Comparison of trihalomethanes in tap water and blood: a case study in the United States.
ABSTRACT: Epidemiological studies have used various measures to characterize trihalomethane (THM) exposures, but the relationship of these indicators to exposure biomarkers remains unclear.We examined temporal and spatial variability in baseline blood THM concentrations and assessed the relationship between these concentrations and several exposure indicators (tap water concentration, water-use activities, multiroute exposure metrics).We measured water-use activity and THM concentrations in blood and residential tap water from 150 postpartum women from three U.S. locations.Blood ?THM [sum of chloroform (TCM), bromodichloromethane (BDCM), dibromo-chloromethane (DBCM), and bromoform (TBM)] concentrations varied by site and season. As expected based on variable tap water concentrations and toxicokinetic properties, the proportion of brominated species (BDCM, DBCM, and TBM) in blood varied by site (site 1, 24%; site 2, 29%; site 3, 57%) but varied less markedly than in tap water (site 1, 35%; site 2, 75%; site 3, 68%). The blood-water ?THM Spearman rank correlation coefficient was 0.36, with correlations higher for individual brominated species (BDCM, 0.62; DBCM, 0.53; TBM, 0.54) than for TCM (0.37). Noningestion water activities contributed more to the total exposure metric than did ingestion, but tap water THM concentrations were more predictive of blood THM levels than were metrics that incorporated water use.Spatial and temporal variability in THM concentrations was greater in water than in blood. We found consistent blood-water correlations across season and site for BDCM and DBCM, and multivariate regression results suggest that water THM concentrations may be an adequate surro-gate for baseline blood levels.
Project description:Exposure to trihalomethanes (or THMs: chloroform, bromoform, bromodichloromethane, and dibromochloromethane [DBCM]) formed via drinking water disinfection has been associated with adverse reproductive outcomes and cancers of the digestive or genitourinary organs. However, few studies have examined potential associations between THMs and liver injury in humans, even though experimental studies suggest that these agents exert hepatotoxic effects, particularly among obese individuals. This study examined participants in the National Health and Nutrition Examination Survey (1999-2006, N=2781) to test the hypothesis that THMs are associated with liver injury as assessed by alanine aminotransferase (ALT) activity in circulation. Effect modification by body mass index (BMI) or alcohol consumption also was examined. Associations between blood THM concentrations and ALT activity were assessed using unconditional multiple logistic regression to calculate prevalence odds ratios (ORs) with 95% confidence intervals (CIs) for exposure among cases with elevated ALT activity (men: >40IU/L, women: >30IU/L) relative to those with normal ALT, after adjustment for variables that may confound the relationship between ALT and THMs. Compared to controls, cases were 1.35 times more likely (95% CI: 1.02, 1.79) to have circulating DBCM concentrations exceeding median values in the study population. There was little evidence for effect modification by BMI, although the association varied by alcohol consumption. Among non-drinkers, cases were more likely than controls to be exposed to DBCM (OR: 3.30, 95% CI: 1.37, 7.90), bromoform (OR: 2.88, 95% CI: 1.21, 6.81), or brominated THMs (OR: 4.00, 95% CI: 1.31, 12.1), but no association was observed among participants with low, or moderate to heavy alcohol consumption. Total THM levels exceeding benchmark exposure limits continue to be reported both in the United States and globally. Results from this study suggest a need for further characterization of ALT activity and possibly other hepatic or metabolic diseases in populations with elevated drinking water THM concentrations.
Project description:Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent.We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer.A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day).We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) ?g/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption.We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations. Citation: Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. 2017. Colorectal cancer and long-term exposure to trihalomethanes in drinking water: a multicenter case---control study in Spain and Italy. Environ Health Perspect 125:56-65;?http://dx.doi.org/10.1289/EHP155.
Project description:We previously conducted a study to assess whether household exposures to tap water increased an individual's internal dose of trihalomethanes (THMs). Increases in blood THM levels among subjects who showered or bathed were variable, with increased levels tending to cluster in two groups.Our goal was to assess the importance of personal characteristics, previous exposures, genetic polymorphisms, and environmental exposures in determining THM concentrations in blood after showering.One hundred study participants completed a health symptom questionnaire, a 48-hr food and water consumption diary, and took a 10-min shower in a controlled setting. We examined THM levels in blood samples collected at baseline and 10 and 30 min after the shower. We assessed the significance of personal characteristics, previous exposures to THMs, and specific gene polymorphisms in predicting postshower blood THM concentrations.We did not observe the clustering of blood THM concentrations observed in our earlier study. We found that environmental THM concentrations were important predictors of blood THM concentrations immediately after showering. For example, the chloroform concentration in the shower stall air was the most important predictor of blood chloroform levels 10 min after the shower (p < 0.001). Personal characteristics, previous exposures to THMs, and specific polymorphisms in CYP2D6 and GSTT1 genes were significant predictors of both baseline and postshowering blood THM concentrations as well as of changes in THM concentrations associated with showering.The inclusion of information about individual physiologic characteristics and environmental measurements would be valuable in future studies to assess human health effects from exposures to THMs in tap water.
