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Cited by 178Water Treatment and DisinfectionCarcinogens and Genotoxicity AssessmentArsenic contamination and mitigation

Trihalomethanes in Drinking Water and Bladder Cancer Burden in the European Union

Open access
Evlampidou, Iro, Font-Ribera, Laia, Rojas-Rueda, David, Gracia-Lavedan, Esther, Costet, Nathalie, Pearce, Neil, Vineis, Paolo, Jaakkola, Jouni J.K. +22 more·2020·Environmental Health Perspectives
DOI 10.1289/ehp4495PMC PMC7015561
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Abstract

BACKGROUND: Trihalomethanes (THMs) are widespread disinfection by-products (DBPs) in drinking water, and long-term exposure has been consistently associated with increased bladder cancer risk. OBJECTIVE: We assessed THM levels in drinking water in the European Union as a marker of DBP exposure and estimated the attributable burden of bladder cancer. METHODS: We collected recent annual mean THM levels in municipal drinking water in 28 European countries (EU28) from routine monitoring records. We estimated a linear exposure-response function for average residential THM levels and bladder cancer by pooling data from studies included in the largest international pooled analysis published to date in order to estimate odds ratios (ORs) for bladder cancer associated with the mean THM level in each country (relative to no exposure), population-attributable fraction (PAF), and number of attributable bladder cancer cases in different scenarios using incidence rates and population from the Global Burden of Disease study of 2016. RESULTS: [standard deviation (SD) of 11.2]. The estimated bladder cancer PAF was 4.9% [95% confidence interval (CI): 2.5, 7.1] overall (range: 0-23%), accounting for 6,561 (95% CI: 3,389, 9,537) bladder cancer cases per year. Denmark and the Netherlands had the lowest PAF (0.0% each), while Cyprus (23.2%), Malta (17.9%), and Ireland (17.2%) had the highest among EU26. In the scenario where no country would exceed the current EU mean, 2,868 (95% CI: 1,522, 4,060; 43%) annual attributable bladder cancer cases could potentially be avoided. DISCUSSION: Efforts have been made to reduce THM levels in the European Union. However, assuming a causal association, current levels in certain countries still could lead to a considerable burden of bladder cancer that could potentially be avoided by optimizing water treatment, disinfection, and distribution practices, among other possible measures. https://doi.org/10.1289/EHP4495.

Integrity signals

Registry

Crossref · 10.1289/ehp4495

Cites

52 of 52 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 56 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Twelve countries supplied bromoform and dibromochloromethane measurements.

    “12 provided bromoform and dibromochloromethane levels”
    Quote in the paperNot a substantial claim
  • Findingreasoning

    The estimated number of bladder cancer cases attributable to THM exposure was 6,561 (95% CI 3,389-9,537) per year.

    “accounting for 6,561 (95% CI: 3,389, 9,537) bladder cancer cases per year.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: PAF calculations treat everyone as exposed at the country's mean THM concentration, compared with a zero-exposure reference.
    • Rests on an assumption: The pooled exposure–response relationship from Costet et al. (2011) applies to European Union populations and to country-specific mean THM levels.
    • Rests on an assumption: Routine monitoring THM measurements are representative of residential long-term THM exposure in each country.
    • Rests on an assumption: THM concentration is a valid marker or surrogate for total disinfection by-product exposure.
  • Findingown data

    Romania had the highest estimated THM level, based on data covering 7.4% of its population.

    “which was the country with the highest estimated THM level based on data reported for 7.4% of the population”
    Quote in the paperNot a substantial claim
  • Findingown data

    The population-weighted mean bromodichloromethane concentration was 2.9 μg/L (SD 3.2; IQR 0.3-6.3).

    “2.9μg/L for bromodichloromethane (SD: 3.2; IQR: 0.3–6.3)”
    Quote in the paperNot a substantial claim
  • Findingown data

    Average population coverage for bromoform was 70%.

