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There are no studies investigating the association of chlorinated drinking water with the risk of cardiovascular diseases (CVDs) among young and middle-aged adults. This study was aimed to assess the associations between trihalomethanes (THMs) in drinking water and the risk of CVDs in in the target group in Petropavlovsk, Kazakhstan. 448 dwellers of Petropavlovsk were asked about their demographic, socioeconomic, lifestyle, behavioural characteristics, and drinking water preferences. THMs exposure was assessed to each participant based on their residence address. We used multivariable logistic regression analysis to assess the risk of CVDs in young and middle-aged adults. The results showed that the risk of hypertension in the adjusted logistic regression model was increased by 68%   and a 2.7-fold   in the second and third THM tertiles, respectively. Participants in the second and third THM exposure tertiles had a 2.3-fold and a 4.8-fold increase in the risk of arrhythmia.

This study aimed to assess the global spatiotemporal variations of trihalomethanes (THMs) in drinking water, evaluate their cancer and non-cancer risks, and THM-attributable bladder cancer burden. THM concentrations in drinking water around fifty years on a global scale were integrated. Health risks were assessed using Monte Carlo simulations and attributable bladder cancer burden was estimated by comparative risk assessment methodology. The results showed that global mean THM concentrations in drinking water significantly decreased from 78.37 μg/L (1973-1983) to 51.99 μg/L (1984-2004) and to 21.90 μg/L (after 2004). The lifestage-integrative cancer risk and hazard index of THMs through all exposure pathways were acceptable with the average level of 6.45 × 10 -5 and 7.63 × 10 -2 , respectively. The global attributable disability adjusted of life years (DALYs) and the age-standardized DALYs rate (ASDR) dropped by 16% and 56% from 1990-1994 to 2015-2019, respectively. A big decline in the attributable ASDR was observed in the United Kingdom (62%) and the United States (27%), while China experienced a nearly 3-fold increase due to the expanded water supply coverage and increased life expectancy. However, China also benefited from the spread of chlorination, which helped reduce nearly 90% of unsafe-water-caused mortality from 1998 to 2018., 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 by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to varying conclusions. This meta-analysis aimed to evaluate the dose-response relationship and the dose-dependent effect of DBPs on cancer risk. We performed a selective search in PubMed, Web of Science, and Embase databases for articles published up to September 15th, 2023. Our meta-analysis eventually included 25 articles, encompassing 8 cohort studies with 6038,525 participants and 10,668 cases, and 17 case-control studies with 10,847 cases and 20,702 controls. We observed a positive correlation between increased cancer risk and higher concentrations of total trihalomethanes (TTHM) in water, longer exposure durations, and higher cumulative TTHM intake. These associations showed a linear trend, with relative risks (RRs) and 95 % confidence intervals (CIs) being 1.02 (1.01-1.03), 1.04 (1.02-1.06), and 1.02 (1.00-1.03), respectively. Gender-specific analyses revealed slightly U-shaped relationships in both males and females, with males exhibiting higher risks. The threshold dose for TTHM in relation to cancer risk was determined to be 55 µg/L for females and 40 µg/L for males. A linear association was also identified between bladder cancer risk and TTHM exposure, with an RR and 95 % CI of 1.08 (1.05-1.11). Positive linear associations were observed between cancer risk and exposure to chloroform, bromodichloromethane (BDCM), and HAA5, with RRs and 95 % CIs of 1.02 (1.01-1.03), 1.33 (1.18-1.50), and 1.07 (1.03-1.12), respectively. Positive dose-dependent effects were noted for brominated THMs above 35 µg/L and chloroform above 75 µg/L. While heterogeneity was observed in the studies for quantitative synthesis, no publication bias was detected. Exposure to TTHM, chloroform, BDCM, or HAA5 may contribute to carcinogenesis, and the risk of cancer appears to be dose-dependent on DBP exposure levels. A cumulative effect is suggested by the positive correlation between TTHM exposure and cancer risk. Bladder cancer and endocrine-related cancers show dose-dependent and positive associations with TTHM exposure. Males may be more susceptible to TTHM compared to females., 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.)

Background: Some disinfection byproducts (DBPs) are teratogens based on toxicological evidence. Conventional use of predominant DBPs as proxies for complex mixtures may result in decreased ability to detect associations in epidemiological studies., Objective: We assessed risks of obstructive genitourinary birth defects (OGDs) in relation to 12 DBP mixtures and 13 individual component DBPs., Methods: We designed a nested registry-based case-control study (210 OGD cases; 2100 controls) in Massachusetts towns with complete quarterly 1999-2004 data on four trihalomethanes (THMs) and five haloacetic acids (HAAs). We estimated temporally-weighted average DBP exposures for the first trimester of pregnancy. We estimated adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for OGD in relation to individual DBPs, unweighted mixtures, and weighted mixtures based on THM/HAA relative potency factors (RPF) from animal toxicology data for full-litter resorption, eye defects, and neural tube defects., Results: We detected elevated aORs for OGDs for the highest of bromodichloromethane (aOR = 1.75; 95% CI: 1.15-2.65), dibromochloromethane (aOR = 1.71; 95% CI: 1.15-2.54), bromodichloroacetic acid (aOR = 1.56; 95%CI: 0.97-2.51), chlorodibromoacetic acid (aOR = 1.97, 95% CI: 1.23-3.15), and tribromoacetic acid (aOR = 1.90; 95%CI: 1.20-3.03). Across unweighted mixture sums, the highest aORs were for the sum of three brominated THMs (aOR = 1.74; 95% CI: 1.15-2.64), the sum of six brominated HAAs (aOR = 1.43; 95% CI: 0.89-2.31), and the sum of nine brominated DBPs (aOR = 1.80; 95% CI: 1.05-3.10). Comparing eight RPF-weighted to unweighted mixtures, the largest aOR differences were for two HAA metrics, which both were higher with RPF weighting; other metrics had reduced or minimally changed ORs in RPF-weighted models., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Disinfection by-products (DBPs) are a concern due to their presence in chlorinated wastewater, sewage treatment plant discharge, and surface water, and their potential for environmental toxicity. Despite some attention to their ecotoxicity, little is known about the phytotoxicity of DBPs. This study aimed to evaluate the individual and combined phytotoxicity of four trihalomethanes (THMs: trichloromethane (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and tribromomethane (TBM) and their mixture (THM4)), and trichloroacetic acid (TCAA) using genotoxic and cytotoxic assays. The analysis included seed germination tests using Vigna radiata and root growth tests, mitosis studies, oxidative stress response, chromosomal aberrations (CA), and DNA laddering using Allium cepa. The results showed a progressive increase in root growth inhibition for both plant species as the concentration of DBPs increased. High concentrations of mixtures of four THMs resulted in significant (p < 0.05) antagonistic interactions. The effective concentration (EC 50 ) value for V. radiata was 5655, 3145, 2690, 1465, 3570, and 725 mg/L for TCM, BDCM, DBCM, TBM, THM4, and TCAA, respectively. For A. cepa, the EC 50 for the same contaminants was 700, 400, 350, 250, 450, and 105 mg/L, respectively. DBP cytotoxicity was observed through CAs, including C-metaphase, unseparated anaphase, lagging chromosome, sticky metaphase, and bridging. Mitotic depression (MD) increased with dose, reaching up to 54.4% for TCAA (50-500 mg/L). The electrophoresis assay showed DNA fragmentation and shearing, suggesting genotoxicity for some DBPs. The order of phytotoxicity for the tested DBPs was TCAA > TBM > DBCM > BDCM > THM4 > TCM. These findings underscore the need for further research on the phytotoxicity of DBPs, especially given their common use in agricultural practices such as irrigation and the use of sludge as manure., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Colorectal cancer is the third most common malignancy worldwide and is strongly linked to lifestyle and environmental risk factors. Although several drinking-water disinfection by-products are confirmed rodent carcinogens, the evidence in humans for carcinogenicity associated with these by-products, including colorectal cancer, is still inconclusive., Methods: We assessed the association of long-term exposure to trihalomethanes (THMs), the most prevalent disinfection by-products in chlorinated drinking water, with incidence of colorectal cancer in 58 672 men and women in 2 population-based cohorts. Exposure was assessed by combining long-term information of residential history with drinking water-monitoring data. Participants were categorized according to no exposure, low exposure (<15 µg/L), and high exposure (≥15 µg/L). Incident cases of colorectal cancer were ascertained by use of the Swedish National Cancer Register., Results: During an average follow-up of 16.8 years (988 144 person-years), 1913 cases of colorectal cancer were ascertained (1176 cases in men and 746 in women, respectively). High THM concentrations in drinking water (≥15 µg/L) were associated with increased risk of colorectal cancer in men (hazard ratio = 1.26, 95% confidence interval = 1.05-1.51) compared with no exposure. When subsites were assessed, the association was statistically significant for proximal colon cancer (hazard ratio = 1.59, 95% confidence interval = 1.11 to 2.27) but not for distal colon cancer or rectal cancer. In women, we observed overall no association of THMs with colorectal cancer., Conclusion: These results add further evidence that disinfection by-products in drinking water may be a possible risk factor for proximal colon cancer in men. This observation was made at THM concentrations lower than those in most previous studies., (© The Author(s) 2023. Published by Oxford University Press.)