Project description:High concentrations of trihalomethanes (THMs) in public water supplies potentially pose a health hazard, but exposure assessment remains a complex task. To interpret research findings and monitoring data for THMs, it is important to evaluate spatial and temporal variations in both total THM and the individual constituent compounds (including brominated species). We therefore aimed to determine the concentrations, and spatial and temporal variability of concentrations, of THMs public water supplies in Perth, Western Australia, which is known historically to have high brominated THM concentrations. We analysed water samples from 21 water distribution zones around Perth (including Busselton and Bunbury) across different seasons over a period of two years. A total of 250 samples provided a median total THM of 72 µg/L (range of 0-157 µg/L), which falls well within Australia's National Health and Medical Research Council guidelines. The concentration of all species, including brominated forms, also fell the World Health Organization's guidelines. Total THM concentrations were typically higher in spring and summer. A high degree of spatial variability was detected and appears to relate to the source water. Both the temporal and spatial variability in THM concentrations have implications for epidemiological studies, and monitoring.
Project description:Trihalomethanes (THMs) are water disinfection by-products that have been associated with bladder cancer and adverse birth outcomes. Four THMs (bromoform, chloroform, bromodichloromethane, dibromochloromethane) were measured in blood and tap water of U.S. adults in the National Health and Nutrition Examination Survey (NHANES) 1999-2006. THMs are metabolized to potentially toxic/mutagenic intermediates by cytochrome p450 (CYP) 2D6 and CYP2E1 enzymes.We conducted exploratory analyses of blood THMs, including factors affecting CYP2D6 and CYP2E1 activity.We used weighted multivariable regressions to evaluate associations between blood THMs and water concentrations, survey year, and other factors potentially affecting THM exposure or metabolism (e.g., prescription medications, cruciferous vegetables, diabetes, fasting, pregnancy, swimming).From 1999 to 2006, geometric mean blood and water THM levels dropped in parallel, with decreases of 32%-76% in blood and 38%-52% in water, likely resulting, in part, from the lowering of the total THM drinking water standard in 2002-2004. The strongest predictors of blood THM levels were survey year and water concentration (n = 4,232 total THM; n = 4,080 bromoform; n = 4,582 chloroform; n = 4,374 bromodichloromethane; n = 4,464 dibromochloromethane). We detected statistically significant inverse associations with diabetes and eating cruciferous vegetables in all but the bromoform model. Medications did not consistently predict blood levels. Afternoon/evening blood samples had lower THM concentrations than morning samples. In a subsample (n = 230), air chloroform better predicted blood chloroform than water chloroform, suggesting showering/bathing was a more important source than drinking.We identified several factors associated with blood THMs that may affect their metabolism. The potential health implications require further study.
Project description:OBJECTIVES:We examined stillbirths in relation to disinfection by-product (DBP) exposures including chloroform, bromodichloromethane (BDCM), dibromochloromethane, bromoform, trichloroacetic acid, dichloroacetic acid (DCAA), monobromoacetic acid and summary DBP measures (trihalomethanes (THM4), haloacetic acids (HAA5), THMBr (brominated trihalomethanes) and DBP9 (sum of THM4 and HAA5)). METHODS:We randomly selected 10 controls for each of the 2460 stillbirth cases with complete quarterly 1997-2004 THM4 and HAA5 town-level drinking water data. Adjusted (aORs) were calculated based on weight-averaged second-trimester DBP exposures. RESULTS:We detected statistically significant associations for stillbirths and the upper DCAA quartiles (aOR range: 1.50-1.71). We also found positive associations for the upper four HAA5 quintiles and different stillbirth cause of death categories that were examined including unexplained stillbirth (aOR range: 1.24-1.72), compression of umbilical cord (aOR range: 1.08-1.94), prematurity (aOR range: 1.37-2.88), placental separation and haemorrhage (aOR range: 1.44-2.01) and asphyxia/hypoxia (aOR range: 1.52-1.97). Additionally, we found positive associations between stillbirths and chloroform exposure (aOR range: 1.29 - 1.36) and unexplained stillbirths and BDCM exposure (aOR range: 1.51 - 1.78). We saw no evidence of exposure-response relationships for any categorical DBP metrics. CONCLUSIONS:Consistent with some previous studies, we found associations between stillbirths and chloroform and unexplained stillbirth and BDCM exposures. These findings strengthen existing evidence of prenatal THM exposures increasing the risk of stillbirth. Additionally, we saw statistically significant associations between DCAA and stillbirth. Future research should examine cause-specific stillbirths in relation to narrower critical windows and additional DBP exposure metrics beyond trihalomethanes and haloacetic acids.
