Co-exposure to boscalid and amoxicillin inhibited the degradation of boscalid and aggravated the threat to the earthworm.

The extensive application of pesticides and antibiotics in agricultural production makes it possible for them to coexist in farmland, and the interaction of the two pollutants can lead to changes in environmental behavior and toxicity, creating uncertainty risks to soil and soil organisms. In this study, we explored the environmental behavior and the effects of earthworms under co-exposure to amoxicillin and boscalid and further explored the accumulation and toxic effects on earthworms. The results showed that amoxicillin increased the adsorption of boscalid in soil and inhibited its degradation. In addition, we noticed that the co-exposure of amoxicillin and boscalid caused intestinal barrier damage, which increased the bioaccumulation of earthworms for boscalid and led to more severe oxidative stress and metabolic disorders in earthworms. In summary, our findings indicate that amoxicillin can increase the ecological risk of boscalid in the environment and imply that the encounter between antibiotics and pesticides in the environment can amplify the toxic effects of pesticides, which provides new insights into the ecological risks of antibiotics.

Nano-selenium repaired the damage caused by fungicides on strawberry flavor quality and antioxidant capacity by regulating ABA biosynthesis and ripening-related transcription factors.

Recently, studies have shown that pesticides may have adverse effects on the flavor quality of the fruits, but there is still a lack of appropriate methods to repair the damage. This study investigated the effects and mechanism of applying the emerging material, nano­selenium, and two fungicides (Boscalid and Pydiflumetofen) alone or together on the flavor quality and antioxidant capacity of strawberries. The results showed that the two fungicides had a negative impact on strawberry color, flavor, antioxidant capacity and different enzymatic systems. The color damage was mainly attributed to the impact on anthocyanin content. Nano­selenium alleviated the quality losses by increasing sugar-acid ratio, volatiles, anthocyanin levels, enzyme activities and DPPH scavenging ability and reducing ROS levels. Results also showed that these damage and repair processes were related to the regulation of flavor and ripening related transcription factors (including FaRIF, FaSnRK1, FaMYB10, FaMYB1, FaSnRK2.6 and FaABI1), the upregulation of genes on sugar-acid, volatile, and anthocyanin synthesis pathways, as well as the increase of sucrose and ABA signaling molecules. In addition, the application of nano-Se supplemented the selenium content in fruits, and was harmless to human health. This information is crucial for revealing the mechanisms of flavor damage caused by pesticides to strawberry and the repaired of nano­selenium, and broadens the researching and applying of nano­selenium in repairing the damage caused by pesticides.

Multi-omics and gut microbiome: Unveiling the pathogenic mechanisms of early-life pesticide exposure.

The extensive application of pesticides in agricultural production has raised significant concerns about its impact on human health. Different pesticides, including fungicides, insecticides, and herbicides, cause environmental pollution and health problems for non-target organisms. Infants and young children are so vulnerable to the harmful effects of pesticide exposure that early-life exposure to pesticides deserves focused attention. Recent research lays emphasis on understanding the mechanism between negative health impacts and early-life exposure to various pesticides. Studies have explored the impacts of exposure to these pesticides on model organisms (zebrafish, rats, and mice), as well as the mechanism of negative health effects, based on advanced methodologies like gut microbiota and multi-omics. These methodologies help comprehend the pathogenic mechanisms associated with early-life pesticide exposure. In addition to presenting health problems stemming from early-life exposure to pesticides and their pathogenic mechanisms, this review proposes expectations for future research. These proposals include focusing on identifying biomarkers that indicate early-life pesticide exposure, investigating transgenerational effects, and seeking effective treatments for diseases arising from such exposure. This review emphasizes how to understand the pathogenic mechanisms of early-life pesticide exposure through gut microbiota and multi-omics, as well as the adverse health effects of such exposure.

Widening the Lens on Prothioconazole and Its Metabolite Prothioconazole-Desthio: Aryl Hydrocarbon Receptor-Mediated Reproductive Disorders through in Vivo, in Vitro, and in Silico Studies.

