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Since the banning of tributyltin, the addition of inorganic (metal oxides) and organic (pesticides, herbicides) biocides in antifouling paint has represented an unavoidable step to counteract biofouling and the resulting biodeterioration of submerged surfaces. Therefore, the development of new methods that balance antifouling efficacy with environmental impact has become a topic of great importance. Among several proposed strategies, natural extracts may represent one of the most suitable alternatives to the widely used toxic biocides. Posidonia oceanica is one of the most representative organisms of the Mediterranean Sea and contains hundreds of bioactive compounds. In this study, we prepared, characterized, and assessed a hydroalcoholic extract of P. oceanica and then compared it to three model species. Together, these four species belong to relevant groups of biofoulers: bacteria (Aliivibrio fischeri), diatoms (Phaeodactylum tricornutum), and serpulid polychaetes (Ficopomatus enigmaticus). We also added the same P. oceanica extract to a PDMS-based coating formula. We tested this coating agent with Navicula salinicola and Ficopomatus enigmaticus to evaluate both its biocidal performance and its antifouling properties. Our results indicate that our P. oceanica extract provides suitable levels of protection against all the tested organisms and significantly reduces adhesion of N. salinicola cells and facilitates their release in low-intensity waterflows., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Nitrogenous disinfection byproducts (N-DBPs), such as halocetamides (HAcAms), haloacetonitriles (HANs) and halonitromethanes (HNMs), are emerging DBPs in drinking water. They are more toxic than currently regulated DBPs, attracting more attention to their toxic effects and mechanism. In this study, human embryonic kidney (HEK) 293T cells were employed to explore the cytotoxicity of 29 N-DBPs. The influence of molecular structures and different halogenations on cytotoxicity has been comparatively analyzed. As toxicity is the downstream of chemico-biological interactions, the thiol reactivity of 29 N-DBPs has thus been evaluated by using glutathione (GSH) as a model nucleophile, which is the most prevalent cellular thiol and acts as an antioxidant to protect cells by detoxifying electrophilic compounds. Results show that the cytotoxicity of N-DBPs follows by the order of HAcAms > HANs > HNMs, which is different from their reactivity with GSH (the median of k GSH ranks as HNMs > HAcAms > HANs). However, a significant correlation (p < 0.001) between log k GSH and log IC 50 (concentration causing 50% inhibition) has been respectively observed for HAcAms and HANs subset and HNMs subset, indicating such chemical reaction is a probable trigger for these DBPs to result in cytotoxicity. Finally, two separate quantitative structure - activity relationship (QSAR) models based on HANs & HAcAms subset and HNMs subset have been developed for estimating IC 50 values. The good statistical performance makes the models possible to quickly and accurately predict IC 50 values of other N-DBPs, providing basic data for their health risk assessment and greatly reducing in vivo and in vitro experiments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Humidifier disinfectant (HD) is a causative agent of atypical lung injury reported in 2011 in South Korea, and various diseases caused by HD after exposure cessation have been reported to date. However, there is limited research on most of the reported diseases in terms of their association with HD exposure, and information on the progression of diseases caused by HD exposure is also limited. Therefore, we investigated the effects of HD inhalation on the body in rats. Rats were exposed to 0.15, 0.50, and 1.60 mg/m 3 polyhexamethylene guanidine-phosphate (PHMG-p), which is the major component of HDs and most closely related to HD-associated lung injury. We conducted necropsy four times during the recovery period (0, 4, 12, and 24 weeks) and evaluated general systemic toxicities. There were significant changes in the mortality rate, body weight, and food consumption in the PHMG-p-exposed groups. Hematology revealed changes in hemoglobin level, hematocrit, red blood cell, reticulocyte, and white blood cell counts until 12 weeks of the recovery period. PHMG-p induced a delay in prothrombin time until 12 weeks of the recovery period. The aspartate aminotransferase, alanine aminotransferase, total bilirubin, and triglyceride levels were higher in the PHMG-p-exposed groups than in the control group at week 4 of the recovery period, and these parameters normalized after 12 weeks of the recovery period. Histopathological examination in PHMG-p exposed groups revealed several changes in the lungs, including the presence of alveolar macrophages, chronic inflammation, squamous metaplasia, alveolar emphysema, and pulmonary fibrosis. The severity of these symptoms was maintained or exacerbated till 24 weeks. Overall, PHMG-p inhalation can induce irreversible histological changes in the lungs and cause various types of damage throughout the body, even after exposure ends., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Benzisothiazolinone (BIT), one of the most widely used antimicrobial agents in consumer products, has frequently been detected in the water environment. The present study was conducted to determine the adverse effects of BIT on the thyroid neuroendocrine system of zebrafish embryos/larvae. Rat pituitary (GH3) cell line was employed to support the underlying mechanism of thyroid hormone disrupting effects. Significant coagulation and hatching delay were observed in embryos exposed to 30 μg/L of BIT, which in turn remarkably decreased hatchability and larval survival. In BIT-exposed larvae, tshβ, tshr, and trh genes were significantly upregulated along with a decrease in thyroxine and triiodothyronine content, indicating that BIT decreased thyroid hormones and increased thyrotropin-releasing hormone and thyroid stimulating hormone secretion through a feedback circuit. The downregulation of trα and deio2 genes in the zebrafish larvae suggests the inhibition of thyroid hormone receptors and deiodination. Similar to the results in zebrafish, upregulation of tshβ and downregulation of trα, trβ, deio1, and deio2 genes were observed in GH3 cells. Our observations suggest that BIT can decrease the level of thyroid hormones by influencing central regulation, receptor binding, and deiodination., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Inhalation exposure to humidifier disinfectants has resulted to various types of health damages in Korea. To determine the epidemiological correlation necessary for presuming the legal causation, we aimed to develop a method to synthesize the entire evidence., Methods: Epidemiological and toxicological studies are systematically reviewed. Target health problems are selected by criteria such as frequent complaints of claimants. Relevant epidemiologic studies are reviewed and the risk of bias and confidence level of the total evidence are evaluated. Toxicological literature reviews are conducted on three lines of evidence including hazard information, animal studies, and mechanistic studies, considering the source-to-exposure-to-outcome continuum. The confidence level of the body of evidence is then translated into the toxicological evidence levels for the causality between humidifier disinfectant exposure and health effects. Finally, the levels of epidemiological and toxicological evidence are synthesized., Results: Under the Special Act revised in 2020, if the history of exposure and the disease occurred/worsened after exposure were approved, and the epidemiological correlation between the exposure and disease was verified, the legal causation is presumed unless the company proves the evidence against it. The epidemiological correlation can be verified through epidemiological investigations, health monitoring, cohort investigations and/or toxicological studies. It is not simply as statistical association as understood in judicial precedents, but a general causation established by the evidence as a whole, i.e., through weight-of-the-evidence approach., Conclusions: The weight-of-the-evidence approach differs from the conclusive single study approach and this systematic evidence integration can be used in presumption of causation.

Background: Polymethylmethacrylate (PMMA) is the most used material for the manufacturing of eye prostheses., Objectives: To investigate the cytotoxicity of different cleaning agents for ocular prostheses on human conjunctival cells., Material and Methods: Six groups of specimens were created (saline, soap, 4% chlorhexidine, hydrogen peroxide, 1% triclosan, and citronella oil). Three specimens were made for each disinfectant at each disinfection period (1, 7, 15, 30, 60, and 90 days), totaling 108 specimens. Thus, the specimens were disinfected, with different disinfectants, for different periods of time. After each disinfection process, the specimens were washed with sterile distilled water. A human conjunctival cell line was grown on the acrylic resin specimens and then cytotoxicity tests (MTT and Neutral Red (NR)) were performed. A negative control (untreated cell cultures) and positive control (Tween 20) were created. Two-way analysis of variance (ANOVA) and Bonferroni test were performed (p < 0.05)., Results: For the MTT and NR tests, when there was a significant difference between the disinfectant and negative control, the disinfectant generated a significant reduction in cell proliferation most of the time., Conclusions: All reductions in cell proliferation caused by the disinfectants were clinically acceptable. All disinfectants tested in this study were found to be non-cytotoxic to human conjunctival cells.

