Maternal periconceptional exposure to drinking water disinfection by-products and neural tube defects in offspring.

BACKGROUND: Associations between maternal periconceptional exposure to disinfection by-products (DBPs) in drinking water and neural tube defects (NTDs) in offspring are inconclusive, limited in part by exposure misclassification. METHODS: Maternal interview reports of drinking water sources and consumption from the National Birth Defects Prevention Study were linked with DBP concentrations in public water system monitoring data for case children with an NTD and control children delivered during 2000-2005. DBPs analyzed were total trihalomethanes, the five most common haloacetic acids combined, and individual species. Associations were estimated for all NTDs combined and selected subtypes (spina bifida, anencephaly) with maternal periconceptional exposure to DBPs in public water systems and with average daily periconceptional ingestion of DBPs accounting for individual-level consumption and filtration information. Mixed effects logistic regression models with maternal race/ethnicity and educational attainment at delivery as fixed effects and study site as a random intercept were applied. RESULTS: Overall, 111 case and 649 control children were eligible for analyses. Adjusted odds ratios for maternal exposure to DBPs in public water systems ranged from 0.8-1.5 for all NTDs combined, 0.6-2.0 for spina bifida, and 0.7-1.9 for anencephaly; respective ranges for average daily maternal ingestion of DBPs were 0.7-1.1, 0.5-1.5, and 0.6-1.8. Several positive estimates (≥1.2) were observed, but all confidence intervals included the null. CONCLUSIONS: Using community- and individual-level data from a large, US, population-based, case-control study, we observed statistically nonsignificant associations between maternal periconceptional exposure to total and individual DBP species in drinking water and NTDs and subtypes.

Lifetime exposure to brominated trihalomethanes in drinking water and swimming pool attendance are associated with chronic lymphocytic leukemia: a Multicase-Control Study in Spain (MCC-Spain).

BACKGROUND: Chronic lymphocytic leukemia (CLL) etiology is poorly understood, and carcinogenic chemicals in drinking and recreational water are candidates. OBJECTIVE: To evaluate the association between drinking-water exposure to trihalomethanes (THMs) and nitrate as well as lifetime swimming pool attendance and CLL. METHODS: During 2010-2013, hospital-based CLL cases and population-based controls were recruited in Spain, providing information on residential histories, type of water consumed and swimming pool attendance. Average THMs and nitrate levels in drinking water were linked to lifetime water consumption. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using mixed models. RESULTS: Final samples for residential tap water analyses and swimming pool attendance analyses were 144 cases/1230 controls and 157 cases/1240 controls, respectively. Mean (SD) values for average lifetime residential brominated THMs and chloroform in tap water (µg/L), and ingested nitrate (mg/day) were 48.1 (35.6), 18.5 (6.7) and 13.7 (9.6) respectively in controls; and 72.9 (40.7), 17.9 (5.4), and 14.1 (8.8) in CLL cases. For each 10 µg/L increase of brominated THMs and chloroform lifetime-average levels, the ORs (95% CI) were 1.22 (1.14, 1.31) and 0.54 (0.34, 0.87), respectively. For each 5 mg/day increase of ingested nitrate, the OR of CLL was 0.91 (0.80, 1.04). The OR of lifetime pool users (vs. non-users) was 2.38 (1.61, 3.52). Upon performing annual frequency of attending pools analysis through categorization, the second and third categories showed an ORs of 2.36 (1.49, 3.72) and 2.40 (1.51, 3.83), respectively, and P-trend of 0.001. IMPACT STATEMENT: This study identifies an association of long-term exposure to THMs in drinking water, at concentrations below the regulatory thresholds and WHO guidelines, and swimming pool attendance, with chronic lymphocytic leukemia (CLL). These unprecedented findings are highly relevant since CLL is an incurable cancer with still unknown etiology and because the widespread exposure to chlorination by-products that remain in drinking and recreational water worldwide. Despite the demonstrated carcinogenicity in animals of several chlorination by-products, little is known about their potential risks on human health. This study makes a significant contribution to the search for environmental factors involved in the etiology of CLL and to the evidence of the health impact of these high prevalent water contaminants.

Associations of blood trihalomethanes with semen quality among 1199 healthy Chinese men screened as potential sperm donors.

