Nitrate In Drinking Water Research Articles

Dose Effect of Drinking Water Nitrate on Health, Feed Intake, Rumen Fermentation and Microbiota, and Nitrogen Excretion in Holstein Heifers for a Sustainable Water Use

The present study aimed to evaluate the potential hazardous effects of NO3− concentration in drinking water on health, feed intake, rumen fermentation and microbiota, and nitrogen excretion of Holstein heifers fed a high-concentrate diet for a sustainable water use. Twenty-four Holstein heifers were individually allocated and assigned to one of four treatments with increasing drinking water NO3− concentration: CTR, without NO3−; LOW, with 44 mg NO3−/L; MOD, with 110 mg NO3−/L; and HIGH, with 220 mg NO3−/L. The entire study lasted 168 days. Fortnightly water NO3− concentration and daily feed and water intake were recorded. Blood parameters, rumen pH, volatile fatty acids, NO3− and NO2− concentration, microbiota, and apparent total tract digestibility were determined at the beginning and at the end of the study. Most of the analyzed parameters were similar among treatments. Denitrifying bacteria population, estimated as nosZ gene copies, were greater in HIGH animals than in CTR animals at the end of the study. In conclusion, drinking water NO3− concentration up to 220 mg/L has no detrimental effect on health, feed intake, rumen fermentation, nor N excretion in dairy beef cattle for periods up to 168 days; moreover, denitrifying bacteria population increased, which are related with the neutralization of the greenhouse gas N2O.

Selenium and concomitant anions removal in a fixed bed bioreactor to satisfy drinking water regulations and subsequent stability check of selenium-laden biosludge

This is the first successful report on selenium bio-attenuation to satisfy drinking water regulations as per Indian Standards (10 μg/L) in the presence of concomitant nitrate and sulfate from water sources utilizing a fixed bed bioreactor. The bioreactor was immunized with blended microbial culture and worked in downflow mode under anoxic conditions at 30 ± 2 °C for around 190 days under varying influent selenate (100–500 μg/L as selenium), nitrate (50 mg/L), sulfate concentrations (as per selenium removal) and necessary dose of acetic acid (as COD, a carbon source) in synthetic groundwater, operated at an empty bed contact time (EBCT) of 45–120 min. After supplying an adequate dosage of sulfate and alteration of EBCT, selenium was found to comply with drinking water regulations and nitrate was completely removed. X-ray diffraction and transmission electron microscopy analyses depicted nanocrystalline selenium sulfides (SeS and SeS2) formation as the possible mechanisms of selenium removal. Extended toxicity characteristic leaching procedure (TCLP) extractions confirmed a maximum selenium leaching of 52 and 282 μg/L during anoxic and oxic extractions, respectively. Long-term column leaching (>3-month equilibration) under aerobic conditions at pH 7 confirmed the produced precipitate to be essentially stable (∼0.14% Se leaching). This work exhibits the synchronous bioremoval of selenium and its co-anions from contaminated water complying with drinking water standards, and leaving a stable and non-hazardous selenium-laden biosludge.

Impact of Droughts on Served Drinking Water Disparities in California, 2007-2020.

Objectives. To quantify the impact of droughts on drinking water arsenic and nitrate levels provided by community water systems (CWSs) in California and to assess whether this effect varies across sociodemographic subgroups. Methods. I integrated CWS characteristics, drought records, sociodemographic data, and regulatory drinking water samples (n = 83 317) from 2378 water systems serving 34.8 million residents from 2007 to 2020. I analyzed differential drought effects using fixed-effect regression analyses that cumulatively accounted for CWS-level trends, income, and agricultural measures. Results. CWSs serving majority Latino/a communities show persistently higher and more variable drinking water nitrate levels. Drought increased nitrate concentrations in majority Latino/a communities, with the effect doubling for CWSs with more than 75% Latino/a populations served. Arsenic concentrations in surface sources also increased during drought for all groups. Differential effects are driven by very small (< 500) and privately owned systems. Conclusions. Impending droughts driven by climate change may further increase drinking water disparities and arsenic threats. This underscores the critical need to address existing inequities in climate resilience planning and grant making. (Am J Public Health. 2024;114(9):935-945. https://doi.org/10.2105/AJPH.2024.307758).

