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Consumption of high NO 3 containing water may pose serious health hazard especially in children (< 5 years). The source of NO 3 in groundwater includes surface leaching from wastewater and waste dump sites, animal excreta disposal, industrial effluents, and N-based fertilizers, etc. This study aimed to investigate the concentration of NO 3 in groundwater of 14 intensively cultivated districts of Malwa Punjab, India, and its possible health hazards in local residents. The sampling of 76 sites revealed the concentration of NO 3 in ranges of 38.45-198.05 mgL -1 , and over 92% sites showed the high level of it than the safe limits as decided by the Bureau of Indian standards (45 mg L -1 ) and World Health Organization (50 mg L -1 ). The possible health hazards of high NO 3 intake was estimated using USEPA human health risk assessment (HHRA) model for both adult and children. Results of this study suggested the chronic daily intake (CDI) in the ranges of 1.09-5.65 and 2.56-13.20 in adult and children population of this region, respectively. The hazard quotient (HQ nitrate ) value was > 1 in most sampling locations ranging 1.09-5.65 for the adult and 2.56-13.20 for children population of Malwa. This study indicates that 93.42% adult and 100% young population of the Malwa are at higher risk of chronic toxicity by excess NO 3 intake. The HHRA results suggested a high vulnerability of a local community to NO 3 toxicity in this region; therefore, there is an instant need to take preventive measures to safeguard the health of local residents.

Purpose: To estimate the nitrate levels in private wells located in different parts of Enugu and discuss the future health implications following chronic ingestion of well water., Materials and Methods: The map of Enugu was used to divide the city into many 25 units, using grid lines 1 cm apart. Cluster sampling method was used to collect samples. These samples were sent to two laboratories for estimation of nitrate levels. The people drawing water from the different wells were interviewed to determine what they used the water for., Result: The subjects who were interviewed said they ingested the water. The nitrate levels found in these wells (median value of 31 mg/L) were significantly higher than the internationally accepted levels of nitrate in water for ingestion, (P < 0.0001)., Conclusion: High nitrate levels drinking water is dangerous to health and can cause methemoglobinemia in children. It may also increase cancer risk in adults because nitrate is endogenously reduced to nitrite and subsequent nitrosation reactions give rise to N-nitroso compounds (NOCs), which are highly carcinogenic and can act systemically.

The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from gastric cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of nitrate on the risk of gastric cancer development. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to gastric cancer and exposure to nitrate in drinking water in Taiwan. All deaths due to gastric cancer in Taiwan residents from 2006 through 2010 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Deaths from other causes served as controls and were pair-matched to cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO(3)-N), Ca, and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was presumed to be the source of the subject's NO(3)-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO(3)-N exposure levels were <0.38 ppm, the adjusted odds ratio (OR) and 95% confidence interval (CI) for gastric cancer occurrence was 1.16 (1.05-1.29) for individuals who resided in municipalities served by drinking water with a NO(3)-N exposure ≥ 0.38 ppm. There was apparent evidence of an interaction between drinking water NO(3)-N levels and low Ca and Mg intake via drinking water. Our findings showed that the correlation between NO(3)-N exposure and risk of gastric cancer development was influenced by Ca and Mg levels in drinking water. This is the first study to report effects modification by Ca and Mg intake from drinking water on the relationship between NO(3)-N exposure and risk of gastric cancer occurrence. Increased knowledge of the mechanistic interactions between Ca, Mg, and NO(3)-N in reducing risk of gastric cancer development will aid in public policy decisions and setting threshold standards.

The retrospective cohort study described in this article examined 150 Iowa private well users' (aged 1-60 years) drinking water below the 10 parts per million nitrate-nitrogen (nitrate-N) maximum contaminant level and analyzed health history data and blood samples including hemoglobin fractions and immunological parameters. Positive associations existed (bivariate fit) between higher nitrate exposure and body mass index, lower recreational activity, perceived poorer health, and perceptions of susceptibility to illness. A directly proportionate relationship was seen between methemoglobin level in the blood and nitrate ingestion. High tumor necrosis factor-beta (TNF-beta) expression was also seen (bivariate fit, f = 3.76, p = .05). Complaints of stomach/ intestinal difficulties (heartburn/reflux > 50%; f = 5.274, p = .0231) and bone, muscle, and nerve complaints (osteoarthritis [rheumatoid excluded] = 47%; f = 6.0533, p = .0150) were found with increasing nitrate exposure. In vivo exposures of nitrate-N associated with complaints of bone/joint disorders or with altered ex vivo production of TNF-beta or Th2/Treg cytokine interleukin-10 have not been previously illustrated with environmental exposures.

Drinking water for approximately one sixth of US households is obtained from private wells. These wells can become contaminated by pollutant chemicals or pathogenic organisms and cause illness. Although the US Environmental Protection Agency and all states offer guidance for construction, maintenance, and testing of private wells, there is little regulation. With few exceptions, well owners are responsible for their own wells. Children may also drink well water at child care or when traveling. Illness resulting from children's ingestion of contaminated water can be severe. This policy statement provides recommendations for inspection, testing, and remediation for wells providing drinking water for children.

