Open access
Review Article
3 January 2014

Assessing Exposure and Health Consequences of Chemicals in Drinking Water: Current State of Knowledge and Research Needs

Publication: Environmental Health Perspectives
Volume 122, Issue 3
Pages 213 - 221


Background: Safe drinking water is essential for well-being. Although microbiological contamination remains the largest cause of water-related morbidity and mortality globally, chemicals in water supplies may also cause disease, and evidence of the human health consequences is limited or lacking for many of them.
Objectives: We aimed to summarize the state of knowledge, identify gaps in understanding, and provide recommendations for epidemiological research relating to chemicals occurring in drinking water.
Discussion: Assessing exposure and the health consequences of chemicals in drinking water is challenging. Exposures are typically at low concentrations, measurements in water are frequently insufficient, chemicals are present in mixtures, exposure periods are usually long, multiple exposure routes may be involved, and valid biomarkers reflecting the relevant exposure period are scarce. In addition, the magnitude of the relative risks tends to be small.
Conclusions: Research should include well-designed epidemiological studies covering regions with contrasting contaminant levels and sufficient sample size; comprehensive evaluation of contaminant occurrence in combination with bioassays integrating the effect of complex mixtures; sufficient numbers of measurements in water to evaluate geographical and temporal variability; detailed information on personal habits resulting in exposure (e.g., ingestion, showering, swimming, diet); collection of biological samples to measure relevant biomarkers; and advanced statistical models to estimate exposure and relative risks, considering methods to address measurement error. Last, the incorporation of molecular markers of early biological effects and genetic susceptibility is essential to understand the mechanisms of action. There is a particular knowledge gap and need to evaluate human exposure and the risks of a wide range of emerging contaminants.
Citation: Villanueva CM, Kogevinas M, Cordier S, Templeton MR, Vermeulen R, Nuckols JR, Nieuwenhuijsen MJ, Levallois P. 2014. Assessing exposure and health consequences of chemicals in drinking water: current state of knowledge and research needs. Environ Health Perspect 122:213–221;


The safety of water supplies is of paramount public health importance. An estimated 13% of the world population lacked access to improved drinking-water sources in 2008 [UNICEF and World Health Organization (WHO) 2011], and almost 10% of the total burden of disease worldwide could be prevented by improving drinking-water supply, sanitation, hygiene, and the management of water resources (Prüss-Üstün et al. 2008). Microbiological contamination is the largest cause of waterborne disease at a global scale. However, chemicals in water supplies can be related to health risks, generally when associated with long-term exposures (Thompson et al. 2007).
There are uncertainties about the safety of current standards for some regulated chemicals, and the potential health impacts of unregulated or emerging chemical contaminants are largely unknown. In May 2012, a workshop was held at the Centre for Research of Environmental Epidemiology (CREAL), Barcelona, Spain, with the aim of advancing the field of epidemiology and chemical contaminants in water and to make recommendations for future research. Our aspiration was that the proposed suggestions be useful and applicable to any type of chemical contaminant occurring in drinking water. Chemicals that we discuss as examples in this review are substances whose main pathway of human exposure is through drinking water. Although the chemical universe is broad and most chemicals do not occur exclusively in drinking water, water is essential for life, and exposures to chemicals in drinking water, even at low concentrations, may have important consequences across the entire population. Here we focus on cancer as an example and summarize the main discussion points and conclusions of the workshop.


