Content uploaded by Trond Peder Flaten
Author content
All content in this area was uploaded by Trond Peder Flaten on Oct 05, 2017
Content may be subject to copyright.
Chlorination of Drinking Water and Cancer Incidence in Norway
Abstract
Flaten T P (Department of Chemistry, College of Arts and Science, The University of Trondheim, Trondheim, Norway). Chlorination
of drinking water and cancer incidence in Norway. Intemationoi Journal of Epidemiology 1992; 21: 6–15. To examine whether chlorination of drinking water was associated with cancer of the digestive or other organs,
an ecological epidemiological study using nationwide incidence data from the Cancer Registry of Norway was earned out. On
two geographical levels (counties and municipalities), both for men and women, chlorination of drinking water was associated
with an increased incidence of cancer of the colon and rectum. After adjusting for potential confounding variables, also measured
on a geographical basis, the associations were still significant at the county level (adjusted for population density, income,
education, fat and fibre intake etc.), but not at the municipality level. The observed associations are weak, chlorination
being associated with a 20–40% increase in colorectal cancer rates. Due to inherent methodological limitations in ecological
studies like the present one, causal interpretations should be made with great care. Thus, although the results give some
support to the hypothesis that drinking water chlorination is associated with colorectal cancer, they do not provide strong
evidence of a causal relationship.
... The disinfectant by-products can include amines, aromatics, halocyclopentenoic acids, haloquinones, nitrosamines, aromatic amines, halofuranones, haloamides and aromatic amines. In a study conducted in Norway, it was identified that consumption of chlorinated water resulted in carcinogenic effects on the digestive tract and a few incidents of colon cancer (FLATEN, 1992). ...
The need of the hour relies on finding new but sustainable ways to curb rising pollution levels. The accelerated levels of urbanization and increase in population deplete the finite resources essential for human sustenance. In this aspect, water is one of the non-renewable sources that is running out very fast and is polluted drastically day by day. One way of tackling the problem is to reduce the pollution levels by decreasing the usage of chemicals in the process, and the other is to find ways to reuse or reduce the contaminants in the effluent by treatment methods. Most of the available water recycling or treatment methods are not sustainable. Some of them even use toxic chemicals in the processing steps. Treatment of organic wastes from industries is a challenging task as they are hard to remove. Electrocoagulation is one of the emerging water treatment technologies that is highly sustainable and has a comparatively cheaper operating cost. Being a broad-spectrum treatment process, it is suitable for treating the most common water pollutants ranging from oils, bacteria, heavy metals, and others. The process is also straightforward, where electrical current is used to coagulate the contaminates. The presence of carcinogens in these waste water increases the need for its treatment towards further use. The present investigation is made as an extensive analysis of the emerging carcinogens and their various sources from process industries, especially in the form of organic waste and their removal by electrocoagulation and its coupled techniques. The paper also aims to ascertain why the electrocoagulation technique may be a better alternative compared with other methods for the removal of carcinogens in organic wastewater, an analysis which has not been explored before.
... 56,[62][63][64] In general, the prevalence of DBRCs is higher in communities supplied with chlorinated surface water than in those supplied with less chlorinated groundwater. Another study conducted in Norway showed that chlorination was associated with a 20 to 40% increase in colorectal cancer rates, 65 and other related studies are also in line with this study. 55,57,66 The crude incidence rate of colo-rectal cancer (CRC) in this study was found to be 3.67/100, 000 that was higher than a report from 2015 in Addis Ababa. ...
Background
Disinfection byproducts (DBPs) from chlorinated drinking water have been linked to an increased risk of cancer in the bladder, stomach, colon, and rectum. No studies showed the independent trends and prevalence of these cancers in Ethiopia. Therefore, this study aimed to determine the prevalence and trends of disinfection byproducts-related cancers in Addis Ababa, Ethiopia.
Methods
Data were collected from the Addis Ababa Cancer Registry. Spatial data sets were produced and classified into households receiving chlorinated surface water and less chlorinated groundwater. The Cochran-Armitage trend test was used to evaluate whether there was a disinfection byproducts-related cancers (DBRCs) trend among communities receiving chlorinated water. Negative binomial regression was used to analyze the incidence rate.