Chronic exposure to drinking water nitrate and trihalomethanes in the French CONSTANCES cohort

Trihalomethanes (THMs) and nitrate are widespread chemicals in drinking water. Chronic exposure has been associated with increased cancer risk despite inconclusive evidence, partly due to the challenges in long-term exposure assessment and potential exposure misclassification.We estimated concentrations of nitrate and THMs in drinking water using a public regulatory monitoring database (SISE-Eaux) for CONSTANCES, a French population-based prospective cohort.We obtained 26,322,366 measurements of drinking water parameters from 2000 to 2020. We excluded missing, implausible and duplicated measurements; we corrected or imputed missing geocodes of sampling locations; we calculated the annual median concentration of nitrate and THMs by surveillance area. To predict missing annual median concentrations, linear mixed models with random intercept using surveillance area as a clustering variable were developed for each region for nitrate and the four THM components (chloroform, chlorodibromomethane, bromodichloromethane and bromoform) separately. Concentrations in the nearest surveillance area from the household were merged per year among 75,462 participants with residential history geocoded for 2000–2020. Estimated concentrations resulting from this approach were compared with measured concentrations in 100 samples collected in Paris, Rennes and Saint-Brieuc in 2021.Median annual concentrations of total THMs and nitrate at study participants’ homes for 2000–2020 were, respectively, 15.7 μg/l (IQR: 15.2) and 15.2 mg/l (IQR: 20.8). Among these, 35% were based on measurements for nitrate (16% for THMs), 44% (46%) were predicted using on linear mixed models, and 21% (38%) were based on distribution unit median values. Conditional R2 predictive models ranged from 0.71 to 0.91 (median: 0.85) for nitrate, and from 0.48 to 0.80 for THMs (median: 0.68).These concentrations will allow future association analyses with risk of breast and colorectal cancer. Our cleaning process introduced here could be adapted to other large drinking water monitoring data.

Immunological and genetic profile of the pediatric population in the nitrate geochemical province

BACKGROUND: Contamination of groundwater with nitrates may result in substantial adverse effects on the health of various population groups.&#x0D; AIM: To study the immune status and genetic profile of children residing in the nitrate geochemical province in the Perm Region.&#x0D; MATERIAL AND METHODS: We conducted a study on a total of 78 preschool children residing in areas with varying levels of nitrate in the underground drinking water sources. The children were divided into two groups for comparison purposes. The first group consisted of 43 children who consumed drinking water that met the acceptable standards for nitrate content. The second group comprised 35 children who consumed drinking water with elevated levels of nitrates. To assess the impact of nitrate content on the children’s health, several measurements were taken. Firstly, the level of nitrates in the household drinking water was analyzed. Additionally, the concentration of N-nitrosamines and nitrate ions in the children’s urine, was determined. To evaluate the immunoregulation parameters, the technology of flow cytometry and enzyme immunoassay were employed, along with PCR to examine genetic polymorphisms.&#x0D; RESULTS: A statistically significant difference (p 0.001) was observed in the nitrate content of drinking water between the observation area and the comparison area, with the former showing levels 2.8 times higher. Furthermore, children in the observation group exhibited a significant increase (p 0.05) of 2.3 times in N-nitrosodiethylamine content and 1.6 times in nitrate ion concentration in their urine compared to children in the comparison group. In addition, the observation group displayed a significant decrease (p 0.05) in the number of NKT cells and an increase in the levels of CD3+CD25+-, CD3+CD95+-cells, bax, IL-17, Annexin V-FITC+PI–-, and Annexin V-FITC+PI+-lymphocytes, when compared to the results obtained from the comparison group. Moreover, the presence of polymorphisms in candidate genes associated with tumor formation (CYP1A1 (rs1048943), MMP9 (rs17576), PPARD (rs2016520), BRCA1 G/A (rs3950989)) was also identified.&#x0D; CONCLUSION: Our results suggest that children who are exposed to chronic low-levels of nitrates (at a concentration of 1.2 MPC) through drinking water from underground sources exhibit an excessive presence of N-nitrosodiethylamine and nitrate ions in their urine. These findings, in conjunction with the genetic profile of genes responsible for tumor formation, influences the characteristics of the immune response.

