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Background: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent., Objectives: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer., Methods: 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)., Results: 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) μg/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., Conclusions: 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., Competing Interests: The authors declare they have no actual or potential competing financial interests.

Background: Evidence for a relationship between trihalomethane (THM) or haloacetic acid (HAA) exposure and adverse fetal growth is inconsistent. Disinfection by-products exist as complex mixtures in water supplies, but THMs and HAAs have typically been examined separately., Objectives: We investigated joint exposure at the individual level to THMs and HAAs in relation to birth weight in the multi-ethnic Born in Bradford birth cohort., Methods: Pregnant women reported their water consumption and activities via questionnaire. These data were combined with area-level THM and HAA concentrations to estimate integrated uptake of THMs into blood and HAA ingestion, accounting for boiling/filtering. We examined the relationship between THM and HAA exposures and birth weight of up to 7,438 singleton term babies using multiple linear regression, stratified by ethnicity., Results: Among Pakistani-origin infants, mean birth weight was significantly lower in association with the highest versus lowest tertiles of integrated THM uptake (e.g., -53.7 g; 95% CI: -89.9, -17.5 for ≥ 1.82 vs. < 1.05 μg/day of total THM) and there were significant trends (p < 0.01) across increasing tertiles, but there were no associations among white British infants. Neither ingestion of HAAs alone or jointly with THMs was associated with birth weight. Estimated THM uptake via showering, bathing, and swimming was significantly associated with lower birth weight in Pakistani-origin infants, when adjusting for THM and HAA ingestion via water consumption., Conclusions: To our knowledge, this is the largest DBP and fetal growth study to date with individual water use data, and the first to examine individual-level estimates of joint THM-HAA exposure. Our findings demonstrate associations between THM, but not HAA, exposure during pregnancy and reduced birth weight, but suggest this differs by ethnicity. This study suggests that THMs are not acting as a proxy for HAAs, or vice-versa., Citation: Smith RB, Edwards SC, Best N, Wright J, Nieuwenhuijsen MJ, Toledano MB. 2016. Birth weight, ethnicity, and exposure to trihalomethanes and haloacetic acids in drinking water during pregnancy in the Born in Bradford cohort. Environ Health Perspect 124:681-689; http://dx.doi.org/10.1289/ehp.1409480.

MX (3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone) is a drinking water disinfection byproduct (DBP). It is a potent mutagen and is of concern to public health. Data on MX levels in drinking water, especially in the UK, are limited. Our aim was to investigate factors associated with variability of MX concentrations at the tap, and to evaluate if routinely measured trihalomethanes (THMs) are an appropriate proxy measure for MX. We conducted quarterly water sampling at consumers' taps in eight water supply zones in and around Bradford, UK, between 2007 and 2010. We collected 79 samples which were analyzed for MX using GC-HRMS. Other parameters such as pH, temperature, UV-absorbance and free chlorine were measured concurrently, and total THMs were modeled from regulatory monitoring data. To our knowledge this is the longest MX measurement survey undertaken to date. Concentrations of MX varied between 8.9 and 45.5 ng/L with a median of 21.3 ng/L. MX demonstrated clear seasonality with concentrations peaking in late summer/early fall. Multivariate regression showed that MX levels were associated with total trihalomethanes, UV-absorbance and pH. However, the relationship between TTHM and MX may not be sufficiently consistent across time and location for TTHM to be used as a proxy measure for MX in exposure assessment.