BACKGROUND: Trihalomethanes (THMs) have demonstrated adverse effects on male reproductive systems in experimental animals, but human evidence has been inconsistent. Prior researches have been limited by small sample sizes and inadequate exposure assessment. OBJECTIVES: To investigate the association between blood THMs and repeated measurements of semen quality parameters among 1199 healthy men screened as potential sperm donors. METHODS: We recruited healthy men presenting to the Hubei Province Human Sperm Bank from April to December 2017. At study entry, each participant provided a spot blood sample which was used to quantify blood concentrations of four THMs: chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM) and bromoform (TBM). The summary measures of exposure for brominated THMs (Br-THMs; molar sum of BDCM, DBCM and TBM) and total THMs (TTHMs; molar sum of TCM and Br-THMs) were also calculated. We used multivariable linear regression models to estimate the cross-sectional associations of tertiles of blood THM concentrations with semen quality parameters measured at study entry, and mixed-effect models to estimate the longitudinal associations accounting for repeated measures of semen quality, adjusting for relevant confounding factors. RESULTS: In the cross-sectional analysis, several inverse dose-response relationships were observed across tertiles of blood TCM concentrations and sperm count, total motility and progressive motility, and between blood DBCM, and Br-THMs, and TTHMs and sperm count and concentration. The inverse associations of blood TCM, DBCM, Br-THMs and TTHMs with sperm count were confirmed in the longitudinal, repeated measure analysis. CONCLUSION: Our results suggest that exposure to THMs from drinking water may be related to decreased semen quality in young healthy men.

Predicting health risk from exposure to trihalomethanes in an Olympic-size indoor swimming pool among elite swimmers and coaches.

Disinfection by-products (DBP) such as trihalomethanes (THM) are formed when chlorine and bromine interact with natural organic materials in chlorine-treated swimming pools. Epidemiological evidence demonstrated an association between exposure to swimming pool environment and adverse health effects. Therefore, this study aimed to assess carcinogenic and non-carcinogenic risk of long-term exposure of elite swimmers and their coaches. In an Olympic-size indoor chlorinated swimming pool, THM levels were determined in water (21-69 µg/L), in the boundary layer above the water surface (59-397 µg/m3), and in the air surrounding the pool (28-390 µg/m3). These values were used to predict multi-pathway chronic daily intake (CDI), cancer risk (CR) and hazard index (HI). Oral and dermal CDI for swimmers were 2.4 × 10-6 and 2.0 × 10-8, respectively. The swimmers' inhalation CDI (1.9 × 10-3 mg/kg/day) was estimated to be sixfold higher than levels obtained for coaches (3.3 × 10-4 mg/kg/day). According to guidelines, the HI was acceptable, but CR exceeded the recommended limit for both, coaches (CR: 5.5 × 10-7-8.5 × 10-5; HI: 6.5 × 10-4-1 × 10-1) and swimmers (CR: 1.4 × 10-5-3.6 × 10-4 HI: 1.6 × 10-2-4.3 × 10-1). Our findings provide further support to the need to develop comprehensive guidelines to safeguard the health of individuals involved in elite swimming.

The Assessment of Trihalomethanes Concentrations in Drinking Water of Hamadan and Tuyserkan Cities, Western Iran and Its Health Risk on the Exposed Population.

BACKGROUND: The aim of the present study was to calculate and to assess the potential lifetime cancer risks for trihalomethanes from consuming chlorinated drinking water in Hamadan and Tuyserkan cities, western Iran in 2016-2017. STUDY DESIGN: A cross-sectional study. METHODS: Seventy-two water samples were collected from the distribution systems and from the outlet of water treatment plants (WTPs) and the experiments were carried out to determine the desired parameters. All the sampling and measurement methods were according to Standard Methods. The obtained data were analyzed using SPSS software. RESULTS: The mean concentration of total THMs in the summer and winter was 42.75 and 17.75 µg/L, respectively, below the WHO and Iranian standard. The positive correlation was observed between temperature and THMs levels. Moreover, THMs concentration in Shahid Beheshti's WTP was several times lower than in Ekbatan's WTP. Chloroform, the dominant species of THMs, was identified at different sampling points. The highest cancer risk in Hamadan was 1.4×10-5 and 4.8×10-5 for male and female, respectively; and the cancer risk was obtained to be 5.6×10-7-2.26×10-6 in Tuyserkan. CONCLUSION: The drinking water obtained from the studied area is safe in terms of THMs concentration. Nevertheless, the highest cancer risk was higher than the EPA's acceptable level of 10-6.

