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Animal studies indicate deleterious effects of nitrate exposure on fecundity, but effects in humans are unknown, both for the prenatal and postnatal periods. We aimed to investigate if exposure to nitrate in maternal drinking water during the sensitive period of fetal life is associated with measures of fecundity in the adult sons. In a sub-analysis, the potential effects of nitrate exposure in adulthood were investigated. This cohort included 985 young adult men enrolled in The Fetal Programming of Semen Quality Cohort (FEPOS). Semen characteristics, testes volume and reproductive hormones were analyzed in relation to nitrate concentration in maternal drinking water, using a negative binomial regression model. The nitrate concentration in drinking water was obtained from monitoring data from Danish waterworks that were linked with the mothers’ residential address during pregnancy. The median nitrate concentration in maternal drinking water was 2 mg/L. At these low exposure levels, which are far below the World Health Organization’s (WHO) guideline value of 50 mg/L, we did not find indications of harmful effects of nitrate on the investigated measures of male fecundity Animal studies indicate deleterious effects of nitrate exposure on fecundity, but effects in humans are unknown, both for the prenatal and postnatal periods. We aimed to investigate if exposure to nitrate in maternal drinking water during the sensitive period of fetal life is associated with measures of fecundity in the adult sons. In a sub-analysis, the potential effects of nitrate exposure in adulthood were investigated. This cohort included 985 young adult men enrolled in The Fetal Programming of Semen Quality Cohort (FEPOS). Semen characteristics, testes volume and reproductive hormones were analyzed in relation to nitrate concentration in maternal drinking water, using a negative binomial regression model. The nitrate concentration in drinking water was obtained from monitoring data from Danish waterworks that were linked with the mothers' residential address during pregnancy. The median nitrate concentration in maternal drinking water was 2 mg/L. At these low exposure levels, which are far below the World Health Organization's (WHO) guideline value of 50 mg/L, we did not find indications of harmful effects of nitrate on the investigated measures of male fecundity.

Background Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth. Methods We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L. Results Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15–2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08–8.94)]. Conclusions The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.

BACKGROUND AND AIM: Only two studies of prenatal exposure to nitrate from drinking water and the risk of preterm birth have been conducted, both with ecologic exposures and from the US. We aimed to...

BACKGROUND: High levels of nitrate ( NO 3 - ) in drinking water cause methemoglobinemia in infants; however, few studies have examined the potential effects of low-level exposure on fetal growth, and the results have been inconsistent.OBJECTIVES: We sought to assess the association between maternal exposure to nitrate in drinking water during pregnancy and offspring size at birth in a nationwide study of full-term ( ≥ 37 wk gestation) live-born singletons.METHODS: We estimated maternal nitrate exposure for 898,206 births in Denmark during 1991-2011 by linkage of individual home address(es) with nitrate data from the national monitoring database. Maternal address during pregnancy, infant size at birth [i.e., birth weight, low birth weight (LBW), body length, and birth head circumference] and covariates were compiled from the Danish Civil Registration System, the Danish Medical Birth Register, and The Integrated Database for Longitudinal Labor Market Research. Linear and logistic models with generalized estimating equations were used to account for multiple births to an individual. Nitrate exposure was modeled using five categories and as a log-transformed continuous variable.RESULTS: There was evidence of a decreasing trend in models for term birth weight using categorical or continuous measures of exposure. Modeling exposure continuously, a difference of - 9.71 g (95% confidence interval: - 14.60 , - 4.81 ) was predicted at 25 mg / L (half the value of the European Union drinking water standard) compared with 0 mg / L NO 3 - . Body length also decreased as nitrate concentrations increased in categorical and continuous models. There was little evidence of an association between NO 3 - and head circumference or LBW.DISCUSSION: Although the estimated effects were small, our findings for live singleton births to Danish-born parents suggest that maternal intake of nitrate from drinking water may reduce term birth weight and length, which are markers of intrauterine growth. However, there was little evidence for an association between nitrate and head circumference or LBW. Future studies in other populations and with data on dietary sources of nitrate are encouraged to confirm or refute these findings. https://doi.org/10.1289/EHP7331.

