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JOURNAL OF HAZARDOUS MATERIALS · 2025 · IF 11.3

Evaluating the combined toxicity of broflanilide and myclobutanil on honeybees (Apis mellifera L.): Molecular mechanisms and protective effects of curcumin

Rongyi Ye,Ran Yi,Yihan Wang,Nan Huang,Yanhua Wang,Chen Chen

Pesticide toxicity to honeybees has become a pressing ecological issue, yet the effects of pesticide co-exposure are still not fully understood. This research investigates the toxicological implications of concurrent exposure to broflanilide (BFL), a novel diamide insecticide, and myclobutanil (MYC), a commonly used triazole fungicide, on honeybees ( Apis mellifera L . ), while exploring potential preventive strategies. Acute toxicity tests revealed a significantly lower 96-hour lethal concentration 50 (LC 50 ) for BFL (0.34 mg a.i. L −1 ) compared to MYC (82.3 mg a.i. L −1 ), and their co-exposure resulted in pronounced synergistic toxicity. Worker bees were exposed to environmentally relevant doses of BFL and MYC for 7 days, and midgut toxicity was assessed. The co-exposure caused severe midgut damage, including G-layer deterioration, loss of columnar epithelium integrity, and downregulation of the tight junction protein Z O-2. Additionally, oxidative stress-related genes ( Sod1 , Catalase , SelK , GstD1 ) were upregulated, accompanied by higher MDA levels and increased CAT and SOD activities. Furthermore, a greater number of TUNEL-positive cells were detected, along with elevated expression of apoptosis-related genes ( Caspase-3-like , Caspase-8-like , Caspase-9-like ) and higher caspase enzyme activities. Curcumin (Cur) was tested for its protective effects, and it significantly alleviated midgut damage, oxidative stress, and apoptosis. This study reveals the synergistic ecotoxicological effects of pesticide combinations and suggests Cur as a potential prevention strategy for mitigating their harmful impact on honeybees.

CAS / MDL: 7558-80-7
研究领域: 生态毒理学 · 昆虫学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2021 · IF 7.963

Synergetic toxicity of silver nanoparticle and glyphosate on wheat (Triticum aestivum L.)

Lan Feng,Nuohan Xu,Qian Qu,Zhenyan Zhang,Mingjing Ke,Tao Lu,Haifeng Qian

Silver nanoparticles (AgNPs) are one of the most commonly used nanomaterials in industrial and agricultural production. Glyphosate is a broad-spectrum systemic herbicide, which mainly acts in the phloem of weeds that compete with crop growth and is widely used in agriculture. This study investigated the interactive effects of AgNPs and glyphosate on the physiological morphology, gene transcription, and rhizosphere microorganisms of wheat. Our results demonstrated that wheat growth, and the structure and diversity of rhizosphere microorganisms were slightly influenced by AgNPs and glyphosate single treatment at the test concentration. However, AgNPs and glyphosate (Gly) combined treatment (AgNPs + Gly) strongly inhibited wheat growth and influenced gene transcription. In total, 955, 601, and 1336 genes were determined to be differentially expressed in AgNPs, glyphosate, and combined treatment, respectively. According to KEGG analysis, the combined groups induced an antioxidant response by upregulating the transcription of phenylpropanoid biosynthesis-related genes. In addition, more energy was needed, and disrupted cell membrane was shown in the combined treatment, which displayed in the upregulation of sucrose, starch, and lipid synthesis. Moreover, the relative abundance of Bradyrhizobium , Devosia , Kribbella , Sphingopyxis (nitrogen-fixing bacteria), and Streptomyces (plant growth-promoting bacteria) in soil microbiota were decreased, implicated that nitrogen fixation and some beneficial substance secretions were inhibited by the combined treatment. This study emphasized that the synergetic effects of AgNPs and glyphosate exerted a negative impact on wheat growth.

CAS / MDL: 1071-83-6
研究领域: 植物学 · 环境科学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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AQUATIC TOXICOLOGY · 2025 · IF 4.3

Combined toxicity of microplastic fibers and dibutyl phthalate on algae: Synergistic or antagonistic?