Boiling is a widely adopted household tap water treatment method because of its ability to inactivate chlorine-resistant pathogenic bacteria, and to reduce certain groups of disinfection byproducts (DBPs). From a more comprehensive point of view, this study revisited the effect of boiling on four groups of 17 aliphatic DBPs and six groups of 44 aromatic DBPs in both simulated chlorinated and chloraminated tap water samples, with a special focus on the changes of total organic halogen (TOX) and cytotoxicity. Results showed that the concentrations of aliphatic DBPs substantially decreased during boiling via volatilization (trihalomethanes and chloral hydrate) and hydrolysis (haloacetamides) in chlorinated and chloraminated tap water samples. The concentrations of aromatic DBPs during boiling generally followed an increasing trend due to decarboxylation of polycarboxylic precursors in chlorinated tap water samples, and showed a first increasing and then decreasing trend in chloraminated tap water samples. A sharp decreasing of TOX occurred in the heating process of tap water samples from room temperature to 100 °C, and a relatively gentle decreasing was kept in the prolonged boiling process till 5 min. The most abundant DBP group in the tap water samples without boiling was trihalomethanes, and was replaced by haloacetic acids with boiling for 5 min. Continuous boiling for 5 min substantially reduced the cytotoxicity of chlorinated and chloraminated water samples by 52.6% and 21.3%, respectively. Reduction of cytotoxicity matched well with the reduction of TOCl (r = 0.907, P < 0.01), TOBr (r = 0.885, P < 0.01) and TOX (r = 0.905, P < 0.01), suggesting that the cytotoxicity reduction during boiling was mainly ascribed to the reduction of halogenated DBPs. Therefore, boiling of tap water to 100 °C was strongly recommended to reduce the potential health risks induced by tap water ingestion., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

One of the impacts of the Coronavirus disease 2019 (COVID-19) pandemic has been a profound increase in the application amounts of disinfectants. Dodecyl dimethyl benzyl ammonium chloride (DDBAC) is a widely used disinfectant, yet its hazards to non-target species remain largely unknown. We are unaware of any studies assessing DDBAC's impacts on honeybee, a pollinator species that is a useful indicator of environmental pollution essential for many forms of agricultural production. Here, we assessed the potentially negative effects of DDBAC on honeybees. After conducting a formal toxicity evaluation of DDBAC on honeybee mortality, we detected an accumulation of DDBAC in the honeybee midgut. We subsequently studied the midgut tissues of honeybees exposed to sub-lethal concentrations of DDBAC: histopathological examination revealed damage to midgut tissue upon DDBAC exposure, microbiome analysis showed a decreased abundance of beneficial midgut microbiota, lipidomics analysis revealed a significant reduction in cell membrane phospholipids with known functions in signal transduction, and a transcriptome analysis detected altered expression of genes involved in calcium signaling pathways (that variously function in calcium absorption, muscle contraction, and neurotransmission). Thus, our study establishes that DDBAC impacts honeybee midgut functions at multiple levels. Our study represents an early warning about the hazards of DDBAC and appeals for the proper stewardship of DDBAC to ensure the protection of our ecological environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Methylisothiazolinone (MIT) and chloroxylenol (PCMX) are popular disinfectants often used in personal care products (PCPs). The unregulated discharge of these micropollutants into the environment, as well as the use of sewage sludge as fertilizer and reclaimed water in agriculture, poses a serious threat to ecosystems. However, research into their ecotoxicity towards nontarget organisms is very limited. In the present study, for the first time, the ecotoxicity of biocides to Pseudomonas putida, Pseudomonas moorei, Sphingomonas mali, and Bacillus subtilis was examined. The toxicity of MIT and PCMX was evaluated using the microdilution method, and their influence on the viability of bacterial cells was investigated by the AlamarBlue® test. The ability of the tested bacteria to form biofilms was examined by a microtiter plate assay. Intracellular reactive oxygen species (ROS) production was measured with CM-H2DCFDA. The effect of MIT and PCMX on phytohormone indole-3-acetic acid (IAA) production was determined by spectrophotometry and LC‒MS/MS techniques. The permeability of bacterial cell membranes was studied using the SYTOX Green assay. Changes in the phospholipid profile were analysed using LC‒MS/MS. The minimal inhibitory concentrations (MICs) values ranged from 3.907 to 15.625 mg L -1 for MIT and 62.5 to 250 mg L -1 for PCMX, indicating that MIT was more toxic. With increasing concentrations of MIT and PCMX, the cell viability, biofilm formation ability and phytohormone synthesis were maximally inhibited. Moreover, the growth of bacterial cell membrane permeability and a significantly increased content of ROS were observed, indicating that the exposure caused serious oxidative stress and homeostasis disorders. Additionally, modifications in the phospholipid profile were observed in response to the presence of sublethal concentrations of the chemicals. These results prove that the environmental threat posed by MIT and PCMX must be carefully monitored, especially as their use in PCPs is still growing., (© 2022. The Author(s).)

To combat unwanted fouling on immersed hulls, biocidal antifouling coatings are commonly applied to vessels trafficking the Baltic Sea. Here, the efficacy, environmental sustainability and market barriers of silicone foul-release coatings (FRCs) was assessed for this region to evaluate their viability as replacements for biocidal coatings. Coated panels were exposed statically over a 1 year period at three locations in the Baltic Sea region to assess the long-term performance of a biocide-free FRC and two copper coatings. The FRC was found to perform equally well or significantly better than the copper coatings. Even though most silicone FRCs on the market are biocide-free, a review of the literature regarding toxic effects and the identity and environmental fate of leachables shows that they may not be completely environmentally benign, simply for the lack of biocides. Nonetheless, FRCs are substantially less toxic compared to biocidal antifouling coatings and their use should be promoted., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Isothiazolinones biocides are water-soluble, low molecular weight, nitrogenous compounds widely used to prevent microbial growth in a variety of applications including personal care products and building façade materials. Because isothiazolinones from buildings wash off and enter stormwater, interactions with terrestrial plants may represent an important part of the environmental fate of these compounds ( e.g. , in green stormwater infrastructure). Using the model plant Arabidopsis thaliana grown hydroponically, we observed rapid (≥99% within 24 hours), plant-driven removal of four commonly used isothiazolinones: benzisothiazolinone (BIT), chloromethylisothiazolinone, methylisothiazolinone, and octylisothiazolinone. No significant differences in uptake rate occurred between the four compounds; therefore, BIT was used for further detailed investigation. BIT uptake by Arabidopsis was concentration-dependent in a manner that implicates transporter-mediated substrate inhibition. BIT uptake was also minimally impacted by multiple BIT spikes, suggesting constituently active uptake. BIT plant uptake rate was robust, unaffected by multiple inhibitors. We investigated plant metabolism as a relevant removal process. Proposed major metabolites that significantly increased in the BIT-exposure treatment compared to the control included: endogenous plant compounds nicotinic acid (confirmed with a reference standard) and phenylthioacetohydroximic acid, a possible amino acid-BIT conjugate, and two accurate masses of interest. Two of the compounds (phenylthioacetohydroximic acid and TP 470) were also present in increased amounts in the hydroponic medium after BIT exposure, possibly via plant excretion. Upregulation of endogenous plant compounds is environmentally significant because it demonstrates that BIT impacts plant biology. The rapid plant-driven isothiazolinone removal observed here indicates that plant-isothiazolinone processes could be relevant to the environmental fate of these stormwater compounds.

Glutaraldehyde (GA) has been cleared by the Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) as a high-level disinfectant for disinfecting heat-sensitive medical equipment in hospitals and healthcare facilities. Inhalation exposure to GA is known to cause respiratory irritation and sensitization in animals and humans. To reproduce some of the known in vivo effects elicited by GA, we used a liquid aerosol exposure system and evaluated the tissue responses in a human in vitro airway epithelial tissue model. The cultures were treated at the air interface with various concentrations of GA aerosols on five consecutive days and changes in tissue function and structure were evaluated at select timepoints during the treatment phase and after a 7-day recovery period. Exposure to GA aerosols caused oxidative stress, inhibition of ciliary beating frequency, aberrant mucin production, and disturbance of cytokine and matrix metalloproteinase secretion, as well as morphological transformation. Some effects, such as those on goblet cells and ciliated cells, persisted following the 7-day recovery period. Of note, the functional and structural disturbances observed in GA-treated cultures resemble those found in ortho-phthaldehyde (OPA)-treated cultures. Furthermore, our in vitro findings on GA toxicity partially and qualitatively mimicked those reported in the animal and human survey studies. Taken together, observations from this study demonstrate that the human air-liquid-interface (ALI) airway tissue model, integrated with an in vitro exposure system that simulates human inhalation exposure, could be used for in vitro-based human hazard identification and the risk characterization of aerosolized chemicals.