Ingested nitrate and nitrite and end-stage renal disease in licensed pesticide applicators and spouses in the Agricultural Health Study

BackgroundNitrate and nitrite ingestion has been linked to kidney cancer, possibly via the endogenous formation of carcinogenic N-nitroso compounds. These exposures might also contribute to end-stage renal disease (ESRD).ObjectivesWe investigated associations of drinking water nitrate and dietary nitrate and nitrite intakes (total and by food type) with incident ESRD in the Agricultural Health Study. We also explored modifying effects of vitamin C and heme iron intake, which may affect endogenous nitrosation.MethodsWe performed complete case analyses among private pesticide applicators and their spouses. We obtained water nitrate estimates for participants whose primary drinking water source at enrollment (1993−1997) was public water supplies (PWS) or private wells (N = 59,632). Average nitrate concentrations were computed from historical data for PWS users and predicted from random forest models for private well users. Analysis of dietary nitrate and nitrite was restricted to the 30,177 participants who completed the NCI Dietary History Questionnaire during follow-up (1999−2003). Incident ESRD through 2018 was ascertained through linkage with the U.S. Renal Data System. We estimated adjusted hazard ratios (HRs) and 95%CI for associations of tertiles (T) of exposure with ESRD overall and explored effects in strata of vitamin C and heme iron intake.ResultsWe identified 469 incident ESRD cases (206 for dietary analysis). Water nitrate and total dietary nitrate/nitrite were not associated with ESRD, but increased ESRD was associated with nitrate and nitrite from processed meats. We found apparent associations between nitrite and ESRD only among participants with vitamin C <median (T3 vs. T1 HR: 2.26, 95%CI: 1.05, 4.86) and with heme iron ≥median (T3 vs. T1 HR: 1.73, 95%CI: 0.89, 3.39).SignificanceESRD incidence was associated with dietary nitrate/nitrite from processed meat among all study participants and with total dietary nitrite among participants with lower vitamin C or higher heme iron intake.Impact statementThere are few well-established environmental risk factors for end-stage renal disease (ESRD), a worldwide public health challenge. Ingestion of nitrate and nitrite, which may lead to endogenous formation of carcinogenic N-nitroso compounds, has been linked to some cancers and chronic diseases. We investigated these exposures in relation to ESRD in an agricultural cohort. ESRD incidence was associated with dietary nitrate/nitrite from processed meat and with total dietary nitrite among subgroups with lower vitamin C or higher heme iron intake. This study provides preliminary evidence that points to dietary nitrite and possibly dietary nitrate intake as a potential contributor to ESRD.

NITRATES IN DRINKING WATER IN VARNA DISTRICT

NITRATES IN DRINKING WATER IN VARNA DISTRICT

Health-economic valuation of lowering nitrate standards in drinking water related to colorectal cancer in Denmark

Nitrate in drinking water is a contaminant which can affect human health and has been associated with an increased risk of, amongst other diseases, colorectal cancer. Based on epidemiologic data from Denmark on the association between drinking water nitrate and colorectal cancer, the health and economic consequences of lowering the standard of nitrate in drinking water from 50 mg/L to 9.25 mg/L and 3.87 mg/L, respectively are analyzed. The drinking water nitrate attributable number of cases was estimated using the risk in the exposed and unexposed population based on current nationwide exposure distributions. The analysis shows that a lower limit of 9.25 mg/L would decrease the annual number of colorectal cancer cases by 72 (95 % confidence interval: 34–114) and by an additional 55 (95 % CI: 10–100) for a stricter limit of 3.87 mg/L. The resulting avoided health-related costs are $179 million per year for the 9.25 mg/L nitrate limit and another $138 million per year for a further reduction to 3.87 mg/L nitrate. The new requirements would incur costs linked to either i) changes in land use management, ii) well reallocation or iii) use of treatment technologies. The additional costs are estimated to $0.03–1.84 per m3 abstracted water from public water companies, which together with costs for owners of private wells, will result in an average additional cost of $9 and $6 million per year for the two levels. The economic health benefits are higher than the costs for both limits with net gains of $170 million (9.25 mg/L) and additionally $132 million (3.87 mg/L) a year. Even in a worst-case scenario (lowest health-related benefits and highest mitigation costs), there is a likely economic gain for society from lowering the limit to 9.25 mg/L, but this might not be the case for the lower limit of 3.87 mg/L.