Numerous disinfection by-products (DBPs) are formed from reactions between disinfectants and organic/inorganic matter during water disinfection. More than seven hundred DBPs that have been identified in disinfected water, only a fraction of which are regulated by drinking water guidelines, including trihalomethanes, haloacetic acids, bromate, and chlorite. Toxicity assessments have demonstrated that the identified DBPs cannot fully explain the overall toxicity of disinfected water; therefore, the identification of unknown DBPs is an important prerequisite to obtain insights for understanding the adverse effects of drinking water disinfection. Herein, we review the progress in identification of unknown DBPs in the recent five years with classifications of halogenated or nonhalogenated, aliphatic or aromatic, followed by specific halogen groups. The concentration and toxicity data of newly identified DBPs are also included. According to the current advances and existing shortcomings, we envisioned future perspectives in this field., 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. Level of confidence in DBP identification based on the level system proposed by Schymanski et al. (2014) (Schymanski et al., 2014): Level 1: structure confirmed with a reference standard; Level 2: exact structure was proposed by different evidence; Level 3: candidate structural isomer exist but exact structure was not confirmed; Level 4: specific molecular formula was determined; Level 5: only exact mass (m/z) was measured while formula was not elucidated., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Chlorination is widely used to disinfect drinking water to keep humans safe from microorganisms. During chlorination, chlorine and its compounds react with contaminants to form disinfection by-products (DBPs). Toxicological and epidemiological studies have demonstrated that trihalomethanes (THMs) are the most widely investigated DBPs in drinking water, and their exposure has been associated with some adverse health effects. However, studies about risk characteristics in this field are limited. We estimated the health risks of THMs exposure in drinking water through multi-pathways, and systematically analyzed the factors influencing health risks of THMs in Wuxi, China. A total of 488 drinking water samples were collected and analyzed for THMs from four water treatment utilities from 2008 to 2016 in Wuxi. And water exposure parameters were obtained from 602 participants by structured questionnaires. The median concentration of THMs ranged from 6.71 μg/L to 9.18 μg/L. The cumulative cancer risk of THMs exposure through multi-pathways was 1.26 × 10 -4 , and CHBr 2 Cl made the largest contribution to the total cancer risk (48.25%). The non-cancer risk of THMs exposure was 2.02 × 10 -1 . Health risks of the exposure to THMs in drinking water in summer were significantly higher than that in winter (P = 0.0003 for cancer risk, and P = 5.95 × 10 -7 for non-cancer risk). In our study, the average individual disability-adjusted life years (DALYs) lost was 1.27 × 10 -4 per person-year (ppy). This study attempted to use DALYs for risk assessment of THMs, which will provide useful information for risk comparison and prioritization of hazards in drinking water. This suggested that potential higher risk might exist, and possible measures could be considered to decrease the health risks., 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 © 2023 Elsevier Ltd. All rights reserved.)

Trichloroisocyanuric acid (TCCA) is a popular disinfectant for swimming pools in China. However, the occurrence and importance of regulated disinfection byproducts (DBPs) in TCCA-disinfected swimming pools are less understood. This study analyzed 12 regulated DBPs (4 trihalomethanes (THMs), 5 haloacetic acid (HAAs), bromate, chlorate, and chlorite) in 85 swimming pool water samples and 17 input tap water samples from one swimming pool for 17 days continuously. Considering water temperature, pH, free chlorine, total chlorine, and urea, most of swimming pool water samples were within the water quality limits for China. Total concentrations of THMs, HAAs, and inorganic DBPs of 20.4-42.2, 82.0-229, and 100-729 μg/L in the swimming pool, and 16.6-28.3, 8.2-12.8, and 64.4-95.6 μg/L in the tap water, indicating inorganic DBPs are the dominant swimming pool and drinking water pollutants. Cancer risk values of regulated DBPs in swimming pools and input tap water are 2.7E-05 and 8.1E-05, respectively, and exceed the US EPA's threshold (1.0E-06). The non-cancer risk is below the US EPA's threshold. Following TCCA disinfection, the concentration and calculated cytotoxicity of regulated DBPs had a 3.6-fold and 1.9-fold increase, respectively. Inorganic DBPs contribute to the calculated concentration and cancer risks of DBPs in swimming pools and tap water at sufficient concentrations warranting regulation. This study provides data on 12 regulated DBPs in TCCA-disinfected indoor swimming pools, highlighting the importance of inorganic DBPs from evidences of concentration, cytotoxicity, and cancer risk for the first time., 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 © 2023 Elsevier Ltd. All rights reserved.)

The formation characteristics of trihalomethanes (THMs) and haloacetamides (HAcAms) from dissolved organic matter and its fractions were investigated during chlorine-based disinfection processes. The relationships between water quality parameters, fluorescence parameters, and the formation levels of THMs and HAcAms were analyzed. The fractions contributing most to the acute toxicity were identified. The trichloromethane (TCM) generation level (72 h) generally followed the order of Cl 2  > NH 2 Cl > NHCl 2 process. The NHCl 2 process was superior to the NH 2 Cl process in controlling TCM formation. Hydrophobic acidic substance (HOA), hydrophobic neutral substance (HON), and hydrophilic substance (HIS) were identified as primary precursors of 2,2-dichloroacetamide and trichloroacetamide during chlorination and chloramination. The formation of TCM mainly resulted from HOA, HON and HIS fractions relatively uniformly, while HOA and HIS fractions contributed more to the formation of bromodichloromethane and dibromomonochloromethane. UV 254 could be used as an alternative indicator for the amount of ΣTHMs formed during chlorination and chloramination processes. Dissolved organic nitrogen was a potential precursor of 2,2-dichloroacetamide during chlorination process. The fractions with the highest potential acute toxicity after the chlorination were water-dependent., 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 © 2023. Published by Elsevier Ltd.)

Quantification of regulated and emerging disinfection byproducts (DBPs) in swimming pool water, as well as the assessment of their lifetime health risk are limited in China. In this study, the occurrence of regulated DBPs (e.g., trihalomethanes, haloacetic acids) and emerging DBPs (e.g., haloacetonitriles, haloacetaldehydes) in indoor swimming pool water and the corresponding source water at a city in Eastern China were determined. The concentrations of DBPs in swimming pool water were 1-2 orders of magnitude higher than that in source water. Lifetime cancer and non-cancer risks of DBPs stemming from swimming pool water were also estimated. Inhalation and dermal exposure were the most significant exposure routes related to swimming pool DBP cancer and non-cancer risks. For the first time, buccal and aural exposure were considered, and were proven to be important routes of DBP exposure (accounting for 17.9%-38.9% of total risk). The cancer risks of DBPs for all swimmers were higher than 10 -6 of lifetime exposure risk recommended by United States Environmental Protection Agency, and the competitive adult swimmers experienced the highest cancer risk (7.82 × 10 -5 ). These findings provide important information and perspectives for future efforts to lower the health risks associated with exposure to DBPs in swimming pool water., 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 article., (Copyright © 2022. Published by Elsevier B.V.)

Background: Nitrate and trihalomethanes (THMs) in drinking water are widespread and are potential human carcinogens., Objective: We evaluated the association between drinking-water exposure to nitrate and THMs and prostate cancer., Methods: During the period 2008-2013, 697 hospital-based incident prostate cancer cases (97 aggressive tumors) and 927 population-based controls were recruited in Spain, providing information on residential histories and type of water consumed. Average nitrate and THMs levels in drinking water were linked with lifetime water consumption to calculate waterborne ingestion. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models with recruitment area as random effect. Effect modification by tumor grade (Gleason score), age, education, lifestyle, and dietary factors was explored., Results: Mean ( ± standard deviation ) adult lifetime waterborne ingested nitrate (milligrams per day), brominated (Br)-THMs (micrograms per day), and chloroform (micrograms per day) were 11.5 ( ± 9.0 ), 20.7 ( ± 32.4 ), and 15.1 ( ± 14.7 ) in controls. Waterborne ingested nitrate > 13.8 vs. < 5.5 mg / d was associated with an OR of 1.74 (95% CI: 1.19, 2.54) overall, and 2.78 (95% CI: 1.23, 6.27) for tumors with Gleason scores ≥ 8 . Associations were higher in the youngest and those with lower intakes of fiber, fruit/vegetables, and vitamin C. Waterborne ingested THMs were not associated with prostate cancer. Residential tap water levels of Br-THMs and chloroform showed, respectively, inverse and positive associations with prostate cancer., Conclusions: Findings suggest long-term waterborne ingested nitrate could be a risk factor of prostate cancer, particularly for aggressive tumors. High intakes of fiber, fruit/vegetables and vitamin C may lower this risk. Association with residential levels but not ingested chloroform/Br-THM may suggest inhalation and dermal routes could be relevant for prostate cancer. https://doi.org/10.1289/EHP11391.