Biocidal disinfectants (BDs) that kill microorganisms or pathogens are widely used in hospitals and other healthcare fields. Recently, the use of BDs has rapidly increased as personal hygiene has become more apparent owing to the pandemic, namely the coronavirus outbreak. Despite frequent exposure to BDs, toxicity data of their potential neurotoxicity (NT) are lacking. In this study, a human-derived SH-SY5Y/astrocyte was used as a co-culture model to evaluate the chemical effects of BDs. Automated high-content screening was used to evaluate the potential NT of BDs through neurite growth analysis. A set of 12 BD substances classified from previous reports were tested. Our study confirms the potential NT of benzalkonium chloride (BKC) and provides the first evidence of the potential NT of poly(hexamethylenebicyanoguanide-hexamethylenediamine) hydrochloride (PHMB). BKC and PHMB showed significant NT at concentrations without cytotoxicity. This test system for analyzing the potential NT of BDs may be useful in early screening studies for NT prior to starting in vivo studies., Competing Interests: Declaration of Competing Interest Authors declare that there is no conflicting interest for the manuscript., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Biocides used in offshore oil and gas operations could be present in water discharges, and thus identifying such chemicals and their hazard could help address concerns regarding non-target organisms. Aquatic toxicity data, queried from different sources and augmented with predictive models, were used to develop species sensitivity distributions and their corresponding 5th percentile hazard concentrations (HC5s). Curated data, including over 1000 empirical records for 137 species, indicated no evidence of bias when comparing sensitivity between marine and freshwater species, even when predicted data were used. HC5s facilitated estimation of an acute-to-chronic ratio (ACR = 10), appropriate for most chemicals and useful in filling data gaps. Comparison of chronic-HC5s with the default approach for deriving predicted no effect concentrations showed that the latter systematically overstates aquatic hazard. The present approach shows promise of using acute-to-chronic HC5 ratios for defining assessment factors for different chemical classes, instead of the use of generic assessment factors., Competing Interests: Declaration of competing interest The authors are all employed by an international energy company, subject to regulation on discharges., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Chemical disinfection of water provides significant public health benefits. However, disinfectants like chlorine can react with naturally occurring materials in the water to form disinfection byproducts (DBPs). Natural levels of iodine have been reported to be too low in some source waters to account for the levels of iodinated DBPs detected. Iodinated X-ray contrast media (ICM) have been identified as a potential source of iodine. The toxicological impact of ICM present in source water at the time of disinfection has not been fully investigated. Iopamidol, iohexol, iopromide, and diatrizoate are among the ICM most frequently detected in water. In this study, source water containing one of these four ICM was chlorinated; non-chlorinated ICM-containing water samples served as controls. Reactions were conducted at an ICM concentration of 5 µM and a chlorine dose of 100 µM over 72 hr. Water concentrates (20,000-fold) were prepared by XAD-resin/ethyl acetate extraction and DMSO solvent exchange. We used the MatTek® reconstituted human epithelial skin irritation model to evaluate the water concentrates and also assessed the dermal irritation and sensitization potential of these concentrates using the LLNA:BrdU ELISA in BALB/c mice. None of the water concentrates tested (2500X) resulted in a skin irritant response in the MatTek® skin irritation model. Likewise, none of the concentrates (2500X, 1250X, 625X, 312.5X, 156.25X) produced a skin irritation response in mice: erythema was minimal; the maximum increase in ear thickness was less than 25%. Importantly, none of the concentrates produced a positive threshold response for allergic skin sensitization at any concentration tested in the LLNA:BrdU ELISA. We conclude that concentrates of water disinfected in the presence of four different ICM did not cause significant skin irritation or effects consistent with skin sensitization at the concentrations tested., 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., (Published by Elsevier B.V.)

Around nine million people have been exposed to toxic humidifier disinfectants (HDs) in Korea. HD exposure may lead to HD-associated lung injuries (HDLI). However, many people who have claimed that they experienced HD exposure were not diagnosed with HDLI but still felt discomfort, possibly due to the unknown effects of HD. Therefore, this study examined HD-exposed subjects with normal-appearing lungs, as well as unexposed subjects, in clusters (subgroups) with distinct characteristics, classified by deep-learning-derived computed-tomography (CT)-based tissue pattern latent traits. Among the major clusters, cluster 0 (C0) and cluster 5 (C5) were dominated by HD-exposed and unexposed subjects, respectively. C0 was characterized by features attributable to lung inflammation or fibrosis in contrast with C5. The computational fluid and particle dynamics (CFPD) analysis suggested that the smaller airway sizes observed in the C0 subjects led to greater airway resistance and particle deposition in the airways. Accordingly, women appeared more vulnerable to HD-associated lung abnormalities than men.

