Dataset Information

Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products.

ABSTRACT: Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An international workshop was held to (1) discuss the qualitative strengths and limitations that inform the association between bladder cancer and CxDBPs in the context of possible causation, (2) identify knowledge gaps for this topic in relation to chlorine/chloramine-based disinfection practice(s) in the United States, and (3) assess the evidence for informing risk management. Epidemiological evidence linking exposures to CxDBPs in drinking water to human bladder cancer risk provides insight into causality. However, because of imprecise, inaccurate, or incomplete estimation of CxDBPs levels in epidemiologic studies, translation from hazard identification directly to risk management and regulatory policy for CxDBPs can be challenging. Quantitative risk estimates derived from toxicological risk assessment for CxDBPs currently cannot be reconciled with those from epidemiologic studies, notwithstanding the complexities involved, making regulatory interpretation difficult. Evidence presented here has both strengths and limitations that require additional studies to resolve and improve the understanding of exposure response relationships. Replication of epidemiologic findings in independent populations with further elaboration of exposure assessment is needed to strengthen the knowledge base needed to better inform effective regulatory approaches.

SUBMITTER: Hrudey SE

PROVIDER: S-EPMC4642182 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products.

Hrudey Steve E SE Backer Lorraine C LC Humpage Andrew R AR Krasner Stuart W SW Michaud Dominique S DS Moore Lee E LE Singer Philip C PC Stanford Benjamin D BD

Journal of toxicology and environmental health. Part B, Critical reviews 20150826 5

Exposure to chlorination disinfection by-products (CxDBPs) is prevalent in populations using chlorination-based methods to disinfect public water supplies. Multifaceted research has been directed for decades to identify, characterize, and understand the toxicology of these compounds, control and minimize their formation, and conduct epidemiologic studies related to exposure. Urinary bladder cancer has been the health risk most consistently associated with CxDBPs in epidemiologic studies. An inte ...[more]

PMID: 26309063

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Project description:The world is not on track to meet Sustainable Development Goal 6.1 to provide universal access to safely managed drinking water by 2030. Removal of priority microbial contaminants by disinfection is one aspect of ensuring water is safely managed. Passive chlorination (also called in-line chlorination) represents one approach to disinfecting drinking water before or at the point of collection (POC), without requiring daily user input or electricity. In contrast to manual household chlorination methods typically implemented at the point of use (POU), passive chlorinators can reduce the user burden for chlorine dosing and enable treatment at scales ranging from communities to small municipalities. In this review, we synthesized evidence from 27 evaluations of passive chlorinators (in 19 articles, 3 NGO reports, and 5 theses) conducted across 16 countries in communities, schools, health care facilities, and refugee camps. Of the 27 passive chlorinators we identified, the majority (22/27) were solid tablet or granular chlorine dosers, and the remaining devices were liquid chlorine dosers. We identified the following research priorities to address existing barriers to scaled deployment of passive chlorinators: (i) strengthening local chlorine supply chains through decentralized liquid chlorine production, (ii) validating context-specific business models and financial sustainability, (iii) leveraging remote monitoring and sensing tools to monitor real-time chlorine levels and potential system failures, and (iv) designing handpump-compatible passive chlorinators to serve the many communities reliant on handpumps as a primary drinking water source. We also propose a set of reporting indicators for future studies to facilitate standardized evaluations of the technical performance and financial sustainability of passive chlorinators. In addition, we discuss the limitations of chlorine-based disinfection and recognize the importance of addressing chemical contamination in drinking water supplies. Passive chlorinators deployed and managed at-scale have the potential to elevate the quality of existing accessible and available water services to meet "safely managed" requirements.

Project description:BackgroundBy-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants.ObjectivesIn this study, we investigated the combined effect on bladder cancer risk contributed by TTHMs, bladder cancer susceptibility variants identified through genome-wide association studies, and variants in several candidate genes.MethodsWe analyzed data from two large case-control studies-the New England Bladder Cancer Study (n/n=989 cases/1,162 controls), a population-based study, and the Spanish Bladder Cancer Study (n/n=706 cases/772 controls), a hospital-based study. Because of differences in exposure distributions and metrics, we estimated effects of THMs and genetic variants within each study separately using adjusted logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CI) with and without interaction terms, and then combined the results using meta-analysis.ResultsOf the 16 loci showing strong evidence of association with bladder cancer, rs907611 at 11p15.5 [leukocyte-specific protein 1 (LSP1 region)] showed the strongest associations in the highest exposure category in each study, with evidence of interaction in both studies and in meta-analysis. In the highest exposure category, we observed OR=1.66 (95% CI: 1.17, 2.34, p-trend=0.005) for those with the rs907611-GG genotype and p-interaction=0.02. No other genetic variants tested showed consistent evidence of interaction.DiscussionWe found novel suggestive evidence for a multiplicative interaction between a putative bladder carcinogen, TTHMs, and genotypes of rs907611. Given the ubiquitous exposure to THMs, further work is needed to replicate and extend this finding and to understand potential molecular mechanisms. https://doi.org/10.1289/EHP9895.

