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Disinfection Byproducts and Cancer - Journal Abstracts

National Library of Medicine

TITLE: Potential carcinogenic hazards of non-regulated disinfection by-products: haloquinones, halo-cyclopentene and cyclohexene derivatives, N-halamines, halonitriles, and heterocyclic amines.
AUTHORS: Bull RJ, Reckhow DA, Li X, Humpage AR, Joll C, Hrudey SE.
SOURCE: Toxicology. 2011 Aug 15;286(1-3):1-19.
ABSTRACT: Drinking water disinfectants react with natural organic material (NOM) present in source waters used for drinking water to produce a wide variety of by-products. Several hundred disinfections by-products (DBPs) have been identified, but none have been identified with sufficient carcinogenic potency to account for the cancer risks projected from epidemiological studies. In a search for DBPs that might fill this risk gap, the present study projected reactions of chlorine and chloramine that could occur with substructures present in NOM to produce novel by-products. ...This analysis indicates that research on the general problem of DBPs requires a more systematic approach than has been pursued in the past. Utilization of predictive chemical tools to guide further research can help bring resolution to the DBP issue by identifying likely DBPs with high toxicological potency.

TITLE: Epidemiological approaches in the investigation of environmental causes of cancer: the case of dioxins and water disinfection by-products.
AUTHOR: Kogevinas M.
SOURCE: Environ Health. 2011 Apr 5;10 Suppl 1:S3
ABSTRACT: Contrary to dioxins, trihalomethanes (THMs) and most of the hundreds of DBPs in drinking water are chemicals of low toxicity. For more than 15 years, the main evidence on the carcinogenicity of DBPs was through ecological or death certificate studies. More recent studies based on individual assessment confirmed increases in bladder cancer risk. However even those studies ignored the toxicological evidence on the importance of routes of exposure to DBPs other than ingestion and, probably, underestimated the risk. Persistence of weak study designs together with delays in advanced exposure assessment models led to delays in confirming early evidence on the carcinogenicity of DBPs. The evaluation of only a few chemicals when exposure is to a complex mixture remains a major problem in exposure assessment for DBPs. The success of epidemiological studies in identifying increased risks lies primarily on the wide contrast of exposure to DBPs in the general population that overcomes the significant exposure misclassification.

TITLE: Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case-control studies.
AUTHOR: Costet N, et. al.
SOURCE: Occup Environ Med. 2011 May;68(5):379-85. Epub 2011 Mar 9.
ABSTRACT: A significant odds-ratio was observed for men exposed to an average residential TTHM level > 50 μg/l (OR = 1.47 (1.05; 2.05)) when compared to men exposed to levels ≤ 5 μg/l. The linear trend of the exposure-risk association was significant (p = 0.01). Risks increased significantly for exposure levels above 25 μg/l and with more than 30 years of exposure to chlorinated water, but were mainly driven by the level rather than the duration of exposure. No significant association was found among women or with cumulative exposure through ingestion.

TITLE: Bladder cancer and exposure to water disinfection by-products through ingestion, bathing, showering, and swimming in pools.
AUTHORS: Villanueva CM, Cantor KP, Grimalt JO, Malats N, Silverman D, Tardon A, Garcia-Closas R, Serra C, Carrato A, Castaņo-Vinyals G, Marcos R, Rothman N, Real FX, Dosemeci M, Kogevinas M.
SOURCE: Am J Epidemiol. 2007 Jan 15;165(2):148-56.
ABSTRACT: Bladder cancer has been associated with exposure to chlorination by-products in drinking water, and experimental evidence suggests that exposure also occurs through inhalation and dermal absorption. The authors examined whether bladder cancer risk was associated with exposure to trihalomethanes (THMs) through ingestion of water and through inhalation and dermal absorption during showering, bathing, and swimming in pools. Lifetime personal information on water consumption and water-related habits was collected for 1,219 cases and 1,271 controls in a 1998-2001 case-control study in Spain and was linked with THM levels in geographic study areas. Long-term THM exposure was associated with a twofold bladder cancer risk, with an odds ratio of 2.10 (95% confidence interval: 1.09, 4.02) for average household THM levels of >49 versus < or =8 micro g/liter. Compared with subjects not drinking chlorinated water, subjects with THM exposure of >35 micro g/day through ingestion had an odds ratio of 1.35 (95% confidence interval: 0.92, 1.99). The odds ratio for duration of shower or bath weighted by residential THM level was 1.83 (95% confidence interval: 1.17, 2.87) for the highest compared with the lowest quartile. Swimming in pools was associated with an odds ratio of 1.57 (95% confidence interval: 1.18, 2.09). Bladder cancer risk was associated with long-term exposure to THMs in chlorinated water at levels regularly occurring in industrialized countries.

TITLE: Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: a review and roadmap for research.
AUTHORS: Richardson SD, Plewa MJ, Wagner ED, Schoeny R, Demarini DM.
SOURCE: Mutat Res. 2007 Nov-Dec;636(1-3):178-242. Epub 2007 Sep 12.
ABSTRACT: 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.

