Binding Mechanism of Nitro Musks to Human Lactoferrin: Multispectral Approach, Docking and Molecular Dynamics Simulation.

Nitro musks are highly bioaccumulative and potentially carcinogenic, commonly used as additives in fabric softeners, detergents, and other household products. Furthermore, these substances have been detected in breast milk and human adipose tissue, posing a risk of direct exposure to pregnant women and infants. Human lactoferrin (HLF) is abundant in colostrum, and plays an important role in the non-specific immune system of the human body. In this study, the mechanisms of action of two nitro musk compounds, typical examples of synthetic musks, with HLF were investigated using molecular docking, dynamics simulation and multispectral methods. The fluorescence findings demonstrated that nitro musks quenched the intrinsic fluorescence of human lactoferrin through static quenching. Thermodynamic analysis of the binding parameters suggested that hydrophobic interactions acted synergistically in the formation of the complex. Moreover, analyses utilizing multispectral techniques, such as Fourier transform infrared (FTIR) spectroscopy, validated that the microenvironment and structure of HLF were altered in the presence of nitro musks. Finally, molecular docking and molecular dynamics simulations were employed to explore the specific binding mode of nitro musks with HLF and to assess the stability of the complex. These findings may provide a reference for assessing health risks to pregnant women and infants.

Molecular dynamics simulations on interactions of five antibiotics with luciferase of Vibrio Qinghaiensis sp.-Q67.

A large number of antibiotics have been used in the medical industry, agriculture, and animal husbandry industry in recent years. It may cause pollution to the aquatic environment and ultimately threaten to human health due to their prolonged exposure to the environment. We aim to study the toxicity mechanism of enrofloxacin (ENR), chlortetracycline hydrochloride (CTC), trimethoprim (TMP), chloramphenicol (CMP), and erythromycin (ETM) to luciferase of Vibrio Qinghaiensis sp.-Q67 (Q67) by using toxicity testing combined with molecular docking, molecular dynamics, and binding free energy analysis. The curve categories for ENR were different from the other four antibiotics, with ENR being J-type and the rest being S-type, and the toxicity of these five antibiotics (pEC50) followed the order of ENR (7.281) > ETM (6.814) > CMP (6.672) > CTC (6.400) > TMP (6.123), the order of toxicity value is consistent with the the magnitude of the binding free energy (ENR (-47.759 kcal/mol), ETM (-46.821 kcal/mol), CMP (-42.905 kcal/mol), CTC (-40.946 kcal/mol), TMP (-28.251 kcal/mol)). The van der Waals force provided the most important contribution to the binding free energy of the five antibiotics in the binding system with Q67 luciferase. Therefore, the dominant factor for the binding of antibiotics to luciferase was shape compensation. The face-to-face π-π stacking interaction between the diazohexane structure outside the active pocket region and the indoles structure of Phe194 and Phe250 in the molecular structure was the main reason for the highest toxicity value of antibiotic ENR. The hormesis effect of ENR has a competitive binding relationship with the α and ß subunits of luciferase. Homology modeling, molecular docking, molecular dynamics simulations and binding free energy calculations were used to derive the toxicity magnitude of different antibiotics against Q67, and insights at the molecular level. The conclusion of toxicological experiments verified the correctness of the simulation results. This study contributes to the understanding of toxicity mechanisms of five antibiotics and facilitates risk assessment of antibiotic contaminants in the aquatic environment.

Mechanism of time-dependent toxicity of quinolone antibiotics on luminescent bacteria Vibrio qinghaiensis sp.-Q67.