Groundwater protection against agricultural diffuse nitrate pollution is of paramount importance for safeguarding groundwater-dependent aquatic ecosystems and protecting human health by securing clean groundwater for drinking water production. Nitrate vulnerability assessment of aquifers is the core of a scientifically sound strategy for management and protection of groundwater by authorities. A multitude of methods exists for assessing intrinsic aquifer vulnerability. The objective of this paper is to develop a nitrate-specific groundwater vulnerability assessment method based on the globally recognized DRASTIC method, which was developed by the US Environmental Protection Agency in the 1980s. We propose a new method “DRASTIC-N″ for assessing aquifer nitrate vulnerability, which for the first time expands the seven original geological and hydrogeological parameters with a geochemical parameter for redox condition. The development of DRASTIC-N is based on the longstanding Danish practice of performing detailed groundwater mapping based on dense sampling of geophysical, geological, and geochemical data. DRASTIC-N is compared to the widely used and documented Danish nitrate vulnerability assessment method SCANVA in a study area where the primary aquifer used for drinking water production is composed of heterogeneous sandy glacial deposits. Both SCANVA and DRASTIC-N result in vulnerability maps, which show similar patterns of nitrate vulnerability with a fair overall agreement of 71%. DRASTIC-N provides a framework for systematic and transparent application, which can facilitate stakeholder involvement and help authorities in groundwater protection and decision-making with regards to nitrate pollution. DRASTIC-N is suitable for nitrate vulnerability assessments of glacially deposited sandy aquifers, an abundant and important water resource worldwide, potentially threatened by nitrate pollution from anthropogenic activities.

BACKGROUND: There is limited evidence that nitrate, a common contaminant in drinking water, increases the risk of childhood cancers. Our objective was to examine this association in Denmark.METHODS: We conducted a nationwide case-control study based on all singletons liveborn to Danish-born parents from 1991 to 2015 (N = 1,219,140) that included 596 leukemias, 180 lymphomas, and 310 central nervous system cancers (CNC) who were ≤15 years of age at diagnosis and were identified from the Danish Cancer Registry. Approximately 100 controls were randomly selected and matched to each case on date of birth and sex. Nitrate measurements in public water systems were linked with an address registry to estimate individual average nitrate concentrations during preconception, prenatal, and postnatal periods. Odd ratios (OR) and 95% confidence intervals (95%CI) were estimated using conditional logistic regression controlling for the matching variables, and birth order, birthweight, urbanicity, maternal education, employment, income and smoking, and parental age.RESULTS: There was no evidence of an association of nitrate with leukemia or lymphoma. An association between CNC and the highest category of nitrate exposure (>25 mg/L nitrate) was observed for preconception (OR = 1.82, 95%CI:1.09 to 3.04), prenatal (OR = 1.65, 95%CI:0.97 to 2.81), and postnatal exposure (OR = 1.48, 95%CI:0.82 to 2.68) in fully-adjusted models. There was also some evidence of an exposure-response in models of continuous nitrate exposure and CNC.CONCLUSIONS: Our findings provide some evidence that exposure to nitrate from drinking water may increase the risk of childhood CNC cancer, but not leukemia or lymphoma.

One in six couples experience fertility problems. Environmental factors may affect reproductive health; however, evidence is lacking regarding drinking water nitrates and outcomes of male and female fertility. The aim of this study was to investigate if exposure to nitrates in drinking water is associated with adverse reproductive outcomes in humans, and animals of fertile age. We conducted a systematic literature search and included case-control studies, cohort studies, and randomized control trials reporting on the association between drinking water nitrate exposure of men, women, or animals and adverse reproductive outcomes, specified as: Semen quality parameters, time to pregnancy (TTP), pregnancy rates, assisted reproductive technologies (ART), and spontaneous abortion. Findings were reported in a narrative synthesis. A total of 12 studies were included. The only human study included reported a decrease in spontaneous abortion at any detectable nitrate level. Overall, the 11 included animal studies support a potential negative effect on semen quality parameters but report equivocal results on TTP and number of offspring produced, and higher risk of spontaneous abortion. In conclusion, animal studies indicate possible effects on semen quality parameters and spontaneous abortion. However, with a few studies, including some with methodological limitations and small sample sizes, caution must be applied when interpreting these results.