TITLE: Disinfection byproducts and bladder cancer: a pooled analysis.
AUTHORS: Villanueva CM, Cantor KP, Cordier S, Jaakkola JJ, King WD, Lynch CF, Porru S, Kogevinas M.
SOURCE: Epidemiology. 2004 May;15(3):357-67.
BACKGROUND: Exposure to disinfection byproducts in drinking water has been associated with an increased risk of bladder cancer. We pooled the primary data from 6 case-control studies of bladder cancer that used trihalomethanes as a marker of disinfection byproducts. METHODS: Two studies were included from the United States and one each from Canada, France, Italy, and Finland. Inclusion criteria were availability of detailed data on trihalomethane exposure and individual water consumption. The analysis included 2806 cases and 5254 controls, all of whom had measures of known exposure for at least 70% of the exposure window of 40 years before the interview. Cumulative exposure to trihalomethanes was estimated by combining individual year-by-year average trihalomethane level and daily tap water consumption. RESULTS: There was an adjusted odds ratio (OR) of 1.24 in men exposed to an average of more than 1 microg/L (ppb) trihalomethanes compared with those who had lower or no exposure (95% confidence interval [CI] = 1.09-1.41). Estimated relative risks increased with increasing exposure, with an OR of 1.44 (1.20-1.73) for exposure higher than 50 microg/L (ppb). Similar results were found with other indices of trihalomethane exposure. Among women, trihalomethane exposure was not associated with bladder cancer risk (0.95; 0.76-1.20). CONCLUSIONS: These findings strengthen the hypothesis that the risk of bladder cancer is increased with long-term exposure to disinfection byproducts at levels currently observed in many industrialized countries.

TITLE: Component-based and whole-mixture techniques for addressing the toxicity of drinking-water disinfection by-product mixtures.
AUTHORS: Simmons JE, Teuschler LK, Gennings C, Speth TF, Richardson SD, Miltner RJ, Narotsky MG, Schenck KD, Hunter ES 3rd, Hertzberg RC, Rice G.
SOURCE: J Toxicol Environ Health A. 2004 Apr 23-May 28;67(8-10):741-54. 
ABSTRACT: Chemical disinfection of water is of direct public health benefit as it results in decreased water-borne illness. The chemicals used to disinfect water react with naturally occurring organic matter, bromide, and iodide in the source water, resulting in the formation of disinfection by-products (DBPs). Despite the identification of several hundred DBPs, more than 50% of the mass of total organic halide formed during chlorination remains unidentified. The toxic contribution of the DBPs that are formed and present but not yet chemically identified, the unidentified fraction, has been largely unexplored. A better understanding of the potential for adverse human health consequences associated with exposure to the DBPs present in drinking water will be gained by integration of knowledge on the toxicity of individual DBPs; simple, defined DBP mixtures; complex, environmentally realistic DBP mixtures with partial chemical characterization; and the unidentified fraction.

TITLE: Different frames, different fears: communicating about chlorinated drinking water and cancer in the Canadian media.
AUTHORS: Driedger SM, Eyles J.
SOURCE: Soc Sci Med. 2003 Mar;56(6):1279-93.
ABSTRACT: Risk issues become complicated when scientific evidence concerning a potential environmental exposure is equivocal; particularly when many argue that the public health benefits of a policy action outweigh any potential negative health effects. Chlorinated drinking water, and chlorinated disinfection byproducts (CDBPs) that are formed during the disinfection process, represent a useful case-study for examining these complications. We conduct a media analysis of chlorinated drinking water stories in the Canadian print media from 1977 to 2000. We examine media presentations of science compared to framings by scientists, regulators, the chlorine industry, water utility representatives, and non-governmental organizations of the CDBP issue based on key informant interviews. We argue that there are two main framings of the debate, each of which are powerful in constructing risk perceptions. On the one hand, many frame the debate as a 'voluntary' risk: we choose chlorine disinfection to protect against microbial risks with a possible adverse consequence of that protection. On the other hand, others frame the issue as an 'involuntary' risk: chlorine disinfection was a 'choice' imposed by public health and water utility officials; a choice that carries a potential cancer risk, and alternative disinfection technologies are advocated. We demonstrate these different frames by examining metaphorical constructs of water, chlorine and cancer contained within them.

 Related Articles, Links
TITLE: Constructing scientific authorities: issue framing of chlorinated disinfection byproducts in public health.
AUTHORS: Driedger SM, Eyles J, Elliott SD, Cole DC.
SOURCE: Risk Anal. 2002 Aug;22(4):789-802.
ABSTRACT: The practice of chlorine disinfection of drinking water to reduce microbial risks provides substantial benefits to public health. However, increasing concern around potential risks of cancer associated with exposure to chlorinated disinfection byproducts confuses this issue. This article examines the science agenda regarding chlorinated disinfection byproducts (CDBP) and cancer in Canada and the United States, focusing on the social construction of scientific knowledge claims and evidence. Data for this analysis were obtained from published documents as well as from in-depth interviews with epidemiologists and toxicologists centrally involved with the issue in both countries. Results of the analysis suggest that toxicological scientists want to close the door on the "chloroform issue" due to increasing evidence that chloroform is safe at low doses, because epidemiological scientists can no longer move forward the cancer science until significant improvements can be made in assessing human exposures, and because the scientific foci of research on DBP have shifted accordingly. Further, a distinction emerges in terms of how scientific uncertainties are interpreted when they cross-cut disciplines in the context of human health risk assessment. We suggest this tension reflects a balance of how uncertainty and authorities are managed in a mandated science-policy domain. Sufficient evidence was provided to keep the DBP issue on the regulatory agenda and to generate additional research, yet authorities and concomitant interpretations of uncertainty were contested. Such science generation and contestation inevitably influences complex risk assessment processes with respect to what water-related health risks are addressed and how.