    “70% each for bromodichloromethane and bromoform”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 21
  • May combine two claims. 41

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Fourteen countries supplied chloroform measurements.

    “A total of 14 countries provided chloroform levels”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Coverage of the population across the 26 countries varied from 22% in Italy to 100% elsewhere, averaging 80%.

    “The population coverage among the 26 countries, shown in Table 2, ranged from 22% in Italy to 100% in different countries (average coverage: 80%).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Spain (22.6%), the UK (20.7%), and Romania (16.0%) contributed the largest estimated numbers of attributable cases.

    “Spain (22.6%), the United Kingdom (20.7%), and Romania (16.0%) accounted for the largest estimated number of attributable cases.”
    • Also stated in: § Discussion · plain
      “Spain was the country with the greatest estimated contribution (23% of attributable EU cases) followed by the United Kingdom (21%) and Romania (16%)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.
    • Rests on an assumption: The exposure-response relationship between THMs and bladder cancer is causal and applies to the EU populations and age/sex groups used.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingnone given

    Denmark mainly relies on aeration and filtration, whereas the Netherlands applies ozone and UV radiation.

    “In Denmark, aeration and filtration are mainly used, and in the Netherlands, ozone and UV radiation are applied.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Italy also uses chlorine dioxide; in Lithuania, chlorination is limited to half of one city and that city uses surface water.

    “Chlorine dioxide is additionally used in Italy, and in Lithuania, chlorine is used only in half of one of the cities and is supplied with surface water.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Denmark had the lowest mean THM level (0.02 μg/L), followed by the Netherlands (0.2), Germany (0.5), Lithuania (1.0), Austria (1.1), Slovenia (2.9), Italy (3.1), and Poland (5.7 μg/L).

    “The lowest mean THM values were observed in Denmark (0.02μg/L), the Netherlands (0.2μg/L), Germany (0.5μg/L), Lithuania (1.0μg/L), Austria (1.1μg/L), Slovenia (2.9μg/L), Italy (3.1μg/L), and Poland (5.7μg/L).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The overall estimated PAF for bladder cancer from THM exposure was 4.9% (95% CI 2.5-7.1), ranging across countries from 0% to 23%.

    “The estimated bladder cancer PAF was 4.9% [95% confidence interval (CI): 2.5, 7.1] overall (range: 0–23%)”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: PAF calculations treat everyone as exposed at the country's mean THM concentration, compared with a zero-exposure reference.
    • Rests on an assumption: The pooled exposure–response relationship from Costet et al. (2011) applies to European Union populations and to country-specific mean THM levels.
    • Rests on an assumption: Routine monitoring THM measurements are representative of residential long-term THM exposure in each country.
    • Rests on an assumption: THM concentration is a valid marker or surrogate for total disinfection by-product exposure.

  • May combine two claims.

    Findingown data

    The lowest PAFs were in Denmark and the Netherlands (0.0% each); the highest among EU26 were Cyprus (23.2%), Malta (17.9%), and Ireland (17.2%).

    “Denmark and the Netherlands had the lowest PAF (0.0% each), while Cyprus (23.2%), Malta (17.9%), and Ireland (17.2%) had the highest among EU26.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Routine monitoring supplied THM data for 26 of the 28 EU countries, covering 75% of the EU26 population; the years were 2005-2018, except Austria, which dated from 1997.

    “We obtained recent (2005–2018) information—with the exception of Austria (1997)—on THM levels in drinking water through routine monitoring for 26 of the 28 countries in the European Union (Table 2), covering 75% of the EU26 population.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Romania's mean THM concentration from published studies was 91.8 μg/L (SD 64.2), but only 7.4% of the population was covered.

    “For Romania, the estimated mean (SD) from the published studies was 91.8μg/L (64.2), but the population coverage was limited (7.4%)”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Thirteen countries supplied bromodichloromethane measurements.

    “13 provided bromodichloromethane levels”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Cyprus had the highest mean THM level (66.2 μg/L), then Malta (49.4), Ireland (47.3), Spain (28.8), and Greece (26.3 μg/L).