Results
A total of 11, 438 cancer cases were registered between 2012 and 2016, and DBRCs accounted for approximately 17%. The majority of the total cancer cases were female; 7,706 (67%). The prevalence of DBRCs was found to be higher in communities supplied with chlorinated water. From 2012 to 2016, the trend of colon cancer increased (β = 10.3, P value = .034); however, esophageal cancer decreased (β = −6.5, P value = .018). Approximately 56% of colorectal cancer patients and 53% of stomach cancer patients are known to be using chlorinated surface water for drinking regularly. In addition, approximately 57.1% and 54% of kidney and bladder cancer patients, respectively, used chlorinated surface water.
Conclusion
The prevalence of DBRCs in this study was found to be high. The colon cancer trend increased substantially from 2012 to 2016. The prevalence of DBRCs was higher in communities supplied with chlorinated surface water. Similarly, the prevalence of DBRCs was higher among males than females. Further study is required to validate the association between DBRCs and water chlorination.
... Trihalomethanes, such as dibromochloromethane, bromodichloromethane, and bromoform, arise from the reaction of chlorine or bromine with organic compounds present in the water. Continuous exposure to dibromochloromethane and bromoform has been associated with kidney and liver cancer, colorectal cancer, bladder cancer, lung cancer, in addition to heart disease and even death at high exposure (ATSDR, 2011;Flaten, 1992;Morris et al., 1992;Yang et al., 1998;Guha et al., 2019). ...
... It has been proved that cancer risks are increasing along with exposure to DBPs through ingestion of drinking water (Mishra, Gupta, & Sinha, 2014 proven, the concentration of chlorine in drinking water began to be considered, and studies in this area failed to show an association between different cancers and standard chlorine concentration (Bove et al., 2007;Chiu, Tsai, Wu, & Yang, 2013;Do et al., 2005;Kasim, Levallois, Johnson, Abdous, & Auger, 2005;King et al., 2000;Villanueva et al., 2016). Interestingly, as seen in the table in Exhibit 2, 10 of the 19 studies included in this review were published before 2000 (Alavanja, Goldstein, & Susser, 1978;Doyle et al., 1997;Gottlieb & Carr 1982a;Hildesheim et al., 1998;IJsselmuiden et al., 1992;King et al., 2000;Koivusalo, Pukkala, Vartiainen, Jaakkola, & Hakulinen, 1997;Koivusalo et al., 1998;Wilkins III & Comstock, 1981;Young, Kanarek, & Tsiatis, 1981 Alavanja et al., 1978;Bove et al., 2007;Doyle et al., 1997;King et al., 2000), and common types of cancers (Parkin, Pisani, & Ferlay, 1999 Flaten, 1992). Others gave a weak positive association between chlorinated drinking water and liver cancer, leukemia, and urinary tract and pancreatic cancers (Brenniman, 1980;Gottlieb et al., 1982;Koivusalo, Vartiainen, Hakulinen, Pukkala, & Jaakkola, 1995;Young et al., 1981). ...
In the present study, a meta‐analysis was carried out to clarify the association between disinfection byproducts (DBPs) in drinking water and human cancer risk worldwide. Kidney, colorectal, esophagus, urinary bladder, brain, breast, leukemia, lung, and rectum cancers were selected to perform this analysis. According to preferred reporting items for systematic review and meta‐analysis protocol (PRISMA) guidelines, the relevant studies were identified and selection criteria (inclusion and exclusion criteria) were applied. Next, effective subgroups in these studies (gender, type of drinking water source, and type of DBPs) were analyzed. The quality of the studies was evaluated using the Newcastle‐Ottawa Scale. In addition, this overall study included analyses of 16 case–control and 3 cohort studies. The overall odds ratio (OR) with 95% confidence intervals (CI) between DBPs and cancer risk was 1.01 (95% CI, 0.94–1.09). The summary ORs of cancer risk were 1.04 (95% CI, 0.89–1.19) for kidney; 0.98 (95% CI, 0.87–1.09) for colorectal; 1.07 (95% CI, 0.84–1.29) for esophagus; 0.93 (95% CI, 0.80–1.06) for pancreatic; 1.00 (95% CI, 0.83–1.18) for brain; 1.13 (95% CI, 0.99–1.26) for breast; 0.93 (95% CI, 0.72–1.13) for leukemia; and 1.18 (95% CI, 1–1.36) for lung cancers. The results of this meta‐analysis suggested that there is not a significant association between DBPs in water and cancer risk. In addition, subgroup analysis shows a positive association with colorectal and kidney cancer risk in men, as well as colon and breast cancers in females. Studies of both genders have shown a significant association between lung and pancreatic cancers. Moreover, this study finds a significant relationship between cancer rate and consumers of city water and bottled water sources. In analyzing different types of DBPs in water, chlorine and trichloromethane show a significant association in increasing cancer risk.
