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Only about 100 disinfection byproducts (DBPs) have been tested for their potential aquatic toxicity. It is not known which specific DBPs, DBP main groups, and DBP subgroups are more toxic due to the lack of experimental toxicity data. Herein, high priority specific DBPs, DBP main groups, DBP subgroups, most sensitive model aquatic species, potential PBT and PMT (persistent, bioaccumulative/mobile, and toxic) DBPs were virtually screened for 1187 updated DBPs inventory. Priority setting based on experimental and predicted acute and chronic aquatic toxicity data found that the aromatic and alicyclic DBPs in four DBPs main groups showed high priority because larger proportions of aromatic and alicyclic DBPs are in high hazard categories (i.e. Acute and/or Chronic Toxic-1 or Toxic-2) according to the criteria in GHS system compared to the aliphatic and heterocyclic DBPs. The halophenols, estrogen-DBPs, nonhalogenated esters, and nonhalogenated aldehydes were recognized as high priority DBPs subgroups. For specific DBPs, 19 and 31 DBPs should be highly concerned in the future study because both acute and chronic toxicity of those DBPs to all of the three aquatic life (algae, Daphnia magna, fish) were classified as Toxic-1 and Toxic-2, respectively. The Daphnia magna and algae were sensitive to the acute toxicity of DBPs, while the fish and Daphnia magna were sensitive to the chronic toxicity of DBPs. One potential PBT (Tetrachlorobisphenol A) and four potential PMT DBPs were identified. For verification, the acute toxicity of four DBPs on three aquatic organism were performed, and their tested acute toxicity data to three aquatic organisms were consistent with the predictions. Our results could be beneficial to government regulators to adopt effective measures to limit the discharge of high priority DBPs and help the scientific community to develop or improve disinfection processes to reduce the production of high priority DBPs., 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 © 2024 Elsevier B.V. All rights reserved.)

The biofilm architecture is significantly influenced by external environmental conditions. Biofilms grown on drinking water distribution systems (DWDS) are exposed to environmental contaminants, including parabens, and disinfection strategies, such as chlorine. Although changes in biofilm density and culturability from chemical exposure are widely reported, little is known about the effects of parabens and chlorine on biofilm morphology and architecture. This is the first study evaluating architectural changes in Stenotrophomonas maltophilia colony biofilms (representatives of bacterial communities presented in DWDS) induced by the exposure to methylparaben (MP) at environmental (15 μg/L) and in-use (15 mg/L) concentrations, and chlorine at 5 mg/L, using widefield epi-fluorescence mesoscopy with Mesolens. The GFP fluorescence of colony biofilms allowed the visualization of internal structures and Nile Red fluorescence permitted the inspection of the distribution of lipids. Our data show that exposure to MP triggers physiological and morphological adaptation in mature colony biofilms by increasing the complexity of internal structures, which may confer protection to embedded cells from external chemical molecules. These architectural modifications include changes in lipid distribution as an adaptive response to MP exposure. Although chlorine exposure affected colony biofilm diameter and architecture, the colony roundness was completely affected by the simultaneous presence of MP and chlorine. This work is pioneer in using Mesolens to highlight the risks of exposure to emerging environmental contaminants (MP), by affecting the architecture of biofilms formed by drinking water (DW) bacteria, even when combined with routine disinfection strategies., 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 © 2024. Published by Elsevier B.V.)

Determining the occurrence of disinfection byproducts (DBPs) in drinking water distribution system (DWDS) remains challenging. Predicting DBPs using readily available water quality parameters can help to understand DBPs associated risks and capture the complex interrelationships between water quality and DBP occurrence. In this study, we collected drinking water samples from a distribution network throughout a year and measured the related water quality parameters (WQPs) and haloacetic acids (HAAs). 12 machine learning (ML) algorithms were evaluated. Random Forest (RF) achieved the best performance (i.e., R 2 of 0.78 and RMSE of 7.74) for predicting HAAs concentration. Instead of using cytotoxicity or genotoxicity separately as the surrogate for evaluating toxicity associated with HAAs, we created a health risk index (HRI) that was calculated as the sum of cytotoxicity and genotoxicity of HAAs following the widely used Tic-Tox approach. Similarly, ML models were developed to predict the HRI, and RF model was found to perform the best, obtaining R 2 of 0.69 and RMSE of 0.38. To further explore advanced ML approaches, we developed 3 models using uncertainty-based active learning. Our findings revealed that Categorical Boosting Regression (CAT) model developed through active learning substantially outperformed other models, achieving R 2 of 0.87 and 0.82 for predicting concentration and the HRI, respectively. Feature importance analysis with the CAT model revealed that temperature, ions (e.g., chloride and nitrate), and DOC concentration in the distribution network had a significant impact on the occurrence of HAAs. Meanwhile, chloride ion, pH, ORP, and free chlorine were found as the most important features for HRI prediction. This study demonstrates that ML has the potential in the prediction of HAA occurrence and toxicity. By identifying key WQPs impacting HAA occurrence and toxicity, this research offers valuable insights for targeted DBP mitigation strategies., Competing Interests: Declaration of competing interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Irgarol 1051 is an herbicide extensively utilized in antifouling paint due to its ability to inhibit photosynthesis. Irgarol and its photodegradation products are highly persistent in waters and sediments, although they are present in low concentrations. However, our understanding of the harmful effects of Irgarol on non-target organisms remains limited. In this study, we assessed the effects of acute (24 h) and chronic (14 days across three generations) exposure to different concentrations (including the 1/10 NOEC, NOEC, and 1/10 LC50 calculated from the 24-h acute toxicity test) of Irgarol using the water flea Moina macrocopa. Acute exposure to 1/10 LC50 significantly decreased survival, feeding rate, thoracic limb activity, heart rate, and acetylcholinesterase activity. Elevated levels of intracellular reactive oxygen species and malondialdehyde, along with a significant increase in catalase and superoxide dismutase activity, suggested the induction of oxidative stress in response to 1/10 LC50. An initial boost in glutathione level and the enzymatic activities of glutathione peroxidase and glutathione reductase, followed by a plunge, implies some compromise in the antioxidant defense system. Upon chronic exposure to the NOEC value, both generations F1 and F2 displayed a significant decrease in survival rate, body length, number of neonates per brood, and delayed sexual maturation, suggesting maternal transfer of potential damage through generations. Taken together, Irgarol induced acute toxicity through physiological and cholinergic damage, accompanied by the induction of oxidative stress, in the water flea. Even its sub-lethal concentrations can induce detrimental effects across generations when consistently exposed., 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 © 2024 Elsevier Inc. All rights reserved.)

Some drugs or chemicals exhibit different safety profiles in newborns/young children compared to adults. Polyhexamethyleneguanidine phosphate (PHMG-P) has been implicated in the humidifier disinfectant tragedy in 2011. There are limited reports on the toxicity of PHMG-P in neonatal animals. This study aimed to assess the toxicity of PHMG-P in neonates and to compare toxicity between young and adult mice. Mice aged 7-10 days and 8 weeks were anesthetized with isoflurane and then intranasally instilled with 0.9 mg/kg and 1.5 mg/kg PHMG-P once weekly for 4 weeks. The control group was given a corresponding volume of saline intranasally. Approximately 20 h after the 4th instillation, all mice (juveniles aged 28‒31 days and adults aged 11 weeks) were euthanized. Assessments included body weights, organ weights, cytokine production, and histopathological examinations. Both juvenile and adult mice exhibited significant pulmonary toxicity. There were no significant changes in body weight in either male or female juveniles, whereas adult mice experienced 5.0‒22.2% weight loss. However, lung weights increased in both age groups, accompanied by rises in cytokines and chemokines. Histopathological analyses revealed significant lung changes in both juvenile and adult mice, including immune cell infiltration, foamy macrophage, and granulomatous inflammation. PHMG-P is known to cause inflammation and fibrotic changes in rodents and humans that persist even during long recovery periods. Further research is required to explore the long-term health effects of PHMG-P following repeated early-life exposure., (© 2024. The Author(s).)