TITLE: Development of a research strategy for integrated technology-based toxicological and chemical evaluation of complex mixtures of drinking water disinfection byproducts.
SOURCE: Simmons JE, Richardson SD, Speth TF, Miltner RJ, Rice G, Schenck KM, Hunter ES 3rd, Teuschler LK.
SOURCE: Environ Health Perspect. 2002 Dec;110 Suppl 6:1013-24
ABSTRACT: Chemical disinfection of water is a major public health triumph of the 20th century. Dramatic decreases in both morbidity and mortality of waterborne diseases are a direct result of water disinfection. With these important public health benefits comes low-level, chronic exposure to a very large number of disinfection byproducts (DBPs), chemicals formed through reaction of the chemical disinfectant with naturally occurring inorganic and organic material in the source water. This article provides an overview of joint research planning by scientists residing within the various organizations of the U.S. Environmental Protection Agency Office of Research and Development. The purpose is to address concerns related to potential health effects from exposure to DBPs that cannot be addressed directly from toxicological studies of individual DBPs or simple DBP mixtures. Two factors motivate the need for such an investigation of complex mixtures of DBPs: a) a significant amount of the material that makes up the total organic halide and total organic carbon portions of the DBPs has not been identified; and b) epidemiologic data, although not conclusive, are suggestive of potential developmental, reproductive, or carcinogenic health effects in humans exposed to DBPs. The plan is being developed and the experiments necessary to determine the feasibility of its implementation are being conducted by scientists from the National Health and Environmental Effects Research Laboratory, the National Risk Management Research Laboratory, the National Exposure Research Laboratory, and the National Center for Environmental Assessment.

TITLE: The epidemiology of chemical contaminants of drinking water.
AUTHORS: Calderon RL
SOURCE: Food Chem Toxicol 2000 Apr 1;38 Suppl 1(2-3):S13-S20 [Record as supplied by publisher]
ABSTRACT: A number of chemical contaminants have been identified in drinking water. These contaminants reach drinking water supplies from various sources, including municipal and industrial discharges, urban and rural run-off, natural geological formations, drinking water distribution materials and the drinking water treatment process. Chemical contaminants for which epidemiologic studies have reported associations include the following: aluminium, arsenic, disinfection by-products, fluoride, lead, pesticides and radon. Health effects reported have included various cancers, adverse reproductive outcomes, cardiovascular disease and neurological disease. In evaluating epidemiologic studies for risk assessment, considering whether the study design was qualitative (hypothesis generating) or quantitative (hypothesis testing) is important and whether sufficient epidemiologic data of a quantitative nature exists to determine the dose-response curve. Each of the chemical contaminants mentioned are summarized by study designs (qualitative and quantitative) and whether a dose-response curve based on epidemiologic data has been proposed. Environmental epidemiology studies are driven by environmental exposures of interest. For drinking water contaminants, the design of epidemiologic studies and their interpretation should consider the following exposure issues: the source of the contaminant; other sources of the contaminant; the route of exposure; the frequency, duration and magnitude of exposure; the ability to document an actual internal dose; and the ability to document the dose to the target organ. Health effects of concern have other risk factors that must be measured in the conduct of these studies. In evaluating epidemiologic studies, potential errors and biases that may occur must be considered given the very low magnitude of associations (less than 2.0 for either odds ratio or risk ratio). Given the issues, the next generation of drinking water epidemiologic studies should include a multidisciplinary team beyond traditional epidemiologists and statisticians. Study teams will require toxicologists, chemists, engineers and exposure assessors. Arsenic is briefly discussed as an example of the importance of susceptible populations. Disinfection by-products are discussed as an example of epidemiologic studies of mixtures.

TITLE: Drinking water source and chlorination byproducts in Iowa. III. Risk of brain cancer.
AUTHORS: Cantor KP; Lynch CF; Hildesheim ME; Dosemeci M; Lubin J; Alavanja M; Craun G
SOURCE: Am J Epidemiol 1999 Sep 15;150(6):552-60
ABSTRACT: The authors conducted a population-based case-control study in Iowa of 375 brain cancer patients and 2,434 controls. A postal questionnaire was used to gather information on lifetime residential history, sources of drinking water, beverage intake, and other potential risk factors. Exposure to chlorination byproducts in drinking water was estimated by combining questionnaire data with historical information from water utilities and trihalomethane levels in recent samples. The analysis included 291 cases (77.6%) and 1,983 controls (81.5%), for whom water quality information was available for at least 70% of lifetime years. Proxies represented 74.4% of cases. The mean number and mean duration of places of residence were comparable between direct and proxy respondents, suggesting little contribution to bias. After multivariate adjustment, odds ratios for brain cancer were 1.0, 1.1, 1.6, and 1.3 for exposure to chlorinated surface water of 0, 1-19, 20-39, and > or =40 years (p trend = 0.1). Among men, odds ratios were 1.0, 1.3, 1.7, and 2.5 (p trend = 0.04), and among women, 1.0, 1.0, 1.6, and 0.7 (p trend = 0.7)). Similar findings were found with estimates of average lifetime level of trihalomethanes. The association was stronger among men with above-median tap water consumption. These observations deserve further attention, especially in view of increasing glioma rates.