Background: In animal and human studies, exposure to trihalomethanes (THMs) has been associated with reduced semen quality. However, the underlying mechanisms remain poorly understood., Objective: To investigate the associations of blood THM concentrations with sperm mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) among healthy men., Methods: We recruited 958 men who volunteered as potential sperm donors. A single blood sample was collected from each participant at recruitment and measured for chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) concentrations. Within a 90-day follow-up, the last semen sample provided by each participant was quantified for sperm mtDNAcn and TL. We used multivariable linear regression models to assess the associations between blood THM concentrations and sperm mtDNAcn and TL. We also performed stratified analyses according to the time intervals between baseline blood THM determinations and semen collection (i.e., 0-9, 10-14, 15-69, or >69 days) to explore potential windows of susceptibility., Results: After adjusting for potential confounders, we found inverse associations between quartiles (or categories) of blood TBM, brominated THM (Br-THM, the sum of BDCM, DBCM, and TBM), and total THM (TTHM, the sum of all four THMs) concentrations and sperm mtDNAcn (all P for trend≤0.03). Besides, we found inverse associations between quartiles of blood TCM, Br-THM, chlorinated THM (Cl-THM, the sum of TCM, BDCM, and DBCM), and TTHM concentrations and sperm TL (all P for trend<0.10). Stratified analyses showed stronger associations between Br-THM concentrations and sperm mtDNAcn determined 15-69 days since baseline exposure determinations, and between blood TCM and TTHM concentrations and sperm TL determined >69 days since baseline exposure determinations., Conclusion: Exposure to THMs may be associated with sperm mitochondrial and telomeric dysfunction., 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 Inc. All rights reserved.)

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.)

Background: Disinfection byproducts (DBPs) in public water systems (PWS) are an unintended consequence resulting from reactions between mostly chlorine-based disinfectants and organic and inorganic compounds in source waters. Epidemiology studies have shown that exposure to DBP (specifically trihalomethanes) was associated with an increased risk of bladder cancer., Objective: Our goal was to characterize the relative differences in exposures and estimated potential bladder cancer risks for people served by different strata of PWS in the United States and to evaluate uncertainties associated with these estimates., Methods: We stratified PWS by source water type (surface vs. groundwater) and population served (large, medium, and small) and calculated population-weighted mean trihalomethane-4 (THM4) concentrations for each stratum. For each stratum, we calculated a population attributable risk (PAR) for bladder cancer using odds ratios derived from published pooled epidemiology estimates as a function of the mean THM4 concentration and the fraction of the total U.S. population served by each stratum of systems. We then applied the stratum-specific PARs to the total annual number of new bladder cancer cases in the U.S. population to estimate bladder cancer incidence in each stratum., Results: Our results show that approximately 8,000 of the 79,000 annual bladder cancer cases in the United States were potentially attributable to DBPs in drinking water systems. The estimated attributable cases vary based on source water type and system size. Approximately 74% of the estimated attributable cases were from surface water systems serving populations of > 10,000 people. We also identified several uncertainties that may affect the results from this study, primarily related to the use of THM4 as a surrogate measure for DBPs relevant to bladder cancer., Discussion: Despite significant reductions in exposure over the past several decades, our study suggests that ∼ 10 % of the bladder cancer cases in the United States may still be attributed to exposure to DBPs found in drinking water systems. https://doi.org/10.1289/EHP9985.

In this study, we report the formation and cancer risk estimation of trihalomethanes (THMs) emanating from 'ex-situ' chlorination of shallow hand-dug well water obtained from a peri-urban area of Mufulira District, Zambia. The aim of the study was to evaluate the potential cancer risks for people in this area where chlorine water disinfection at the household level is commonly practiced. Water samples from 13 randomly selected hand-dug wells (4-8 m deep) were collected and analyzed for pH, turbidity, and dissolved organic carbon before chlorination. Then another set of water samples from the same 13 wells was chlorinated using the methods commonly practiced in this area, consistent with WHO recommended doses. The chlorination degradation products, THMs, trichloromethane, bromodichloromethane (CHCl 2 Br), dibromochloromethane (CHClBr 2 ), and tribromomethane, were determined at three different times of 60, 180, and 300 min after chlorination, while residual chlorine was determined immediately after chlorination and at 60 and 1,440 min after chlorination. THMs were determined using gas chromatography (GC), while residual chlorine was determined colorimetrically. Then cancer risk estimation from ingestion, inhalation, and dermal routes was carried out. All water samples from the 13 wells showed elevated amounts of THMs, which also increased with increasing contact time. For instance, the concentrations of THMs at 60 min after chlorination ranged from 24.3 ± 2.0 to 61.3 ± 1.0 μg/L, while at 180 and 300 min, ranged between 85.6 ± 4.3-146.9 ± 2.5 μg/L and 188.1 ± 7.1-250.1 ± 7.1 μg/L, respectively. It was observed that tribromomethane was not detected at all in all samples, while CHCl 2 Br and CHClBr 2 were only detected at 180 and 300 min post chlorination. The lifetime cancer risk estimation results showed negligible risk at 60 min post chlorination. However, at 180 and 300 min post chlorination, the results were far above negligible, but within the regulatory US EPA limits. The overall risk, however, could not be ignored, given a multiplicity of exposure to various other contaminants, raising concerns over additivity and synergistic interactive effects, particularly for non-cancer hazard indices.

Ship ballast water can control the roll, trim, and draft of the ship, and thus ensuring the balance and stability of the ship in the course of sailing, and playing a vital role in the safe navigation of ships. The annual discharge of ship ballast water is very large in China. About three to five billion cubic meters of ship ballast water is discharged into offshore or inland waters every year. This water contains plankton, pathogens, and their larvae or spores. If not be handled appropriately, this will have a serious impact on the ecological environment of the discharge waters. Ballast water is usually treated by electrolysis before being discharged. Sodium hypochlorite can be generated, which can kill microorganisms; however, the by-products trihalomethanes (THMs) are cytotoxic and biotoxic. Studies have shown that THMs may cause fetal growth retardation, spontaneous abortion, or death. The concentration of THMs in drinking water is closely related to the risk of bladder cancer death. Hence, it is important to establish a method for the determination of THMs in ship ballast water. The four kinds of THMs are chloroform, dichlorobromomethane, chlorodibromomethane, and tribromomethane. At present, ship ballast water is mostly analyzed by gas chromatography (GC) using an electron capture detector (ECD) or by gas chromatography-mass spectrometry (GC-MS). Given the low boiling point of THMs, headspace injection and purge-and-trap can be used. Gas chromatography-negative chemical ionization-mass spectrometry (GC-NCI-MS), was adopted. NCI is a soft ionization technique that shows special response to compounds bearing electronegative elements or groups. THMs contain electronegative chlorine atoms and bromine atoms. Therefore, NCI is a good choice for their analysis. The samples were processed by the headspace injection technique. The NaCl content in 10 mL sample was optimized in headspace injection. The results showed that 3.0 g NaCl was the most suitable dosage. The analytes were separated on a DB-5MS UI capillary-column (30 m×0.25 mm×1.0 μm). The target compounds were quantified by using the external standard method in selected ion monitoring (SIM) mode. The four THMs were not only well separated but also showed a high response at 0.2 μg/L. The four THMs showed good linear relationships in the range of 0.2-50 μg/L, with correlation coefficients≥0.995. The limits of quantification (LOQs, S/N =10) were 0.1-0.2 μg/L, and the average recoveries of the four THMs were 90.3%-106.8% at the three spike levels of 0.2, 0.5, and 2.0 μg/L. The relative standard deviations were 1.4%-6.2%. The LOQs of the THMs in the GB/T 5750.8-2006 Standard Test Method of Drinking Water Organic Matter Index are 0.3-6.0 μg/L. It can be seen that the LOQs of the THMs are greatly reduced in this study. The proposed method is accurate, stable, and reliable, and it can be used for monitoring the four THMs in ship ballast water. The method was applied for the detection of 36 ship ballast water samples. In all cases, the detection rates of tribromomethane, chlorodibromomethane, dichlorobromomethane, and chloroform were 83.3%, 69.4%, 22.2%, and 19.4%, respectively. The detection values of tribromomethane, chlorodibromomethane, dichlorobromomethane, and chloroform were 34.25-221.5 μg/L, 3.52-41.87 μg/L, 1.52-8.56 μg/L, and 0.02-5.46 μg/L, respectively. Based on the analysis of several ship ballast water samples (electrolytic water), it was concluded that the greater the number of bromine atoms in the THMs, the higher are the detection rate and detection value in ship ballast water. Compared to chloroform, tribromomethane is more harmful to living beings. China has acceded to the International Convention on Ship Ballast Water and Sediment Control and Management. There is an urgent need to establish analysis methods with high sensitivity, good stability, and high accuracy in addition to determining standards and regulations for ship ballast water.

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.)