Disinfection by-products (DBPs) generated from water treatment have serious adverse effects on human health and natural ecosystems. However, research on the mutagenicity of DBPs with different chemical structures is still limited. In the present study, we compared the mutagenicity of 8 typical DBPs in human-hamster hybrid (A L ) cells and clarified the mechanisms involved. Our data displayed that the rank order for mutagenicity was as follows: iodoacetamide (IAcAm) > iodoacetonitrile (IAN) > iodoacetic acid (IAA) > bromoacetamide (BAcAm) ≈ bromoacetonitrile (BAN) > bromoacetic acid (BAA), which was confirmed by DNA double strand breaks and oxidative DNA damage. In contrast, bromoform (TBM) and iodoform (TIM) had minimal mutagenicity. The mutation spectrum analysis further revealed that IAN, IAcAm, and IAA could induce multilocus deletions in mammalian cells. Interestingly, nitrogenous DBPs (N-DBPs) and IAA were found to cause varying degrees of iron overload and lipid peroxidation, which was mediated by the activation of the Nrf2/HO-1 signaling pathway. Moreover, the presence of deferoxamine (DFO), an iron ion inhibitor, effectively reduced γ-H2AX and 8-OHdG induced by N-DBPs and IAA. These results indicated that the variations in genotoxicity among DBPs with different structures were associated with their ability to disrupt iron homeostasis. This study provided new insights into the mechanisms underlying the structure-dependent toxicity of DBPs and established a foundation for a more comprehensive understanding and intervention of the health risks associated with DBPs., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Quaternary ammonium compounds are a class of chemicals commonly used as disinfectants in household and healthcare settings. Their usage has significantly increased in recent years due to the COVID-19 pandemic. In addition, quaternary ammonium compounds have replaced the recently banned disinfectants triclosan and triclocarban in consumer products. Quaternary ammonium compounds are found in daily antimicrobial and personal care products such as household disinfectants, mouthwash, and hair care products. Due to the pervasiveness of quaternary ammonium compounds in daily use products, humans are constantly exposed. However, little is known about the health effects of everyday quaternary ammonium compound exposure, particularly effects on human reproduction and development. Studies that investigate the harmful effects of quaternary ammonium compounds on reproduction are largely limited to high-dose studies, which may not be predictive of low-dose, daily exposure, especially as quaternary ammonium compounds may be endocrine-disrupting chemicals. This review analyzes recent studies on quaternary ammonium compound effects on reproductive health, identifies knowledge gaps, and recommends future directions in quaternary ammonium compound-related research. Summary Sentence  Quaternary ammonium compounds, a class of disinfecting compounds that have skyrocketed in usage during the COVID-19 pandemic, are emerging as reproductive and developmental toxicants., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Polyhexamethylene guanidine (PHMG) is a positively charged polymer used as a disinfectant that kills microbes but can cause pulmonary fibrosis if inhaled. After the long-term risks were confirmed in South Korea, it became crucial to measure toxicity through diverse surrogate biomarkers, not only proteins, especially after these hazardous chemicals had cleared from the body. These biomarkers, identified by their biological functions rather than simple numerical calculations, effectively explained the imbalance of pulmonary surfactant caused by fibrosis from PHMG exposure. These long-term studies on children exposed to PHMG has shown that blood protein indicators, primarily related to apolipoproteins and extracellular matrix, can distinguish the degree of exposure to humidifier disinfectants (HDs). We defined the extreme gradient boosting models and computed reflection scores based on just ten selected proteins, which were also verified in adult women exposed to HD. The reflection scores successfully discriminated between the HD-exposed and unexposed groups in both children and adult females (AUROC: 0.957 and 0.974, respectively) and had a strong negative correlation with lung function indicators. Even after an average of more than 10 years, blood is still considered a meaningful specimen for assessing the impact of environmental exposure to toxic substances, with proteins providing in identifying the pathological severity of such conditions., 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 © 2024 Elsevier B.V. All rights reserved.)

Chloro-haloacetonitrile (Cl-HAN), belongs to a group of nitrogenous disinfection by-products (N-DBPs) found in surface water, and are known to pose a major risk to the safety of human drinking water. However, the exact biological toxicity mechanism and the extent of the stress response caused by Cl-HAN remain unclear, resulting in a lack of effective measures to control its presence. Thus, the quantitative toxicological genomics and bioinformatics methods were applied to explore the effects of three chloro-haloacetonitriles (Cl-HANs) on the transcription of fusion genes under varying concentrations of stress in E. coli over 2-hour period. The initial stress response and their toxic mechanism were analyzed. The study also identified the molecular toxicity endpoint, and the core genes that are responsible for the specific toxicity of different Cl-HANs. Cl-HANs exhibited concentration-dependent characteristics of toxic effects, and caused changes in gene expression related oxidative and membrane stress. The stress response results showed that dichloroacetonitrile (dCAN) still caused significant DNA damage under the lowest concentration stress. Chloroacetonitrile (CAN) and trichloroacetonitrile (tCAN) exhibited lower genetic toxicity levels at 513 μg/L and 10.7 μg/L, respectively. The toxic effects of tCAN were widespread. And there was a good correlation between the molecular endpoint (EC-TELI 1.5 ) and the phenotypic endpoint (LD50) with r p =-0.8634 (P=0.0593). In all concentrations of stress in CAN, dCAN, and tCAN, the number of overexpressed genes shared was 15, 2, and 14, respectively. Furthermore, bioinformatics analysis demonstrated that Cl-HANs affected genes associated with general stress pathways, such as cell biochemistry and physical homeostasis, resulting in changes in biological processes. And for CAN-induced DNA damage, polA played a dominant role, while katG, oxyR, and ahpC were the core genes involved in oxidative stress induced by dCAN and tCAN, respectively. These findings provide valuable data for the toxic effect of Cl-HANs., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ferrate (Fe(VI)) is an environmentally friendly disinfectant that is widely used to eradicate microbes in reclaimed water. However, the potential health risks associated with inhalation of Fe(VI)-treated bacteria-laden reclaimed water remains uncertain. We aimed to explore the inhalation hazards and potential mechanisms of K 2 FeO 4 -treated Escherichia coli (E. coli, ATCC 25922). Our findings indicated that Fe(VI) disinfection induced a dose- and time-dependent E. coli inactivation, accompanied by a rapid release of the bacterial endotoxin, lipopolysaccharide (LPS). Scanning electron microscopy (SEM) observations indicate that Fe(VI)-induced endotoxin production consists of at least two stages: initial binding of endotoxin to bacteria and subsequent dissociation to release free endotoxin. Furthermore, Fe(VI) disinfection was not able to effectively eliminate pure or E. coli-derived endotoxins. The E. coli strain used in this study lacks lung infection capability, thus the inhalation of bacteria alone failed to induce severe lung injury. However, mice inhaled exposure to Fe(VI)-treated E. coli showed severe impairment of lung structure and function. Moreover, we observed an accumulation of neutrophil/macrophage recruitment, cell apoptosis, and ROS generation in the lung tissue of mice subjected to Fe(VI)-treated E. coli. RNA sequencing (RNA-seq) and PCR results revealed that genes involved with endotoxin stimuli, cell apoptosis, antioxidant defence, inflammation response, chemokines and their receptors were upregulated in response to Fe(VI)-treated E. coli. In conclusion, Fe(VI) is ineffective in eliminating endotoxins and can trigger secondary hazards owing to endotoxin release from inactivated bacteria. Aerosol exposure to Fe(VI)-treated E. coli causes considerable damage to lung tissue by inducing oxidative stress and inflammatory responses., Competing Interests: Declaration of competing interest The authors declare that there are no personal or financial conflicts of interest in this research., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although biocides are important materials in modern society and help protect human health and the environment, increasing exposure to combined biocides can cause severe side effects in the human body, such as lung fibrosis. In this study, we developed a receptonics system to screen for biocides in combined household chemical products based on biocides. The system contains transient receptor potential ankyrin 1 (TRPA1) nanovesicles (NVs) to sense biocides based on pain receptors and a side-gated field-effect transistor (SGFET) using a single-layer graphene (SLG) micropattern channel. The binding affinities between the TRPA1 receptor and the various biocides were estimated by performing biosimulation and using a calcium ion (Ca 2+ ) assay, and the sensitivity of the system was compared with that of TRPA1 NV receptonics systems. Based on the results of the TRPA1 NV receptonics system, the antagonistic and potentiation effects of combined biocides and household chemical products depended on the concentration. Finally, the TRPA1 NV receptonics system was applied to screen for biocides in real products, and its performance was successful. Based on these results, the TRPA1 NV receptonics system can be utilized to perform risk evaluations and identify biocides in a simple and rapid manner., 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 © 2024 Elsevier B.V. All rights reserved.)

The environmental transmission of antibiotic resistance genes (ARGs) and metal resistance genes (MRGs) exerted devastating threats to global public health, and their interactions with other emerging contaminants (ECs) have raised increasing concern. This study investigated that the abundances of ARGs and MRGs with the predominant type of efflux pump were simultaneously increased (8.4-59.1%) by disinfectant polyhexamethylene guanidine (PHMG) during waste activated sludge (WAS) anaerobic digestion. The aggregation of the same microorganisms (i.e., Hymenobacter and Comamonas) and different host bacteria (i.e., Azoarcus and Thauera) were occurred upon exposure to PHMG, thereby increasing the co-selection and propagation of MRGs and ARGs by vertical gene transfer. Moreover, PHMG enhanced the process of horizontal gene transfer (HGT), facilitating their co-transmission by the same mobile genetic elements (20.2-223.7%). Additionally, PHMG up-regulated the expression of critical genes (i.e., glnB, trpG and gspM) associated with the HGT of ARGs and MRGs (i.e., two-component regulatory system and quorum sensing) and exocytosis system (i.e., bacterial secretion system). Structural equation model analysis further verified that the key driver for the simultaneous enrichment of ARGs and MRGs under PHMG stress was microbial community structure. The study gives new insights into the aggravated environmental risks and mechanisms of ECs in sludge digestion system, providing guidance for subsequent regulation and control of ECs., 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 © 2024 Elsevier Ltd. All rights reserved.)