How Can Dangerous Levels of Nitrogen in Water be Remediated Using Nanofibers

Freshwater is vital for plant, animal, and human life. Due to increased demand for agricultural and animal products, excess reactive nitrogen species are seen in the environment as synthetic fertilizers. Consequently, increased instances of eutrophication occur in surface waters coupled with increased levels of nitrates in groundwaters. Both of these are common drinking water sources. Current nitrate treatment technologies require expensive infrastructure to build and maintain, have long treatment periods due to biological processes, and can generate copious amounts of waste and byproducts (ex: granular activated carbon and anion exchange resins). Safe, affordable, and sustainable reactive nitrogen removal water treatment technologies are needed. Nanotechnologies are an emerging, novel treatment for the removal of reactive nitrogen species in the form of nitrate in both drinking water and wastewater. In particular, chitosan nanofiber mats with algal substrate show promise in removing nitrate from water sources and have the added benefit of providing a sustainable source of biofuel. This article includes a review of nitrate contamination in the environment and chitosan nanofiber mats with an algal substrate possible solution.

Prenatal exposure to tap water containing nitrate and the risk of small-for-gestational-age: A nationwide register-based study of Danish births, 1991–2015

BackgroundPrenatal nitrate exposure from household tap water has been associated with increased risk of fetal growth restriction, preterm birth, birth defects, and childhood cancer. We aim to examine the association between maternal consumption of drinking-water nitrate during pregnancy and small-for-gestational-age (SGA) in a nationwide study of Danish-born children, as only one prior study has examined this association. MethodsWe linked individual-level household estimates of nitrate in tap water and birth registry data to all live singleton Danish births during 1991–2015 from Danish-born parents where the mother resided in Denmark throughout the pregnancy. Exposure was both binned into four categories and modeled as an ln-transformed continuous variable. SGA was defined as the bottom 10% of births by birth weight per sex and gestational week. Multiple logistic regression models with generalized estimating equations were used to account for siblings born to the same mother while controlling for relevant confounders. ResultsIn the cohort of 1,078,892 births, the median pregnancy nitrate exposure was 1.9 mg/L nitrate. Compared to the reference group (≤2 mg/L), we found an increased risk of SGA in the second category (>2–5 mg/L) (OR = 1.04, 95% CI: 1.03–1.06) and third category (>5–25 mg/L) (OR = 1.02, 95% CI: 1.00–1.04) but not in the highest (>25 mg/L). There was strong (p = 0.002) evidence of an increase in SGA with nitrate in the model with continuous exposure (OR = 1.02, 95% CI: 1.01–1.04 per 10-fold increase in nitrate). Results were robust when restricting to households with nitrate levels at or below the current Danish and European Union regulatory drinking water standard (50 mg/L nitrate). ConclusionsOur findings suggest that exposure from nitrate in household tap water, even below current regulatory standards, may increase risk of SGA, raising concerns of whether current allowable nitrate levels in drinking water protect children from SGA.

Relationship between serum nitric oxide of patients with thyroid disorders and metabolic syndrome indices and nitrate concentration of water

This case–control study aimed to assess the effect of drinking water nitrate on serum nitric oxide concentration and the risk of metabolic syndrome (MetS) in the population in the Middle East. The study included 50 control and 50 thyroid disorder cases who were referred to two medical centers in 2021. In this study, serum nitric oxide concentration, drinking water nitrate, and metabolic syndrome components were measured in the two groups. The results showed there was a statistically significant difference between serum NO in the case and control groups (p-value < 0.001). There was a positive correlation between the concentration of nitrate in drinking water and serum nitric oxide in the case and control groups; however, this relationship was not significant statistically. A statistically significant difference was found between serum nitric oxide and systolic blood pressure in the cases (p-value < 0.05), but there was no significant difference between MetS and nitric oxide. Therefore, we concluded that the relationship between nitric oxide and nitrate in consuming water should be determined in thyroid patients. In addition to their water consumption, it is better to study the nitrate of foods, especially vegetables.

Nitrate in Maternal Drinking Water during Pregnancy and Measures of Male Fecundity in Adult Sons.