Drinking water for approximately one sixth of US households is obtained from private wells. These wells can become contaminated by pollutant chemicals or pathogenic organisms, leading to significant illness. Although the US Environmental Protection Agency and all states offer guidance for construction, maintenance, and testing of private wells, there is little regulation, and with few exceptions, well owners are responsible for their own wells. Children may also drink well water at child care or when traveling. Illness resulting from children's ingestion of contaminated water can be severe. This report reviews relevant aspects of groundwater and wells; describes the common chemical and microbiologic contaminants; gives an algorithm with recommendations for inspection, testing, and remediation for wells providing drinking water for children; reviews the definitions and uses of various bottled waters; provides current estimates of costs for well testing; and provides federal, national, state, and, where appropriate, tribal contacts for more information.

The relationship between nitrate levels in drinking water and risk of pancreatic cancer development remains inconclusive. A matched case-control and nitrate ecology study was used to investigate the association between mortality attributed to pancreatic cancer and nitrate exposure from Taiwan's drinking water. All pancreatic cancer deaths of Taiwan residents from 2000 through 2006 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO(3)-N) levels of drinking water throughout Taiwan were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cancer cases and controls was assumed to be the source of the subject's nitrate exposure via drinking water. The adjusted odds ratios and confidence limits for pancreatic cancer death for those with high nitrate levels in their drinking water, as compared to the lowest tertile, were 1.03 (0.9-1.18) and 1.1 (0.96-1.27), respectively. The results of the present study show that there was no statistically significant association between the levels of nitrate in drinking water and increased risk of death from pancreatic cancer.

Context: Nitrate is ubiquitous in environmental media (air, water and soil) and other sources (some medicines, inorganic fertilizers and household's chemicals). It is a hemoglobin-oxidizing agent that can cause methemoglobinemia. The effect of nitrate on infants is well known but less is known about nitrate-induced methemoglobinemia in young children., Method: Two cross-sectional studies were carried out in Salé, Morocco to determine the prevalence of methemoglobinemia among 411 infants and children aged 1-7 years in two adjacent areas that were similar in terms of the air quality, available vegetables and medicines but different in terms of the drinking water quality (nitrate-contaminated well water versus municipal water)., Results: In the exposed area, nitrate concentration was measured in 78 wells and ranged from 15.39 to 246.90mg/l as NO3-. Nitrate levels were higher than 50mg/l in 69.2% of the surveyed wells, and 64.2% of the participants were drinking nitrate contaminated well waters. The prevalence of methemoglobinemia among study children was 36.2% in the exposed area, and 27.4% in the non-exposed area. Study children drinking well water with a nitrate concentration >50mg/l were significantly more likely to have methemoglobinemia than those drinking well water with a nitrate concentration <50mg/l (p=0.001 at 95% CI=[1.22-2.64]) or than those drinking municipal water (p<0.01 at 95% CI=[1.16-2.21]). In the exposed area, the mean methemoglobin (MetHb) level increased with age (R2= 0.79, p=0.04), whereas in the unexposed area, the mean MetHb level remained relatively stable in the first 6 years of life (R2=0.21, p=0.44). Mean MetHb was normal when the nitrate concentration in water was below 50mg/l as NO3-, and reached an abnormal level, when the nitrate concentration in water ranged between 50 and 90mg/l as NO3-. This last level was statistically similar to mean MetHb at nitrate level above 90mg/l as NO3- (up to 246.9mg/l as NO3-). No association was observed between methemoglobinemia prevalence and gender. This is the first study about methemoglobinemia conducted in Morocco.

One unintentional result of widespread adoption of nitrogen application to croplands over the past 50 years has been nitrate contamination of drinking water with few studies evaluating the risk of colorectal cancer. In our population-based case-control study of 475 women age 20-74 years with colorectal cancer and 1447 community controls living in rural Wisconsin, drinking water nitrate exposure were interpolated to subjects residences based on measurements which had been taken as part of a separate water quality survey in 1994. Individual level risk factor data was gathered in 1990-1992 and 1999-2001. Logistic regression models estimated the risk of colorectal cancer for the study period, separately and pooled. In the pooled analyses, an overall colorectal cancer risk was not observed for exposure to nitrate-nitrogen in the highest category (> or =10 ppm) compared to the lowest category (<0.5 ppm). However, a 2.9 fold increase risk was observed for proximal colon cancer cases in the highest compared to the lowest category. Statistically significant increased distal colon or rectal cancer risk was not observed. These results suggest that if an association exists with nitrate-nitrogen exposure from residential drinking water consumption, it may be limited to proximal colon cancer.

We conducted a population-based case-control study of adenocarcinoma of the stomach and esophagus in Nebraska, U.S.A. Nitrate concentrations in public drinking water supplies were linked to residential water source histories. Among those using private wells at the time of the interview, we measured nitrate levels in water samples from wells. Dietary nitrate and nitrite were estimated from a food-frequency questionnaire. Among those who primarily used public water supplies (79 distal stomach, 84 esophagus, 321 controls), average nitrate levels were not associated with risk (highest versus lowest quartile: stomach OR=1.2, 95% CI [0.5-2.7]; esophagus OR=1.3, 95% CI [0.6-3.1]). We observed the highest ORs for distal stomach cancer among those with higher water nitrate ingestion and higher intake of processed meat compared with low intakes of both; however, the test for positive interaction was not significant (p=0.213). We did not observe this pattern for esophagus cancer. Increasing intake of nitrate and nitrite from animal sources was associated with elevated ORs for stomach cancer and with a significant positive trend in risk of esophagus cancer (P-trend=0.325 and 0.015, respectively). Larger studies with higher exposures to drinking water sources of nitrate are warranted to further evaluate N-nitroso compound precursors as risk factors for these cancers.