The present study aims to assess the probable lifetime cancer and non-cancer risks of exposure to the trihalomethanes in Egypt's drinking water through ingestion, dermal contact, and inhalation. A total of 1667 drinking water samples were collected from twenty-three Egyptian governorates over a three-years period. The concentrations of total trihalomethanes ranged between 29.07 and 86.01 μg/L and were always below the maximum contamination level recommended by the Egyptian standards (100 μg/L). Chloroform was the most prominent trihalomethanes species, while bromoform was rarely detected. The cancer risk study revealed that, among the investigated paths, inhalation poses the greatest risk. And bromodichloromethane had the highest impact to cancer (69%), followed by chlorodibromomethane (28%). Geographically, the highest cancer risk value was found in Matruh governorate (42.2 × 10 -6 ) and the lowest was in Minya governorate (1.0 × 10 -6 ). The cancer risk for the studied governorates, except Minya governorate, was higher than the level recommended by the USEPA (1.0 × 10 -6 ). Hazard index (HI) study revealed that the ingestion pathway caused higher HI values than the dermal pathway and that chloroform had the highest contribution to HI value. However, the values of HI were below unity in all studied governorates demonstrating that there would be negligible non-cancer risk., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants., Objectives: In this study, we investigated the combined effect on bladder cancer risk contributed by TTHMs, bladder cancer susceptibility variants identified through genome-wide association studies, and variants in several candidate genes., Methods: We analyzed data from two large case-control studies-the New England Bladder Cancer Study ( n / n = 989 cases/1,162 controls), a population-based study, and the Spanish Bladder Cancer Study ( n / n = 706 cases/772 controls), a hospital-based study. Because of differences in exposure distributions and metrics, we estimated effects of THMs and genetic variants within each study separately using adjusted logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CI) with and without interaction terms, and then combined the results using meta-analysis., Results: Of the 16 loci showing strong evidence of association with bladder cancer, rs907611 at 11p15.5 [leukocyte-specific protein 1 ( LSP1 region)] showed the strongest associations in the highest exposure category in each study, with evidence of interaction in both studies and in meta-analysis. In the highest exposure category, we observed OR = 1.66 (95% CI: 1.17, 2.34, p -trend = 0.005 ) for those with the rs907611-GG genotype and p -interaction = 0.02 . No other genetic variants tested showed consistent evidence of interaction., Discussion: We found novel suggestive evidence for a multiplicative interaction between a putative bladder carcinogen, TTHMs, and genotypes of rs907611. Given the ubiquitous exposure to THMs, further work is needed to replicate and extend this finding and to understand potential molecular mechanisms. https://doi.org/10.1289/EHP9895.

Background: Disinfection byproducts (DBPs) and N -nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited., Objectives: We investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort., Methods: Among postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen ( NO 3 -N ) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS > 10 y at enrollment ( n = 10 , 501 ; cases = 261 ), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible ≥ 95 th percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level ( >½  MCL ; 40 μ g / L TTHM; 30 μ g / L HAA5; 5 mg / L   NO 3 -N ). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors [e.g., body mass index, hormone replacement therapy (HRT)], and mutually adjusted for DBPs  or  NO 3 -N . We evaluated associations for low-grade ( cases = 99 ) vs. high-grade ( cases = 114 ) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation., Results: Higher average concentrations of DBPs (95th percentile: TTHM ≥ 93 μ g / L , HAA5 ≥ 49 μ g / L ) were associated with endometrial cancer risk (TTHM: HR 95 vsQ 1 = 2.19 , 95% CI: 1.41, 3.40; HAA5: HR 95 vsQ 1 = 1.84 , 95% CI: 1.19, 2.83; p trend < 0.01 ). Associations were similarly observed for women greater than median years of PWS use with levels >½  MCL , in comparison with zero years (TTHM: HR 36 + vs 0 y = 1.61 , 95% CI: 1.18, 2.21; HAA5: HR 38 + vs 0 y = 1.85 , 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: HR Q 4 vsQ 1 = 2.12 , 95% CI: 1.17, 3.83; p -trend = 0.008 ) than for high-grade tumors (TTHM: HR Q 4 vsQ 1 = 1.40 , 95% CI: 0.80, 2.44; p -trend = 0.339 ), but differences were not statistically significant ( p -heterogeneity = 0.43 ). Associations with TTHM were stronger among ever HRT users than non-HRT users ( p -interaction < 0.01 ). We observed no associations with NO 3 -N in drinking water or diet., Discussion: We report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.

The study aimed to examine the associations between the level of trihalomethanes and its metabolites in pregnancy and the risks of adverse birth outcomes. We searched the databases of the China National Knowledge Infrastructure, WanFang, Vip, PubMed, and Elsevier Science Direct from database establishment to July 14, 2021 and performed a systematic review and meta-analysis of observational studies reporting associations between trihalomethanes level and abnormally low birth weight and preterm birth. The pooled odds ratio (OR), pooled risk ratio, and pooled risk difference with their 95% confidence interval (CI) were calculated for risk estimates. A total of 24 studies involving 1,118,037 pregnant women were finally enrolled in the present systematic review and meta-analysis. Our research found that abnormally low birth weight was associated with higher levels of total trihalomethanes (OR = 2.45, 95% CI: 1.28, 4.68; P = 0.007). Unexpectedly, the meta-analysis indicated that higher total trihalomethanes level was associated with lower odds of preterm birth (OR = 0.90, 95% CI: 0.81, 0.99; P = 0.03). Our findings indicate that trihalomethanes exposure might be a risk factor for abnormally low birth weight and that it would be prudent to minimize exposure to trihalomethanes during pregnancy because of the risk of abnormally low birth weight. Given some limitations of the systematic review and meta-analysis, our results should be interpreted with caution., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In developing countries, the evaluation of disinfection by-products in drinking water has been neglected because most water utility companies focus on microbial elimination. As a result, this study aimed at evaluating trihalomethane formation, the relation between water quality parameters and trihalomethane formation, and the estimation of the associated potential health risks in drinking water. The headspace purge and trap coupled with a gas chromatography-mass spectrometry technique was used to quantify trihalomethane. The concentrations of trihalomethane found in the water were within the National Water and Sewerage Corporation, World Health Organization guidelines, and the United States Environmental Protection Agency standards. Total organic carbon, ultraviolet absorbance at 254 nm, bromide concentration, and the temperature had a positive and significant correlation, pH had a positive but non-significant correlation, while the residual chlorine had a negative but significant correlation with trihalomethane formation. The potential health risk using the WHO index was 0.4, indicating no noncarcinogenic risk to human health in the study area. The lifetime carcinogenic risks of trihalomethane due to oral ingestion, dermal, and inhalation were 2.5×10 -5 , 9.1×10 -6 , and 8.3×10 -6 for females and 2.4×10 -5 , 1×10 -5 , and 7.9×10 -6 for males, and the values were within the USEPA acceptable low-risk range of 1×10 -6 -5 .

Disinfection byproduct (DBP) exposure has been associated with birth size, pregnancy oxidative stress, and other adverse perinatal outcomes. However, little is known about the potential effect of prenatal DBP exposure on intrauterine growth. The present study included 1516 pregnant women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort who were measured for four blood trihalomethanes [i.e., chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] and two urinary haloacetic acids [i.e., dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA)] across pregnancy trimesters. Second- and third-trimester fetal ultrasound measures of the abdominal circumference (AC), head circumference, biparietal diameter, femur length, and estimated fetal weight and birth weight were converted into z-scores. After adjusting for potential confounders, linear mixed models showed a decreasing AC z-score across tertiles of blood brominated THM (Br-THMs, the sum of BDCM, DBCM, and TBM) and total THM (THM4, the sum of Br-THMs and TCM) concentrations (both p for trend <0.01). We also observed a decreasing AC z-score across categories of blood TBM during pregnancy trimesters ( p for trend = 0.03). Urinary haloacetic acids were unrelated to fetal growth parameters. In summary, prenatal exposure to THMs, particularly during the first trimester, was associated with reduced fetal abdominal circumference.