    “The highest mean THM values were observed in Cyprus (66.2μg/L), Malta (49.4μg/L), Ireland (47.3μg/L), Spain (28.8μg/L), and Greece (26.3μg/L) (Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingcitation

    Few samples exceeded the limit; among the nine countries, noncompliance averaged 0.7% overall, 0.3% for large systems, and 1.1% for small systems.

    “However, the proportion of samples exceeding this limit was low, and average noncompliance in the nine countries was 0.7% overall, 0.3% in large water systems, and 1.1% in small water systems (EIONET).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites EIONET

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Measured THM values spanned from 0.0 μg/L in several countries up to 301 μg/L in Portugal, 439 μg/L in Spain, and 771 μg/L in Hungary; the Hungarian value was a single confirmed atypical result.

    “The actual measurements ranged from 0.0μg/L in multiple countries to 301μg/L in Portugal, 439μg/L in Spain, and 771μg/L in Hungary (corresponding in this last case to one confirmed and atypical observation).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The population-weighted mean THM level among the 26 countries was 11.7 μg/L, with SD 11.2, median 10, and IQR 3.1-24.2.

    “The estimated population-weighted mean THM level was 11.7μg/L [standard deviation (SD) of 11.2].”
    • Also stated in: § Trihalomethane Levels · plain
      “Among these countries, the population-weighted mean THM level was 11.7μg/L [SD: 11.2, median: 10, interquartile range (IQR): 3.1–24.2].”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    Bulgaria received the EU26 mean THM concentration of 11.7 μg/L and SD 11.2.

    “the EU26 mean to Bulgaria (11.7μg/L) and SD (11.2)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    This study is the first Europe-wide assessment of THM levels in drinking water and of the THM-attributable bladder cancer burden, using monitoring data covering 75% of the population in 26 EU countries.

    “We conducted the first Europe-wide assessment of THM levels in drinking water and estimated the THM-attributable burden of bladder cancer using monitoring data covering 75% of the population in 26 EU countries.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.

  • May combine two claims.

    Findingown data

    The estimated PAF for France was 4.6%, corresponding to 737 attributable cases per year.

    “We estimated a PAF of 4.6% for France (737 attributable cases/year)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.
    • Rests on an assumption: The exposure-response relationship between THMs and bladder cancer is causal and applies to the EU populations and age/sex groups used.

  • May combine two claims.

    Findingown data

    The largest absolute reductions would be in Romania (891 cases), Spain (860 cases), and the UK (685 cases).

    “The largest absolute reduction would occur in Romania (891 cases), Spain (860 cases), and the United Kingdom (685 cases).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.
    • Rests on an assumption: The exposure-response relationship between THMs and bladder cancer is causal and applies to the EU populations and age/sex groups used.

  • May combine two claims.

    Findingown data

    The largest relative reductions were in Romania (85.1%), Cyprus (80.3%), Malta (74.5%), and Ireland (73.5%).

    “The largest reduction relative to the current number of attributable cases occurred in Romania (85.1%), Cyprus (80.3%), Malta (74.5%), and Ireland (73.5%).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.
    • Rests on an assumption: The exposure-response relationship between THMs and bladder cancer is causal and applies to the EU populations and age/sex groups used.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    In France, bladder cancer cases in 2011 among men were considerably lower (n=9,100) than the Global Burden of Disease 2016 estimates for 2016 among men (n=13,959).

    “In the French study, for example (Corso et al. 2017), bladder cancer cases were considerably lower in all ages (n=9,100 in 2011, men only) than the ones reported in the Global Burden of Disease 2016 study (n=13,959 in 2016, men only).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Corso et al. 2017

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    In the Czech Republic, 94% of the population is served by public water supply systems, but THM data were available for only 74%.

    “For example, in the Czech Republic, 94% of the population is served by public water supply systems, but we had THM data only for 74%.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For Italy, websites covering 54% of the population were checked, and only 35% of these included THM information.