Reproductive disorders are a serious public health problem worldwide. Epidemiological data suggest that exposure to environmental pollutants is associated with the onset of reproductive disorders. However, the effects in reproductive health and exact mechanism of action of representative agricultural compounds prothioconazole (PTC) and its metabolite prothioconazole-desthio (dPTC) on mammals remain unclear. Here, we studied the physiological effects of the exposure to environmentally relevant doses of PTC and dPTC in mice reproductive systems. Combining in vivo, in vitro, and in silico studies, we observed that PTC and dPTC disrupt reproductive health by inducing metabolic perturbation, induction of apoptosis, and inflammation in gonadal tissue, which are achieved via activation of the aryl hydrocarbon receptor (AhR). Convincingly, the addition of alternate-day injections of CH223191 (an AhR inhibitor) to the 30-day exposure regimen ameliorated ovarian tissue damage, as evidenced by decreased TUNEL-positive cells and partially restored the inflammation and apoptotic factor levels. This study comprehensively reports the toxic effects of low-dose PTC and dPTC in the reproductive system in vivo and identifies AhR as a potential therapeutic target for the amelioration of reproductive disorders caused by similar endocrine-disrupting chemicals.

Possible changes in trade-off strategy in female lizards (Eremias argus) during hibernation following exposure to chlorantraniliprole: Impact on the HPG axis and the energy mobilization.

Hibernation is a short-term survival strategy for ectotherms to cope with cold weather and food shortages. The energy sources stored before hibernation are used not only in the winter, but also in preparation for reproduction. Reproductive physiology and behavior are primarily regulated by the hypothalamus-pituitary-gonad (HPG) axis. In this study, we examined endocrine hormone changes in the HPG axis of female lizards (Eremias argus) after chlorantraniliprole insecticide (CAP) exposure during hibernation. The levels of gonadotropin-releasing hormone, luteinizing hormone, follicle-stimulating hormone and progesterone were significantly decreased and the level of testosterone (T) was significantly increased after 135d experiment. This study verified the possible endocrine disrupting effects of CAP. More energy material consumption was observed in CAP treated group. Female E. argus preferred to invest energy to present survival when exposed to CAP, rather than to reserve material for following reproductive activity.

Imazalil and its metabolite imazalil-M caused developmental toxicity in zebrafish (Danio rerio) embryos via cell apoptosis mediated by metabolic disorders.

Imazalil (IMZ) is a highly effective fungicide employed in crop production. It has been consistently detected in aquatic environments. The main environmental metabolite of IMZ is imazalil-M (IMZ-M). Limited studies have focused on the toxicity of IMZ and IMZ-M in aquatic organisms. This study systematically evaluated the developmental toxicity of IMZ and IMZ-M on zebrafish (Danio rerio) embryos and explored the potential mechanisms involved. The results showed that IMZ and IMZ-M caused developmental toxicity, characterized by decreased heart rate, hatching inhibition, and pericardial cyst in zebrafish embryos. Subsequently, acridine orange (AO) staining revealed cell apoptosis in the area around the heart regions of zebrafish larvae. Besides, the expression levels of apoptosis-related genes also varied significantly. Furthermore, 1H NMR-based metabolomics analysis showed that IMZ and IMZ-M exposure could induce metabolic profiles disorder in zebrafish larvae. Importantly, zebrafish exposure to IMZ and IMZ-M significantly affected the metabolism of branched - chain amino acids, energy, and ketone bodies, which are related to cell apoptosis. Overall, the toxicity of IMZ and IMZ-M in zebrafish embryos and larvae was characterized, suggesting a theoretical basis for the potential environmental risks of IMZ and its metabolite IMZ-M on non-target organisms.

Prothioconazole and prothioconazole-desthio induced different hepatotoxicities via interfering with glycolipid metabolism in mice.

Prothioconazole (PTA), a new triazole fungicide, has been widely used worldwide. A recent study has confirmed that PTA and its main metabolite prothioconazole-desthio (dPTA) interfere with the liver metabolism in reptiles. However, little is known about liver toxicity of these two pollutants in mammals. Here, female mice were orally exposed to PTA (1.5 mg/kg body weight/day) and dPTA (1.5 mg/kg body weight/day) for 30 days. Additionally, growth phenotype and indexes related to serum and liver function were examined. Using metabolomics and gene expression analysis, PTA- and dPTA-induced hepatotoxicity was studied to clarify its potential underlying mechanism of action. Together, the results indicated that PTA and dPTA exposure caused changes in growth phenotypes, including elevated blood glucose levels, triglyceride accumulation, and damage of liver function. Additionally, exposure to PTA and dPTA caused changes in genes and metabolites related to glycolipid metabolism in female mice, thereby interfering with the pyruvate metabolism and glycolysis/gluconeogenesis pathways, ultimately leading to hepatic metabolism disorders. In particular, the effect of dPTA on hepatotoxicity has been proven to be more significant than that of PTA. Thus, these findings help us understand the underlying mechanism of action of PTA and dPTA exposure-induced hepatotoxicity in mammals and possibly humans.