Le Liang,Yangyang Liang,Min Su,Zhe Wang,Zhendong Zhou,Xiaotao Zhou,Zhongguan Jiang

Plastics, combined with plasticizers, have been widely utilized worldwide. Microplastic fibers (MPFs) and dibutyl phthalate (DBP) account for the most predominant microplastics and plasticizers detected in freshwater ecosystem, with their joint toxicity being limited studied. In this study, we employed freshwater algae ( Chlorella vulgaris ) as toxicity test model organism to assess their growth, photosynthesis, metabolism, and oxidative response when exposing to different concentrations of polypropylene MPFs and the co-exposure of DBP. In addition, the toxic interaction between MPFs and DBP was assessed by combining the integrated toxicity value (Integrated Biomarker Response version 2, IBRv2) and the mixture toxicity index (Effect Addition Index, EAI). Our results demonstrated significant toxic effects of MPFs and DBP on C. vulgaris , and highlighted their dynamic interactions with C. vulgaris . Specifically, when combining with DBP, MPFs with high concentrations exhibited significantly increase in algae growth inhibition, photosynthetic pigment contents (Chl-a, Chl-b, and carotenoids), protein contents, and oxidative enzymes (SOD, CAT, and MDA). In terms of integrated toxicity values, higher IBRv2 values were recorded by the combined exposure of MPFs and DBP in contrast with the sole exposure groups, indicating that the combined exposure caused more severe damage to photosynthesis, oxidation and metabolism. In addition, our study recorded synergistic combined toxicity when MPFs were in high concentrations, whereas antagonistic combined toxicity when MPFs were in low concentrations. Our study highlights the MPFs concentration-dependent combined toxicity (synergistic or antagonistic) when exposing to microplastics and plasticizers in freshwater ecosystems.

CAS / MDL: 84-74-2 67-64-1
研究领域: 环境科学 · 生态毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2019 · IF 3.571

Combination of Patulin and Chlorpyrifos Synergistically Induces Hepatotoxicity via Inhibition of Catalase Activity and Generation of Reactive Oxygen Species

Shangyun Lu,Shuo Liu,Jinling Cui,Xiaoyi Liu,Chong Zhao,Lihong Fan,Shutao Yin,Hongbo Hu

Patulin (PAT) is the most common food-borne mycotoxin found in fruits and fruit-derived products, while chlorpyrifos (CPF) is a widely used pesticide on fruit and other crops. On the basis of the residue data, certain types of fruits can be contaminated simultaneously by patulin and chlorpyrifos. However, there are no available data about the combined toxicity. Since liver is a possible toxic target of both patulin and chlorpyrifos, we tested whether the combination exposure can cause enhanced hepatotoxicity using both cell culture and animal models. Results showed that the combination resulted in synergistic cytotoxicity in vitro and significantly enhanced liver toxicity in vivo. Mechanistically, PAT inhibited catalase activity via PIG3 induction, while CPF decreased catalase expression. These two mechanisms were converged in response to the combination, leading to enhanced inactivating catalase and boosted reactive oxygen species generation. The finding implicated that it is necessary to consider the combined toxicity in safety assessment of these food-borne contaminants.

CAS / MDL: 2921-88-2
研究领域: 毒理学 · 食品安全 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2019 ·Vol. 20 ·期 21 ·5330 · IF 4.183

Integrative Assessment of Mixture Toxicity of Three Ionic Liquids on Acetylcholinesterase Using a Progressive Approach from 1D Point, 2D Curve, to 3D Surface

