|Chemical||WHO||U.S. EPA||EU||Chemical group|
|Aldrin + dieldrin||0.03||—||—||Organic|
|Asbestos (million fibers >10 μm per liter)||—||7||—||Inorganic|
|Chloramines (as Cl2)||—||4,000||—||Disinfectant|
|2,4-D (dichlorophenoxyacetic acid)||30||70||—||Organic|
|2,4-DB (dichlorofenoxybutyric acid)||90||—||—||Organic|
|DDT (dichlorodiphenyltrichloroethane) and metabolites||1||—||—||Organic|
|Fenoprop/Silvex/2,4,5-TP/2-(2,4,5- trichlorophenoxy)propionic acid||9||50||—||Organic|
|Haloacetic acids (HAAs)c||—||60||—||DBP|
|4-(2-Methyl-4-chlorophenoxy) acetic acid (MCPA)||2||—||—||Organic|
|Polychlorinated biphenyls (PCBs)||—||0.5||—||Organic|
|Polycyclic aromatic hydrocarbons||—||—||0.10||Organic|
|Sodium dichloroisocyanurate/cyanuric acid||50,000/40,000||—||—||Disinfectant|
|Tetrachloroethylene + trichloroethylene||—||—||10||Organic|
|2,4,5-T (2,4,5-trichlorophenoxyacetic acid)||9||—||—||Organic|
|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.|
|Chemical group||Source||Chemicals||Suspected or known health effects|
|Algal toxins||Produced 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 sweeteners||Consumers > 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 retardants||Used 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).|
|Benzotriazoles||Complexing 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.|
|DBPs||Generated 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 liquids||Organic 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 drugs||Found 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.|
|Musks||Highly 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 acids||Result 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.|
|Nanomaterials||Heterogeneous 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-products||Result 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.|
|Pharmaceuticals||Human 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.|
|Siloxanes||Used 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 filters||Personal 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.|
|Dioxane||High-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.|
|Perchlorate||Highly 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.||Perchlorate||Unknown. Perchlorate can cross the placenta.|
Global Indicators of Toxicity
|Low exposure levels||Accuracy 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 mixtures||Examples 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 variability||Repeated 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 windows||Longer 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 data||This 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 exposure||Currently 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.|
|Agent||Human evidence||Animal evidence||Overall evaluationa (group)||IARC Monograph|
|Arsenic||Sufficient||Sufficient||1||Vol. 100 C (IARC 2012a)|
|Fluoride||Inadequate||Inadequate||3||Suppl. 7 (IARC 1987)|
|Nitrate||Inadequate||Inadequate/sufficientb||2Ac||Vol. 94 (IARC 2010)|
|Microcystin-LR||Inadequate||Inadequate||2B||Vol. 94 (IARC 2010)|
|Chloroform||Inadequate||Sufficient||2B||Vol. 73 (IARC 1999)|
|Bromodichloromethane||Inadequate||Sufficient||2B||Vol. 52 (IARC 1991)|
|Dibromochloromethane||Inadequate||Limited||3||Vol. 52 (IARC 1991)|
|Bromoform||Inadequate||Limited||3||Vol. 52 (IARC 1991)|
|DBPs: Haloacetic acids|
|Dichloroacetic acid||Inadequate||Sufficient||2B||Vol. 106 (IARC 2013)|
|Trichloroacetic acid||Inadequate||Sufficient||2B||Vol. 106 (IARC 2013)|
|Bromochloroacetic acid||Inadequate||Sufficient||2B||Vol. 101 (IARC 2012b)|
|Dibromoacetic acid||Inadequate||Sufficient||2B||Vol. 101 (IARC 2012b)|
|DBPs: Halogenated acetonitriles|
|Bromochloroacetonitrile||No data||Inadequate||3||Vol. 52 (IARC 1991)|
|Chloroacetonitrile||No data||Inadequate||3||Vol. 52 (IARC 1991)|
|Dibromoacetonitrile||No data||Inadequate||3||Vol. 52 (IARC 1991)|
|Dichloroacetonitrile||No data||Inadequate||3||Vol. 52 (IARC 1991)|
|Trichloroacetonitrile||No data||Inadequate||3||Vol. 52 (IARC 1991)|
|Dibromoacetonitrile||No data||Sufficient||2B||Vol. 101 (IARC 2012b)|
|Chloral hydrate||Inadequate||Sufficient||2A||Vol. 106 (IARC 2013)|
|MX (3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone)||Inadequate||Limited||2Bd||Vol. 84 (IARC 2004)|
|Bromate (evaluated as potassium bromate)||Inadequate||Sufficient||2B||Vol. 73 (IARC 1999)|
|Chlorite (evaluated as sodium chlorite)||No data||Inadequate||3||Vol. 52 (IARC 1991)|
|Chlorinated drinking water||Inadequate||Inadequate||3||Vol. 52 (IARC 1991)|
|Chemicals used in the disinfection of drinking water|
|Hypochlorite salts||No data||Inadequate||3||Vol. 52 (IARC 1991)|
|Chloramine||Inadequate||Inadequate||3||Vol. 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.|
Mechanisms and Biomarkers
Final Remarks and Recommendations
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- Hilz E, Gore A, Endocrine-Disrupting Chemicals: Science and Policy, Policy Insights from the Behavioral and Brain Sciences, 10.1177/23727322231196794, 10, 2, (142-150), (2023).
- Escher B, Blanco J, Caixach J, Cserbik D, Farré M, Flores C, König M, Lee J, Nyffeler J, Planas C, Redondo-Hasselerharm P, Rovira J, Sanchís J, Schuhmacher M, Villanueva C, 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).
- Sikder R, Zhang T, Ye T, Predicting THM Formation and Revealing Its Contributors in Drinking Water Treatment Using Machine Learning, ACS ES&T Water, 10.1021/acsestwater.3c00020, (2023).
- Chen Y, Liang Q, Liang W, Li W, Liu Y, Guo K, Yang B, Zhao X, Yang M, 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).
- Bawa R, Dwivedi P, Hoghooghi N, Kalin L, Huang Y, 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).
- Villanueva C, Evlampidou I, Ibrahim F, Donat-Vargas C, Valentin A, Tugulea A, Echigo S, Jovanovic D, Lebedev A, Lemus-Pérez M, Rodriguez-Susa M, Luzati A, de Cássia dos Santos Nery T, Pastén P, Quiñones M, Regli S, Weisman R, Dong S, Ha M, Phattarapattamawong S, Manasfi T, Musah S, Eng A, Janák K, Rush S, Reckhow D, Krasner S, Vineis P, Richardson S, Kogevinas M, 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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