Regulated chemicals. Drinking-water quality is regulated in most countries, and monitoring is conducted routinely. A complete list of chemicals that are currently regulated in drinking water, and the regulatory limits promulgated for each chemical by the WHO (2011), the U.S. Environmental Protection Agency (EPA 2009), and the European Union (EU) Council (1998) are provided in Table 1. These regulatory guidelines require periodic review to be updated according to new evidence. For example, the U.S. EPA reduced its maximum contaminant level (MCL) for arsenic from 50 μg/L in 1942 to the current level of 10 μg/L in response to growing scientific evidence of its adverse health effects (Smith et al. 2002). Epidemiological studies have reported associations of trihalomethane (THM) levels in drinking water (a surrogate measure of the disinfection by-product mixture) and bladder cancer (Villanueva et al. 2004) at THM levels lower than the current regulations in the United States and the European Union (80 and 100 μg/L, respectively; Table 1). The current MCL for nitrate was set based on methemoglobinemia among infants, but there is uncertainty concerning the safety of this MCL for chronic effects over longer exposure periods (e.g., on cancer) (Ward et al. 2005). Manganese is a neurotoxin associated with learning disabilities and deficits in intellectual function in children (Zoni and Lucchini 2013). The WHO manganese guideline has been fluctuating from the initial 500 μg/L in 1958 (Ljung and Vahter 2007) to its discontinuation in the current (fourth) edition of the WHO guidelines (WHO 2011). This has generated controversy in the scientific community because the last guideline before discontinuation (400 μg/L) was questionable according to some authors (Ljung and Vahter 2007) and the discontinuation of the manganese guidelines has received criticisms (Frisbie et al. 2012). Although many contaminants are monitored and regulated, the adequacy of the MCL approach is open to debate, in part because these limits are often based on toxicological studies of animals because human studies are not available or are inconclusive.
Table 1 Regulatory limits [μg/L (except for asbestos)] for chemicals in drinking water established by the WHO (2011), the U.S. EPA (2009), and the EU Council (1998).
ChemicalWHOU.S. EPAEUChemical group
Aldrin + dieldrin0.03Organic
Asbestos (million fibers >10 μm per liter)7Inorganic
Carbon tetrachloride45Organic
Chloramines (as Cl2)4,000Disinfectant
Chlorine dioxide800Disinfectant
Chromium (total)5010050Inorganic
2,4-D (dichlorophenoxyacetic acid)3070Organic
2,4-DB (dichlorofenoxybutyric acid)90Organic
DDT (dichlorodiphenyltrichloroethane) and metabolites1Organic
1,2-Dibromo-3-chloropropane (DBCP)10.2Organic
1,2-Dichlorobenzene (o-dichlorobenzene)1,000600Organic
1,4-Dichlorobenzene (p-dichlorobenzene)30075Organic
Di(2-ethylhexyl) adipate400Organic
Di(2-ethylhexyl) phtalate86Organic
Dioxin (2,3,7,8-TCDD)0.00003Organic
Edetic acid600Organic
Ethylene dibromide0.05Organic
Fenoprop/Silvex/2,4,5-TP/2-(2,4,5- trichlorophenoxy)propionic acid950Organic
Haloacetic acids (HAAs)c60DBP
Heptachlor epoxide0.2Organic
4-(2-Methyl-4-chlorophenoxy) acetic acid (MCPA)2Organic
Microcystin-LR1Algal toxin
Nitrilotriacetic acid200Organic
N-Nitrosodimethylamine (NDMA)0.1DBP
Oxamyl (Vydate®)200Organic
Pesticides (total)0.50Organic
Polychlorinated biphenyls (PCBs)0.5Organic
Polycyclic aromatic hydrocarbons0.10Organic
Sodium dichloroisocyanurate/cyanuric acid50,000/40,000Disinfectant
Tetrachloroethene (tetrachloroethylene)405Organic
Tetrachloroethylene + trichloroethylene10Organic
2,4,5-T (2,4,5-trichlorophenoxyacetic acid)9Organic
Trihalomethanes (total)80100DBP
Vinyl chloride0.320.50Organic
DBP, disinfection by-product.aEach water system must certify annually that when it uses acrylamide and/or epichlorohydrin to treat water, the combination of dose and monomer level does not exceed the ­levels specified, as follows: acrylamide = 0.05% dosed at 1 mg/L (or equivalent); epichlorohydrin = 0.01% dosed at 20 mg/L (or equivalent). bIncludes its chloro-s-triazine metabolites. ­cIncludes the sum of monochloroacetic acid, dichloroacetic acid, trichloroacetic acid, monobromoacetic acid, and dibromoacetic acid.
Emerging chemical contaminants. Non-regulated chemicals are of particular concern and constitute a main focus of current research (Richardson and Ternes 2011). Wastewater from human activities may contaminate water supply sources with pharmaceuticals, nanoparticles, consumer products (such as sunscreens), and other contaminants (Table 2), and these chemicals have been identified in drinking water (Ternes 2007). For example, iodinated or nitrogenated disinfection by-products (DBPs) [which are unregulated DBPs that are more toxic than their chlorinated and carbonaceous DBP analogs (Plewa et al. 2008b)] may occur in water supplies at very low concentrations (Plewa et al. 2004, 2008a). Degradation by-products of pharmaceuticals, which may be more toxic than their parent compounds, also have been identified in drinking water (Shen and Andrews 2011). The contribution of drinking water as a source of exposure to perfluorinated chemicals may be as important as dietary intake (Ericson et al. 2008), and evidence suggests that continued human exposure to even relatively low concentrations of perfluorooctanoic acid (PFOA) in drinking water results in elevated body burdens that may increase the risk of health effects (Post et al. 2012). Although concentrations are generally low (usually in the range of nanograms per liter) and some individual chemicals may pose no appreciable risks to human health (Schriks et al. 2010), there are concerns about potential risks of exposures to mixtures (Silva et al. 2002). The removal efficiency by drinking-water treatment processes has been evaluated for some substances (WHO 2012) but is poorly known for many emerging pollutants.
Table 2 Emerging chemical contaminants that may occur in water sources or treated drinking water [data from Richardson and Ternes (2011)], with the current state of information regarding their health effects.
Chemical groupSourceChemicalsSuspected or known health effects
Algal toxinsProduced by algal blooms from an excess of nutrients (in agricultural runoff and wastewater discharges).Microcystins (e.g., microcystin-LR), nodularins, anatoxins, cylindrospermopsin, and saxitoxins.Microscystin-LR is hepatotoxic, genotoxic, and carcinogenic (IARC 2010).
Artificial sweetenersConsumers > urban wastewater > natural waters > drinking-­water source.Sucralose (Splenda®, SucraPlus™), acesulfame, saccharin, cyclamate, etc.Unknown. Sucralose is a persistent chemical in the environment (half-life up to several years).
Brominated flame retardantsUsed during many years in commercial products such as children’s sleepwear, foam cushions in chairs, computers, plastics, and electronics. Diet is a source of exposure because some are persistent and accumulate in fish, eggs, milk, and meat.Several chemicals classified in different groups such as polybrominated diphenyl ethers (PBDEs), polybrominated biphenyl (PBB), hexabromocyclododecane (HBCD).Neurotoxicity and thyroid disruption (Dingemans et al. 2011).
BenzotriazolesComplexing agents widely used as anticorrosives and for silver protection in dishwashing liquids.The two most common forms are benzotriazole and tolytriazole.Unknown. Soluble in water, resistant to biodegradation, and only partly removed in wastewater treatment.
DBPsGenerated through chemical reaction between organic matter and a disinfectant (e.g., chlorine, chloramine, chlorine dioxide) in the treatment of drinking water and swimming pools.More than 700 compounds identified to date, which together are estimated to account for ~ 50% of the total organic halogen content.Genotoxic, carcinogenic, reprotoxic.
Ionic liquidsOrganic salts with low melting point (< 100ºC) promoted as “green chemistry” replacements to traditional solvents in industry. They exhibit some unique properties, including tunable viscosity, miscibility, and electrolytic conductivity, which make them useful for many applications, including organic synthesis and catalysis, production of fuel cells, batteries, coatings, oils, and nanoparticles, as well as other chemical engineering and biotechnology applications.The chemical structures typically involve a cationic or anionic polar head group with accompanying alkyl side chains. Cationic head groups include imidazolium, pyridinium, pyrrolidinium, morpholinium, piperidium, quinolinium, quaternary ammonium, and quaternary phosphonium moieties; anionic head groups include tetrafluoroborate (BF4), hexafluorophosphate (PF6), bis(trifluoromethylsulfonyl)-imide [(CF3SO2)2N], dicyanamide [(CN)2N], chloride, and bromide.Different toxicity in animals (Pham et al. 2010). No human studies.
Illicit drugsFound in surface waters, but generally removed by treatment in water utilities (Huerta-Fontela et al. 2008).Several chemicals, including amphetamine-like compounds, benzodiazepines, cannabinoids, cocainics, lysergic acid diethylamine (LSD), opioids, and metabolites (Valcárcel et al. 2012).The effect of the mixture is unknown.
MusksHighly lipophilic chemicals widely used as fragrance additives in many consumer products including perfumes, lotions, sunscreens, deodorants, and laundry detergents.Several chemicals. May have nitroaromatic structures [as in the case of musk xylene (1-tert-butyl-3,5-dimethyl-2,4,6-trinitrobenzene) or musk ketone (4-tert-butyl-2,6-dimethyl-3,5-dinitroacetophenone)] or polycyclic structures [as in the case of 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN; trade name, tonalide), 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-(g)-2-benzopyran (HHCB; trade name, galaxolide), 4-acetyl-6-tert-butyl-1,1-dimethylindan (ADBI; trade name, celestolide), dihydropentamethylindanone (DPMI; trade name, cashmeran), or 5-acetyl-1,1,2,3,3,6-examethylindan (AHMI, trade name phantolide)].Endocrine disruption, according to animal evidence (Schreurs et al. 2004).
Naphtenic acidsResult from petroleum extraction. Occur naturally in crude oil deposits across the world (up to 4% by weight) and in coal.Complex mixture of alkyl-substituted acyclic and cyclo-aliphatic carboxylic acids that dissolve in water at neutral or alkaline pH and have surfactant-like properties.Liver toxicity in mammals (Rogers et al. 2002). No human studies.
NanomaterialsHeterogeneous group of chemicals sized 1–100 nm, highly stable, strong, conductors, and with low permeability.Several chemical groups and structures including fullerenes, nanotubes, quantum dots, metal oxanes, titanium dioxide, nanoparticles, nanosilver, and zerovalent iron nanoparticles.Unknown.
Perfluorinated compounds (PFCs)Used to make stain repellents (such as Teflon), and in the manufacture of paints, adhesives, waxes, polishes, metals, electronics, fire-fighting foams, and caulks as well as grease-proof coatings for packaging. Diet is the main route of exposure, followed by drinking water, house dust, and air.Different types. The most common are perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS).Liver, pancreatic, and testicular tumor in animals. Inmunotoxicity (DeWitt et al. 2012), thyroid function disruption (Boas et al. 2012; Melzer et al. 2010).
Pesticide transformation by-productsResult from the hydrolysis, oxidation, biodegration, or photolysis of pesticides. Can be present at higher levels than the parent compound and can be as toxic or more toxic. Diet is a source of exposure.Several chemicals, such as alachlor ethanesulfonic acid (ESA), alachlor oxanilic acid (OA), acetochlor ESA, acetochlor OA, metolachlor ESA, metolachlor OA, 3-hydroxycarbofuran, and terbufos sulfone.Unknown.
PharmaceuticalsHuman consumption > excretion > urban wastewater > natural waters > drinking-­water source.Several chemicals, including antidepressants, antiviral drugs, glucocorticoids, antimycotics, antibiotics, beta-blockers.The effect of the mixture is unknown.
SiloxanesUsed in cosmetics, deodorants, soaps, hair conditioners, hair dyes, car waxes, baby pacifiers, cookware, cleaners, furniture polishes, and water-repellent windshield coatings.Cyclic siloxanes [octamethylcyclotetrasiloxane (D4), decamethylcyclopentasiloxane (D5), dodecamethylcyclohexasiloxane (D6), and tetradecamethylcycloheptasiloxane (D7)] and linear siloxanes.Unknown.
Sunscreens/ultraviolet filtersPersonal care products > urban wastewater > natural waters > drinking-­water source. Identified in drinking water (in Barcelona, Spain) with average concentrations up to 295 ng/L (Díaz-Cruz et al. 2012).Several chemicals. The ones identified in drinking water are benzophenone-3 (BP3), octocrylene (OC), 2-ethylhexyl 4-methoxycinnamate (EHMC), 3-(4-methylbenzylidene) camphor (4-MBC), and 2-ethylhexyl 4-(dimethylamino) benzoate (OD-PABA).Unknown.
Single chemicals
DioxaneHigh-production chemical used as a solvent stabilizer in the manufacture and processing of paper, cotton, textile products, automotive coolants, cosmetics, and shampoos and as a stabilizer of 1,1,1-trichloroethane (a degreasing agent).1,4-Dioxane. Regulated by U.S. EPA (50 mg/L).Unknown.
PerchlorateHighly stable and soluble chemical used in solid propellants in rockets, missiles, and fireworks as well as in highway flares. Can be found as a contaminant in sodium hypochlorite. Perchlorate can accumulate in plants and has been found in biological samples.PerchlorateUnknown. Perchlorate can cross the placenta.