Huilin Ge,Shanshan Tao,Min Zhou,Bingjun Han,Hongqiu Yuan

The joint toxicities of [BMIM]BF4, [BMIM]PF6, and [HMIM]BF4on acetylcholinesterase (AChE) were systematically investigated by using a progressive approach from 1D single effect point, 2D concentration-response curve (CRC), to 3D equivalent-surface (ES) level. The equipartition equivalent-surface design (EESD) method was used to design 10 ternary mixtures, and the direct equipartition ray (EquRay) design was used to design 15 binary mixtures. The toxicities of ionic liquids (ILs) and their mixtures were determined using the microplate toxicity analysis (MTA) method. The concentration addition (CA), independent action (IA), and co-toxicity coefficient (CTC) were used as the additive reference model to analyze the toxic interaction of these mixtures. The results showed that the Weibull function fitted well the CRCs of the three ILs and their mixtures with the coefficient of determination (R2) greater than 0.99 and root-mean-square error (RMSE) less than 0.04. According to the CTC integrated with confidence interval (CI) method (CTCICI) developed in this study, the 25 mixtures were almost all additive action at 20% and 80% effect point levels. At 50% effect, at least half of the 25 mixtures were slightly synergistic action, and the remaining mixtures were additive action. Furthermore, the ESs and CRCs predicted by CA and IA were all within the CIs of mixture observed ESs and CRCs, respectively. Therefore, the toxic interactions of these 25 mixtures were actually additive action. The joint toxicity of the three ILs can be effectively evaluated by the ES method. We also studied the relationship between the mixture toxicities and component concentration proportions. This study can provide reference data for IL risk assessment of combined pollution.Keywords:ionic liquids;acetylcholinesterase;equivalent-surface;mixture toxicity;concentration addition;independent action;co-toxicity coefficient

研究领域: 环境毒理学 · 生物化学
✓ 已验证 DOI PubMed 高影响因子
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ENVIRONMENTAL TOXICOLOGY · 2016 ·Vol. 32 ·期 4 ·1202-1212 · IF 2.868

Synergistic toxicity of zno nanoparticles and dimethoate in mice: Enhancing their biodistribution by synergistic binding of serum albumin and dimethoate to zno nanoparticles

Xincheng Yan,Xiaolong Xu,Mingchun Guo,Shasha Wang,Shang Gao,Shanshan Zhu,Rui Rong

The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate (DM) have increased the risk of humans' co-exposure to nano ZnO and DM. Here, we report the synergistic effect of nano ZnO and DM on their biodistribution and subacute toxicity in mice. Nano ZnO and DM had a synergistic toxicity in mice. In contrast, bulk ZnO and DM did not cause an obvious synergistic toxicity in mice. Although nano ZnO was low toxic to mice, coexposure to nano ZnO and DM significantly enhanced DM-induced oxidative damage in the liver. Coadministration of nano ZnO with DM significantly increased Zn accumulation by 30.9 ± 1.9% and DM accumulation by 45.6 ± 2.2% in the liver, respectively. The increased accumulations of DM and Zn in the liver reduced its cholinesterase activity from 5.65 ± 0.32 to 4.37 ± 0.49 U/mg protein and induced hepatic oxidative stress. Nano ZnO had 3-fold or 2.4-fold higher binding capability for serum albumin or DM, respectively, than bulk ZnO. In addition, serum albumin significantly increased the binding capability of nano ZnO for DM by approximately four times via the interaction of serum albumin and DM. The uptake of serum albumin- and DM-bound nano ZnO by the macrophages significantly increased DM accumulation in mice. Serum albumins play an important role in the synergistic toxicity of nano ZnO and DM. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1202–1212, 2017.

CAS / MDL: 96-31-1 2128308-79-0
研究领域: 环境毒理学 · 纳米技术 · 药理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2025 · IF 8.5

Redefining the synergistic toxicity of nano-plastics and cadmium in earthworm coelomocytes: the mechanism of α-amylase molecular docking orientation and energy crisis