This study addresses the need for accurate structural data regarding the toxicity of fragrances in sanitizers and disinfectants. We compare the predictive and descriptive (model stability) potential of multiple linear regression (MLR) and partial least squares (PLS) models optimized through variable selection (VS). A novel hybrid chaotic neural network algorithm with competitive learning (CCLNNA)-PLS modeling strategy can offer specific optimization with satisfactory results, even for a limited dataset. While also exploring the preliminary comparative analysis, the goal is to introduce an adapted novel CCLNNA optimization strategy for VS, inspired by neural networks, along with exploring the influence of the percentage of significant descriptors in the optimization function to enhance the final model's capabilities. We analyzed an available dataset of 24 molecules, incorporating ADMET and PaDEL descriptors as predictor variables, to explore the relationship between the response/target variable (pLC 50 ) and the meticulously optimized set of descriptors. The suitability of the selected PLS models (cross- and external-validated accuracy combined with percentage of significant descriptors at a level equal to or >80 %) underscores the importance of expanding the dataset to amplify the validation protocols, thus enhancing future model reliability and environmental impact., 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 © 2024. Published by Elsevier B.V.)

Ultrafiltration (UF) is widely used in drinking water plants; however, membrane fouling is unavoidable. Natural organic matter (NOM) is commonly considered as an important pollutant that causes membrane fouling. Herein, we proposed VUV/H 2 O 2 as a UF pretreatment and used UV/H 2 O 2 for comparison. Compared to UV/H 2 O 2 , the VUV/H 2 O 2 system presented superior NOM removal. In the VUV/H 2 O 2 system, the steady-state concentration of HO• was approximately twice that in the UV/H 2 O 2 system, which was ascribed to the promoting effect of the 185 nm photons. Specifically, 185 nm photons promoted HO• generation by decomposing mainly H 2 O at a low H 2 O 2 dose or by decomposing mainly H 2 O 2 at a high H 2 O 2 dose. The VUV/H 2 O 2 pretreatment also demonstrated better membrane fouling mitigation performance than did UV/H 2 O 2 . An increase in the H 2 O 2 dose promoted HO• generation, thereby enhancing the performance of NOM degradation and membrane fouling alleviation and shifting the major membrane fouling mechanism from cake filtration to standard blocking. The VUV/H 2 O 2 (0.60 mM) pretreatment effectively reduced disinfection byproducts (DBPs) formation during chlorine disinfection. Additionally, the oxidant H 2 O 2 affected the membrane surface morphology and performance but had no evident effect on the mechanical properties. In actual water treatment, the VUV/H 2 O 2 pretreatment exhibited better performance than the UV/H 2 O 2 pretreatment in easing membrane fouling, ameliorating water quality, and reducing DBPs formation and acute toxicity., 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 © 2024 Elsevier B.V. All rights reserved.)

Nitrogenous disinfection byproducts (N-DBPs) in water are carcinogenic, teratogenic, and mutagenic. In this work, we developed a biomimetic reduction approach based on the cysteine thiol that destructed the highly toxic, select nitrogenous haloacetamides (HAMs) and haloacetonitriles (HANs) while effectively controlling the cytotoxicity of the degradation products to serve as a basis for further technological applications (e.g. immobilized contact bed for terminal users). Mechanisms on toxicity control were elucidated. Results showed the degradation and cytotoxicity control of HAMs as more efficient than that of the HANs. The cytotoxicity of the chlorinated, brominated, and iodinated HAMs and HANs was reduced to 25 %- 0.25 % of the original after biomimetic reduction using a reasonable concentration ratio. Through a combination of thiol-specific reactivity, dehalogenation, and quantitative structure-activity relationship analyses, the major toxicity control mechanisms were found to be the reductive dehalogenation of the N-DBPs. The halogenated functional groups on the N-DBPs had a more pronounced effect than the amide and nitrile groups on the cytotoxicity and detoxification effect. Patterns of toxicity interaction variations with DBPs concentrations were identified to detect possible synergistic cytotoxicity interactions under various combinations of HAMs and HANs in the presence of the cysteine thiol. Results could benefit future N-DBPs control efforts., 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 © 2024 Elsevier B.V. All rights reserved.)

Disinfection of public drinking water and swimming pools is crucial for preventing waterborne diseases, but it can produce harmful disinfection by-products (DBPs), increasing the risk of various diseases for those frequently exposed to such environments. Bromoacetic acid (BAA) is a ubiquitous DBP, with toxicity studies primarily focused on its in vitro cytotoxicity, and insufficient research on its neurodevelopmental toxicity. Utilizing zebrafish as a model organism, this study comprehensively explored BAA's toxic effects and uncovered the molecular mechanisms through neurobehavioral analysis, in vivo two-photon imaging, transcriptomic sequencing, pharmacological intervention and molecular biological detection. Results demonstrated BAA induced significant changes on various indicators in the early development of zebrafish. Furthermore, BAA disrupted behavioral patterns in zebrafish larvae across locomotion activity, light-dark stimulation, and vibration stimulation paradigms. Subsequent investigation focused on larvae revealed BAA inhibited neuronal development, activated neuroinflammatory responses, and altered vascular morphology. Transcriptomic analysis revealed BAA-stressed zebrafish exhibited downregulation of visual transduction-related genes and activation of ferroptosis and cellular apoptosis. Neurobehavioral disorders were recovered by inhibiting ferroptosis and apoptosis. This study elucidates the neurodevelopmental toxicity associated with BAA, which is crucial for understanding health risks of DBPs and for the development of more effective detection methods and regulatory strategies., Competing Interests: Declaration of Competing Interest We confirm that this manuscript has not been published in whole or in part and is not being considered for publication elsewhere. There are no any ethical conflicts of interest for all authors., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Next-generation risk assessment (NGRA) has emerged as a promising alternative to non-animal studies owing to the increasing demand for the risk assessment of inhaled toxicants. In this study, NGRA was used to assess the inhalation risks of two biocides commonly used as humidifier disinfectants: polyhexamethylene guanidine phosphate (PHMG-p) and chloromethylisothiazolinone/methylisothiazolinone (CMIT/MIT). Human bronchial epithelial cell transcriptomic data were processed based on adverse outcome pathways and used to establish transcriptome-based points of departure (tPODs) for each biocide. tPOD values were 0.00500-0.0510 μg/cm 2 and 0.0342-0.0544 μg/cm 2 for PHMG-p and CMIT/MIT, respectively. tPODs may provide predictive power comparable to that of traditional animal-based PODs (aPODs). The tPOD-based NGRA determined that both PHMG-p and CMIT/MIT present a high inhalation risk. Moreover, the identified PHMG-p posed a higher risk than CMIT/MIT, and children were identified as more susceptible population compared to adults. This finding is consistent with observations from actual exposure events. Our findings suggest that NGRA with transcriptomics offers a reliable approach for risk assessment of specific humidifier disinfectant biocides, while acknowledging the limitations of current models and in vitro systems, particularly regarding uncertainties in pharmacokinetics (PK) and pharmacodynamics (PD)., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Iodoacetic acid (IAA) is an emerging unregulated iodinated disinfection byproduct with high toxicity and widespread exposure. IAA has potential reproductive toxicity and could damage male reproduction. However, the underlying mechanisms and toxicological targets of IAA on male reproductive impairment are still unclear, and thus Sprague-Dawley rats and Leydig cells were used in this work to decode these pending concerns. Results showed that after IAA exposure, the histomorphology and ultrastructure of rat testes were abnormally changed, numbers of Leydig cells were reduced, the hypothalamic-pituitary-testis (HPT) axis was disordered, and testosterone biosynthesis was inhibited. Proteomics analyses displayed that oxidative stress, endoplasmic reticulum stress, and steroid hormone biosynthesis were involved in IAA-caused reproductive injury. Antioxidant enzymes were depleted, while levels of ROS, MDA, 8-OHdG, and γ-H2A.X were increased by IAA. IAA triggered oxidative stress and DNA damage, and then activated the GRP78/IRE1/XBP1s and cGAS/STING/NF-κB pathways in Leydig cells. The two signaling pathways constructed an interactive network by synergistically regulating the downstream transcription factor CHOP, which in turn directly bound to and negatively modulated steroidogenic StAR, finally refraining testosterone biosynthesis in Leydig cells. Collectively, IAA as a reproductive toxicant has anti-androgenic effects, and the GRP78/IRE1 and cGAS/STING pathway crosstalk through CHOP facilitates IAA-mediated testosterone decline., 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 © 2024 Elsevier B.V. All rights reserved.)

The heterotrophic nitrification-aerobic denitrification (HNAD) strain Exiguobacterium H1 (H1) was isolated in this study. The changes in nitrogen metabolism functions of H1 strain were discussed in presence of disinfectants chloroxylenol (PCMX) and benzethonium chloride (BEC) alone and combined pollution (PCMX+BEC). The H1 strain could use NH 4 + -N, NO 2 - -N and NO 3 - -N as nitrogen sources and had good nitrogen removal performance under conditions of C/N ratio 25, pH 5-8, 25-35  o C and sodium acetate as carbon. PCMX and BEC alone exhibited hormesis effects on H1 strain which promoted the growth of H1 strain at low concentrations but inhibited it at high concentrations, and combined pollution showed synergistic inhibitory on H1 strain. H1 strain owned a full nitrogen metabolic pathway according to functional genes quantification. PCMX encouraged nitrification process of H1, while BEC and combined pollution mostly blocked nitrogen removal. PCMX, but not BEC, mainly led to the enrichment of resistance genes. These findings will aid in systematic assessment of contaminant tolerance characteristics of HNAD strain and its application prospects., 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 © 2024 Elsevier B.V. All rights reserved.)