Exposure to disinfection byproducts and risk of type 2 diabetes: a nested case-control study in the HUNT and Lifelines cohorts.

INTRODUCTION: Environmental chemicals acting as metabolic disruptors have been implicated with diabetogenesis, but evidence is weak among short-lived chemicals, such as disinfection byproducts (trihalomethanes, THM composed of chloroform, TCM and brominated trihalomethanes, BrTHM). OBJECTIVES: We assessed whether THM were associated with type 2 diabetes (T2D) and we explored alterations in metabolic profiles due to THM exposures or T2D status. METHODS: A prospective 1:1 matched case-control study (n = 430) and a cross-sectional 1:1 matched case-control study (n = 362) nested within the HUNT cohort (Norway) and the Lifelines cohort (Netherlands), respectively, were set up. Urinary biomarkers of THM exposure and mass spectrometry-based serum metabolomics were measured. Associations between THM, clinical markers, metabolites and disease status were evaluated using logistic regressions with Least Absolute Shrinkage and Selection Operator procedure. RESULTS: Low median THM exposures (ng/g, IQR) were measured in both cohorts (cases and controls of HUNT and Lifelines, respectively, 193 (76, 470), 208 (77, 502) and 292 (162, 595), 342 (180, 602). Neither BrTHM (OR = 0.87; 95% CI: 0.67, 1.11 | OR = 1.09; 95% CI: 0.73, 1.61), nor TCM (OR = 1.03; 95% CI: 0.88, 1.2 | OR = 1.03; 95% CI: 0.79, 1.35) were associated with incident or prevalent T2D, respectively. Metabolomics showed 48 metabolites associated with incident T2D after adjusting for sex, age and BMI, whereas a total of 244 metabolites were associated with prevalent T2D. A total of 34 metabolites were associated with the progression of T2D. In data driven logistic regression, novel biomarkers, such as cinnamoylglycine or 1-methylurate, being protective of T2D were identified. The incident T2D risk prediction model (HUNT) predicted well incident Lifelines cases (AUC = 0.845; 95% CI: 0.72, 0.97). CONCLUSION: Such exposome-based approaches in cohort-nested studies are warranted to better understand the environmental origins of diabetogenesis.

The unveiling of a new risk factor associated with bladder cancer in Lebanon.

BACKGROUND: No accurate evaluation of smoking and water pollution on bladder cancer has been conducted in the Lebanese population. Our aim is to examine the significance of smoking and one of the main water pollutants Trihalomethanes (THM) on bladder cancer risk. METHODS: Population Attributable Fraction (PAF) was used to quantify the contribution of the risk factors smoking and THMs on bladder cancer in Lebanon. To calculate PAF for each risk factor, we used the proportion of the population exposed and the relative risk for each risk factor. Relative risks for each risk factor were obtained from published meta-analyses. The population at risk values were obtained from a report on chronic disease risk factor surveillance in Lebanon which was conducted by the World Health Organization between 2008 and 2009 and a national study by Semerjian et al. that conducted a multipathway exposure assessment of selected public drinking waters of Lebanon for the risk factors smoking and THMs, respectively. RESULTS: Bladder cancer cases that were the result of smoking in Lebanon among males and females are 33.4 and 18.6%, respectively. Cases attributed to mid-term exposure to THM contamination of drinking water is estimated at 8.6%. CONCLUSION: This paper further highlights the negative impact of smoking on bladder cancer risk and adds an overlooked and often underestimated risk that THMs have on this type of cancer. Thus, it is imperative that a national based study which assesses THM exposure by gender and smoking status be implemented to determine the real risk behind this byproduct.

Occupational exposure to trichloramine and trihalomethanes: adverse health effects among personnel in habilitation and rehabilitation swimming pools.