Airborne pathogenic bacteria and fungi transmitted through air-conditioning (AC) systems have been identified as a major public health risk. Air scrubbing is a promising liquid-based air disinfection technique that captures and inactivates airborne pathogens in liquid disinfectants. However, owing to the drawbacks of irritating odor and toxicity, the commonly-used chemical disinfectants cannot be employed for AC systems. This study aimed to unveil the inactivation performance and mechanism of non-toxic and chemically stable aqueous lithium chloride (LiCl) solution-the popular liquid desiccant in the AC systems-as a user-friendly disinfectant. Four prominent airborne pathogenic bacteria and fungi were exposed to the LiCl solution under various conditions. The inactivation effects were quantified with fluorescence-staining-based confocal microscopy and verified with the pathogens' membrane integrity variations, intracellular substance leakage, and morphological changes. Results showed that LiCl solution was remarkably efficient in inactivating the pathogens within 60 min, with an efficacy of 35.2-96.2%. The solution's inactivation ability was promoted by increasing the temperatures and concentrations; however, it appeared insensitive to exposure time over 30 min. We then explored the inactivation mechanism of LiCl solution by assessing cellular protein leakages and compared the inactivation rates with those of NaCl solution. The extracellular protein increased by over 470% after being exposed to LiCl solution. The inactivation rate was also considerably higher than in NaCl solution under the same osmotic pressure (24.79 MPa). We suggest that apart from osmotic pressure, the inactivation is reinforced by Li + -specific properties, including its strong water attraction that deprived the solvation shells of microbial protein and caused protein denaturation. We propose that aqueous LiCl solution may act as a user-friendly disinfectant for air-scrubbing due to its attractive characteristics, including its non-toxicity, odorless nature, and chemical stability. These findings may open up a "green" way to disinfect airborne pathogens and safeguard public health., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The goal of this study was to evaluate the impact of thermal and chemical aging processes on high-density polyethylene (HDPE), low-density polyethylene (LDPE), unplasticized polyvinyl chloride (U-PVC), and high-impact polyvinyl chloride (Hi-PVC) pipes. The materials were exposed to 1-10 ppm chemical disinfectants [chlorine dioxide (ClO 2 ) and hypochlorite (HOCl)] at 40-80 °C for 1200 h. The diffusion properties of the materials were systematically analyzed based on the change in their sorption characteristics and activation energies according to the Arrhenius model. Moreover, the structural changes were analyzed with scanning electron microscopy (SEM), Fourier transform infrared (FTIR) radiation, and thermogravimetric analysis (TGA). The results show that the materials have Fickian characteristics in the aging environment. Specifically, the water sorption rates of HDPE and LDPE increase first and then decrease after reaching saturation (Ms); those of U-PVC and Hi-PVC its increasing continuously with different rate. This behavior of materials was prominent for ClO 2 at high temperature and disinfectant dose because of polymeric chains crosslinking and rearrangement, extraction of monomers, and stable compounds removal during aging under exposed conditions. The deleterious effects decreased the activation energies of the materials and increased the concentrations of carbonyl groups [CO] via the formation of ketones, aldehydes, and carboxylic acids. The decomposition temperature increased with the changes in the material morphology and elemental contents under the investigated conditions. Moreover, LDPE and Hi-PVC were more severely affected in the thermal aging process with 10 mg.L -1 ClO 2 at 80 °C., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Due to the Covid-19 pandemic, the worldwide biocides application has been increased, which will eventually result in enhanced residuals in treated wastewater. At the same time, chlorine disinfection of secondary effluents and hospital wastewaters has been intensified. With respect to predicted elevated exposure in wastewater, the chlorination kinetics, transformation pathways and toxicity evolution were investigated in this study for two typical isothiazolinone biocides, methyl-isothiazolinone (MIT) and chloro-methyl-isothiazolinone (CMIT). Second-order rate constants of 0.13 M -1 ·s -1 , 1.95 × 10 5 M -1 ·s -1 and 5.14 × 10 5 M -1 ·s -1 were determined for the reaction of MIT with HOCl, Cl 2 O and Cl 2 , respectively, while reactivity of CMIT was around 1-2 orders of magnitude lower. While chlorination of isothiazolinone biocides at pH 7.1 was dominated by Cl 2 O-oxidation, acidic pH and elevated Cl - concentration favored free active chlorine (FAC) speciation into Cl 2 and increased overall isothiazolinone removal. Regardless of the dominant FAC species, the elimination of MIT and CMIT resulted in an immediate loss of acute toxicity under all experimental conditions, which was attributed to a preferential attack at the S-atom resulting in subsequent formation of sulfoxides and sulfones and eventually an S-elimination. However, chlorination of isothiazolinone biocides in secondary effluent only achieved <10% elimination at typical disinfection chlorine exposure 200 mg·L -1 ·min, but was predicted to be remarkably increased by acidizing solution to pH 5.5. Alternative measures might be needed to minimize the discharge of these toxic chemicals into the aquatic environment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Chlorination disinfection has been widely used to kill the pathogenic microorganisms in wastewater sludge during the special Covid-19 period, but sludge chlorination might cause the generation of harmful disinfection byproducts (DBPs). In this work, the transformation of extracellular polymeric substance (EPS) and mechanisms of Cl-DBPs generation during sludge disinfection by sodium hypochlorite (NaClO) were investigated using multispectral analysis in combination with Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS). The microorganism Escherichia coli (E. coli) was effectively inactivated by active chlorine generated from NaClO. However, a high diversity of Cl-DBPs were produced with the addition of NaClO into sludge, causing the increase of acute toxicity on Q67 luminous bacteria of chlorinated EPS. A variety of N-containing molecular formulas were produced after chlorination, but N-containing DBPs were not detected, which might be the indicative of the dissociation of -NH 2 groups after Cl-DBPs generated. Additionally, the release of N-containing compounds was increased in alkaline environment caused by NaClO addition, resulted in more Cl-DBPs generation via nucleophilic substitutions. Whereas, less N-compounds and Cl-DBPs were detected after EPS chlorination under acidic environment, leading to lower cell cytotoxicity. Therefore, N-containing compounds of lignin derivatives in sludge were the major Cl-DBPs precursors, and acidic environment could control the release of N-compounds by eliminating the dissociation of functional groups in lignin derivatives, consequently reducing the generation and cytotoxicity of Cl-DBPs. This study highlights the importance to control the alkalinity of sludge to reduce Cl-DBPs generation prior to chlorination disinfection process, and ensure the safety of subsequential disposal for wastewater sludge., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: It has been 10 years since the outbreak of lung disease caused by humidifier disinfectants in Korea, but the health effects have not yet been summarized. Therefore, this study aims to systematically examine the health effects of humidifier disinfectants that have been discovered so far., Methods: All literature with humidifier disinfectants and their representative components as the main words were collected based on the web, including PubMed, Research Information Sharing Service, and government publication reports. A total of 902 studies were searched, of which 196 were selected. They were divided into four groups: published human studies (group 1), published animal and cytotoxicology studies (group 2), technical reports (group 3), and gray literature (group 4)., Results: Out of the 196 studies, 97 (49.5%) were published in peer-reviewed journals as original research. Group 1 consisted of 49 articles (50.5%), while group 2 consisted of 48 articles (49.5%). Overall, respiratory diseases such as humidifier disinfectant associated lung injury, interstitial lung disease, and asthma have a clear correlation, but other effects such as liver, heart, thymus, thyroid, fetal growth, metabolic abnormalities, and eyes are observed in toxicological experimental studies, but have not yet been identified in epidemiologic studies., Conclusion: The current level of evidence does not completely rule out the effects of humidifier disinfectants on extrapulmonary disease. Based on the toxicological evidence so far, it is required to monitor the population of humidifier disinfectant exposure continuously to see if similar damage occurs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Antifouling (AF) coatings containing booster biocides are used worldwide as one of the most cost-effective ways to prevent the attachment of marine organisms to submerged structures. Nevertheless, many of the commercial biocides, such as Econea ® (tralopyril), are toxic in marine environments. For that reason, it is of extreme importance that new efficient AF compounds that do not cause any harm to non-target organisms and humans are designed. In this study, we measured the half-maximal inhibitory concentration (IC 50 ) of a promising nature-inspired AF compound, a triazolyl glycosylated chalcone (compound 1 ), in an immortalized human retinal pigment epithelial cell line (hTERT-RPE-1) and compared the results with the commercial biocide Econea ® . We also investigated the effects of these biocides on the cellular lipidome following an acute (24 h) exposure using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Our results showed that compound 1 did not affect viability in hTERT-RPE-1 cells at low concentrations (1 μM), in contrast to Econea ® , which caused a 40% reduction in cell viability. In total, 71 lipids were found to be regulated upon exposure to 10 µM of both compounds. Interestingly, both compounds induced changes in lipids involved in cell death, membrane modeling, lipid storage, and oxidative stress, but often in opposing directions. In general, Econea ® exposure was associated with an increase in lipid concentrations, while compound 1 exposure resulted in lipid depletion. Our study showed that exposure to human cells at sublethal Econea ® concentrations results in the modulation of several lipids that are linked to cell death and survival.

1,3-diphenylguanidine (DPG) is a commonly used rubber and polymer additive, that has been found to be one of the main leachate products of tire wear particles and from HDPE pipes. Its introduction to aquatic environments and potentially water supplies lead to further questions regarding the effects of disinfection by-products potentially formed. Using different bioassay approaches and NGS RNA-sequencing, we show that some of the chlorinated by-products of DPG exert significant toxicity. DPG and its chlorinated by-products also can alter cell bioenergetic processes, affecting cellular basal respiration rates and ATP production, moreover, DPG and its two chlorination products, 1,3-bis-(4-chlorophenyl)guanidine (CC04) and 1-(4-chlorophenyl)-3-(2,4-dichlorophenyl)guanidine (CC11), have an impact on mitochondrial proton leak, which is an indicator of mitochondria damage. Evidence of genotoxic effects in the form of DNA double strand breaks (DSBs) was suggested by RNA-sequencing results and further validated by an increased expression of genes associated with DNA damage response (DDR), specifically the canonical non-homologous end joining (c-NHEJ) pathway, as determined by qPCR analysis of different pathway specific genes (XRCC6, PRKDC, LIG4 and XRCC4). Immunofluorescence analysis of phosphorylated histone H2AX, another DSB biomarker, also confirmed the potential genotoxic effects observed for the chlorinated products. In addition, chlorination of DPG leads to the formation of different chlorinated products (CC04, CC05 and CC15), with analysed compounds representing up to 42% of formed products, monochloramine is not able to effectively react with DPG. These findings indicate that DPG reaction with free chlorine doses commonly applied during drinking water treatment or in water distribution networks (0.2-0.5 mg/L) can lead to the formation of toxic and genotoxic chlorinated products., (Copyright © 2022. Published by Elsevier B.V.)

Halobenzoquinones (HBQs) have been reported as an emerging category of disinfection byproducts (DBPs) in drinking water with relatively high toxicity, and the previously reported HBQs include 2,6-dichloro-1,4-benzoquinone, 2,3,6-trichloro-1,4-benzoquinone, 2,6-dichloro-3-methyl-1,4-benzoquinone, 2,6-dibromo-1,4-benzoquinone, 2,6-diiodo-1,4-benzoquinone, 2-chloro-6-iodo-1,4-benzoquinone, and 2-bromo-6-iodo-1,4-benzoquinone. In this study, another HBQ species, 2-bromo-6-chloro-1,4-benzoquinone (2,6-BCBQ), was newly detected and identified in drinking water. The occurrence frequency and levels of 2,6-BCBQ were investigated, and its cytotoxicity was evaluated. Since the formed 2,6-BCBQ was found to be not stable in chlorination, its transformation kinetics and mechanisms in chlorination were further studied. The results reveal that 2,6-BCBQ was generated from Suwannee River humic acid with concentrations in the range of 4.4-47.9 ng/L during chlorination within 120 h, and it was present in all the tap water samples with concentrations ranging from 1.5 to 15.7 ng/L. Among all the tested bromochloro-DBPs, 2,6-BCBQ showed the highest cytotoxicity on the human hepatoma cells. The transformation of 2,6-BCBQ in chlorination followed a pseudo-first-order decay, which was significantly affected by the chlorine dose, pH, and temperature. Seven polar chlorinated and brominated intermediates (including HBQs, halohydroxybenzoquinones, and halohydroxycyclopentenediones) were detected in chlorinated 2,6-BCBQ samples, according to which the transformation pathways of 2,6-BCBQ in chlorination were proposed. Besides, four trihalomethanes and four haloacetic acids were also generated during chlorination of 2,6-BCBQ with molar transformation percentages of 1.6-13.7%., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Atrazine and diuron are among the most widely used antifoulant biocides in the world. Due to their persistence in the environment, they can induce adverse effects on non-targeted organisms. In this study, we investigated the chronic in vivo toxicity of atrazine and diuron with further assessments on oxidative stress responses (e.g., oxidative stress, antioxidant) and multixenobiotic resistance (MXR) function in the rotifer Brachionus koreanus, a non-targeted microzooplanktonic grazer at the primary level of the marine food chain. Although similar oxidative response was shown by both biocides, diuron induced stronger retardation on reproduction and population growth rates of B. koreanus while moderate effects were observed by atrazine. This higher toxicity of diuron was shown to be associated with its stronger inhibition of MXR conferred by P-glycoprotein and multidrug resistance proteins which play as a first line of defense by transporting various toxicants out of a cell. Our study provides new insight into non-targeted effects of biocides on marine zooplankton and mechanisms beyond their different degrees of toxicity., (Copyright © 2022. Published by Elsevier Inc.)