During 2003-2004, United Utilities water company in North West England introduced enhanced coagulation (EC) to four treatment works to mitigate disinfection by-product (DBP) formation. This enabled examination of the relation between DBPs and birth outcomes whilst reducing socioeconomic confounding. We compared stillbirth, and low and very low birth weight rates three years before (2000-2002) with three years after (2005-2007) the intervention, and in relation to categories of THM change. We created exposure metrics for EC and trihalomethane (THM) concentration change (n=258 water zones). We linked 429,599 live births and 2279 stillbirths from national birth registers to the water zone at birth. We used Poisson regression to model the differences in birth outcome rates with an interaction between before/after the intervention and EC or THM change. EC treatment reduced chloroform concentrations more than non-treatment (mean -29.7 µg/l vs. -14.5 µg/l), but not brominated THM concentrations. Only 6% of EC water zones received 100% EC water, creating exposure misclassification concerns. EC intervention was not associated with a statistically significant reduction in birth outcome rates. Areas with the highest chloroform decrease (30 - 65 μg/l) had the greatest percentage decrease in low -9 % (-12, -5) and very low birth weight -16% (-24, -8) rates. The interaction between before/after intervention and chloroform change was statistically significant only for very low birth weight, p=0.02. There were no significant decreases in stillbirth rates. In a novel approach for studying DBPs and adverse reproductive outcomes, the EC intervention to reduce DBPs did not affect birth outcome rates. However, a measured large decrease in chloroform concentrations was associated with statistically significant reductions in very low birth weight rates., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Water disinfection by-products have been associated with an increased cancer risk. Micronuclei (MN) frequency in lymphocytes is a marker of genomic damage and can predict adult cancer risk., Objective: We evaluated maternal exposure to drinking water brominated trihalomethanes (BTHM) in relation to MN frequency in maternal and cord blood lymphocytes., Methods: MN frequency was examined in 214 mothers and 223 newborns from the Rhea mother-child cohort in Crete, Greece, in 2007-2008. Residential BTHM water concentrations were estimated during pregnancy using tap water analyses and modeling. Questionnaires on water related habits were used to estimate BTHM exposure from all routes. Associations between BTHM and MN frequency were estimated using negative binomial regression., Results: BTHM concentrations in residential tap water during pregnancy ranged from 0.06 to 7.1 μg/L. MN frequency in maternal binucleated lymphocytes was found to increase with BTHM concentrations in residential water for exposure during the first [rate ratio (RR) for 1 μg/L=1.05; 95% CI: 1.00, 1.11] and second trimesters (RR for 1 μg/L=1.03; 95% CI: 1.00, 1.06), and through all routes of BTHM exposure during the first trimester (RR for 1 μg/week=3.14; 95% CI: 1.16, 8.50)., Conclusions: These findings suggest that exposure to BTHM may increase the frequency of MN in maternal binucleated lymphocytes.

Objectives: Disinfection by-products (DBPs) have been associated with adverse semen outcomes in laboratory animals, although the evidence for trihalomethanes (THMs) is limited. Three small epidemiological studies found little evidence for an association between DBPs and adverse semen outcomes in humans. Using data from a large case-referent study (Chemicals and Pregnancy Study, Chaps-UK), we investigated the association between total THM (TTHM), chloroform and total brominated THMs and sperm concentration, percent motile sperm and motile sperm concentration (MSC)., Methods: Chaps-UK recruited men from 13 fertility clinics in nine urban centres across England and Wales between 1999 and 2002. We linked modelled THM concentrations in water zones to semen quality data for 642 cases (men with low MSC) and 926 referents (other men investigated for infertility), based on the men's residence during semen sampling. We assessed risk of low MSC in relation to DBP exposure using continuous THM concentrations. A secondary analysis investigated continuous outcomes (MSC, sperm concentration and percent motile sperm)., Results: In the case-referent analysis there was little evidence of elevated risk associated with chloroform, total brominated THM or TTHM concentration after adjustment (OR per 10 µg/L TTHM 1.01; 95% CI 0.91 to 1.12). Similarly, there was no significant effect of THMs on the continuous outcomes., Conclusions: In the largest study to date on DBPs in public water supplies, and semen quality we found that concentrations of THMs were not associated with poor semen quality. Large-scale investigation of other DBPs (eg, haloacetic acids) and other semen quality parameters (eg, sperm morphology and/or sperm DNA integrity) is recommended.