Four quinolone antibiotics (ciprofloxacin (CIP), enrofloxacin (ENR), sparfloxacin (SPA), gatifloxacin (GAT)) and their binary mixtures at environmentally relevant concentrations exhibited time-dependent hormesis on Vibrio qinghaiensis sp.-Q67 (Q67). The study aims to investigate the time-dependent toxicity of low-dose pollutants and the occurrence of hormesis. These indicators, total protein (TP), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and luminescence-related chemicals flavin mononucleotide (FMN), nicotinamide adenine dinucleotide (NADH), were measured to explore the mechanism of hormesis. The results showed a trend of increases in all indicators after 12 h of exposure, reaching maximal effects at 60 h and then decreasing as time progressed. At 36 h, 60 h and 84 h, the results showed a gradual increase followed by a decreasing trend in TP, FMN and NADH as the concentration in the group increased, whereas ROS, CAT, SOD and MDA showed the opposite trend. Notably, the degree of changes was related to the magnitude of hormesis. At low concentrations, the content of ROS and MDA decreased, the activity of CAT and SOD was lower, but the content of TP, FMN, NADH gradually increased, positively correlated with the promotion of Q67. At high concentrations, ROS and MDA content in Q67 increased, triggering the antioxidant defense mechanism (CAT and SOD activity increased), but TP, FMN, NADH content decreased, negatively correlated with the inhibited Q67. Therefore, our findings demonstrated two common patterns in these seven biochemical indicators on Q67. These findings have important practical implications for the ecological risk assessment of antibiotics in aquatic environment.

Toxicity interactions of azole fungicide mixtures on Chlorella pyrenoidosa.

It is acknowledged that azole fungicides may release into the environment and pose potential toxic risks. The combined toxicity interactions of azole fungicide mixtures, however, are still not fully understood. The combined toxicities and its toxic interactions of 225 binary mixtures and 126 multi-component mixtures on Chlorella pyrenoidosa were performed in this study. The results demonstrated that the negative logarithm 50% effect concentration (pEC50 ) of 10 azole fungicides to Chlorella pyrenoidosa at 96 h ranged from 4.23 (triadimefon) to 7.22 (ketoconazole), while the pEC50 values of the 351 mixtures ranged from 3.91 to 7.44. The high toxicities were found for the mixtures containing epoxiconazole. According to the results of the model deviation ratio (MDR) calculated from the concentration addition (MDRCA ), 243 out of 351 (69.23%) mixtures presented additive effect at the 10% effect, while the 23.08% and 7.69% of mixtures presented synergistic and antagonistic effects, respectively. At the 30% effect, 47.29%, 29.34%, and 23.36% of mixtures presented additive effects, synergism, and antagonism, respectively. At the 50% effect, 44.16%, 34.76%, and 21.08% of mixtures presented additive effects, synergism, and antagonism, respectively. Thus, the toxicity interactions at low concentration (10% effect) were dominated by additive effect (69.23%), whereas 55.84% of mixtures induced synergism and antagonism at high concentration (50% effect). Climbazole and imazalil were the most frequency of components presented in the additive mixtures. Epoxiconazole was the key component induced the synergistic effects, while clotrimazole was the key component in the antagonistic mixtures.

Probing the Mechanism of Hepatotoxicity of Hexabromocyclododecanes through Toxicological Network Analysis.

The prediction and mechanism analysis of hepatotoxicity of contaminants, because of their various phenotypes and complex mechanisms, is still a key problem in environmental research. We applied a toxicological network analysis method to predict the hepatotoxicity of three hexabromocyclododecane (HBCD) diastereoisomers (α-HBCD, ß-HBCD, and γ-HBCD) and explore their potential mechanisms. First, we collected the hepatotoxicity related genes and found that those genes were significantly localized in the human interactome. Therefore, these genes form a disease module of hepatotoxicity. We also collected targets of α-, ß-, and γ-HBCD and found that their targets overlap with the hepatotoxicity disease module. Then, we trained a model to predict hepatotoxicity of three HBCD diastereoisomers based on the relationship between the hepatotoxicity disease module and targets of compounds. We found that 593 genes were significantly located in the hepatotoxicity disease module (Z = 11.9, p < 0.001) involved in oxidative stress, cellular immunity, and proliferation, and the accuracy of hepatotoxicity prediction of HBCD was 0.7095 ± 0.0193 and the recall score was 0.8355 ± 0.0352. HBCD mainly affects the core disease module genes to mediate the adenosine monophosphate-activated kinase, p38MAPK, PI3K/Akt, and TNFα pathways to regulate the immune reaction and inflammation. HBCD also induces the secretion of IL6 and STAT3 to lead hepatotoxicity by regulating NR3C1. This approach is transferable to other toxicity research studies of environmental pollutants.

Involvement of glutamate receptors in regulating calcium influx in rice seedlings under Cr exposure.