Global Indicators of Toxicity

Water supplies often include mixtures of chemical contaminants that vary in time and space. In addition, the epidemiological and toxicological evaluation of mixtures involves significant challenges, in many cases beyond the limits of current research methods. In vitro bioassays (or biosensors) developed through toxicological research are promising tools for measuring the global toxicity of chemical mixtures in water samples and may be coupled with more in-depth analysis of specific contaminants when a positive response is detected. For example, Jeong et al. (2012) evaluated in vitro mammalian cell toxicity for a range of DBPs in an attempt to identify specific DBPs responsible for genomic DNA damage. End points that can be measured by in vitro bioassays include mutagenicity (Ames test) (Richardson et al. 2010), genotoxicity (micronuclei, Comet assay) (Plewa et al. 2010), endocrine disruption (DR-CALUX bioassay) (Brand et al. 2013; Sato et al. 2010), and cytotoxicity (Plewa et al. 2010). Although the use of these markers is not without limitations (such as the need for complex and nonstandardized sample pretreatment methods in order to obtain concentrates before laboratory analysis and the uncertain validity for some of the assays, limited throughput development, elevated cost, low sensitivity, and results reflecting only short-term exposure evaluations). Further development of these techniques and their incorporation into epidemiological research may improve our understanding of the effects of mixtures. These efforts will require improved, interdisciplinary communication and collaboration including analytical chemists, toxicologists, and epidemiologists.

Human Exposure

Accurate exposure assessment in human observational studies is essential to obtain valid results and constitutes a main methodological challenge, as summarized in Table 3. Difficulties in identifying and measuring contaminants in water supplies at very low concentrations and substances occurring in mixtures hamper the evaluation of human exposure, requiring new methods in health risk analysis (Schwarzenbach et al. 2006).
Table 3 Challenges of exposure assessment for chemical contaminants in drinking water.
Low exposure levelsAccuracy of analytical measurements in water is particularly important at the low range of exposure. In addition, detailed personal information of water use behavior is convenient.
Chemicals occurring in mixturesExamples include pharmaceutical residues and disinfection by-products. Depending on the individual constituents of the mixture, chemical-by-chemical exposure assessment may not be feasible or could result in simplistic exposure estimates.
Time–space variabilityRepeated measurements and distribution of sampling points covering different water zones is necessary to evaluate geographical and temporal variation during the relevant exposure period.
Long-term exposure windowsLonger exposure periods are likely to result in greater exposure misclassification. In the case of chronic diseases such as cancer, data collection must include accurate location of study participants (residence and workplace) and water use over the duration of an exposure period relevant to disease etiology. Combined with environmental levels, quantitative estimation of exposure can be conducted. An added challenge is the lack of historical monitoring data.
Lack of monitoring dataThis is particularly problematic to evaluate some exposures (such as emerging contaminants) and some outcomes (such as cancer because historical records are frequently unavailable). More research is needed to develop validated simulation models that can be used to estimate levels and exposure over the relevant time period.
Lack of validated biomarkers of exposureCurrently available validated biomarkers typically reflect recent exposures and thus may not be useful for outcomes with latency periods longer than the half-life of the biomarker compound. Exceptions may occur if the time between consecutive exposure events is shorter than the elimination half-life or exposure can be regarded as constant within the relevant time window (such as for trichloroacetic acid).
Multiple exposure routes (ingestion, inhalation, dermal absorption)Exposure to a number of water contaminants can occur through multiple routes. For example, some DBPs can be incorporated through inhalation, dermal absorption and ingestion. For other waterborne contaminants, such as nitrate (at levels in water < 50 mg/L) and per- and polyfluorinated compounds, diet is the main source of exposure (Ericson Jogsten 2011; IARC 2010). For such contaminants, exposure by all plausible routes should be assessed in order to produce the most accurate estimate of disease risk.
DBPs are an example of chemicals occurring in complex mixtures, and this has been addressed in part by using a few compounds as surrogates for the DBP mixture as a whole. For example, observational studies of human DBP exposures and health effects have focused on a small subset of the several hundred DBPs that may occur in public water supplies (Richardson et al. 2007), particularly the THMs and haloacetic acids (HAAs) (Hinckley et al. 2005; Hoffman et al. 2008; Righi et al. 2012). However, although these compounds are often used as a surrogate for other DBPs, the assumption that they correlate with other DBPs is not universally supported, and correlations can vary in time and space (Villanueva et al. 2012).
Methods of exposure assessment are influenced by the specific outcome under study. For instance, for end points with a long latency, such as cancer, long time periods of more than several decades need to be evaluated, whereas for reproductive outcomes, it is very important to accurately capture the temporal variation in exposure over a shorter period covering the relevant time windows before and during gestation.
Chemicals or metabolites have been measured in biological samples in epidemiological studies to estimate exposures [e.g., urinary or toenail arsenic measurements in cancer studies (Karagas et al. 2004)]. Urinary trichloroacetic acid is a promising biomarker of DBPs that requires methodological development before a generalized use in epidemiological studies (Savitz 2012). In addition, among the available biomarkers specific for drinking-water contaminants, many have short half-lives (e.g., urinary trichloroacetic acid) and are thus of limited value to associate with health outcomes that require long-term exposures (Savitz 2012). Consequently, exposure assessment in most instances relies on assessing personal behavior (ascertained through questionnaires) and measuring environmental levels of the chemicals (Hoffman et al. 2008; Levallois et al. 2012).
Inhalation and dermal contact may be relevant exposure routes for volatile or skin-permeable chemicals. In such cases, activities involving different water uses at home (e.g., showering, bathing), in recreation (e.g., swimming in pools), and through occupations involving water contact should be considered.
Alternative methods of exposure assessment may involve statistical modeling; for example, modeling based on known geographic distributions of contaminants (Toledano et al. 2005), hydrological modeling of underground plumes of contaminants (Gallagher et al. 2010), and/or the use of surrogate parameters such as land use (Aschebrook-Kilfoy et al. 2012). Several methods can be used in combination, tailored to the availability of data; for example, in a recent study on the long-term exposure to arsenic and cancer, Nuckols et al. (2011) combined arsenic data from their own measurements in water samples collected at homes of the participants, data from public water utilities, and historical data for aquifers.
Exposure estimates with minimal measurement error are necessary to produce valid effect estimates. Misclassification of exposure is of particular concern at the low exposure range because it tends, under most scenarios, to attenuate associations toward the null (Cantor and Lubin 2007; Waller et al. 2001) or to reduce the precision of associations (Wright and Bateson 2004). Strategies to minimize measurement error are necessary from study design to data analysis, and include, for example, the collection of repeated measures of individual water use over the relevant exposure period (Forssen et al. 2009) and assessing reliability of interviews to exclude unreliable questionnaires (Villanueva et al. 2009).