Drinking water and dietary sources of nitrate and nitrite can react in vivo with amines and amides to form N-nitroso compounds (NOC), potent animal carcinogens. Nitrate is a widespread contaminant of drinking water supplies especially in agricultural areas. We conducted a population-based case-control study of renal cell carcinoma in 1986-1989 in Iowa, a state with elevated levels in many public water supplies. We collected a lifetime water source history, but due to limited monitoring data, most analyses focused on the subpopulation, who used Iowa public supplies with nitrate measurements (actual or imputed data) for > or = 70% of their person-years since 1960 (201 cases, 1,244 controls). We computed the average nitrate level and years using a public supply with nitrate levels >5 and >10 mg/l. Dietary nitrate and nitrite were estimated from a 55-item food frequency questionnaire. There was no association of renal cell carcinoma with the average nitrate level and years using public supplies >5 and >10 mg/l nitrate-nitrogen (10+ years >5 mg/l odds ratio (OR) = 1.03, 95% confidence interval (CI) 0.66, 1.60). However, higher nitrate exposure was associated with an increased risk among subgroups with above the median red meat intake (10+ years >5 mg/l OR = 1.91, 95% CI 1.04-3.51) or below the median vitamin C intake (10+ years >5 mg/l OR = 1.90, 95% CI 1.01, 3.56), dietary factors that increase the endogenous formation of NOC. Exclusion of long-term Des Moines residents, a large proportion of the high exposure categories, attenuated the association. These findings deserve additional study in populations with high water nitrate intake and information on dietary intakes.

A descriptive, cross-sectional and analytical study was carried out in 3 areas of the Gaza Strip, Palestine, in 2002, to determine the factors associated with high methaemoglobin (Met-Hb) levels in infants and the relationship with nitrate concentration in drinking water wells. Drinking water sources were likely to be the main factor for high levels of Met-Hb. Out of 338 infants attending for vaccination, having supplemental feeding, use of boiled water and age 3-6 months were associated with high Met-Hb levels. The highest mean Met-Hb level was in Khan-Younis, where the highest mean nitrate concentration was recorded in drinking water. The results emphasize the importance of exclusive breastfeeding for infants < 6 months old, and the choice of a suitable source of water for these infants.

In this review, we present an update on maternal exposure to nitrates in drinking water in relation to possible adverse reproductive and developmental effects, and discuss nitrates in drinking water in the United States. The current standard for nitrates in drinking water is based on retrospective studies and approximates a level that protects infants from methemoglobinemia, but no safety factor is built into the standard. The current standard applies only to public water systems. Animal studies have found adverse reproductive effects resulting from higher doses of nitrate or nitrite. The epidemiologic evidence of a direct exposure-response relationship between drinking water nitrate level and adverse reproductive effect is still not clear. However, some reports have suggested an association between exposure to nitrates in drinking water and spontaneous abortions, intrauterine growth restriction, and various birth defects. Uncertainties in epidemiologic studies include the lack of individual exposure assessment that would rule out confounding of the exposure with some other cause. We conclude that the current literature does not provide sufficient evidence of a causal relationship between exposure to nitrates in drinking water and adverse reproductive effects.

Several authors have suggested that it is safe to raise the health standard for nitrate in drinking water, and save money on measures associated with nitrate pollution of drinking water resources. The major argument has been that the epidemiologic evidence for acute and chronic health effects related to drinking water nitrate at concentrations near the health standard is inconclusive. With respect to the chronic effects, the argument was motivated by the absence of evidence for adverse health effects related to ingestion of nitrate from dietary sources. An interdisciplinary discussion of these arguments led to three important observations. First, there have been only a few well-designed epidemiologic studies that evaluated ingestion of nitrate in drinking water and risk of specific cancers or adverse reproductive outcomes among potentially susceptible subgroups likely to have elevated endogenous nitrosation. Positive associations have been observed for some but not all health outcomes evaluated. Second, the epidemiologic studies of cancer do not support an association between ingestion of dietary nitrate (vegetables) and an increased risk of cancer, because intake of dietary nitrate is associated with intake of antioxidants and other beneficial phytochemicals. Third, 2-3 % of the population in Western Europe and the US could be exposed to nitrate levels in drinking water exceeding the WHO standard of 50 mg/l nitrate, particularly those living in rural areas. The health losses due to this exposure cannot be estimated. Therefore, we conclude that it is not possible to weigh the costs and benefits from changing the nitrate standard for drinking water and groundwater resources by considering the potential consequences for human health and by considering the potential savings due to reduced costs for nitrate removal and prevention of nitrate pollution.

