Trihalomethanes in global drinking water: Distributions, risk assessments, and attributable disease burden of bladder cancer.

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.

Exposure to disinfection by-products and risk of cancer: A systematic review and dose-response meta-analysis.

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.

Disinfection by-products in drinking water and risk of colorectal cancer: a population-based cohort study.

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.

Occurrence and multi-pathway health risk assessment of trihalomethanes in drinking water of Wuxi, China.

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 CHBr2Cl 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.

Overlooked inorganic DBPs in trichloroisocyanuric acid (TCCA) disinfected indoor swimming pool: Evidences from concentration, cytotoxicity, and human health risk.

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.

Long-Term Exposure to Nitrate and Trihalomethanes in Drinking Water and Prostate Cancer: A Multicase-Control Study in Spain (MCC-Spain).

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. <5.5mg/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.

Disinfection byproducts in indoor swimming pool water: Detection and human lifetime health risk assessment.

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.

Estimating National Exposures and Potential Bladder Cancer Cases Associated with Chlorination DBPs in U.S. Drinking Water.

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.

Potential cancer risk estimates from trihalomethanes in peri-urban settings of Kawama East of Mufulira, Zambia.

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 (CHCl2Br), dibromochloromethane (CHClBr2), 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 CHCl2Br and CHClBr2 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.

Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women.

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 (NO3-N) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS >10y at enrollment (n=10,501; cases=261), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible ≥95th percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (>½ MCL; 40µg/L TTHM; 30µg/L HAA5; 5mg/L NO3-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 NO3-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 ≥93µg/L, HAA5 ≥49µg/L) were associated with endometrial cancer risk (TTHM: HR95vsQ1=2.19, 95% CI: 1.41, 3.40; HAA5: HR95vsQ1=1.84, 95% CI: 1.19, 2.83; ptrend<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: HR36+vs0y=1.61, 95% CI: 1.18, 2.21; HAA5: HR38+vs0y=1.85, 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: HRQ4vsQ1=2.12, 95% CI: 1.17, 3.83; p-trend=0.008) than for high-grade tumors (TTHM: HRQ4vsQ1=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 NO3-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.

[Determination of four trihalomethanes in ship ballast water by gas chromatography-negative chemical ionization-mass spectrometry].

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.

Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case-Control Studies.

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.

Evaluation of formation and health risks of disinfection by-products in drinking water supply of Ggaba waterworks, Kampala, Uganda.

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

Potential risks and approaches to reduce the toxicity of disinfection by-product - A review.

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.

Multi-exposure human health risks assessment of trihalomethanes in drinking water of Egypt.

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.

Exposure to widespread drinking water chemicals, blood inflammation markers, and colorectal cancer.

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.

Exposure to drinking water trihalomethanes and nitrate and the risk of brain tumours in young people.

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.

Associations of public water system trihalomethane exposure during pregnancy with spontaneous preterm birth and the cervicovaginal microbial-immune state.

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 (ß 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 (ß -0.75 [95%CI: -1.43, -0.08]) but not among Black participants (ß 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.

Cancer risk assessment from exposure to trihalomethanes in showers by inhalation.

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.

Spatial/temporal distribution and multi-pathway cancer risk assessment of trihalomethanes in low TOC and high bromide groundwater.

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).