Personnel in swimming pool facilities typically experience ocular, nasal, and respiratory symptoms due to water chlorination and consequent exposure to disinfection by-products in the air. The aim of the study was to investigate exposure to trichloramine and trihalomethanes (chloroform, bromodichloromethane, dibromochloromethane, and bromoform) from the perspective of adverse health effects on the personnel at Swedish habilitation and rehabilitation swimming pools. The study included 10 habilitation and rehabilitation swimming pool facilities in nine Swedish cities. The study population comprised 24 exposed swimming pool workers and 50 unexposed office workers. Personal and stationary measurements of trichloramine and trihalomethanes in air were performed at all the facilities. Questionnaires were distributed to exposed workers and referents. Spirometry, fraction of exhaled nitric oxide (FENO), and peak expiratory flow (PEF) were measured. Personal and stationary measurements yielded trichloramine levels of 1-76 µg/m3 (average: 19 µg/m3) and 1-140 µg/m3 (average: 23 µg/m3), respectively. A slightly higher, but not significant, prevalence of reported eye- and throat-related symptoms occurred among the exposed workers than among the referents. A significantly increased risk of at least one ocular symptom was attributed to trichloramine exposure above the median (20 µg/m3). Lung function (FVC and FEV1) was in the normal range according to the Swedish reference materials, and no significant change in lung function before and after shift could be established between the groups. Average FENO values were in the normal range in both groups, but the difference in the values between the exposed workers and referents showed a significant increase after shift. Hourly registered PEF values during the day of the investigation did not show any unusual individual variability. In conclusion, the increased risk of developing at least one ocular symptom at personal trichloramine concentrations over 20 µg/m3 combined with an increase in the difference in FENO during the work shift of the exposed workers should not be neglected as an increased risk of respiratory inflammation in the habilitation and rehabilitation swimming pool environment.

First-trimester blood concentrations of drinking water trihalomethanes and neonatal neurobehavioral development in a Chinese birth cohort.

Toxicological evidence indicates that exposure to drinking water trihalomethanes (THMs) can impair neural development. However, no epidemiologic study to date has evaluated the relation of trihalomethanes exposure with neonatal neurobehavioral development. Here we aimed to evaluate if prenatal exposure to THMs during early pregnancy is associated with neonatal neurobehavioral development in 451 Chinese mother-child pairs. First trimester blood THMs [chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM)] were determined by solid phase micro-extraction gas chramatography. Neonatal neurobehavioral development was assessed using neonatal behavioral neurological assessment (NBNA) on the third day after birth. Multivariable linear regression models and restricted cubic spline models were constructed to evaluate the associations between blood THMs and neonatal neurological development scores. Blood concentrations of BDCM, whether modeled as continuous or categorical variables, were inversely associated with total NBNA score of newborns based on the multivariable linear regression. The association was further confirmed in the cubic spline model, and a linear dose-response relationship was observed. Stratified analysis showed that the inverse association between blood BDCM and total NBNA score was more evident in male infants than females. Our findings suggest that exposure to THMs during early pregnancy may be associated with impaired neonatal neurobehavioral development.

Long-term exposure to trihalomethanes in drinking water and breast cancer in the Spanish multicase-control study on cancer (MCC-SPAIN).

BACKGROUND: Exposure to trihalomethanes (THMs) in drinking water has consistently been associated with an increased risk of bladder cancer, but evidence on other cancers including the breast is very limited. OBJECTIVES: We assessed long-term exposure to THMs to evaluate the association with female breast cancer (BC) risk. METHODS: A multi case-control study was conducted in Spain from 2008 to 2013. We included 1003 incident BC cases (women 20-85years old) recruited from 14 hospitals and 1458 population controls. Subjects were interviewed to ascertain residential histories and major recognized risk factors for BC. Mean residential levels of chloroform, brominated THMs (Br-THMs) and the sum of both as total THM (TTHMs) during the adult-lifetime were calculated. RESULTS: Mean adult-lifetime residential levels ranged from 0.8 to 145.7µg/L for TTHM (median=30.8), from 0.2 to 62.4µg/L for chloroform (median=19.7) and from 0.3 to 126.0µg/L for Br-THMs (median=9.7). Adult-lifetime residential chloroform was associated with BC (adjusted OR=1.47; 95%CI=1.05, 2.06 for the highest (>24µg/L) vs. lowest (<8µg/L) quartile; p-trend=0.024). No association was detected for residential Br-THMs (OR=0.91; 95%CI=0.68, 1.23 for >31µg/L vs. <6µg/L) or TTHMs (OR=1.14; 95%CI=0.83, 1.57 for >48µg/L vs. <22µg/L). CONCLUSIONS: At common levels in Europe, long-term residential total THMs were not related to female breast cancer. A moderate association with chloroform was suggested at the highest exposure category. This large epidemiological study with extensive exposure assessment overcomes several limitations of previous studies but further studies are needed to confirm these results.