TITLE: [Chlorination of drinking water--possible cancer risk from a by-product]
AUTHORS: Holme JA; Steffensen IL; Brunborg G; Becher G; Alexander J
SOURCE: Tidsskr Nor Laegeforen 1999 Jun 30;119(17):2528-30
ABSTRACT: In a recent study, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX; CAS no 77439-76-0) which is formed during chlorination of water containing organic substances, was found to be carcinogenic in the rat, at multiple sites in both sexes. MX is known as a potent bacterial mutagen. Epidemiological studies have suggested an association between chlorinated water consumption and a moderate increase in the risk of cancer. Although MX is a strong mutagen in prokaryotes, its genotoxic effects in mammalian cells are not so large, and more variable results are obtained. Very low concentrations of MX are found in drinking water (ng/L), whereas the genotoxic and carcinogenic effects in experimental animals of this compound are detectable at relatively high doses (mg/kg body weight). Relative to the risk for infectious diseases from the consumption of contaminated drinking water, the possible cancer risk associated with MX exposure appears to be low. Even so, efforts should be made to reduce disinfection byproduct formation by removing organic matter before chlorination.

TITLE: Drinking Water Disinfection Byproducts: Review and Approach to Toxicity Evaluation.
SOURCE: Environ Health Perspect 1999 Feb;107 Suppl 1:207-217 [Record as supplied by publisher
ABSTRACT: There is widespread potential for human exposure to disinfection byproducts (DBPs) in drinking water because everyone drinks, bathes, cooks, and cleans with water. The need for clean and safe water led the U.S. Congress to pass the Safe Drinking Water Act more than 20 years ago in 1974. In 1976, chloroform, a trihalomethane (THM) and a principal DBP, was shown to be carcinogenic in rodents. This prompted the U.S. Environmental Protection Agency (U.S. EPA) in 1979 to develop a drinking water rule that would provide guidance on the levels of THMs allowed in drinking water. Further concern was raised by epidemiology studies suggesting a weak association between the consumption of chlorinated drinking water and the occurrence of bladder, colon, and rectal cancer. In 1992 the U.S. EPA initiated a negotiated rulemaking to evaluate the need for additional controls for microbial pathogens and DBPs. The goal was to develop an approach that would reduce the level of exposure from disinfectants and DBPs without undermining the control of microbial pathogens. The product of these deliberations was a proposed stage 1 DBP rule. It was agreed that additional information was necessary on how to optimize the use of disinfectants while maintaining control of pathogens before further controls to reduce exposure beyond stage 1 were warranted. In response to this need, the U.S. EPA developed a 5-year research plan to support the development of the longer term rules to control microbial pathogens and DBPs. A considerable body of toxicologic data has been developed on DBPs that occur in the drinking water, but the main emphasis has been on THMs. Given the complexity of the problem and the need for additional data to support the drinking water DBP rules, the U.S. EPA, the National Institute of Environmental Health Sciences, and the U.S. Army are working together to develop a comprehensive biologic and mechanistic DBP database. Selected DBPs will be tested using 2-year toxicity and carcinogenicity studies in standard rodent models; transgenic mouse models and small fish models; in vitro mechanistic and toxicokinetic studies; and reproductive, immunotoxicity, and developmental studies. The goal is to create a toxicity database that reflects a wide range of DBPs resulting from different disinfection practices. This paper describes the approach developed by these agencies to provide the information needed to make scientifically based regulatory decisions.

TITLE: Assessment of disinfection by-products in drinking water in Korea.
AUTHORS: Shin D; Chung Y; Choi Y; Kim J; Park Y; Kum H
SOURCE: J Expo Anal Environ Epidemiol 1999 May-Jun;9(3):192-9
ABSTRACT: The main purpose of applying the chlorination process during water treatment is for disinfection. Research results, however, indicate that disinfection byproducts (DBPs) including trihalomethanes (THMs), haloacetic acids (HAAs), haloacetonitriles (HANs), haloketones (HKs), and chloropicrin (CP) can be produced by the chlorination process. Some of these DBPs are known to be potential human carcinogens. This 3-year project is designed to establish a standard analysis procedure for DBPs in drinking water of this country and investigate the distribution and sources of specific DBPs. The occurrence level of DBPs in drinking water was below 50 micrograms/l in most cases. THMs in plant effluent accounted for 60% of all DBPs measured, whereas HAAs accounted for 20%, HANs 12%, HKs 5% and CP 3%. Chloroform was found to be the major THMs compound (77%), followed by bromodichloromethane (BDCM, 18%) and bromoform (BF, 3%). The concentration of DBPs formed in distribution systems increased from those detected in plant effluent. Comparison of humic acid and sewage as precursors for THMs formation showed that humic acid was the major THMs precursor. Results would play an important role in exposure assessment as a part of the risk assessment process, and would give basic information for establishment of DBPs reduction and management procedures