Glutamate receptors (GLRs) are ligand-gated Ca2+-permeable channels that govern and modulate the dynamic influx of cytosolic Ca2+ in plants. The present study investigated the interaction of OsGLR3 gene expression with subcellular Ca distribution in rice seedlings exposed to chromium (Cr) solution containing Cr(III) or Cr(VI). The results displayed that the accumulation of Ca was evaluated or higher in shoots compared to roots under Cr exposure, and a similar pattern of subcellular Ca distribution was observed between rice tissues exposed to Cr(III) and Cr(VI). Real-time quantitative polymerase chain reaction (qRT-PCR) analysis revealed that eight OsGLR3 isogenes were distinctly expressed in different rice tissues at different levels of Cr exposures. This differential expressions could possible be due to the uptake variations, subcellular distribution and chemical speciation of the two Cr species. Notably, distinct expression patterns of OsGLR3 genes were found between Cr(III) and Cr(VI) exposures, suggesting that different regulation strategies are used to mediate Ca influx in rice materials under different Cr exposures. These results demonstrated a full picture of Cr-induced transcriptional alterations in OsGLR3 expression levels in rice seedlings, and provided suggestive evidence for further investigation on specific OsGLR3 genes participated in the regulation of cytosolic Ca2+ concentrations under Cr exposure.

Simultaneous hyperaccumulation of cadmium and manganese in Celosia argentea Linn.

To indentify Mn/Cd co-hyperaccumulatoion in Celosia argentea Linn., 2 pot experiments were conducted using Cd/Mn-amended and real contaminated soils, respectively. The interaction between Cd and Mn with regard to their accumulation in the plants was also assessed. The results indicated that C. argentea can simultaneously hyperaccumulate Cd and Mn. The maximum Cd and Mn concentrations in leaves were 276 and 29,000 mg/kg, respectively. Mn application significantly enhanced the biomass production and Cd accumulation in shoots (p < 0.05). However, Cd addition did not reduce Mn accumulation in the plants. The interactions between Cd and Mn in C. argentea differ from what was previously found in hydroponic experiments. This species grew healthy in soils taken from a Cd/Mn-contaminated site, indicating a high tolerance to Cd and Mn. The transfer and bioaccumulation factors of Cd and Mn were greater than 1, which showed that C. argentea had potential for Cd and Mn phytoextraction. Besides its potential practical benefits, C. argentea is an important resource to study the mechanisms of Cd/Mn hyperaccumulation and tolerance in plants.

Predictive QSAR Models for the Toxicity of Disinfection Byproducts.

Several hundred disinfection byproducts (DBPs) in drinking water have been identified, and are known to have potentially adverse health effects. There are toxicological data gaps for most DBPs, and the predictive method may provide an effective way to address this. The development of an in-silico model of toxicology endpoints of DBPs is rarely studied. The main aim of the present study is to develop predictive quantitative structure-activity relationship (QSAR) models for the reactive toxicities of 50 DBPs in the five bioassays of X-Microtox, GSH+, GSH-, DNA+ and DNA-. All-subset regression was used to select the optimal descriptors, and multiple linear-regression models were built. The developed QSAR models for five endpoints satisfied the internal and external validation criteria: coefficient of determination (R²) > 0.7, explained variance in leave-one-out prediction (Q²LOO) and in leave-many-out prediction (Q²LMO) > 0.6, variance explained in external prediction (Q²F1, Q²F2, and Q²F3) > 0.7, and concordance correlation coefficient (CCC) > 0.85. The application domains and the meaning of the selective descriptors for the QSAR models were discussed. The obtained QSAR models can be used in predicting the toxicities of the 50 DBPs.

Two-Stage Prediction on Effects of Mixtures Containing Phenolic Compounds and Heavy Metals on Vibrio qinghaiensis sp. Q67.

Two-stage prediction (TSP) model had been developed to predict toxicities of mixtures containing complex components, but its prediction power need to be further validated. Six phenolic compounds and six heavy metals were selected as mixture components. One mixture (M1) was built with equivalent-effect concentration ratio and four mixtures (M2-M5) were designed with fixed concentration ratio. In M1-M5, the toxicities were well predicted by TSP model, while CA overestimated and IA underestimated the toxicities. In M1-M5, compared with the actual mixture EC50 value, the prediction errors of TSP model (13.9%, 17.9%, 19.2%, and 17.3% and 15.8%, respectively) were significantly lower than those in the CA (higher than 30%) and IA models (20.9%, 33.0%, 20.6%, 21.8% and 12.5%, respectively). Thus, the TSP model performed better than the CA and IA model.