Health Effects

The following is an overview of epidemiological findings from individual-based studies of chemical contaminants in water and cancer. Table 4 displays a summary of the evidence of carcinogenicity as evaluated and concluded by the WHO International Agency for Research on Cancer (IARC).
Table 4 Evidence of carcinogenicity as concluded by the IARC for some chemicals whose main pathway of human exposure is through drinking water [modified from the General Remarks to IARC Monograph, Volume 101 (IARC 2012b)].
AgentHuman evidenceAnimal evidenceOverall evaluationa (group)IARC Monograph
ArsenicSufficientSufficient1Vol. 100 C (IARC 2012a)
FluorideInadequateInadequate3Suppl. 7 (IARC 1987)
NitrateInadequateInadequate/sufficientb2AcVol. 94 (IARC 2010)
Microcystin-LRInadequateInadequate2BVol. 94 (IARC 2010)
DBPs: Trihalomethanes
ChloroformInadequateSufficient2BVol. 73 (IARC 1999)
BromodichloromethaneInadequateSufficient2BVol. 52 (IARC 1991)
DibromochloromethaneInadequateLimited3Vol. 52 (IARC 1991)
BromoformInadequateLimited3Vol. 52 (IARC 1991)
DBPs: Haloacetic acids
Dichloroacetic acidInadequateSufficient2BVol. 106 (IARC 2013)
Trichloroacetic acidInadequateSufficient2BVol. 106 (IARC 2013)
Bromochloroacetic acidInadequateSufficient2BVol. 101 (IARC 2012b)
Dibromoacetic acidInadequateSufficient2BVol. 101 (IARC 2012b)
DBPs: Halogenated acetonitriles
BromochloroacetonitrileNo dataInadequate3Vol. 52 (IARC 1991)
ChloroacetonitrileNo dataInadequate3Vol. 52 (IARC 1991)
DibromoacetonitrileNo dataInadequate3Vol. 52 (IARC 1991)
DichloroacetonitrileNo dataInadequate3Vol. 52 (IARC 1991)
TrichloroacetonitrileNo dataInadequate3Vol. 52 (IARC 1991)
DibromoacetonitrileNo dataSufficient2BVol. 101 (IARC 2012b)
Chloral hydrateInadequateSufficient2AVol. 106 (IARC 2013)
MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone)InadequateLimited2BdVol. 84 (IARC 2004)
Bromate (evaluated as potassium bromate)InadequateSufficient2BVol. 73 (IARC 1999)
Chlorite (evaluated as sodium chlorite)No dataInadequate3Vol. 52 (IARC 1991)
Chlorinated drinking waterInadequateInadequate3Vol. 52 (IARC 1991)
Chemicals used in the disinfection of drinking water
Hypochlorite saltsNo dataInadequate3Vol. 52 (IARC 1991)
ChloramineInadequateInadequate3Vol. 84 (IARC 2004)
aGroup 1 (the agent is carcinogenic to humans), 2A (the agent is probably carcinogenic to humans), 2B (the agent is possibly carcinogenic to humans), 3 (the agent is not classifiable as to its carcinogenicity to humans). bThere is sufficient evidence in experimental animals for the carcinogenicity of nitrite in combination with amines or amides. cIngested nitrate or nitrite under conditions that result in endogenous nitrosation is probably carcinogenic to humans. dOther relevant data were used to upgrade the evaluation.
There is sufficient evidence in humans that arsenic in drinking water causes cancers of the urinary bladder, lung, and skin (IARC 2004). Studies conducted in areas with lower levels of arsenic in drinking water (i.e., at or below the MCL) have reported inconsistent results, and cancer risks associated with exposure to low arsenic levels over decades remain uncertain.
Bladder cancer has been consistently associated with DBP exposure (Cantor 2010), and pooled analyses combining data from studies conducted in different countries have reported associations between bladder cancer and THM at levels below current MCLs (Costet et al. 2011; Villanueva et al. 2004). Some (Cragle et al. 1985; King et al. 2000; Wilkins and Comstock 1981), but not all (Doyle et al. 1997; Hildesheim et al. 1998; Koivusalo et al. 1997), studies of DBP exposure and colon cancer have reported positive associations. Similarly, positive associations for DBP exposure have been found for rectal cancer (Bove et al. 2007; Doyle et al. 1997; Hildesheim et al. 1998) not replicated in other studies (King et al. 2000; Koivusalo et al. 1997; Wilkins and Comstock 1981).
The epidemiological investigation for nitrate and cancer has been challenging. Drinking water may be a primary source of nitrate exposure when drinking-water concentrations are > 50 mg/L (IARC 2010). Below this threshold, diet is the main exposure route, involving complex mechanisms of action through endogenous formation of N-nitroso compounds (IARC 2010). Long-term exposure to nitrate in drinking water has been evaluated in relation to multiple cancer sites including the esophagus, stomach, bladder, and colon (IARC 2010). Although there is inadequate human evidence for carcinogenicity, there is sufficient evidence from experimental animals for the carcinogenicity of nitrite in combination with amines or amides, and ingested nitrate under conditions that result in endogenous nitrosation has been classified as probably carcinogenic to humans (IARC 2010).
Other contaminants have been less extensively investigated in relation to cancer risk. Fluoride is added to drinking water at low concentrations in some countries to prevent dental caries, and naturally occurs in water at higher levels in certain parts of the world such as the Rift Valley in Africa (Malde et al. 2011). The IARC (1987) evaluated fluoride carcinogenicity and concluded that human and animal evidence was inadequate (Table 3). Some epidemiological studies on osteosarcoma have been published after this evaluation (Bassin et al. 2006; Kim et al. 2011), but consistent associations have not been observed.
The liver is a target organ for microcystin-LR (IARC 2010), which are toxins produced by cyanobacteria as a result of algae blooms and the eutrophication of surface waters. Individual-based studies evaluated by IARC (2010) have assessed exposure by comparing water consumed from ponds or ditches versus other sources and no measurements of toxins or bacteria were considered. In consequence, IARC concluded that evidence in humans for the carcinogenicity of microcystin-LR is inadequate (IARC 2010). Other carcinogens such as heavy metals, pesticides, and solvents may occur in drinking water as a consequence of human activities and natural hydrogeochemical processes. However, evidence on the cancer risk on human populations is limited.

Mechanisms and Biomarkers

The elucidation of mechanisms of action to provide biological plausibility and support causality suggested by epidemiological associations is a priority in current research. Biomarkers of early effect can be used in epidemiological studies to provide evidence about subclinical or intermediate effects of exposures (e.g., cytogenetic changes), and effects of very low exposure levels, and they can be used in experimental studies to evaluate the effect of an intervention. For an intermediate biomarker to be informative, it should be associated with both the disease and exposure of interest and reflect an intermediate step in the pathway between exposure and disease. For example, a suggested mechanism of action for arsenic is through epigenetic dysregulation, although there are limited human studies available (Ren et al. 2011). In addition, the evaluation of genetic variants may be used to identify susceptible populations underlying the biological mechanisms of action. For example, the evaluation of genetic variants of DBP-metabolizing enzymes in an epidemiological study on bladder cancer and THM exposure has shown that polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk (Cantor et al. 2010). In addition, the consistency of these findings with experimental observations of GSTT1 (glutathione S-transferase theta 1), GSTZ1 (glutathione S-transferase zeta 1), and CYP2E1 (cytochrome P450, family 2, subfamily E, polypeptide 1) enzymatic activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms, as well as the classes of compounds likely to be implicated (Cantor et al. 2010).
There are few validated biomarkers specific for chemical contaminants in drinking water. However, the availability of prospective studies with biobanked samples and biotechnological development allowing large numbers of compounds to be measured in small amounts of biological samples (e.g., urine, plasma, serum) is encouraging. These technologies include genomics, epigenomics, transcriptomics, adductomics, proteomics, and metabolomics (Rappaport and Smith 2010; Wild 2005). Application of these techniques will facilitate a comprehensive approach to identify perturbations in biological systems and associated mechanisms of action (Moore et al. 2013). These technologies have not been widely applied in water research but have shown promising results in other areas of environmental research.