Objectives: Congenital anomalies have been inconsistently associated with maternal crude estimated exposure to drinking water trihalomethane (THM). We investigated the relationship between individual THM uptake during the first trimester of pregnancy and congenital anomalies., Methods: We estimated maternal THM uptake for 3074 live births using residential tap water concentrations, drinking water ingestion, showering and bathing, and uptake factors of THM in the blood. Multiple logistic regression was used to investigate the association of THM exposure with congenital anomalies., Results: We observed no statistically significant relationships between congenital anomalies and the total THM internal dose. We found little indication of a dose-response relationship for brominated THM and congenital heart anomalies. The relationship was statistically significant for bromodichloromethane (BDCM) (OR=2.16, 95% CI 1.05 to 4.46, highest vs lowest tertile) during the first month of pregnancy. During the first trimester of pregnancy, the probability of developing heart anomalies increased for every 0.1 μg/d increase in the BDCM and for every 0.01 μg/d increase in the internal dibromochloromethane (DBCM) dose (OR 1.70, 95% CI 1.09 to 2.66, and OR 1.25, 95% CI 1.01 to 1.54, respectively). A dose-response relationship was evident for musculoskeletal anomalies and DBCM exposure during the first and second months of pregnancy, while BDCM exposure tended to increase the risk of urogenital anomalies., Conclusions: This study shows some evidence for an association between the internal dose of THM and the risk of congenital anomalies. In particular, increased prenatal exposure to brominated THM might increase the risk of congenital heart and musculoskeletal anomalies.

Disinfection by-products (DBPs) are ubiquitous contaminants in tap drinking water with the potential to produce adverse health effects. Filtering and boiling tap water can lead to changes in the DBP concentrations and modify the exposure through ingestion. Changes in the concentration of 4 individual trihalomethanes (THM4) (chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)), MX, and bromate were tested when boiling and filtering high bromine-containing tap water from Barcelona. For filtering, we used a pitcher-type filter and a household reverse osmosis filter; for boiling, an electric kettle, a saucepan, and a microwave were used. Samples were taken before and after each treatment to determine the change in the DBP concentration. pH, conductivity, and free/total chlorine were also measured. A large decrease of THM4 (from 48% to 97%) and MX concentrations was observed for all experiments. Bromine-containing trihalomethanes were mostly eliminated when filtering while chloroform when boiling. There was a large decrease in the concentration of bromate with reverse osmosis, but there was a little effect in the other experiments. These findings suggest that the exposure to THM4 and MX through ingestion is reduced when using these household appliances, while the decrease of bromate is device dependent. This needs to be considered in the exposure assessment of the epidemiological studies.

Little is known about genetic susceptibility to individual trihalomethanes (THM) in relation to adverse pregnancy outcomes. We conducted a nested case-control study of 682 pregnant women in Kaunas (Lithuania) and, using individual information on drinking water, ingestion, showering and bathing, and uptake factors of THMs in blood, estimated an internal THM dose. We used logistic regression to evaluate the relationship between internal THM dose, birth outcomes and individual and joint (modifying) effects of metabolic gene polymorphisms. THM exposure during entire pregnancy and specific trimesters slightly increased low birth weight (LBW) risk. When considering both THM exposure and maternal genotypes, the largest associations were found for third trimester among total THM (TTHM) and chloroform-exposed women with the GSTM1-0 genotype (OR: 4.37; 95% CI: 1.36-14.08 and OR: 5.06; 95% CI: 1.50-17.05, respectively). A test of interaction between internal THM dose and GSTM1-0 genotype suggested a modifying effect of exposure to chloroform and bromodichloromethane on LBW risk. However, the effect on small for gestational age (SGA) was not statistically significant. These data suggest that THM internal dose may affect foetal growth and that maternal GSTM1 genotype modifies the THM exposure effects on LBW.

