chiral pesticides and consequent secondary exposure or poisoning of the Réunion harrier has been observed (73% of prevalence in a group of 58 harriers). Commercial formulations of SGARs are a mixture of trans- and cis-diastereoisomers. Both diastereoisomers of all SGARs have been shown to inhibit coagulation function with the same potency. On the other hand, they have been shown to have a significant difference in terms of tissue-persistence. This difference has led to residue levels in rats with a significantly lower proportion of one of the isomers compared to the bait composition. In this study, residue levels of the diastereoisomers of all SGARs were evaluated in the livers of 58 harrier carcasses. The respective concentrations and proportions of cis- and trans- diastereoisomers of all SGARs are presented. cis-Brodifacoum and trans-bromadiolone had the highest concentrations (up to 438 and 573ng/g ww respectively), while trans-brodifacoum was less than 46ng/g and cis-bromadiolone was barely detected. cis-Difenacoum showed the highest prevalence and the highest concentration was 82ng/g ww, while trans-difenacoum was never detected. This study demonstrated that only cis-brodifacoum and trans-bromadiolone (and cis-difethialone, but with a low prevalence) had hepatic concentrations above a toxic threshold. The cis- and trans-diastereoisomers of SGARs had differential bioaccumulation in the food chain of the Réunion harrier compared to commercial baits. This suggests that a change of the proportions of SGARs diastereoisomers in baits could reduce the risk of secondary poisoning of predators, but maintain primary toxicity.

Effects of the herbicides quizalofop-p-ethyl and quizalofop-ethyl on the physiology, oxidative damage, synthesis, and release of microcystin-LR in Microcystis aeruginosa

Quizalofop-Ethyl (QE) is a widely used phenoxy herbicide. It contains two enantiomers, and only its R-enantiomer quizalofop-p-ethyl (QpE) has herbicidal activity. Cyanobacterial blooms caused by Microcystis aeruginosa pose a threat to human health and aquatic environments, but the potential effects of chiral herbicides on M. aeruginosa are rarely studied. In this study, we carried out experiments using 0, 0.5, 1, 2, and 5 mg/L of QE and QpE to explore the effects on the growth, metabolism, synthesis, and release of microcystin-LR (MC-LR) in M. aeruginosa, which is the dominant species of algal blooms and indicator organism of water contamination. The biomass and chlorophyll a and protein content were consistent, showing that QpE at high concentrations (2 and 5 mg/L) showed greater acute toxicity than QE. On the expression of photosynthesis-related genes psaB and psbD1, QpE at 2 and 5 mg/L showed a stronger inhibition effect than QE. The oxidative stress caused by QE and QpE indicated that 144 h of exposure increased the concentration of MDA and enhanced the activities of superoxide dismutase and catalase. The synthesis of intracellular MC-LR in M. aeruginosa was stimulated by 144 h of QpE and QE exposure, and QpE showed a stronger stimulation effect than QE at high concentrations. The content of extracellular MC-LR increased after 144 h of QpE exposure and remained stable under QE exposure compared with that in the control group. Moreover, the expression of MC-LR-related gene mcyH was upregulated by QpE (144 h exposure) but downregulated by QE. These results are helpful to understand the toxicological effects of chiral herbicides on nontarget aquatic organisms, thus providing a theoretical basis for the rational use and the ecological risk assessment of chiral pesticides.

Different Degradation Patterns of Chiral Contaminant Enantiomers: Paclobutrazol as a Case Study

Studies often neglect the different trends between enantiomers in soil chiral contaminants. In the present study, paclobutrazol was chosen as the target analyte and the selective degradation patterns of this chiral pesticide were investigated in soils. After 14 days of culture, the degradation kinetics results demonstrated the degradation process of the two enantiomers conforms to first‑order degradation kinetics equation, and the degradation rates were significantly different (paired t-test, P < 0.05). The degradation rate of (2S,3S)-paclobutrazol (S-paclobutrazol) was higher than that of (2R,3R)-paclobutrazol (R-paclobutrazol), with the concentration decrease of 42.6 and 28.7%, respectively. Meanwhile, the enantiomer fraction (EF) was 0.43 at final sampling point, and the half-life (t1/2) of S-paclobutrazol and R-paclobutrazol were 17.3 and 28.9 days,which demonstrated significant enantioselective degradation. Results from this study served to enhance our understanding about the enantioselective degradation behaviors of chiral pesticides, which provided some scientific basis for the potential risk assessment of chiral pesticides in the environment.

