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.

Blood trihalomethane concentrations in relation to sperm mitochondrial DNA copy number and telomere length among 958 healthy men.

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.

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.

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.

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 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.

Prenatal Exposure to Disinfection Byproducts and Intrauterine Growth in a Chinese Cohort.

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.

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.

Meta-analysis of small for gestational age births and disinfection byproduct exposures.

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.

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.

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.

Age-sex specific and cause-specific health risk and burden of disease induced by exposure to trihalomethanes (THMs) and haloacetic acids (HAAs) from drinking water: An assessment in four urban communities of Bushehr Province, Iran, 2017.

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.

Formation, speciation and toxicity of CX3R-type disinfection by-products (DBPs) from chlor(am)ination of 2,4-diaminobutyric acid (DAB).

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 CX3R-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 CX3R-type DBPs generated from DAB during chlor(am)ination, of which dichloroacetic acid yielded the highest. The formation and total toxicity of four CX3R-type DBPs from DAB during chloramination was significantly lower than that during chlorination at each Cl2: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 CX3R-type DBPs were also evaluated during chlor(am)ination. The plausible formation pathways of CX3R-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 (C4H9O2N2Cl) were more likely to be attacked by electrophiles, supporting the proposed pathway schemes.

Health risk assessment of trihalomethanes in water treatment plants in Jiangsu Province, China.

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.

Health risk assessment of trihalomethanes mixtures from daily water-related activities via multi-pathway exposure based on PBPK model.

In this study, the concentrations of trihalomethanes (THMs) in tap water and direct drinking water were analyzed, and based on the human behavior patterns and building parameters, the concentrations of THMs in indoor air were simulated with the water-air concentration conversion model. In addition, concentrations of THMs in human tissues were predicted based on physiologically based pharmacokinetic (PBPK) model, and the health risk of THMs for participants were estimated. Furthermore, the carcinogenic risk of mixtures according to the method proposed by USEPA and PBPK model based method were calculated and compared. The concentrations of chloroform, bromodichloromethane, dibromochloromethane and bromoform in tap water were 11.28-16.21, 4.83-6.28, 0.81-1.32 and 0.08-0.21 µg/L, and those in direct drinking water were 3.29-6.88, 0.35-0.47, 0.03-0.08 and 0.04-0.08 µg/L, respectively. The results of water-air concentration conversion model demonstrated that pollutants in air had a strong correlation with water-related activities. Multi-pathway PBPK model showed that THMs concentrations in liver, kidney and richly perfused tissue were higher than those in other tissues. The results of risk assessment showed that the mean risk levels of mixtures were 1.69 × 10-4 and 1.72 × 10-4 calculated by the USEPA recommended method and PBPK based method, which seriously exceeded the acceptable level. TCM and BDCM were the major risk factors, and inhalation was the main exposure route of THMs.

Ames and random amplified polymorphic DNA tests for the validation of the mutagenic and/or genotoxic potential of the drinking water disinfection by-products chloroform and bromoform.

Chloroform and Bromoform are two abundant trihalomethanes found in Algerian drinking water. The investigation of the mutagenic hazard of these disinfection by-products was studied by Ames test as prokaryotic bioassay to show their mutagenic effects. For this, Salmonella typhimurium TA98 and TA100 strains were employed. Both chloroform and bromoform showed a direct mutagenic effect since the number of revertant colonies gradually increase in dose-dependent manner with all concentrations tested with the two bacterial strains and these were both in the absence and presence of S9 metabolic activation. The genotoxic hazard was also studied by random amplified polymorphic DNA test on the root cells of Allium cepa as eukaryotic bioassay. DNA extracted from the roots of the onion were incubated at different concentrations of chloroform and bromoform and then amplified by polymerase chain reaction. This was based on demonstrating a major effect of disappearance of bands compared to roots incubated in the negative control (distilled water). The results showed that these two compounds affected genomic DNA by breaks although by mutations.

Effect of trihalomethanes (chloroform and bromoform) on human haematological count.