The usage of quaternary ammonium compounds (QACs) as disinfectants has increased dramatically since the outbreak of COVID-19 pandemic, leading to potentially accelerated emergence of antibiotic resistance. Long-term exposure to subinhibitory level QACs can lead to multidrug resistance, but the contribution of mutagenesis to resistance evolution is obscure. In this study, we subcultured E. coli K-12 under subinhibitory (0.25 × and 0.5 × Minimum Inhibitory Concentration, MIC) or inhibitory (1 × and 2 × MIC) concentrations of benzalkonium chloride (BAC, mono-chained) or didecyldimethylammonium chloride (DDAC, twin-chained) for 60 days. The sensitivity of QAC-adapted cells to five typical antibiotics decreased significantly, and in particular, the MIC of rifampicin increased by 85 times. E. coli adapted faster to BAC but developed 20-167% higher antibiotic resistance with 56% more mutations under DDAC exposure. The broader mutations induced by QACs, including negative regulators (acrR, marR, soxR, and crp), outer membrane proteins and transporters (mipA and sbmA), and RNA polymerase (rpoB and rpoC), potentially contributed to the high multi-drug resistance. After QACs stresses were removed, the phenotypic resistance induced by subinhibitory concentrations of QACs was reversible, whereas that induced by inhibitory concentrations of QACs was irreversible. The different patterns and molecular mechanism of antibiotic resistance induced by BAC and DDAC is informative to estimating the risks of broader QACs present at varied concentrations in the environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The mixture of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT, chloromethylisothiazolinone) and 2-methyl-4-isothiazolin-3-one (MIT, methylisothiazolinone) is a commonly used biocide in consumer products. Despite the health issues related to its usage in cosmetics and humidifier disinfectants (HD), understanding its adverse outcome is still limited. Using in vitro cell lines and ex vivo rat models, we examined the effects of CMIT/MIT on the cellular redox homeostasis and energy metabolism in the brain microvascular endothelium, a highly restrictive interface between the bloodstream and brain. In murine bEND.3 and human hCMEC/D3, CMIT/MIT significantly amplified the mitochondrial-derived oxidative stress causing disruption of the mitochondrial membrane potential and oxidative phosphorylation at a sub-lethal concentration (1 μg/mL) or treatment duration (1 h). In addition, CMIT/MIT significantly increased a dynamic imbalance between mitochondrial fission and fusion, and endogenous pathological stressors significantly potentiated the CMIT/MIT-induced endothelial dysfunction. Notably, in the brain endothelium isolated from intravenously CMIT/MIT-administered rats, we observed significant mitochondrial damage and decreased tight junction protein. Taken together, we report that CMIT/MIT significantly impaired mitochondrial function and dynamics resulting in endothelial barrier dysfunction, giving an insight into the role of mitochondrial damage in CMIT/MIT-associated systemic health effects., (Copyright © 2022 Elsevier B.V. All rights reserved.)

In this study, the potential effects of 30-day exposure to environmentally relevant concentrations of chlorothalonil (0, 5, 10, and 20 μg L -l ) were tested in the blood of the economically important olive flounder, Paralichthys olivaceus, using biochemical endpoints. Significant decreases in the enzymatic activities of immunity markers, alternative complements, and lysozymes were detected in the fish exposed to 10 or 20 μg L -l of chlorothalonil at day 20 or 30. The total immunoglobulin content was lowered in response to 20 μg L -l chlorothalonil at day 10 and 20, even when later exposed to 5 μg L -l at day 30. Among the essential blood components, the cortisol level was increased in response to chlorothalonil throughout the study with a decrease in white blood cells, while no changes were observed in hemoglobin, red blood cells, total protein concentration, and glucose in all exposures. The enzymatic activities of the three hepatic toxicity markers, alanine transferases, aspartate transaminase, and alkaline phosphatase, increased by 10 and/or 20 μg L -l of chlorothalonil. Significant oxidative stress was induced by chlorothalonil in the fish exposed to 10 or 20 μg L -l of chlorothalonil, as revealed by increased malondialdehyde and fluctuating glutathione levels with increase in the enzymatic activities of antioxidant defense system, including catalase and superoxide dismutase, during exposure. Taken together, these results suggest that long-term exposure to environmentally relevant concentrations of chlorothalonil can affect susceptibility to pathogens through immunosuppression, hepatic toxicity, and oxidative stress in olive flounder. These results can contribute to the monitoring of aquatic environments and ecotoxicological research through the measurement of blood components against waterborne chlorothalonil., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts (DBPs) in water; evaluating each compound is practically impossible and very time consuming. A bioanalytical approach could be an answer to this challenge. In this work, the response of four major classes of DBPs toward mitochondrial membrane potential (ΔΨm) and cytoplasmic adenosine triphosphate (C-ATP) was investigated with human carcinoma (HepG2) cells. Within 90 min of cell exposure, only the haloacetic acid (HAA) mixture caused a cytotoxic response as measured by C-ATP. All four groups (haloacetonitriles (HANs), trihalomethanes (THMs), nitrosamines (NOAs), and HAAs) responded well to ΔΨm, R 2 > 0.70. Based on the half-maximum concentration that evoked a 50% response in ΔΨm, the response gradient was HANs >> HAAs ∼ THM > NOAs. The inhibition of the ΔΨm by HANs is driven by dibromoacetonitrile (DBAN), while dichloroacetonitrile (DCAN) did not cause a significant change in the ΔΨm at less than 2000 µM. A mixture of HANs exhibited an antagonistic behavior on the ΔΨm compared to individual compounds. If water samples are concentrated to increase HAN concentrations, especially DBAN, then ΔΨm could be used as a biomonitoring tool for DBP toxicity., (Copyright © 2022. Published by Elsevier B.V.)

Although the health benefits of swimming are well-documented, health effects such as asthma and bladder cancer are linked to disinfection by-products (DBPs) in pool water. DBPs are formed from the reaction of disinfectants such as chlorine (Cl) or bromine (Br) with organics in the water. Our previous study (Daiber et al., Environ. Sci. Technol. 50, 6652; 2016) found correlations between the concentrations of classes of DBPs and the mutagenic potencies of waters from chlorinated or brominated swimming pools and spas. We extended this study by identifying significantly different concentrations of 21 individual DBPs in brominated or chlorinated pool and spa waters as well as identifying which DBPs and additional DBP classes were most associated with the mutagenicity of these waters. Using data from our previous study, we found that among 21 DBPs analyzed in 21 pool and spa waters, the concentration of bromoacetic acid was significantly higher in Br-waters versus Cl-waters, whereas the concentration of trichloroacetic acid was significantly higher in Cl-waters. Five Br-DBPs (tribromomethane, dibromochloroacetic acid, dibromoacetonitrile, bromoacetic acid, and tribromoacetic acid) had significantly higher concentrations in Br-spa versus Cl-spa waters. Cl-pools had significantly higher concentrations of Cl-DBPs (trichloroacetaldehyde, trichloromethane, dichloroacetic acid, and chloroacetic acid), whereas Br-pools had significantly higher concentrations of Br-DBPs (tribromomethane, dibromoacetic acid, dibromoacetonitrile, and tribromoacetic acid). The concentrations of the sum of all 4 trihalomethanes, all 11 Br-DBPs, and all 5 nitrogen-containing DBPs were each significantly higher in brominated than in chlorinated pools and spas. The 8 Br-DBPs were the only DBPs whose individual concentrations were significantly correlated with the mutagenic potencies of the pool and spa waters. These results, along with those from our earlier study, highlight the importance of Br-DBPs in the mutagenicity of these recreational waters., (Copyright © 2022. Published by Elsevier B.V.)