Xenopus laevis tadpoles exposed to metamifop: Changes in growth, behavioral endpoints, neurotransmitters, antioxidant system and thyroid development.

Pesticides are a major cause of the reduction in the global amphibian population. In this study, the acute toxicity and chronic effects of metamifop on Xenopus laevis (X. laevis) tadpoles were investigated. The 96 h-LC50 value of metamifop on X. laevis tadpoles was 0.634 mg/L, which indicated that metamifop was highly toxic to tadpoles. In the chronic toxicity study, tadpoles were exposed to 0.063 mg/L of metamifop. After 14, 21 and 35 d of exposure, metamifop significantly inhibited the body weight and neurotransmitter synthesis of tadpoles, caused abnormal behavior and interfered with fat metabolism. According to the results of antioxidant enzymes and malondialdehyde (MDA), tadpoles exposed to 0.063 mg/L metamifop suffered severe lipid oxidative damage. Compared with the control group, the thyroid hormone (TH) levels and related gene expression in tadpoles in the treatment group were affected, reflecting the endocrine interference effect of metamifop. The data of this study can enrich our knowledge of the effects of aryloxyphenoxy propionate pesticides on amphibians and highlight the role of metamifop and other pesticides play in global decline of amphibians.

Thermal effects on tissue distribution, liver biotransformation, metabolism and toxic responses in Mongolia racerunner (Eremias argus) after oral administration of beta-cyfluthrin.

Effects of temperature on metabolism/biotransformation and toxicokinetics to lizards are significant, but frequently ignored in toxicology studies. Beta-cyfluthrin (BC) is a pyrethroid insecticide and has been widely used globally. The study aimed to understand the diverse adverse effects of BC to the lizard (Eremias argus) at different temperature regimes. We carried out a single oral BC treatment (20 mg/kg bw) for toxicokinetic study and a 7-day BC (10 mg/kg bw) gavage to look at toxicology by monitoring changes in the biomarkers HSP70, SOD, MDA, CarE, UDPGT, GST, cyp genes, and other metabolic responses. Results showed that BC was lethal to lizards, showing oxidative damages in the liver at ambient temperature (25 °C). Heat stress (35 °C) could exacerbate the oxidative damage (MDA increased) caused by BC, due to the disorder of the antioxidant defense system. The result of tissue distribution and toxicokinetic study also showed that temperature affected the BC biotransformation in lizards. The biotransformation of BC maybe relates to the activation of CarE and UDGPT by heat stress. However, the cyp system and GST didn't increase under BC or/and heat treatments. 1H-NMR metabolomics analysis showed that BC or/and heat stress interfered with energy and amino acid metabolism of the liver. Unlike acute lethal toxicity, the occurrence of the BC and heat stresses has detrimental effects on lizard individuals and populations on sub-lethal levels. Our results indicate that pollution and global warming (or some other extremely weather) may generate significant and harmful effects on lizards.

Enantioselective mechanism of toxic effects of triticonazole against Chlorella pyrenoidosa.