Future Challenges

A significant and growing body of evidence suggests that climate change will have a detrimental effect on the quality of water available for human consumption in the future. For example, increasing temperatures may enhance conditions for the proliferation of cyanobacteria and algae (Joehnk et al. 2008; Newcombe et al. 2012; Paerl and Huisman 2008). Cyanobacteria are of particular concern for human populations because they can produce cyanotoxins such as microcystin that have carcinogenic effects (IARC 2010). The frequency of extreme weather events is expected to increase as a consequence of climate change, and the concentrations of chemical contaminants may be affected by extreme precipitation events. For example, tests conducted in models of different types of soils showed that certain mobile pharmaceuticals occur at higher concentrations in soil and groundwater during and directly after intense precipitation events (Oppel et al. 2004). Simulation studies have shown that pesticide concentrations fluctuate with changes in precipitation intensity and seasonality (Bloomfield et al. 2006; Probst et al. 2005). Evidence concerning the effect of drought is mixed. For example, concentrations of heavy metals (e.g., chrome, mercury, lead, cadmium) introduced primarily from anthropogenic activities in the Rhine River basin are higher during drought years (Zwolsman and van Bokhoven 2007). In contrast, no significant changes during drought conditions, but significant variability between seasons, has been described in the Dommel River, a tributary of the Meuse river in the Netherlands where increased groundwater flow in winter led to increased metal concentrations (Wilbers et al. 2009). In summary, it is expected that climate change could adversely affect drinking-water quality, but there is limited knowledge concerning the magnitude and distribution of the impact at different scales (global, regional, local).

Final Remarks and Recommendations

General aspects. Although microbiological contamination is the largest contribution to waterborne disease and mortality at a global scale, chemical contaminants in water supplies also can cause disease, sometimes after long periods of exposure. The concentrations in drinking water, the prevalence of human exposure in the population, and the level of toxicity can be used to prioritize chemicals for further research. These characteristics may vary geographically and, therefore, further research should be designed to local-, region-, or country-specific circumstances as appropriate. Finally, exposures and risks affecting vulnerable populations (e.g., children and pregnant women) require special attention and are of particular interest.
Arsenic is a unique example of a substance in drinking water with conclusive evidence from human epidemiological studies. There is no doubt that arsenic is a human carcinogen at high concentrations (IARC 2004); however, there is inadequate information to determine the carcinogenic potential of other chemicals that occur in drinking water (Table 4). Arsenic has several unique characteristics—including the fact that drinking water represents the predominant source of exposure in humans; the levels in water, and thus the magnitude of the exposure, is very high in certain areas (e.g., Bangladesh); the availability of measurements in drinking water has allowed the development of epidemiological studies; the wide variability in exposures facilitates the detection of risks; the occurrence as an isolated substance rather than in mixtures allows the direct measurement of the putative agent; the magnitude of the risks are high compared with other chemicals; and the existence of biomarkers—all of which have helped to improve exposure assessment and elucidation of mechanisms of action of arsenic.
Recommendations on occurrence and exposure assessment. Improved exposure assessment to water contaminants is essential to derive valid exposure–response curves and useful knowledge for risk assessment and regulation, and here we provide some suggestions.
The research need concerning regulated chemicals is to clarify the effects at or below their MCLs, which are suspected for some contaminants. Access to water utility monitoring data, which is necessary to conduct such studies, should be encouraged and facilitated. Access to large databases would facilitate improved exposure assessment in epidemiological studies, if the data are reliable and sufficient to evaluate temporal and geographical variations applicable to study areas.
The measurement of emerging contaminants needs advanced and specialized analytical methods, and close collaboration between epidemiologists and analytical chemists is required to provide contaminant occurrence data suitable in format and quantity for epidemiological research. Better communication between epidemiologists and environmental analytical chemists would facilitate human health studies in this area. A mechanism to converge interests might be to collect water samples for analytical chemistry method development alongside ongoing epidemiological studies, or training analytical chemists in exposure assessment procedures.
The evaluation of mixtures requires some attention in future studies because this remains a challenge beyond current methods. New developments may contribute to understand the health effects of chemical contaminants in drinking water.
Some in vitro assays as indicators of water toxicity are promising tools deserving incorporation in future studies to complement exposure assessment and health risk analyses. These bioassays may be especially effective to evaluate the global effect of chemical mixtures and identify “hot spots” of toxicity. Such findings can be useful in generating hypotheses for more in-depth and resource-intensive analysis of specific contaminants and health outcomes. Incorporating these methods in epidemiological research should be encouraged, and further validation should be conducted when necessary.
Epidemiological research generally requires large numbers of measurements and data. This may constitute a challenge in the collaboration with analytical chemists and toxicologists if experimental methods are manual or laborious but should be overcome in the future with, for example, the development of high-throughput techniques able to analyze large amounts of water samples.
Ongoing cohort studies should be encouraged to incorporate a water dimension because retrospective assessment is challenging, particularly for outcomes with a long latency such as cancer. This would require water sample collection, measurements, and personal questionnaires in ongoing cohort studies, and new or reinforced collaborations between research groups. New cohorts (or data collections in existing cohorts) should be also encouraged to implement environmental sampling and storage of such samples (envirobanking) for use in future nested case–control studies.
Methods developed for environmental and geospatial sciences, including geographical information systems and fate/transport modeling of chemicals, have been demonstrated to be useful in exposure assessment for risk analysis for waterborne chemical contaminants. Consequently, greater emphasis on incorporating these methodologies into environmental epidemiological studies should be made.
Climate change is likely to affect water quality with uncertain implications for human health. Research to evaluate these impacts and the potential human health consequences at different regional scales and in different climates is necessary.
Recommendations on epidemiological methods. Epidemiological studies based on rigorous study design are essential to properly evaluate the human health risks associated with chemical contaminants in drinking water. Here we summarize some suggestions in this direction.
There is a need to investigate the potential health outcomes of emerging (i.e., non-regulated) contaminants because current knowledge on health effects is mainly limited to regulated chemicals. However, there are still uncertainties and further research is needed to evaluate potential effects below MCLs for certain regulated chemicals.
Studies capturing widely contrasting exposure levels are particularly useful to estimate risks. Therefore, environmental epidemiologists should influence the decision as to the location of study sites on this basis.
Large studies with sufficient statistical power are necessary when the expected health risks are small in magnitude. It is advisable to know contaminant levels and exposure prevalence before undertaking an epidemiological study to allow the estimation of sample size to reach sufficient statistical power.
The incorporation of biomarkers of exposure, effect, and genetic susceptibility in epidemiological studies is encouraged to identify molecular mechanisms of action and to contribute to the assessment of causality. Studies evaluating biomarkers could be companion studies within ongoing larger or small- to medium-sized experimental studies. In particular, -omic technologies can add to the current understanding of biological mechanisms and generate new hypotheses, requiring advanced and complex statistical tools to deal with the large amounts of data generated. However, biomarkers must be validated and biomarker studies generally require large numbers of observations and replication in multiple populations. Additional drawbacks of biomarker studies are the relatively high cost, the limitation of biomarkers with regard to capturing past exposures, their invasiveness, and the possibility for reverse causation (i.e., in cross-sectional or case–control studies).
General conclusions. Assessing the health impacts of chemical contaminants in drinking water is a challenge that requires improved methodologies and enhanced interdisciplinarity in future epidemiological studies. Useful and valuable knowledge will increase if future studies successfully integrate existing and new developments from analytical chemistry, toxicology, exposure science, molecular epidemiology, statistics, environmental epidemiology, environmental sciences, engineering, and geospatial sciences. Improved cooperation and collaboration with stakeholders such as the water industry, regulatory, and public health agencies and affected communities would serve to produce higher-quality risk analyses, as well as to improve the likelihood of implementing effective and early intervention measures. Institutional support promoting access to reliable routine monitoring data at all levels and collaboration with stakeholders (e.g., water utilities, regulators, and consumer groups) would be beneficial. Finally, research efforts in this area are frequently hampered by the lack of specific funding for this research field, and the availability of stable and substantial financial support is needed, either from governmental or nongovernmental sources.