TITLE: Safe drinking water: a public health challenge.
OURCE: Chronic Dis Can 1998;19(3):103-7
ABSTRACT: Disinfection of drinking water through processes including filtration and chlorination was one of the major achievements of public health, beginning in the late 1800s and the early 1900s. Chloroform and other chlorination disinfection by-products (CBPs) in drinking water were first reported in 1974. Chloroform and several other CBPs are known to cause cancer in experimental animals, and there is growing epidemiologic evidence of a causal role for CBPs in human cancer, particularly for bladder cancer. It has been estimated that 14 16% of bladder cancers in Ontario may be attributable to drinking water containing relatively high levels of CBPs; the US Environmental Protection Agency has estimated the attributable risk to be 2 17%. These estimates are based on the assumption that the associations observed between bladder cancer and CBP exposure reflect a cause-effect relation. An expert working group (see Workshop Report in this issue) concluded that it was possible (60% of the group) to probable (40% of the group) that CBPs pose a significant cancer risk, particularly of bladder cancer. The group concluded that the risk of bladder and possibly other types of cancer is a moderately important public health problem. There is an urgent need to resolve this and to consider actions based on the body of evidence which, at a minimum, suggests that lowering of CBP levels would prevent a significant fraction of bladder cancers. In fact, given the widespread and prolonged exposure to CBPs and the epidemiologic evidence of associations with several cancer sites, future research may establish CBPs as the most important environmental carcinogens in terms of the number of attributable cancers per year.

TITLE: Drinking water mutagenicity and urinary tract cancers: a population- based case-control study in Finland.
AUTHORS: Koivusalo M; Hakulinen T; Vartiainen T; Pukkala E; Jaakkola JJ; Tuomisto J
SOURCE: Am J Epidemiol 1998 Oct 1;148(7):704-12
ABSTRACT: The detection of mutagenic and carcinogenic chlorination by-products in chlorinated drinking water has raised concern in many countries over the potential health effects of long-term exposure to these products. The relation between estimated exposure to historical drinking water mutagenicity and cancer was studied in Finland by using a population- based case-control study comprising 732 bladder cancer cases, 703 kidney cancer cases, and 914 controls. The cases were obtained from the nationwide Finnish Cancer Registry for the years 1991-1992. The controls, frequency matched by age and sex, were randomly selected from the national population registry. Information on past drinking water sources and confounding factors was acquired through a questionnaire. Historical exposure to drinking water mutagenicity was estimated by using information on past residence, past water source, and historical data on water quality and treatment. Odds ratios were calculated for an increase of 3,000 net revertants per liter (net rev/liter) in average exposure from 1950 to 1987, adjusting for age, sex, socioeconomic status, and smoking in logistic regression models. A small, statistically significant, exposure-related excess risk was found for kidney cancer for men (odds ratio = 1.49, 95 percent confidence interval (CI) 1.05-2.13) for 3,000 net rev/liter exposure level. For women, the association remained nonsignificant, with a lower odds ratio of 1.08 (95% CI 0.69-1.68). For bladder cancer, the odds ratio for both men and women was 1.22 (95% CI 0.92-1.62) for 3,000 net rev/liter exposure. However, a higher odds ratio of 2.59 (95% CI 1.13-5.94) for 3,000 net rev/liter exposure was observed for male nonsmokers.

TITLE: Chlorination of drinking water and cancer mortality in Taiwan.
AUTHORS: Yang CY; Chiu HF; Cheng MF; Tsai SS
SOURCE: Environ Res 1998 Jul;78(1):1-6
ABSTRACT: Chlorination has been the major strategy for disinfection of drinking water in Taiwan. An ecologic epidemiological study design was used to examine whether chlorination of drinking water was associated with cancer risks. A "chlorinating municipality" (CHM) was defined as one in which more than 90% of the municipality population was served by the chlorinated water while an "nonchlorinating municipality" (NCHM) was one in which less than 5% of the municipality population was served by chlorinated water. Age-adjusted mortality rates for cancer during 1982- 1991 among the 14 CHMs were compared to rates among the 14 matched NCHMs with similar urbanization level and sociodemographic characteristics. The results of this study suggest a positive association between consumption of chlorinating drinking water and cancer of the rectum, lung, bladder, and kidney. Although these findings must be interpreted with caution because of limitations in the ecological study design, their public health significance should not be disregarded because chlorination of water is so widely practiced in Taiwan.

TITLE: Drinking water source and chlorination byproducts. I. Risk of bladder cancer [see comments]
AUTHORS: Cantor KP; Lynch CF; Hildesheim ME; Dosemeci M; Lubin J; Alavanja M; Craun G
SOURCE: Epidemiology 1998 Jan;9(1):21-8 Comment in: Epidemiology 1998 Jan;9(1):7-8
ABSTRACT: We conducted a population-based case-control study of bladder cancer in Iowa in 1986-1989 to evaluate the risk posed by tapwater containing chlorination byproducts. We combined information about residential history, drinking water source, beverage intake, and other factors with historical data from water utilities and measured contaminant levels to create indices of past exposure to chlorination byproducts. The study comprised 1,123 cases and 1,983 controls who had data relating to at least 70% of their lifetime drinking water source. After we adjusted for potential confounders, we calculated odds ratios for duration of chlorinated surface water of 1.0 (referent), 1.0, 1.1, 1.2, and 1.5 for 0, 1-19, 20-39, 40-59, and > or =60 years of use. We also found associations with total and average lifetime byproduct intake, as represented by trihalomethane estimates. Positive findings were restricted to men and to ever-smokers. Among men, odds ratios were 1.0 (referent), 1.1, 1.3, 1.5, and 1.9, and among ever-smokers, 1.0, 1.1, 1.3, 1.8, and 2.2, after adjustment for intensity and timing of smoking. Among nonsmoking men and women, regardless of smoking habit, there was no association. Among men, smoking and exposure to chlorinated surface water mutually enhanced the risk of bladder cancer. The overall association of bladder cancer risk with duration of chlorinated surface water use that we found is consistent with the findings of other investigations, but the differences in risk between men and women, and between smokers and nonsmokers, have not been widely observed.