Key Component Analysis of the Time Toxicity Interaction of Five Antibiotics to Q67.

Antibiotics are considered as persistent emerging contaminants. The phenomenon of mixed exposure to the environment is a common occurrence causing serious harm to human health and the environment. Therefore, we employed enrofloxacin (ENR), chlortetracycline (CTC), methotrexate (TMP), chloramphenicol (CMP), and erythromycin (ETM) in this study. Nine treatments were designed using the uniform design concentration ratio (UDCR) method to systematically determine the toxicity of individual contaminants and their mixtures on Vibrio qinghaiensis sp.-Q67 through the time-dependent microplate toxicity assay. The combinatorial index (CI) method and the dose reduction index (DRI) were used to analyze the toxic interactions of the mixtures and the magnitude of the contribution of each component to the toxic interactions. The results showed that the toxicities of ENR, CTC, TMR, CMP, and ETM and their mixtures were time-dependent, with toxic effects being enhanced except when exposure time was prolonged. The types of toxic interactions in the ENR-CTC-TMR-CMP-ETM mixtures were found to be correlated with the proportion of each component's concentration, where the proportion of the components exerted the most significant influence. Through DRI extrapolation, it was determined that the primary components of the mixture exhibited a pronounced dependency on time. Specifically, at the 4 h mark, TMP emerged as the predominant component, gradually giving way to ENR as time advanced. Upon analyzing the frequency of mixture interactions under specified effects, the additive effect appeared most frequently (66.6%), while the antagonist effect appeared the least frequently (15.9%) among the nine rays.

Integrated transcriptomic and metabolomic analysis of the hepatotoxicity of dichloroacetonitrile.

Dichloroacetonitrile (DCAN), an emerged nitrogenous disinfection by-product (N-DBP) in drinking water, has garnered attention owing to its strong cytotoxicity, genotoxicity, and carcinogenicity. However, there are limited studies on its potential hepatotoxicity mechanisms. Understanding hepatotoxicity is essential in order to identify and assess the potential risks posed by environmental pollutants on liver health and to safeguard public health. Here, we investigated the viability, reactive oxygen species (ROS) levels, and cell cycle profile of DCAN-exposed HepG2 cells and analyzed the mechanism of DCAN-induced hepatotoxicity using both transcriptomic and metabolomic techniques. The study revealed that there was a decrease in cell viability, increase in ROS production, and increase in the number of cells in the G2/M phase with an increase in the concentration of DCAN. Omics analyses showed that DCAN exposure increased cellular ROS levels, leading to oxidative damage in hepatocytes, which further induced DNA damage, cell cycle arrest, and cell growth impairment. Thus, DCAN has significant toxic effects on hepatocytes. Integrated analysis of transcriptomics and metabolomics offers new insights into the mechanisms of DCAN-induced hepatoxicity.

Toxic interactions at the physiological and biochemical levels of green algae under stress of mixtures of three azole fungicides.

Assessing the interactions between environmental pollutants and these mixtures is of paramount significance in understanding their negative effects on aquatic ecosystems. However, existing research often lacks comprehensive investigations into the physiological and biochemical mechanisms underlying these interactions. This study aimed to reveal the toxic mechanisms of cyproconazole (CYP), imazalil (IMA), and prochloraz (PRO) and corresponding these mixtures on Auxenochlorella pyrenoidosa by analyzing the interactions at physiological and biochemical levels. Higher concentrations of CYP, IMA, and PRO and these mixtures resulted in a reduction in chlorophyll (Chl) content and increased total protein (TP) suppression, and malondialdehyde (MDA) content exhibited a negative correlation with algal growth. The activity of catalase (CAT) and superoxide dismutase (SOD) decreased with increasing azole fungicides and their mixture concentrations, correlating positively with growth inhibition. Azole fungicides induced dose-dependent apoptosis in A. pyrenoidosa, with higher apoptosis rates indicative of greater pollutant toxicity. The results revealed concentration-dependent toxicity effects, with antagonistic interactions at low concentrations and synergistic effects at high concentrations within the CYP-IMA mixtures. These interactions were closely linked to the interactions observed in Chl-a, carotenoid (Car), CAT, and cellular apoptosis. The antagonistic effects of CYP-PRO mixtures on A. pyrenoidosa growth inhibition can be attributed to the antagonism observed in Chl-a, Chl-b, Car, TP, CAT, SOD, and cellular apoptosis. This study emphasized the importance of gaining a comprehensive understanding of the physiological and biochemical interactions within algal cells, which may help understand the potential mechanism of toxic interaction.

