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      Estimating National Exposures and Potential Bladder Cancer Cases Associated with Chlorination DBPs in U.S. Drinking Water

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          Abstract

          Background:

          Disinfection byproducts (DBPs) in public water systems (PWS) are an unintended consequence resulting from reactions between mostly chlorine-based disinfectants and organic and inorganic compounds in source waters. Epidemiology studies have shown that exposure to DBP (specifically trihalomethanes) was associated with an increased risk of bladder cancer.

          Objective:

          Our goal was to characterize the relative differences in exposures and estimated potential bladder cancer risks for people served by different strata of PWS in the United States and to evaluate uncertainties associated with these estimates.

          Methods:

          We stratified PWS by source water type (surface vs. groundwater) and population served (large, medium, and small) and calculated population-weighted mean trihalomethane-4 (THM4) concentrations for each stratum. For each stratum, we calculated a population attributable risk (PAR) for bladder cancer using odds ratios derived from published pooled epidemiology estimates as a function of the mean THM4 concentration and the fraction of the total U.S. population served by each stratum of systems. We then applied the stratum-specific PARs to the total annual number of new bladder cancer cases in the U.S. population to estimate bladder cancer incidence in each stratum.

          Results:

          Our results show that approximately 8,000 of the 79,000 annual bladder cancer cases in the United States were potentially attributable to DBPs in drinking water systems. The estimated attributable cases vary based on source water type and system size. Approximately 74% of the estimated attributable cases were from surface water systems serving populations of > 10,000 people. We also identified several uncertainties that may affect the results from this study, primarily related to the use of THM4 as a surrogate measure for DBPs relevant to bladder cancer.

          Discussion:

          Despite significant reductions in exposure over the past several decades, our study suggests that 10 % of the bladder cancer cases in the United States may still be attributed to exposure to DBPs found in drinking water systems. https://doi.org/10.1289/EHP9985

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          Most cited references46

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          Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: a review and roadmap for research.

          Disinfection by-products (DBPs) are formed when disinfectants (chlorine, ozone, chlorine dioxide, or chloramines) react with naturally occurring organic matter, anthropogenic contaminants, bromide, and iodide during the production of drinking water. Here we review 30 years of research on the occurrence, genotoxicity, and carcinogenicity of 85 DBPs, 11 of which are currently regulated by the U.S., and 74 of which are considered emerging DBPs due to their moderate occurrence levels and/or toxicological properties. These 74 include halonitromethanes, iodo-acids and other unregulated halo-acids, iodo-trihalomethanes (THMs), and other unregulated halomethanes, halofuranones (MX [3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone] and brominated MX DBPs), haloamides, haloacetonitriles, tribromopyrrole, aldehydes, and N-nitrosodimethylamine (NDMA) and other nitrosamines. Alternative disinfection practices result in drinking water from which extracted organic material is less mutagenic than extracts of chlorinated water. However, the levels of many emerging DBPs are increased by alternative disinfectants (primarily ozone or chloramines) compared to chlorination, and many emerging DBPs are more genotoxic than some of the regulated DBPs. Our analysis identified three categories of DBPs of particular interest. Category 1 contains eight DBPs with some or all of the toxicologic characteristics of human carcinogens: four regulated (bromodichloromethane, dichloroacetic acid, dibromoacetic acid, and bromate) and four unregulated DBPs (formaldehyde, acetaldehyde, MX, and NDMA). Categories 2 and 3 contain 43 emerging DBPs that are present at moderate levels (sub- to low-mug/L): category 2 contains 29 of these that are genotoxic (including chloral hydrate and chloroacetaldehyde, which are also a rodent carcinogens); category 3 contains the remaining 14 for which little or no toxicological data are available. In general, the brominated DBPs are both more genotoxic and carcinogenic than are chlorinated compounds, and iodinated DBPs were the most genotoxic of all but have not been tested for carcinogenicity. There were toxicological data gaps for even some of the 11 regulated DBPs, as well as for most of the 74 emerging DBPs. A systematic assessment of DBPs for genotoxicity has been performed for approximately 60 DBPs for DNA damage in mammalian cells and 16 for mutagenicity in Salmonella. A recent epidemiologic study found that much of the risk for bladder cancer associated with drinking water was associated with three factors: THM levels, showering/bathing/swimming (i.e., dermal/inhalation exposure), and genotype (having the GSTT1-1 gene). This finding, along with mechanistic studies, highlights the emerging importance of dermal/inhalation exposure to the THMs, or possibly other DBPs, and the role of genotype for risk for drinking-water-associated bladder cancer. More than 50% of the total organic halogen (TOX) formed by chlorination and more than 50% of the assimilable organic carbon (AOC) formed by ozonation has not been identified chemically. The potential interactions among the 600 identified DBPs in the complex mixture of drinking water to which we are exposed by various routes is not reflected in any of the toxicology studies of individual DBPs. The categories of DBPs described here, the identified data gaps, and the emerging role of dermal/inhalation exposure provide guidance for drinking water and public health research.
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            Epidemiology of Bladder Cancer

            Based on the latest GLOBOCAN data, bladder cancer accounts for 3% of global cancer diagnoses and is especially prevalent in the developed world. In the United States, bladder cancer is the sixth most incident neoplasm. A total of 90% of bladder cancer diagnoses are made in those 55 years of age and older, and the disease is four times more common in men than women. While the average 5-year survival in the US is 77%, the 5-year survival for those with metastatic disease is a measly 5%. The strongest risk factor for bladder cancer is tobacco smoking, which accounts for 50–65% of all cases. Occupational or environmental toxins likewise greatly contribute to disease burden (accounting for an estimated 20% of all cases), though the precise proportion can be obscured by the fact bladder cancer develops decades after exposure, even if the exposure only lasted several years. Schistosomiasis infection is the common cause of bladder cancer in regions of Africa and the Middle East and is considered the second most onerous tropical pathogen after malaria. With 81% of cases attributable to known risk factors (and only 7% to heritable mutations), bladder cancer is a prime candidate for prevention strategies. Smoking cessation, workplace safety practices, weight loss, exercise and schistosomiasis prevention (via water disinfection and mass drug administration) have all been shown to significantly decrease the risk of bladder cancer, which poses a growing burden around the world.
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              Drinking Water Disinfection Byproducts (DBPs) and Human Health Effects: Multidisciplinary Challenges and Opportunities

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                Author and article information

                Journal
                Environ Health Perspect
                Environ Health Perspect
                EHP
                Environmental Health Perspectives
                Environmental Health Perspectives
                0091-6765
                1552-9924
                1 August 2022
                August 2022
                : 130
                : 8
                : 087002
                Affiliations
                [ 1 ]U.S. Environmental Protection Agency (U.S. EPA) , Washington, DC, USA
                [ 2 ]The Cadmus Group LLC , Waltham, Massachusetts, USA
                Author notes
                Address correspondence to Richard Weisman, U.S. EPA, 1200 Pennsylvania Ave., N.W. (MC: 4607M), Washington, DC, USA 20460. Email: Weisman.richard@ 123456epa.gov
                Author information
                https://orcid.org/0000-0002-4433-0410
                https://orcid.org/0000-0002-5631-6181
                https://orcid.org/0000-0002-9730-3651
                Article
                EHP9985
                10.1289/EHP9985
                9342685
                35913906
                a8d7f618-83a9-4a25-ac1c-efbcd5f31e3e

                EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.

                History
                : 13 July 2021
                : 21 June 2022
                : 27 June 2022
                Categories
                Research

                Public health
                Public health

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