Respiratory and Ocular Symptoms Among Employees at Swedish Indoor Swimming Pools.

BACKGROUND: This study investigated trichloramine exposure and prevalence of respiratory and ocular symptoms among Swedish indoor swimming pool workers. METHODS: Questionnaires were distributed to pool workers and referents. Lung function and fraction of exhaled nitric oxide (FeNO) were measured before and after work. Exposure to trichloramine and trihalomethanes was measured over work shifts. RESULTS: The mean personal trichloramine exposure was 36 µg/m. Significantly more exposed workers reported ocular and nasal symptoms. There were significant differences between groups in FeNO change following work, with exposed showing increased FeNO, which grew when analyses included only nonsmokers. CONCLUSIONS: The findings indicate that indoor swimming pool environments may have irritating effects on mucous membranes. FeNO data also indicate an inflammatory effect on central airways, but the clinical relevance is unclear. Low trichloramine levels found in this study were not associated with health effects.

Atrazine in public water supplies and risk of ovarian cancer among postmenopausal women in the Iowa Women's Health Study.

BACKGROUND: Few studies have evaluated environmental chemical exposures in relation to ovarian cancer. We previously found an increased risk of ovarian cancer among postmenopausal women in Iowa associated with higher nitrate levels in public water supplies (PWS). However, elevated nitrate levels may reflect the presence of other agricultural chemicals, such as atrazine, one of the most commonly detected pesticides in Iowa PWS. METHODS: We evaluated the association between atrazine in drinking water and incident ovarian cancer (N=145, 1986-2010) among 13 041 postmenopausal women in the Iowa Women's Health Study who used their PWS for ≥11 years as reported in 1989. Average levels of atrazine (1986-1987), nitrate-nitrogen (NO3-N, 1955-1988) and estimated levels of total trihalomethanes (TTHM, 1955-1988) from PWS monitoring data were linked to the participants' cities of residence. We computed HRs and 95% CIs by categories of the average atrazine level (not detected, ≤ or >0.37 parts per billion=median) using Cox proportional hazards regression adjusting for ovarian cancer risk factors. RESULTS: Atrazine was detected in water samples from 69 cities where 4155 women (32%) lived and levels were moderately correlated with NO3-N (ρ=0.35) and TTHM (ρ=0.24). Atrazine levels were not associated with ovarian cancer risk with or without adjusting for NO3-N and TTHM levels (p-trend=0.50 and 0.81, respectively). Further, there was no evidence for effect modification of the atrazine association by NO3-N or TTHM levels. CONCLUSIONS: In our study with low atrazine detection rates, we found no association between atrazine in PWS and postmenopausal ovarian cancer risk.

Estimating Potential Increased Bladder Cancer Risk Due to Increased Bromide Concentrations in Sources of Disinfected Drinking Waters.

Public water systems are increasingly facing higher bromide levels in their source waters from anthropogenic contamination through coal-fired power plants, conventional oil and gas extraction, textile mills, and hydraulic fracturing. Climate change is likely to exacerbate this in coming years. We estimate bladder cancer risk from potential increased bromide levels in source waters of disinfecting public drinking water systems in the United States. Bladder cancer is the health end point used by the United States Environmental Protection Agency (EPA) in its benefits analysis for regulating disinfection byproducts in drinking water. We use estimated increases in the mass of the four regulated trihalomethanes (THM4) concentrations (due to increased bromide incorporation) as the surrogate disinfection byproduct (DBP) occurrence metric for informing potential bladder cancer risk. We estimate potential increased excess lifetime bladder cancer risk as a function of increased source water bromide levels. Results based on data from 201 drinking water treatment plants indicate that a bromide increase of 50 µg/L could result in a potential increase of between 10(-3) and 10(-4) excess lifetime bladder cancer risk in populations served by roughly 90% of these plants.

Overview of Disinfection By-products and Associated Health Effects.