Stereoselective environmental fate of fosthiazate in soil and water-sediment microcosms

The stereoselective fates of chiral pesticides in the environment has been reported in many studies. However, there is little data focused on the fate of chiral fosthiazate in the soil and aquatic ecosystems at chiral view. This study investigated the stereoselective fate of fosthiazate in the soil and aquatic ecosystems using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography tandem time-of-flight mass spectrometry (LC-TOF/MS/MS). Significant stereoselective degradation among four fosthiazate stereoisomers were found in both greenhouse soil and water-sediment microcosms. In greenhouse soil, (1R,3S)-fosthiazate degraded faster than other three stereoisomers with the half-life of 2.7 d. The fosthiazate stereisomers in the seawater-sediment microcosm degraded more rapidly than in the river water-sediment microcosm. However, (1S,3R)-fosthiazate and (1S,3S)-fosthiazate possessed shorter degradation half-lives than their enantiomers in both microcosms, with the half-lives ranging from 3.4 d to 15.8 d. Ten degradation products were identified in the water-sediment microcosms, and, six of them were reported for the first time. Oxidation and hydrolysis were confirmed as the main degradation pathways of fosthiazate in the water-sediment microcosms. Our results revealed that the (1R,3S)-fosthiazate and (1R,3R)-fosthiazate may cause more serious ecotoxicity due to the longer half-lives than the other two stereoisomers in environment.

Preparation of a New β-Cyclodextrin-bonded Chiral Stationary Phase with Thiocarbamated Benzamide Spacer for HPLC.

A new β-cyclodextrin-bonded chiral stationary phase (TCDP) with a thiocarbamated benzamide spacer was prepared and evaluated on HPLC by separating a series of chiral pesticides and drugs. TCDP resolved all 24 analytes (11 triazoles, 8 flavanones and 5 β-blockers), and 18 of them were completely separated. The enantioresolution ranges were 1.45 - 3.33 for triazoles, 0.35 - 2.45 for flavanones and 1.26 - 1.58 for β-blockers. Among them the best resolution of tebuconazole was up to 3.33 within 13 min. Bitertanol (two chiral centers) and triticonazole with cis/trans isomers were separated into four peaks, respectively. TCDP could also completely resolve myclobutanil (Rs = 1.68), which was difficult to be separated on other CD-CSPs. Common CDSP only resolved a few analytes. The results showed that the thiocarbamated benzamide spacer of TCDP may provide a synergistic effect of hydrogen bonding and coordination. The spacer deserved full utilization, by which may avoid troublesome derivatization at low cost.

Enantioselective residues and toxicity effects of the chiral triazole fungicide hexaconazole in earthworms (Eisenia fetida)

The enantioselective toxic effect and environmental behavior of chiral pesticides have attracted increasing research attention. In this study, the enantioselective toxicity and residues of hexaconazole (HEX) in earthworms ( Eisenia fetida ) were investigated. In the present study, significant enantioselective degradation characteristics were observed in artificial soil with the R -enantiomer preferentially degrading ( p < 0.05); however, no significant enantioselective bioaccumulation was observed in the earthworms ( p > 0.05). The acute toxicity of S -(+)-HEX was higher than that of R- (−)-HEX in earthworms, with 48-h LC 50 values of 8.62 and 22.35 μg/cm 2 , respectively. At 25 mg/kg, enantiospecific induction of oxidative stress was observed in earthworms; moreover, S -(+)-HEX had a greater influence on the contents of malonaldehyde, cytochrome P450, and 8-hydroxy-2-deoxyguanosine than R- (−)-HEX. These results were consistent with those of the enrichment analysis of differentially expressed genes. The transcriptome sequencing results showed that S -(+)-HEX had a more significant influence on steroid biosynthesis, arachidonic acid metabolism, and cell cycle processes than R- (−)-HEX, leading to abnormal biological function activities. These results indicate that S -(+)-HEX may pose a higher risk to soil organisms than R- (−)-HEX. This study suggests that the environmental risk of chiral pesticides to nontarget organisms should be assessed at the enantiomeric level. • S -(+)-HEX exhibited higher toxicity to earthworms than R -(−)-HEX. • .HEX enantiomers had significant enantioselective degradation in artificial soil. • No significant difference was found in earthworm bioaccumulation between HEX enantiomers. • S -(+)-HEX induced more seriously oxidative stress than that of R -(−)-HEX. • S -(+)-HEX affected steriod biosynthesis, arachidonic acid metabolism and cell cycle.