... Epidemiological studies have not clearly demonstrated an association between consumption of chlorinated drinking water and increased tumor incidence in humans (Doyle et al., 1997;Cantor et al., 1998;Flaten, 1992;King and Marrett, 1996). However, some studies suggest a small increase in the incidence of bladder cancer in older males consuming chlorinated drinking water (reviewed in U.S. EPA, 1998). ...
Bromodichloromethane (BDCM) is a common municipal drinking water disinfection by-product, resulting in widespread trace human exposure via ingestion and inhalation. The present studies were designed to define organ-specific, BDCM-induced toxicity in wild type (p53 1/1 ) and heterozygous (p53 1/‐ ) mice on both the FVB/N and C57BL/6 genetic backgrounds. Mice were exposed to BDCM vapor daily for 6 h/day and 7 days/week at concentrations of 0, 1, 10, 30, 100, or 150 ppm for 1 week and at 0, 0.3, 1, 3, 10, or 30 ppm for 3 weeks. In the 1-week exposure study, dosedependent mortality and morbidity were observed at concentrations of 30 ppm and above and were as high as 100% at 150 ppm. In the 3-week exposure study, mortality and morbidity were found only in the 30-ppm exposure groups and were 0, 17, 67, and 33% for the wild-type C57BL/6, p53 1/‐ C57BL/6, wild-type FVB/N, and p53 1/‐ FVB/N mice, respectively. BDCM was a particularly potent kidney cytotoxicant. Dose-dependent tubular degeneration, necrosis, and associated regenerative cell proliferation greater than 10-fold over controls were seen at concentrations as low as 10 ppm in the kidneys of all strains at 1 week. Similar dose-dependent increases in hepatic necrosis, degeneration, and regenerative cell proliferation were observed but were induced only at concentrations of 30 ppm and higher. Pathological changes were more severe in the FVB/N compared to the C57BL/6 mice and were more severe in the heterozygotes compared to the wild-type mice. However, recovery and return of the percentage of kidney cells in S-phase to control levels was seen at 3 weeks. The estimated maximum tolerated dose for longer-term exposures was 15 ppm, based on mortality, induced kidney pathology, and regenerative cell proliferation. A one-year cancer bioassay was initiated with doses of 0, 0.5, 3, 10, and 15 ppm, based on this information. No pathological changes in the livers were found at the 13-week time point of that study. At 13 weeks, the kidney lesions and regenerative cell proliferation seen at the 1-week time point at doses of 10 ppm and above had resolved, and the cell proliferation rates had returned to baseline. Differences in toxicity indicate that caution be used in substituting wild-type mice for transgenic mice for range-finding studies to select doses for p53 1/‐ cancer studies. Resolution of the kidney lesions indicates that periods of very high regenerative cell proliferation, potentially important in the carcinogenic process, may not be observed if measurements are taken only at 3 weeks of exposure or later.