Introduction: Nitrate and nitrite are precursors in the in vivo formation of N-nitroso compounds, potent animal carcinogens., Methods: We conducted a population-based case-control study of non-Hodgkin lymphoma (NHL) in 1998 to 2000 in Iowa, Detroit, Seattle, and Los Angeles. Because nitrate levels were elevated in many drinking water supplies in Iowa, but not in the other study centers, we evaluated water nitrate levels and risk of NHL in Iowa only. Monitoring data for public supplies were linked to water source histories from 1960 onward. Nitrate was measured at interview homes with private wells. We limited most analyses to those with nitrate estimates for > 70% of their person-years since 1960 (181 cases, 142 controls). For those in the diet arm of the study (458 cases, 383 controls from 4 centers) and for Iowa participants in both the diet and drinking water analyses, we estimated dietary nitrate and nitrite intake using a 117-item food-frequency questionnaire that included foods high in nitrate and nitrite. Odds ratios and 95% confidence intervals were calculated using logistic regression, adjusting for the study matching factors, education, and caloric intake (diet analyses only)., Results: We found no overall association with the highest quartile of average drinking water nitrate (> 2.90 mg/L nitrate-N: odds ratios = 1.2; 95% confidence interval = 0.6-2.2) or with years > or = 5 mg/L (10+ years: 1.4; 0.7-2.9). We observed no evidence of an interaction between drinking water nitrate exposure and either vitamin C or red meat intake, an inhibitor and precursor, respectively, of N-nitroso compound formation. Among those in the diet arm, dietary nitrate was inversely associated with risk of NHL (highest quartile: 0.54; 0.34-0.86). Dietary nitrite intake was associated with increasing risk (highest quartile: 3.1; 1.7-5.5) largely due to intakes of bread and cereal sources of nitrite., Conclusion: Average drinking water nitrate levels below 3 mg/L were not associated with NHL risk. Our study had limited power to evaluate higher levels that deserve further study.

A study was made on the physico-chemical characteristics of water samples mixed with effluent discharged from textile industries at Chellandipalayam (Site--I), Senaparatti (Site--II) and Pasupathipalayam (Sites--III and IV) revealed the elevated levels of Ca, Mg, Na, Cr, K, Ni, Cu, Zn, CO3, SO4, NO3 and Cl- . The concentrations of these ions exceeded the limit prescribed by ISI. The increase in the concentrations of ions was revealed by higher values of electrical conductivity (EC). Water at these sites was found to be hard, brackish and unsuitable for drinking purpose. In all these sites, the seed germination of rice alone was significantly affected among the other crops tested. Irrigation of crops with ground water notably lowered the quantity of reserve food in rice, wheat (starch), and sugarcane (sugar), indicating the interference of their metabolic pathway by polluted ground water.

This study explored two hypotheses relating elevated concentrations of nitrogen species in drinking water and the disease Balkan Endemic Nephropathy (BEN). Drinking water samples were collected from a variety of water supplies in both endemic and non-endemic villages in the Vratza and Montana districts of Bulgaria. The majority of well water samples exceeded US drinking water standards for nitrate + nitrite. No statistically significant difference was observed for any of the nitrogen species between villages classified as endemic and non-endemic. Other constituents (sodium, potassium and chloride) known to be indicators of anthropogenic pollution were also found at elevated concentrations and all followed the order wells > springs > taps. This ordering coincides with the proximity of human influences to the water sources. Our results clearly establish an exposure pathway between anthropogenic activity and drinking water supplies, suggesting that the causative agent for BEN could result from surface contamination.

N-Nitroso compounds, known animal carcinogens, are formed endogenously from drinking water and dietary sources of nitrate and nitrite. The authors conducted a population-based case-control study of pancreatic cancer in Iowa to determine whether increased consumption of nitrate and nitrite from drinking water and dietary sources was associated with risk. They linked detailed water source histories to nitrate measurements for Iowa community water supplies. After exclusions for insufficient data, 1,244 controls and 189 pancreatic cancer cases were available for analysis. Among controls, the median average nitrate level (1960-1987) was 1.27 (interquartile range, 0.6-2.8) mg of nitrate nitrogen per liter of water. No association was observed between pancreatic cancer risk and increasing quartiles of the community water supplies' nitrate level. Increasing intake of dietary nitrite from animal sources was associated with an elevated risk of pancreatic cancer among men and women (highest quartile odds ratios = 2.3, 95% confidence interval: 1.1, 5.1, for men and 3.2, 95% confidence interval: 1.6, 6.4, for women). In contrast, dietary nitrate intake showed an inverse association with risk among women and no association among men. This study suggests that long-term exposure to drinking water nitrate at levels below the maximum contaminant level of nitrate nitrogen (10 mg/liter) is not associated with pancreatic cancer; however, the consumption of dietary nitrite from animal products may increase risk.