TITLE: Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers.
AUTHORS: Hildesheim ME; Cantor KP; Lynch CF; Dosemeci M; Lubin J; Alavanja M; Craun G
SOURCE: Epidemiology 1998 Jan;9(1):29-35 CITATION IDS: PMID: 9430265 UI: 98090130
ABSTRACT: We evaluated the association between chlorination byproducts and colon and rectal cancer risk in a population-based case-control study conducted in Iowa in 1986-1989. Data were gathered from 685 colon cancer cases, 655 rectal cancer cases, and 2,434 controls. We calculated odds ratios for the 560 colon cancer cases, 537 rectal cancer cases, and 1,983 controls for whom water exposure information was available for at least 70% of their lifetime. We estimated exposure to chlorination byproducts with two types of measures: duration of lifetime at residences served by chlorinated water and estimated lifetime trihalomethane exposure. For rectal cancer, we observed an association with duration of chlorinated surface water use, with adjusted odds ratios of 1.1, 1.6, 1.6, and 2.6 for 1-19, 20-39, 40-59, and > or =60 years of exposure, compared with no exposure. Rectal cancer risk was also associated with several different measures of estimated lifetime trihalomethane exposure. For colon cancer and subsites, we detected no important increase in risk associated with duration of chlorinated surface water, nor with trihalomethane estimates. When we evaluated chlorination byproducts jointly with other factors, we found larger relative risk estimates for rectal cancer among subjects with low dietary fiber intake. The risk related to > or =40 years of exposure to a chlorinated surface water source was 2.4 (95% confidence interval = 1.5-4.0) for persons with low fiber intake and 0.9 (95% confidence interval = 0.4-1.8) for persons with high fiber intake, relative to the risk of persons with high-fiber diets and no exposure to chlorinated surface water. We observed a similar risk differential for low and high levels of physical activity.

TITLE: Drinking water chlorination by-products and cancer.
AUTHORS: Koivusalo M; Vartiainen T
SOURCE: Rev Environ Health 1997 Apr-Jun;12(2):81-90
ABSTRACT: This review discusses the relation between by-products of drinking water chlorination and cancer in the light of present toxicological and epidemiologic evidence. During the chlorination of drinking water, a complex mixture of by-products forms from chlorine and the organic and inorganic compounds present in raw water. The quality and quantity of such compounds depend on the specific nature of the organic material in raw waters, the inorganic material in raw water, pH, temperature, other water treatment practices, and the chlorine timing and dose added. Chlorination by-products are important mainly when surface water is used for drinking water as more organic compounds are present in surface waters than in ground waters. The gastrointestinal and urinary tract are the cancer sites that are most often associated with the use of chlorinated surface water or with the quantity of chlorination by- products in the water-supply network. Yet the microbial quality of drinking water should not be compromised by excessive caution over the potential long-term effects of disinfection by-products because the risk of illness and death resulting from exposure to pathogens in untreated drinking water may be several orders of magnitude greater than the cancer risks from chlorination by-products.

TITLE: Case-control study of bladder cancer and chlorination by-products in treated water (Ontario, Canada).
AUTHORS: King WD; Marrett LD
SOURCE: Cancer Causes Control 1996 Nov;7(6):596-604
ABSTRACT: Chlorine is by far the most commonly used chemical for the disinfection of water supplies in North America. However, chlorine reacts with organic material in the raw water producing a number of halogenated hydrocarbon by-products. This population-based case-control study in Ontario, Canada examined the relationship between bladder cancer and exposure to chlorination by-products in public water supplies. Residence and water source histories and data from municipal water supplies were used to estimate individual exposure according to water source, chlorination status, and by-product levels (represented by trihalomethane [THM] concentration). Exposures were estimated for the 40-year period prior to the interview, using 696 cases diagnosed with bladder cancer between 1 September 1992 and 1 May 1994 and 1,545 controls with at least 30 years of exposure information. Odds ratios (OR) adjusted for potential confounders were used to estimate relative risk. Those exposed to chlorinated surface water for 35 or more years had an increased risk of bladder cancer compared with those exposed for less than 10 years (OR = 1.41, 95 percent confidence interval [CI] = 1.10-1.81). Those exposed to an estimated THM level > or = 50 micrograms/liter for 35 or more years had 1.63 times the risk of those exposed for less than 10 years (CI = 1.08-2.46). These results indicate that the risk of bladder cancer increases with both duration and concentration of exposure to chlorination by-products, with population attributable risks of about 14 to 16 percent. Chlorination by-products represent a potentially important risk factor for bladder cancer.

Title Water chlorination: essential process or cancer hazard?
Author Bull RJ; Birnbaum LS; Cantor KP; Rose JB; Butterworth BE; Pegram R; Tuomisto J
Source Fundam Appl Toxicol, 1995 Dec, 28:2, 155-66
The paper discusses trihalomethanes and disinfection by-products produced by chlorination. Alternatives to chlorination have their own risks associated with their by-products that are even less well established than for chlorination. Moreover, the use of these alternatives vary in their effectiveness and some require greater sophistication in their application. This can mean less protection to public health as a result of inappropriate application and control. Therefore, hazards associated with the use of such a clearly beneficial process as chlorination must be carefully considered not only in an absolute sense, but also in the context of alternative approaches for producing a safe drinking water.