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.

PSXVI-5 Rumen Parameters and Microbial Population Changes in Fattening Holstein Heifers fed with Nitrate-Contaminated Water

Abstract The aim of this study was to evaluate the effect of drinking water nitrate concentration on rumen parameters and its microbial population that may affect greenhouse gases in fattening cattle. Holstein heifers (n = 24; 161 ± 19.9 kg of initial BW, and 183 ± 25.3 d of age) were housed individually and fed ad libitum. Animals were assigned to 4 treatments according to nitrate concentration in drinking water: 1) Control (n=6), without NO3-; 2) Low (n=6), with 44 mg/L of NO3-; 3) Moderate (n=6), with 110 mg/L of NO3-, and 4) High (n=6), with 220 mg/L of NO3-. After 14 and 168 days the ruminal content was sampled to determine pH, volatile fatty acids (VFA), nitrate and nitrite concentration, and rumen microbiota (except for Moderate). To assess the rumen microbiota, DNA-based qPCR of total bacterial population (16S rRNA), dissimilatory sulfate-reducing prokaryotes (aprA), ammonia-oxidizing bacteria and archaea (amoA-AOB and amoA-AOA), typical complete denitrifiers (nosZ-clade I linked to the transformation of N2O to N2), and anammox bacteria (hzo) was determined. Rumen pH, VFA, nitrate and nitrite were analyzed with a mixed effects model. Rumen microbial populations were statistically treated by analysis of variance applying pairwise comparisons (Fisher's least). Rumen pH, VFA, nitrate and nitrite were not affected by nitrate concentration in drinking water; however, rumen nitrite concentrations were greater (P &amp;lt; 0.01) in d 14 than in d 168 (32.1 vs. 6.3 ± 4.20 mg/L, respectively). Nitrate drinking water concentration did not affect rumen microbial populations, except for complete-denitrifying population (nosZ-clade I) which were slightly greater (P=0.01) in High than in Control in d 168. In conclusion, nitrate-contaminated water did not show a significant impact on rumen parameters and microbial populations but increased the bacterial denitrifying potential after a long term, which could decrease ruminal N2O emissions and nitrite ruminal accumulation in fattening heifers.

Drinking water nitrate and risk of pregnancy loss: a nationwide cohort study

BackgroundNitrate contamination is seen in drinking water worldwide. Nitrate may pass the placental barrier. Despite suggestive evidence of fetal harm, the potential association between nitrate exposure from drinking water and pregnancy loss remains to be studied. We aimed to investigate if nitrate in drinking water was associated with the risk of pregnancy loss.MethodsWe conducted a nationwide cohort study of 100,410 pregnancies (enrolled around gestational week 11) in the Danish National Birth Cohort (DNBC) during 1996–2002. Spontaneous pregnancy losses before gestational week 22 were ascertained from the Danish National Patient Registry and DNBC pregnancy interviews. Using the national drinking water quality-monitoring database Jupiter, we estimated the individual and time-specific nitrate exposure by linking geocoded maternal residential addresses with water supply areas. The nitrate exposure was analyzed in spline models using a log-transformed continuous level or classified into five categories. We used Cox proportional hazards models to estimate associations between nitrate and pregnancy loss and used gestational age (days) as the time scale, adjusting for demographic, health, and lifestyle variables.ResultsNo consistent associations were found when investigating the exposure as a categorical variable and null findings were also found in trimester specific analyses. In the spline model using the continuous exposure variable, a modestly increased hazard of pregnancy loss was observed for the first trimester at nitrate exposures between 1 and 10 mg/L, with the highest.adjusted hazard ratio at 5 mg/L of nitrate of 1.16 (95% CI: 1.01, 1.34). This trend was attenuated in the higher exposure ranges.ConclusionNo association was seen between drinking water nitrate and the risk of pregnancy loss when investigating the exposure as a categorical variable. When we modelled the exposure as a continuous variable, a dose-dependent association was found between drinking water nitrate exposure in the first trimester and the risk of pregnancy loss. Very early pregnancy losses were not considered in this study, and whether survival bias influenced the results should be further explored.

Nitrate in Drinking Water and Time to Pregnancy or Medically Assisted Reproduction in Women and Men: A Nationwide Cohort Study in the Danish National Birth Cohort.