With the increasing concerns about the harmful effects of disinfection products, the process of chlorination is becoming questionable. Bromoform and chloroform are among the most frequently occurring disinfection by-products. Haematological parameters are an important indicator of human well-being which is why the prime objective of the current study was to conduct a dose-response assessment to investigate the effects of trihalomethanes on human haematological count. Blood samples of healthy subjects were exposed to different concentrations (10, 30 and 50 µg/mL) of chloroform and bromoform in vitro to analyse how these compounds affected the haematological count with increasing dose concentrations. Headspace gas chromatography analysis was also conducted on samples to assess the difference between measured and spiked values of doses. The results indicated that the damage caused by bromoform was statistically more significant as compared to chloroform. Haemoglobin (HGB) and mean corpuscular haemoglobin concentration levels lowered as they were significantly affected (p < 0.05) by bromoform at all administered doses. It also significantly damaged platelet level at doses of 30 (p < 0.05) and 50 µg/mL (p < 0.01). Conversely, the damage caused by chloroform was statistically less significant (p > 0.05).

TIC-Tox: A preliminary discussion on identifying the forcing agents of DBP-mediated toxicity of disinfected water.

The disinfection of drinking water is a major public health achievement; however, an unintended consequence of disinfection is the generation of disinfection by-products (DBPs). Many of the identified DBPs exhibit in vitro and in vivo toxicity, generate a diversity of adverse biological effects, and may be hazards to the public health and the environment. Only a few DBPs are regulated by several national and international agencies and it is not clear if these regulated DBPs are the forcing agents that drive the observed toxicity and their associated health effects. In this study, we combine analytical chemical and biological data to resolve the forcing agents associated with mammalian cell cytotoxicity of drinking water samples from three cities. These data suggest that the trihalomethanes (THMs) and haloacetic acids may be a small component of the overall cytotoxicity of the organic material isolated from disinfected drinking water. Chemical classes of nitrogen-containing DBPs, such as the haloacetonitriles and haloacetamides, appear to be the major forcing agents of toxicity in these samples. These findings may have important implications for the design of epidemiological studies that primarily rely on the levels of THMs to define DBP exposure among populations. The TIC-Tox approach constitutes a beginning step in the process of identifying the forcing agents of toxicity in disinfected water.

Gene expression changes in blood RNA after swimming in a chlorinated pool.

Exposure to disinfection by-products (DBP) such as trihalomethanes (THM) in swimming pools has been linked to adverse health effects in humans, but their biological mechanisms are unclear. We evaluated short-term changes in blood gene expression of adult recreational swimmers after swimming in a chlorinated pool. Volunteers swam 40min in an indoor chlorinated pool. Blood samples were drawn and four THM (chloroform, bromodichloromethane, dibromochloromethane and bromoform) were measured in exhaled breath before and after swimming. Intensity of physical activity was measured as metabolic equivalents (METs). Gene expression in whole blood mRNA was evaluated using IlluminaHumanHT-12v3 Expression-BeadChip. Linear mixed models were used to evaluate the relationship between gene expression changes and THM exposure. Thirty-seven before-after pairs were analyzed. The median increase from baseline to after swimming were: 0.7 to 2.3 for MET, and 1.4 to 7.1µg/m3 for exhaled total THM (sum of the four THM). Exhaled THM increased on average 0.94µg/m3 per 1 MET. While 1643 probes were differentially expressed post-exposure. Of them, 189 were also associated with exhaled levels of individual/total THM or MET after False Discovery Rate. The observed associations with the exhaled THM were low to moderate (Log-fold change range: -0.17 to 0.15). In conclusion, we identified short-term gene expression changes associated with swimming in a pool that were minor in magnitude and their biological meaning was unspecific. The high collinearity between exhaled THM levels and intensity of physical activity precluded mutually adjusted models with both covariates. These exploratory results should be validated in future studies.

Drinking Water Disinfection By-products, Genetic Polymorphisms, and Birth Outcomes in a European Mother-Child Cohort Study.

BACKGROUND: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility. METHODS: We enrolled 14,005 mothers (2002-2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case-control studies. RESULTS: Average levels of trihalomethanes ranged from around 10 µg/L to above the regulatory limits in the EU of 100 µg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (ß = 2.2 g in birth weight per 10 µg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 µg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene-environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age. CONCLUSIONS: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. (See video abstract at http://links.lww.com/EDE/B104.).