Water samples from 20 artesian wells, chosen by the multistage sampling procedure from 5 zones in the city of Enugu, Southeast Nigeria, were analyzed by the disulfonic acid method in duplicate for the presence of nitrate (NO3) and nitrite (NO2). The zonal mean values for NO3 were 0.45 mmol/l, 0.46 mmol/l, 0.55 mmol/l, 0.59 mmol/l, and 0.65 mmol/l (mean = 0.54 mmol/l), and for NO2 the values were 0.34 mmol/l, 0.32 mmol/l, 0.21 mmol/l, 0.14 mmol/l, and 0.20 mmol/l (mean = 0.24 mmol/l), respectively. The mean values were reciprocally related (r = -.7356, p = 0.0002), indicating fecal contamination of well water. There were no significant differences between the mean values and the sum of the NO3 and NO2 values of the samples (p > 0.05), indicating uniform nitrogen content in the region. The mean value for NO3 (0.54 mmol/l) was below the guideline values set by the World Health Organization, but the mean NO2 concentration of 0.24 mmol/l was much higher (290%) than what is considered safe for humans.

Background: Nitrate is a precursor compound in the formation of N-nitroso compounds, most of which are potent animal carcinogens. N-nitroso compounds and their precursors have not been extensively evaluated as bladder cancer risk factors., Methods: We conducted a population-based case-control study of bladder cancer in Iowa. Cases were men and women newly diagnosed with bladder cancer in 1986-1989. Nitrate data for Iowa public water supplies were sparse before the 1960s. To reduce misclassification by unknown nitrate levels, we included only those who used public supplies with nitrate data for 70% or more of their person-years since 1960 (808 cases, 1259 controls)., Results: Among controls, the median average nitrate level for their Iowa residences with public water supplies was 1.3 mg/liter nitrate-nitrogen (interquartile range = 0.6-3.0). After adjustment for confounders, we found no increased risk of bladder cancer with increasing average nitrate levels in drinking water; the highest quartile odds ratio for women was 0.8 (95% confidence interval = 0.4-0.8), and for men 0.5 (0.4-0.8). We observed no association among those with high water nitrate exposure (>median) and low (

Nitrate from drinking water is converted in the body to nitrite by bacteria in the gut. This project examined effects of nitrate/nitrite on immune functions, i.e., human lymphocyte proliferation and cytokine production. Nitrate had no effect on lymphocyte growth, but nitrite decreased proliferation. Neither inhibited fibroblast growth. In 1/3 to 2/3 of the subjects tested, sodium nitrate or nitrite decreased production of Th1 cytokines (interleukin-2, interferon-gamma, and tumor necrosis factor-beta). Nitrate and nitrite either increased or had no effect on the production of the Th2 cytokine interleukin-10. A Th1 immune response is associated with resistance to a variety of infectious diseases; a Th2 response is associated with disease susceptibility. Because nitrate/nitrite shifted the balance from a Th1 to a Th2 response in some individuals, exposure to these compounds may decrease these persons' responsiveness to infectious diseases. The levels of nitrate used in this study are relevant to human health because they are present in the liquid portion (nonbreastfed) of some 2-month-old infants' diets in rural Romania.

Contaminated tap water can become a health risk, e.g. by metals or environmental pollution particularly for sensitive population groups such as infants and young children. There is a lack of data on exactly measured water intake. In the DONALD Study, individual food and fluid intakes were measured by use of 3-day weighed diet records. Here we report on the distribution of individual intakes of tap water in 504 healthy normally nourished subjects aged 3-36 months (1962 diet records) between 1990 and 1998. We calculate scenarios for potential tap water contamination. Tap water intake per kg body weight was significantly higher in formula-fed (FF) infants than in breast-fed (BF) infants. The estimated median intake of lead and nitrate per kg body weight from tap water was higher in FF infants than in BF infants or mixed fed (MF) young children. The scenarios based on intakes at the median, P95 or maximums show that higher risks for exceeding the presently existing maximums could be expected in FF infants. Our data could also be used for estimations of potential risks from other contaminants of tap water.

In this nested case-control study, we investigated the risk factors for methemoglobinemia (MHG) in 71 children in the Transylvania region of Romania. This study was unique in that the exposures for cases and controls were calculated as continuous values and were reported in milligrams per kilogram per day of nitrate/nitrite based on careful dietary reconstruction and environmental sampling. This procedure allowed us to compare point estimates of nitrate/nitrite exposure with other continuous, categoric, and ranked risk factors such as the presence or absence of diarrheal disease, reported severity of diarrheal disease, the use of vitamin supplements, the presence, absence, and/or duration of breast-feeding, and whether or not first-generation relatives experienced MHG. Analysis of these factors and exposure levels using both univariate and multivariate whole-model tests was performed to understand the relative significance of risk factors at varying levels of exposure to the development of MHG. Univariate and multifactorial analysis of risk factors for MHG underscored that, for this population, MHG is most strongly associated with nitrate/nitrite exposure through the dietary route (p = 0.0318), via feeding of formula and tea made with water containing high levels of nitrates, and that breast-feeding protects infants younger than 6 months of age (p = 0.0244). Our findings also raise questions about the role of diarrheal disease in the development of MHG, as likelihood ratios (likelihood 4.323, p = 0.0376) and multifactorial analysis indicated a significant role for diarrheal disease for some individuals.