PurposeNo studies have investigated if drinking water nitrate affects human fecundity. Experimental studies point at detrimental effects on fetal development and on female and male reproduction. This cohort study aimed to explore if female and male preconception and long-term exposure to nitrate in drinking water was associated with fecundability measured as time to pregnancy (TTP) or use of medically assisted reproduction (MAR) treatment.MethodsThe study population consisted of pregnant women recruited in their first trimester in 1996–2002 to the Danish National Birth Cohort. Preconception drinking-water nitrate exposure was estimated for the pregnant women (89,109 pregnancies), and long-term drinking water nitrate exposure was estimated from adolescence to conception for the pregnant women (77,474 pregnancies) and their male partners (62,000 pregnancies) by linkage to the national drinking water quality-monitoring database Jupiter. Difference in risk of TTP >12 months or use of MAR treatment between five exposure categories and log-transformed continuous models of preconception and long-term nitrate in drinking water were estimated. Binominal regression models for risk ratios (RR) were adjusted for age, occupation, education, population density, and lifestyle factors.ResultsNitrate in drinking water (median preconception exposure: 1.9 mg/L; median long-term exposure: 3.3 mg/L) was not associated with TTP >12 months or use of MAR treatment, neither in the categorical nor in the continuous models.ConclusionWe found no association between preconception or long-term exposure to drinking water nitrate and fecundability.

Exposure to nitrate from food and drinking-water in New Zealand. Can these be considered separately?

Recent epidemiological studies have reported associations between colorectal cancer incidence and nitrates in drinking-water, but not from the diet. The toxicokinetics of nitrates were reviewed and exposure data from New Zealand were analysed. Dietary (including drinking-water) exposure of New Zealanders to nitrates was found to be very similar to most other countries and within internationally-established acceptable daily intakes. Less than 10% of nitrate exposure was from drinking-water, with little difference between adults and children. Approximately half of the total water-based exposure is through water alone, the remainder was consumed as tea and coffee (adults), or water-based fruit drinks (children). For children, drinking-water as a beverage is generally consumed close to a meal time, with 83% of servings consumed within an hour of eating. For adults, this is reduced to 51% of servings consumed within an hour of a meal. Only 2.6% of nitrate exposure for adults and 0.7% of nitrate exposure for children is from drinking-water consumed on its own and not in close temporal association to food consumption. It was concluded from the combination of the biology and the exposure assessment that there is little reason to differentiate between drinking-water and food nitrate exposure.

Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997\u20132017

BackgroundNitrosatable 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.MethodsWe 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.ResultsDrinking 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)].ConclusionsThe 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.

Drinking Water Sources and Water Quality in the Agricultural Health Study

BACKGROUND AND AIM: Drinking water contaminants have been associated with adverse health effects. However, little is known about exposures in agricultural communities where farm practices and well use may enhance exposures to specific contaminants. We describe the exposure assessment and exposure distributions for common drinking water contaminants by water source in an agricultural population. METHODS: We used questionnaire data from the Agricultural Health Study (AHS), a cohort of licensed pesticide applicators (mostly farmers) and their spouses in Iowa (IA) and North Carolina (NC) to ascertain drinking water source at enrollment (1993-1997). For users of public water supplies (PWS), we linked participants’ geocoded addresses to monitoring data for regulated contaminants, including five haloacetic acids (HAA5), total trihalomethanes (TTHM), and nitrate-nitrogen (NO₃-N). For private well users, we estimated nitrate levels using previously developed random forest models based on well depth, land use, soil characteristics, nitrogen inputs, and other relevant factors. RESULTS:We assigned drinking water source for 84% (N=74,919) of AHS participants; approximately 70% in IA and 75% in NC used private wells. Median nitrate concentrations (mg/L NO₃-N) in PWS were higher in IA (0.8, interquartile range (IQR): 0.2-3.1) than NC (0.5, IQR: 0.5-0.6), while median concentrations of HAA5 (µg/L) and TTHM (µg/L) were higher in NC (HAA5: 12.1, IQR: 3.8-33.4; TTHM: 35.4, IQR: 8.8-54.7) than IA (HAA5: 4.3, IQR: 3.0-10.5; TTHM: 13.0, IQR: 3.7-32.3). Private well nitrate concentrations in IA (1.5, IQR: 0.8-4.9) and NC (1.9, IQR: 1.4-2.5) were higher than in PWS. A larger proportion of private wells exceeded the 10mg/L regulatory limit in IA (12%) than NC (1%). CONCLUSIONS:Drinking water nitrate levels were higher for private well users and in IA PWS, while TTHM and HAA5 levels were higher in NC PWS. This work will facilitate future analyses of the health effects of drinking water contaminants in the AHS. KEYWORDS: Water quality, Exposure assessment, Environmental epidemiology