Parabens are emerging contaminants that have been detected in drinking water. Their presence in DW distribution systems (DWDS) can alter bacterial behaviour, characteristics, and structure, which may compromise DW disinfection. This work provides insights into the impact of methylparaben (MP) on the tolerance to chlorine disinfection and antibiotics from dual-species biofilms formed by Acinetobacter calcoaceticus and Stenotrophomonas maltophilia isolated from DW and grown on high-density polyethylene (HDPE) and polypropylene (PPL). Results showed that dual-species biofilms grown on PPL were more tolerant to chlorine disinfection, expressing a decrease of over 50 % in logarithmic reduction values of culturable cells in relation to non-exposed biofilms. However, bacterial tolerance to antibiotics was not affected by MP presence. Although MP-exposed dual-species biofilms grown on HDPE and PPL were metabolically more active than non-exposed counterparts, HDPE seems to be the material with lower impact on DW risk management and disinfection, if MP is present. Overall, results suggest that MP presence in DW may compromise chlorine disinfection, and consequently affect DW quality and stability, raising potential public health issues., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Recently, seven dihalohydroxybenzonitriles (diHHBNs) have been determined as concerning nitrogenous aromatic disinfection byproducts (DBPs) in drinking water. Herein, eight new monohalohydroxybenzonitriles (monoHHBNs), including 3-chloro-2-hydroxybenzonitrile, 5-chloro-2-hydroxybenzonitrile, 3-chloro-4-hydroxybenzonitrile, 3-bromo-2-hydroxybenzonitrile, 5-bromo-2-hydroxybenzonitrile, 3-bromo-4-hydroxybenzonitrile, 5-iodo-2-hydroxybenzonitrile, and 3-iodo-4-hydroxybenzonitrile, were detected and identified in drinking water for the first time. Thereafter, the relative concentration-cytotoxicity contribution of each HHBN was calculated based on the acquired occurrence level and cytotoxicity data in this study, the genome-scale cytotoxicity mechanism was explored, and a quantitative structure-activity relationship (QSAR) model was developed. Results indicated that new monoHHBNs were present in drinking water at concentrations of 0.04-1.83 ng/L and exhibited higher cytotoxicity than some other monohalogenated aromatic DBPs. Notably, monoHHBNs showed concentration - cytotoxicity contribution comparable to diHHBNs, which have been previously identified as potential toxicity drivers in drinking water. Transcriptomic analysis revealed immunotoxicity and genotoxicity as dominant cytotoxicity mechanisms for HHBNs in Chinese hamster ovary (CHO-K1) cells, with potential carcinogenic effects. The QSAR model suggested oxidative stress and cellular uptake efficiency as important factors for their cytotoxicity, highlighting the importance of potential iodinated HHBNs in drinking water, such as 3,5-diiodo-2-hydroxybenzonitrile, for future studies. These findings are meaningful for better understanding the health risk and toxicological significance of HHBNs in drinking water.

Micro/nanoplastics can act as vectors for organic pollutants and enhance their toxicity, which has been attributed to the ingestion by organisms and the "Trojan horse effect". In this study, we disclosed a non-ingestion pathway for the toxicity enhancement effect of nanoplastics. Initially, the combined toxicity of polystyrene microplastics (40 μm) or nanoplastics (50 nm) with three disinfection byproducts (DBPs) to a marine polychaete, Platynereis dumerilii, was investigated. No toxic effect was observed for the micro/nanoplastics alone. The microplastics showed no effect on the toxicity of the three DBPs, whereas the nanoplastics significantly enhanced the toxicity of two aromatic DBPs when the polychaete was in its non-feeding early life stage throughout the exposure period. The microplastics showed no interaction with the P. dumerilii embryos, whereas the nanoplastics agglomerated strongly on the embryonic chorion and fully encapsulated the embryos. This could contribute to higher actual exposure concentrations in the microenvironment around the embryos, as the concentrations of the two aromatic DBPs on the nanoplastics were 1200 and 120 times higher than those in bulk solution. Our findings highlight an important and previously overlooked mechanism by which nanoplastics and organic pollutants, such as DBPs, pose a higher risk to marine species at their vulnerable early life stages. This study may contribute to a broader understanding of the environmental impacts of plastic pollution and underscore the necessity to mitigate their risks associated with DBPs., 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 © 2024 Elsevier Ltd. All rights reserved.)

Since the onset of the SARS-CoV-2 pandemic in early 2020, there has been a notable rise in sodium hypochlorite disinfectants. Sodium hypochlorite undergoes hydrolysis to generate hypochlorous acid for virus eradication. This chlorine-based disinfectant is widely utilized for public disinfection due to its effectiveness. Although sodium hypochlorite disinfection is convenient, its excessive and indiscriminate use can harm the water environment and pose a risk to human health. Hypochlorous acid, a reactive oxygen species, plays a crucial role in the troposphere, stratospheric chemistry, and oxidizing capacity. Additionally, hypochlorous acid is vital as a reactive oxygen species in biological systems, and its irregular metabolism and level is associated with several illnesses. Thus, it is crucial to identify hypochlorous acid to comprehend its environmental and biological functions precisely. Here, we constructed a new fluorescent probe, utilizing the twisted intramolecular charge transfer mechanism to quickly and accurately detect hypochlorous acid in environmental water and biosystems. The probe showed a notable increase in fluorescence when exposed to hypochlorous acid, demonstrating its excellent selectivity, fast response time (less than 10 seconds), a large Stokes shift (∼ 102 nm), and a low detection limit of 15.5 nM., 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 © 2024. Published by Elsevier Inc.)

Dosimetry modeling and point of departure (POD) estimation using in vitro data are essential for mechanism-based hazard identification and risk assessment. This study aimed to develop a putative adverse outcome pathway (AOP) for humidifier disinfectant (HD) substances used in South Korea through a systematic review and benchmark dose (BMD) modeling. We collected in vitro toxicological studies on HD substances, including polyhexamethylene guanidine hydrochloride (PHMG-HCl), PHMG phosphate (PHMG-p), a mixture of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (CMIT/MIT), CMIT, and MIT from scientific databases. A total of 193 sets of dose-response data were extracted from 34 articles reporting in vitro experimental results of HD toxicity. The risk of bias (RoB) in each study was assessed following the office of health assessment and translation (OHAT) guideline. The BMD of each HD substance at different toxicity endpoints was estimated using the US Environmental Protection Agency (EPA) BMD software (BMDS). Interspecies- or interorgan differences or most critical effects in the toxicity of the HD substances were analyzed using a 95% lower confidence limit of the BMD (BMDL). We found a critical molecular event and cells susceptible to each HD substance and constructed an AOP of PHMG-p- or CMIT/MIT-induced damage. Notably, PHMG-p induced ATP depletion at the lowest in vitro concentration, endoplasmic reticulum (ER) stress, epithelial-to-mesenchymal transition (EMT), inflammation, leading to fibrosis. CMIT/MIT enhanced mitochondrial reactive oxygen species (ROS) production, oxidative stress, mitochondrial dysfunction, resulting in cell death. Our approach will increase the current understanding of the effects of HD substances on human health and contribute to evidence-based risk assessment of these compounds., 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 © 2024 Elsevier Ltd. All rights reserved.)

The presence of microplastics (MPs) in water may affect the efficacy of the disinfection process and induce toxicity changes to MPs themselves during disinfection. Therefore, this study evaluated the two-way effects of polyethylene microplastic (MP) particles in water and wastewater during sodium hypochlorite (NaClO) disinfection. On the one hand, it has been confirmed that the presence of MPs reduced the disinfection efficiency of NaClO. The required CT (concentration of the disinfection × contact time) for a 2-4-log inactivation of Escherichia coli (E. coli) in different water samples was in the order of deionized water < turbid water (1 NTU) < water with MPs (1 mg/L) < turbid water (10 NTU). On the other hand, although exposure to MPs did induce significant changes in the activities of superoxide dismutase and glutathione, compared to pristine MPs, the MPs treated by NaClO at current conditions (0.3 and 3.0 mg/L for 30 min) did not show significant changes in their toxicity on zebrafish, at an MP exposure concentration of 1 mg/L. There was no significant difference in the survival rate and weight growth rate, neither as in the activities of the oxidative stress-related enzymes (superoxide dismutase, catalase, glutathione, glutathione peroxidase, and glutathione s-transferase) in both gut and muscle tissues of the zebrafish, between exposure to the pristine and NaClO-treated MPs. It is indicated that NaClO disinfection commonly applied for water and wastewater treatment would not pose a serious concern to effluent safety in the presence of mild levels of MPs., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ning Ding reports financial support was provided by National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. 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 © 2024 Elsevier Ltd. All rights reserved.)