Preparation and evaluation of diureido bridged β-cyclodextrin-bonded chiral stationary phase by high-performance liquid chromatography

A diureido bridged β-cyclodextrin dimer was synthesized by the reaction of 6-deoxy-6-hydroxyethylamino-β-cyclodextrin with hexamethylene diisocyanate. The dimer was then bonded onto silica to obtain a novel diureido bridged β-cyclodextrin-bonded stationary phase (UBCDP). The structure of diureido bridged stationary phase was characterized by infrared spectroscopy, mass spectrometry, and elemental analysis. By using racemic drugs and pesticides as probes (flavanones, triazoles, and dansylated amino acids), the chromatographic properties of UBCDP were evaluated. The separation mechanism was elucidated by comparison with a single β-cyclodextrin chiral stationary phase (CDCSP). The composition, pH value of the mobile phase and column temperature were optimized. The results showed that the UBCDP can resolve 25 chiral compounds, especially 2'-hydroxyflavanone, hexaconazole and dansyl leucine with high resolutions (Rs, 1.52-4.35), and the larger volume hesperidin could also be separated. This trend was related to the synergistic inclusion of bridged cyclodextrins. CDCSP can separate only a small number of enantiomers with low resolutions. UBCDP exhibited better enantio-separation ability and hence had potential application in chiral drugs and chiral pesticide residues analysis.

Simultaneous enantiomeric determination of multiple triazole fungicides in fruits and vegetables by chiral liquid chromatography/tandem mass spectrometry on a bridged bis(β-cyclodextrin)-bonded chiral stationary phase

A LC-MS/MS method for simultaneous determination of twelve triazole enantiomers (hexaconazole, tebuconazole, triticonazole, flutriafol, diniconazole, paclobutrazol) in six fruits and vegetables was established based on a stable and self-made bridged bis(β-cyclodextrin)-bonded chiral stationary phase. Simultaneous enantio-separation of multiple analytes was achieved with resolution ca. 1.67–2.14. Magnetically assisted QuECHERS was used to simplify and optimize sample pre-treatment. The new method was validated (accuracy, precision, matrix effect, etc.). Good linearity (0.5–20 μg/L, R2 > 0.99) and high recoveries (76.1–103.4%) based on intra- and inter-day relative standard deviation (RSDs) (2.6–11.9%), were obtained. Furthermore, a total of 90 samples were analyzed using this method and enantiomeric fractions (EF) for tebuconazole in strawberry and cucumber (0.63 and 0.43, respectively) were determined as well as 0.57 for flutriafol in tomato. This high-throughput detection method supported a convenient enantiomeric monitoring for chiral pesticides in fruits and vegetables.

Low-dose cadmium stress increases the bioaccumulation and toxicity of dinotefuran enantiomers in zebrafish (Danio rerio)?

Co-occurrence of pesticides and heavy metals has attracted extensive attention. The enantioselective behaviors of dinotefuran to aquatic organisms have not been reported, and the effects of cadmium (Cd) was absent, which were investigated in this study at environmentally relevant concentrations. The enantioselective accumulation and elimination of dinotefuran enantiomers were observed in zebrafish, and it had tissue specificity. The S-dinotefuran concentrations were higher than R-dinotefuran in heads and viscera, but it was opposite in muscles. There existed competition between S-dinotefuran and R-dinotefuran, and the existence of S-dinotefuran might decrease the accumulation and elimination of the R-dinotefuran in zebrafish. When co-exposure to Cd and dinotefuran, the accumulation concentrations of dinotefuran enantiomers increased in zebrafish at the initial stage, which were opposite latterly. The accumulation concentrations of R-dinotefuran in R+Cd treatment in fish were 3.4 times higher than those in R-dinotefuran treatment, and the enantiomer fraction (EF) values changed from 0.484 to 0.195. The oxidative stress of S-dinotefuran on zebrafish was highest, followed by rac- and R-dinotefuran. Co-exposure to Cd led to toxicity increase for R-dinotefuran, the malonaldehyde (MDA) content decreased significantly in R+Cd treatment during 7-28 days, while obvious declination of MDA contents was found on the 28th day in R-dinotefuran treatment. Furthermore, compared to R-dinotefuran treatment, Cd increased the relative expression of cz-sod (3.4 times), cas3 (1.6 times) and p53 (5.7 times) in R+Cd treatment. The co-exposure of Cd might alter the environmental behaviors and toxicity effects of dinotefuran enantiomers in zebrafish, including the enantioselectivity. The effects of Cd on accumulation and toxicity of R-dinotefuran were greater than those on S-dinotefuran. Thus, it is necessary to consider the effects of coexistent metals to chiral pesticides in ecological risk. SUMMARIZES: The enantioselective accumulation and elimination of dinotefuran enantiomers had tissue specificity. Cd increased the accumulation and toxicity of R-dinotefuran in zebrafish.

Study on stereoselective bioactivity, acute toxicity, and degradation in cucurbits and soil of chiral fungicide famoxadone.