Fei Du,Xiangxiang Li,Shuqi Guo,Yuntao Qi,Tingting Wang,Shaoyang Hu,Rutao Liu

Nanoplastics (NPs) and cadmium (Cd), as ubiquitous environmental pollutants, are frequently detected in ecosystems, and their combined toxicity has received increasing attention. However, evidence and mechanisms regarding the cellular toxicity of NPs and Cd co-exposure in soil organisms remain insufficient. This study employed a multi-scale approach to investigate the toxic effects and mechanisms of NPs and Cd co-exposure on Eisenia fetida coelomocytes, and the structural changes of α -amylase. Results revealed that NPs-Cd co-exposure significantly reduced coelomocytes viability to 70.33 %, lower than Cd-alone exposure (78.41 %). Mechanically, compared to Cd exposure, co-exposure induced stronger reactive oxygen species (ROS) generation. NPs amplified Cd toxicity, leading to severe antioxidant system disruption, lipid peroxidation and mitochondrial dysfunction. At the molecular level, compared to Cd alone (74.03 %), NPs-Cd exposure induced lower α-amylase activity (66.33 %). Cd exposure caused protein skeleton damage, fluorescence sensitization, which were further exacerbated by NPs. Protein aggregation and docking simulation speculates that NPs-Cd cause greater toxicity in the form of protein corona. Linking NPs-Cd-induced oxidative stress with energy metabolism, this study highlighted the potential role of NPs as carriers in Cd accumulation. These findings highlight NPs' environmental risks and advance ecological risk assessment strategies for combined pollution.

CAS / MDL: 10108-64-2
研究领域: 环境毒理学 · 生态毒理学 · 纳米毒理学 · 生物化学 · 土壤生物学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SCIENCE OF THE TOTAL ENVIRONMENT · 2024 · IF 8.2

Insight into the mechanisms of combined toxicity of cadmium and flotation agents in luminescent bacteria: Role of micro/nano particles

Jiacheng Sun,Bo Yan,Hongxing Chen,Shuchen Tu,Junhao Zhang,Tao Chen,Qinzi Huang,Yuting Zhang,Lingtian Xie

Currently, risk assessment and pollution management in mines primarily focus on toxic metals, with the flotation agents being overlooked. However, the combined effects of metals and flotation agents in mines remain largely unknown. Therefore, this study aimed to evaluate the combined effects of Cd and two organic flotation agents (ethyl xanthate (EX) and diethyldithiocarbamate (DDTC)), and the associated mechanisms. The results showed that Cd + EX and Cd + DDTC exhibited synergistic toxicity. The EC 50 values for luminescent bacteria were 1.6 mg/L and 1.0 mg/L at toxicity unit ratios of 0.3 and 1, respectively. The synergistic effects were closely related with the formation of Cd(EX) 2 and Cd(DDTC) 2 micro/nano particles, with nano-particles exhibiting higher toxicity. We observed severe cell membrane damage and cell shrinkage of the luminescent bacteria, which were probably caused by secondary harm to cells through the released CS 2 during their decomposition inside cells. In addition, these particles induced toxicity by altering cellular levels of biochemical markers and the transcriptional levels of transport proteins and lipoproteins, leading to cell membrane impairment and DNA damage. This study has demonstrated that particulates formed by Cd and flotation agents contribute to the majority of the toxicity of the binary mixture. This study helps to better understand the complex ecological risk of inorganic metals and organic flotation agents in realistic mining environments.

研究领域: 环境科学 · 毒理学 · 矿物加工 · 生态毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ENVIRONMENTAL SCIENCE & TECHNOLOGY · 2018 · IF 6.653

Heavy Metal Exposure Alters the Uptake Behavior of 16 Priority Polycyclic Aromatic Hydrocarbons (PAHs) by Pak Choi (Brassica chinensis L.)

Songqiang Deng,Tan Ke,Yanfang Wu,Chao Zhang,Zhiquan Hu,Hongmei Yin,Limin Guo,Lanzhou Chen,Dayi Zhang

Polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) are predominant pollutants normally coexisting at electronic waste dumping sites or in agricultural soils irrigated with wastewater. The accumulation of PAHs and HMs in food crops has become a major concern for food security. This study explored the hydroponic uptake of 16 priority PAHs and 5 HMs (Cd, Cr, Cu, Pb, and Zn) by pak choi (Brassica chinensis L.). PAHs exhibited stronger inhibition on pak choi growth and physiological features than HMs. Five HMs were categorized into high-impact HMs (Cr, Cu, and Pb) and low-impact HMs (Cd and Zn) with distinct behavior under the coexposure with PAHs, and low-impact HMs showed synergistic toxicity effects with PAHs. Coexposure to PAHs and HMs slightly decreased the uptake and translocation of PAHs by pak choi, possibly attributing to the commutative hindering effects on root adsorption or cation−π interactions. The bioconcentration factors in PAHs + HMs treatments were independent of the octanol–water partition coefficient (Kow), owing to the cation-π interaction associated change of Kow and induced defective root system. This study provides new insights into the mechanisms and influential factors of PAHs uptake in Brassica chinensis L. and gives clues for reassessing the environmental risks of PAHs in food crops.