Background: Evidence for an association between exposure during pregnancy to trihalomethanes (THMs) in drinking water and impaired fetal growth is still inconsistent and inconclusive, in particular, for various exposure routes. We examined the relationship of individual exposures to THMs in drinking water on low birth weight (LBW), small for gestational age (SGA), and birth weight (BW) in singleton births., Methods: We conducted a cohort study of 4,161 pregnant women in Kaunas (Lithuania), using individual information on drinking water, ingestion, showering and bathing, and uptake factors of THMs in blood, to estimate an internal dose of THM. We used regression analysis to evaluate the relationship between internal THM dose and birth outcomes, adjusting for family status, education, smoking, alcohol consumption, body mass index, blood pressure, ethnic group, previous preterm, infant gender, and birth year., Results: The estimated internal dose of THMs ranged from 0.0025 to 2.40 mg/d. We found dose-response relationships for the entire pregnancy and trimester-specific THM and chloroform internal dose and risk for LBW and a reduction in BW. The adjusted odds ratio for third tertile vs. first tertile chloroform internal dose of entire pregnancy was 2.17, 95% CI 1.19-3.98 for LBW; the OR per every 0.1 μg/d increase in chloroform internal dose was 1.10, 95% CI 1.01-1.19. Chloroform internal dose was associated with a slightly increased risk of SGA (OR 1.19, 95% CI 0.87-1.63 and OR 1.22, 95% CI 0.89-1.68, respectively, for second and third tertile of third trimester); the risk increased by 4% per every 0.1 μg/d increase in chloroform internal dose (OR 1.04, 95% CI 1.00-1.09)., Conclusions: THM internal dose in pregnancy varies substantially across individuals, and depends on both water THM levels and water use habits. Increased internal dose may affect fetal growth.

Objectives: Hypospadias is a congenital anomaly that affects up to 70 in 10 000 males. Ingestion of drinking-water-disinfection byproducts such as trihalomethanes (THMs) has been associated with hypospadias in a small sample. We examined risk of hypospadias and exposure to THMs through water consumption and use., Methods: Between September 2000 and March 2003, we interviewed mothers of 471 boys with hypospadias and 490 controls in southeast England about maternal water consumption, dishwashing, showering, bathing and swimming. We obtained residential THM concentrations from the water companies and linked them by using Geographical Information Systems, which provided data on 468 case-subjects and 485 controls., Results: THM exposures, except for ingestion of ≥ 6 μg/day of bromodichloromethane (odds ratio [OR]: 1.65 [95% confidence interval (CI): 1.02-2.69]), were not associated with risk of hypospadias. Elevated risk of hypospadias was associated with estimates of consumption of cold tap water at home (OR: 1.71 [95% CI: 1.07-2.76]), total water (OR: 1.70 [95% CI: 1.09-2.67]), bottled water (OR: 1.64 [95% CI: 1.09-2.48]), and total fluid (OR: 1.55 [95% CI: 1.01-2.39]) for the highest versus the lowest categories; the first 2 showed dose-response trends., Conclusions: Evidence for an association between maternal water consumption and risk of hypospadias did not seem to be explained by THM exposure. Factors that influence maternal water consumption or other contaminants in tap or bottled water might explain this finding. It is important that women maintain an adequate fluid intake during pregnancy.