... Although chlorine disinfection reduces mortality and morbidity due to water-borne diseases (Calderon, 2000;Golfinopoulos and Nikolaou, 2005), chlorine can react with natural organic matter (NOM) and form various types of disinfection byproducts (DBPs), chiefly trihalomethanes (THMs). Epidemiological and clinical studies have revealed that several health effects are associated with the exposure to DBPs, such as elevated rates of bladder, colonrectum and brain cancers McGeehin et al., 1993;Hildesheim et al., 1998;Cantor et al., 1999;Wilkins et al., 1979;Flaten, 1992;King et al., 2000a), cardiac anomalies, stillbirths, miscarriages, low birth weights and pre-term deliveries, and neural tube defects (Mills et al., 1998;Richardson., 2005;King et al., 2000b). Epidemiological data availability in Pakistan from population-based registries is mostly unavailable, and institutional based registries seldom provide estimates of disease distribution. ...
Background: Chlorine, in the form of sodium hypochlorite (NaClO), is widely used in water treatment to make it safe for human consumption. There are three main forms of chlorine: chlorine gas (Cl2), sodium hypochlorite (NaClO), and calcium hypochlorite. All are effective in water disinfection. Chlorine dosage is controlled to eliminate pathogenic microorganisms without exceeding safe limits for human consumption, aiming to avoid the use of excessive chlorine that can generate undesirable by-products. Measurement was carried out using DPD reagent to determine the concentration of free chlorine in the water. Aim: This work aims to facilitate the adjustment of chlorine dosage in water treatment, to reduce additional corrections. Methods: The Hach method 8021 was used to adjust chlorine dosage based on measurements of the interval between dosing pump pulsations and observed chlorine concentration. The concentration was adjusted from 1.68 mg/L to 1.20 mg/L. Additionally, the appropriate time for correct chlorine reading was determined, and the time needed for the corrected chlorine quantity to be observable in the system, adhering to the minimum limits set by legislation, was verified. Results: The adjustment of the initial chlorine concentration (1.66 mg/L) was carried out using the Hach method 8021, resulting in a stable concentration of approximately 1.19 mg/L. The desired dosage was 1.20 mg/L. The time required for correct chlorine measurement and observation of the corrected value was approximately 40 minutes. The use of the script allowed achieving a result 99.2% close to the planned value with just one adjustment. Discussion: The proper use of chlorine in water treatment is essential to ensure the safety and quality of supply. This research emphasized the need for careful monitoring of chlorine dosage, requiring time and accurate analysis of representative samples. The application of the developed script brought significant benefits, ensuring satisfactory disinfection and preventing overdosing issues. The results showed high efficacy and time savings, enhancing treatment efficiency and economic advantages. Moreover, the script reduced paper usage in calculations, promoting environmental sustainability. Conclusions: The script for adjusting the chlorine dosage used in water treatment made the operation more practical and efficient, with a user-friendly interface and accurate results achieved faster.
Sustaining a reliable and contaminant-free drinking water is becoming an increasing challenge worldwide due to human activity, industrial waste, and agricultural overuse. Surface water is the main source of drinking water around the world. However, groundwater is also becoming increasingly popular, due to its clarity and minimal need for processing to reduce turbidity. Over the years, the demand and growth in the agricultural industry has also been the means of groundwater contamination. Due to the health burden that raw water can pose, water must be processed and purified prior to consumption. Raw water quality can be compromised by physical, chemical (heavy metals and disinfection by-products), and biological contaminants. Biological contaminants can significantly impact immunocompromised populations, while chemical contaminants can impact the growth and development of young children. Although obtaining a steady and high-quality water flow to the general population is an increasing challenge, developed countries have utilized state-of-the-art technologies and techniques to provide contaminant-free water to their citizens. This research aims to provide information about the regulatory parameters, characteristics, and sources of safe drinking water in the world as a model for future use in the developing world. In this, secondary data was used to compare and contrast drinking water quality among countries in the European Union, the United States, Canada, the United Kingdom, Singapore, New Zealand, Australia, Qatar, and the United Arab Emirates. The data indicates that Ireland and the United Kingdom have relatively lower amounts of contaminants in their drinking water. Upon completing this research, it is recommended that countries desiring clean drinking water systems should initiate and invest in programs that control and protect treatment plants, water distribution systems, water sources, and catchments.