The toxicity and safety of a veterinary anti-salmonella disinfectant based on three highly virulent bacteriophage strains (titers 10 10 PFU/ml) were studied. Acute, chronic, and inhalation toxicity, as well as local irritancy of the disinfectant were evaluated on outbred white mice CD1 (n=65), Soviet chinchilla rabbits (n=20), and rats (n=20). No toxic effects of the disinfectant was observed after its intraperitoneal or intragastric administration to mice and intragastric administration to rats; in rabbits, application on the skin and eyes produced no local irritation effect. Inhalation of 10% of the disinfectant did not cause any pathologies in mice. Thus, the tests confirmed the high level of safety of the disinfectant based on a mixture of bacteriophages for use as an additional specific disinfection agent against Salmonella in veterinary and livestock facilities., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

5-Chloro-2-methyl-4-isothiazolin-3-one (CMIT) and 2-methyl-4-isothiazolin-3-one (MIT) used as preservatives in various products, including humidifier disinfectants, presents substantial health hazards. This research delves into the toxicological assessments of CMIT/MIT in the respiratory system using animal models. Through the synthesis of radiolabeled [ 14 C]CMIT and [ 14 C]MIT, we investigated the biological uptake and in vivo behaviors of CMIT/MIT in the respiratory tissues following intratracheal exposure. Quantitative whole-body autoradiography (QWBA) revealed significant persistence of CMIT/MIT in lung tissue. In addition, radio high-performance liquid chromatography (radio-HPLC) with tandem mass spectrometry (LC-MS/MS) was employed for metabolite profiling and identification. Notably, around 28% of the radiolabel was retained in tissue after the extraction step, suggesting covalent binding of CMIT/MIT and their metabolites with pulmonary biomolecules. This observation demonstrates the propensity of the electrophilic isothiazolinone ring in CMIT/MIT to undergo chemical interactions with biothiols in proteins and enzymes, fostering irreversible alterations of biomolecules. Such accumulations of transformations could result in direct toxicity at both cellular and organ levels. Additionally, the detection of metabolites, including a MIT dimer conjugated with glutathione (GSH), as analyzed by mass spectrometry indicates the possible reduction of cellular GSH levels and subsequent oxidative stress. This investigation offers an in-depth insight into the toxic mechanisms of CMIT/MIT, underlying their capability to engage in complex formations with biomacromolecules and induce pronounced respiratory toxicity. These results highlight the imperative for stringent safety assessments of these chemicals, advocating for improved public health and safety measures in the use of chemicals., 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 © 2024 Elsevier Ltd. All rights reserved.)

Although unregulated aliphatic disinfection byproducts (DBPs) had a much higher concentration and cytotoxicity than known aromatic DBPs, a recent study indicated that seven classes of regulated and unregulated priority DBPs (one and two-carbon-atom DBPs) just accounted for 16.2% of disinfected water cytotoxicity in the U.S., meaning some of the highly toxic aliphatic DBPs may be overlooked. Haloketones (HKs) are an essential class of priority DBPs with a 1-100 µg/L concentration in drinking water but lack cytotoxicity data. This study investigated the cytotoxicity of seven HKs using Chinese hamster ovary (CHO) cells. The order for cytotoxicity of HKs from most to least toxic was: 1,3-dichloroacetone (LC 50 : 1.0 ± 0.20 μM) ≈ 1,3-dibromoacetone (1.5 ± 0.19 μM) ≈ bromoacetone (1.9 ± 0.49 μM) > chloroacetone (4.3 ± 0.22 μM) > 1,1,3-trichloropropanone (6.6 ± 0.46 μM) > 1,1,1-trichloroacetone (222 ± 7.7 μM) > hexachloroacetone (3269 ± 344 μM). The cytotoxicity of HKs was higher than most regulated and priority aliphatic DBPs in mono-halogenated, di-halogenated, and tri-halogenated categories. A prediction model of HK cytotoxicity was developed based on the quantitative structure-activity relationship (QSAR), optimizing structures and computing descriptors with Gaussian 09 W. The average concentrations of HKs in representative drinking water samples from South Carolina (U.S.) and Suzhou (China) were 12.4 and 0.9 μg/L, respectively, accounting for 18.8% and 1.7% of their specific total DBPs measured (i.e. not TOX). For South Carolina drinking water, their contributions to total calculated additive cytotoxicity of aliphatic DBPs and overall drinking water cytotoxicity were 86.7% and 14.0%, respectively, demonstrating that HKs are an essential class of overlooked DBPs with a high contribution to drinking water cytotoxicity. Our study can help to explain the conflict that why regulated and priority DBPs (except HKs) just accounted for 16% of chlorinated drinking water cytotoxicity even enough they had much higher concentration and cytotoxicity than known aromatic DBPs., 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 © 2024 Elsevier Ltd. All rights reserved.)

Marine biofouling remains a huge concern for maritime industries and for environmental health. Although the current biocide-based antifouling coatings can prevent marine biofouling, their use has been associated with toxicity for the marine environment, being urgent to find sustainable alternatives. Previously, our research group has identified a prenylated chalcone (1) with promising antifouling activity against the settlement of larvae of the macrofouling species Mytilus galloprovincialis (EC 50 = 16.48 µM and LC 50 > 200 µM) and lower ecotoxicity when compared to Econea®, a commercial antifouling agent in use. Herein, a series of chalcone 1 analogues were designed and synthesized in order to obtain optimized antifouling compounds with improved potency while maintaining low ecotoxicity. Compounds 8, 15, 24, and 27 showed promising antifouling activity against the settlement of M. galloprovincialis larvae, being dihydrochalcone 27 the most potent. The effect of compound 24 was associated with the inhibition of acetylcholinesterase activity. Among the synthesized compounds, compound 24 also showed potent complementary activity against Navicula sp. (EC 50 = 4.86 µM), similarly to the lead chalcone 1 (EC 50 = 6.75 µM). Regarding the structure-activity relationship, the overall results demonstrate that the substitution of the chalcone of the lead compound 1 by a dihydrochalcone scaffold resulted in an optimized potency against the settlement of mussel larvae. Marine polyurethane (PU)-based coatings containing the best performed compound concerning anti-settlement activity (dihydrochalcone 27) were prepared, and mussel larvae adherence was reduced compared to control PU coatings., 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 © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Recently, a new group of halopyridinol disinfection byproducts (DBPs) was reported in drinking water. The in vivo developmental and acute toxicity assays have shown that they were more toxic than a few commonly known aliphatic DBPs such as bromoform and iodoacetic acid. However, many pyridinol DBPs with the same main structures but different halogen substitutions were still unknown due to complicated water quality conditions and various disinfection methods applied in drinking water treatment plants. Studies on their transformation mechanisms in drinking water disinfection were quite limited. In this study, comprehensive detection and identification of halopyridinols were conducted, and five new halopyridinols were first reported, including 2-chloro-3-pyridinol, 2,6-dichloro-3-pyridinol, 2-bromo-5-chloro-3-pyridinol, 2,4,6-trichloro-3-pyridinol and 2,5,6-trichloro-3-pyridinol. Formation conditions and mechanisms of the halopyridinols were explored, and results showed that chlorination promoted their formation compared with chloramination. Halopyridinols were intermediate DBPs that could undergo further transformation/degradation with increasing contact time, disinfectant dose, bromide concentration, and pH. The in vitro cytotoxicity of the halopyridinols was evaluated using human hepatocellular carcinoma cells. Results showed that the cytotoxicity of 3,5,6-trichloro-2-pyridinol was the highest (EC 50 = 474.3 μM), which was 13.0 and 1.6 times higher than that of 2-bromo-3-pyridinol (EC 50 = 6214.5 μM) and tribromomethane (EC 50 = 753.6 μM), respectively., 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 © 2024 Elsevier B.V. All rights reserved.)