Halogenated disinfection byproducts (DBPs) are an unintended consequence of drinking water disinfection, and can have significant toxicity. XAD resins are commonly used to extract and enrich trace levels of DBPs for comprehensive, nontarget identification of DBPs and also for in vitro toxicity studies. However, XAD resin recoveries for complete classes of halogenated DBPs have not been evaluated, particularly for low, environmentally relevant levels (ng/L to low µg/L). Thus, it is not known whether levels of DBPs or the toxicity of drinking water might be underestimated. In this study, DAX-8/XAD-2 layered resins were evaluated, considering both adsorption and elution from the resins, for extracting 66 DBPs from water. Results demonstrate that among the 7 classes of DBPs investigated, trihalomethanes (THMs), including iodo-THMs, were the most efficiently adsorbed, with recovery of most THMs ranging from 50%-96%, followed by halonitromethanes (40%-90%). The adsorption ability of XAD resins for haloacetonitriles, haloacetamides, and haloacetaldehydes was highly dependent on the individual species. The adsorption capacity of XAD resins for haloacetic acids was lower (5%-48%), even after adjusting to pH 1 before extraction. Recovery efficiency for most DBPs was comparable with their adsorption, as most were eluted effectively from XAD resins by ethyl acetate. DBP polarity and molecular weight were the two most important factors that determine their recovery. Recovery of trichloromethane, iodoacetic acid, chloro- and iodo-acetonitrile, and chloroacetamide were among the lowest, which could lead to underestimation of toxicity, particularly for iodoacetic acid and iodo-acetonitrile, which are highly toxic., (Copyright © 2022. Published by Elsevier B.V.)

Chlorine, chlorine dioxide, and ozone are widely used as disinfectants in drinking water treatments. However, the combined use of different disinfectants can result in the formation of various organic and inorganic disinfection byproducts (DBPs). The toxic interactions, including synergism, addition, and antagonism, among the complex DBPs are still unclear. In this study, we established and verified a real-time cell analysis (RTCA) method for cytotoxicity measurement on Chinese hamster ovary (CHO) cell. Using this convenient and accurate method, we assessed the cytotoxicity of a series of binary combinations consisting of one of the 3 inorganic DBPs (chlorite, chlorate, and bromate) and one of the 32 regulated and emerging organic DBPs. The combination index (CI) of each combination was calculated and evaluated by isobolographic analysis to reflect the toxic interactions. The results confirmed the synergistic effect on cytotoxicity in the binary combinations consisting of chlorite and one of the 5 organic DBPs (2 iodinated DBPs (I-DBPs) and 3 brominated DBPs (Br-DBPs)), chlorate and one of the 4 organic DBPs (3 aromatic DBPs and dibromoacetonitrile), and bromate and one of the 3 organic DBPs (2 I-DBPs and dibromoacetic acid). The possible synergism mechanism of organic DBPs on the inorganic ones may be attributed to the influence of organic DBPs on cell membrane and cell antioxidant system. This study revealed the toxic interactions among organic and inorganic DBPs, and emphasized the latent adverse outcomes in the combined use of different disinfectants., (Copyright © 2022. Published by Elsevier B.V.)

MA-T (Matching Transformation System®) is a proprietary chemical mixture for on-demand production of aqueous chlorine dioxide that is used for the treatment of oral malodor. MA-T is also an effective disinfectant against at least 39 pathological microorganisms, including severe acute respiratory syndrome coronavirus 2, and therefore may be useful as a disinfectant mouthwash to prevent the spread of infection. Accidental ingestion is the putative worst hazard scenario associated with mouthwash use; therefore, here we investigated the safety of MA-T ingestion in mice. Mice were provided drinking water containing 0-3000 μg/ml MA-T for 7 days followed by non-spiked drinking water for an additional 14 days. At day 7, mice ingesting 1000 or 3000 μg/ml MA-T showed significantly decreased body weight and significantly increased liver, kidney, and heart tissue injury biomarkers compared with control. However, at 14 days after stopping MA-T ingestion, body weight and tissue injury biomarkers had returned to normal. Histological analysis revealed that MA-T-induced injuries in liver, kidney, spleen, stomach, duodenum, colon, and rectum had also recovered at 14 days after stopping MA-T ingestion; however, mild vascular endothelial injuries remained in heart, jejunum, and ileum in the worst-case scenario. Taken together, MA-T may be potentially safety for further development as a disinfectant mouthwash by risk management, such as placing a caution of the label and adding a distinctive flavor., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Swimming pools adopt chlorination to ensure microbial safety. Giardia has attracted attention in swimming pool water because of its occurrence, pathogenicity, and chlorine resistance. To control Giardia concentrations in pool water and reduce the microbial risk, higher chlorine doses are required during disinfection. Unfortunately, this process produces carcinogenic disinfection byproducts that increase the risk of chemical exposure. Therefore, quantitatively evaluating the comparative microbial vs. chemical exposure risks that stem from chlorination inactivation of Giardia in swimming pool water is an issue that demands attention. We simulated an indoor swimming pool disinfection scenario that followed common real-world disinfection practices. A quantitative microbial risk assessment coupled with a chemical exposure risk assessment was employed to compare the Giardia microbial exposure risk (MER) and the trihalomethane chemical exposure risk (CER) to humans. The results demonstrated a 22% decrease in MER- and CER-induced health exposure risk, from 8.45E-5 at 8:00 to 6.60E-5 at 19:00. Both the MER and CER decreased gradually, dropping to 3.26E-5 and 3.35E-5 at 19:00, respectively. However, the CER exceeded the MER after 18:30 and became the dominant factor affecting the total exposure risk. Past the 18 hr mark, the contribution of trihalomethane CER far exceeded the risk aversion from microbial inactivation, leading to a net increase in total exposure risk despite the declining MER. Swimmers may consider swimming after 19:00, when the total exposure risk is the lowest. Lowering water temperature and/or pH were identified as the most sensitive factors to minimize the overall health exposure risk., (Copyright © 2022. Published by Elsevier B.V.)

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

Ammonia nitrogen (NH 3 -N) significantly affects the occurrence of disinfection byproducts (DBPs) and residual chlorine in chlorinated wastewater, thereby affecting the acute toxicity to aquatic organisms. In this paper, the formation of thirty-five halogenated DBPs and the changes in acute toxicity of luminescent bacteria and zebrafish embryos were evaluated after chlorination of seven secondary wastewater effluents with different NH 3 -N concentrations. Results showed that NH 3 -N significantly reduced the formation of most DBPs by 82-100%. The acute toxicity was enhanced after chlorination and increased linearly with increasing NH 3 -N concentration for luminescent bacteria (r = 0.986, p < 0.05) and zebrafish embryos (r = 0.972, p < 0.05) due to the coexistence of DBPs and monochloramine. According to the toxicity classification system of wastewater, the fitting results indicated that the toxicity level was acceptable for chlorinated wastewater with NH 3 -N concentration below 1.00 mg-N/L. DBPs might be the main toxicant to luminescent bacteria in the wastewater with low NH 3 -N concentrations (0.06-0.31 mg-N/L), which accounted for 68-97% of the toxicity contribution. By contrast, monochloramine contributed over 80% to the toxicity of luminescent bacteria and zebrafish embryos in the wastewater with high NH 3 -N concentrations (2.66-7.17 mg-N/L). Compared to chlorination, chlorine dioxide and ultraviolet disinfection unaffected by NH 3 -N could reduce acute toxicity by nearly 100%, primarily due to the lack of residual disinfectant. In view of the high toxicity caused by chlorination, chlorination-dechlorination or chlorine dioxide and UV disinfection are highly recommended for the treatment of wastewater with high NH 3 -N concentration., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Biocides based on chemical synthetic compounds have been commonly used to counteract damages caused by microorganisms on stone cultural heritage. However, in the last few years, the use of commercial and traditional biocides has been banned and/or limited due to their dangerous profile for the environment, as well as human and animal health. Natural products could be used as suitable alternatives for cultural heritage purposes, as they have low toxicity and stability compared with synthetic pesticides. Even if most of the investigated solutions have already shown promising results, their efficiency, ecotoxicological, and chemical features are poorly investigated. In this manuscript, we aimed to evaluate the ecotoxicological profile of four fungal metabolites-namely, cavoxin, epi -epoformin, seiridin, and sphaeropsidone-with potential antimicrobial properties for monumental artworks. A battery of ecotoxicological tests using Aliivibrio fischeri (bacterium), Raphidocelis subcapitata (alga), Raphanus sativus L. (macrophyte), Daphnia magna (crustacean), and Caenorhabditis elegans (nematode) revealed a relative lower toxicity of these compounds, especially when compared with Preventol ® and Rocima ® , commercial biocides mainly used for the conservation of cultural heritage.