    “For example, for Italy, we checked relevant websites covering 54% of the Italian population, and, of these, only 35% included THM information.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Not all municipalities or water utilities report water quality analysis results, and among those that do, only a subset includes THM values.

    “Not all municipalities or water utilities report their water quality analysis results, and among the ones that do, only a subset includes THMs values.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In the EU, total THMs and bromate are the sole regulated DBPs; the regulatory maximum is 100 μg/L.

    “Together with bromate, total THM concentrations representing the sum of chloroform, bromodichloromethane, dibromochloromethane, and bromoform are the only DBPs regulated in the European Union, with a maximum contaminant level of 100μg/L (EC 1998).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites EC 1998

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    THM variability was attributed mainly to differences in source-water properties, disinfection practices, and distribution-system conditions.

    “This variability was based primarily on variations in the characteristics of raw water, drinking water disinfection methods, and conditions of the water distribution system (Charisiadis et al. 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Charisiadis et al. 2015

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Prior burden estimates for France and the United States suggest that about one-sixth of bladder cancer incidence is attributable to drinking-water DBP exposure.

    “Burden of disease estimates for bladder cancer due to DBP exposure have been previously assessed in France (Corso et al. 2017) and the United States (Regli et al. 2015; U.S. EPA 2005), indicating that around 16% of bladder cancer incidence is currently attributable to exposure to DBPs in drinking water.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Corso et al. 2017

      Not checked in the free run.

    • cites Regli et al. 2015

      Not checked in the free run.

    • cites U.S. EPA 2005

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Countries differ in water testing collection points and in the geographical level used to report THM levels.

    “Some differences between countries are also present in the various water testing collection points and the geographical level for reporting THM levels (Table 1).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Data on showering, bathing, or swimming were incomplete across studies and were therefore omitted from the analysis.

    “Showering, bathing, or swimming information was not available for all studies and was not included in the analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The pooled dataset contained 9,458 people with long-term residential THM estimates: 3,481 cases and 5,977 controls, aged 30-80, each with THM information covering at least 70% of a 40-year exposure period.

    “We pooled data from 9,458 subjects with estimates of long-term average residential THM levels, including 3,481 cases (2,776 men, 705 women) and 5,977 controls (4,199 men, 1,778 women) 30–80 years of age with THM data for ≥70% of the 40-y exposure window.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Costet et al. (2011)

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Austria was expected to have very low THMs, as nearly all its drinking water is groundwater and UV treatment predominates.

    “The literature search identified reports of THM levels measured before the year 2000 for Austria (Premazzi et al. 1997), where expected THM levels are very low, since 99.7%% of drinking water is from underground sources and ultraviolet (UV) radiation is the predominant disinfection method (A Indra, personal communication).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Premazzi et al. 1997

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    If the association is causal, present THM concentrations in some countries may produce a substantial bladder cancer burden, much of which might be preventable through better water treatment, disinfection, and distribution, among other measures.

    “However, assuming a causal association, current levels in certain countries still could lead to a considerable burden of bladder cancer that could potentially be avoided by optimizing water treatment, disinfection, and distribution practices, among other possible measures.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: THM exposure is causally associated with bladder cancer.

  • May combine two claims.

    Premisecitation

    Costet et al. (2011) pooled and meta-analysed six case-control studies, with two based in the United States and one each in Canada, France, Finland, and Spain.

    “This is an international pooled analysis and meta-analysis including six case–control studies: two from the United States (Cantor et al. 1998; Lynch et al. 1989) and one each from Canada (King and Marrett 1996), France (Cordier et al. 1993), Finland (Koivusalo et al. 1998), and Spain (Villanueva et al. 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Costet et al. (2011)

      Not checked in the free run.

    • cites Cantor et al. 1998

      Not checked in the free run.