Background: Toxicological studies suggest that maternal exposure to disinfection by-products (DBPs) can impair fetal neurodevelopment. However, evidence from epidemiological studies is scarce and the underlying mechanisms remain unclear., Objective: To explore the trimester-specific associations between maternal blood trihalomethane (THM) and urinary haloacetic acid (HAA) concentrations and neonatal neurobehavioral development, and the potential mediating role of oxidative stress (OS)., Methods: We included 438 pregnant Chinese women from the Xiaogan Disinfection By-Products (XGDBP) birth cohort. Biospecimens were repeatedly collected across trimesters and measured for blood THMs, urinary HAAs, and urinary OS biomarker concentrations. On the third day after birth, the Neonatal Behavioral Neurological Assessment (NBNA) test was administered to newborns. Associations of trimester-specific DBP measurements and OS biomarkers with neonatal NBNA scores were assessed using linear regression models with generalized estimating equations. The potential mediating role of maternal OS biomarkers was also investigated using mediation analyses., Results: After adjusting for potential confounders, blood bromodichloromethane (BDCM) concentrations in the first trimester were inversely associated with NBNA scores [percent change comparing the extreme BDCM tertiles = -28.1% (95% CI: -55.2%, -0.88%); p for trend = 0.043]. Besides, third-trimester urinary trichloroacetic acid (TCAA) concentrations were inversely associated with NBNA scores [percent change comparing the extreme TCAA tertiles = -32.9% (95% CI: -64.7%, -1.0%); p for trend = 0.046]. These inverse associations differed across pregnancy trimesters (Type 3p-value = 0.066 and 0.053, respectively) and were stronger in male infants and mothers aged ≥25 years. There was no evidence of mediating effect by 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), or 8-iso-prostaglandin F 2α (8-isoPGF 2α )., Conclusions: Higher prenatal BDCM and TCAA concentrations during specific pregnancy trimesters were associated with lower NBNA scores. However, additional research is required to investigate underlying mechanisms., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water associated with colorectal cancer risk but mechanisms are not well understood., Objectives: We explored the association between exposure to THMs and nitrate in drinking water and inflammation markers, and the link with colorectal cancer risk., Methods: A subset of 198 colorectal cancer cases and 205 controls from the multicase-control study MCC-Spain were included. Average concentration of THMs (chloroform, bromodichloromethane, dibromochloromethane, bromoform) and nitrate in tap water at the residence was estimated from age 18 until 2 years before the interview ("long term") and for a recent period (3 years before diagnosis). Serum levels of EGF, eotaxin, G-CSF, IL-17E, IL-1rA, IL-8, IP-10, MDC, MPO, periostin, VEGF, and C-reactive protein (CRP) were measured. We estimated the linear association between inflammation markers and exposure among controls, and the odds ratio of colorectal cancer associated with THM and nitrate exposure, and inflammation markers. A mediation analysis was conducted to identify inflammation markers in the pathway between THM/nitrate exposure and colorectal cancer., Results: Serum concentrations of EGF, IL-8, IL-17E and eotaxin increased with recent residential levels of brominated THMs, chloroforom and/or total THM. No associations were observed for nitrate and for long-term residential THM levels. All residential exposures except chloroform were positively associated with colorectal cancer. Serum concentrations of VEGF and periostin were positively associated with colorectal cancer, while EGF was inversely associated. One protein-exposure combination (periostin-recent ingested brominated THMs) slightly mediated the association with colorectal cancer risk., Discussion: Results suggest that estimated THM exposure is involved in inflammation processes. However, the study design was limited to stablish etiologically relevant associations between the protein levels and colorectal cancer risk. The lack of association between nitrate exposure and inflammation markers suggests other biological mechanisms are involved in the link with colorectal cancer., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Brain tumours (BTs) are one of the most frequent tumour types in young people. We explored the association between tap water, exposure to trihalomethanes (THM) and nitrate and neuroepithelial BT risk in young people. Analysis of tap water consumption were based on 321 cases and 919 appendicitis controls (10-24 years old) from 6 of the 14 participating countries in the international MOBI-Kids case-control study (2010-2016). Available historical residential tap water concentrations of THMs and nitrate, available from 3 countries for 86 cases and 352 controls and 85 cases and 343 for nitrate, respectively, were modelled and combined with the study subjects' personal consumption patterns to estimate ingestion and residential exposure levels in the study population (both pre- and postnatal). The mean age of participants was 16.6 years old and 56% were male. The highest levels and widest ranges for THMs were found in Spain (residential and ingested) and Italy and in Korea for nitrate. There was no association between BT and the amount of tap water consumed and the showering/bathing frequency. Odds Ratios (ORs) for BT in relation to both pre- and postnatal residential and ingestion levels of THMs were systematically below 1 (OR = 0.37 (0.08-1.73)) for postnatal average residential THMs higher than 66 μg/L. For nitrate, all ORs were above 1 (OR = 1.80 (0.91-3.55)) for postnatal average residential nitrate levels higher than 8.5 mg/L, with a suggestion of a trend of increased risk of neuroepithelial BTs with increasing residential nitrate levels in tap water, which appeared stronger in early in life. This, to our knowledge, is the first study on this topic in young people. Further research is required to clarify the observed associations., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Drinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive., Objective: We conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns., Methods: We included all births during 2005-2015 (live and stillbirths) of mothers residing in Swedish localities having > 10,000 inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and < 5 , 5-15, and > 15 μ g TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression., Results: Based on 623,468 births and a prevalence of congenital malformation of ∼ 2 cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system ( OR = 1.82 ; 95% CI: 1.07, 3.12), urinary system ( OR = 2.06 ; 95% CI: 1.53, 2.78), genitals ( OR = 1.77 ; 95% CI: 1.38, 2.26), and limbs ( OR = 1.34 ; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite., Discussion: TTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. https://doi.org/10.1289/EHP9122.

Restoring woody vegetation to riparian zones helps to protect waterways from excessive sediment and nutrient inputs. However, the associated leaf litter can be a major source of dissolved organic matter (DOM) leached into surface waters. DOM can lead to the formation of disinfection by-products (DBPs) during drinking water treatment. This study investigated the DBPs formed during chlorination of DOM leached from leaf litter and assessed the potential toxicity of DBPs generated. We compared the leachate of two native Australian riparian trees, Casuarina cunninghamiana and Eucalyptus tereticornis, and a reservoir water source from a catchment dominated by Eucalyptus species. Leachates were diluted to dissolved organic carbon concentrations equivalent to the reservoir (~9 mg L -1 ). E. tereticornis leachates produced more trihalomethanes (THMs), haloacetic acids (HAAs), and haloketones after chlorination, while C. cunninghamiana produced more chloral hydrate and haloacetonitriles. Leachate from both species produced less THMs and more HAAs per mole of carbon than reservoir water. This may be because reservoir water had more aromatic, humic characteristics while leaf leachates had relatively more protein-like components. Using in vitro bioassays to test the mixture effects of all chemicals, chlorinated E. tereticornis leachate induced oxidative stress in HepG2 liver cells and bacterial toxicity more frequently and at lower concentrations than C. cunninghamiana and reservoir water. Overall, this study has shown that the DOM leached from litter of these species has the potential to generate DBPs and each species has a unique DBP profile with differing bioassay responses. E. tereticornis may pose a relatively greater risk to drinking water than C. cunninghamiana as it showed greater toxicity in bioassays. This implies tree species should be considered when planning riparian zones to ensure the benefits of vegetation to waterways are not offset by unintended increased DBP production and associated toxicity following chlorination at downstream drinking water intakes., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Water total trihalomethanes (TTHMs) are disinfectant byproducts found in municipal water supplies. TTHM exposure has been linked to cancer and may be associated with adverse reproductive outcomes. A non-optimal cervicovaginal microbiota and low cervicovaginal beta-defensin-2 levels are associated with increased risk of spontaneous preterm birth. Whether TTHM exposure increases the risk of spontaneous preterm birth or alters the cervicovaginal microbial or immune state is unknown., Objective: Investigate associations of water TTHM levels with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and beta-defensin-2 levels in a completed, diverse, urban pregnancy cohort. We hypothesized that higher TTHM levels would be associated with spontaneous preterm birth, a non-optimal cervicovaginal microbiota, and lower beta-defensin-2 levels., Design: Methods: This was a secondary analysis of participants (n = 474) in the Motherhood & Microbiome (M&M) study (n = 2000), who lived in Philadelphia and had cervicovaginal samples analyzed for cervicovaginal microbiota composition and beta-defensin-2 levels. The microbiota was classified into community state types (CSTs). CST IV (non-optimal microbiota) is characterized by a paucity of Lactobacillus species and wide array of anaerobes. Municipal water TTHM levels were obtained from 16 sites monthly across the city of Philadelphia to establish mean residential water supply levels for each participant for the first four months of pregnancy (prior to vaginal swab collection at 16-20 weeks' gestation). Associations of water TTHM levels with spontaneous preterm birth and a non-optimal cervicovaginal microbiota birth were analyzed using multivariable logistic regression. Multivariable linear regression was used to model associations of water TTHM levels with log-transformed cervicovaginal beta-defensin-2 levels. Since water TTHM levels vary by season and beta-defensin-2 levels have been shown to differ by race, stratified models by warm (April-September) and cold (October-March) seasons as well as by self-identified race were utilized., Results: Participants' water supply TTHM levels (mean μg/L [SD]) were higher in the warm (53.5 [9.4]) than cold (33.4 [7.5]) season (p < 0.0001). TTHM levels were non-significantly higher among Black participants than non-Black participants (44.8 [13.5] vs. 41.8 [11.8], p = 0.07). No associations were detected between TTHM with spontaneous preterm birth (per SD increment of TTHM, aOR 0.94, 95%CI: 0.66, 1.34) or with CST IV (aOR 0.94, 95%CI: 0.86, 1.16). Counter to our hypothesis, we observed positive associations of water TTHM with log-transformed cervicovaginal beta-defensin-2 levels in unadjusted models (β 0.20 [95%CI: 0.02, 0.39]) per SD increment of TTHM), but the association was null after adjustment for season. However, in models adjusted for covariates including season and stratified by race, TTHM was significantly associated with lower beta-defensin-2 levels among non-Black participants (β -0.75 [95%CI: -1.43, -0.08]) but not among Black participants (β 0.17 [95%CI: -0.15, 0.49]), interaction p = 0.013)., Conclusion: We did not detect associations of water TTHM levels with spontaneous preterm birth or the structure of the cervicovaginal microbiota. However, the finding of a significant interaction between TTHM and race on beta-defensin-2 levels suggest that environmental exposures may contribute to differences in reproductive tract innate immune function by race. Future studies to delineate environmental contributions to the cervicovaginal microbial-immune state, a potentially important biologic underpinning for preterm birth, are warranted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study investigated the effect of powdered activated carbon and calcium on trihalomethane toxicity in zebrafish embryos and larvae in hybrid membrane bioreactors. Two hybrid membrane bioreactors were configured with the addition of powdered activated carbon or calcium to reduce the trihalomethane formation potential. Trihalomethane formation decreased by approximately 37.2% and 30.3% in membrane bioreactor-powdered activated carbon and membrane bioreactor-calcium, respectively. Additionally, the toxic effect of trihalomethane formation was examined on zebrafish embryos and larvae. About 35% of the embryos exposed to trihalomethanes (800 ppb) showed signs of deformation, with the majority displaying coagulation within 24 h after exposure. Color preference tests, which were conducted to identify any abnormal activities of the embryos, showed an increase in preference from short to longer wavelengths upon exposure to high levels of trihalomethanes. This may indicate damage to the optical organs in zebrafish when exposed to trihalomethanes. Behavioral analysis showed reduced mobility of zebrafish larvae under different trihalomethane concentrations, indicating a decrease in the average activity time with an increasing trihalomethane concentration. The membrane bioreactor effluents were toxic to zebrafish embryos and larvae in the presence of high trihalomethane concentrations. To understand the mechanism behind trihalomethane toxicity, further studies are needed., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In many countries water disinfection for human consumption is still carried out via chlorination which generates by-products such as trihalomethanes (THM). Exposure to THM constitutes a public health risk as such substances are known to be carcinogenic. This study evaluated exposure to THMs by inhalation in showers and assessed the carcinogenic risk for lifetime exposure. The study population involved students at Universidad de los Andes residing in Bogotá, Colombia. The risk assessment was performed stochastically and the exposure parameters were taken as probability distributions. Most variables were measured in relation to the chosen population. The risk was calculated using two different methodologies but no significant variations were obtained. The average risk calculated for men and women was 56 cases in a million (5.6 × 10 -5 ). A sensitivity analysis was carried out where it was found that the parameters that increase risk the most are the concentration of chloroform in the water, exposure time, and the volume of the shower cubicle., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Some epidemiological studies show associations between disinfection byproducts (DBPs) and adverse developmental outcomes., Objectives: We undertook a meta-analysis of epidemiological studies on maternal exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) and risk of small for gestational age (SGA) birth., Methods: We identified forty-five publications including two reports and five theses via a 2020 literature search. Nineteen study populations from 16 publications met the inclusion criteria and were systematically evaluated. Effect measures were pooled using random effects meta-analytic methods along with cumulative, sub-group and meta-regression analyses to examine between-study heterogeneity and variation in risk across different DBP measures., Results: We detected a small increased risk for SGA with exposure to the sum of four (i.e., THM4) THM4 (odds ratio (OR) = 1.07; 95%CI: 1.03, 1.11), chloroform (OR = 1.05; 95%CI: 1.01, 1.08), bromodichloromethane (OR = 1.08; 95%CI: 1.05, 1.11) and the sum of the brominated THM4 (OR = 1.05; 95%CI: 1.02, 1.09). Larger ORs were detected for the sum of five haloacetic acids (i.e., HAA5) (OR = 1.12; 95%CI: 1.01, 1.25), dichloroacetic acid (OR = 1.25; 95%CI: 1.01, 1.41) and trichloroacetic acid (OR = 1.21; 95%CI: 1.07, 1.37). We detected larger SGA risks for several THM4 among the prospective cohort and case-control studies compared to retrospective cohorts and for the SGA3/5% (vs. SGA10%) studies. The THM4 meta-regression showed associations between SGA and the total quality score based on categorical or continuous measures. For example, an OR of 1.03 (95%CI: 1.01, 1.06) was detected for each 10-point increase in the study quality score based on our systematic review., Conclusions: We detected a small increased risk of SGA based on 18 THM4 study populations that was comparable to a previous meta-analysis of eight THM4 study populations. We also found increased risks for other THM4 and HAA measures not previously examined; these results were robust after accounting for outliers, publication bias, type of SGA classification, different exposure windows, and other factors., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Drinking water disinfection by-products (DBPs), including the ubiquitous trihalomethanes (THMs), are formed during the treatment of water with disinfectants (e.g., chlorine, chloramines) to produce and distribute potable water. Brominated THMs (Br-THMs) are activated to mutagens via glutathione S-transferase theta 1 (GSTT1); however, iodinated THMs (I-THMs) have never been evaluated for activation by GSTT1. Among the I-THMs, only triiodomethane (iodoform) has been tested previously for mutagenicity in Salmonella and was positive (in the absence of GSTT1) in three strains (TA98, TA100, and BA13), all of which have error-prone DNA repair (pKM101). We evaluated five I-THMs (chlorodiiodomethane, dichloroiodomethane, dibromoiodomethane, bromochloroiodomethane, and triiodomethane) for mutagenicity in Salmonella strain RSJ100, which expresses GSTT1, and its homologue TPT100, which does not; neither strain has pKM101. We also evaluated chlorodiiodo-, dichloroiodo-, and dibromoiodo-methanes in strain TA100 +/- rat liver S9 mix; TA100 has pKM101. None was mutagenic in any of the strains. The I-THMs were generally more cytotoxic than their brominated and chlorinated analogues but less cytotoxic than analogous trihalonitromethanes tested previously. All five I-THMs showed similar thresholds for cytotoxicity at ~2.5 μmoles/plate, possibly due to release of iodine, a well-known antimicrobial. Although none of these I-THMs was activated by GSTT1, iodoform appears to be the only I-THM that is mutagenic in Salmonella, only in strains deficient in nucleotide excision repair (uvrB) and having pKM101. Given that only iodoform is mutagenic among the I-THMs and is generally present at low concentrations in drinking water, the I-THMs likely play little role in the mutagenicity of drinking water., (© 2021 Wiley Periodicals LLC.)