Mechanism of the Synergistic Toxicity of Ampicillin and Cefazoline on Selenastrum capricornutum.

Ampicillin (AMP) and cefazolin (CZO) are commonly used ß-lactam antibiotics which are extensively globally produced. Additionally, AMP and CZO are known to have relatively high ecotoxicity. Notably, the mix of AMP and CZO creates a synergistic effect that is more harmful to the environment, and how exposure to AMP-CZO can induce synergism in algae remains virtually unknown. To yield comprehensive mechanistic insights into chemical toxicity, including dose-response relationships and variations in species sensitivity, the integration of multiple endpoints with de novo transcriptomics analyses were used in this study. We employed Selenastrum capricornutum to investigate its toxicological responses to AMP and CZO at various biological levels, with the aim of elucidating the underlying mechanisms. Our assessment of multiple endpoints revealed a significant growth inhibition in response to AMP at the relevant concentrations. This inhibition was associated with increased levels of reactive oxygen species (ROS) and perturbations in nitrogen metabolism, carbohydrate metabolism, and energy metabolism. Growth inhibition in the presence of CZO and the AMP-CZO combination was linked to reduced viability levels, elevated ROS production, decreased total soluble protein content, inhibited photosynthesis, and disruptions in the key signaling pathways related to starch and sucrose metabolism, ribosome function, amino acid biosynthesis, and the production of secondary metabolites. It was concluded from the physiological level that the synergistic effect of Chlorophyll a (Chla) and Superoxide dismutase (SOD) activity strengthened the growth inhibition of S. capricornutum in the AMP-CZO synergistic group. According to the results of transcriptomic analysis, the simultaneous down-regulation of LHCA4, LHCA1, LHCA5, and sodA destroyed the functions of the photosynthetic system and the antioxidant system, respectively. Such information is invaluable for environmental risk assessments. The results provided critical knowledge for a better understanding of the potential ecological impacts of these antibiotics on non-target organisms.

LC-QTOF/MS-based non-targeted metabolomics to explore the toxic effects of di(2-ethylhexyl) phthalate (DEHP) on Brassica chinensis L.

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer known to pose health risks to humans upon exposure. Recognizing the toxic nature of DEHP, our study aimed to elucidate the response mechanisms in Brassica chinensis L. (Shanghai Qing) when subjected to varying concentrations of DEHP (2 mg kg-1, 20 mg kg-1, and 50 mg kg-1), particularly under tissue stress. The findings underscored the substantial impact of DEHP treatment on the growth of Brassica chinensis L., with increased DEHP concentration leading to a notable decrease in chlorophyll levels and alterations in the content of antioxidant enzyme activities, particularly superoxide dismutase (SOD) and peroxidase (POD). Moreover, elevated DEHP concentrations correlated with increased malondialdehyde (MDA) levels. Our analysis detected a total of 507 metabolites in Brassica chinensis L., with 331 in shoots and 176 in roots, following DEHP exposure. There was a significant difference in the number of metabolites in shoots and roots, with 79 and 64 identified, respectively (VIP > 1, p < 0.05). Metabolic pathway enrichment in Brassica chinensis L. shoots revealed significant perturbations in valine, leucine, and isoleucine biosynthesis and degradation, aminoacyl-tRNA, and glucosinolate biosynthesis. In the roots of Brassica chinensis L., varying DEHP levels exerted a substantial impact on the biosynthesis of zeatin, ubiquinone terpenoids, propane, piperidine, and pyridine alkaloids, as well as glutathione metabolic pathways. Notably, DEHP's influence was more pronounced in the roots than in the shoots, with higher DEHP concentrations affecting a greater number of metabolic pathways. This experimental study provides valuable insights into the molecular mechanisms underlying DEHP-induced stress in Brassica chinensis L., with potential implications for human health and food safety.