Few studies characterizing trihalomethane (THM) exposure or examining potential health effects were conducted in children. The present study describes patterns of water use in children as a source of THM exposure, and estimates the daily THM uptake and the relative contribution of each pathway of exposure. A cross-sectional population-based study was conducted in children 9-12 years of age in Sabadell, Catalonia, Spain (N=2037). We collected individual information on ingestion, frequency and duration of showering, bathing and swimming, source of drinking water, age, sex and parental education. Chloroform, dibromochloroform, bromodichloroform and bromoform in tap, bottled and swimming pool water were measured. The daily chloroform and brominated THM uptakes were estimated combining environmental levels with individual water activities using algorithms reported in the literature. Among the studied group, 80% of children drank bottled water and 20% regularly attended swimming pools. Mean THM concentration in bottled, tap and chlorinated pool water were, respectively, 0.3, 117 and 92 microg/L. Brominated THM predominated in the tap water (84% of total THM) and chloroform predominated in the swimming pool (84% of total THM). Children attending swimming pools had four times higher THM uptake compared to non-swimmers (p-value<0.05). Showering was the main pathway of exposure for non-swimmers. Girls and children with low parental education had a higher THM uptake (p-value<0.05) as they reported taking longer showers and more frequent baths. In conclusion, total and specific THM uptake varied considerably with the personal water uses among children. As drinking water was mainly bottled and bathing was infrequent, showering and swimming in pools were the main pathways of THM exposure. Specific water uses among children slightly differed by sociodemographic characteristics., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Exposure to total trihalomethanes in drinking water has been associated with several adverse birth outcomes relating to fetal growth and prematurity., Methods: We carried out a systematic review and meta-analysis of epidemiologic studies featuring original peer-reviewed data on the association of total trihalomethane exposure and health outcomes related to fetal growth and prematurity., Results: A comprehensive literature search yielded 37 studies, 15 of which were selected for the extraction of relative risks relating adverse birth outcomes to trihalomethane exposure. Sufficient data were available for meta-analyses to be carried out for 4 adverse birth outcomes: low birth weight (LBW), term low birth weight (term LBW), preterm delivery, and small for gestational age (SGA) (including intra uterine growth retardation). We found little or no evidence for associations between third trimester trihalomethane exposure and LBW (odds ratio per 10 microg total trihalomethane/L = 1.00 [95% confidence interval = 0.97-1.03]), term LBW (1.03 [0.93-1.15]), or preterm delivery (0.99 [0.98-1.00]), but some evidence for SGA (1.01 [1.00-1.02])., Conclusions: There was little or no evidence for associations between total trihalomethane concentration and adverse birth outcomes relating to fetal growth and prematurity, with the possible exception of SGA. We discuss these findings and the uncertainties-relating particularly to exposure-that may have affected them.

There appears to be very good epidemiological evidence for a relationship between chlorination by-products, as measured by trihalomethanes (THMs), in drinking water and bladder cancer, but the evidence for other cancers, including colorectal cancer appears to be inconclusive and inconsistent. There appears to be some evidence for a relationship between chlorination by-products, as measured by THMs, and small for gestational age (SGA)/intrauterine growth retardation (IUGR) and preterm delivery, but evidence for other outcomes such as low birth weight (LBW), stillbirth, congenital anomalies and semen quality appears to be inconclusive and inconsistent.The overall aim of the HIWATE study is to investigate potential human health risks (e.g. bladder and colorectal cancer, premature births, SGA, semen quality, stillbirth, congenital anomalies) associated with long-term exposure to low levels of disinfectants (such as chlorine) and DBPs occurring in water for human consumption and use in the food industry. The study will comprise risk-benefit analyses including quantitative assessments of risk associated with microbial contamination of drinking water versus chemical risk and will compare alternative treatment options. The outcome will be improved risk assessment and better information for risk management. The work is divided into different topics (exposure assessment, epidemiology, risk assessment and management) and studies.

In the framework of a cohort study of pregnant women conducted in Brittany (France), we assessed the exposure to trihalomethanes (THM) during pregnancy in a subset by evaluating (1) potential sources of variability in household THM levels; (2) the between- and within-subject variability in THM levels; (3) THM levels in swimming pools; and (4) the role of water-related habits on total THM uptake. We visited 109 women from the ongoing cohort study at home for an interview and collection of tap water from October to December 2004. Forty-three of them were re-contacted to obtain a second tap water sample in April-May 2005. We designed a questionnaire to collect individual information on source and amount of drinking water, frequency of showering, bathing, and swimming pool attendance, and household characteristics. We obtained 282 THM measurements, 152 specifically for the study and 130 from a regulatory agency. Personal information and environmental data were combined using two methodologies (method 1 using regulatory data and method 2 using our THM measurements) with a different set of assumptions. We calculated ingestion, showering, bathing, and swimming pool THM uptakes and added up those uptakes to calculate total THM uptake. Average THM levels from our measurements in October, November-December, and April-May were 61.3, 45.1, and 54.5 microg/l, respectively. Geographical variability was low and characteristics of the household did not influence THM levels. Within-subject variability in THM levels was three times higher than between-subject variability. Average THM level in swimming pools was 80.4 microg/l. Average water consumption during pregnancy was 1.9l/day. The source of the household drinking water was 90% bottled, 8% municipal, and 2% from other sources. Forty-seven per cent attended swimming pools during pregnancy. Using method 1, the geometric mean of total THM uptake was 0.93 microg/day. Showering contributed 64%, swimming in pools 23%, bathing 12%, and drinking water 1% to the total THM uptake. In a setting with low geographical variability and limited environmental measurements, individual data is highly relevant to determine personal THM exposure and uptake. In a population that mainly drinks bottled water (e.g., pregnant women), individual THM uptakes are dominated by inhalation and dermal absorption during, showering, swimming in pools, and bathing.