The rational use and the environmental safety of chiral pesticides have attracted significant research interest. Here, enantioselective toxic effects and the selective toxic mechanism of triticonazole (TRZ) against the aquatic microalgae Chlorella pyrenoidosa were studied. The 96h-EC50 values of rac-, (R)-(-)-, and (S)-(+)-TRZ were 1.939, 0.853, and 22.002 mg/L, respectively. At a concentration of 1 mg/L, the contents of photosynthetic pigments of C. pyrenoidosa exposed to (R)-(-)-TRZ were lower than if exposed to S-(+)-form and racemate. Transmission electron microscopic images showed that the R-(-)-form compromised the integrity of cells and disrupted the chloroplast structure. R-(-)-TRZ stimulated vast reactive oxygen species (ROS) and significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, as well as malondialdehyde (MDA) content. For lipid accumulation experiments, nicotinamide adenine dinucleotide (NADH) and triacylglycerol (TAG) accumulations in algal cells treated with R-(-)-TRZ were 171.50% and 280.76%, respectively, compared with the control group. This far exceeded levels of algal cells treated with S-(+)- and rac-TRZ. Based on these data, R-(-)-TRZ was concluded to selectively affect the photosynthetic system, antioxidant system, and lipid synthesis of algal cells, thus causing enantioselective toxic effects of TRZ against C. pyrenoidosa, which indicating that the use of racemate may cause unpredictable environmental harm. Therefore, to reduce the hidden dangers of chiral pesticides for the ecological environment, the environmental risk of TRZ should be evaluated at the stereoselective level.

Ecological risk assessment of alpha-cypermethrin-treated food ingestion and reproductive toxicity in reptiles.

Pesticides are proposed as one of the many causes for the global decline in reptile population. To understand the potential impact of alpha-cypermethrin (ACP) in reptiles, in the current study, we used a tri-trophic food web (plants - herbivores - natural enemies of predators) to examine the reproductive toxicity and biomarker changes. Based on the Maximum Residue Limit (MRL) of ACP in several agricultural products, we designed three concentrations 0, 2 (MRL), and 20 mg/kg wet weight as three treatment groups for this research. Male and female lizards were fed ACP contaminated or uncontaminated diets for eight weeks during the breeding phase. The number of deaths was different among the three groups, and a dose-dependent trend was found. Decreases in food consumption of 26.6% and 28.1% were observed in the low- and high-dose group, respectively. Dietary exposure significantly induced a dose-dependent decrease in body mass index in lizards. Significant variations in glutathione-S-transferaseb activities, catalase activities, and malondialdehyde levels in gonads, suggest that lizards were under oxidative stress. In addition, ACP exposure altered sexual hormone levels in males, reduced reproductive output of females, and induced histopathological changes in testes. These negative effects highlight that ACP dietary exposure is a potential threat to lizards' reproduction.

Enantioselective toxic effects and digestion of furalaxyl enantiomers in Scenedesmus obliquus.

Research on the enantioselective environmental behavior of chiral pesticides has been a hot spot of environmental chemistry recently. In this study, the acute toxicity and digestion of furalaxyl enantiomers were determined on the aquatic algae Scendesmus obliquus. After exposure for 96 hours, the EC50 values for (S)-furalaxyl and (R)-furalaxyl were 13.59 and 15.26 mg/L, respectively. In addition, enantioselectivity was observed from the determined chlorophyll contents and antioxidant enzyme (CAT and SOD) activities of algae cells after exposure to furalaxyl enantiomers for 96 hours. The digestion rate of (S)-furalaxyl and (R)-furalaxyl were almost the same in S. obliquus. On the basis of these data, the inactive enantiomers (S)- furalaxyl is more toxic than the active one on the non-target species S. obliquus, indicating that such enantiomeric differences should be taken into consideration in the study of pesticide risk assessment.

Comparison of triadimefon and its metabolite on acute toxicity and chronic effects during the early development of Rana nigromaculata tadpoles.

Pesticides are one of major causes for amphibian population declines and the behavior of pesticide metabolite products to amphibians has become a rising concern. In this study, the acute toxicity and the chronic effects of triadimefon and triadimenol (the metabolite of triadimefon) on Rana. nigromaculata were investigated. In the acute assay, significant differences were observed in antioxidant enzyme activities and malondialdehyde levels between the triadimefon and triadimenol. The 96 h-acute toxicity of triadimefon (25.97 mg/L) and triadimenol (34.55 mg/L) to tadpoles was low. In 28d-chronic exposure, we studied the relative expression of tadpoles genes related to thyroid hormone-dependent metamorphic development, histological examination of liver and some biological index, including wet weight, snout-to-vent length (SVL) and development stages. The results revealed that the effects of triadimefon and triadimenol on tadpole development are driven by a disruption of the hormonal pathways involved in metamorphosis. Interestingly, triadimefon was more harmful on R. nigromaculata than triadimenol at high dose, whereas the reverse result was observed at low doses. According to the relative expression of thyroid hormone-dependent genes, we also found that the two compounds may have different mechanisms of toxic action on R. nigromaculata. Our study developed a pragmatic approach for use in the risk assessment of pesticide and its metabolite，and increased the information and understanding of the impacts of fungicides and other potential endocrine disrupting environmental contaminants on amphibians.