The purpose of this study was to estimate the association between 2nd and 3rd degree hypospadias and maternal exposure to disinfection by-products (DBPs) using data from a large case-control study in the United States. Concentration estimates for total trihalomethanes (TTHMs), the sum of the five most prevalent haloacetic acids (HAA5), and individual species of each were integrated with data on maternal behaviors related to water use from the National Birth Defects Prevention Study (NBDPS) to create three different exposure metrics: (1) household DBP concentrations; (2) estimates of DBP ingestion; (3) predicted uptake (i.e., internal dose) of trihalomethanes (THMs) via ingestion, showering, and bathing. The distribution of DBP exposure was categorized as follows: (Q1/referent) < 50%; (Q2) ≥ 50% to < 75%; and (Q3) ≥ 75%. Logistic regression was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Generally, null associations were observed with increasing TTHM or HAA5 exposure. An increased risk was observed among women with household bromodichloromethane levels in the second quantile (aOR: 1.8; 95% CI: 1.2, 2.7); however, this association did not persist after the inclusion of individual-level water-use data. Findings from the present study do not support the hypothesis that maternal DBP exposures are related to the occurrence of hypospadias.

This study aims (1) to determine the seasonal and spatial distribution of THMs formed in chlorinated groundwater containing low levels of organic matter (0.4-0.8 mg L -1 ) and low to high levels of bromine (40-380 μg L -1 ), and (2) to evaluate the multi-route cancer risks associated with them. The study was conducted in Kayseri (Turkey), where drinking water is supplied from groundwater after chlorination only. THM formation in 50 water samples from 18 storage tanks and 32 distribution points was investigated to evaluate the spatial and temporal changes in THM concentrations for 12 months. The lifetime cancer risk associated with exposure to THMs through multiple pathways (i.e., oral ingestion, dermal absorption, and inhalation) was estimated for males and females. For a 12 month sampling period, the minimum and maximum THM concentrations varied from 2 μg L -1 to 17 μg L -1 and from 2 μg L -1 to 29 μg L -1 in storage tanks and distribution points, respectively. The ranges of median concentrations of THM were 5 μg L -1 to 9 μg L -1 in storage tanks and 5 μg L -1 to 12 μg L -1 in distribution points. In all samples dibromochloromethane was the dominant species, followed by bromoform, chloroform, and bromodichloromethane. The average values of total cancer risk associated with exposure to THMs via oral ingestion, dermal absorption, and inhalation for females and males were 1.31 × 10 -5 and 1.25 × 10 -5 in storage tanks, and 1.46 × 10 -5 and 1.39 × 10 -5 in distribution points, respectively. Although THM concentrations were very low, cancer risk values are 1.0 × 10 -6 < CR < 1.0 × 10 -4 , which are higher than the negligible risk level (1.0 × 10 -6 ).

Seasonal algal blooms in surface waters can impact water quality through an input of algal organic matter (AOM) to the pool of dissolved organic matter as well as the release of cyanotoxins. The formation and speciation of disinfection byproducts (DBPs) during chlorination of algal-impacted waters, collected from growth of Microcystis aeruginosa were studied. Second-order rate constants for the reactions of microcystins (MCs) with chlorine and bromine were determined. Finally, the toxicity of chlorinated algal-impacted waters was evaluated by Chinese hamster ovary (CHO) cytotoxicity and genotoxicity assays. Under practical water treatment conditions, algal-impacted waters produced less regulated trihalomethanes (THMs) and haloacetic acids (HAAs), haloacetonitriles (HANs), and total organic halogen (TOX) than natural organic matter (NOM). For example, the weight ratios of DBP formation from AOM to NOM (median levels) were approximately 1:5, 1:3, 1:2 and 1:3 for THMs, HAAs, HANs, and TOX, respectively. Increasing initial bromide level significantly enhanced THM and HAN concentrations, and therefore unknown TOX decreased. The second-order rate constant for the reactions of MC-LR (the most common MC species) with chlorine was 60 M -1  s -1 at pH 7.5 and 21 °C, and the rate constants for MC congeners follow the order: MC-WR > MC-LW > MC-YR > MC-LY > MC-LR ≈ MC-RR. The reaction rate constant of bromine with MC-LR is two orders of magnitude higher than that of chlorine. Unchlorinated algal-impacted waters were toxic owning to the presence of MCs, and chlorination enhanced their cytotoxicity and genotoxicity due to the formation of toxic halogenated DBPs. However, the toxicity of treated waters depended on the evolution of cyanotoxins and formation of DBPs (particularly unknown or emerging 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 © 2020 Elsevier Ltd. All rights reserved.)