    • cites Lynch et al. 1989

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Most DBPs are unregulated; many are considered carcinogenic or genotoxic and have been linked to bladder cancer, such as nitrosamines, but their health effects are insufficiently studied.

    “Most of them are not regulated, and many are considered carcinogenic and/or genotoxic and have been associated with bladder cancer (e.g., nitrosamines) (Richardson et al. 2007), but their effect on human health has not been sufficiently studied.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Richardson et al. 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In a study of 43 adults, changes in exhaled DBPs after a 40-minute swim in a chlorinated pool were associated with microRNA and gene expression patterns that may indicate increased bladder cancer risk.

    “while another study of 43 adults (Espín-Pérez et al. 2018) reported that changes in exhaled DBPs following a 40-min swim in a chlorinated pool were associated with microRNA and gene expression patterns that may indicate an increased risk of bladder cancer.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Espín-Pérez et al. 2018

      Not checked in the free run.

  • May combine two claims.

    Study design and conductcitation

    The analysis did not account for bottled or filtered water use, which may be substantial in some countries and may cause exposure misclassification through ingestion.

    “We have not considered the proportion of use of bottled or filtered water, which, in some countries, may be substantial and account for exposure misclassification through the ingestion route (Wright et al. 2006)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wright et al. 2006

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Polymorphisms in DBP-metabolizing genes modify the exposure-response relationship.

    “Polymorphisms in DBP-metabolizing genes have been shown to modify the exposure–response relationship (Cantor et al. 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Cantor et al. 2010

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Uncertainties remain in the THM-bladder cancer association: the causal agent is unidentified, biological pathways are not fully established, and the inconsistent association in women is not well understood.

    “However, some uncertainties in the association still exist, e.g., the putative agent(s) is yet to be identified, the biological pathways are not completely established, and the inconsistent association in some studies in women is not well understood.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    The European population is growing and aging.

    “since the European population is growing and getting older (Eurostat)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Eurostat

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Previous European studies found THM levels similar to this study's in Italy, Lithuania, Spain, and the UK, but lower in Crete, Greece, and higher in Rennes, France, than the national averages reported here.

    “Previous studies in European regions found THM levels similar to the ones in our study in Italy, Lithuania, Spain, and the United Kingdom, but Greece (the island of Crete) showed lower levels, and France (Rennes region) showed higher levels than the national averages reported in the present study (Goslan et al. 2014; Krasner et al. 2016).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Goslan et al. 2014

      Not checked in the free run.

    • cites Krasner et al. 2016

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In 2016, the EU had 135,011 bladder cancer cases, of which 134,976 (99.97%) were in the ≥20 age group.

    “In 2016, a total of 135,011 bladder cancer cases occurred in the European Union, of which 134,976 (99.97%) were in the ≥20-y age group (IHME 2016a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites IHME 2016a

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    DBPs are a complex mixture of hundreds of chemicals.

    “DBPs constitute a complex mixture of hundreds of chemicals (Richardson et al. 2007)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Richardson et al. 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    Population differences in DBP-metabolizing gene polymorphisms are unlikely to affect the overall results.

    “but these population differences are unlikely to affect our overall results.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    No published THM data were available for Bulgaria, so the EU mean was assigned for that country.

    “In addition, for Bulgaria, we could not find any published data at all, and we assigned the EU mean, but it is a small country (1.5% of the EU population) and therefore has little influence in the overall European estimates.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The large contributions of Spain, the UK, and Romania are explained mainly by high incidence rates (Spain, Romania), large population size (UK), or high average THM levels (Romania).

    “explained largely by high incidence rates (Spain, Romania), large population size (the United Kingdom ranks the second EU country in inhabitants), or high average THM levels (Romania).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.
    • Rests on an assumption: The exposure-response relationship between THMs and bladder cancer is causal and applies to the EU populations and age/sex groups used.

  • May combine two claims.

    Interpretationreasoning

    The accuracy of Global Burden of Disease 2016 bladder cancer incidence data may differ across countries because not all countries maintain nationwide cancer registries or because of discrepancies with national databases.