We measured concentrations of haloacetic acids (HAAs) in the water supply in regions covered by three water companies in the UK Approximately 30 samples in each region were obtained for analysis of both THMs and HAAs to assess the levels of HAAs and the relationship between HAAs and THMs, temperature, pH, free and total chlorine. We have found that there is a range of HAA levels in drinking water with the means ranging from 35-95mug/l and a maximum concentration of 244mug/l. In two out of the three regions there was a high correlation between total THMs and total HAAs, but whereas the HAA and THM levels in one of these companies were approximately equal, in another company the HAA levels were 3-4 times higher than the THM levels. In the third region there was no correlation between total THMs and total HAAs even though the average levels were approximately equal. The ratio of total THM and total HAAs levels was significantly correlated with temperature, pH, free and total chlorine. Overall total THM levels are therefore not considered to be a good indicator of HAA levels. Epidemiological studies using total THM levels should be taking this into account in the interpretation of their results, and regulatory authorities when setting water guidelines.

We investigated the association between total trihalomethanes (TTHMs) and risk of stillbirth and low and very low birth weight in three water regions in England, 1992-1998; associations with individual trihalomethanes (THMs) were also examined. Modeled estimates of quarterly TTHM concentrations in water zones, categorized as low (< 30 microg/L), medium (30-59 microg/L), or high (> or = 60 microg/L), were linked to approximately 1 million routine birth and stillbirth records using maternal residence at time of birth. In one region, where there was a positive socioeconomic deprivation gradient across exposure categories, there was also a positive, significant association of TTHM with risk of stillbirth and low and very low birth weight. Overall summary estimates across the three regions using a random-effects model to allow for between-region heterogeneity in exposure effects showed small excess risks in areas with high TTHM concentrations for stillbirths [odds ratio (OR) = 1.11; 95% confidence interval (CI), 1.00-1.23), low birth weight (OR = 1.09; 95% CI, 0.93-1.27), and very low birth weight (OR = 1.05; 95% CI, 0.82-1.34). Among the individual THMs, chloroform showed a similar pattern of risk as TTHM, but no association was found with concentrations of bromodichloromethane or total brominated THMs. Our findings overall suggest a significant association of stillbirths with maternal residence in areas with high TTHM exposure. Further work is needed looking at cause-specific stillbirths and effects of other disinfection by-products and to help differentiate between alternative (noncausal) explanations and those that may derive from the water supply.

Samples of drinking water are routinely analysed for four trihalomethanes (THMs), which are indicators of by-products of disinfection with chlorine, by UK water suppliers to demonstrate compliance with regulations. The THM data for 1992-1993 to 1997-1998 for three water suppliers in the north and midlands of England were made available for a UK epidemiological study of the association between disinfection by-products and adverse birth outcomes. This paper describes the THM levels in these three supply regions and discusses possible sources of variation. THM levels varied between different suppliers' water, and average THM levels were within the regulatory limits. Chloroform was the predominant THM in all water types apart from the ground water of one supplier. The supplier that distributed more ground and lowland surface water had higher dibromochloromethane (DBCM) and bromoform levels and lower chloroform levels than the other two suppliers. In the water of two suppliers, seasonal fluctuations in bromodichloromethane (BDCM) and DBCM levels were found with levels peaking in the summer and autumn. In the other water supplier, chloroform levels followed a similar seasonal trend whereas BDCM and DBCM levels did not. For all three water suppliers, chloroform levels declined throughout 1995 when there was a drought period. There was a moderate positive correlation between the THMs most similar in their structure (chloroform and BDCM, BDCM and DBCM, and DBCM and bromoform) and a slight negative correlation between chloroform and bromoform levels.