Water disinfection, primarily by chlorination, is one of the greatest achievements of public health. However, more than half a century after its introduction, studies in the 1970s reported that (a) chlorine interacted with organic matter in the water to form disinfection by-products (DBPs); (b) two DBPs, chloroform and bromoform, both trihalomethanes (THMs), were rodent carcinogens; (c) three brominated THMs were mutagenic; in six studies chlorinated drinking waters in the United States and Canada were mutagenic; and (d) in one epidemiological study there was an association between bladder cancer mortality and THM exposure. This led the U.S. Environmental Protection Agency to issue its first DBP regulation in 1979. Forty years later, >600 DBPs have been characterized, 20/22 have been shown to be rodent carcinogens, >100 have been shown to be genotoxic, and 1000s of water samples have been found to be mutagenic. Data support a hypothesis that long-term dermal/inhalation exposure to certain levels of the three brominated THMs, as well as oral exposure to the haloacetic acids, combined with a specific genotype may increase the risk for bladder cancer for a small but significant population group. Improved water-treatment methods and stricter regulations have likely reduced such risks over the years, and further reductions in potential risk are anticipated with the application of advanced water-treatment methods and wider application of drinking water regulations. This 40-year research effort is a remarkable example of sustained cooperation between academic and government scientists, along with public/private water companies, to find answers to a pressing public health question., (Published 2020. This article is a U.S. Government work and is in the public domain in the USA.)

Ballast Water Managements Systems (BWMS) installed on vessels may use Active Substances (AS) to inactivate organisms. This paper provides new insights in the global issue of noxious Disinfection By-Products (DBP) produced with primarily oxidant-based BWMS, and the risk assessment for workers, including port State control officers, while performing tasks on a vessel that involve exposure to treated ballast water. The Joint Group of Experts on the Scientific Aspects of Marine Environmental Protection - Ballast Water Working Group (GESAMP-BWWG) plays a role in the certification process of BWMS that make use of AS evaluating potential negative effects. All BWMS that passed GESAMP-BWWG Final Approval until mid 2019 were analyzed providing an overview of chemicals in the treated ballast water before and after neutralization. The ballast tank cleaning scenario, the sampling scenario, and the ballast tank inspection scenario all showed elevated human health risks using the Derived Minimal Effect Levels approach. The most critical exposure occurs in the ballast tank cleaning scenario through the inhalation of volatile DBP, such as tribromomethane. This substance may cause acute effects such as headache, dizziness and also has carcinogenic properties. The two risk reducing options available in the GESAMP-BWWG Tier 2 calculations were compared, one being mitigation measures such as protective gloves and coveralls, the other option is taking into account a time correction factor. The results showed that the trihalomethanes in air are most problematic, however, there is a possibility that the calculated values may be overestimated as generally worst case assumptions were used., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Chlorination is globally used to produce of safe drinking water. Chlorination by-products are easily formed, and there are indications that these are associated with adverse reproductive outcomes., Objectives: We conducted a nationwide register-based prospective study to assess whether gestational exposure to the four most common chlorination by-products [total trihalomethanes (TTHMs)] via tap water was associated with risk of small for gestational age (SGA), preterm delivery, and very preterm delivery. To date, this is one of the largest studies assessing drinking water TTHM-associated adverse reproductive outcomes., Methods: We included all singleton births 2005-2015 (live and stillbirths) of mothers residing in Swedish localities having > 10,000 inhabitants, ≤ 2 operating waterworks, adequate information on chlorination treatment, and a sufficient number of routine TTHM measurements in tap water. Individual maternal second and third trimester exposure was obtained by linking TTHM measurements to residential history, categorized into no chlorination, < 5 , 5-15, and > 15 μ g TTHM/L. Outcomes and covariates were obtained via the linkage to Swedish health and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression using inverse probability weighting. We stratified the analyses by chlorination treatment (chloramine, hypochlorite)., Results: Based on approximately 500,000 births, we observed a TTHM dose-dependent association with increased risk of SGA, confined to treatment with hypochlorite, corresponding to a multivariable-adjusted OR = 1.20 (95% CI: 1.08, 1.33) comparing drinking water TTHM > 15 μ g to the unexposed. Similar results were obtained when, instead of unexposed, the lowest exposure category ( < 5 μ g / L TTHM) was used as reference. No clear associations were observed for preterm delivery and very preterm delivery., Discussion: Chlorination by-products exposure via drinking water was associated with increased risk of SGA in areas with hypochlorite treatment. https://doi.org/10.1289/EHP6012.

Swimming pool disinfection byproducts (DBPs) are becoming increasingly common worldwide. Precise exposure and health risk assessment for DBPs in swimming pool water with optimized parameters for local and specific population is more urgently needed. This study aimed to determine the levels of trihalomethanes (THMs) and haloacetic acids (HAAs) in 16 public indoor swimming pools in Shanghai, China. Swimming habits were also investigated to obtain more accurate exposure assessment parameters. Precise exposure assessment through multiple pathways, resulting cancer risk, and disability-adjusted life years (DALYs) were assessed. Results indicated that the highest total level of THMs and HAAs occurred in autumn. The surveyed swimmers 9-17 years of age had higher average daily dose (ADD) of DBPs than swimmers ≥18 years of age. The total lifetime cancer risk (LCR) attributable to THMs and HAAs exceeded 10 -6 , which represents a negligible risk level (NRL). The cancer risk from inhalation exposure predominantly by THMs contributed more than 99% of the total risk. Annual disease burden was 19.0 person-years attributed to exposure of DBPs in swimming pool water in Shanghai. This study provides a paradigm and strategic reference of precise exposure assessments, risk assessments, and disease burden estimation of hazards in swimming pool water for other regions., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2019 Elsevier B.V. All rights reserved.)

2,4-diaminobutyric acid (DAB), a newly identified algal toxins in water, pose a great threat to human health. DAB may react with chlorine or chloramine to produce CX 3 R-type disinfection by-products (DBPs) during water treatment processes. This study mainly investigated the formation and speciation of DBPs from chlor(am)ination of DAB. The results revealed that haloacetic acids (HAAs), trihalomethanes (THMs) and haloacetonitriles (HANs) were the main kinds of CX 3 R-type DBPs generated from DAB during chlor(am)ination, of which dichloroacetic acid yielded the highest. The formation and total toxicity of four CX 3 R-type DBPs from DAB during chloramination was significantly lower than that during chlorination at each Cl 2 :N molar ratio. However, more formation of Br-THMs and I-THMs were observed during chloramination in the presence of Br - /I - . Futhermore, the effects of chlor(am)ine dosage, solution pH, reaction time, and the concentration of Br - and I - on the formation and speciation of CX 3 R-type DBPs were also evaluated during chlor(am)ination. The plausible formation pathways of CX 3 R-type DBPs from DAB were proposed and verified by theoretical calculation. The quantum chemistry calculations indicate that 1N in DAB and 8N in 2,4-diaminochlorobutyric acid (C 4 H 9 O 2 N 2 Cl) were more likely to be attacked by electrophiles, supporting the proposed pathway schemes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Health risk and burden of disease induced by exposure to trihalomethanes (THMs, four compounds) and haloacetic acids (HAAs, 5 compounds) from drinking water through ingestion, dermal absorption, and inhalation routes were assessed based on one-year water quality monitoring in four urban communities (Bandar Deylam, Borazjan, Bushehr, and Choghadak) of Bushehr Province, Iran. The total average concentrations of THMs and HAAs at all the communities level were determined to be 92.9 ± 43.7 and 70.6 ± 26.5 μg/L, respectively. The dominant components of the THMs and HAAs were determined to be tribromomethane (TBM, 41.6%) and monobromoacetic acid (MBAA, 60.8%), respectively. The average contributions of ingestion, dermal absorption, and inhalation routes in exposure to the chlorination by-products (CBPs) were respectively 65.0, 15.4, and 19.6%. The total average non-carcinogenic risk as the hazard index (HI) and incremental lifetime cancer risk (ILCR) of the CBPs at all the communities level were found to be 4.03 × 10 -1 and 3.16 × 10 -4 , respectively. The total attributable deaths, death rate (per 100,000 people), age-weighted disability-adjusted life years (DALYs), and age-weighted DALY rate for all ages both sexes combined at all the communities level were estimated to be 1.0 (uncertainty interval: UI 95% 0.3 to 2.8), 0.27 (0.08-0.75), 30.8 (11.3-100.1), and 8.1 (3.0-26.4), respectively. The average contribution of mortality (years of life lost due to premature mortality: YLLs) in the attributable burden of disease was 94.7% (94.4-95.6). Although in most of cases the average levels of the CBPs were in the permissible range of Iranian standards for drinking water quality, the average values of ILCRs as well as attributable burden of disease were not acceptable (the ILCRs were higher than the boundary limit of 10 -5 ); therefore, implementation of interventions for reducing exposure to CBPs through drinking water especially in Kowsar Dam Water Treatment Plant is strictly recommended., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Response surface methodology (RSM) approach was used for optimization of the process parameters and identifying the optimal conditions for the removal of both trihalomethanes (THMs) and natural organic matter (NOM) in drinking water supplies. Co-precipitation process was employed for the synthesis of magnetic nano-adsorbent (sMNP), and were characterized by field emission scanning electron microscopy (SEM), trans-emission electron microscopy (TEM), BET (Brunauer-Emmett-Teller), energy dispersive X-ray (EDX) and zeta potential. Box-Behnken experimental design combined with response surface and optimization was used to predict THM and NOM in drinking water supplies. Variables were concentration of sMNP (0.1 g to 5 g), pH (4-10) and reaction time (5 min to 90 min). Statistical analysis of variance (ANOVA) was carried out to identify the adequacy of the developed model, and revealed good agreement between the experimental data and proposed model. The experimentally derived RSM model was validated using t-test and a range of statistical parameters. The observed R 2 value, adj. R 2 , pred. R 2 and "F-values" indicates that the developed THM and NOM models are significant. Risk analysis study revealed that under the RSM optimized conditions, a marked reduction in the cancer risk of THMs was observed for both the groups studied. Therefore, the study observed that the developed process and models can be efficiently applied for the removal of both THM and NOM from drinking water supplies.

