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In this study, a chlorophenol (CP) 3D-QSAR model with a double activity (bioaccumulation and degradation) combination was established. 19 CPs were divided into a training set and test set according to the ratio of 4:1. The cross-validation coefficient (q 2 ) and non-cross-validation coefficient (R 2 ) of the model were 0.803 (> 0.5) and 0.925 (> 0.9), respectively, indicating a good stability and predictive ability of the 3D-QSAR. 2,4,6-trichlorophenol (2,4,6-TCP) was used as a target molecule, and 46 derivatives with low comprehensive effects were designed. Out of the 46 derivatives, 11 derivatives were screened to have the good insecticidal and preservative properties. From the perspective of the toxicity of zebrafish, 4 out of the 11 derivatives were found to have lower aquatic toxicity effects. Through the food chain simulation of cyanobacteria-daphnia-swamp-mandarin fish, it was found that the bioaccumulation effect of the four derivatives was lower than that of 2,4, 6-TCP. Finally, molecular dynamics simulation was conducted using 2-CH 2 NH 2 substituted derivatives, and it was found that the degradation effect by laccase (white rot fungi) was significantly improved in the presence of violuric acid, hydroxybenzotriazole, and syringaldehyde. This study can provide theoretical support for the development of environment-friendly technology for emerging pollutants., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Biological toxicity testing plays an essential role in identifying the possible negative effects induced by substances such as organic pollutants or heavy metals. As an alternative to conventional methods of toxicity detection, paper-based analytical device (PAD) offers advantages in terms of convenience, quick results, environmental friendliness, and cost-effectiveness. However, detecting the toxicity of both organic pollutants and heavy metals is challenging for a PAD. Here, we show the evaluation of biotoxicity testing for chlorophenols (pentachlorophenol, 2,4-dichlorophenol, and 4-chlorophenol) and heavy metals (Cu 2+ , Zn 2+ , and Pb 2+ ) by a resazurin-integrated PAD. The results were achieved by observing the colourimetric response of bacteria ( Enterococcus faecalis and Escherichia coli ) to resazurin reduction on the PAD. The toxicity responses of E. faecalis -PAD and E. coli -PAD to chlorophenols and heavy metals can be read within 10 min and 40 min, respectively. Compared to the traditional growth inhibition experiments for toxicity measuring which takes at least 3 h, the resazurin-integrated PAD can recognize toxicity differences between studied chlorophenols and between studied heavy metals within 40 min.

Chlorophenols (CPs) are widespread pollutants in nature. CPs have raised significant concern due to their potential hepatotoxic effects on humans. This research aimed to ascertain the inhibitory potential of eleven CPs (2-CP, 3-CP, 4-CP, 2,4-DCP, 2,3,4-TCP, 2,4,5-TCP, 2,4,6-TCP, 2,3,4,5-TeCP, 2,3,4,6-TeCP, 2,3,5,6-TeCP, and PCP) on nine human CYP isoforms (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4). The CPs that inhibit the activity of CYP isoforms were detected with human liver microsomes (HLM) using a cocktail approach in vitro. The results demonstrated that trichlorophenols, tetrachlorophenols, and PCP strongly inhibited CYP2C8 and CYP2C9. The half inhibition concentration (IC 50 ) value of 2,3,4,6-TeCP and PCP for CYP2C8 inhibition was 27.3 μM and 12.3 μM, respectively. The IC 50 for the inhibition of 2,4,6-TCP, 2,3,4,6-TeCP and PCP towards CYP2C9 were calculated to be 30.3 μM, 5.8 μM and 2.2 μM, respectively. 2,3,4,6-TeCP, and PCP exhibited non-competitive inhibition towards CYP2C8. 2,4,6-TCP, 2,3,4,6-TeCP, and PCP exhibited competitive inhibition towards CYP2C9. The inhibition kinetics parameters (Ki) were 51.51 μM, 22.28 μM, 37.86 μM, 7.27 μM, 0.68 μM for 2,3,4,6-TeCP-CYP2C8, PCP-CYP2C8, 2,4,6-TCP-CYP2C9, 2,3,4,6-TeCP-CYP2C9, PCP-CYP2C9, respectively. This study also defined clear structure-activity relationships (SAR) of CPs on CYP2C8, supported by molecular docking studies. Overall, CPs were found to cause inhibitory effects on CYP isoforms in vitro, and this finding may provide a basis for CPs focused on CYP isoforms inhibition endpoints., Competing Interests: Declaration of Competing Interest All authors declare that they have no actual or potential competing financial interests or personal relationships that may influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Microplastics (MPs) can absorb halogenated organic compounds and transport them into marine anaerobic zones. Microbial reductive dehalogenation is a major process that naturally attenuates organohalide pollutants in anaerobic environments. Here, we aimed to determine the mechanisms through which MPs affect the microbe-mediated marine halogen cycle by incubating 2,4,6-trichlorophenol (TCP) dechlorinating cultures with various types of MPs. We found that TCP was dechlorinated to 4-chlorophenol in biotic control and polypropylene (PP) cultures, but essentially terminated at 2,4-dichlorophenol in polyethylene (PE) and polyethylene terephthalate (PET) cultures after incubation for 20 days. Oxygen-containing functional groups such as peroxide and aldehyde were enriched on PE and PET after incubation and corresponded to elevated levels of intracellular reactive oxygen species (ROS) in the microorganisms. Adding PE or PET to the cultures exerted limited effects on hydrogenase and ATPase activities, but delayed the expression of the gene encoding reductive dehalogenase (RDase). Considering the limited changes in the microbial composition of the enriched cultures, these findings suggested that microbial dechlorination is probably affected by MPs through the ROS-induced inhibition of RDase synthesis and/or activity. Overall, our findings showed that extensive MP pollution is unfavorable to environmental xenobiotic detoxification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose of the Research: To evaluate the association of the exposure of trichlorophenols (TCPs) on the morbidity and mortality of patients with Parkinson's disease (PD) and Alzheimer's disease (AD) using the data from the National Health and Nutrition Examination Survey (NHANES) 2003-2010. Multivariable logistic regression models and COX regression were used to evaluate the association between TCP exposure and the AD and PD risk. Least Absolute Shrinkage and Selection Operator (LASSO) methods were used to screen latent covariates., Principal Results: A total of 6333 participants over the age of 18 years were included in the analysis. After the adjustments for major confounders, participants with higher concentrations of urinary 2,4,6-TCP had higher risk of AD (odds ratios (ORs), 3.19; 95% CI: 1.07, 9.45) than the group below the limit of detection (LOD). Compared to group of below the LOD, higher urinary concentrations of 2,4,5-TCP was associated with higher risk of all-cause mortality in PD patients (log-rank P = 0.022) and all participants (log-rank P < 0.001) without adjustments for confounders. In addition, a higher risk of all-cause mortality in all participants with high urinary concentrations of 2,4,6-TCP (log-rank P = 0.001) was found without adjustments for confounders. With the adjustments for major confounders, participants with higher concentrations of urinary 2,4,5-TCP had a higher risk of death in patients with PD (hazard ratios (HRs), 53.19; 95% CI: 2.82, 1004.13) than in the group below the LOD., Major Conclusions: Exposure to high concentration of 2,4,6-TCP may increase the risk of AD, and the level of 2,4,5-TCP may be associated with the risk of death in patients with PD. Our findings reveal the potential toxicity of TCPs, highlight the potential impact of TCPs on neurodegenerative diseases, and express concerns regarding the use of organochlorine pesticides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In account of environmental remediation, an ideal photocatalyst was fabricated for the effective treatment of water systems. Herein, dual heterojunctions framed CuWO 4 /Bi 2 WO 6 /MnS nanocomposite (NCs) was synthesized via simple co-precipitation method followed by ultra-sonicated assisted route. The prepared NCs were investigated its photocatalytic degradation performance using para-chlorophenol (4-CP) and reduction of chromium VI (Cr (VI)) under visible light irradiation. The photocatalyst were characterized by various analytical techniques including XRD, HR-TEM, XPS, UV-vis DRS, FE-SEM, EIS, PL, ESR, Raman and N 2 adsorption and desorption studies. The excellent photodegradation of 4-CP was observed within 180 min by the NCs. Similarly, the Cr (VI) reduction was about 97% within 140 min. The effect of pH and influence of different dosage of NCs and 4-CP on the photodegradation efficiency was investigated. The reusability and stability of the NCs was examined over 6 consecutive runs where the XRD and XPS confirm the structural stability of the prepared NCs. The scavenging experiment were carried out to elucidate the mechanism and the active species involved were O 2- • and OH• radicals. The TOC analysis affirmed the complete mineralization of the prepared NCs. The ecotoxicity analysis was carried out to determine the toxicity effect of intermediates using ECOSAR software and the end product toxicity was also evaluated against E. coli and S. epidermis. The end product toxicity study also confirmed that the degraded product was less toxic compared to parent compound. Further, the genotoxicity study was done to understand the environmental impact using allium cepa and results confirms that there are no causes of cytotoxicity & genotoxicity by the prepared NCs. Therefore, the prepared NCs can be economical, efficient with excellent photocatalytic performance and environment friendly., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