Drinking water disinfection byproducts have been associated with an increased risk for congenital defects including cardiac defects. Using Swedish health registers linked to information on municipal drinking water composition, individual data on drinking water characteristics were obtained for 58,669 women. Among the infants born, 753 had a cardiac defect. The risk for a cardiac defect was determined for ground water versus surface water, for different chlorination procedures, and for trihalomethane and nitrate concentrations. Ground water was associated with an increased risk for cardiac defect when crude rates were analyzed but after suitable adjustments this excess rate was found to be determined by chlorination procedures including chlorine dioxide. Chlorine dioxide appears itself as an independent risk factor for cardiac defects (adjusted odds ratio 1.61 (95%CI 1.00-2.59)). The risk for cardiac defects increased with increasing trihalomethane concentrations (P=0.0005). There was an indicated but statistically nonsignificant excess risk associated with nitrate concentration. The individual risk for congenital cardiac defect caused by chlorine dioxide and trihalomethanes is small but as a large population is exposed to public drinking water, the attributable risk for cardiac defects may not be negligible.

An attempt has been made to classify ground waters in various districts of Rajasthan based on distribution of nitrate in their drinking water samples. It is seen that nitrate in ground water is unevenly distributed in the state. Major parts of Churu, Alwar, Bharatpur, Jalore, Jaipur, Sikar, Tonk and Jhunjhunu, are inherited by nitrate rich ground waters while districts like Banswara, Bundi, Bikaner, Chittor, Kota and Jhalawar have low nitrates in their ground waters at many places. It is well documented internationally that water supplied containing high levels of nitrate have been responsible for cases of infantile methemoglobinemia which may ultimately lead to death. A very high infant mortality rate in Rajasthan might be a consequence of high nitrates in drinking water supply. Some recent studies have shown that nitrates in drinking water besides causing methemoglobinemia can result in various other clinical manifestations like recurrent stomatitis, recurrent respiratory tract infections (RRTI) etc. These findings have indicated that a rethinking has to be given to the existing standards for nitrates in drinking water. Based on potential nitrate toxicity studies in view of above health effects the whole region has been classified into five water quality zones, namely, safe, mild, moderately problematic, highly problematic and dangerous. For areas falling under fourth and fifth zones it is recommended that immediate measures be taken to overcome the adverse health effects.

Contamination of drinking water by nitrate is an evolving public health concern since nitrate can undergo endogenous reduction to nitrite, and nitrosation of nitrites can form N-nitroso compounds, which are potent carcinogens. We conducted an ecologic study to determine whether nitrate levels in drinking water were correlated with non-Hodgkin lymphoma and cancers of the digestive and urinary tracts in an agricultural district (Trnava District; population 237,000) of the Slovak Republic. Routinely collected nitrate data (1975-1995) for villages using public water supplies were computerized, and each village was categorized into low (0-10 mg/L), medium (10.1-20 mg/L), or high (20.1-50 mg/L) average levels of total nitrate in drinking water. Observed cases of cancer in each of these villages were ascertained through the district cancer registry for the time period 1986-1995. Standardized incidence ratios (SIRs) and 95% confidence intervals (CI) for all cancer and selected cancer sites were calculated by indirect standardization using age- and sex-specific incidence rates from the entire district. For all cancer in women, SIRs increased from villages with low (SIR=0.87; 95% CI 0.72-0.95) to medium (SIR=1.07; 95% CI 1.00-1.13) to high (SIR=1.14; 1.06-1.22) levels of nitrate (P for trend <0.001); there was a similar trend for all cancer in men from low (SIR=0.90; 95% CI 0.81-0.99) to medium (SIR=1.08, 95% CI 1.02-1.16), but not for high (SIR=0.94; 0.88-1.02), nitrate levels (P for trend <0.001). This pattern in the SIRs (from low to high nitrate level) was also seen for stomach cancer in women (0.81, 0.94, 1.24; P for trend=0.10), colorectal cancer in women (0.64, 1.11, 1.29; P for trend <0.001) and men (0.77, 0.99, 1.07; P for trend=0.051), and non-Hodgkin lymphoma in women (0.45, 0.90, 1.35; P for trend=0.13) and men (0.25, 1.66, and 1.09; P for trend=0.017). There were no associations for kidney or bladder cancer. These ecologic data support the hypothesis that there is a positive association between nitrate in drinking water and non-Hodgkin lymphoma and colorectal cancer., ((c) 2002 Elsevier Science (USA).)

Nitrate contamination of drinking water may increase cancer risk, because nitrate is endogenously reduced to nitrite and subsequent nitrosation reactions give rise to N-nitroso compounds; these compounds are highly carcinogenic and can act systemically. We analyzed cancer incidence in a cohort of 21,977 Iowa women who were 55-69 years of age at baseline in 1986 and had used the same water supply more than 10 years (87% > 20 years); 16,541 of these women were on a municipal supply, and the remainder used a private well. We assessed nitrate exposure from 1955 through 1988 using public databases for municipal water supplies in Iowa (quartile cutpoints: 0.36, 1.01, and 2.46 mg per liter nitrate-nitrogen). As no individual water consumption data were available, we assigned each woman an average level of exposure calculated on a community basis; no nitrate data were available for women using private wells. Cancer incidence (N = 3,150 cases) from 1986 through 1998 was determined by linkage to the Iowa Cancer Registry. For all cancers, there was no association with increasing nitrate in drinking water, nor were there clear and consistent associations for non-Hodgkin lymphoma; leukemia; melanoma; or cancers of the colon, breast, lung, pancreas, or kidney. There were positive associations for bladder cancer [relative risks (RRs) across nitrate quartiles = 1, 1.69, 1.10, and 2.83] and ovarian cancer (RR = 1, 1.52, 1.81, and 1.84), and inverse associations for uterine cancer (RR = 1, 0.86, 0.86, and 0.55) and rectal cancer (RR = 1, 0.72, 0.95, and 0.47) after adjustment for a variety of cancer risk/protective factors, agents that affect nitrosation (smoking, vitamin C, and vitamin E intake), dietary nitrate, and water source. Similar results were obtained when analyses were restricted to nitrate level in drinking water from 1955 through 1964. The positive association for bladder cancer is consistent with some previous data; the associations for ovarian, uterine, and rectal cancer were unexpected.