    “Accuracy may differ, since not all keep nationwide cancer registries or there may be discrepancies with national databases.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductnone given

    The quality of Romanian THM data was low, with few published studies and very low population coverage, and may not reflect the current national average.

    “However, the quality of THM data for Romania was low (few published studies with very low population coverage) and may not accurately reflect the current country average.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Some case-control studies show higher bladder cancer risks in women than in men.

    “there are also case–control studies showing higher risks in women than men (Beane Freeman et al. 2017)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Beane Freeman et al. 2017

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Bladder cancer incidence is expected to increase in some European countries and decrease in others over the next decade.

    “the bladder cancer incidence is expected to increase in some European countries and decrease in others over the next decade (Antoni et al. 2017; Wong et al. 2018)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Antoni et al. 2017

      Not checked in the free run.

    • cites Wong et al. 2018

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Disinfectants are highly reactive, and any one of them will form DBPs.

    “Disinfectants are highly reactive by definition, and any one of them will lead to the formation of DBPs (Hua and Reckhow 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hua and Reckhow 2007

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    THMs occur in mixtures with other DBPs, and their effects cannot be fully separated.

    “are present in mixtures with other DBPs and their effects cannot be fully separated (Rice et al. 2009)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rice et al. 2009

      Not checked in the free run.

    • Rests on an assumption: THMs are an adequate surrogate for total DBP exposure despite their limitations.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    National averages may conceal within-country disparities, such as lower THM levels in areas supplied by ground versus surface water.

    “Although national averages may hide disparities within countries, i.e., areas supplied with ground vs. surface water may have lower THM levels”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.

  • May combine two claims.

    Interpretationcitation

    The pooled analysis by Costet et al. (2011) is the most comprehensive currently available, but it is limited to case-control studies and does not include a recent U.S. study.

    “Although this is the most comprehensive pooled analysis currently available, it is limited to case–control studies and does not include a recent U.S. study of 1,213 bladder cancer cases and 1,418 controls (Beane Freeman et al. 2017).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Costet et al. (2011)

      Not checked in the free run.

    • cites Beane Freeman et al. 2017

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    The models were adjusted for main bladder cancer risk factors, but residual confounding cannot be ruled out.

    “Although models are adjusted for the main risk factors of bladder cancer, the potential for residual confounding cannot be ruled out.”
    Quote in the paperNot a substantial claim
54 of 54

  • The paper relies on this without support.

    There is no published report on current THM exposure levels in the European Union.

    “there is no published report on current levels of exposure in the European Union.”

  • The authors state this as an assumption.

    THM exposure is causally associated with bladder cancer.

    “assuming a causal association”

  • The authors state this as an assumption.

    PAF calculations treat everyone as exposed at the country's mean THM concentration, compared with a zero-exposure reference.

    “assuming 100% exposure to the mean THM level (ORi) vs. no exposure (ORref=1.0)”

  • The paper relies on this without support.

    The pooled exposure–response relationship from Costet et al. (2011) applies to European Union populations and to country-specific mean THM levels.

    “We estimated population-attributable fractions (PAFs) for each country based on an exposure–response function derived using pooled data from an analysis of residential THM exposure and bladder cancer (Costet et al. 2011)”

  • The paper relies on this without support.

    Routine monitoring THM measurements are representative of residential long-term THM exposure in each country.

    “We obtained recent (2005–2018) information—with the exception of Austria (1997)—on THM levels in drinking water through routine monitoring for 26 of the 28 countries in the European Union”

  • The paper relies on this without support.

    THM concentration is a valid marker or surrogate for total disinfection by-product exposure.

    “THMs, used as a surrogate of DBPs”

  • The paper relies on this without support.

    The country-specific average THM concentrations used in the burden calculation represent the exposure of the corresponding national populations.

    “Although national averages may hide disparities within countries, i.e., areas supplied with ground vs. surface water may have lower THM levels, we prioritized width to depth in the data collection in order to compare the average situation between countries.”

