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Pesticide exposure remains one of the main factors in the population decline of insect pollinators. It is urgently necessary to assess the effects of mixtures on pollinator risk assessments because they are often exposed to numerous agrochemicals. In the present study, we explored the mixture toxic effects of thiacloprid (THI) and cyproconazole (CYP) on honey bees (Apis mellifera L.). Our findings revealed that THI possessed higher acute toxicity to A. mellifera (96-h LC 50 value of 216.3 mg a.i. L -1 ) than CYP (96-h LC 50 value of 601.4 mg a.i. L -1 ). It's worth noting that the mixture of THI and CYP exerted an acute synergistic effect on honey bees. At the same time, the activities of detoxification enzyme cytochrome P450s (CYP450s) and neuro target enzyme Acetylcholinesterase (AChE), as well as the expressions of seven genes (CRBXase, CYP306A1, CYP6AS14, apidaecin, defensing-2, vtg, and gp-93) associated with detoxification metabolism, immune response, development, and endoplasmic reticulum stress, were significantly altered in the combined treatment compared with the corresponding individual exposures of THI or CYP. These data indicated that a mixture of THI and CYP could disturb the physiological homeostasis of honey bees. Our study provides a theoretical basis for in-depth studies on the impacts of pesticide mixtures on the health of honey bees. Our study also provides important guidance for the rational application of pesticide mixtures to protect pollinators in agricultural production effectively., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Pesticides commonly occur as mixtures in an aqueous environment, causing deleterious effects on human health and the environment. However, the mechanism underlying the combined effects on aqueous organisms remains largely unknown, especially at low concentrations. In the current study, we inspected the interactive toxicity of tebuconazole (TEB), a triazole fungicide, and bifenthrin (BIF), a pyrethroid insecticide, to zebrafish (Danio rerio) using various toxicological assays. Our data revealed that the 96 h-LC 50 (lethal concentration 50) values of BIF to fish at different life periods (embryonic, larval, juvenile, and adult periods) ranged from 0.013 (0.011-0.016) to 0.41 (0.35-0.48) mg a.i. L -1 , which were lower than that of TEB ranging from 1.1 (0.88-1.3) to 4.8 (4.1-5.7) mg a.i. L -1 . Combination of TEB and BIF induced synergetic acute toxicity to embryonic fish. Activities of T-SOD, POD, and GST were distinctly altered in most individual and joint administrations. Expressions of 16 genes associated with oxidative stress, cellular apoptosis, immune system, and endocrine system at the mRNA level were evaluated, and the information revealed that embryonic zebrafish were impacted by both individual compounds and their combinations. Six genes (cas9, P53, gr, TRα, IL-8, and cxcl-clc) exhibited greater changes when exposed to pesticide mixtures. Therefore, the joint effects induced by the pesticides at low concentrations should be considered in the risk assessment of mixtures and regulated as priorities for mixture risk management in the aqueous ecosystem. More research is needed to identify the threshold concentrations of the realistic pesticide mixtures above which synergistic interactions occur., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The natural co-occurrence of multiple mycotoxins has been reported in cereals and cereal products worldwide. Even though the dietary exposure to mycotoxins constitutes a serious human health, most reports are limited to the toxic effect of individual mycotoxins. The purpose of the present study was to assess the combined toxic effects of zearalenone (ZEN) and fumonisin B1 (FB1) and the potential interaction of their mixture on zebrafish (Danio rerio) embryos. Our results showed that ZEN possessed the higher toxicity to embryonic zebrafish (7-day LC 50 value of 0.78 mg a.i. L -1 ) compared with FB1 (7-day LC 50 value of 227.7 mg a.i. L -1 ). The combination of ZEN and FB1 exerted an additive effect on zebrafish embryos. Meanwhile, the activities of antioxidant CAT, caspase-3, and detoxification enzyme CYP450, as well as the expressions of six genes (Mn-sod, cas9, bax, cc-chem, ERα, and crh) associated with oxidative stress, cellular apoptosis, immune system, and endocrine system were prominently altered in the mixture exposure compared with the corresponding single treatment group of ZEN or FB1. Taken together, the regulatory standards of mycotoxins in food and feed should be updated based on the mixture effects of mycotoxins, and there is an increased need on effective detoxification methods for controlling and reducing the toxicity of multiple mycotoxins in animal feed and throughout the food supply chain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Though pesticide mixtures can reflect the real-life situation in the water ecosystem, the quantification of their toxicity is still not fully understood. Combined effects of thiophanate-methyl (THM) and fenvalerate (FEN) on embryonic zebrafish (Danio rerio) and underlying mechanism were conducted in this study. Results showed that the 96-h LC 50 values of THM to D. rerio at different growth periods ranged from 12.1 to 26.1 mg L -1 , which were lower in comparison with those of FVR ranging from 0.025 to 2.8 mg L -1 . Mixture of THM and FVR exhibited a synergetic response to zebrafish embryos. Activities of Cu/Zn-SOD, POD, caspase 3 and caspase 9 were significantly different in most of single and mixture administrations compared with the control group. In addition, five genes (P53, Cu/Zn-sod, crh, ERα and IL-8) associated with oxidative stress, cellular apoptosis, immune system and endocrine system showed greater variations of expressions when administrated to pesticide mixtures compared with single chemicals. Our experimental results exhibited that mixtures of thiophanate-methyl and fenvalerate produced higher toxicity towards aqueous vertebrates than when determined singly. Collectively, upcoming environmental risk assessments established according to single administrations might not be enough to protect the water ecosystem., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aquatic organisms are usually exposed to a mixture of pesticides instead of individual chemicals. However, risk assessment of pesticides is traditionally based on toxicity data of individual compounds. In this study, we aimed to examine the joint toxicity of two fungicides cyprodinil (CYP) and kresoxim-methyl (KRM) to zebrafish (Danio rerio) using a systematic experimental approach. Results from 96-h semi-static test indicated that the LC 50 values of KRM to D. rerio at multiple life stages (embryonic, larval, juvenile and adult stages) ranged from 0.034 (0.015-0.073) to 0.61 (0.39-0.83) mg a.i. L -1 , which were higher than those of CYP ranging from 1.05 (0.88-1.52) to 4.42 (3.24-6.02) mg a.i. L -1 . Pesticide mixtures of CYP and KRM exhibited synergistic effect on embryonic zebrafish. The activities of carboxylesterase (CarE) and cytochrome P450 (Cyp450) were significantly altered in most of the individual and combined exposures compared with the control group. The expressions of seven genes (Mnsod, cyp17, crhr 2, crh, gnrhr 4, gnrhr 1 and hmgrb) were significantly altered upon exposure to combined pesticides compared with their individual pesticides. Collectively, these findings suggested joint effects should be considered in the risk assessment of pesticides and development of water quality criteria for the protection of aquatic environment., (Copyright © 2018 Elsevier B.V. All rights reserved.)