2,4,6-Trichlorophenol (2,4,6-TCP) is a common waste among the resulting chlorophenols generated in the production of common products classified as an extremely toxic, mutagenic, carcinogenic and highly persistent xenobiotic in the environment. To evaluate the impact of 2,4,6-TCP in aquatic systems, the catfish species Clarias batrachus has been selected to test its toxicity due to its high market value and consumption in India. Here is presented the impact of this compound on different physiological parameters of fish: haematological parameters (haemoglobin, total erythrocyte count, total leucocyte count and mean corpuscular haemoglobin), biochemical parameters (total serum protein and total serum glucose), growth and reproductive parameters (condition factor, hepatosomatic index, maturity index, specific growth rate, growth hormone, 17β-estradiol and testosterone), exposed to two concentrations of 2,4,6-TCP (0.5 mg/L and 1 mg/L - 1/10th and 1/20th of the LC 50 ) for a period of 15, 30 and 45 days. The results showed that C. batrachus even when exposed to the lower concentration (0.5 mg/L) for the shortest time (15 days) negatively impacted the organism in all the assessed parameters. This was highlighted by the Integrated Biomarker Response index (IBR), showing worse scores for the treatments (up to 20 × worse than the control). This work highlights the importance of continued research on the impact of 2,4,6-TCP, on an important commercial, supported by the high environmental persistence of this compound that can reach the same range of tested concentrations., (© 2022. The Author(s).)

Halophenolic disinfection byproducts (DBPs) in drinking water have attracted considerable concerns in recent years due to their wide occurrence and high toxicity. The liver has been demonstrated as a major target organ for several halophenolic DBPs. However, little is known about the underlying mechanisms of liver damage caused by halophenolic DBPs. In this study, 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP) and 2,4,6-triiodiophenol (TIP) were selected as representative halophenolic DBPs and exposed to C57BL/6 mice at an environmentally-relevant concentration (0.5 μg/L) and two toxicological concentrations (10 and 200 μg/L) for 12 weeks. Then, a combination of histopathologic and biochemical examination, liver transcriptome, serum metabolome, and gut microbiome was adopted. It was found that trihalophenol exposure significantly elevated the serum levels of alkaline phosphatase and albumin. Liver inflammation was observed at toxicological concentrations in the histopathological examination. Transcriptome results showed that the three trihalophenols could impact immune-related pathways at 0.5 μg/L, which further contributed to the disturbance of pathways in infectious diseases and cancers. Notably, TBP and TIP had higher immunosuppressive effects than TCP, which might lead to uncontrolled infection and cancer. In terms of serum metabolic profiles, energy metabolism pathway of citrate cycle and amino acid metabolism pathways of valine, leucine, and isoleucine were also significantly affected. Integration of the metabolomic and transcriptomic data suggested that a 12-week trihalophenol exposure could prominently disturb the glutathione metabolism pathway, indicating the impaired antioxidation and detoxification abilities in liver. Moreover, the disorder of the intestinal flora could interfere with immune regulation and host metabolism. This study reveals the toxic effects of halophenolic DBPs on mammalian liver and provides novel insights into the underlying mechanisms of hepatotoxicity., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aryl chlorides are among the most versatile synthetic precursors, and yet inexpensive and benign chlorination techniques to produce them are underdeveloped. We propose a process to generate aryl chlorides by chloro-group transfer from chlorophenol pollutants to arenes during their mineralization, catalyzed by Cu(NO3)2/NaNO3 under aerobic conditions. A wide range of arene substrates have been chlorinated using this process. Mechanistic studies show that the Cu catalyst acts in cooperation with NOx species generated from the decomposition of NaNO3 to regulate the formation of chlorine radicals that mediate the chlorination of arenes together with the mineralization of chlorophenol. The selective formation of aryl chlorides with the concomitant degradation of toxic chlorophenol pollutants represents a new approach in environmental pollutant detoxication. A reduction in the use of traditional chlorination reagents provides another (indirect) benefit of this procedure.

Emission of 2-chlorophenols (2-CPs) can cause serious air pollution and health problems. Here, the reaction kinetics and products of key radicals in 2-CPs photo-oxidation are explored in both gaseous and heterogeneous reactions. Quantum chemical calculations show that •OH-addition pathways are more preferable than H-abstraction pathways in gas phase, while that is opposite in heterogeneous phase. At 298 K, the overall rate coefficients of the title reactions in gas and heterogeneous phases are 3.48 × 10 -13 and 2.37 × 10 -13  cm 3 molecule -1  s -1 with half-lives of 55.3 h and 81.2 h, respectively. The strong H-bonds between linear Si 3 O 2 (OH) 8 and 2-CPs change the energy barriers of initial •OH-addition and H-abstraction reactions, resulting in the competition between heterogeneous reactions and gas phase reactions. The products in heterogeneous reactions are chloroquinone and HONO, which can cause atmospheric acid deposition and eco-toxicity. In gas phase, self-cyclization of alkoxy radical (RO•) leads to formation of •HO 2 and highly‑oxygenated molecules, which cause formation of secondary organic aerosol. It is emphasized that oxidation of 2-CPs by •OH leads to formation of more toxic products for aquatic organisms. Therefore, more attention should be focused on the products originated from •OH-initiated reactions of (2-)CPs in gaseous and heterogeneous reactions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Metabolic uncoupling technology was one of the methods widely used to on-site control the production of excess sludge in wastewater treatment processes. However, the uncoupler effects on soluble microbial products (SMP), microbial activity, and environment impact have few been reported. This study showed that sludge yield was reduced by 33.3% at 2,6-dichlorophenol (2,6-DCP) concentrations of 10 mg/L. The addition of 2,6-DCP also reduced the content of polysaccharide and protein in SMP, and the three-dimension excitation emission matrix (3D-EEM) suggested that the fluorescence intensities of humic acid-like, fulvic acid-like, and tryptophan protein-like substances decreased, proving that 2,6-DCP addition will weaken the interaction between microorganisms and the environmental matrix. Moreover, 2,6-DCP addition will change the microbial morphology and community of activated sludge. The active or respiring bacteria portion was lessened, and sludge flocs become dispersed, but it will not affect its settling performance. Surprisingly, 2,6-DCP has certain biodegradability and could be used as an environmentally friendly metabolic uncoupler under low-concentration dosing conditions. This study systematically evaluated the effect of 2,6-DCP on sludge production, SMP contents, microbial morphology, microbial community, demonstrating the environmental impact and application feasibility in the wastewater treatment systems., (Copyright © 2021. Published by Elsevier Ltd.)

2,4-DCP (2,4-dichlorophenol) is an environmental estrogen that is ubiquitously distributed in the environment and widely used to produce herbicides and pharmaceutical intermediates. Although 2,4-DCP is suspected to have endocrine disruption, the reproductive toxicity of 2,4-DCP in mammals has not been adequately assessed. In the present study, we examined the effect of 2,4-DCP on the fertility of mouse eggs. The data showed that oral administration of 2,4-DCP (180 mg/kg/day for 7 days) compromises the fertilization rate of mouse oocytes. To further analyze the mechanism by which 2,4-DCP decreases fertilization, the key regulators and events during fertilization of mouse eggs were investigated. We found that the dynamics of cortical granules (CGs) were disrupted by showing the redistribution of CG free domain in 2,4-DCP-administered oocytes. This abnormality perturbed the sperm binding site in the zona pellucida (ZP) and dramatically reduced the number of sperm binding to the ZP of 2,4-DCP-administered oocytes. In addition, the abundance of Juno, a sperm receptor on the egg membrane, was also decreased and its distribution was mislocated in 2,4-DCP-administered oocytes. Finally, we validated that the defects of fertilization participants and events caused by 2,4-DCP might be mediated by the increased level of reactive oxygen species-induced apoptosis of oocytes. Therefore, we demonstrate that 2,4-DCP compromises the fertilization ability of mouse oocytes via inducing oxidative stress., (© 2021 Wiley Periodicals LLC.)