In this population-based case-control study conducted in California between June 1989 and May 1991, the authors investigated the association between maternal periconceptional exposure to nitrate from drinking water and diet and risk for neural tube defects. The mothers of 538 cases and 539 nonmalformed controls were interviewed regarding residential history, consumption of tap water at home, and dietary intake during the periconceptional period. Dietary nitrate exposure was not associated with increased risk for neural tube defects. Exposure to nitrate in drinking water at concentrations above the 45 mg/liter maximum contaminant level was associated with increased risk for anencephaly (odds ratio (OR) = 4.0, 95% confidence interval (CI): 1.0, 15.4), but not for spina bifida. Increased risks for anencephaly were observed at nitrate levels below the maximum contaminant level among groundwater drinkers only (OR = 2.1, 95% CI: 1.1,4.1 for 5-15 mg/liter; OR = 2.3, 95% CI: 1.1, 4.5 for 16-35 mg/liter; and OR = 6.9, 95% CI: 1.9, 24.9 for 36-67 mg/liter compared with <5 mg/liter). Adjustment for identified risk factors for anencephaly did not substantially alter these associations, nor did control for maternal dietary nitrate, total vitamin C intake, and quantity of tap water consumed. The lack of an observed elevation in risk for anencephaly in association with exposure to mixed water containing nitrate at levels comparable with the concentration in groundwater may indicate that something other than nitrate accounts for these findings.

Unlabelled: The authors compared the size of the thyroid gland, assessed by ultrasonographic examination of its volume and the functional state of the thyroid by examination of the serum level of TSH and anti-TPO antibodies in 492 pupils aged 10 and 13 years in two close agricultural areas. The areas differed above all as to the nitrate content of drinking water. In communities where the source of drinking water were private wells (nitrate area), as much as 68.1% of the water samples had a nitrate content > 50 mg/l and 46.4% samples > 100 mg/l. In communities where the source of drinking water was a water main with a known source (control area) the water samples did not exceed 50 mg/l (73.7% > 15 mg/l and 26.3% > 50 mg/l., Results: Pupils from the nitrate area had a larger thyroid gland similarly as older pupils from the control area. A volume above 7 ml/m2 in the nitrate area was recorded in the group of 10-year olds in 25/99 (27.7%) and in the group of 13-year-old ones in 33/154 (21.4%), while in the control area it was in the 10-year-old ones 11/92 (11.9%) and in the 13-year-old ones 16/156 (10.2%, P < or = 0.01). In the nitrate area TSH > 5 mIU/l was recorded in 5.6% and higher anti-TPO antibodies in 2.6% pupils. In the control area the corresponding figure was 1.1% pupils, P < or = 0.01.

Nitrate in drinking water has been implicated as a possible risk factor for non-Hodgkin's lymphoma. The authors examined the association between non-Hodgkin's lymphoma and waterborne nitrate through a population-based case-control study of white men in Minnesota. The authors, by linking residential histories with community water records, estimated average long-term exposure to nitrate in drinking water from 1947 to 1975 for 73 cases diagnosed between 1980 and 1982 and for 147 controls who used community water supplies. No association was found between nitrate levels in community water supplies and non-Hodgkin's lymphoma within the range of study exposures (median of highest exposure category = 2.4 mg nitrate/l [range = 0.1-7.2 mg/l]). The findings provide some safety assurance for those who use water systems that have nitrate levels that are less than 2.4 mg/l.

The role of nitrates in goitre genesis has been discussed for a long time. In the present report a comparative analysis is made of results obtained in villages with nitrate pollution of the drinking water. In two pairs of villages children aged between 3 and 14 were included, whose thyroid status was investigated by a clinical examination. The study was carried out in 2 stages--in 1995 and 1998. In this period the goitre incidence was significantly reduced in both sexes. Both investigations showed a higher relative risk of goitre in children exposed to water pollution by nitrates. In the first, as well as in the second examination, goitre was diffuse. We concluded that nitrate pollution of drinking water undoubtedly participated in goitre genesis. We did not underestimate the strumigenic effect of nitrates in the diet as they were not the object of our investigation and which, according to WHO experts, have a less strumigenic effect. After the first investigation we recommended a higher antistrumin dose as prophylaxis. That is why we conclude that the considerable goitre reduction in the second investigation was the positive result of the doubled antistrumin prophylaxis during the period between the two investigations.