Aschebrook-Kilfoy B, Heltshe SL, Nuckols JR, Sabra MM, Shuldiner AR, Mitchell BDet al. 2012. Modeled nitrate levels in well water supplies and prevalence of abnormal thyroid conditions among the Old Order Amish in Pennsylvania. Environ Health 11:6;
Bassin EB, Wypij D, Davis RB, Mittleman MA. 2006. Age-specific fluoride exposure in drinking water and osteosarcoma (United States). Cancer Causes Control 17:421-428
Bloomfield JP, Williams RJ, Gooddy DC, Cape JN, Guha P. 2006. Impacts of climate change on the fate and behaviour of pesticides in surface and groundwater—a UK perspective. Sci Total Environ 369:163-177
Boas M, Feldt-Rasmussen U, Main KM. 2012. Thyroid effects of endocrine disrupting chemicals. Mol Cell Endocrinol 355:240-248
Bove GE, Rogerson PA, Vena JE. 2007. Case control study of the geographic variability of exposure to disinfectant byproducts and risk for rectal cancer. Int J Health Geogr 6:18;
Brand W, de Jongh CM, van der Linden SC, Mennes W, Puijker LM, van Leeuwen CJet al. 2013. Trigger values for investigation of hormonal activity in drinking water and its sources using CALUX bioassays. Environ Int 55:109-118
Cantor KP. 2010. Carcinogens in drinking water: the epidemiologic evidence. Rev Environ Health 25:9-16
Cantor KP, Lubin JH. 2007. Arsenic, internal cancers, and issues in inference from studies of low-level exposures in human populations. Toxicol Appl Pharmacol 222:252-257
Cantor KP, Villanueva CM, Silverman DT, Figueroa JD, Real FX, Garcia-Closas Met al. 2010. Polymorphisms in GSTT1, GSTZ1, and CYP2E1, disinfection by-products, and risk of bladder cancer in Spain. Environ Health Perspect 118:1545-1550;
Costet N, Villanueva CM, Jaakkola JJ, Kogevinas M, Cantor KP, King WDet al. 2011. Water disinfection by-products and bladder cancer: Is there a European specificity? A pooled and meta-analysis of European case–control studies. Occup Environ Med 68:379-385
Cragle DL, Shy CM, Struba RJ, Siff EJ. 1985. A case-control study of colon cancer and water chlorination in North Carolina. In: Water Chlorination: Chemistry, Environmental Impact and Health Effects, Vol. 5 (Jolley RL, Bull RJ, Davis WP, Katz S, Roberts MH Jr, Jakobs VA, eds). Chelsea, MI Lewis Publishers, 153–160.
DeWitt JC, Peden-Adams MM, Keller JM, Germolec DR. 2012. Immunotoxicity of perfluorinated compounds: recent developments. Toxicol Pathol 40:300-311
Díaz-Cruz MS, Gago-Ferrero P, Llorca M, Barceló D. 2012. Analysis of UV filters in tap water and other clean waters in Spain. Anal Bioanal Chem 402:2325-2333
Dingemans MM, van den Berg M, Westerink RH. 2011. Neurotoxicity of brominated flame retardants: (in)direct effects of parent and hydroxylated polybrominated diphenyl ethers on the (developing) nervous system. Environ Health Perspect 119:900-907;
Doyle TJ, Zheng W, Cerhan JR, Hong CP, Sellers TA, Kushi LHet al. 1997. The association of drinking water source and chlorination by-products with cancer incidence among postmenopausal women in Iowa: a prospective cohort study. Am J Public Health 87:1168-1176
Ericson I, Nadal M, van Bavel B, Lindstrom G, Domingo JL. 2008. Levels of perfluorochemicals in water samples from Catalonia, Spain: Is drinking water a significant contribution to human exposure? Environ Sci Pollut Res Int 15:614-619
Ericson Jogsten I. 2011. Assessment of Human Exposure to Per- and Polyfluorinated Compounds (PFCs). Exposure through Food, Drinking Water, House Dust and Indoor Air [PhD Dissertation]. Örebro, Sweden:Örebro University.
EU (European Union) Council. 1998. Council Directive 98/83/EC of 3 November 1998 on the Quality of Water Intended for Human Consumption. Available: [accessed 23 July 2013].
Forssen UM, Wright JM, Herring AH, Savitz DA, Nieuwenhuijsen MJ, Murphy PA. 2009. Variability and predictors of changes in water use during pregnancy. J Expo Sci Environ Epidemiol 19:593-602
Frisbie SH, Mitchell EJ, Dustin H, Maynard DM, Sarkar B. 2012. World Health Organization discontinues its drinking-water guideline for manganese. Environ Health Perspect 120:775-778.;
Gallagher LG, Webster TF, Aschengrau A, Vieira VM. 2010. Using residential history and groundwater modeling to examine drinking water exposure and breast cancer. Environ Health Perspect 118:749-755;
Hildesheim ME, Cantor KP, Lynch CF, Dosemeci M, Lubin J, Alavanja Met al. 1998. Drinking water source and chlorination byproducts. II. Risk of colon and rectal cancers. Epidemiology 9:29-35
Hinckley AF, Bachand AM, Reif JS. 2005. Late pregnancy exposures to disinfection by-products and growth-related birth outcomes. Environ Health Perspect 113:1808-1813;
Hoffman CS, Mendola P, Savitz DA, Herring AH, Loomis D, Hartmann KEet al. 2008. Drinking water disinfection by-product exposure and fetal growth. Epidemiology 19:729-737
Huerta-Fontela M, Galceran MT, Ventura F. 2008. Stimulatory drugs of abuse in surface waters and their removal in a conventional drinking water treatment plant. Environ Sci Technol 42:6809-6816
IARC (International Agency for Research on Cancer). 1987. Supplement 7. Overall Evaluations of Carcinogenicity: An Updating of IARC Monographs Volumes 1 to 42. IARC Monogr Eval Carcinog Risk Hum Suppl 7. Available: [accessed 26 July 2013].
IARC (International Agency for Research on Cancer). 1991. Chlorinated Drinking-water; Chlorination By-products; Some Other Halogenated Compounds; Cobalt and Cobalt Compounds. IARC Monogr Eval Carcinog Risk Hum 52. Available: [accessed 15 January 2014].
IARC (International Agency for Research on Cancer). 1999. Some Chemicals that Cause Tumours of the Kidney or Urinary Bladder in Rodents and Some Other Substances. IARC Monogr Eval Carcinog Risk Hum 73. Available: [accessed 15 January 2014].
IARC (International Agency for Research on Cancer). 2004. Some Drinking-water Disinfectants and Contaminants, including Arsenic. IARC Monogr Eval Carcinog Risk Hum 84. Available: [accessed 26 July 2013].
IARC (International Agency for Research on Cancer). 2010. Ingested Nitrate and Nitrite, and Cyanobacterial Peptide Toxins. IARC Monogr Eval Carcinog Risk Hum 94. Available: [accessed 26 July 2013].
IARC (International Agency for Research on Cancer). 2012a. Review of Human Carcinogens: Arsenic, Metals, Fibres, and Dusts. IARC Monogr Eval Carcinog Risk Hum 100 C. Available: [accessed 15 January 2014].
IARC (International Agency for Research on Cancer). 2012b. Some Chemicals Present in Industrial and Consumer Products, Food and Drinking-water. IARC Monogr Eval Carcinog Risk Hum 101. Available: [accessed 21 January 2014].
IARC (International Agency for Research on Cancer). 2013. Trichloroethylene, Tetrachloroethylene and Some Other Chlorinated Agents. IARC Monogr Eval Carcinog Risk Hum 106. Available: [accessed 17 January 2014].
Jeong CH, Wagner ED, Siebert VR, Anduri S, Richardson SD, Daiber EJet al. 2012. Occurrence and toxicity of disinfection byproducts in European drinking waters in relation with the HIWATE Epidemiology Study. Environ Sci Technol 46:12120-12128
Joehnk KD, Huisman J, Sharples J, Sommeijer B, Visser PM, Stroom JM. 2008. Summer heatwaves promote blooms of harmful cyanobacteria. Global Change Biology 14:495-512.
Karagas MR, Tosteson TD, Morris JS, Demidenko E, Mott LA, Heaney Jet al. 2004. Incidence of transitional cell carcinoma of the bladder and arsenic exposure in New Hampshire. Cancer Causes Control 15:465-472
Kim FM, Hayes C, Williams PL, Whitford GM, Joshipura KJ, Hoover RNet al. 2011. An assessment of bone fluoride and osteosarcoma. J Dent Res 90:1171-1176
King WD, Marrett LD, Woolcott CG. 2000. Case-control study of colon and rectal cancers and chlorination by-products in treated water. Cancer Epidemiol Biomarkers Prev 9:813-818
Koivusalo M, Pukkala E, Vartiainen T, Jaakkola JJ, Hakulinen T. 1997. Drinking water chlorination and cancer—a historical cohort study in Finland. Cancer Causes Control 8:192-200
Levallois P, Gingras S, Marcoux S, Legay C, Catto C, Rodriguez Met al. 2012. Maternal exposure to drinking-water chlorination by-products and small-for-gestational-age neonates. Epidemiology 23:267-276
Ljung K, Vahter M. 2007. Time to re-evaluate the guideline value for manganese in drinking water? Environ Health Perspect 115:1533-1538;
Malde MK, Scheidegger R, Julshamn K, Bader HP. 2011. Substance flow analysis: a case study of fluoride exposure through food and beverages in young children living in Ethiopia. Environ Health Perspect 119:579-584;
Melzer D, Rice N, Depledge MH, Henley WE, Galloway TS. 2010. Association between serum perfluorooctanoic acid (PFOA) and thyroid disease in the U.S. National Health and Nutrition Examination Survey. Environ Health Perspect 118:686-692;