Ozonation plays an important role in wastewater treatment for reuse. However, the toxicity of wastewater treated with ozone considerably increases with bromide (Br - ) concentration >100 μg/L. Nine newly identified brominated disinfection byproducts (Br-DBPs) that are highly toxic in ozonated Br - -containing wastewater were found in our recent work, including 2-bromostyrene, 1-bromo-1-phenylethylene, 2-bromobenzaldehyde, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-bromophenylacetonitrile, 3-bromophenylacetonitrile, 4-bromophenylacetonitrile, and 2,4,6-tribromophenol. In the present study, the formation and calculated toxicity index of the nine newly identified Br-DBPs were evaluated. The correlations between the water quality index and the formation of nine Br-DBPs were also analyzed. With the increase of ozone dosage, the concentrations of bromostyrenes, 3-bromobenzaldehyde, 4-bromobenzaldehyde, 2-bromophenylacetonitrile, and 2,4,6-tribromophenyl in the ozonated samples gradually increased. With the increase of Br - concentration, the concentrations of bromostyrene, 2-bromobenzaldehyde, and 2,4,6-tribromophenol gradually increased. With the increase of NH 4 + concentration, the concentrations of bromophenylacetonitriles gradually increased. Among the nine Br-DBPs, the bromophenylacetonitriles and 2,4,6-tribromophenol contributed the most to the cytotoxicity index, 2,4,6-tribromophenol and bromostyrenes contributed the most to the genotoxicity index, and bromophenylacetonitriles and bromostyrenes contributed the most to the oxidative damage index. The dissolved organic carbon levels strongly correlated with the formation of 3-bromophenylacetonitrile and 4-bromophenylacetonitrile, and the fluorescence I-V region intensity integral was correlated with the formation of 4-bromobenzaldehyde and 2,4,6-tribromophenol. The results of the present study clarified the formation potential of the nine widely existing newly identified Br-DBPs, confirmed the high calculated toxicity indices, and are of great value for future research on Br-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 © 2022 Elsevier B.V. All rights reserved.)

Following the humidifier disinfectant incident in Korea, polyhexamethylene guanidine phosphate (PHMG-P) has been used to establish lung fibrosis model animals. Herein, we investigated time-dependent changes after a single PHMG-P instillation (22 μg/lung) to identify the underlying pathogenesis and immune response involved in PHMG-P-induced lung fibrosis. Compared to control mice, body weight loss and blood biochemical and hematological changes were more remarkable in PHMG-P-instilled mice, an increase of total cell counts, infiltration of macrophages and neutrophils and necrotic cell death were also more notable in the lungs of PHMG-P-instilled mice. Pathological lesions were detected from Day 1 after exposure, deteriorating with time. In addition, secretion of anti-inflammatory mediators was rapidly inhibited from 6 h after exposure, and level of IL-24, a tissue repair-related cytokine, was up-regulated in the lungs of PHMG-P-instilled mice until Day 21 post-exposure. In vitro tests using BEAS-2B cells showed that PHMG-P disturbed structural and functional homeostasis of organelles and that intracellular ROS increase was considered as an important cause of PHMG-P-induced cell death. Additionally, co-culture with DNA, a polyanionic compound, clearly inhibited PHMG-P-induced necrosis, and increased IL-1β and TNF-α level and decreased IL-6 and IL-8 levels were observed following exposure to PHMG-P. Meanwhile, IL-8 secretion increased in cells exposed to PHMG-P-induced cell debris. Therefore, we suggest that necrotic cell debris may importantly contribute to the PHMG-P-induced inflammatory response and pathogenesis. In addition, PHMG-P-induced necrosis may be initiated by high affinity between PHMG-P and cell membrane., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Eco-toxicity profiles for commonly used disinfectants were lacking. Available traditional toxicity techniques have some limitations (assessments and ethical issues). Behaviour toxicology is a promising research area towards early warning and non-invasive approaches. We studied the potential eco-toxic effects of sodium hypochlorite (NaOCl) on the swimming behaviour of zebrafish. Zebrafish were exposed to different concentrations (Treatment I, Treatment II, Treatment III, and Treatment IV) of NaOCl for 360 h. Recovery study (144 h) was conducted for NaOCl treatment groups. The swimming behaviour of zebrafish was quantified efficiently using an online monitoring system (OMS). OMS dataset was processed for determination of behavioural differences by MATLAB and SPSS. Compared to the control group, the swimming strength of zebrafish under NaOCl treatments declined significantly (p < 0.001). Avoidance behaviour has occurred on zebrafish under NaOCl exposure periods. Furthermore, NaOCl toxicity also adjusted circadian rhythms on zebrafish. Zebrafish swimming strength was significantly (p < 0.001) improved under-recovery periods. Moreover, normal diurnal patterns have occurred. NaOCl could cause behavioural abnormalities in non-target organisms. Continuous exposure to common disinfectants could cause external and internal stress on non-target organisms, resulting in behavioural changes and circadian rhythm adjustments. Continuous changes in behavioural and circadian rhythms might reduce organisms' fitness and adaptation capacity. This study highlights (1) the importance of computer-based toxicity assessments, and (2) swimming behaviour is an early warning biomarker for eco-toxicity studies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Water contamination through anthropogenic and industrial activities has led to the emergence and necessity of disinfection methods. Chlorine and bromine gases, often used to disinfect water, resulted in the by-product formation by reacting with organic matter. The Disinfectant by-products (DBP) led to the formation of Trihaloaceticacid (TAA), Trihalomethane (THM), and other minor components. The release of chemicals has also led to the outbreak of diseases like infertility, asthma, stillbirth, and types of cancer. There are new approaches that are found to be useful to compensate for the generation of toxic by-products and involve membrane technologies, namely reverse osmosis, ultrafiltration, and nanofiltration. This review mainly focuses on the toxicology effects of DBPs and various approaches to mitigate the same. The health hazards caused by different DBPs and the various treatment techniques available for the removal are discussed. In addition, a critical comparison of the different removal techniques was discussed., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2022 Elsevier B.V. All rights reserved.)