In this paper we report the findings of a European survey of regulated and emerging disinfection byproducts (DBPs) in drinking waters in selected regions that were part of epidemiology studies. The levels of DBPs found reflected the diverse regions from which the samples were collected, the different treatment/disinfection processes and the different source waters. In addition to a wide range of concentrations of DBPs (e.g. median trihalomethanes (THMs) of 8-85 μg L-1), bromine incorporation was quite diverse (e.g. some waters were highly dominated by bromine-containing DBPs, whereas others only had chlorine-containing species). Bromine incorporation was highest in the haloacetonitriles (HANs) and was lowest in the trihalogenated haloacetic acids (THAAs). In addition, the ratios of THMs to HAAs, THMs to HANs, and THAAs to dihalogenated HAAs varied. Exposure assessment based on THMs alone was not sufficient for indicating the presence of emerging DBPs of health concern. Occurrence studies must include a more diverse group of analytes to better understand exposure to DBPs of health concern. [ABSTRACT FROM AUTHOR]

Background: Evidence for an association between exposure during pregnancy to trihalomethanes (THMs) in drinking water and impaired fetal growth is still inconsistent and inconclusive, in particular, for various exposure routes. We examined the relationship of individual exposures to THMs in drinking water on low birth weight (LBW), small for gestational age (SGA), and birth weight (BW) in singleton births.Methods: We conducted a cohort study of 4,161 pregnant women in Kaunas (Lithuania), using individual information on drinking water, ingestion, showering and bathing, and uptake factors of THMs in blood, to estimate an internal dose of THM. We used regression analysis to evaluate the relationship between internal THM dose and birth outcomes, adjusting for family status, education, smoking, alcohol consumption, body mass index, blood pressure, ethnic group, previous preterm, infant gender, and birth year.Results: The estimated internal dose of THMs ranged from 0.0025 to 2.40 mg/d. We found dose-response relationships for the entire pregnancy and trimester-specific THM and chloroform internal dose and risk for LBW and a reduction in BW. The adjusted odds ratio for third tertile vs. first tertile chloroform internal dose of entire pregnancy was 2.17, 95% CI 1.19-3.98 for LBW; the OR per every 0.1 μg/d increase in chloroform internal dose was 1.10, 95% CI 1.01-1.19. Chloroform internal dose was associated with a slightly increased risk of SGA (OR 1.19, 95% CI 0.87-1.63 and OR 1.22, 95% CI 0.89-1.68, respectively, for second and third tertile of third trimester); the risk increased by 4% per every 0.1 μg/d increase in chloroform internal dose (OR 1.04, 95% CI 1.00-1.09).Conclusions: THM internal dose in pregnancy varies substantially across individuals, and depends on both water THM levels and water use habits. Increased internal dose may affect fetal growth. [ABSTRACT FROM AUTHOR]

Background: Swimming in chlorinated pools involves exposure to disinfection by-products (DBPs) and has been associated with impaired respiratory health. OBJECTIONS: We evaluated short-term changes in several respiratory biomarkers to explore mechanisms of potential lung damage related to swimming pool exposure. Methods: We measured lung function and biomarkers of airway inflammation [fractional exhaled nitric oxide (FeNO), eight cytokines, and vascular endothelial growth factor (VEGF) in exhaled breath condensate], oxidative stress (8-isoprostane in exhaled breath condensate), and lung permeability [surfactant protein D (SP-D) and the Clara cell secretory protein (CC16) in serum] in 48 healthy nonsmoking adults before and after they swam for 40 min in a chlorinated indoor swimming pool. We measured trihalomethanes in exhaled breath as a marker of individual exposure to DBPs. Energy expenditure during swimming, atopy, and CC16 genotype (rs3741240) were also determined. RESULTS: Median serum CC16 levels increased from 6.01 to 6.21 μg/L (average increase, 3.3%; paired Wilcoxon test p = 0.03), regardless of atopic status and CC16 genotype. This increase was explained both by energy expenditure and different markers of DBP exposure in multivariate models. FeNO was unchanged overall but tended to decrease among atopics. We found no significant changes in lung function, SP-D, 8-isoprostane, eight cytokines, or VEGF. CONCLUSIONS: We detected a slight increase in serum CC16, a marker of lung epithelium permeability, in healthy adults after they swam in an indoor chlorinated pool. Exercise and DBP exposure explained this association, without involving inflammatory mechanisms. Further research is needed to confirm the results, establish the clinical relevance of short-term serum CC16 changes, and evaluate the long-term health impacts. [ABSTRACT FROM AUTHOR]