This chapter discusses water contaminants that may contribute to the human cancer burden. Specifically, it addresses the epidemiologic evidence for several contaminants and includes information on their levels and environmental distribution, as well as individual susceptibility, where data exist. The three categories of drinking water contaminants that may be carcinogenic and that have been studied most systematically are arsenic, disinfection by-products, and nitrate. In addition, radionuclides, microbiological agents, organic compounds from human commerce, and asbestiform particles have been reported to cause cancer, either as they occur in drinking water or in other media, giving rise to suspicion about their carcinogenicity when ingested. Future research priorities and prevention strategies are discussed.
Water samples were collected from 384 waterworks that supply 70.9% of the Norwegian population. The samples were collected after water treatment and were analysed for 30 constituents. Although most constituents show wide concentration ranges, Norwegian drinking water is generally soft. The median values obtained are: 0.88 mg Si l-1, 0.06 mg Al l-1, 47 micrograms Fe l-1, 0.69 mg Mg l-1, 2.9 mg Ca l-1, 3.8 mg Na l-1, 6 micrograms Mn l-1, 12 micrograms Cu l-1, 14 micrograms Zn l-1, 9 micrograms Ba l-1, 15 micrograms Sr l-1, 0.14 mg K l-1, 58 micrograms F- l-1, 6.4 mg Cl- l-1, 11 micrograms Br- l-1, 0.46 mg NO3- l-1, 5.3 mg SO4(2-) l-1, 2.4 mg TOC l-1, 6.8 (pH), 5) microseconds cm-1 (conductivity) and 11 mg Pt l-1 (colour). Titanium, Pb, Ni, Co, V, Mo, Cd, Be and Li were seldom or never quantified, due to insufficient sensitivity of the ICP (inductively coupled plasma) method. Norwegian quality criteria, which exist for 17 of the constituents examined, are generally fulfilled, indicating that the chemical quality of drinking water, by and large, is good in Norway. For Fe, Ca, Mn, Cu, pH, TOC and colour, however, the norms for good drinking water are exceeded in more than 9% of the samples, reflecting two of the major problems associated with Norwegian drinking water supplies: (i) many water sources contain high concentrations of humic substances; (ii) in large parts of the country, the waters are soft and acidic, and therefore corrosive towards pipes, plumbing and other installations. Most constituents show marked regional distribution patterns, which are discussed in the light of different mechanisms contributing to the chemical composition of drinking water, namely: chemical weathering of mineral matter; atmospheric supply of salt particles from the sea; anthropogenic pollution (including acid precipitation); corrosion of water pipes and plumbing; water treatment; decomposition of organic matter; and hydrological differences.
A sensitive short-term mutagenicity test, the microscale fluctuation test has been coupled with a concentration method based on adsorption on Sep-PakR C18 cartridges as a method for screening drinking water mutagens. Comparison with XAD-2 concentration method showed that Sep-Pak adsorbed 5 times higher quantity of organics but was slightly less efficient for adsorbing TOX.Microscale fluctuation test was found to be more sensitive than Ames test by testing known direct-acting mutagens and concentrates of drinking water. Samples derived from conventional treatment including chlorination from eight surface water supplies in Norway were concentrated at pH 2 by adsorption on the disposable columns. The adsorbates were tested at different doses by the microscale fluctuation assay. The mutagenic properties of drinking water samples were also related to total organic carbon (TOC), total organic halogen (TOX) and trihalomethanes (THM) concentrations. Dose-related mutagenic responses were found for all the samples with S. typhimurium TA 100 and TA98 strains without metabolic activation. Good relationship was found between mutagenicity data and TOX and THM results. The method showed to be simple, rapid and suitable for routine screening of mutagens in drinking water.
Several large epidemiological studies in the Nordic countries have failed to confirm an association between age at first birth and breast cancer independent of parity. To assess whether lack of power or heterogeneity between the countries could explain this, a meta-analysis was performed of 8 population-based studies (3 cohort and 5 case-control) of breast cancer and reproductive variables in the Nordic countries, including a total of 5,568 cases. It confirmed that low parity and late age at first birth are significant and independent determinants of breast-cancer risk. Nulliparity was assoclated with a 30% increase in risk compared with parous women, and for every 2 births, the risk was reduced by about 16%. There was a significant trend of increasing risk with increasing age at first birth, women giving first birth after the age of 35 years having a 40% increased risk compared to those with a first birth before the age of 20 years. Tests for heterogeneity between studies were not significant for any of the examined variables. In the absence of bias, this suggests that several individual Nordic studies may have had too little power to detect the weak effect of age at first birth observed in the meta-analysis.
