The quality of drinking water is paramount for public health. Despite important improvements in the last decades, access to safe drinking water is not universal. The World Health Organization ...estimates that almost 10% of the population in the world do not have access to improved drinking water sources. Among other diseases, waterborne infections cause diarrhea, which kills nearly one million people every year, mostly children under 5 years of age. On the other hand, chemical pollution is a concern in high-income countries and an increasing problem in low- and middle-income countries. Exposure to chemicals in drinking water may lead to a range of chronic non-communicable diseases (e.g., cancer, cardiovascular disease), adverse reproductive outcomes, and effects on children’s health (e.g., neurodevelopment), among other health effects. Although drinking water quality is regulated and monitored in many countries, increasing knowledge leads to the need for reviewing standards and guidelines on a nearly permanent basis, both for regulated and newly identified contaminants. Drinking water standards are mostly based on animal toxicity data, and more robust epidemiologic studies with accurate exposure assessment are needed. The current risk assessment paradigm dealing mostly with one-by-one chemicals dismisses the potential synergisms or interactions from exposures to mixtures of contaminants, particularly at the low-exposure range. Thus, evidence is needed on exposure and health effects of mixtures of contaminants in drinking water. Finally, water stress and water quality problems are expected to increase in the coming years due to climate change and increasing water demand by population growth, and new evidence is needed to design appropriate adaptation policies.
This Special Issue of International Journal of Environmental Research and Public Health (IJERPH) focuses on the current state of knowledge on the links between drinking water quality and human health.
Ingested nitrate leads to the endogenous synthesis of N‐nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated ...with nitrate exposure in drinking water and diet. A case‐control study in Spain and Italy during 2008‐2013 was conducted. Hospital‐based incident cases and population‐based (Spain) or hospital‐based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long‐term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects’ residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure‐response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure‐response relationship among men. Animal‐derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.
What's new?
Nitrate ingested in food and water can react with amines and amides in the gastrointestinal tract, leading to the formation of N‐nitroso compounds (NOCs), which are carcinogenic in animals. In humans, nitrate and several NOCs are probable carcinogens. The aim of the present investigation, a case–control study in Europe, was to examine links between nitrate intake and colorectal cancer (CRC). The findings indicate that CRC risk is increased for waterborne nitrate intake at levels below current international guidelines, particularly in subgroups with other risk factors. Nitrate intake from animal sources was further associated with increased rectal cancer risk.
A few studies in high-income countries have investigated the relationship between ambient temperature and/or precipitation and the occurrence of gastroenteritis. In most of the cases, hot ...temperatures and heavy precipitation events have been related to increases in infections. This is of concern as climate change predictions indicate an increase of those extreme events. Our aim was to evaluate the association between meteorological variables and daily gastroenteritis hospitalizations in Spain for the period 1997–2013.
We obtained data on all hospitalizations which occurred in Spain for the study period from administrative databases and selected those with gastroenteritis as the main diagnosis. Meteorological data was obtained from the European Climate Assessment & Dataset. Daily counts of hospitalizations were linked to meteorological variables in a retrospective ecological time series study using quasi-Poisson regression models with overdispersion and applying the Distributed Lag Non-linear Model (DLNM) framework.
Both high and cold temperatures increased the risk of gastroenteritis hospitalizations (relative risk (RR) = 1.21, 95% confidence interval (CI): 1.09, 1.34; and RR = 1.07, 95% CI: 1.00, 1.15, respectively), whereas heavy precipitation was found protective for those hospitalizations (RR = 0.74, 95% CI: 0.63, 0.86). Hot temperatures increased hospitalizations for gastroenteritis classified as foodborne or idiopathic but not those in the group of Others, which were composed mainly of infections by rotavirus and were associated with cold temperatures.
Our findings suggest an important role of ambient temperatures, especially hot temperatures, in increasing gastroenteritis hospitalizations, while the exposure to heavy precipitation events pose opposite and unexpected effects on these infections.
•The study linked weather and gastroenteritis hospitalizations in Spain.•Both hot and cold temperatures were associated with increased risks.•Precipitation showed a protective association with gastroenteritis hospitalizations.•Gastroenteritis more likely to be foodborne were associated with hot temperatures.•Conversely, the group including rotavirus was associated with cold.