A new health threat was appeared in 2019 known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19). The new coronavirus distributed all over the world and caused millions of deaths. One way to incomplete the process of COVID-19 transfer from one person to another is using disinfectants. A narrative review study was done on manuscript published documents about the stability of the virus, different types of disinfectants and the effects of disinfectants on SARS-CoV2 and environment from 2005 to 2022 based on Searched databases included Google Scholar, Springer, PubMed, Web of Science and Science Direct (Scopus). All relevant studies published 2005 until 2022 gathered. According to the databases, 670 articles were retrieved. Thirty studies were screened after review and 30 full-text articles entered into the analysis process. Finally, 14 articles were selected in this study. New coronavirus could survive until 9 days in room temperature; the surviving time decreases if temperature increases. The virus can survive in various plastic, glass, and metal surfaces for hours to days. Disinfectants, such as alcohol, isopropanol, formaldehyde, glutaraldehyde, and ethanol, can kill 70-90% viruses in up to 30 s but should be noted that these disinfectants are recognized by Occupational Safety and Health Administration (OSHA) as a potential carcinogen. According to the different reports, increased duration and level of disinfectant exposure can have negative impacts on human and animal health including upper and lower respiratory tract irritation, inflammation, edema, ulceration, and allergic reactions., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Algal organic matter (AOM) in water reservoirs is a worldwide concern for drinking water treatment; once it is one of the main precursors for disinfection by-products formation (DBPs). In this context, this study investigated the ecotoxicity of DBPs from chlorination of AOM to Ceriodaphnia silvestrii and Daphnia similis (Crustacea, Cladocera). The bioassays evaluated three scenarios, including the AOM extracted from Chlorella sorokiniana, the quenching condition used in the tests, and the DBPs formed after the chlorination of the two test waters with AOM (with and without bromide presence). The results showed that AOM has no toxic effects for the tested species under typical environmental concentration (5 mg∙L -1 ). However, since AOM is a potential precursor of DBPs, the toxicity of two test waters (TW-1 and TW-2) after the chlorination process (25 mg Cl 2 ·L -1 , for 7 days, at 20 °C) was tested. The sample with higher toxicity to the tested species was TW-1, in which chloroform and chloral hydrate were quantified (615 and 267 µg∙L -1 , respectively). However, TW-2 showed lower concentration of chloroform and chloral hydrate (260 and 157 µg∙L -1 , respectively), although bromodichloromethane, dibromochloromethane, and bromoform were also detected (464, 366, and 141 µg∙L -1 , respectively). Although free chlorine is highly toxic to the tested species, the quenching conditions also affected the organisms' survival due to the use of ascorbic acid and the presence of reaction intermediates. Nonetheless, both species were more affected by TW-1 and TW-2 than the quenching condition. These results endorse the importance of removing the AOM before the disinfection process to avoid the formation of DBPs. In addition, ecotoxicological analyses could provide a more comprehensive assessment of water quality, especially considering the challenges of quantifying DBPs and other emerging contaminants., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The extensive use of quaternary ammonium compounds (QACs) has raised concerns regarding their environmental fate and potential risks to the ecosystem. As sensitive pollution indicators, green microalgae could readily monitor the aquatic toxicity of QACs as reflective of the changes in cell viability. Recent microfluidic-based systems have been designed for environmental biomonitoring and ecotoxicity studies while overall information of cell viability cannot be directly visualized under flowing conditions. In the present study, we developed a multifunctional microfluidic platform with the integration of analytical techniques including laser speckle contrast imaging and fluorescence spectroscopy for monitoring algal activity in response to QAC treatment. The biocidal efficiency of a representative QAC benzalkonium bromide (BAB) on a typical aquatic algae Chlorella vulgaris was determined by collecting the bio-speckles and chlorophyll autofluorescence in real-time, where dose-dependent and time-dependent decrease of algal growth was found with the increase of BAB concentration and interaction time. The integrated system was capable of rapid detection of the aquatic toxicity of QACs along with macroscopical visualization of algal activities under flowing conditions in time-course, which could be extended to future implementation for broad ecotoxicity analysis of versatile environmental samples., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Identifying disinfection byproducts (DBPs) with high health risk is an unresolved challenge. In this study, six members of a new class of aromatic nitrogenous DBPs─2-chloroaniline, 2-bromoaniline, 2,4-dichloroaniline, 2-chloro-4-bromoaniline, 4-chloro-3-nitroaniline, and 2-chloro-4-nitroaniline─are reported as DBPs in drinking water for the first time. Haloanilines completely degraded within 1 h in the presence of chlorine (1 mg/L), while about 20% remained in the presence of chloramine (1 mg/L) after 120 h. Haloanilines showed high stability in the absence of disinfectants, with <30% degradation at pH 5-9 over 120 h. Eight haloanilines were determined in chloraminated finished water and tap water at total concentrations of up to 443 ng/L. The most abundant was 2-bromoaniline, with a median concentration of 104 ng/L. The cytotoxicity of eight haloanilines and regulated trichloromethane and dichloroacetic acid (DCAA) was evaluated using Hep G2 cell assay. The EC 50 values of eight haloanilines were 1-2 orders of magnitude lower than those of the regulated DBPs. The lowest toxic concentration of 2-chloro-4-nitroaniline was 1 μM, 500 times lower than that of DCAA. The formation and control of haloanilines in drinking water warrant further investigation.

Levels of booster biocides (Irgarol, diuron, chlorothalonil, dichlofluanid and DCOIT), organotins (TBT, DBT, MBT, TPhT, DPhT and MPhT) and antifouling paint particles (APPs) were assessed in sediments of sites under the influence of maritime activities along the coastal zone of the Yucatán Peninsula, Mexico. Imposex incidence and organotin levels were also evaluated in seven caenogastropod species. The incidence of imposex was detected in five species from sites nearby fishing harbors and marinas, including the first reports to Gemophos tinctus and Melongena bispinosa. Butyltins levels were higher than phenyltins in gastropod tissues, sediments, and APPs. Regarding booster biocides, chlorothalonil was the most frequently detected compound and DCOIT was the most abundant biocide in sediments. DCOIT levels were registered in APPs from fishing harbors and marina areas. In addition, the highest levels of TBT, Irgarol, diuron and DCOIT exceeded the threshold limits set by international sediment quality guidelines, indicating that toxic effects could be expected in some of the studied areas, thus being a potential threat to marine life. Based on such outputs, Mexico urgently needs to adopt restrictive actions aiming at conserving the rich biological heritage of the Yucatán Peninsula., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The association between lung injury and exposure to humidifier disinfectant (HD) containing a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) has been controversial in South Korea. This study conducts a literature review in order to evaluate the likelihood of CMIT/MIT reaching the lower part of the respiratory tract and causing lung injury. A literature review focused on the inhalation risk of HD containing a mixture of CMIT and MIT. The major contents included the physicochemical properties of CMIT and MIT contained in HDs and methodological reviews on substance analysis, toxicity tests and clinical cases. HD products marketed in South Korea have been reported to contain approximately 1-2% CMIT and 0.2-0.6% MIT along with magnesium nitrate (20-25%), magnesium chloride (0.2-1.0%), and water (70-75%). The types of CMIT and MIT dispersed into the air and deposited in the respiratory tract are assumed to be either gaseous substances or nanoparticles mixed with magnesium salts. The result of the literature review including clinical cases of lung injury among CMIT/MIT HD product users, demonstrated that these chemicals likely reach the lower respiratory tract and accordingly cause lung injury. A number of humidifier disinfectant-associated lung injury cases with clinical evidence should be prioritized in risk assessment of HD containing CMIT and MIT, even though there might be insufficient evidence in all related areas, including inhalation exposure assessment studies, animal testing, and epidemiological studies., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Recent advances in nanotechnology have allowed the encapsulation of hazardous antifouling (AF) biocides in silica mesoporous nanocapsules (SiNC) reducing their short-term toxicity. However, the chronic effects of such novel nanoadditives remain understudied. The present study aimed to assess short- and long-term sub-lethal effects of soluble forms (DCOIT and Ag) and nanostructured forms (SiNC-DCOIT and SiNC-DCOIT-Ag) of two AF biocides and the "empty" nanocapsule (SiNC) on juveniles of Crassostrea gigas after 96 h and 14 days of exposure. Juvenile oysters exposed for a short period to free DCOIT and AgNO 3 presented worse physiological status comparing with those exposed to the nanostructured forms. The long-term exposure to DCOIT and Ag + caused an extensive biochemical impairment comparing with the tested nanomaterials, which included oxidative damage, activation of the antioxidant defense system, and neurotransmission impairment. Despite the negative effects mostly observed on the health condition index and AChE, the encapsulation of the abovementioned AF biocides into SiNC seems to be a technological advantage towards the development of AF nanoadditives with lower long-term toxicity comparing with the soluble forms of such biocides., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Antifouling paints incorporate biocides in their composition seeking to avoid or minimize the settlement and growing of undesirable fouling organisms. Therefore, biocides are released into the aquatic environments also affecting several nontarget organisms and, thus, compromising ecosystems. Despite global efforts to investigate the environmental occurrence and toxicity of biocides currently used in antifouling paints, the specific active ingredients that have been used in commercial products are poorly known. Thus, the present study assessed the frequencies of occurrence and relative concentrations of biocides in antifouling paint formulations registered for marketing worldwide. The main data were obtained from databases of governmental agencies, business associations, and safety data sheets from paint manufacturers around the world. The results pointed out for 25 active ingredients currently used as biocides, where up to six biocides have been simultaneously used in the examined formulations. Cuprous oxide, copper pyrithione, zinc pyrithione, zineb, DCOIT, and cuprous thiocyanate were the most frequent ones, with mean relative concentrations of 35.9 ± 12.8%, 2.9 ± 1.6%, 4.0 ± 5.3%, 5.4 ± 2.0%, 1.9 ± 1.9%, and 18.1 ± 8.0% (w/w) of respective biocide present in the antifouling paint formulations. Surprisingly, antifouling paints containing TBT as an active ingredient are still being registered for commercialization nowadays. These results can be applied as a proxy of biocides that are possibly being used by antifouling systems and, consequently, released into the aquatic environment, which can help to prioritize the active ingredients that should be addressed in future studies., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)