The strong Ames test mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2-(5H)-furanone (MX) was found to occur in chlorinated drinking and humic waters in sub μg L−1 concentrations. Quantitation by GC/MS using Selective Ion Monitoring in parallel with Ames tests of waters indicated that this furanone accounted for 15 – 30% of the Ames test mutagenicity of both a drinking water and a humic water.
Two chlorinated hydroxylated furanones, 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) and 3,4-(dichloro)-5-hydroxy-2[5H]-furanone (MA), are bacterial mutagens and they are also byproducts of chlorine disinfection, and frequent contaminants of drinking water. In this work MX is shown to induce nuclear anomalies in the gastrointestinal tract of the B6C3F1 mouse. The other chlorohydroxy-furanone, MA, gives suggestive evidence of activity. In this bioassay MX was approximately equivalent in potency to epichlorohydrin (ECH) but was much less potent than methylnitrosourea (MNU). The latter two chemicals are confirmed rodent gastrointestinal tract carcinogens. The duodenum was the most sensitive tissue responding with both increased numbers of nuclear anomalies per mouse and increased incidence of animals presenting the nuclear aberrations 24 hr after a single oral dose of 0.37 mmol/kg-1 of MX. MA also induced a significant increase in duodenal nuclear anomalies, but only at the highest dose (0.46 mmol/kg-1). The proximal colon and forestomach responded to MX but not MA. This is the first study demonstrating that chlorohydroxyfuranones are capable of inducing nuclear toxicity in vivo. However, it is clear, for MX at least, that its potency in the gastrointestinal tract nuclear anomalies assay is not commensurate with its extreme bacterial mutagenicity. Since the gastrointestinal tract tissues are directly exposed to orally administered genotoxins, one possible explanation for the weak response observed in this study could be that mammalian cells can effectively detoxify chlorohydroxyfuranones.
Finished drinking water samples were collected from 384 waterworks that supply 70.9% of the Norwegian population. For 97 municipalities where a majority of the population has had a stable drinking water supply from at least 1965, analytical results for Si, Al, Fe, Mg, Ca, Na, Mn, Cu, Zn, Ba, Sr, K, F-, Cl-, Br-, NO3-, SO4(2-), pH, electrical conductivity, total organic carbon (TOC) and colour are correlated with municipal rates for morbidity of 16 groups of cancer (1975-84), and for mortality of 17 groups of other diseases (1974-83). Several associations are found, some of which may be real, while others are incidental due to the large number of correlations involved. The ecological design of this study implies that cause-and-effect interpretations should be made with great care.
The information summarized in this review provides substantial evidence for the widespread presence of genotoxins in drinking water. In many, if not most cases, the genotoxic activity can be directly attributed to the chlorination stage of drinking water treatment. The genotoxic activity appears to originate primarily from reactions of chlorine with humic substances in the source waters. Genotoxic activity in drinking water concentrates has been most frequently demonstrated using bacterial mutagenicity tests but results with mammalian cell assay systems are generally consistent with the findings from the bacterial assays. There is currently no evidence for genotoxic damage following in vivo exposures to animals. In some locations genotoxic contaminants of probable industrial and/or agricultural origin occur in the source waters and contribute substantially to the genotoxic activity of finished drinking waters.
Concentrated extracts prepared from chlorinated drinking water samples were tested for their ability to induce sex-linked recessive lethal mutations in Drosophila melanogaster. Adult flies were allowed to feed on sucrose solutions prepared using neat or half-strength water extract. The drinking water extracts used for this study were also tested in bacterial fluctuation assays using Salmonella typhimurium TA100 and TA98 and in an in vitro cytogenetic assay using CHO cells. Although the water extracts gave positive results in both of these in vitro tests, there was no evidence of mutagenic activity in the Drosophila studies.