2,4-Dichlorophenol (2,4-DCP), an estrogenic endocrine disruptor, is widely spread in aquatic environments and may interfere with normal physiological functions in fish. However, the influence of this chemical on the synthesis of sex hormones is not well understood. In the present study, zebrafish (Danio rerio) were exposed to 2,4-DCP (80 and 160 μg/L) with or without fadrozole (an aromatase inhibitor which inhibits the synthesis of estradiol) from 20 to 40 days post fertilization. Then, the sex ratio, the content of vitellogenin (VTG) and sex hormones (androstenedione (ASD), estrone (E1), 17β-estradiol (E2), estriol (E3), testosterone (T) and 11-ketotestosterone (11-KT)) were studied. Furthermore, the expression of genes involved in synthesis of sex hormones (cyp19a1a, cyp19a1b, 17β-hsd, 11β-hsd and cyp11b) along with the DNA methylation in cyp19a1a and cyp19a1b promoters was analyzed. The results showed that 2,4-DCP exposure led to female-biased ratio, increased the content of ASD, E2 and VTG, as well as the ratio of E2/11-KT, while decreased the levels of androgens (T and 11-KT). The sex hormonal change can be explained by the significant up-regulation of cyp19a1a, cyp19a1b, 17β-hsd and 11β-hsd genes. In addition, hypomethylation of cyp19a1a promoter was involved in this process. Notably, fadrozole can partly attenuate 2,4-DCP-induced feminization, and recover the levels of ASD, E2 and 11-KT. Thus, these results demonstrate that 2,4-DCP induces feminization in fish by disrupting the synthesis of sex hormones., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Biological safety evaluation and toxic by-products identification are critical issues in the partial oxidation process. Previous studies have shown that the whole toxicity increased in the effluent of an ozonation process for chlorophenols removal. Here, this study systematically investigated the changes of acute toxicity during the ozonation of 3-chlorophenol under four key operational conditions, including initial 3-chlorophenol concentration (20-60 mg/L), ozone concentration (14-42 mg/L), reaction pH (3-10) and ozonation time (0-50 min). The results found that the ozonation process induced a significant increase in the acute toxicity, followed by its gradual decrease. The observation of higher acute toxicity increase generally happened at higher initial 3-chlorophenol concentration, lower ozone concentration and lower reaction pH. At the toxicity peaks, the oxidizing intermediates posed acute toxicity equal to 65.8%-96.3% of the whole toxicity. Among them, free active chlorine (FAC) contributed 21.4%-51.6%, and its concentrations significantly correlated to the acute toxicity change. Therefore, two possible FAC generation pathways initiated by ozone molecule were proposed: (i) bond breaking of the oxychloride complex formed by the combination of chloride ion and zwitterion; or (ii) hydrolysis of ozonides formed by the electrophilic reaction of ozone molecule. Together, these results firstly revealed the significant toxicity contribution of oxidizing intermediates during the ozonation of chlorophenols, supporting further development of safe and effective ozone-based water treatment schemes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bacteria detection and toxicity measurement are essential in many aspects. Becoming increasingly popular in recent years, paper-based analytical devices (PADs) have proven to be cost-effective, portable and eco-friendly with quantitative diagnostic results. In this work, by a straightforward soaking-drying method, a resazurin-deposited PAD has been developed for rapid bacteria detection and biotoxicity measurement. The colorimetric response on the PAD was generated from metabolic reduction of resazurin by Enterococcus faecalis, a facultative anaerobic bacterial strain. After recording and quantifying the colorimetric response with Hue value by a smartphone, the bioassay on PAD enables the detection of resazurin reduction kinetics difference among bacteria at various densities in 10 min. Thereby, the bioassay on PAD was applied to study the toxicity of two chlorophenols, i.e. pentachlorophenol (PCP) and 4-chlorophenol (4-CP), to E. faecalis. Compared to growth-based inhibition test, which takes 5 h, this assay shows higher efficiency, i.e. in 30 min, the biotoxicity difference between PCP and 4-CP can be identified., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Considering the extensive usage of chlorophenols as well as their refractory and toxic characteristics, 2,4,6-trichlorophenol (2,4,6-TCP) and its metabolic intermediates that cause the acute toxicity of sludge were comprehensively evaluated using a bioassay including Photobacterium phosphoreum in a sequencing batch bioreactor (SBR), and the effects of 2,4,6-TCP wastewater treatment on mRNA expression were explored. The results showed that acute toxicity of sludge and effluent chemical oxygen demand greatly exceeded that of the other SBR without 2,4,6-TCP acclimation when 2,4,6-TCP wastewater treatment in the range of 10-50 mg/L was used. The identified intermediates and 2,4,6-TCP largely contributed to the acute toxicity of sludge, which favorably fitted the Fit Exponential Decay (R 2  > 0.93). During the stable stages for treating 50 mg/L 2,4,6-TCP in the influent, the mRNA expression for encoding functional proteins based on the genus Pseudomonas was markedly inhibited after the completion of the SBR operation., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A total of 90 wooden toys were collected, and six wood preservatives (chlorophenols and lindane) were analyzed by using gas chromatography-tandem mass spectrometry to assess the exposure risk of children to wood preservatives through oral contact with wooden toys. The detection rates of six preservatives ranged from 2.2% to 22.2%. The contents of the preservatives ranged from 0.6 µg/kg to 9.6 µg/kg. 2,4-Dichlorophenol (2,4-DCP) and 2,4,6-trichlorophenol (2,4,6-TCP) had higher detection rates and contents than other preservatives. Thus, their migration behaviors from toys to saliva were further investigated. In 11 positive samples, the max migration ratios of 2,4-DCP and 2,4,6-TCP ranged from 7.1% to 20.3% and from 11.1% to 24.8%, respectively. For children aged 3-36 months, the daily average 2,4-DCP exposure level associated with wooden toys ranged from 2.7 pg/(kg day) to 46.9 pg/(kg day), and the daily average 2,4,6-TCP exposure ranged from 3.6 pg/(kg day) to 69.4 pg/(kg day). The contribution to exposure provided by the saliva mobilization pathway was more than that provided by the ingestion of scraped-off toys, and the exposure level of 2,4,6-TCP was greater than that of 2,4-DCP. The max hazard quotient for 2,4-DCP was 1.9 × 10 -4 , and the max cancer risk for 2,4,6-TCP was 1.2 × 10 -9 . The above results indicated that although wood preservatives were distributed in wooden toys, exposure arising from directly mouthing these materials currently does not pose unacceptable risks to children., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Humic acid (HA) is ubiquitous organic matter derived by microbial metabolisms. This polymeric substance has both hydrophilic and hydrophobic moieties, and it is known that they affect to bioavailability of environmental pollutants. Objective of this study is to investigate the toxicological effects of chlorophenols to green algae observed at various pH and concentration of HA. Toxicity was determined by algal growth inhibition rate and EC 50 of green algae Chlorella vulgaris. As a result, toxicity of 2,4-dichlorophenol was mitigated with increase of the coexisting amount of HA and solution pH. In the case of coexisting 2.5 ppm HA, EC 50 of 2,4-dichlorophenol was 12.2 ppm and approximately three times higher than the case of absence of HA at pH 7.5. Meanwhile, Toxicity of 2,4,6-trichlorophenol was enhanced with increase of the coexisting amount of HA. In the case of absence of HA, EC 50 of 2,4,6-trichlorophenol was 13.1 ppm and approximately two times higher than the case of coexisting 2.5 ppm HA at pH 7.5. Results suggested that toxicity of chlorophenols is influenced by the electrostatic and hydrophobic interaction between HA and chlorophenols. The hypothesis of toxicity enhancement pathway was proposed in the case of equilibrium-state 2,4,6-trichlorophenol between anionic and nonionic states., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Tetrachlorobisphenol A (TCBPA) can promote intracellular reactive oxygen species (ROS) accumulation. However, limited attention has been given to mechanisms underlying TCBPA exposure-associated ROS accumulation. Here, such mechanisms were explored in the simple eukaryotic model organism Saccharomyces cerevisiae exposed to multiple concentrations of TCBPA. Addition of diphenyleneiodonium, a specific inhibitor of NADPH oxidase, blocked TCBPA treatment-associated intracellular ROS accumulation. NADPH oxidase can be activated by calcineurin, mitogen-activated protein kinase (MAPK), and tyrosine kinase. Therefore, corresponding specific inhibition respectively on these three kinases was performed and results suggested that the Ca 2+ signaling pathway, MAPK pathway, and tyrosine kinase pathway all contributed to the TCBPA exposure-associated intracellular ROS accumulation. In addition, TCBPA exposure-associated up-regulation of genes involved in ROS production and down-regulation of catalase promoted ROS accumulation in S. cerevisiae. To sum up, our current results provide insights into the understanding of TCBPA exposure-associated ROS accumulation., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The correlation between sludge reduction induced by 2,4,6-trichlorophenol (2,4,6-TCP) as an uncoupler and sludge toxicity was investigated in sequence batch reactors over a 100-d operation period. The influent concentrations of 2,4,6-TCP tested were 10 mg/L, 30 mg/L, and 50 mg/L. Sludge reduction, chemical oxygen demand (COD) removal rate, and sludge toxicity were measured. The results showed that from 30 to 80 d, when the COD removal rate was at an acceptable level, the sludge reduction levels for the 10 mg/L, 30 mg/L, and 50 mg/L groups were 9.7%, 31.6%, and 41.5%, respectively, and the average sludge toxicity values were 24.2%, 38.0%, and 53.0%, respectively. Sludge reduction was positively correlated with sludge toxicity. The two-dimensional polyacrylamide gel electrophoresis/results showed that extracellular and intracellular proteins secreted by the activated sludge during uncoupling metabolism were positively correlated with sludge toxicity. Taking the COD removal rate, sludge reduction, and sludge toxicity into consideration, the optimal influent concentration of the uncoupler 2,4,6-TCP was 30 mg/L when the initial mixed liquid suspended solids of sludge was 2,500 mg/L.