  • The paper relies on this without support.

    The exposure-response relationship between THMs and bladder cancer is causal and applies to the EU populations and age/sex groups used.

    “Country-specific ORs were derived by converting the pooled OR for a 1-μg/L THM increment (OR=1.004), derived using pooled data for men and women age 30–80 from Costet et al. 2011) to a country-specific ORi for bladder cancer in association with the country-specific mean exposure vs. no exposure”

  • The paper relies on this without support.

    THMs are an adequate surrogate for total DBP exposure despite their limitations.

    “THMs have been used in epidemiological studies as surrogates of total DBP content. THMs have limitations as markers of total DBPs since they are not the most toxic (Plewa et al. 2008), are present in mixtures with other DBPs and their effects cannot be fully separated (Rice et al. 2009), and correlations with specific DBPs are variable (Villanueva et al. 2012).”
9 of 9

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Bulgaria sensitivity contribution is understated

    Minor

    Bulgaria's 67 sensitivity-analysis attributable cases are about 1.2% of the stated EU total of 5,711, rather than 0.2%.

    Reported 0.2 · recomputed 1.173175

  • Table 5's title gives a different EU THM mean

    Minor

    The Table 5 title states 11.9 μg/L, whereas its reduced-exposure entries and note use 11.7 μg/L as the cap.

  • Czech Republic sensitivity contribution is overstated tenfold

    Minor

    The Czech Republic's 138 sensitivity-analysis attributable cases are about 2.4% of the stated EU total of 5,711, not 24%.

    Reported 24 · recomputed 2.416389

  • The two tables give different totals for annual bladder cancer cases

    Minor

    Both tables describe EU28 men and women aged 20 years and above, but Table 3 reports 134,976 annual bladder cancer cases while Table 5 reports 123,805. Table 5 retains the same 6,561 attributable cases, so the conflicting denominator also affects interpretation of the reported burden.

  • The pooled analysis is described as containing both six and seven studies

    Minor

    The methods repeatedly identify six case-control studies as the source of the pooled data, but the discussion says the same case and control counts came from seven studies.

  • Spain's odds ratio lies outside its reported confidence interval

    Minor

    The point estimate of 1.122 exceeds its stated upper 95% confidence limit of 1.118.

  • Hungary and Slovakia have different odds-ratio intervals for the same exposure

    Minor

    Both rows give a mean THM level of 10.0 μg/L and a point odds ratio of 1.041, but Hungary's lower confidence limit is 1.041 while Slovakia's is 1.020. Their reported PAF intervals are identical.

7 of 7

Cites

Flagged first, then by citations

Research works printed but not linked: 8

  1. Babayigit MA, 2016, Evaluation of the effects of disinfection methods on volatile organic pollutant levels and some physicochemical parameters of water, J Environ Prot Ecol, 17, 460
  2. Bujar DH, 2017, Seasonal variation of trihalomethanes concentration in Tetova’s drinking water (part B), World J Appl Environ Chem, 1, 42
  3. Cohl M, 2015, Trihalomethanes issues drinking water after chlorination treatment, Revista de chimie, 66, 1282
  4. Dirtu D, 2016, Occurrence and assessment of selected chemical contaminants in drinking water from Eastern Romania, Revista de chimie, 67, 2059
  5. EC (European Commission), 1998, Council directive of 3 November 1998 on the quality of water intended for human consumption. European Council Directive 98/83/EC, Off J Eur Communities, 330, 23
  6. EC, 2018, Proposal for a Directive of the European Parliament and of the Council on the quality of water intended for human consumption (recast), Off J Eur Communities, 64, 55
  7. Premazzi G, 1997, Exposure of the European Population to Trihalomethanes (THMs) in Drinking Water
  8. Thach TT, 2012, An analysis of trihalomethane levels in the distribution networks of three Romanian cities, Carpathian J Earth Environ Sci, 7, 81