Moore LE, Karami S, Steinmaus C, Cantor KP. 2013. Use of OMIC technologies to study arsenic exposure in human populations. Environ Mol Mutagen 54:589-595
Newcombe G, Chorus I, Falconer I, Lin TF. 2012. Cyanobacteria: impacts of climate change on occurrence, toxicity and water quality management. Water Res 46:1347-1348
Nuckols JR, Freeman LE, Lubin JH, Airola MS, Baris D, Ayotte JDet al. 2011. Estimating water supply arsenic levels in the New England Bladder Cancer Study. Environ Health Perspect 119:1279-1285;
Oppel J, Broll G, Löffler D, Meller M, Römbke J, Ternes T. 2004. Leaching behaviour of pharmaceuticals in soil-testing-systems: a part of an environmental risk assessment for groundwater protection. Sci Total Environ 328:265-273
Paerl HW, Huisman J. 2008. Climate. Blooms like it hot. Science 320:57-58
Pham TP, Cho CW, Yun YS. 2010. Environmental fate and toxicity of ionic liquids: a review. Water Res 44:352-372
Plewa MJ, Muellner MG, Richardson SD, Fasano F, Buettner KM, Woo YTet al. 2008a. Occurrence, synthesis, and mammalian cell cytotoxicity and genotoxicity of haloacetamides: an emerging class of nitrogenous drinking water disinfection byproducts. Environ Sci Technol 42:955-961
Plewa MJ, Simmons JE, Richardson SD, Wagner ED. 2010. Mammalian cell cytotoxicity and genotoxicity of the haloacetic acids, a major class of drinking water disinfection by-products. Environ Mol Mutagen 51:871-878
Plewa MJ, Wagner ED, Muellner MG, Hsu KM, Richardson SD. 2008b. Comparative mammalian cell toxicity of N-DBPs and C-DBPs. In: Disinfection By-Products in Drinking Water: Occurrence, Formation, Health Effects and Control (Karanfil T, Krasner S, Westerhoff P, Xie Y (eds). ACS Symposium Series 995. Washington, DC American Chemical Society, 36–50.
Plewa MJ, Wagner ED, Richardson SD, Thurston AD, Woo YT, McKague AB. 2004. Chemical and biological characterization of newly discovered iodoacid drinking water disinfection byproducts. Environ Sci Technol 38:4713-4722
Post GB, Cohn PD, Cooper KR. 2012. Perfluorooctanoic acid (PFOA), an emerging drinking water contaminant: a critical review of recent literature. Environ Res 116:93-117
Probst M, Berenzen N, Lentzen-Godding A, Schulz R. 2005. Scenario-based simulation of runoff-related pesticide entries into small streams on a landscape level. Ecotoxicol Environ Saf 62:145-159
Prüss-Üstün A, Bos R, Gore F, Bartram J. 2008. Safer Water, Better Health: Costs, Benefits and Sustainability of Interventions to Protect and Promote Health. Geneva:World Health Organization. Available: [accessed 26 July 2013].
Rappaport SM, Smith MT. 2010. Epidemiology. Environment and disease risks. Science 330:460-461
Ren X, McHale CM, Skibola CF, Smith AH, Smith MT, Zhang L. 2011. An emerging role for epigenetic dysregulation in arsenic toxicity and carcinogenesis. Environ Health Perspect 119:11-19;
Richardson SD, DeMarini DM, Kogevinas M, Fernandez P, Marco E, Lourencetti Cet al. 2010. What’s in the pool? A comprehensive identification of disinfection by-products and assessment of mutagenicity of chlorinated and brominated swimming pool water. Environ Health Perspect 118:1523-1530;
Richardson SD, Plewa MJ, Wagner ED, Schoeny R, DeMarini DM. 2007. Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: a review and roadmap for research. Mutat Res 636:178-242
Richardson SD, Ternes TA. 2011. Water analysis: emerging contaminants and current issues. Anal Chem 83:4614-4648
Righi E, Bechtold P, Tortorici D, Lauriola P, Calzolari E, Astolfi Get al. 2012. Trihalomethanes, chlorite, chlorate in drinking water and risk of congenital anomalies: a population-based case-control study in Northern Italy. Environ Res 116:66-73
Rogers VV, Wickstrom M, Liber K, MacKinnon MD. 2002. Acute and subchronic mammalian toxicity of naphthenic acids from oil sands tailings. Toxicol Sci 66:347-355
Sato M, Takigami H, Hayakawa K, Sakai S. 2010. Water-quality monitoring technique for dioxins during dredging using on-site solid phase extraction with graphitic carbon and analysis with DR-CALUX. J Environ Sci Health A Tox Hazard Subst Environ Eng 45:867–874.
Savitz DA. 2012. Invited commentary: Biomarkers of exposure to drinking water disinfection by-products—are we ready yet? Am J Epidemiol 175:276-278
Schreurs RH, Legler J, Artola-Garicano E, Sinnige TL, Lanser PH, Seinen Wet al. 2004. In vitro and in vivo antiestrogenic effects of polycyclic musks in zebrafish. Environ Sci Technol 38:997-1002
Schriks M, Heringa MB, van der Kooi MM, de Voogt P, van Wezel AP. 2010. Toxicological relevance of emerging contaminants for drinking water quality. Water Res 44:461-476
Schwarzenbach RP, Escher BI, Fenner K, Hofstetter TB, Johnson CA, von Gunten Uet al. 2006. The challenge of micropollutants in aquatic systems. Science 313:1072-1077
Shen R, Andrews SA. 2011. Demonstration of 20 pharmaceuticals and personal care products (PPCPs) as nitrosamine precursors during chloramine disinfection. Water Res 45:944-952
Silva E, Rajapakse N, Kortenkamp A. 2002. Something from “nothing”—eight weak estrogenic chemicals combined at concentrations below NOECs produce significant mixture effects. Environ Sci Technol 36:1751-1756
Smith AH, Lopipero PA, Bates MN, Steinmaus CM. 2002. Public health. Arsenic epidemiology and drinking water standards. Science 296:2145-2146
Ternes T. 2007. The occurrence of micopollutants in the aquatic environment: a new challenge for water management. Water Sci Technol 55:327-332
Thompson T, Fawell J, Kunikane S, Darryl Jackson D, Appleyard S, Callan P, et al. 2007. Chemical Safety of Drinking-Water: Assessing Priorities for Risk Management. Geneva:World Health Organization. Available: [accessed 26 July 2013].
Toledano MB, Nieuwenhuijsen MJ, Best N, Whitaker H, Hambly P, de Hoogh Cet al. 2005. Relation of trihalomethane concentrations in public water supplies to stillbirth and birth weight in three water regions in England. Environ Health Perspect 113:225-232;
UNICEF and World Health Organization. 2011. Drinking Water Equity, Safety and Sustainability. Available: [accessed 26 July 2013].
U.S. EPA (U.S. Environmental Protection Agency). 2009. National Primary Drinking Water Regulations. Available: [accessed 23 July 2013].
Valcárcel Y, Martínez F, González-Alonso S, Segura Y, Catalá M, Molina Ret al. 2012. Drugs of abuse in surface and tap waters of the Tagus River basin: heterogeneous photo-Fenton process is effective in their degradation. Environ Int 41:35-43
Villanueva CM, Cantor KP, Cordier S, Jaakkola JJ, King WD, Lynch CFet al. 2004. Disinfection byproducts and bladder cancer: a pooled analysis. Epidemiology 15:357-367
Villanueva CM, Castano-Vinyals G, Moreno V, Carrasco-Turigas G, Aragones N, Boldo Eet al. 2012. Concentrations and correlations of disinfection by-products in municipal drinking water from an exposure assessment perspective. Environ Res 114:1-11
Villanueva CM, Silverman DT, Malats N, Tardon A, Garcia-Closas R, Serra Cet al. 2009. Determinants of quality of interview and impact on risk estimates in a case-control study of bladder cancer. Am J Epidemiol 170:237-243
Waller K, Swan SH, Windham GC, Fenster L. 2001. Influence of exposure assessment methods on risk estimates in an epidemiologic study of total trihalomethane exposure and spontaneous abortion. J Expo Anal Environ Epidemiol 11:522-531
Ward MH, deKok TM, Levallois P, Brender J, Gulis G, Nolan BTet al. 2005. Workgroup report: Drinking-water nitrate and health—recent findings and research needs. Environ Health Perspect 113:1607-1614;
WHO (World Health Organization). 2011. Guidelines for Drinking-Water Quality. 4th ed. Available: [accessed 23 July 2013].
WHO (World Health Organization). 2012. Pharmaceuticals in Drinking-Water. Available: [accessed 23 July 2013].
Wilbers GJ, Zwolsman G, Klaver G, Hendriks AJ. 2009. Effects of a drought period on physico-chemical surface water quality in a regional catchment area. J Environ Monit 11:1298-1302
Wild CP. 2005. Complementing the genome with an “exposome”: the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol Biomarkers Prev 14:1847-1850
Wilkins JR, Comstock GW. 1981. Source of drinking water at home and site-specific cancer incidence in Washington County, Maryland. Am J Epidemiol 114:178-190
Wright JM, Bateson TF. 2004. A sensitivity analysis of bias in relative risk estimates due to disinfection by-product exposure misclassification. J Expo Anal Environ Epidemiol 15:212-216
Zoni S, Lucchini RG. 2013. Manganese exposure: cognitive, motor and behavioral effects on children: a review of recent findings. Curr Opin Pediatr 25:255-260
Zwolsman JJ, van Bokhoven AJ. 2007. Impact of summer droughts on water quality of the Rhine River—a preview of climate change? Water Sci Technol 56:45-55