Background: Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water. Objectives: In this study we investigated the combined influence of DBP ...exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based casecontrol study in Spain. Methods: Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms. Results: THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8-1.8), 1.8 (1.1-2.9), and 1.8 (0.9-3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/— versus GSTT1 null (Pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (Pinteraction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (Pinteraction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7-3.5), 3.4 (1.4-8.2), and 5.9 (1.8-19.0), respectively. Conclusions: Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.
Most studies on endocrine-disrupting chemicals and breast cancer have focused on single compounds and have produced inconclusive findings.
We assessed the combined estrogenic effects of mixtures of ...xenoestrogens in serum and their relationship to breast cancer risk.
A total of 186 incident pretreatment breast cancer cases and 196 frequency-matched controls were randomly sampled from a large population-based multicase-control study in Spain. The total effective xenoestrogen burden attributable to organohalogenated xenoestrogens (TEXB-α) and endogenous hormones and more polar xenoestrogens (TEXB-β) was determined in serum samples using high-performance liquid chromatography and E-Screen bioassay. Odds ratios for breast cancer comparing tertiles of serum TEXB-α and TEXB-β were estimated using logistic models, and smooth risk trends were obtained using spline models.
Cases had higher geometric mean TEXB-α and TEXB-β levels (8.32 and 9.94 Eeq pM/mL, respectively) than controls (2.99 and 5.96 Eeq pM/mL, respectively). The fully adjusted odds ratios for breast cancer (95% confidence intervals) comparing the second and third tertiles of TEXB-α with the first tertile were 1.77 (0.76, 4.10) and 3.45 (1.50, 7.97), respectively, and those for TEXB-β were 2.35 (1.10, 5.03) and 4.01 (1.88, 8.56), respectively. A steady increase in risk was evident across all detected TEXB-α levels and a sigmoidal trend was observed for TEXB-β. Individual xenoestrogens showed weak and opposing associations with breast cancer risk.
This is the first study to show a strong positive association between serum total xenoestrogen burden and breast cancer risk, highlighting the importance of evaluating xenoestrogen mixtures, rather than single compounds, when studying hormone-related cancers.
Pastor-Barriuso R, Fernández MF, Castaño-Vinyals G, Whelan D, Pérez-Gómez B, Llorca J, Villanueva CM, Guevara M, Molina-Molina JM, Artacho-Cordón F, Barriuso-Lapresa L, Tusquets I, Dierssen-Sotos T, Aragonés N, Olea N, Kogevinas M, Pollán M. 2016. Total effective xenoestrogen burden in serum samples and risk for breast cancer in a population-based multicase-control study in Spain. Environ Health Perspect 124:1575-1582; http://dx.doi.org/10.1289/EHP157.
Bottled water consumption is increasing worldwide, despite its huge economic and environmental cost. We aim to describe personal and tap water quality determinants of bottled water use in the city of ...Barcelona. This cross-sectional study used data from the Health Survey of Barcelona in 2006（N = 5417 adults）. The use of bottled water to drink and to cook was evaluated in relation to age, gender, educational level, district and levels of trihalomethanes（THMs）, free chlorine, conductivity, chloride, sodium, p H, nitrate and aluminium in municipal tap water using Robust Poisson Regression. The prevalence of bottled water use to drink and cook was 53.9% and 6.7%, respectively. Chemical parameters in water had a large variability（interquartile range of THMs concentrations： 83.2–200.8 μg/L）and were correlated between them, except aluminium. Drinking bottled water increased with educational level, while cooking with bottled water was higher among men than among women and decreased with age. After adjusting by these personal determinants, a dose–response relationship was found between concentrations of all chemicals except aluminium in tap water and bottled water use. The highest association was found for THMs,with a Prevalence Ratio of 2.00（95%CI = 1.86, 2.15） for drinking bottled water and 2.80（95%CI = 1.72, 4.58） for cooking with bottled water, among those with 〉 150 μg/L vs. 〈 100 μg/L THMs in tap water. Conclusion： More than half of Barcelona residents regularly drank bottled water, and the main determinant was the chemical composition of tap water,particularly THM level.