Urban ecosystems are subjected to multiple anthropogenic stresses, which impact aquatic communities. Artificial light at night (ALAN) for instance can significantly alter the composition of algal communities as well as the photosynthetic cycles of autotrophic organisms, possibly leading to cellular oxidative stress. The combined effects of ALAN and chemical contamination could increase oxidative impacts in aquatic primary producers, although such combined effects remain insufficiently explored. To address this knowledge gap, a one-month experimental approach was implemented under controlled conditions to elucidate effects of ALAN and dodecylbenzyldimethylammonium chloride (DDBAC) on aquatic biofilms. DDBAC is a biocide commonly used in virucidal products, and is found in urban aquatic ecosystems. The bioaccumulation of DDBAC in biofilms exposed or not to ALAN was analyzed. The responses of taxonomic composition, photosynthetic activity, and fatty acid composition of biofilms were examined. The results indicate that ALAN negatively affects photosynthetic yield and chlorophyll production of biofilms. Additionally, exposure to DDBAC at environmental concentrations induces lipid peroxidation, with an increase of oxylipins. This experimental study provides first insights on the consequences of ALAN and DDBAC for aquatic ecosystems. It also opens avenues for the identification of new biomarkers that could be used to monitor urban pollution impacts in natural environments., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The gut microbiome is crucial in maintaining fish health homeostasis. Disinfectants can kill important pathogens and disinfect fish eggs, yet their effect on the immune pathways and intestinal microbiome in healthy fish remains unknown. In this study, we investigated the effects of two disinfectants on the transcriptome profiles, immunological response, and gut microbiota dynamics of grass carp over a four-week trial. In particular, aquatic water was disinfected with 80 μg/L glutaraldehyde or 50 μg/L povidone-iodine. We found that glutaraldehyde and povidone-iodine induced gut antioxidant system and depressed the function of grass carp digestive enzymes. The results of the 16S rDNA high-throughput sequencing identified a reduction in the diversity of grass carp gut microbiota following the disinfectant treatment. Moreover, transcriptome profiling revealed that disinfectant exposure altered the immune-related pathways of grass carp and inhibited the expression of inflammation and tight junction related genes. Finally, the histopathological observation and apoptosis detection results suggested that the long-term diet of disinfectant destroyed intestinal structural integrity and promoted apoptosis. In conclusion, long-term exposure to disinfectants was observed to reduce oxidation resistance, suppress the immune response, dysbiosis of the intestinal flora, and resulted in increasing the apoptosis in intestinal of grass carp., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objective: To clarify the effect of iodoacetic acid(IAA) on the blood system and electrolyte balance, hence further study the intrinsic relation of blood routine parameters and electrolyte levels, major hematological toxicity effects and their pattern after IAA treatment., Methods: Forty-eight 21-day-old male SPF grade Sprague-Dawley(SD) rats were gavaged with 0, 6.25, 12.5 and 25 mg/kg IAA for 31 days. After detections of blood routine and plasma inorganic ion levels, Spearman correlation coefficients were performed to evaluate their relationship. Changes in ferritin, transferrin, hepcidin, C-reactive protein and glyceraldehyde-3-phosphate dehydrogenase(GAPDH) were assessed by enzyme-linked immunosorbent assays. The EDock bioinformatics tool was applied to docking model of IAA and GAPDH., Results: Compared to the control, high-dose IAA exposure had obvious inhibition effect on rat leukocytes with the total number declined by 51.12%, and neutrophils were particularly sensitive to IAA with the number reduced by 73.66%(P&lt;0.01), and rat erythrocytes exhibited a small cell low pigment effect with hemoglobin and hematocrit decreased by 8.60% and 8.70%, respectively(P&lt;0.05). But IAA had little effects on the platelet. Plasma iron, phosphorus, zinc and potassium levels were repressed significantly, while chlorine, sodium and magnesium levels were elevated obviously through IAA exposure. However, plasma calcium levels were hardly affected by IAA. In comparison with the control, iron levels declined by 67.09%, whereas magnesium levels increased by 131.82% in the high-dose group(P&lt;0.01). Overall, correlation analyses uncovered that plasma iron metabolism was most strongly and positively correlated with levels of leukocyte, erythrocyte and platelet system parameters after IAA exposure, and the correlation coefficients of leukocyte number, mean hemoglobin content and mean erythrocyte volume were 0.637, 0.410 and 0.365, respectively(P&lt;0.05). Compared to the control, in the high-dose IAA group, the plasma content of C-reactive protein was significantly upregulated by 13.30%(P&lt;0.05), and plasma levels of transferrin and ferromodulin were also respectively elevated by 12.73% and 11.02%(P&lt;0.05). But plasma levels of ferritin and GAPDH did not differ between groups. The docking model exhibited that IAA could bind to the 150 Cys active site of rat GAPDH did., Conclusion: IAA not only had toxic effects on rat leukocytes and the plasma electrolyte balance, but also generated inflammation and iron deficiency, leading to smaller erythrocytes and lower pigment.

Aquatic ecosystems and their communities are exposed to numerous stressors of various natures (chemical and physical), whose impacts are often poorly documented. In urban areas, the use of biocides such as dodecyldimethylbenzylammonium chloride (DDBAC) and their subsequent release in wastewater result in their transfer to urban aquatic ecosystems. DDBAC is known to be toxic to most aquatic organisms. Artificial light at night (ALAN) is another stressor that is increasing globally, especially in urban areas. ALAN may have a negative impact on photosynthetic cycles of periphytic biofilms, which in turn may result in changes in their metabolic functioning. Moreover, studies suggest that exposure to artificial light could increase the biocidal effect of DDBAC on biofilms. The present study investigates the individual and combined effects of DDBAC and/or ALAN on the functioning and structure of photosynthetic biofilms. We exposed biofilms in artificial channels to a nominal concentration of 30 mg.L -1 of DDBAC and/or ALAN for 10 days. ALAN modified DDBAC exposure, decreasing concentrations in the water but not accumulation in biofilms. DDBAC had negative impacts on biofilm functioning and structure. Photosynthetic activity was inhibited by > 90% after 2 days of exposure, compared to the controls, and did not recover over the duration of the experiment. Biofilm composition was also impacted, with a marked decrease in green algae and the disappearance of microfauna under DDBAC exposure. The integrity of algal cells was compromised where DDBAC exposure altered the chloroplasts and chlorophyll content. Impacts on autotrophs were also observed through a shift in lipid profiles, in particular a strong decrease in glycolipid content was noted. We found no significant interactive effect of ALAN and DDBAC on the studied endpoints., 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 © 2024 Elsevier B.V. All rights reserved.)

While wastewater and paint particles discharged from the in-water cleaning process of ship hulls are consistently released into benthic ecosystems, their hazardous effects on non-target animals remain largely unclear. In this study, we provide evidence on acute harmful effects of hull cleaning wastewater in marine polychaete Perinereis aibuhitensis by analyzing physiological and biochemical parameters such as survival, burrowing activity, and oxidative status. Raw wastewater samples were collected during ship hull cleaning processes in the field. Two wastewater samples for the exposure experiment were prepared in the laboratory: 1) mechanically filtered in the in-water cleaning system (MF) and 2) additionally filtered with a 0.45 μm filter in the laboratory (LF). These wastewater samples contained high concentrations of metals (zinc and copper) and metal-based booster biocides (copper pyrithione and zinc pyrithione) compared to those analyzed in seawater. Polycheates were exposed to different concentrations of the two wastewater samples for 96 h. Higher mortality was observed in response to MF compared to LF-exposed polychaetes. Both wastewater samples dose-dependently decreased burrowing activity and AChE activity. Drastic oxidative stress was observed in response to the two wastewater samples. MDA levels were significantly increased by MF and LF samples. Significant GSH depletion was observed with MF exposure, while increased and decreased GSH contents were observed in LF-exposed polychaetes. Enzymatic activities of antioxidant components, catalase, superoxide dismutase, and glutathione S-transferase were significantly modulated by both wastewater samples. These results indicate that even filtered hull cleaning wastewater can have deleterious effects on the health status of polychaetes., 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 © 2024 Elsevier Inc. All rights reserved.)

The evaluation of the ecotoxicological effects of the effluent after treatment with peracetic acid is relevant to help establish reference concentrations for the disinfection process and waste recovery. Therefore, the objective of this work was to evaluate the ecotoxicity of effluent from a bovine slaughterhouse treated with peracetic acid on Girardia tigrina. The toxicity bioassays for planaria were the acute test (LC 50 ) and chronic assays: locomotion, regeneration, reproduction and fertility. The results showed that the effluent treated with peracetic acid showed less toxicity than the effluent without application of peracetic acid. The effluent after peracetic acid application showed a chronic toxic effect in the reduction of locomotor speed in all studied disinfectant concentrations (0.8, 1.6, 3.3 and 6.6 μg L -1 of peracetic acid) and a delay in the formation of G. tigrina photoreceptors at the concentration of 6.6 μg L -1 of peracetic acid. Peracetic acid concentrations of 0.8, 1.6 and 3.3 μg L -1 were not toxic for blastema regeneration, photoreceptor and auricle formation, fecundity and fertility. In addition, this study assists in defining doses of peracetic acid to be recommended in order to ensure the wastewater disinfection process without causing harm to aquatic organisms., 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 © 2024 Elsevier Inc. All rights reserved.)

Dissolved black carbon (DBC), the soluble component of black carbon, which mainly comes from the incomplete combustion of fossil fuels or biomass, is widely spread in source water and significantly contributes to the formation of dissolved organic matter (DOM). However, the origin of DBC in different types of source water in China has not been well studied, as well as its subsequent transformation and toxicity contribution during disinfection of source water DOM by chlor(am)ine. In this study, DBC from 17 different source water in East China at different seasons was collected. The δ 13 C compositions indicated that straw burning was the main origin of DBC in source water. After simulated chlor(am)ination of DBC, 5 categories of aliphatic disinfection byproducts (DBPs) including trihalomethanes, haloacetic acids, haloacetonitriles, haloketones, halonitromethanes and 6 categories of aromatic DBPs including halophenols, halonitrophenols, halohydroxybenzaldehyde, halohydroxybenzoic acid, halobenzoquinones and haloaniline were detected. Compared with chlorination of DBC, higher levels of nitrogenous DBPs and aromatic DBPs were generated during chloramination. Detected DBPs accounted for 42 % of total organic halogen. What's more, Chinese hamster ovary cells cytotoxicity tests showed that the cytotoxicity of DBPs formed by chlor(am)ination of DBC was 4 times higher than that by chlor(am)ination of DOM. Haloacetonitriles contributed to the highest cytotoxicity in the chloramination of DBC, and haloacetic acids contributed to the highest cytotoxicity in chlorination. 67 % of the total cytotoxicity attributed to the undetected DBPs. As a result, DBPs generated from DBC contributed to 11.7 % of the total cytotoxicity in the chlor(am)ination of the source water DOM although DBC only took up 2 % of DOC in the source water. Results obtained from this study systematically revealed the DBPs formation from DBC and their potential cytotoxicity contribution in the chlor(am)ination of source water DOM, which should not be ignored in drinking water treatment., 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 © 2024 Elsevier B.V. All rights reserved.)