Information & Authors


Published In

Environmental Health Perspectives
Volume 122Issue 3March 2014
Pages: 213 - 221
PubMed: 24380896


Received: 5 November 2012
Accepted: 24 December 2013
Published online: 3 January 2014



Cristina M. Villanueva
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
Manolis Kogevinas
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
National Institute of Public Health, Athens, Greece
Sylvaine Cordier
Inserm (Institut National de la Santé et de la Recherche Médicale) UMR 1085, IRSET (Institut de Recherche Santé Environnement et Travail), Université de Rennes 1, Rennes, France
Michael R. Templeton
Imperial College London, Department of Civil and Environmental Engineering, London, United Kingdom
Roel Vermeulen
Environmental Epidemiology Division, Institute for Risk Assessment Sciences (IRAS), Utrecht University, Utrecht, the Netherlands
John R. Nuckols
Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, USA
Mark J. Nieuwenhuijsen
Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain
IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
Patrick Levallois
Université Laval, Québec, Québec, Canada
Institut National de Santé Publique du Québec, Québec, Canada
Centre de recherche du Centre hospitalier universitaire (CHU) de Québec, Québec, Canada


Address correspondence to C.M. Villanueva, CREAL–Centre for Research in Environmental Epidemiology, Barcelona Biomedical Research Park, Doctor Aiguader, 88, 08003-Barcelona (Spain). Telephone: (34) 93 214 73 44. E-mail: [email protected]

Competing Interests

The authors declare they have no actual or potential competing financial interests.

Funding Information

This review is based on a meeting funded by the European Science Foundation (EW11-006) with the collaboration of B-DEBATE (International Center for Scientific Debate, Barcelona, Spain). Participants of the workshop included the authors and A. Bernard (Catholic University of Louvain, Belgium), T. De Kok (Maastricht University, the Netherlands), J. Fawell (independent consultancy and advisory services on drinking water and environment, United Kingdom), A. Gómez (Public Health Agency of Barcelona, Spain), J. Grimalt [Institute of Environmental Assessment and Water Research (IDÆA), Spanish Council for Scientific Research (CSIC), Spain], T. Grummt (Federal Environment Agency, Germany), M. Heringa (KWR Watercycle Research Institute, the Netherlands), P. Hunter (University of East Anglia, United Kingdom), G. Lindstrom (Örebro University, Sweden), P. Marsden (Drinking Water Inspectorate, United Kingdom), M. Pedersen (CREAL, Spain), M. Plewa (University of Illinois at Urbana-Champaign, USA), E. Righi (Università degli Studi di Modena e Reggio Emilia, Italy), M. Schriks (KWR Watercycle Research Institute, the Netherlands), L. Stayner (University of Illinois, USA), F. Valero (Aigües Ter-Llobregat, Spain), E.D. Wagner (University of Illinois at Urbana-Champaign, USA), E. Zuccato (Mario Negri Institute for Pharmacological Research, Italy).

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  • In vitro bioassays for monitoring drinking water quality of tap water, domestic filtration and bottled water, Journal of Exposure Science & Environmental Epidemiology, 10.1038/s41370-023-00566-6, (2023).
  • Predicting THM Formation and Revealing Its Contributors in Drinking Water Treatment Using Machine Learning, ACS ES&T Water, 10.1021/acsestwater.3c00020, (2023).
  • Identification of Toxicity Forcing Agents from Individual Aliphatic and Aromatic Disinfection Byproducts Formed in Drinking Water: Implications and Limitations, Environmental Science & Technology, 10.1021/acs.est.2c07629, 57, 3, (1366-1377), (2023).
  • Designing Watersheds for Integrated Development (DWID): Combining hydrological and economic modeling for optimizing land use change to meet water quality regulations, Water Resources and Economics, 10.1016/j.wre.2022.100209, 41, (100209), (2023).
  • Global assessment of chemical quality of drinking water: The case of trihalomethanes, Water Research, 10.1016/j.watres.2023.119568, 230, (119568), (2023).
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