Ingested nitrate leads to endogenous formation of N-nitroso compounds that are breast carcinogens in animals, but human evidence is limited.
We evaluated ingested nitrate as a risk factor for breast ...cancer (BC) in a multicase-control study.
Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008-2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940-2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis.
Among the study regions, average ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (≥ 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate.
Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status.
Espejo-Herrera N, Gracia-Lavedan E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano P, Zabala AJ, Ardanaz E, Guevara M, Molina AJ, Barrio JP, Gómez-Acebo I, Tardón A, Peiró R, Chirlaque MD, Palau M, Muñoz M, Font-Ribera L, Castaño-Vinyals G, Kogevinas M, Villanueva CM. 2016. Ingested nitrate and breast cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain). Environ Health Perspect 124:1042-1049; http://dx.doi.org/10.1289/ehp.1510334.
BACKGROUND: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive. OBJECTIVE: We assessed exposure to ...trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LEW), and preterm delivery. METHODS; Mother-child cohorts set up in five Spanish areas during the years 2000—2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We denned outcomes following standard definitions and included 2,158 newborns in the analysis. RESULTS: Median residential THM ranged from 5.9 μg/L (Valencia) to 114.7 μg/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was -0.45 g (95% confidence interval: -1.36,0.45 g) for chloroform and 0.16 g (-1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery. CONCLUSIONS: Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain.
Epidemiological studies provide evidence that environmental exposures may affect health through complex mixtures. Formal investigation of the effect of exposure mixtures is usually achieved by ...modelling interactions, which relies on strong assumptions relating to the identity and the number of the exposures involved in such interactions, and on the order and parametric form of these interactions. These hypotheses become difficult to formulate and justify in an exposome context, where influential exposures are numerous and heterogeneous. To capture both the complexity of the exposome and its possibly pleiotropic effects, models handling multivariate predictors and responses, such as partial least squares (PLS) algorithms, can prove useful. As an illustrative example, we applied PLS models to data from a study investigating the inflammatory response (blood concentration of 13 immune markers) to the exposure to four disinfection by-products (one brominated and three chlorinated compounds), while swimming in a pool. To accommodate the multiple observations per participant (n=60; before and after the swim), we adopted a multilevel extension of PLS algorithms, including sparse PLS models shrinking loadings coefficients of unimportant predictors (exposures) and/or responses (protein levels). Despite the strong correlation among co-occurring exposures, our approach identified a subset of exposures (n=3/4) affecting the exhaled levels of 8 (out of 13) immune markers. PLS algorithms can easily scale to high-dimensional exposures and responses, and prove useful for exposome research to identify sparse sets of exposures jointly affecting a set of (selected) biological markers. Our descriptive work may guide these extensions for higher dimensional data.
This work was carried out within the EXPOsOMICS Project, which was funded by the European Commission (grant agreement 308610-FP7 European Commission, to PV). The Centre for Environment and Health is supported by the Medical Research Council and Public Health England (MR/L01341X/1). MC-H acknowledges support from Cancer Research UK, Population Research Committee Project grant ‘Mechanomics’ (project 22184)
BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent. OBJECTIVES: We assessed long-term exposure to ...trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer. METHODS: A multicenter case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases and population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, type of water consumed in each residence, frequency and duration of showering/bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant's residential tap water (micrograms/liter; from age 18 to 2 years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (micrograms/day). RESULTS: We analyzed 2,047 cases and 3,718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR = 0.92, 95% CI: 0.66, 1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR = 0.31, 95% CI: 0.24, 0.41 for highest vs. lowest quartile). Brominated THM concentrations showed a positive association among men in the highest versus the lowest quartile (OR = 1.43, 95% CI: 0.83, 2.46). Patterns of association were similar for estimated average THM ingestion through residential water consumption. CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposure and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings should be confirmed in other study populations.
This work was supported by the Acción Transversal del Cáncer del Consejo de Ministros del 11/10/2007
(M.K. and M.Pollan), from the Instituto de Salud Carlos III-FEDER (M.K.: PI08/1770; C.M.V.: PI08/0533 and PI11/00226) FIS grants and Hiwate EU project (036224), and the Italian Foundation for Research on Cancer (FIRC; C.L.V.).
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