The chiral pesticide famoxadone is mainly applied to control fungal diseases on fruiting vegetables. The fungicidal activity, ecotoxicological effects, and degradation behavior of famoxadone enantiomers are less well known. In this study, a systemic assessment of the stereoselectivity of famoxadone was performed in cucurbits and soil. Famoxadone enantiomers presented distinct inhibitory activities among different fungal species. The bioactivities of R-(-)-famoxadone were 2.7-178 times higher than S-(+)-famoxadone toward five phytopathogens. Based on the obtained LC50 values, famoxadone was super toxic to Eisenia foetida (E. foetida). Moreover, the acute toxicity of R-(-)-famoxadone presented 167 times greater to E. foetida than that of S-(+)-famoxadone, indicating that R-(-)-famoxadone showed higher bioactivity toward target organisms and non-target organisms than S-(+)-famoxadone. In addition, a simple high-performance liquid chromatography (HPLC) method was established to determine the stereoselective degradation of famoxadone in two species of cucurbits (cucumber and chieh-qua) and in field soil. The half-life values of famoxadone degradation were from 5.4 to 14.1days, indicating that famoxadone was easily degraded. Additionally, no stereoselective degradation was found in cucurbits and soil. The results may provide promising implications for comprehensive environmental and ecological risk assessments of famoxadone.

Effects of fenvalerate concentrations and its chiral isomers on bacterial community structure in the sediment environment of aquaculture ponds.

To investigate the effect of chiral pesticide fenvalerate (FV) on the micro-ecological environment of aquaculture pond sediment, we used an indoor static experiment to observe the effects of FV added at different concentrations with different chiral isomers on the changes in the sediment bacterial community. The 16S rDNA high-throughput sequencing technique was used to conduct sequencing and analysis of the bacterial community structure as well as changes in aquaculture pond sediments after 4weeks of cultivation. The results showed that the microbial alpha diversity indices (Sobs and Shannon indices) of the treated groups were significantly lower than those of the control group after 4weeks (P < 0.05), and the values in the high-concentration group were significantly lower than those of the low-concentration group (P < 0.05). In terms of bacterial group composition, the proportion of abundance of Proteobacteria and Acidobacteria in the treated groups were greater than in the control group after 4weeks, while the proportion of abundance of Bacteroidetes and Verrucomicrobia were lower. In the high-concentration FV treatment group, the proportion of abundance of Bacteroidetes, Acidobacteria, Chloroflexi, Nitrospinae, unclassified_k_norank, Ignavibacteriae, and Nitrospirae were significantly different from those of the other groups (P < 0.05). Principal coordinate analysis (PCoA) and ANONISIM/Adonis analysis showed that the cis-enantiomer had a stronger effect on the bacterial community as the concentration of FV increased. In addition, the linear discriminant analysis effect size (LEfSe) and linear discriminant analysis (LDA) results revealed differences in the level of enrichment of bacterial groups caused by FV at different concentrations and isomer levels. Collectively, this study showed that FV residue has a pronounced effect on bacterial communities in sediment, which becomes more significant with increasing exposure concentration. The effects of the cis- and trans-enantiomers of FV on the sediment environment are different; the cis-enantiomer has a stronger effect on the bacterial community.

Influence of multi-walled carbon nanotubes on enantioselective bioaccumulation and oxidative stress toxicity of indoxacarb in zebrafish(Danio rerio)

Carbon nanotubes (CNTs) have been widely used in various fields with the rapid development of nanotechnology. Pesticides have an irreplaceable role in agricultural production, which leads to their massive utilization and their inevitably penetrate into the aquatic environment. However, limited information is available regarding the impact of CNTs on the toxicity and enrichment of chiral compounds to organisms. Using zebrafish as a model to study whether the enantioselective bioaccumulation and oxidative stress of chiral pollutants may be altered in the presence of MWCNTs. Significant enantioselective bioaccumulation was observed in zebrafish with the preferential accumulation of R-(−)-indoxacarb during the 28-day bioaccumulation. The combined exposure of MWCNTs does not affect the enantioselectivity of zebrafish bioaccumulation, but increase the bioaccumulation amount of R-(−)-indoxacarb by 65%. Moreover, the average degradation half-life of indoxacarb enantiomers was 1.30 days. The indoxacarb causes oxidative stress toxicity in zebrafish liver and exhibited enantioselectivity, while the addition of MWCNTs did not significantly change the enantioselectivity of oxidative stress toxicity of indoxacarb, but enhanced the toxicity 20% with increased MWCNTs concentrations. This study suggests that the risk of the co-presence of nanomaterials and chiral pesticides in aquatic environments should be taken into consideration.