TITLE: Drinking water and cancer.
SOURCE: Environ Health Perspect 1995 Nov;103 Suppl 8:225-31
ABSTRACT: Any and all chemicals generated by human activity can and will find their way into water supplies. The types and quantities of carcinogens present in drinking water at the point of consumption will differ depending on whether they result from contamination of the source water, arise as a consequence of treatment processes, or enter as the water is conveyed to the user. source-water contaminants of concern include arsenic, asbestos, radon, agricultural chemicals, and hazardous waste. Of these, the strongest evidence for a cancer risk involves arsenic, which is linked to cancers of the liver, lung, bladder, and kidney. The use of chlorine for water treatment to reduce the risk of infectious disease may account for a substantial portion of the cancer risk associated with drinking water. The by-products of chlorination are associated with increased risk of bladder and rectal cancer, possibly accounting for 5000 cases of bladder cancer and 8000 cases of rectal cancer per year in the United States. Fluoridation of water has received great scrutiny but appears to pose little or no cancer risk. Further research is needed to identify and quantify risks posed by contaminants from drinking-water distribution pipes, linings, joints, and fixtures and by biologically active micropollutants, such as microbial agents. We need more cost-effective methods for monitoring drinking-water quality and further research on interventions to minimize cancer risks from drinking water.

TITLE: Trihalomethanes in drinking water and cancer: risk assessment and integrated evaluation of available data, in animals and humans.
AUTHORS: Attias L; Contu A; Loizzo A; Massiglia M; Valente P; Zapponi GA
SOURCE: Sci Total Environ 1995 Oct 27;171(1-3):61-8
ABSTRACT: In our study, we attempted to jointly consider THM concentration data collected from drinking waters and carcinogenic risk assessment derived from mathematical models commonly used in this field (multi-stage models for laboratory animal experimentation data, and 'unit risk' derived from the relative risk in the case of epidemiological data). In order to estimate the risks related to joint exposure to different THMs, in this study the risk additivity hypothesis is taken into account. Based on animal data for the various tumors, carcinogenic risk estimates for different THM combinations vary from 2.7 x 10(-7) to 4.6 x 10(-6) per micrograms/l in relation to different carcinogenic substances published in the literature or specifically calculated in this study. The carcinogenic risk parameters derived from experimental studies and from epidemiological data were substantially consistent. Our study uses also as an example some data on concentration levels of THMs for drinking water supplies in Sardinia. The area mean THM concentration values for each supply varied, for ground waters, from 8.1 to 13.6 micrograms/l and, for surface waters, from 52.8 to 168 micrograms/l. For the 1976-1989 period, bladder cancer standardized mortality rates in the water distribution system areas where the THMs were measured indicate values similar, but generally lower, than the national ones, except in the province of Cagliari where the values were not significantly different. The risk estimates derived from animal studies are of the same order of magnitude as the epidemiological data in literature.

Title: Public drinking water contamination and birth outcomes.
Author Bove FJ; Fulcomer MC; Klotz JB; Esmart J; Dufficy EM; Savrin JE
Source Am J Epidemiol, 1995 May 1, 141:9, 850-62
The paper discusses the effects of public drinking water contamination on birth outcomes in an area of northern New Jersey

TITLE: Disinfection of drinking water, disinfection by-products and cancer: what about Australia?
SOURCE: Aust J Public Health 1995 Feb;19(1):89-93
ABSTRACT: Chlorine, commonly used to disinfect drinking water, produces by-products known from animal studies to be carcinogenic and mutagenic. Most epidemiological studies into the possible association between chlorination by-products in drinking water and cancer have been ecological in nature, or have relied on case-control designs based on death certificates. Interpretation of results arising from these studies is limited. Individual levels of toxicant exposure and many potential confounders and effect modifiers are unable to be accounted for in the analyses. At best, these studies generate hypotheses that require more definitive investigation. Misclassification of individuals based on inaccurate assessment of the level of exposure is probable. The few analytic studies able to overcome or minimise these problems suggest a clear link between exposure to chlorinated drinking water and the development of urinary bladder cancer. They also suggest a possible link with rectal cancer. However, these studies have ubjects by exposure to chlorinated drinking water, rather than to levels of chlorine and its by-products in drinking water. To date, the link between levels of chlorine and its by-products in water, levels of consumption and cancer has not been made. Information on the levels of chlorine and some by-products is available in many water jurisdictions in Australia. Further, epidemiological methods can be employed to quantify water consumption. Case-control studies linking these parameters would help us to understand the magnitude of the risk to human populations and provide a basis to investigate mechanisms for risk reduction.