Joint probabilistic risk of organic micropollutants in the aquaculture seawater around Liaodong Peninsula.

The limited number of organic micropollutants (OMPs) investigated in aquaculture seawater may underestimate the risk to marine organisms. It is critical to comprehensively investigate the occurrence of diverse OMPs in mariculture area and assess their joint risks to coastal marine organisms. Herein, the joint risks caused by multiple substances were assessed based on the screened results of approximately 1300 non-polar to polar OMPs in the seawater of mariculture ponds and raft culture areas around Liaodong Peninsula. In this study, 48 out of 886 non-polar to low-polar OMPs were detected at least once in 36 seawater samples, including 16 alkanes, 6 phthalate esters, 6 pesticides, 5 polycyclic aromatic hydrocarbons, etc. For 99 detected OMPs from both this study and our previously reported study, their aquatic toxicity data were comprehensively collected to assess the probabilistic risk. For 14 OMPs with sufficient toxicity data, their species sensitivity distribution curves were established. The results show that only three pollutants - ametryn, atrazine and diuron - alone adversely affect >5 % of coastal marine organisms. However, for the joint risks, up to 15.2 % of coastal marine organisms were affected by 14 OMPs under long-term exposure, suggesting that the OMP mixtures could enhance adverse effects. Although the ecological risks for most of compounds were acceptable, the joint risks of co-pollution by various OMPs cannot be ignored. The findings could support risk management of pollutants in aquaculture seawater, thereby contributing to the conservation of coastal marine biodiversity.

Classification and regression machine learning models for predicting the combined toxicity and interactions of antibiotics and fungicides mixtures.

Antibiotics and triazole fungicides coexist in varying concentrations in natural aquatic environments, resulting in complex mixtures. These mixtures can potentially affect aquatic ecosystems. Accurately distinguishing synergistic and antagonistic mixtures and predicting mixture toxicity are crucial for effective mixture risk assessment. We tested the toxicities of 75 binary mixtures of antibiotics and fungicides against Auxenochlorella pyrenoidosa. Both regression and classification models for these mixtures were developed using machine learning models: random forest (RF), k-nearest neighbors (KNN), and kernel k-nearest neighbors (KKNN). The KKNN model emerged as the best regression model with high values of determination coefficient (R2 = 0.977), explained variance in prediction leave-one-out (Q2LOO = 0.894), and explained variance in external prediction (Q2F1 = 0.929, Q2F2 = 0.929, and Q2F3 = 0.923). The RF model, the leading classifier, exhibited high accuracy (accuracy = 1 for the training set and 0.905 for the test set) in distinguishing the synergistic and antagonistic mixtures. These results provide crucial value for the risk assessment of mixtures.

Time-Dependent Toxicity and Health Effects Mechanism of Cadmium to Three Green Algae.

As algae are extremely sensitive to heavy-metal ions and can be critical biological indicators in the heavy-metal toxicity analyses conducted by environmental health researchers, this paper explores the sensitivity to temporal toxicity of three species of green algae: Scenedesmus obliquus, Chlorella pyrenoidosa, and Selenastrum capricornutum. The method of time-dependent microplate toxicity analysis was used to systematically investigate the changes in the toxicities of the three green-algae species induced by different concentrations of cadmium (Cd). The chlorophyll a content, antioxidant enzyme activity, and malondialdehyde (MDA) content in the algae were analyzed to explore the mechanism of Cd toxicity after 96 h of exposure. The results showed that the toxic effects of Cd on the three algae species were time-dependent. By comparing the toxic effect of Cd, indicated by pEC50 (the negative logarithm of EC50), on the algae species at four durations of exposure (24, 48, 72, and 96 h), this study found that the indicator organisms had different sensitivities to Cd. The order of sensitivity was C. pyrenoidosa > S. obliquus > S. capricornutum. Cd exposure had significant effects on the chlorophyll a and MDA content and on the enzyme activity of superoxide dismutase (SOD) and catalase (CAT) in the algae species. The chlorophyll a content in the cells of the algae decreased with increasing Cd concentration. The enzyme activity of CAT and content of MDA increased with increasing Cd concentration, which indicated that Cd had an oxidative stress effect on the three algae species.