Association between nitrate concentration in drinking water and rate of colorectal cancer: a case study in northwestern Iran

ABSTRACT Nitrate, as a major pollutant of drinking water, is associated with colorectal cancer (CRC) and serves as an environmental health concern, especially in the districts with unregulated agriculture. In this case study in northwestern Iran, we used two databases of nitrate concentration (1999–2013) and age-standardized incidence rate (ASR) for CRC (2002–2012) from 19 counties of East Azerbaijan province. The trend and correlation between nitrate and ASR was investigated. Inverse distance weighted technique was used to spatially interpolate the maps. Expectedly, drinking water nitrate has increased throughout the province (8–20.5 mg/L) as well as the ASR for CRC of men (from 2.07 to 18.05 mg/L) and women (from 1.57 to 10.94 mg/L). While ASR for CRC of men was positively correlated to nitrate (Pearson’s r = 0.624, p-value = 0.040), no statistically significant correlation was found between nitrate and ASR for women’s CRC (Pearson’s r = 0.289, p-value = 0.351). According to our findings, the incidence of CRC was not higher for those residing in the regions with higher nitrate, suggesting that risk factors such as genetic predisposition and diet that were not taken into account could be determinants of this pattern. However, even a small increase in CRC rate due to water nitrate could translate into a large public health concern. The incremental pattern observed in nitrate levels of different counties over the years gives the health policymakers a better perspective of the problem and how the control of water nitrate level as a CRC risk factor might contribute to the prevention of CRC.

Effects of processed meat and drinking water nitrate on oral and fecal microbial populations in a controlled feeding study

BackgroundOne mechanism that can explain the link between processed meat consumption and colorectal cancer (CRC) is the production of carcinogenic N-nitroso compounds (NOCs) in the gastrointestinal tract. Oral and gut microbes metabolize ingested proteins (a source of secondary and tertiary amines and amides) and can reduce nitrate to nitrite, generating potentially carcinogenic NOCs. ObjectiveWe evaluated whether nitrate/nitrite in processed meat or water influences the fecal or salivary microbiota. DesignIn this dietary intervention study, 63 volunteers consumed diets high in conventional processed meats for two weeks, switched to diets high in poultry for two weeks, and then consumed phytochemical-enriched conventional processed or low-nitrite processed meat diets for two weeks. During the intervention, they drank water with low nitrate concentrations and consumed a healthy diet with low antioxidants. Then the volunteers drank nitrate-enriched water for 1 week, in combination with one of the four different diets. We measured creatinine-adjusted urinary nitrate levels and characterized the oral and fecal microbiota using 16S rRNA amplicon sequencing. ResultsUsing linear mixed models, we found that, compared to baseline, urinary nitrate levels were reduced during the phytochemical-enriched low-nitrite meat diet (p-value = 0.009) and modestly during the poultry diet (p-value = 0.048). In contrast, urinary nitrate increased after 1-week of drinking nitrate-enriched water (p-value<10−5). Nitrate-enriched water, but not processed meats with or without phytochemicals, altered the saliva microbial population (p-value ≤0.001), and significantly increased abundance of 8 bacterial taxa, especially genus Neisseria and other nitrate-reducing taxa. Meats, phytochemicals and nitrate-enriched water had no significant effects on saliva alpha diversity or any diversity parameter measured for the fecal microbiota. ConclusionThese findings support the hypothesis that drinking high nitrate water increases oral nitrate-reducing bacteria, which likely results in increased NOC. However, meat nitrate/nitrite at the levels tested had no effect on either the gut or oral bacteria. ClinicalTrials.gov IdentifierNCT04138654.