Catalpa sawdust (CSW) is a promising biomass-based biofuel. However, the complex lignocellulosic structure limits its efficient utilization in biorefinery applications. It is even more so when chlorophenols (CPs), highly toxic organic substances widely used as wood preservatives, are present. Hence, it is crucial to develop effective and eco-friendly approaches to attain deconstruction of lignocellulose and chlorophenols simultaneously as well as to improve methane (CH 4 ) production efficiently. This study might be the first to explore the performance of the novel constructed microbial consortia CS-5 and BC-4 on woody biomass degradation and CPs detoxification simultaneously with CH 4 production. After the degradation of CSW and CPs for 15 days by C5-5 or BC-4, significant reduction in lignocellulosic components and CPs mixture was realized with a total weight loss of 69.2 and 56.3 % and CPs degradation of 89 and 95 %, respectively. The toxicity of individual or mixed CPs after 15 days of degradation was reduced by approximately 90 %. The synergistic action of CS-5 and BC-4 enhanced biogas and CH 4 yields over 76 and 64 % respectively, higher than control. Furthermore, CH 4 production increased by 113.7 % at the peak phase of AD process. Methanosataceae represented 45.1 % of the methanogenic Archaea in digester G-III., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

2,4-Dichlorophenol (2,4-DCP) is ubiquitous in aquatic environment and has potential estrogenic effect on fish. However, the effect of 2,4-DCP on sex differentiation of zebrafish (Danio rerio) and the underlying mechanism are largely unknown. To address these questions, zebrafish larvae at 20 or 30 days post fertilization (dpf) were exposed to 2,4-DCP (0, 80 and 160 μg L -1 ) with/without 5-aza-2'-deoxycytidine (5AZA, 50 μg L -1 ) for 10 days. The sex ratios and the expressions of male-related genes including amh, gata4, nr5a1a, nr5a2 and sox9a were analyzed. In addition, the DNA methylation levels of amh, nr5a2 and sox9a were examined. The results showed that 2,4-DCP exposure resulted in significant increase of female ratios both in 20-30 and 30-40 dpf groups. Correspondingly, the expressions of gata4, nr5a1a, nr5a2 and sox9a were decreased by 2,4-DCP exposure in two treatment periods. However, the transcript of amh was decreased by 2,4-DCP exposure only from 30 to 40 dpf. The DNA methylation levels of amh, nr5a2 and sox9a were increased following 2,4-DCP exposure. Moreover, the addition of 5AZA could counteract the effects including feminization, disturbance of gene expression and DNA hypermethylation caused by 2,4-DCP. These results indicated that the feminizing effect of 2,4-DCP was accomplished by regulating the expression of male-related genes through DNA methylation., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In biosensors fabrication, entrapment in polymeric matrices allows efficient immobilization of the biorecognition elements without compromising their structure and activity. When considering living cells, the biocompatibility of both the matrix and the polymerization procedure are additional critical factors. Bio-polymeric gels (e.g. alginate) are biocompatible and polymerize under mild conditions, but they have poor stability. Most synthetic polymers (e.g. PVA), on the other hand, present improved stability at the expense of complex protocols involving chemical/physical treatments that decrease their biological compatibility. In an attempt to explore new solutions to this problem we have developed a procedure for the immobilization of bacterial cells in polyethersulfone (PES) using phase separation. The technology has been tested successfully in the construction of a bacterial biosensor for toxicity assessment. Biosensors were coated with a 300  μm bacteria-containing PES membrane, using non-solvent induced phase separation (membrane thickness ≈ 300 μm). With this method, up to 2.3 × 10 6  cells were immobilized in the electrode surface with an entrapment efficiency of 8.2%, without compromising cell integrity or viability. Biosensing was performed electrochemically through ferricyanide respirometry, with metabolically-active entrapped bacteria reducing ferricyanide in the presence of glucose. PES biosensors showed good stability and reusability during dry frozen storage for up to 1 month. The analytical performance of the sensors was assessed carrying out a toxicity assay in which 3,5-dichlorophenol (DCP) was used as a model toxic compound. The biosensor provided a concentration-dependent response to DCP with half-maximal effective concentration (EC 50 ) of 9.2 ppm, well in agreement with reported values. This entrapment methodology is susceptible of mass production and allows easy and repetitive production of robust and sensitive bacterial biosensors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Acute toxicity changes during ozonation of 2-chlorophenol (2-CP), 3-chlorophenol (3-CP) and 4-chlorophenol (4-CP) under various conditions were studied using the luminescence inhibition test. Though the concentrations of mono-chlorophenols (CPs) and TOC decreased constantly, the acute toxicity evidently increased with reaction time until a maximum value was reached during ozonation of 2-CP at pH 3 to 7, 3-CP at pH 3 to 10, and 4-CP at pH 3 and 5. Principal component analysis (PCA) was applied to understand the relationships between acute toxicity and other physicochemical parameters. The intense interrelations between acute toxicity and SUVA280 were evident under all the pH conditions for 2-CP and 3-CP, and except at pH 12 for 4-CP, which implied that high-weight intermediates were formed and contributed to the increased toxicity. SUVA280 was a possible surrogate measure of acute toxicity during the ozonation of all three CPs. Profiling of acute toxicity in ozonated CPs was conducted using solid phase extraction with a series of different cartridges, high performance liquid chromatography (HPLC) fractionation and the luminescence inhibition bioassay. Considering the acute toxicity evolution under different conditions and profiles of acute toxicity in HPLC fractions, the highly toxic intermediates probably included same non-chlorine carboxylic acids though the three CPs had different substituent positions with higher polarity than their parent compounds. In this study, the acute toxicity evolution during ozonation of CPs and the forcing agents were thoroughly discussed. Therefore, ozonation is expected to be carefully operated and monitored, and toxicity tests should be used to evaluate whether effluent detoxification takes place.