Cited by

Sorted by citations

Related

Authors
Evlampidou, I., Font-Ribera, L., Rojas-Rueda, D., Gracia-Lavedan, E., Costet, N., Pearce, N., Vineis, P., Jaakkola, J. J. K., Delloye, F., Makris, K. C., Stephanou, E. G., Kargaki, S., Kozisek, F., Sigsgaard, T., Hansen, B., Schullehner, J., Nahkur, R., Galey, C., Zwiener, C., Vargha, M., Righi, E., Aggazzotti, G., Kalnina, G., Grazuleviciene, R., Polanska, K., Gubkova, D., Bitenc, K., Goslan, E. H., Kogevinas, M., & Villanueva, C. M.
Affiliations
  • Universitat Pompeu Fabra (ES)
  • ISGlobal, Barcelona, Spain
  • Inserm (FR)
  • London School of Hygiene & Tropical Medicine (GB)
  • Imperial College London (GB)
  • University of Oulu (FI)
  • Service Public de Wallonie (BE)
  • Cyprus University of Technology (CY)
  • University of Crete (GR)
  • National Institute of Public Health, Prague, Czech Republic
  • Aarhus University (DK)
  • Geological Survey of Denmark and Greenland (DK)
  • Ministry of Social Affairs (EE)
  • Santé Publique France (FR)
  • University of Tübingen (DE)
  • National Public Health Center, Budapest, Hungary
  • University of Modena and Reggio Emilia (IT)
  • Public Health Division, Ministry of Health of the Republic Latvia, Health Inspectorate, Riga, Latvia
  • Department of Environmental Sciences, Faculty of Natural Sciences, Vytautas Magnus University, Kaunas, Lithuania
  • Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, Lodz, Poland
  • Public Health Authority of the Slovak Republic (SK)
  • National Institute of Public Health (SI)
  • Cranfield University (GB)
Corresponding author
Villanueva, Cristina M.
ORCID
Venue
Environmental Health Perspectives
Publisher
American Chemical Society (ACS)
Published
2020-01
Volume
128
Issue
1
Pages
17001-17001
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
DOI
10.1289/ehp4495
PMC
PMC7015561
OpenAlex
W2999609260
Semantic Scholar
778c81b2af6a09381ffc32f48981bb51a59ba0d1
Cited by
178
References
52
Citations by year
2026: 16 · 2025: 28 · 2024: 23 · 2023: 34 · 2022: 29 · 2021: 23 · 2020: 24 · 2019: 1
FWCI
10.99
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
  • HAL (submittedVersion, public-domain)
  • CERES (Cranfield University) (submittedVersion, cc-by)
  • Ktisis at Cyprus University of Technology (Cyprus University of Technology) (submittedVersion, cc-by-nc-nd)
  • Repositori digital de la UPF (Universitat Pompeu Fabra) (submittedVersion, public-domain)
  • Vytautas Magnus University (submittedVersion)
Funders
  • Università degli Studi di Cagliari
  • Centres de Recerca de Catalunya
  • European Commission (308610)
  • Institut National de la Santé et de la Recherche Médicale
  • Universiteit Utrecht
  • Generalitat de Catalunya
  • Queen's University
  • Università degli Studi di Palermo
  • École des Hautes Études en Santé Publique
  • Terveyden ja hyvinvoinnin laitos
  • National Institutes of Health
  • Medical Research Council (MR/S019669/1)
  • National Cancer Institute
Topics
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Water Treatment and Disinfection
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Physical Sciences › Environmental Science › Environmental Chemistry › Arsenic contamination and mitigation
Keywords
trihalomethanes, disinfection by-products, drinking water, bladder cancer, attributable burden, population attributable fraction, exposure-response relationship, water disinfection, water treatment, European Union
MeSH terms
Urinary Bladder Neoplasms, Environmental Exposure, Europe, European Union, Humans, Water Pollutants, Chemical, Water Purification, Trihalomethanes, Drinking Water

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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