研究领域: 环境科学 · 农业科学 · 毒理学 · 植物生理学
✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF HAZARDOUS MATERIALS · 2024 · IF 12.2

Polyethylene nanoplastics, tebuconazole and cadmium affect soil-wheat system by altering rhizosphere microenvironment under single or combined exposure

Bo Zhao,Fang Chen,Kexin Zhou,Manfeng Lin,Lihu Shi,Shican Mi,Haixia Pan,Qiang Yao,Xin Zhao

Microplastics and nanoplastics (NPs) are pollutants of global concern. However, the understanding of the combined effects of NPs and other pollutants in the soil-plant system remains limited, particularly for polyethylene (PE), the primary component of agricultural films. This study investigated the effects of PE NPs (0.5%, w/w), fungicide tebuconazole (Te, 10   mg·kg -1 ), and cadmium (Cd, 4.0   mg·kg -1 ) on the soil-wheat system under single and combined exposures. The synergistic toxicity observed between NPs and Te impacted the nutritional conditions and antioxidant mechanisms of the soil-wheat system. The NPs increased the concentration of Cd in roots and the proportion of bioavailable Cd, exacerbating oxidative stress in wheat and inhibiting biomass. The soil-wheat system responded to stress by upregulating or downregulating pathways related to carbohydrate, amino acid, and sugar metabolism under various treatments. Sixteen functional genes associated with carbohydrate metabolism, amino acid metabolism, energy utilization, and gene repair at KEGG level 3 were employed to sustain microenvironmental homeostasis. Correlation analysis between microorganisms and environmental factors showed that various PGPG played roles in maintaining the health of the soil-wheat system. These results help to elucidate the comprehensive effects of NPs with other pollutants on the soil-plant system and provide new perspectives for toxic mechanisms.

CAS / MDL: 13494-80-9
研究领域: 环境科学 · 农业 · 土壤学 · 植物生理学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Environmental Chemical Engineering · 2025 · IF 7.2

Design of bifunctional resin-microbe complex guided by density functional theory and machine learning for enhanced phenol degradation and Cr (VI) reduction

Yan Hai,Qiyao Cong,Yingnan Pang,Yunxing Zhao,Weilun Yan,Jianfeng Zhang,Jing Liang

Hexavalent chromium and phenol coexist in wastewater and exhibit synergistic toxicity, enhancing biological harmful effects. The integration of Density Functional Theory (DFT) and Machine Learning (ML) offers a promising approach to addressing complex environmental challenges, through bridging macroscopic and microscopic regular analysis. DFT simulations revealed that the tertiary amine (-N(CH 3 ) 2 ) and quaternary ammonium (-N + (CH 3 ) 3 ) groups on D301, carrying positive charges, can assemble phenol-degrading microorganisms through electrostatic interactions. HOMO/LUMO energy and the Fukui function revealed a low energy gap of 0.128 Ha between D301 and Cr(VI), suggesting the potential for spontaneous Cr(VI) reduction by D301. experiments demonstrated that the resin–microorganism composite material could degrade 1500 mg/L of phenol and reduce 20 mg/L of Cr(VI), which is higher than most of the currently reported co-removal levels. Using Bayesian regression, a synergistic metabolic model is established to predict the removal performance. The resin-microbe system can remove 34–36 % of 1800 mg/L phenol under 20 mg/L Cr(VI), with a prediction error of less than 5 %. This study, through DFT and integrated ML, revealed the active sites of the resin and constructed a co-metabolism model of phenol and Cr(VI), providing a new strategy for material design and microbial assembly in the removal of co-contaminants.

研究领域: 环境科学 · 计算化学 · 机器学习应用 · 微生物生物技术 · 水处理技术
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