Many antibiotic disinfection byproducts have been detected but their toxicity has not been evaluated adequately. In this report, the chlorination reaction kinetics of five common sulfamides (SAs), reaction intermediates and their toxicity were investigated. Chlorination of sulfapyridine (SPD), sulfamethazine (SMT), sulfathiazole (STZ), and sulfisoxazole (SIZ) followed the second-order kinetics, and were degraded completely within 10 min. A large number of reaction intermediates were deteced by LC-MS, among which a total of 16 intermediates were detected for the first time. Toxicity of the five SAs chlorination solutions was evaluated separately by examining their effects on the growth rate of S. salivarius K12, a commensal bacterium in the human digestive system. After 30 min chlorination, solutions of SMT, STZ and sulfadiazine (SDZ) each exhibited severe toxicity by inhibiting the bacteria growth completely, whereas the inhibition was only 50 % and 20  % by SIZ and SPD respectively. Based on the comparison between toxicity test results and mass spectra, three SA chlorination intermediates, m/z 187.2 (C 10 H 10 N 4 ), m/z 287.2 (C 9 H 7 N 3 O 4 S 2 ) and m/z 215 (C 7 H 10 N 4 O 2 S/C 12 H 14 N 4 ) were proposed to be the primary toxicants in the chlorination products. Our study demonstrated the power of combined approach of chemical analysis and toxicity testing in identifying toxic disinfection byproducts, and highlighted the ne ed for more research on the toxicity evaluation and risk assessment of antibiotic disinfection byproducts., 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 © 2024 Elsevier Ltd. All rights reserved.)

Haloacetaldehyde disinfection by-products (HAL-DBPs) are among the top three unregulated DBPs found in drinking water. The cytotoxicity and genotoxicity of HALs are much higher than that of the regulated trihalomethanes and haloacetic acids. Previous studies have mainly focused on the toxic effects of single HAL, with few examining the toxic effects of mixed exposures to HALs. The study aimed to observe the effects of mixed exposures of 1∼1000X the realistic level of HALs on the hepatotoxicity and lipid metabolism of C57BL/6J mice, based on the component and concentration of HALs detected in the finished water of Shanghai. Exposure to realistic levels of HALs led to a significant increase in phosphorated acetyl CoA carboxylase 1 (p-ACC1) in the hepatic de novo lipogenesis (DNL) pathway. Additionally, exposure to 100X realistic levels of HALs resulted in significant alterations to key enzymes of DNL pathway, including ACC1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2), as well as key proteins of lipid disposal such as carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator activated receptor α (PPARα). Exposure to 1000X realistic levels of HALs significantly increased hepatic and serum triglyceride levels, as well as total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase levels, significantly decreased high-density lipoprotein. Meanwhile, histopathological analysis demonstrated that HALs exacerbated tissue vacuolization and inflammatory cell infiltration in mice livers, which showed the typical phenotypes of non-alcoholic fatty liver disease (NAFLD). These results suggested that the HALs mixture is a critical risk factor for NAFLD and is significantly highly toxic to C57BL/6J mice., 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 © 2024 Elsevier Ltd. All rights reserved.)

Halophenylacetamides (HPAcAms) have been identified as a new group of nitrogenous aromatic disinfection byproducts (DBPs) in drinking water, but the toxicity mechanisms associated with HPAcAms remain almost completely unknown. In this work, the cytotoxicity of HPAcAms in human hepatoma (HepG2) cells was evaluated, intracellular oxidative stress/damage levels were analyzed, their binding interactions with antioxidative enzyme were explored, and a quantitative structure-activity relationship (QSAR) model was established. Results indicated that the EC 50 values of HPAcAms ranged from 2353 μM to 9780 μM, and the isomeric structure as well as the type and number of halogen substitutions could obviously induce the change in the cytotoxicity of HPAcAms. Upon exposure to 2-(3,4-dichlorophenyl)acetamide (3,4-DCPAcAm), various important biomarkers linked to oxidative stress and damage, such as reactive oxygen species, 8‑hydroxy-2-deoxyguanosine, and cell apoptosis, exhibited a significant increase in a dose-dependent manner. Moreover, 3,4-DCPAcAm could directly bind with Cu/Zn-superoxide dismutase and induce the alterations in the structure and activity, and the formation of complexes was predominantly influenced by the van der Waals force and hydrogen bonding. The QSAR model supported that the nucleophilic reactivity as well as the molecular compactness might be highly important in their cytotoxicity mechanisms in HepG2 cells, and 2-(2,4-dibromophenyl)acetamide and 2-(3,4-dibromophenyl)acetamide deserved particular attention in future studies due to the relatively higher predicted cytotoxicity. This study provided the first comprehensive investigation on the cytotoxicity mechanisms of HPAcAm DBPs., 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 © 2024 Elsevier Ltd. All rights reserved.)

So far, about 130 disinfection by-products (DBPs) and several DBPs-groups have had their potential endocrine-disrupting effects tested on some endocrine endpoints. However, it is still not clear which specific DBPs, DBPs-groups/subgroups may be the most toxic substances or groups/subgroups for any given endocrine endpoint. In this study, we attempt to address this issue. First, a list of relevant DBPs was updated, and 1187 DBPs belonging to 4 main-groups (aliphatic, aromatic, alicyclic, heterocyclic) and 84 subgroups were described. Then, the high-priority endocrine endpoints, DBPs-groups/subgroups, and specific DBPs were determined from 18 endpoints, 4 main-groups, 84 subgroups, and 1187 specific DBPs by a virtual-screening method. The results demonstrate that most of DBPs could not disturb the endocrine endpoints in question because the proportion of active compounds associated with the endocrine endpoints ranged from 0 (human thyroid receptor beta) to 32% (human transthyretin (hTTR)). All the endpoints with a proportion of active compounds greater than 10% belonged to the thyroid system, highlighting that the potential disrupting effects of DBPs on the thyroid system should be given more attention. The aromatic and alicyclic DBPs may have higher priority than that of aliphatic and heterocyclic DBPs by considering the activity rate and potential for disrupting effects. There were 2 (halophenols and estrogen DBPs), 12, and 24 subgroups that belonged to high, moderate, and low priority classes, respectively. For individual DBPs, there were 23 (2%), 193 (16%), and 971 (82%) DBPs belonging to the high, moderate, and low priority groups, respectively. Lastly, the hTTR binding affinity of 4 DBPs was determined by an in vitro assay and all the tested DBPs exhibited dose-dependent binding potency with hTTR, which was consistent with the predicted result. Thus, more efforts should be performed to reveal the potential endocrine disruption of those high research-priority main-groups, subgroups, and individual DBPs., 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 © 2024 Elsevier Ltd. All rights reserved.)