The occurrence and transformation behaviors of disinfection byproducts (DBPs) were investigated in the finished water and tap water of 14 water treatment plants in rural areas of eastern China. Mammalian cell toxicity data from previous studies were used to evaluate the cytotoxicity of trihalomethanes (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), trichloronitromethane (TCNM) and the genotoxicity of HAAs, HANs and TCNM. Correlation analysis was conducted to identify the factors that might influence the variability of DBPs. The measured median values were 29.76 μg/L for THMs, 20.47 μg/L for HAAs, 3.98 μg/L for HANs, 0.76 μg/L for haloketones (HKs) and 0.03 μg/L for TCNM. The spatial variability analysis showed that the total concentrations of HAAs and HANs decreased during long hydraulic residence time (HRT) in seven drinking water distribution systems, which could result in reduced mammalian cell cytotoxicity and genotoxicity at consumers' taps. The concentrations of trihalogenated-DBPs were more stable than those of dihalogenated-DBPs and monohalogenated-DBPs during long HRT. Bromine acted as a more efficient substituting agent than chlorine for THMs and dihaloacetonitriles (DHANs) in actual drinking water. The dominant chlorinated-THMs and chlorinated-DHANs would transfer to brominated -THMs and brominated-DHANs when the concentration of bromide ion exceeds 450.67 and 610.25 μg/L, respectively. Correlation analysis indicated that particulate and soluble manganese (Mn) might play critical roles in promoting the production of DBPs in bulk water. Hydraulic disturbance could also result in secondary release of DBPs from loose deposits accumulated on distribution pipe walls., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Water chlorination is the most widely used technique to avoid microbial contamination and biofouling. Adding chlorine to bromide-rich waters leads to the rapid oxidation of bromide ions and leads to the formation of brominated disinfection by-products (bromo-DBPs) that exert adverse effects on various biological models. Bromo-DBPs are regularly encountered within industrialized embayments, potentially impacting marine organisms. Of these, bromoform, tribromoacetic acid and tribromophenol are among the most prevalent. In the present study, we tested the potential toxicity and genotoxicity of these disinfection by-products, using sea urchin, Paracentrotus lividus, embryos. We highlighted that tribromophenol showed higher toxicity compared to bromoform and tribromoacetic acid. Furthermore, a synergistic effect was detected when tested in combination. Pluteus cells exposed for 1 h to mixtures of DBPs at several concentrations demonstrated significant DNA damage. Finally, when compared to a non-exposed population, sea urchins living in a bromo-DPB-polluted area produced more resistant progenies, as if they were locally adapted. This hypothesis remains to be tested in order to better understand the obvious impact of complex bromo-DBPs environments on marine wildlife.

Formation of trihalomethanes (THMs) through excessive chlorination in the supplied water and its carcinogenic nature is a public health concern in many parts of the world, including a couple of neighboring countries in Asia. However, the issue was not yet addressed either in the public health policy or in academia in Bangladesh. Therefore, the objectives of this study are to determine the THM concentration in supplied water, its multiple pathways to the human body, and an estimation of resultant carcinogenic risk to urban dwellers in six different regions of Dhaka city. Thirty-one supplied water samples were collected from 31 different water points located in Purana Paltan, Naya Paltan, Kallyanpur, Shyamoli, Malibagh-Rampura, and Panthapath regions in premonsoon time. Total chlorine and chlorine dioxide (ClO 2 ) and trihalomethane (THM) concentration were determined using UV-VIS spectrophotometer; total organic carbon (TOC), total inorganic carbon, and total carbon concentration were measured using TOC analyzer, and chloroform concentration was determined by applying gas chromatography-mass spectroscopy (GC-MS-MS) in the supplied water samples. Research findings indicate that THM concentration exceeded the USEPA acceptable limit (80 ppb) in all regions except Panthapath. Study results showed that carcinogenic risk via ingestion was higher than the USEPA acceptable limit of 10 -6 . Carcinogenic risk via dermal absorption and inhalation exposure was lower according to USPEA acceptable limit. To conclude, this study represents the current knowledge about THM concentration in supplied pipeline water and adverse health risk, which signifies that regulatory measures should be taken to reduce the THM concentration.

Probabilistic lifetime cancer risks and non-cancer risks of trihalomethanes (THMs) through ingestion, dermal contact, and inhalation exposure in 88 drinking water treatment plants (WTPs) with raw waters from five water systems (WSs) in Jiangsu Province were analyzed and compared. Concentrations of THMs in finished water of study WTPs varied, ranging from 18.81 to 38.96 μg/L, which are lower than the maximum of 80 μg/L recommended by USEPA. The results of health risk assessment indicated that cancer risk as well as non-cancer risks of THMs in WTPs sourced from five water systems decreased in the order of WS3 > WS5 > WS2 > WS1 > WS4. The comparison among multiple exposure routes indicated that when non-boiled drinking water is consumed, ingestion has the highest exposure route, with exposure values greater than dermal contact and inhalation for WTPs with raw water from all five water systems. However, when drinking boiled water, dermal contact is the major risk source for WTPs with raw water from WS1 and WS2, instead of dermal contact, inhalation becomes the major risk source for WTPs with raw water from WS3, WS4, and WS5. In WTPs with raw water from water systems WS1, WS3, WS4, and WS5, dibromochloromethane (DBCM) in THMs has the highest contribution to cancer risk, while chloroform in THMs has the highest contribution to non-cancer risk. However, in WTPs with raw water from water system WS2, bromodichloromethane (BDCM) has the highest contribution to both cancer risk and non-cancer risk. The results also indicated that females are prone to cancer risk induced by THMs since Chinese people are accustomed to drinking boiled water. The results supply valuable information for health departments to put forward more specific and efficient policies to control water borne diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The organic toxicants formed in chlorinated water cause potential harm to human beings, and it is extensively concentrated all over the world. Various disinfection by-products (DBPs) occur in chlorinated water are genotoxic and carcinogenic. The toxicity is major concern for chlorinated DBPs which has been present more in potable water. The purpose of the work was to evaluate genotoxic properties of DBPs in Allium cepa as a plant model system. The chromosomal aberration and DNA laddering assays were performed to examine the genotoxic effect of trichloroacetic acid (TCAA), trichloromethane (TCM), and tribromomethane (TBM) in a plant system with distinct concentrations, using ethyl methanesulfonate (EMS) as positive control and tap water as negative control. In Allium cepa root growth inhibition test, the inhibition was concentration dependent, and EC 50 values for trichloroacetic acid (TCAA), trichloromethane (TCM), and tribromomethane (TBM) were 100 mg/L, 160 mg/L, and 120 mg/L respectively. In the chromosome aberration assay, root tip cells were investigated after 120 h exposure. The bridge formation, sticky chromosomes, vagrant chromosomes, fragmented chromosome, c-anaphase, and multipolarity chromosomal aberrations were seen in anaphase-telophase cells. It was noticed that with enhanced concentrations of DBPs, the total chromosomal aberrations were more frequent. The DNA damage was analyzed in roots of Allium cepa exposed with DBPs (TCAA, TCM, TBM) by DNA laddering. The biochemical assays such as lipid peroxidation, H 2 O 2 content, ascorbate peroxidase, guaiacol peroxidase, and catalase were concentration dependent. The DNA interaction studies were performed to examine binding mode of TCAA, TCM, and TBM with DNAs. The DNA interaction was evaluated by spectrophotometric and spectrofluorometric studies which revealed that TCAA, TCM, and TBM might interact with Calf thymus DNA (CT- DNA) by non-traditional intercalation manner.

Chlorine is considered the most used chemical agent for water disinfection worldwide. However, water chlorination can lead to by-product generation which can be toxic to humans. The present study aimed to perform a systematic review on the toxicity of trihalomethanes (THMs) through bioindicators of cytotoxicity, genotoxicity, and mutagenicity. The results showed that studies on the effects of THMs on DNA are a current research concern for evaluating the toxicity of the pure compounds and real samples involving several types including water for recreational use, reused water, and drinking water. THMs deleterious effects have been assessed using several biosystems, where the Ames test along with experimental animal models were the most cited. A wide range of THM concentrations have been tested. Nevertheless, DNA damage was demonstrated, highlighting the potential human health risk. Among the studied THMs, chloroform presented a different action mechanism when compared with brominated THMs, with the former being cytotoxic while brominated THMs (bromodichloromethane, bromoform, and dibromochloromethane) were cytotoxic, genotoxic, and mutagenic. The described evidence in this research highlights the relevance of this topic as a human health issue. Nevertheless, research aimed to represent THMs current exposure conditions in a more accurate way would be needed to understand the real impact on human health.