Tissue distribution and toxicity effects of myclobutanil enantiomers in lizards (Eremias argus).

In recent years, serious environmental pollution has caused a decrease in the abundance of many species worldwide. Reptiles are the most diverse group of terrestrial vertebrates. There are large amounts of toxicological data available regarding myclobutanil, but the adverse effects of myclobutanil on lizards has not been widely reported. In this study, treatment groups were orally administered a single-dose of myclobutanil (20mg/kg body weight (bw)). Subsequently, it was found that there were differences in myclobutanil levels between the different tissues and concentrations also changed with degradation time. The tissue concentrations of myclobutanil decreased in the order of: stomach > liver > lung > blood > testis > kidney > heart > brain. Based on our results, the liver and testis were considered to be the main target organs in lizards, indicating that the myclobutanil could induce potential hepatic and reproductive toxicity on lizards. Meanwhile, it was also demonstrated that the toxic effects of myclobutanil was different in different species, and the distribution of different pesticides in lizards were different.

Stereoselective Behavior of the Chiral Herbicides Diclofop-Methyl and Diclofop During the Soy Sauce Brewing Process.

Chiral pesticides are now receiving more and more attention in the food-making process. This experiment studied the enantioselective behavior of diclofop-methyl (DM) and its main metabolite, diclofop (DC), during the soy sauce brewing process. Two kinds of commonly used strains, Aspergillus oryzae and Saccharomyces rouxii, were investigated. However, they showed a different degradation ability to the enantiomers of DM and DC. It was observed that (-)-(S)-DM was degraded much faster than (+)-(R)-DM by Saccharomyces rouxii, while no stereoselective degradation was found by Aspergillus oryzae. DC represented a relatively long residue period in this fermentation process and both strains showed a weak degradation ability to DC, especially Saccharomyces rouxii. There was little DC detected in the final product, while most of the DC residues persisted in the lees, which were usually used as animal feeds or discarded into the environment directly as waste. Therefore, more attention should be paid to the soy sauce brewing process concerning pesticide residues both in the final product and byproducts.

Stereoselective Behavior of the Fungicide Benalaxyl During Grape Growth and the Wine-Making Process.

Benalaxyl is widely applied as a fungicide during grape planting processing. In this experiment, the stereoselective behavior of benalaxyl was studied during the grape growth and wine-making process. A simple method based on high-performance liquid chromatography (HPLC) equipped with a chiral column and UV detector was established to separate and determine the enantiomers of benalaxyl. Stereoselective degradation of the two enantiomers of benalaxyl was found in grapes. The degradation of both enantiomers followed pseudofirst-order kinetics, and the degradation rate of R-(-)-benalaxyl was faster than S-(+)-benalaxyl. The half-life of R-(-)-benalaxyl was 27 h, while the half-life of S-(+)-benalaxyl was 31 h. The enantiomer fraction value decreased from 0.50 to 0.34 and finally only S-(+)-benalaxyl could be detected. In the fermentation process, both enantiomers of benalaxyl were hardly degraded, and no configuration interconversion was observed. Meanwhile, both enantiomers of benalaxyl showed little influence on the growth of the yeast, consumption of carbon sources, or production of alcohol. The result of this study might provide more sufficient data for the evaluation of food safety and potential risk. Chirality 28:394-398, 2016. © 2016 Wiley Periodicals, Inc.

Effects of benthic organism Tubifex tubifex on hexachlorocyclohexane isomers transfer and distribution into freshwater sediment.