Flame retardants are detected in the environment worldwide, and thus pose great risks to human health. The potential effects of these chemicals on the development of the central nervous system, have recently raised public concern. In this study, to explore the toxicity of these chemicals during the early developmental stages of the human central nervous system, we induced human embryonic stem cells to differentiate into neural ectoderm in the presence of five halogenated flame retardants, BDE-47, BDE-209, TBBPA, TBBPS and TCBPA, individually or in combination. We identified a set of neural development-related biological processes that responded to these chemicals, by analyzing the whole transcriptional changes. We confirmed the RNA-seq results by qRT-PCR and found that transcription factors crucial for neural development, such as ZIC1, ZIC3, HES3, IGFBP3 and DLX5, were dysregulated by those chemicals. In addition, the five flame retardants might also influence axon growth/guidance and neuron transmission-related processes, by dysregulating genes including CNTN2, SLIT1, LRRC4C, RELN, CBLN1, CHRNB4 and GDF7. Furthermore, the chemical treatments seemed to interfere with the WNT and AHR signaling pathways. Overall, our findings revealed that BDE-209 had similar toxicity as BDE-47, whereas TBBPS and TCBPA might not be safe alternatives to TBBPA. Interestingly, we observed no obvious synergistic effects when we mixed those five flame retardants together., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Halogenated bisphenol A analogues (X-BPA) have been widely used in industrial production, such as flame retardant. Although BPA exposure was found to result in cytotoxicity, toxicity of X-BPA and molecular mechanism remain under-explored. In this study, we employed human breast cancer cell as a model to investigate the concentration-dependent toxicity and underlying mechanisms of tetrabromo bisphenol A (TBBPA) and tetrachloro bisphenol A (TCBPA). An integrated method involving molecular toxicology and mass spectrometry (MS)-based global metabolomics was applied to evaluate the toxicity of TCBPA and TBBPA on cell viability, reactive oxygen species (ROS), and metabolic alterations. The results demonstrated that low micromolar levels (0-10 μM) of TCBPA/TBBPA exposure induced cell proliferation and activated the energy metabolism of both glycolysis and amino acid. On the other hand, high micromolar levels (10-50 μM) of TCBPA/TBBPA exposure perturbed the balance between ROS and antioxidative defense process by promoting the ROS generation via the down-regulation of glutathione biosynthesis and up-regulation of nucleotide metabolism. This study, for the first time, provides evidence and mechanism for better understanding the cytotoxicity of TCBPA and TBBPA by regulating the specific metabolic pathways., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A novel synthetic route was designed, developed, and utilized to synthesize six high-purity 2-monochloropropanediol fatty acid esters (2-MCPD esters), a group of potential processing-induced food contaminants. A chlorine atom was introduced to C-2 of a diethyl malonate molecule, which was reduced by NaBH 4 and followed by esterification using fatty acids. The reaction products were isolated and purified using silica gel columns to obtain three 2-MCPD monoesters and three diesters at about 50-54% and 56-59% yields, respectively. In addition, 2-MCPD monopalmitate and dipalmitate were examined for their acute oral toxicities in Swiss mice. The LD 50 values of 2-MCPD mono- and dipalmitate were greater than 5000 mg/kg body weight (BW), along with detectable nephrotoxicity and testicular toxicity. The results of this study may promote future investigation of MCPD ester toxicology and detection.

Objective: 2,4,6-trichlorophenol (TCP), 2,4,6-tribromophenol (TBP), and 2,4,6-triiodophenol (TIP) are three aromatic halogenated disinfection byproducts (DBPs) identified in chlorinated saline effluents. This study aimed to evaluate and compare their immunotoxicity and immunomodulatory effects on macrophages. Materials and methods: CCK-8 assay was used to evaluate cytotoxicity of TCP, TBP, and TIP in mouse macrophage RAW264.7 cells. A light microscope and digital camera were used to record the morphological changes of RAW264.7 cells. qRT-PCR was used to measure the mRNA levels of polarization markers and secreted cytokines. Cytokine production was also detected by ELISA. Flow cytometry was performed to analyze the expression of M1 and M2 markers on macrophages. Results: TCP, TBP, and TIP had different cytotoxic effects on macrophages. The rank order of cytotoxicity was TIP > TBP > TCP. Furthermore, the three halogenated DBPs displayed different preferences for macrophage polarization. Intriguingly, 200 μM TIP remarkably induced the M2-dominant polarization of macrophages, while 200 μM TCP induced an M1-dominant polarization of macrophages. TBP has a moderate ability in inducing M1 and M2 polarization compared with TCP and TIP. Conclusions: TIP displayed higher cytotoxicity against macrophages than TBP and TCP, its brominated and chlorinated analogs. Since M1 and M2 macrophages facilitate the inflammatory and anti-inflammatory responses, respectively, the discrepancy of TCP, TBP, and TIP in inducing macrophage polarization may lead to distinct immunomodulatory and toxicological outcomes, thus giving rise to different types of diseases. This finding may provide novel insights into evaluating the toxicity of environmental pollutants on the immune system.

In this study, the effects of 4-chlorophenol (4-CP) influent concentrations ranging from 10 to 100 mg L -1 on sludge toxicity, enzymatic activity and microbial community, along with their correlations, were investigated in a sequencing batch bioreactor (SBR), which was defined as the acclimated SBR. Another SBR was set as a control group that did not receive the influent 4-CP. The results showed that the sludge toxicity increased as the influent 4-CP increased, exhibiting a positive correlation with 4-CP loads. The enzymatic activity was stimulated after long-term acclimation with 4-CP and was positively related to the 4-CP loads and sludge toxicity. During the stable operational stages of the acclimated SBR, the microbial diversity first increased and then decreased as the 4-CP loads increased, while the similarity of the microbial community between the acclimated and control SBRs decreased with increasing 4-CP loads. The aim of this study is to provide theoretical support for reducing sludge toxicity in industrial wastewater treatment.

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are persistent toxic environmental pollutants that cause severe reproductive toxicity in animals. The goal of this study was to compare the reproductive toxic effects of TBBPA and TCBPA on male Rana nigromaculata and to expound on the mechanisms leading to these effects. Healthy adult frogs were exposed to 0, 0.001, 0.01, 0.1, and 1 mg/L of TBBPA and TCBPA for 14 days. Sperm numbers were counted by erythrometry. Sperm mobility and deformities were observed under a light microscope (400 × ). We used commercial ELISA kits to determine the serum content of testosterone (T), estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH). Expression of androgen receptor (AR) mRNA was detected using real-time qPCR. Sperm numbers and sperm mobility were significantly decreased and sperm deformity was significantly increased in a concentration dependent manner following exposure to TBBPA and TCBPA. Sperm deformity was significantly greater in the 1 mg/L TCBPA (0.549) treatment group than in the 1 mg/L TBBPA (0.397) treatment group. Serum T content was significantly greater in the 0.01, 0.1 and 1 mg/L TBBPA and TCBPA experimental groups compared with controls, while E2 content was significantly greater in only the 1 mg/L TBBPA and TCBPA experimental groups. Expression levels of LH and FSH significantly decreased in the 1 mg/L TBBPA and TCBPA treatment groups. AR mRNA expression decreased markedly in all the treated groups. Our results indicated that TBBPA and TCBPA induced reproductive toxicity in a dose-dependent manner, with TCBPA having greater toxicity than TBBPA. Furthermore, changes in T, E2, LH, and FSH levels induced by TBBPA and TCBPA exposure, which led to endocrine disorders, also caused disturbance of spermatogenesis through abnormal gene expressions of AR in the testes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

It is well established that aquatic wildlife in marine and freshwater of the European Union is exposed to natural and synthetic endocrine disruptor compounds (EDCs) which are able to interfere with the hormonal system causing adverse effects on the intact physiology of organisms. The traditional wastewater treatment processes are inefficient on the removal of EDCs in low concentration. Moreover, not only the efficiency of treatment must be considered but also toxicological aspects. Taking into account all these aspects, the main goal of the study was to investigate the photochemical decomposition of hazardous phenolic compounds under simulated as well as natural sunlight from the toxicity point of view. The studies were focused on photodegradation of 2,4-dichlorophenol as well as mixture of phenol, 2-chlorophenol and 2,4-dichlorophenol. Photosensitized oxidation process was carried out in homogeneous and heterogeneous system. V. fischeri luminescence inhibition was used to determine the changes of toxicity in mixture during simulated and natural irradiation. The photodegradation was carried out in three kinds of water matrix; moreover, the influence of presence of inorganic matter on the treatment process was investigated. The experiments with natural sunlight proved applicability of photosensitive chitosan for visible-light water pollutant degradation. The results of toxicity investigation show that using photosensitive chitosan for visible-light, the toxicity of reaction mixture towards V. fischeri has significantly decreased. The EC 50 was found to increase over the irradiation time; this increase was not proportional to the transformation of the parent compounds.