Combined toxicity of the mixtures of phenol and aniline derivatives to Vibrio qinghaiensis sp.-Q67.

To test whether the dose addition and independent action models can predict the combined toxicity of the mixtures of phenol and aniline derivatives, six phenolic and two aniline derivatives were selected as the test components. The inhibition toxicity of the derivatives and their mixtures to Vibrio qinghaiensis sp.-Q67 indicated that all dose-response relationships could be effectively described by the Weibull function with correlation coefficients greater than 0.99. The combined toxicity of two equivalent-effect concentration ratio mixtures and eight uniform design concentration ratio mixtures could be predicted successfully by the dose addition model within 95% confidence intervals. However, it was also well predicted by the independent action model, especially at lower concentrations.

Reproductive toxicities of 1-ethyl-3-methylimidazolium bromide on Caenorhabditis elegans with oscillation between inhibition and stimulation over generations.

Ionic liquids (ILs) become emerging pollutants and their toxicities earn increasing attentions. Yet, their effects were seldom explored on reproduction which connects generations and also effects across generations. In the present study, reproductive effects of 1-ethyl-3-methylimidazolium bromide ([C2mim]Br), one representative IL, were studied on C. elegans with 11 continuously exposed generations (F1 to F11). At 8.20E-5 g/L, the effects on the initial reproduction showed oscillatory changes between stimulation (in F1, F3, F4, F6 and F10) and inhibition (in F2, F5, F7, F8 and F11). At 8.20E-3 g/L, the effects on the reproduction over generations also showed such oscillation despite of different stimulation or inhibition levels, and even opposite influences in F4 and F11. The effects of [C2mim]Br on the total reproduction also showed the concentration-dependent oscillation between stimulation and inhibition over generations, though they had less alteration frequencies than those on the initial reproduction. Biochemical and molecular indicators were further measured in F1, F4, F7 and F11 to explore potential mechanisms. Results showed that the effects on spermatocyte protein 8 (SPE8) showed positive correlation with those on reproduction while the influences on major sperm protein (MSP) and sperm transmembrane protein 9 (SPE9) showed negative correlation with SPE8. Moreover, the dysregulation on expressions of acs-2 and akt-1 indicated the involvement of glucolipid metabolism. The changes in expressions of set-2, met-2, set-25 and mes-4 demonstrated that the long-term reproductive impacts of [C2mim]Br over generations also involved histone methylation at H3K4, H3K9 and H3K36, which also connected with the glucolipid metabolism.

Toxic mechanism of three azole fungicides and their mixture to green alga Chlorella pyrenoidosa.

Currently, few studies have investigated the joint toxicity mechanism of azole fungicides at different exposure times and mixed at the relevant environmental concentrations. In this study, three common azole fungicides, namely, myclobutanil (MYC), propiconazole (PRO), and tebuconazole (TCZ), were used in studying the toxic mechanisms of a single substance and its ternary mixture exposed to ambient concentrations of Chlorella pyrenoidosa. Superoxide dismutase (SOD), catalase (CAT), chlorophyll a (Chla), and total protein (TP), were used as physiological indexes. Results showed that three azole fungicides and ternary mixture presented obvious time-dependent toxicities at high concentrations. MYC induced a hormetic effect on algal growth, whereas PRO and TCZ inhibit algal growth in the entire range of the tested concentrations. The toxicities of the three azole fungicides at 7 days followed the order PRO > TCZ > MYC. Three azole fungicides and their ternary mixture induced different levels of SOD and CAT activities in algae at high concentrations. The ternary mixture showed additive effects after 4 and 7 days exposure, but no effect was observed at actual environmental concentrations. The toxic mechanisms may be related to the continuous accumulation of reactive oxygen species, which not only affected protein structures and compositions but also damaged thylakoid membranes, hindered the synthesis of proteins and chlorophyll a, and eventually inhibited algal growth. These findings increase the understanding of the ecotoxicity of azole fungicides and use of azole fungicides in agricultural production.