Title Case-control study of bladder cancer and water disinfection methods in Colorado.
Author McGeehin MA; Reif JS; Becher JC; Mangione EJ
Source Am J Epidemiol, 1993 Oct 1, 138:7, 492-501
The paper discusses a population-based case-control study of bladder cancer and drinking water disinfection methods conducted during 1990-1991 in Colorado. A total of 327 histologically verified bladder cancer cases were frequency matched by age and sex to 261 other-cancer controls. After adjustment for cigarette smoking, tap water and coffee consumption, and medical history factors by logistic regression, years of exposure to chlorinated surface water were significantly associated with risk for bladder cancer (p = 0.0007). The odds ratio for bladder cancer increased for longer durations of exposure to a level of 1.8 (95% confidence interval 1.1-2.9) for more than 30 years of exposure to chlorinated surface water compared with no exposure. The increased bladder cancer risk was similar for males and females and for nonsmokers and smokers. Levels of total trihalomethanes, nitrates, and residual chlorine were not associated with bladder cancer risk after controlling for years of exposure to chlorinated water. Language of Publication English

Title The association of waterborne chloroform with intrauterine growth retardation.
Author Kramer MD; Lynch CF; Isacson P; Hanson JW
Source Epidemiology, 1992 Sep, 3:5, 407-13
The paper discusses the association of waterborne chloroform with low birthweight (less than 2,500 gm), prematurity (less than 37 weeks gestation), and intrauterine growth retardation (less than 5th percentile of weight for gestational age). After adjustment for maternal age, parity, adequacy of prenatal care, marital status, education, and maternal smoking by multiple logistic regression, residence in municipalities where chloroform concentrations were greater than or equal to 10 micrograms/liter was associated with an increased risk for intrauterine growth retardation (odds ratio = 1.8, 95% confidence interval = 1.1-2.9). The limitations of the study were discussed.

 Title Problems in assessing the risks of mixtures of contaminants in drinking water.
Author Vanderslice RR; Orme J; Ohanian EV; Sonich-Mullin C
Source Toxicol Ind Health, 1989 Oct, 5:5, 747-55
Partial abstract In conducting risk assessments on drinking water contaminants, the U.S. Environmental Protection Agency (EPA) attempts to evaluate all available toxicity data to develop Health Advisory (HA) and Maximum Contaminant Level Goal (MCLG) values. Potential toxic interactions between drinking water contaminants are difficult to predict because experimental studies are generally performed only at high doses relative to environmental levels. Although the contamination of drinking water involves mixtures of contaminants, drinking water regulations are generally based on an assessment of the risks of individual contaminants. This paper discusses three issues of major concern to the EPA: the synergistic effects of solvent mixtures, vehicle effects in laboratory studies, and setting standards for essential trace nutrients where the absorption and/or toxicity are affected by an individual's nutritional status or other dietary components.

Title Cancer mortality and the method of chlorination of public drinking water: St. Louis City and St. Louis County, Missouri.
Author Marienfeld CJ; Collins M; Wright H; Reddy R; Shoop G; Rust P
Source J Environ Pathol Toxicol Oncol, 1986 Sep-Dec, 7:1-2, 141-57
The paper discusses an apparent association between a probable increase in trihalomethane production in the St. Louis County water since 1955 and an increase in specific cancer (large bowel, liver and bladder cancers) rates which exceed the increases in the St. Louis City rates. This does not imply causality but is in general agreement with other studies which have examined water chlorination and cancer mortality.

TITLE: Health significance of chlorination byproducts in drinking water: the Houston experience.
AUTHORS: Cech I; Holguin AH; Littell AS; Henry JP; O'Connell J
SOURCE: Int J Epidemiol 1987 Jun;16(2):198-207
ABSTRACT: In 1954, following the construction of Lake Houston, a change from lightly chlorinated ground sources to a heavily chlorinated surface source of drinking water took place for a sizable part of the population in the city of Houston, Texas. This has provided the opportunity to compare the incidence of urinary tract cancer mortality in populations exposed to heavily chlorinated and lightly chlorinated drinking water. The spatial, diurnal, and seasonal concentrations of chlorination byproducts (trihalomethanes) in Houston water were assessed. The range of concentrations varied from below the limits of detection in treated ground water, to more than 200 mg/l (twice the level allowed by US drinking water standards) in treated lake water. The mortality experience by gender, by race, and by age cohorts for the period 1940 to 1970 from urinary tract cancers and three comparison causes was determined for 56 of Houston's census tracts classified by the duration of exposure to the surface water. By the 1970's 20 years following the switch to surface water, an increase was detected in urinary cancer mortality rates for white females without a corresponding increase observed for white males. No clear-cut trends were found for the non-white population. On balance, a detrimental urinary cancer effect associated with a switch to chlorinated surface water has not been demonstrated yet.

Title Epidemiological studies on cancer and organic compounds in U.S. drinking waters.
Author Williamson SJ
Source Sci Total Environ, 1981 Apr, 18:, 187-203
The paper discusses two national surveys of U. S. drinking waters conducted to determine the presence and concentration levels of organic compounds, particularly trihalomethanes. Most drinking water supplies from surface water sources have been shown to contain numerous organic compounds at very low levels. Chloroform is present in virtually all drinking water supplies that are treated with chlorine as a disinfectant. A summary of fourteen epidemiological studies conducted to determine if there is a positive association between drinking water and increased cancer mortality studies is presented, which indicates that there is potentially an increased risk of bladder, colon, and rectum cancer from drinking waters containing trihalomethanes.

Title Associations of cancer mortality with halomethanes in drinking water.
Author Cantor KP; Hoover R; Mason TJ; McCabe LJ
Source J Natl Cancer Inst, 1978 Oct, 61:4, 979-85
The paper discusses associations between site- and sex-specific county cancer mortality rates and levels of trihalomethanes (THM's) in drinking water examined after adjustment of rates for the influence of multiple socioeconomic, industrial, and demographic factors. Positive correlations with THM levels were observed for several cancers, including bladder and brain cancers in both sexes, and non-Hodgkin's lymphoma and kidney cancer in males. Stomach cancer in females showed a negative association.

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