2-Chlorophenol (2-CP), a class of chlorinated organic pollutants like other chlorophenols, is used as intermediate in the synthesis of the higher chlorinated congeners, certain dyes, preservatives, herbicides, fungicides, and plastics. In this study, cytotoxic and genotoxic effects of 2-CP were investigated on the root meristem cells of Allium cepa for its effects on root growth, mitotic index (MI), mitotic phases, chromosomal abnormalities (CAs), and DNA damage by using Allium anaphase-telophase and Comet assays. EC 50 of 2-CP value was determined as approximately 25 mg/L by Allium root growth inhibition test. Three concentrations of 2-CP (12.5, 25, and 50 mg/L), distilled water (negative control), and methyl methane sulfonate (MMS, 10 mg/L, positive control) were applied to onion stem cells under different exposure periods (24, 48, 72, and 96 h). All the applied doses of 2-CP slightly decreased MIs. 2-CP induced total CAs such as disturbed anaphase-telophase, chromosome laggards, stickiness, and bridges and also DNA damage at significant levels. These results demonstrate that 2-CP has genotoxic effects in A. cepa root meristematic cells.

2,4-Dichlorophenol (2,4-DCP) is one of the most abundant chlorophenols in the aquatic environment and has been frequently detected in surface waters. Although ecological and cellular toxicity of 2,4-DCP has aroused the public concern, few reports focus on the genotoxicity, especially on DNA double strand breaks (DSBs), of 2,4-DCP in fish. The present study aims to explore the genotoxic effect of 2,4-DCP on DSBs in goldfish Carassius auratus and to further elucidate its potential mechanism. The results showed that 2,4-DCP significantly induced DSBs (detected by neutral comet assay) in erythrocytes and hepatocytes of goldfish in a dose-dependent manner, indicating a genotoxicity of 2,4-DCP on fish. The total antioxidant capability and the content of reduced glutathione (GSH) were significantly decreased, while the level of reactive oxygen species (ROS) was significantly increased in a dose-dependent manner in erythrocytes and hepatocytes, suggesting an oxidative stress caused by 2,4-DCP in fish. N-acetyl-l-cysteine, a precursor of GSH and a ROS scavenger, significantly impaired 2,4-DCP-induced ROS overproduction and DSBs, which proves that ROS accumulation and GSH depletion are involved in 2,4-DCP-induced DNA damage in fish. Environ. Mol. Mutagen. 59:798-9, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Tetrachlorobisphenol A (TCBPA), which is widely used as flame retardant, can be released into various environments, thereby being absorbed by wildlife or human beings through food chain's bio-magnification and causing some adverse influences on wildlife or human beings. However, limited data are currently available on TCBPA-associated cytotoxicity and related mechanisms. Here, the cytotoxicity induced by different concentrations of TCBPA (i.e., 5, 10 and 20 μM) was studied using Saccharomyces cerevisiae, a simple eukaryotic model organism. TCBPA treatment inhibited the growth and survival rate of yeast cell in a dose-dependent manner. Moreover, TCBPA promoted the increasing of intracellular oxidative stress by enhancing accumulation of intracellular reactive oxygen species (ROS). Meanwhile, lipid peroxidation degree (represented by malondialdehyde (MDA) content) and DNA damage degree (represented by 8-hydroxy deoxyguanosine (8-oxodG) content) in yeast cell also increased after TCBPA treatment. However, yeast cell mitochondrial membrane potential (Δψm) decreased after TCBPA treatment. It was noteworthy that there was no significant inhibitory effect on yeast cell growth or survival rate in 5 μM TCBPA-treated cells, but the intracellular MDA content and Δψm level changed significantly, suggesting the potential cell damage secondary to the relative low dose of TCBPA exposure. Results presented here would highlight our knowledge about TCBPA-associated cytotoxicity in organisms., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The mechanism and toxicity of TCS degradation by ClO 2 was investigated. Intermediate products during the oxidation process were identified by GC/MS and LC/MS. A microtox bioassay and a SOS/umu assay were employed to evaluate the acute toxicity and genotoxicity of the resulting solutions during the chlorination process. The results showed that the reaction between TCS and ClO 2 was of second-order overall. The pseudo first-order rate constants (k obs ) exhibited significant dependence on solution pH and chlorine dioxide concentration, with the apparent second-order rate constant, k app , being 7.07 × 10 4  M -1 s -1 in the pH range of 6.80-7.02. TCS decomposition was accompanied by the accumulation of 2,4-dichlorophenol (2,4-DCP), and the maximum molar yield ratios of 2,4-DCP/TCS were in the range of 31.71%-35.43%. The major intermediates identified were 2,7/2,8-dichlorodibenzop-dioxin (2,7/2.8-Cl 2 DD), 2,4-DCP, 2,4,6-trichlorophenol (2,4,6-TCP), tetraclosan and pentaclosan. The proposed mechanism for TCS oxidation involved the cleavage of the ether link in TCS, chlorination of the phenolic ring and ring closure of a single TCS molecule. The transformation and degradation of TCS led to reduction of the acute toxicity and genotoxicity. However, irregular fluctuations in the toxicity changes indicated that the oxidation of TCS was not a simultaneous detoxification process., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Numerous research works have shown that synthesis of pesticides leads to the formation of impurities that may substantially enhance pesticide toxicity. In this study, the effect of manufacturing impurities of pesticide bromfenvinphos (BFVF) such as 1-bromo-2-(2,4-dichlorophenyl)-2-ethoxy ethene (BDCEE) and diethyl [2-(2,4-dichlorophenyl)-2-oxo-ethyl] phosphonate (β-ketophosphonate) on human erythrocytes, being significantly exposed to xenobiotics has been studied. The cells were treated with the compounds studied in the concentrations ranging from 0.1 μM to 250 μM for 4 h. In order to assess the effect of BDCEE and β-ketophosphonate on red blood cells hemolytic changes, changes in cell size (FSC parameter) and oxidation of hemoglobin were studied. Moreover, alterations in reactive oxygen species (ROS) formation, reduced glutathione (GSH) level and acetylcholinesterase (AChE) activity were determined. BDCEE induced an increase in ROS level and caused strong oxidation of hemoglobin as well as a slight change in erythrocytes size and hemolysis, while it did not change GSH level and AChE activity. β-ketophosphonate has not been shown to affect most parameters studied, but it strongly reduced AChE activity. Because changes in the parameters examined were noted at low concentrations of BFVF impurities (5-250 µM), those substances should not negatively affect on red blood cells of humans environmentally exposed to this pesticide.

Chlorinated phenols are a class of contaminants found in water and have been regarded as a great potential risk to environment and human health. It is thus urgent to develop effective techniques to remove chlorinated phenols in wastewater. For this purpose, we employed dielectric barrier discharge (DBD) in this work and studied the efficiency of DBD for the degradation of 2,4-dichlorophenol (2,4-DCP), one of the most typical chlorophenols in the environment. The effects of pH value, applied voltage and plasma-working gases on the dichlorophenol-removal efficiency were investigated. The results demonstrate that DBD plasma could successfully degrade 2,4-DCP, achieving efficiency of 98.16% (k = 1.09 min -1 ) in the Ar-DBD system, and 77.60% (k = 0.48 min -1 ) in the N 2 -DBD system, with the process following the first-order kinetics. The removal efficiency was reduced in the presence of radical scavengers, confirming that hydroxyl radicals played a key role in the degradation process, while other active substances were also found such as nitrogen radicals in the N 2 -DBD system, which was found to have also contribution to the degradation of 2,4-DCP. The intermediates and final products generated in the degradation process were analyzed using gas chromatography-mass spectrometry (GC-MS). Based on the identification of intermediates, the degradation pathways and mechanism were proposed and discussed. Besides, the toxicity of the DBD treated 2,4-DCP solution was also assessed using GFP-expressing recombinant Escherichia coli (E. coli) as the testing organism, showing that plasma treatment could substantially reduce the toxic effect of 2,4-DCP., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Standard chemical toxicity testing guidelines using aquatic plant Lemna minor have been developed by several international standardisation organisations. Although being highly useful for regulatory purposes by focusing on traditional adverse endpoints, these tests provide limited information about the toxic mechanisms and modes of action (MoA). The present study aimed to use selected functional assays in L. minor after exposure to 3,5-dichlorophenol (3,5-DCP) as a model to characterise the toxic mechanisms causing growth inhibition and lethality in primary producers. The results demonstrated that 3,5-DCP caused concentration-dependent effects in chloroplasts and mitochondria. Uncoupling of oxidative phosphorylation (OXPHOS), reduction in chlorophyll (Chlorophyll a and b) content, reproduction rate and frond size were the most sensitive endpoints, followed by formation of reactive oxygen species (ROS), lipid peroxidation (LPO), reduction of carotenoid content and impairment of photosynthesis efficiency. Suppression of photosystem II (PSII) efficiency, electron transport rate (ETR), chlorophyll (a and b) contents and oxidative phosphorylation (OXPHOS) were closely correlated while ROS production and LPO were negative correlated with ETR, carotenoid content and growth parameters. A network of conceptual Adverse Outcome Pathways (AOPs) was developed to decipher the causal relationships between molecular, cellular, and apical adverse effects occurring in L. minor to form a basis for future studies with similar compounds., (Copyright © 2018 Elsevier B.V. All rights reserved.)