Drinking water disinfection can result in the formation disinfection byproducts (DBPs, > 700 have been identified to date), many of them are reportedly cytotoxic, genotoxic, or developmentally toxic. Analyzing the toxicity levels of these contaminants experimentally is challenging, however, a predictive model could rapidly and effectively assess their toxicity. In this study, machine learning models were developed to predict DBP cytotoxicity based on their chemical information and exposure experiments. The Random Forest model achieved the best performance (coefficient of determination of 0.62 and root mean square error of 0.63) among all the algorithms screened. Also, the results of a probabilistic model demonstrated reliable model predictions. According to the model interpretation, halogen atoms are the most prominent features for DBP cytotoxicity compared to other chemical substructures. The presence of iodine and bromine is associated with increased cytotoxicity levels, while the presence of chlorine is linked to a reduction in cytotoxicity levels. Other factors including chemical substructures (CC, N, CN, and 6-member ring), cell line, and exposure duration can significantly affect the cytotoxicity of DBPs. The similarity calculation indicated that the model has a large applicability domain and can provide reliable predictions for DBPs with unknown cytotoxicity. Finally, this study showed the effectiveness of data augmentation in the scenario of data scarcity., Competing Interests: Declaration of Competing Interest The authors declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Glutaraldehyde-Didecyldimethylammonium bromides (GDs) has been frequently and widely employed in livestock and poultry breeding farms to avoid epidemics such as African swine fever, but its long-term effect on the active sludge microorganisms of the receiving wastewater treatment plant was keep unclear. Four simulation systems were built here to explore the performance of aerobic activated sludge with the long-term exposure of GDs and its mechanism by analyzing water qualities, resistance genes, extracellular polymeric substances and microbial community structure. The results showed that the removal rates of COD Cr and ammonia nitrogen decreased with the exposure concentration of GDs increasing. It is worth noting that long-term exposure to GDs can induce the horizontal transfer and coordinated expression of a large number of resistance genes, such as qacE, sul1, tetx, and int1, in drug-resistant microorganisms. Additionally, it promotes the secretion of more extracellular proteins, including arginine, forming a "barrier-like" protection. Therefore, long-term exposure to disinfectants can alter the treatment capacity of activated sludge receiving systems, and the abundance of resistance genes generated through horizontal transfer and coordinated expression by drug-resistant microorganisms does pose a significant threat to ecosystems and health. It is recommended to develop effective pretreatment methods to eliminate disinfectants., Competing Interests: Declaration of Competing Interest We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Intensified sanitation practices amid the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak might result in the increased release of chloramine disinfectants into surface water, significantly promoting the formation of nitrosamine disinfection by-products (DBPs) in drinking water. Unfortunately, these nitrosamine DBPs exhibit significant genotoxic, carcinogenic, and mutagenic properties, whereas chlorinating disinfectants remain in global practice. The current review provides valuable insights into the occurrence, identification, contamination status, exposure limits, and toxicity of the new unregulated disinfection by-products (nitrosamine DBPs) in drinking water. As a result, concentrations of nitrosamine DBPs far exceed allowable limits in drinking water, and prolonged exposure has the potential to cause metabolic disorders, a critical step in tumor initiation and progression. Importantly, based on recent research, we have concluded the role of nitrosamines DBPs in different metabolic pathways. Remarkably, nitrosamine DBPs can induce chronic inflammation and initiate tumors by activating sphingolipid and polyunsaturated fatty acid metabolism. Regarding amino acid and nucleotide metabolism, nitrosamine DBPs can inhibit tryptophan metabolism and de novo nucleotide synthesis. Moreover, inhibition of de novo nucleotide synthesis fails to repair DNA damage induced by nitrosamines. Additionally, the accumulation of lactate induced by nitrosamine DBPs may act as a pivotal signaling molecule in communication within the tumor microenvironment. However, with the advancement of tumor metabolomics, understanding the role of nitrosamine DBPs in causing cancer by inducing metabolic abnormalities significantly lags behind, and specific mechanisms of toxic effects are not clearly defined. Urgently, further studies exploring this promising area are needed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Disinfectants and antibiotics are widely used for the prevention and control of bacterial infectious diseases. Frequent disinfection is thought to exacerbate antibiotic resistance. However, little is known about how disinfectants and antibiotics co-induce changes in the soil antibiotic resistance genes (ARGs). This study determined the ARG profiles and bacterial community dynamics between unamended soil and manure-amended soil exposed to benzalkonium chloride (C 12 ) (BC, 10 mg kg -1 ) disinfectant and sulfamethazine (SMZ, 1 mg kg -1 ), using high-throughput quantitative PCR and 16 S rRNA gene sequencing. Manure application enriched the soil in terms of ARGs abundance and diversity, which synergistically amplified the co-selection effect of BC and SMZ on soil antibiotic resistome. Compared with the control treatment, BC and SMZ exposure had a smaller impact on the bacterial infectious diseases and antimicrobial resistance-related functions in manure-amended soil, in which bacterial communities with greater tolerance to antimicrobial substances were constructed. Manure application increased the proportion of rank I ARGs and potential human pathogenic bacteria, while BC and SMZ exposure increased the drug-resistant pathogens transmission risk. This study validated that BC and SMZ aggravated the antimicrobial resistance under manure application, providing a reference for managing the spread risk of antimicrobial resistance in agricultural activities., 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 © 2024 Elsevier B.V. All rights reserved.)

The use of disinfectants, such as Sodium Dodecylbenzene Sulfonic acid salt (SDBS), has grown since the SARS-CoV-2 pandemic, with environmentally unknown consequences. The present study analyzed SDBS effects in the fish species Danio rerio, using a combination of biomarkers. Our data reported that larvae had their total locomotor activity increased when exposed to 1 mg/L of SDBS, but this parameter was decreased in fish exposed to 5 mg/L. A significant increment of erratic movements was reported in fish exposed to 1 and 5 mg/L of SDBS. These concentrations inhibited CYP1A1/CYP1A2, and of GSTs inhibition, suggesting SDBS is not preferentially biotransformed by these routes. Results concerning the antioxidant defense biomarkers (CAT and GPx) showed no straightforward pattern, suggesting SDBS exposure may have resulted in changes in redox balance. Finally, acetylcholinesterase activity increased. In summary, increased use of SDBS in a near future may result in deleterious effects in environmentally exposed fish., 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 © 2024 Elsevier B.V. All rights reserved.)

Sodium dichloroisocyanurate (NaDCC, C 3 Cl 2 N 3 NaO 3 ) is a solid chlorine-containing product that is widely used as a disinfectant in living environments, which has potential toxic effects on human and rats. Phascolosoma esculenta is a species native to the southeast coast of China and can be used as an indicator organism. In the present study, 150 P. esculenta were used to determine the LC50 of NaDCC for P. esculenta, then 100 P. esculenta were used to analysis the change of histopathology, oxidative stress and transcriptome after NaDCC exposure. The results showed that the LC50 of NaDCC for 48 h was 50 mg/L. NaDCC stress induced pathological events in P. esculenta, including blisters, intestinal structural damage and epithelial cell ruptured or even loss. The highest and lowest intestinal activity of superoxide dismutase in individual survivors was detected at 12 h and 72 h, respectively. Malondialdehyde levels in the intestine declined gradually from 3 h and increased at 9 h, and peaked at 12 h. Total antioxidant capacity declined at 3 h and dropped below the levels of control group after 9 h. Transcriptome sequencing analysis yielded a total of 48.65 Gb of clean data. A total of 34,759 new genes were found including 957 differentially expressed genes (DEGs). The DEGs were significantly enriched in ferroptosis, response to chemicals, response to stress, immune system, ion transport, cell death, oxidation-reduction, cellular homeostasis, protein ubiquitination, and protein neddylation. Additionally, the levels of detoxification enzymes, such as glutathione-S-transferase, cytochrome P450, ABC, UDP-glycosyltransferase and SLC transporters of endogenous and exogenous solutes were significantly changed. Overall, the results provide reference for reasonable use of disinfectants during farming, and also provide insight into the mechanisms related to NaDCC toxicity in P. esculenta., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Inc.)

Mouse macrophages and human blood cells exposed to very high levels of three trihalophenols showed changes in RNA methylation, pointing to one mechanism by which disinfection by-products may harm health, even as disinfection protects it in other ways.

Complex mixtures of disinfection by-products (DBPs) are present in disinfected waters, but their mixture toxicity has been rarely described. Apart from ingestion, DBP exposure can occur through inhalation, which may lead to respiratory effects in highly exposed individuals. However, the underlying biological mechanisms have yet to be elucidated. This study aimed to investigate the toxicity of a mixture of 10 DBPs, including haloacetic acids and haloaromatics, on human alveolar A549 cells by assessing their cytotoxicity, genotoxicity, and impact on the cell lipidome. A DBP mixture up to 50 μM slightly reduced cell viability, induced the generation of reactive oxygen species (ROS) up to 3.5-fold, and increased the frequency of micronuclei formation. Exposure to 50 μM DBP mixture led to a significant accumulation of triacylglycerides and a decrease of diacylglycerides and phosphatidylcholines in A549 cells. Lipidomic profiling of extracellular vesicles (EVs) released in the culture medium revealed a marked increase in cholesterol esters, sphingomyelins, and other membrane lipids. Overall, these alterations in the lipidome of cells and EVs may indicate a disruption of lipid homeostasis, and thus, potentially contribute to the respiratory effects associated with DBP exposure., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Quaternary ammonium compounds (QACs) are commonly used as disinfectants for industrial, medical, and residential applications. However, adverse health outcomes have been reported. Therefore, biocompatible disinfectants must be developed to reduce these adverse effects. In this context, QACs with various alkyl chain lengths (C12-C18) were synthesized by reacting QACs with the counterion silane. The antimicrobial activities of the novel compounds against four strains of microorganisms were assessed. Several in vivo assays were conducted on Drosophila melanogaster to determine the toxicological outcomes of Si-QACs, followed by computational analyses (molecular docking, simulation, and prediction of skin sensitization). The in vivo results were combined using a cheminformatics approach to understand the descriptors responsible for the safety of Si-QAC. Si-QAC-2 was active against all tested bacteria, with minimal inhibitory concentrations ranging from 13.65 to 436.74 ppm. Drosophila exposed to Si-QAC-2 have moderate-to-low toxicological outcomes. The molecular weight, hydrophobicity/lipophilicity, and electron diffraction properties were identified as crucial descriptors for ensuring the safety of the Si-QACs. Furthermore, Si-QAC-2 exhibited good stability and notable antiviral potential with no signs of skin sensitization. Overall, Si-QAC-2 (C14) has the potential to be a novel disinfectant., 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 © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)