Project description:BackgroundDrinking water chlorination by-products have been associated with adverse reproductive outcomes, although the findings for congenital malformations are still inconclusive.ObjectiveWe conducted a nationwide register-based prospective study to assess whether first trimester maternal exposure to the four most common trihalomethanes [total trihalomethanes (TTHM)] via municipal drinking water was associated with risk of congenital malformation among newborns.MethodsWe included all births during 2005-2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, two or fewer operating water works, and sufficient municipal TTHM monitoring data. Individual maternal first trimester exposure was obtained by linking TTHM measurements to residential information, categorized into no chlorination and <5, 5-15, and >15μg TTHM/L. We also made chlorination treatment-specific analyses (exclusive use of chloramine or hypochlorite). Outcomes and covariates were obtained via linkage to health care and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression.ResultsBased on 623,468 births and a prevalence of congenital malformation of ∼2 cases/100 births, we observed associations between TTHM exposure in areas using chloramine and malformations of the nervous system (OR=1.82; 95% CI: 1.07, 3.12), urinary system (OR=2.06; 95% CI: 1.53, 2.78), genitals (OR=1.77; 95% CI: 1.38, 2.26), and limbs (OR=1.34; 95% CI: 1.10, 1.64), comparing the highest exposed category with the unexposed. No associations were observed in areas using exclusively hypochlorite as the primary water treatment method. By contrast, for malformations of the heart, a significant inverse association was observed only in areas using hypochlorite.DiscussionTTHM exposure was associated with the increased risk of malformations of the nervous system, urinary system, genitals, and limbs in areas exclusively using chloramine. An association between chloramine-related chlorination by-products and congenital malformations has not previously been highlighted and needs further attention. https://doi.org/10.1289/EHP9122.

Project description:BackgroundKnowledge about human exposure and health effects associated with non-routinely monitored disinfection by-products (DBPs) in drinking water is sparse.ObjectiveTo provide insights to estimate exposure to regulated and non-regulated DBPs in drinking water.MethodsWe collected tap water from homes (N = 42), bottled water (N = 10), filtered tap water with domestic activated carbon jars (N = 6) and reverse osmosis (N = 5), and urine (N = 39) samples of participants from Barcelona, Spain. We analyzed 11 haloacetic acids (HAAs), 4 trihalomethanes (THMs), 4 haloacetonitriles (HANs), 2 haloketones, chlorate, chlorite, and trichloronitromethane in water and HAAs in urine samples. Personal information on water intake and socio-demographics was ascertained in the study population (N = 39) through questionnaires. Statistical models were developed based on THMs as explanatory variables using multivariate linear regression and machine learning techniques to predict non-regulated DBPs.ResultsChlorate, THMs, HAAs, and HANs were quantified in 98-100% tap water samples with median concentration of 214, 42, 18, and 3.2 μg/L, respectively. Multivariate linear regression models had similar or higher goodness of fit (R2) compared to machine learning models. Multivariate linear models for dichloro-, trichloro-, and bromodichloroacetic acid, dichloroacetonitrile, bromochloroacetonitrile, dibromoacetonitrile, trichloropropnanone, and chlorite showed good predictive ability (R 2 = 0.8-0.9) as 80-90% of total variance could be explained by THM concentrations. Activated carbon filters reduced DBP concentrations to a variable extent (27-80%), and reverse osmosis reduced DBP concentrations ≥98%. Only chlorate was detected in bottled water samples (N = 3), with median = 13.0 µg/L. Creatinine-adjusted trichloroacetic acid was the most frequently detected HAA in urine samples (69.2%), and moderately correlated with estimated drinking water intake (r = 0.48).SignificanceFindings provide valuable insights for DBP exposure assessment in epidemiological studies. Validation of predictive models in a larger number of samples and replication in different settings is warranted.Impact statementOur study focused on assessing and describing the occurrence of several classes of DBPs in drinking water and developing exposure models of good predictive ability for non-regulated DBPs.

Project description:BACKGROUND:Chlorination is globally used to produce of safe drinking water. Chlorination by-products are easily formed, and there are indications that these are associated with adverse reproductive outcomes. OBJECTIVES:We conducted a nationwide register-based prospective study to assess whether gestational exposure to the four most common chlorination by-products [total trihalomethanes (TTHMs)] via tap water was associated with risk of small for gestational age (SGA), preterm delivery, and very preterm delivery. To date, this is one of the largest studies assessing drinking water TTHM-associated adverse reproductive outcomes. METHODS:We included all singleton births 2005-2015 (live and stillbirths) of mothers residing in Swedish localities having >10,000 inhabitants, ?2 operating waterworks, adequate information on chlorination treatment, and a sufficient number of routine TTHM measurements in tap water. Individual maternal second and third trimester exposure was obtained by linking TTHM measurements to residential history, categorized into no chlorination, <5, 5-15, and >15?g TTHM/L. Outcomes and covariates were obtained via the linkage to Swedish health and administrative registers. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression using inverse probability weighting. We stratified the analyses by chlorination treatment (chloramine, hypochlorite). RESULTS:Based on approximately 500,000 births, we observed a TTHM dose-dependent association with increased risk of SGA, confined to treatment with hypochlorite, corresponding to a multivariable-adjusted OR=1.20 (95% CI: 1.08, 1.33) comparing drinking water TTHM >15?g to the unexposed. Similar results were obtained when, instead of unexposed, the lowest exposure category (<5?g/L TTHM) was used as reference. No clear associations were observed for preterm delivery and very preterm delivery. DISCUSSION:Chlorination by-products exposure via drinking water was associated with increased risk of SGA in areas with hypochlorite treatment. https://doi.org/10.1289/EHP6012.

Dataset Information

Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products.

Publications

Evaluating Evidence for Association of Human Bladder Cancer with Drinking-Water Chlorination Disinfection By-Products.

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