This study was undertaken to determine the association of four chlorophenol pesticides with cardiometabolic risk factors and obesity in children and adolescents. This cross-sectional study was conducted in 2016 on 242 children and adolescents, aged 6 to 18 years. The concentrations of 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), and 2,4,6-trichlorophenol (2,4,6-TCP) in the urine were examined and their association with indices of obesity and cardiometabolic risk factors was determined. Multivariate linear regression and multinomial logistic regression analyses were applied. Overall, 242 participants with mean (SD) ages of 11.3 (2.5) years completed the survey. After adjustment for confounders, a significant positive association was found between body mass index (BMI) z-score and waist circumference (WC) with 2,5-DCP (0.07 (95% CI 0.04, 0.1)) and 0.79 (95% CI 0.54, 1.03), respectively. A significant association of 2,4,5-TCP was only found with WC (0.23 (95% CI 0.0, 0.46), but the relationship with 2,4-DCP was not significant. 2,5-DCP had a significant relationship only with obesity (1.09 (95% CI 1.1, 1.19)), while 2,4-DCP and 2,4,5-TCP showed no significant correlation with overweight or obesity. 2,4-DCP showed a significant positive relationship with high density lipoprotein-cholesterol (HDL-C). Moreover, 2,5-DCP showed a significant negative relationship only with systolic blood pressure and 2,4,5-TCP had a statistically significant inverse association with total cholesterol and HDL-C (-0.71 (95% CI -0.98, -0.45)). This study suggests potential associations of chlorophenol pesticides with overweight, obesity, lipid profile, and blood pressure in children and adolescents. Longitudinal studies are necessary to assess the clinical impact of these findings.

Ionic liquids consisting of a combination of herbicidal anions with a quaternary ammonium cation act as efficient herbicides, which are under consideration to be used in the agriculture. In the present study, we used embryos of the zebrafish (Danio rerio) as a model to assess the toxic potential of ammonium-based ionic liquids for aquatic organisms. As we assumed interference of the partially hydrophobic ionic liquid cation with lipids, we investigated the adaptation response in the lipid composition of the zebrafish embryos, triggered by the ionic compound. Therefore, the impact of ammonium-based ionic liquids with different lengths of the alkyl chain ([C6,C6,C1,C1N][Br], [C8,C8,C1,C1N][Br]) on the phospholipid fatty acid (PLFA) profile of zebrafish embryos up to 72 hours post fertilization (hpf) was examined. Furthermore, the changes in the unsaturation index (UI) of PLFAs, as the sum parameter of membrane fluidity in eukaryotic cells, were presented. The PLFA's UI in the zebrafish embryos upon exposure to quaternary ammonium salts was compared to the UI of the embryos upon exposure to nonionic 2,4-dichlorophenol, which has a similar hydrophobicity but is structurally different to [C8,C8,C1,C1N][Br]. It was shown that for ammonium-based ionic liquid precursors non-specific mode of action occurs and the toxic effect on lipid composition of zebrafish embryos can be well predicted based on chemical properties, like hydrophobicity. Furthermore, the changes in PLFAs, expressed by the UI, can be useful to study toxic effects of organic contamination. However, for zebrafish embryos, after ionic liquids and 2,4-DCP exposure, the changes were observed at high lethal concentrations, which caused the incidence of lethality of 30 and 50% of a group of test animals.

The knowledge of gene-chemical interaction can be used to derive toxicological mechanism of chemical pollutants, therefore, it might be useful to discriminate chemicals with different mechanisms. In this study, three narcotic chemicals (4-chlorophenol (4-CP), 3, 4-dichloroaniline (DCA) and 2, 2, 2-trichloroethanol (TCE)) and three specific acting chemicals (triclosan (TCS), clarithromycin (CLARY), sulfamethoxazole (SMX)) were assessed by Escherichia coli (E. coli) genome-wide knockout screening. 66, 97, 88, 144, 198 and 180 initial robust hits were identified by exposure to 4-CP, DCA, TCE, TCS, CLARY and SMX with two replicates at the concentration of IC50, respectively. The average fold change values of responsive mutants to the three narcotic chemicals were smaller than the three specific acting chemicals. The common gene ontology (GO) term of biological process enriched by the three narcotic chemicals was "response to external stimulus" (GO: 0009605). Other GO terms like "lipopolysaccharide biosynthetic process" (induced by 4-CP) and "purine nucleotide biosynthetic process" (induced by DCA) were also influenced by the narcotic chemicals. The toxic target of three known specific acting chemicals could be validated by GSEA of responsive genes. Four genes (flhC, fliN, fliH and flhD) might serve as potential biomarkers to distinguish narcotic chemicals and specific acting chemicals. The E. coli functional genomic approach presented here has shown great potential not only for the molecular mechanistic screening of chemicals, rather it can discriminate chemicals based on their mode-of-action., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Triclosan (TCS), 2,4,6-trichlorophenol (2,4,6-TCP) and 2,4-dichlorophenol (2,4-DCP) are the most prevalent chlorinated phenolic pollutants in aquatic environments. Our results showed LC 50 and EC 50 values of 0.51, 1.11, 2.45mg/L, and 0.36, 0.74, 1.53mg/L for TCS, 2,4,6-TCP and 2,4-DCP, respectively, to 120hpf zebrafish. The highest TCSD (the mixture of TCS, 2,4,6-TCP and 2,4-DCP) toxicity was observed at a TCS:2,4,6-TCP:2,4-DCP concentration ratio of 1:2:4. LC 50 and EC 50 values of TCSD mixtures for 120-hpf zebrafish were 2.28 and 1.16mg/L, respectively. Two toxicity assessment methods (Toxic Unit and Mixture Toxicity Index) indicated that TCSD interactions produced partly additive toxicity. TCSD exposure decreased zebrafish hatching rate and led to a series of malformations. Following alkaline phosphatase staining, a large area of vascular ablation was observed with almost complete disappearance of vascular branches and a smaller coverage range. Prominent reddening of the yolk sac and visceral mass after oil red O staining implied that TCSD exposure severely affected fat metabolism. Following acridine orange staining, cell death occurred in eyes while high TCSD concentrations (0.84mg/L) induced cardiovascular circulation dysfunction. Alcian blue staining increased the α angle between Meckel's cartilages and β angle between two ceratobranchial. Basihyal and palatoquadrate became shorter and developmental abnormality or defects occurred in the fifth ceratobranchial. Overall, these results provide a theoretical basis for systematically evaluating the combined toxicity of the prevalent chlorinated phenolic pollutants in real-world aquatic environments., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Olfaction is a key sensory mechanism in humans. Deficits in this chemosensory function have wide-ranging impacts on overall health and quality of life. This study examines the role of environmental phenols as risk factors for olfactory dysfunction among a random sample of 839 middle-aged and older U.S. adults. Olfactory function assessment was carried out using a short 8-item test, scores on which were used to classify subjects into normal or impaired olfactory function groups. Logistic regression models were used to test for associations between olfactory impairment and creatinine-adjusted urinary levels of 8 common environmental phenols, adjusting for potentially confounding covariates. A statistically significant association between 2,4-dichlorophenol levels and olfactory impairment (OR = 1.02 [95 % CI: (1.003, 1.04)]; p = 0.02) was found. 2,4-dichlorophenol is a hazardous pollutant with widespread exposure via industrial and indoor air pollution, diet, and the use of pesticides and herbicides. This study is the first to reveal its role in olfactory impairment.