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Abstract: The use of population-level indices to estimate individual exposures is an important limitation of previous epidemiologic studies of disinfection by-products (DBPs). We examined exposure misclassification resulting from the use of system average DBP concentrations to estimate individual-level exposures. Data were simulated (n =1000 iterations) for 100 subjects across 10 water systems based on the following assumptions: DBP concentrations ranged from 0–99 μg/L with limited intra-system variability; water intake ranged from 0.5–2.5 L/day; 20% of subjects used bottled water exclusively; 20% of subjects used filtered tap water exclusively; DBP concentrations were reduced by 50% or 90% following filtration. DBP exposure percentiles were used to classify subjects into different exposure levels (e.g., low, intermediate, high and very high) for four classification approaches. Compared to estimates of DBP ingestion that considered daily consumption, source type (i.e., unfiltered tap, filtered tap, and bottled water), and filter efficiency (with 90% DBP removal), 48–62% of subjects were misclassified across one category based on system average concentrations. Average misclassification across at least two exposure categories (e.g., from high to low) ranged from 4–14%. The median classification strategy resulted in the least misclassification, and volume of water intake was the most influential modifier of ingestion exposures. These data illustrate the importance of individual water use information in minimizing exposure misclassification in epidemiologic studies of drinking water contaminants. [Copyright &y& Elsevier]

Background: Epidemiological evidence of an association between disinfection by-products (DBPs) exposure via drinking water and reproductive outcomes is still inconclusive. Objective: The aim of this study was to investigate the association between trihalomethanes (THMs), chlorite and chlorate exposure and congenital anomalies. Methods: A case-control study was carried out in Emilia-Romagna Region (Italy). Data on 1917 different congenital anomalies (neural tube, cardiac, diaphragm and abdominal wall, oesophagus, cleft lip and palate, respiratory, urinary tract and chromosomal anomalies) observed in the period 2002–2005 were extracted from the Regional Malformation Registry. Four controls (newborns without anomalies) were randomly selected form the Regional Birth Register and frequency matched to cases according to pregnancy period. The network supplying water during the first trimester of pregnancy was identified on the basis of mother's address: DBPs data, technical and structural information were linked to each subject. Results: Overall, THMs exposure was very low (mean: 3.8±3.6μg/l), and no risk excess was observed. Chlorite and chlorate values were fairly high (mean: 427±184μg/l and 283±79μg/l, respectively). Women exposed to chlorite level >700μg/l were at higher risk of newborns with renal defects (OR: 3.30; 95% IC: 1.35–8.09), abdominal wall defects (OR: 6.88; 95% IC: 1.67–28.33) and cleft palate (OR: 4.1; 95% IC: 0.98–16.8); women exposed to chlorate level >200μg/l were at higher risk of newborns with obstructive urinary defects (OR: 2.88; 95% IC: 1.09–7.63), cleft palate (OR: 9.60; 95% IC:1.04–88.9) and spina bifida (OR: 4.94; 95% IC:1.10–22). Conclusions: This was the first study showing an excess risk of different congenital anomalies related to chlorite and chlorate exposure via drinking water: further research is needed to confirm the observed relationships in large datasets, specifically for chlorate, an unregulated DBP. [Copyright &y& Elsevier]