Project description:Epidemiological studies suggest that women exposed to disinfection by-products (DBPs) have an increased risk of delivering babies with cardiovascular defects (CVDs).We examined nine CVDs in relation to categorical DBP exposures including bromoform, chloroform, dibromochloromethane (DBCM), bromodichloromethane (BDCM), monobromoacetic acid (MBAA), dichloroacetic acid (DCAA), trichloroacetic acid (TCAA), and summary DBP measures (HAA5, THMBr, THM4, and DBP9).We calculated adjusted odds ratios (aORs) in a case-control study of birth defects in Massachusetts with complete quarterly 1999-2004 trihalomethane (THM) and haloacetic acid (HAA) data. We randomly matched 10 controls each to 904 CVD cases based on week of conception. Weight-averaged aggregate first-trimester DBP exposures were assigned to individuals based on residence at birth.We detected associations for tetralogy of Fallot and the upper exposure categories for TCAA, DCAA, and HAA5 (aOR range, 3.34-6.51) including positive exposure-response relationships for DCAA and HAA5. aORs consistent in magnitude were detected between atrial septal defects and bromoform (aOR = 1.56; 95% CI: 1.01, 2.43), as well as DBCM, chloroform, and THM4 (aOR range, 1.26-1.67). Ventricular septal defects (VSDs) were associated with the highest bromoform (aOR = 1.85; 95% CI: 1.20, 2.83), MBAA (aOR = 1.81; 95% CI: 0.85, 3.84), and DBCM (aOR = 1.54; 95% CI: 1.00, 2.37) exposure categories.To our knowledge, this is the first birth defect study to develop multi-DBP adjusted regression models as well as the first CVD study to evaluate HAA exposures and the second to evaluate bromoform exposures. Our findings, therefore, inform exposure specificity for the consistent associations previously reported between THM4 and CVDs including VSDs. Citation: Wright JM, Evans A, Kaufman JA, Rivera-Núñez Z, Narotsky MG. 2017. Disinfection by-product exposures and the risk of specific cardiac birth defects. Environ Health Perspect 125:269-277;?http://dx.doi.org/10.1289/EHP103.
Project description:Typhoon Soudelor was one of the strongest storms in the world in 2015. The category 5 hurricane made landfall in Taiwan on August 8, causing extensive damage and severe impacts on the environment. This paper describes the changes of trihalomethane (THM) concentrations in tap and drinking fountain water in selected typhoon-affected areas in Taipei before and after the typhoon. Samples were taken from water transmission mains at various distances from the local water treatment plant. The results showed that organic matter increased between pre- and post-typhoon periods with a greater proportion of aromatic compounds. Although drinking fountains showed moderately less total trihalomethane (TTHM) levels than that of tap water, the intake of high turbidity water considerably diminished the efficiency of their purification systems after the typhoon. The percentage distribution of THM species increased throughout the distribution network, probably due to a longer contact time between chlorine and the organic matter in the pipelines. After 2 to 5 min of boiling, THM reduction was considerable in all cases with the greater extent in post-typhoon samples. It is evident that extreme weather conditions may have a severe impact on water quality, and thus more cautious strategies should be adopted in such cases.
Project description:BACKGROUND: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive. OBJECTIVE: We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery. METHODS: Mother-child cohorts set up in five Spanish areas during the years 2000-2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We defined outcomes following standard definitions and included 2,158 newborns in the analysis. RESULTS: Median residential THM ranged from 5.9 ?g/L (Valencia) to 114.7 ?g/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was -0.45 g (95% confidence interval: -1.36, 0.45 g) for chloroform and 0.16 g (-1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery. CONCLUSIONS: Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain.
Project description:Lifetime exposure to trihalomethanes (THM) has been associated with increased risk of bladder cancer. We explored methods of analyzing bladder cancer risk associated with 4 THM (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) as surrogates for disinfection by-product (DBP) mixtures in a case-control study in Spain (1998-2001). Lifetime average concentrations of THM in the households of 686 incident bladder cancer cases and 750 matched hospital-based controls were calculated. Several exposure metrics were modeled through conditional logistic regression, including the following analyses: total THM (?g/L), cytotoxicity-weighted sum of total THM (pmol/L), 4 THM in separate models, 4 THM in 1 model, chloroform and the sum of brominated THM in 1 model, and a principal-components analysis. THM composition, concentrations, and correlations varied between areas. The model for total THM was stable and showed increasing dose-response trends. Models for separate THM provided unstable estimates and inconsistent dose-response relationships. Risk estimation for specific THM is hampered by the varying composition of the mixture, correlation between species, and imprecision of historical estimates. Total THM (?g/L) provided a proxy measure of DBPs that yielded the strongest dose-response relationship with bladder cancer risk. A variety of metrics and statistical approaches should be used to evaluate this association in other settings.