In this study, the metabolic effects of waterborne exposure of medaka (Oryzias latipes) to nominal concentrations of 20 (L group) and 2000 μg/L (H group) 2,4-dichlorophenol (DCP) were examined using a gas chromatography/mass spectroscopy (GC/MS) metabolomics approach. A principal component analysis (PCA) separated the L, H, and control groups along PC1 to explain the toxic effects of DCP at 24 h of exposure. Furthermore, the L and H groups were separated along PC1 at 96 h on the PCA score plots. These results suggest that the effects of DCP depended on exposure concentration and time. Changes in tricarboxylic cycle metabolites suggested that fish exposed to 2,4-DCP require more energy to metabolize and eliminate DCP, particularly at 96 h of exposure. A time-dependent response in the fish exposed to DCP was observed in the GC/MS data, suggesting that the higher DCP concentration had greater effects at 24 h than those observed in response to the lower concentration. In addition, several essential amino acids (arginine, histidine, lysine, isoleucine, leucine, methionine, phenylalanine, threonine, tryptophan, and valine) decreased after DCP exposure in the H group, and starvation condition and high concentration exposure of DCP could consume excess energy from amino acids.

Tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are bisphenol A (BPA) analogs, where the phenolic moieties are substituted with halogens (Br or Cl). Previous studies indicate that BPA has significant proliferative effects on in vitro cultured epithelial ovarian cancer (EOC) cells. Considering this, we analyzed the effects of both TBBPA and TCBPA at 1, 10, and 50nM on ovarian cancer cell proliferation. The majority of malignant ovarian tumors are epithelial in origin, but approximately 10% are classified as ovarian sex cord tumors, with the most common type being granulosa cell tumors (GCTs). OVCAR-3 and KGN cells were used as in vitro models to represent EOCs and GCTs, respectively. Here, we found that TBBPA, but not TCBPA, stimulated OVCAR-3 and KGN cell proliferation, with lower potency than BPA. The stimulatory effects of TBBPA and BPA on cell proliferation were reversed by pre-treatment with a G protein-coupled receptor 30 (GPR30) antagonist in both cell lines, which possess similar basal GPR30 expression levels. Taken together, our results show for the first time that TBBPA, which has lower potency than BPA, stimulates ovarian cancer cell proliferation through the GPR30 pathway., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Photocatalytically active TiO 2 -patterned polyimide (PI) films (PI-TiO 2 ) were fabricated using thermal transfer patterning (TTP). When subjected to hot pressing, the TiO 2 nanoparticles electrosprayed on steel mesh templates were successfully transferred and formed checker plate patterns on PI film. FE-SEM studies confirmed that pressing at 350°C and 100MPa was optimum for obtaining patterns with uniform TiO 2 coverage. When the quantity of TiO 2 on the template increased, the amount of it immobilized on PI film also increased from 0.3245 to 1.2378mg per 25cm 2 . XPS studies confirmed the presence TiO 2 on the patterns, and indicated the formation of carboxylic acid and amide groups on the PI surface during TTP. When tested under UVA irradiation, PI-TiO 2 with 1.2378mg/25cm 2 TiO 2 loading exhibited the highest photocatalytic performance for methylene blue (10μM) degradation, with a rate constant of 0.0225min -1 and stable photocatalytic efficacy for 25 cycles of reuse. The PI-TiO 2 was also successfully used to degrade amoxicillin, atrazine, and 4-chlorophenol. During photocatalysis, the toxicity of 4-chlorophenol against Vibrio fischeri and the antibiotic activity of amoxicillin against Escherichia coli were decreased. Overall, TTP was found to be a potentially scalable method for fabricating robust immobilized TiO 2 photocatalyst., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The aim of this study was to investigate lithium and 2,4-dichlorophenol (2,4-DCP)-induced circadian rhythm disorder and their genome-wide effects in zebrafish. Zebrafish larvae were exposed to 250 ppm LiCl (n = 40) or 20 ppm 2,4-DCP. RNA was subsequently extracted and determined quantitatively. The mRNA levels of circadian clock-related genes, including clock1a, bmal1b, per2, and per1b, were determined. Microarray datasets were generated and the differentially expressed genes (DEGs) were identified. The mRNA levels of some upregulated and downregulated DEGs were examined by quantitative real-time polymerase chain reaction (RT-PCR). Finally, gene ontology (GO) enrichment analysis was applied to determine the roles of the DEGs. The mRNA expression levels of circadian rhythm-related genes in the daily cycle were significantly affected after incubation of zebrafish with LiCl and 2,4-DCP. Many genes were differentially expressed during the light phase (97 h) and RT-PCR validation tests revealed that the expression patterns of DEGs were in accordance with those obtained by microarray analysis. GO functional enrichment analysis showed that the DEGs in LiCl- and 2,4-DCP-treated groups were associated with signal transduction and development. Collectively, our findings indicate that LiCl and 2,4-DCP could affect signal transduction pathways and immune response, thereby inducing circadian rhythm disorder.

Tetrachlorobisphenol A (TCBPA) is a common flame retardant detected in different environments. However, its toxic effects on animals and humans are not fully understood. Here, the differential intracellular metabolites and associated gene expression were used to clarify the metabolic interference of TCBPA in Saccharomyces cerevisiae, a simple eukaryotic model organism. The results indicated that TCBPA treatment promoted the glycolysis pathway but inhibited the tricarboxylic acid (TCA) cycle, energy metabolism and the hexose monophosphate pathway (HMP) pathway. Thus, the HMP pathway produced less reducing power, leading to the accumulation of reactive oxygen species (ROS) and aggravation of oxidative damage. Accordingly, the carbon flux was channelled into the accumulation of fatty acids, amino acids and glycerol instead of biomass production and energy metabolism. The accumulation of these metabolites might serve a protective function against TCBPA stress by maintaining the cell membrane integrity or providing a stable intracellular environment in S. cerevisiae. These results enhance our knowledge of the toxic effects of TCBPA on S. cerevisiae via metabolic interference and pave the way for clarification of the mechanisms underlying TCBPA toxicity in animals and humans.

There is increasing interest in the use of quantitative transcriptomic data to determine benchmark dose (BMD) and estimate a point of departure (POD) for human health risk assessment. Although studies have shown that transcriptional PODs correlate with those derived from apical endpoint changes, there is no consensus on the process used to derive a transcriptional POD. Specifically, the subsets of informative genes that produce BMDs that best approximate the doses at which adverse apical effects occur have not been defined. To determine the best way to select predictive groups of genes, we used published microarray data from dose-response studies on six chemicals in rats exposed orally for 5, 14, 28, and 90 days. We evaluated eight approaches for selecting genes for POD derivation and three previously proposed approaches (the lowest pathway BMD, and the mean and median BMD of all genes). The relationship between transcriptional BMDs derived using these 11 approaches and PODs derived from apical data that might be used in chemical risk assessment was examined. Transcriptional BMD values for all 11 approaches were remarkably aligned with corresponding apical PODs, with the vast majority of toxicogenomics PODs being within tenfold of those derived from apical endpoints. We identified at least four approaches that produce BMDs that are effective estimates of apical PODs across multiple sampling time points. Our results support that a variety of approaches can be used to derive reproducible transcriptional PODs that are consistent with PODs produced from traditional methods for chemical risk assessment.

The main objective of the present study was to improve the reliability and practicability of aquatic toxicity testing of hydrophobic chemicals based upon the model substance bromochlorophene (BCP). Therefore, we adapted a passive dosing format to test the toxicity of BCP at different concentrations and in multiple test systems with aquatic organisms of various trophic levels. At the same time, the method allowed for the accurate determination of exposure concentrations (i.e., in the presence of exposed organisms; C test ) and freely dissolved concentrations (i.e., without organisms present; C free ) of BCP in all tested media. We report on the joint adaptation of three ecotoxicity tests - algal growth inhibition, Daphnia magna immobilization, and fish-embryo toxicity - to a silicone O-ring based equilibrium passive dosing format. Effect concentrations derived by passive dosing methods were compared with corresponding effect concentrations derived by standard co-solvent setups. The passive dosing format led to EC 50 -values in the lower μgL -1 range for algae, daphnids, and fish embryos, whereas increased effect concentrations were measured in the co-solvent setups for algae and daphnids. This effect once more shows that passive dosing might offer advantages over standard methods like co-solvent setups when it comes to a reliable risk assessment of hydrophobic substances. The presented passive dosing setup offers a facilitated, practical, and repeatable way to test hydrophobic chemicals on their toxicity to aquatic organisms, and is an ideal basis for the detailed investigation of this important group of chemicals., (Copyright © 2017 Elsevier B.V. All rights reserved.)