The presence of chemical compounds formed as disinfection by-products (DBPs) is widespread in developed countries, and virtually whole populations are exposed to these chemicals through ingestion, inhalation, or dermal absorption from drinking water and swimming pools. Epidemiological evidence has shown a consistent association between long-term exposure to trihalomethanes and the risk of bladder cancer, although the causal nature of the association is not conclusive. Evidence concerning other cancer sites is insufficient or mixed. Numerous studies have evaluated reproductive implications, including sperm quality, time to pregnancy, menstrual cycle, and pregnancy outcomes such as fetal loss, fetal growth, preterm delivery, and congenital malformation. The body of evidence suggests only minor effects from high exposure during pregnancy on fetal growth indices such as small for gestational age (SGA) at birth. Populations highly exposed to swimming pools such as pool workers and professional swimmers show a higher prevalence of respiratory symptoms and asthma, respectively, although the direction of the association, and thus causality, is not clear among professional swimmers. The risk of asthma, wheezing, eczema, and other respiratory outcomes among children attending swimming pools has been the object of extensive research. Early studies suggested a positive association, while subsequent larger studies found no correlations or showed a protective association. Future research should develop methods to evaluate the effects of the DBP mixture and the interaction with personal characteristics (e.g., genetics, lifestyle), clarify the association between swimming pools and respiratory health, evaluate the occurrence of DBPs in low- and middle-income countries, and evaluate outcomes suggested by animal studies that have not been considered in epidemiological investigations.

Occupational Exposure to Trichloramine and Trihalomethanes in Swedish Indoor Swimming Pools: Evaluation of Personal and Stationary Monitoring.

INTRODUCTION: Chlorination is a method commonly used to keep indoor swimming pool water free from pathogens. However, chlorination of swimming pools produces several potentially hazardous by-products as the chlorine reacts with nitrogen containing organic matter. Up till now, exposure assessments in indoor swimming pools have relied on stationary measurements at the poolside, used as a proxy for personal exposure. However, measurements at fixed locations are known to differ from personal exposure. METHODS: Eight public swimming pool facilities in four Swedish cities were included in this survey. Personal and stationary sampling was performed during day or evening shift. Samplers were placed at different fixed positions around the pool facilities, at ~1.5 m above the floor level and 0-1 m from the poolside. In total, 52 personal and 110 stationary samples of trichloramine and 51 personal and 109 stationary samples of trihalomethanes, were collected. RESULTS: The average concentration of trichloramine for personal sampling was 71 µg m(-3), ranging from 1 to 240 µg m(-3) and for stationary samples 179 µg m(-3), ranging from 1 to 640 µg m(-3). The air concentrations of chloroform were well below the occupational exposure limit (OEL). For the linear regression analysis and prediction of personal exposure to trichloramine from stationary sampling, only data from personal that spent >50% of their workday in the pool area were included. The linear regression analysis showed a correlation coefficient (r2) of 0.693 and a significant regression coefficient ß of 0.621; (95% CI = 0.329-0.912, P = 0.001). CONCLUSION: The trichloramine exposure levels determined in this study were well below the recommended air concentration level of 500 µg m(-3); a WHO reference value based on stationary sampling. Our regression data suggest a relation between personal exposure and area sampling of 1:2, implying an OEL of 250 µg m(-3) based on personal sampling.

Nitrate and nitrite ingestion and risk of ovarian cancer among postmenopausal women in Iowa.

Nitrate and nitrite are precursors in the endogenous formation of N-nitroso compounds (NOC), potential human carcinogens. We evaluated the association of nitrate and nitrite ingestion with postmenopausal ovarian cancer risk in the Iowa Women's Health Study. Among 28,555 postmenopausal women, we identified 315 incident epithelial ovarian cancers from 1986 to 2010. Dietary nitrate and nitrite intakes were assessed at baseline using food frequency questionnaire data. Drinking water source at home was obtained in a 1989 follow-up survey. Nitrate-nitrogen (NO3 -N) and total trihalomethane (TTHM) levels for Iowa public water utilities were linked to residences and average levels were computed based on each woman's duration at the residence. We computed multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazards regression. We tested interactions of nitrate with TTHMs and dietary factors known to influence NOC formation. Ovarian cancer risk was 2.03 times higher (CI = 1.22-3.38, ptrend = 0.003) in the highest quartile (≥2.98 mg/L) compared with the lowest quartile (≤0.47 mg/L; reference) of NO3 -N in public water, regardless of TTHM levels. Risk among private well users was also elevated (HR = 1.53, CI = 0.93-2.54) compared with the same reference group. Associations were stronger when vitamin C intake was

Use of urinary trichloroacetic acid as an exposure biomarker of disinfection by-products in cancer studies.