In this study, bioaccumulation and elimination of HCHs in tubifex, and the distribution of HCHs in overlying water and sediment, were studied during a 10-d experiment. A sensitive method was developed for the determination of HCHs in samples based on gas chromatograph (GC) equipped with a nickel-63 electron capture detector (µECD). The limit of detection (LOD) was 0.35 µg/kg for α-HCH and 0.82 µg/kg for ß-HCH. Tubifex accumulated HCHs rapidly, and the curves were approximately M-type. The highest level was reached on the 7th day, with 0.34 mg/kg(wwt) for α-HCH and 0.87 mg/kg(wwt) for ß-HCH in worms. The AFs of ß-HCH in tubifex were higher than those of α-HCH. Moreover, the existence of tubifex significantly reduced ß-HCH fluxes from the overlying water to sediment by uptake or degradation and decreased the concentrations of ß-HCH in the sediment, but it had little influence on α-HCH fluxes. Moreover, enantioselectivity of α-HCH enantiomers was not observed in tubifex, whether in the bioaccumulation or elimination experiments. At the end of the elimination experiment, approximately 80% and 70% of α-HCH and ß-HCH were eliminated, and the depuration half-lives were 4.43 and 5.39 days, respectively.

Comparison of Different Extraction Methods for Analysis of 10 Organochlorine Pesticides: Application of MAE-SPE Method in Soil from Beijing.

Four commonly applied extraction techniques for organochlorine pesticides, microwave-assisted extraction (MAE), accelerated solvent extraction (ASE), quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction and ultrasonic solvent extraction, were applied on soil samples in order to evaluate their performances. The extracts were analyzed by GC-ECD and confirmed by GC-MS/MS. The MAE and QuEChERS extraction methods generally yielded higher results compared to the ultrasonication and ASE methods, while the lowest recovery (56.8 %) for o,p'-DDD was obtained using the QuEChERS method. The MAE method was further applied to six different soils from Beijing. In the soil samples only α-endosulfan and ß-endosulfan were not detected. The ratios of α-HCH/γ-HCH and α-HCH/ß-HCH indicated HCH residues likely originated from historical use of HCHs, and that technical HCHs were not likely being currently applied in Beijing.

Stereoselective bioaccumulation and metabolite formation of triadimefon in Tubifex tubifex.

Triadimefon, a chiral fungicide, could be metabolized to triadimenol which has two chiral centers. In this work, Tubifex tubifex was exposed to triadimefon through the aqueous and soil phase to explore the relative importance of the routes of uptake. Bioaccumulation of triadimefon in tubifex was detected in both treatments, and the kinetics of the accumulation processes were significantly different in these two experiments. In spiked water treatment, (S)-triadimefon was preferentially accumulated over the (R)-triadimefon, whereas the enantioselective bioaccumulation was not detected in the spiked soil microenvironment. Simultaneously, four stereoisomers of triadimenol were also found in the tubifex tissue. Although the amount of these stereoisomers were different from each other with relatively more accumulation of the most fungi-toxic stereoisomer (1S,2R), the abundance ratios in the two exposure treatments were similar at the same sampling, following the order (1S,2S) > (1R,2S) > (1R,2R) > (1S,2R). The bioaccumulation factor was calculated for parent compound triadimefon and metabolite enrichment factor for metabolite. The results showed that both uptake routes, epidermal contact in the aqueous phase and ingestion of solid particles in soil, were important to the bioaccumulation of the triadimefon and triadimenol in tubifex.

Enantioselective bioaccumulation and dissipation of soil-associated metalaxyl enantiomers in tubifex.

Many pesticides are chiral compounds and stereochemistry is an important factor for any reaction of chiral structures in biological systems. In this study, experiment about bioaccumulation of the two metalaxyl enantiomers in Tubifex (Oligochaeta, Tubificida) was conducted in laboratory aquatic ecosystems. Terrestrial soil spiked with two dose levels of metalaxyl was employed as the artificial bottom substrate. A method of determination of metalaxyl enantiomers in tubifex tissue, soil and overlying water were developed by HPLC. During a 14-day exposure, concentrations of metalaxyl in tubifex increased with the of soil concentration, however, the enantioselective bioaccumulation was only detected at high-dose exposure group, with the preferential accumulation of (-)-(R)-metalaxyl. The bioturbation activity of tubifex decreased water clarity and released soil-associated metalaxyl to overlying water. In those experiments where tubifex was exposed to metalaxyl from soil, pore water and overlying water, each route contributed to the total body burden, and our results indicated the pore water and soil are the primary exposure routes for high-dose exposure concentration treatment.