Nitrate in drinking water may increase risk of colorectal cancer due to endogenous transformation into carcinogenic N-nitroso compounds. Epidemiological studies are few and often challenged by their limited ability of estimating long-term exposure on a detailed individual level. We exploited population-based health register data, linked in time and space with longitudinal drinking water quality data, on an individual level to study the association between long-term drinking water nitrate exposure and colorectal cancer (CRC) risk. Individual nitrate exposure was calculated for 2.7 million adults based on drinking water quality analyses at public waterworks and private wells between 1978 and 2011. For the main analyses, 1.7 million individuals with highest exposure assessment quality were included. Follow-up started at age 35. We identified 5,944 incident CRC cases during 23 million person-years at risk. We used Cox proportional hazards models to estimate hazard ratios (HRs) of nitrate exposure on the risk of CRC, colon and rectal cancer. Persons exposed to the highest level of drinking water nitrate had an HR of 1.16 (95% CI: 1.08-1.25) for CRC compared with persons exposed to the lowest level. We found statistically significant increased risks at drinking water levels above 3.87 mg/L, well below the current drinking water standard of 50 mg/L. Our results add to the existing evidence suggesting increased CRC risk at drinking water nitrate concentrations below the current drinking water standard. A discussion on the adequacy of the drinking water standard in regards to chronic effects is warranted.

This study presents an approach making drinking water quality data from the Danish national geodatabase Jupiter available for epidemiological studies on long-term health effects of drinking water quality. Drinking water quality was assigned to all Danish households using spatial methods, and the related uncertainty due to sampling density was identified. Nitrate was used as an example contaminant. From 1978, 98% of all Danish households were geocoded with their precise location, yielding a total of 69 million evaluated household-years. Households supplied by a private well (4% of all household-years) were identified; the remaining majority was supplied by public waterworks. Water supply areas were connected to the Jupiter geodatabase to estimate drinking water quality at publicly supplied households. For privately supplied households, the exposure estimate had a substantially higher uncertainty, with 52% of household-years never being sampled, compared with 1% of publicly supplied household-years. For the 18% of all household-years with no nitrate samples, concentrations were estimated by interpolation and an uncertainty score based on the closest nitrate measurement was introduced. While nitrate was used as an example contaminant, the proposed approach is generic and can be used for all monitored drinking water parameters, after preprocessing and validation of the specific data and assumptions.

Accurate assessments of exposure to nitrate in drinking water is a crucial part of epidemiological studies investigating long-term adverse human health effects. However, since drinking water nitrate measurements are usually collected for regulatory purposes, assumptions on (1) the intra-distribution system variability and (2) short-term (seasonal) concentration variability have to be made. We assess concentration variability in the distribution system of nitrate, nitrite, and ammonium, and seasonal variability in all Danish public waterworks from 2007 to 2016. Nitrate concentrations at the exit of the waterworks are highly correlated with nitrate concentrations within the distribution net or at the consumers' taps, while nitrite and ammonium concentrations are generally lower within the net compared with the exit of the waterworks due to nitrification. However, nitrification of nitrite and ammonium in the distribution systems only results in a relatively small increase in nitrate concentrations. No seasonal variation for nitrate, nitrite, or ammonium was observed. We conclude that nitrate measurements taken at the exit of the waterworks are suitable to calculate exposures for all consumers connected to that waterworks and that sampling frequencies in the national monitoring programme are sufficient to describe temporal variations in longitudinal studies.

Throughout the world, nitrogen (N) losses from intensive agricultural production may end up as undesirably high concentrations of nitrate in groundwater with a long-term impact on groundwater quality. This has human and environmental health consequences, due to the use of groundwater as a drinking water resource, and causes eutrophication of groundwater-dependent ecosystems such as wetlands, rivers and near-coastal areas. At national scale, the measured nitrate concentrations and trends in Danish oxic groundwater in the last 70 years correlate well with the annual agricultural N surpluses. We also show that the N use efficiency of agriculture is related to the groundwater nitrate concentrations. We demonstrate an inverted U-shape of annual nitrate concentrations as a function of economic growth from 1948 to 2014. Our analyses evidence a clear trend of a reversal at the beginning of the 1980s towards a more sustainable agricultural N management. This appears to be primarily driven by societal demand for groundwater protection linked to economic prosperity and an increased environmental awareness. However, the environmental and human health thresholds are still exceeded in many locations. Groundwater protection is of fundamental global importance, and this calls for further development of environmentally and economically sustainable N management in agriculture worldwide.