Urinary trichloroacetic acid (TCAA) has been proposed as a valid exposure biomarker for ingested disinfection by-products (DBP) for reproductive studies. However, it has never been used in epidemiologic studies on cancer. We investigate the performance of urinary TCAA as a biomarker of DBP exposure in the framework of an epidemiologic study on cancer. We conducted home visits to collect tap water, first morning void urine, and a 48h fluid intake diary among 120 controls from a case-control study of colorectal cancer in Barcelona, Spain. We measured urine TCAA and creatinine, and 9 haloacetic acids and 4 trihalomethanes (THM) in tap water. Lifetime THM exposure was estimated based on residential history since age 18 plus routine monitoring data. Robust linear regressions were used to estimate mean change in urinary TCAA adjusted by covariates. Among the studied group, mean age was 74 years (range 63-85) and 41 (34%) were females. Mean total tap water consumption was 2.2l/48h (standard error, 0.1l/48h). Geometric mean urine TCAA excretion rate was 17.3pmol/min [95%CI: 14.0-21.3], which increased 2% for a 10% increase in TCAA ingestion and decreased with total tap water consumption (-17%/l), water intake outside home (-32%), plasmatic volume (-64%/l), in smokers (-79%), and in users of non-steroidal anti-inflammatory drugs (-50%). Urinary TCAA levels were not associated with lifetime THM exposure. In conclusion, our findings support that urine TCAA is not a valid biomarker in case-control studies of adult cancer given that advanced age, comorbidites and medication use are prevalent and are determinants of urine TCAA levels, apart from ingested TCAA levels. In addition, low TCAA concentrations in drinking water limit the validity of urine TCAA as an exposure biomarker.

Total trihalomethanes in public drinking water supply and birth outcomes: a cross-sectional study.

Reproductive effects of long-term, low-dose exposure to disinfectant by-products have not been consistently documented in large populations despite the known toxicity of high exposures and the wide-spread occurrence of low concentrations in public drinking water. We investigated the effect of low-dose exposure to total trihalomethanes (TTHM) on birth weight and gestational term in New York State. All singleton live births from 1998 through 2003 in 62 counties in New York State were linked with public water supply (PWS) system boundaries based on mother's residential address on birth certificate. Using the data from public water supply system, TTHM measurements were assigned geographically and temporally to each birth record linked with PWS boundary. Individual level maternal information including mother's race, ethnicity, education, employment status, smoking, age, along with adequacy of prenatal care utilization and infant's gender was used in a logistic model to adjust for potential confounding. A small non-linear association was detected between TTHM exposure and low birth weight (<2,500 g) births (OR 1.14; 95 % confidence interval (CI) 1.08-1.21), preterm births (OR 1.14; 95 % CI 1.08-1.20) and for small for gestational age births (OR 1.10; 95 % CI 1.04-1.16) suggesting a small increase in risk for these birth outcomes with chronic low maternal exposure to drinking water containing trihalomethanes. Maternal exposure to TTHMs during pregnancy may be associated with low birth weight, preterm births and small for gestational age births.

Association of brominated trihalomethane and haloacetic acid exposure with fetal growth and preterm delivery in Massachusetts.

OBJECTIVES: We examined the relationship between adverse reproductive outcomes and exposure to several disinfection by-products including haloacetic acids (HAAs), trihalomethanes (THMs), and the brominated THMs sum (THMBr). METHODS: Second- and third-trimester exposure scores were estimated from quarterly town-level average THM and HAA concentration data and were examined relative to mean birth weight (BWT), small for gestational age (SGA), and preterm delivery (PTD). RESULTS: We found an increased risk of PTD for second-trimester chloroform, bromodichloromethane, and all HAA exposure metrics (adjusted odds ratio range: 1.04 to 1.15), but detected no associations for SGA and third-trimester exposures. Mean BWT deficits were observed across all HAA (26 to 33 g) and THMBr (11 to 23 g) exposure categories. CONCLUSIONS: We detected consistent associations for adjusted mean BWT and THMBr exposures; these data reinforce the need to consider different disinfection by-product exposure metrics in epidemiological studies.