The use of nitrate-contaminated drinking water to prepare infant formula is a well-known risk factor for infant methemoglobinemia. Affected infants develop a peculiar blue-gray skin color and may become irritable or lethargic, depending on the severity of their condition. The condition can progress rapidly to cause coma and death if it is not recognized and treated appropriately. Two cases of blue baby syndrome were recently investigated. Both cases involved infants who became ill after being fed formula that was reconstituted with water from private wells. Water samples collected from these wells during the infants' illnesses contained nitrate-nitrogen concentrations of 22.9 and 27.4 mg/L.

In recent years, several studies have addressed a possible relationship between nitrate exposure and childhood type 1 insulin-dependent diabetes mellitus. The present ecologic study describes a possible relation between the incidence of type 1 diabetes and nitrate levels in drinking water in The Netherlands, and evaluates whether the World Health Organization and the European Commission standard for nitrate in drinking water (50 mg/L) is adequate to prevent risk of this disease. During 1993-1995 in The Netherlands, 1,104 cases of type 1 diabetes were diagnosed in children 0-14 years of age. We were able to use 1,064 of these cases in a total of 2,829,020 children in this analysis. We classified mean nitrate levels in drinking water in 3,932 postal code areas in The Netherlands in 1991-1995 into two exposure categories. One category was based on equal numbers of children exposed to different nitrate levels (0.25-2.08, 2.10-6.42, and 6.44-41.19 mg/L nitrate); the other was based on cut-off values of 10 and 25 mg/L nitrate. We determined standardized incidence ratios (SIRs) for type 1 diabetes in subgroups of the 2,829,020 children with respect to both nitrate exposure categories, sex, and age and as compared in univariate analysis using the chi-square test for trend. We compared the incidence rate ratios (IRRs) by multivariate analysis in a Poisson regression model. We found an effect of increasing age of the children on incidence of type 1 diabetes, but we did not find an effect of sex or of nitrate concentration in drinking water using the two exposure categories. For nitrate levels > 25 mg/L, an increased SIR and an increased IRR of 1.46 were observed; however, this increase was not statistically significant, probably because of the small number of cases (15 of 1,064). We concluded that there is no convincing evidence that nitrate in drinking water at current exposure levels is a risk factor for childhood type 1 diabetes mellitus in The Netherlands, although a threshold value > 25 mg/L for the occurrence of this disease can not be excluded.

A review of the literature indicated an association among high nitrate ingestion, methemoglobinemia, and pathologic changes in bronchi and lung parenchyma. The present study examined a possible correlation among drinking water nitrate concentration, methemoglobin levels, cytochrome b(5) reductase activity, and acute respiratory tract infection with a history of recurrence (RRTI). Our study was conducted in five village units in the state of Rajasthan, India, with nitrate concentrations of 26, 45, 95, 222, and 459 mg NO(3) ion/L. We randomly selected 88 children. The children were up to 8 years of age, age matched, and represented 10% of the total population of these areas. We obtained detailed RRTI histories and conducted medical examinations. Methemoglobin levels and cytochrome b(5) reductase activity were estimated biochemically. The data collected were statistically analyzed using spreadsheet software on a personal computer. We observed strong interdependence between methemoglobin levels and RRTI in children up to 8 years of age. Methemoglobin levels alone explained 80% of the variation in the RRTI cases. This study indicates that methemoglobinemia, secondary to high nitrate ingestion in drinking water, causes RRTI. Increased production of methemoglobin and free radicals of nitric oxide and oxygen due to nitrate metabolism in the body lead to alveolar damage and mismatching of ventilation and perfusion, which may be the reason for high mortality in children due to RRTI.

Nitrate exposure was investigated in a group of 187 people using well water and living in four areas of rural Quebec (Canada) with intensive agricultural activities. Nitrate intake was evaluated using a 24-h dietary recall and a food frequency questionnaire, in conjunction with a validated food database and measurements of nitrate concentrations in private wells. The total internal dose was estimated by means of the 24-h urinary nitrate excretion, while taking into account risk factors for endogenous nitrate formation. Mean (geometric) 24-h urinary nitrate excretion was 16.9 mg N for the 100 people with low groundwater contamination (mean nitrate concentration=0.18 mg N/l) and 23.3 mg N in the 87 individuals with moderate groundwater contamination (mean nitrate concentration=7.1 mg N/l). A multivariate analysis revealed that dietary nitrate intake during the last 24 h was the principal source of exposure, followed by water intake during the last 24 h. The Quetelet index was also a significant predictor of urinary excretion. The total predictive model explained only 29% of the variability in urinary nitrate excretion (R2=0.286). Neither the inflammatory status as indicated by elevated C reactive protein, the presence of Helicobacter pylori antibodies nor the occurrence of diarrhea during the last 24 h prior to urine collection were associated with urinary nitrate excretion. In conclusion, food and to a lesser extent water contribute to nitrate exposure in this rural setting with moderate water contamination. Better predictors of endogenous nitrate production are needed to improve our ability to model nitrate body burden and estimate associated health risks.

This study was carried out in 1997 to 1998, to determine the prevalence of intestinal parasite infestations due to groundwater pollution at Yeumbeul, Senegal, and to follow the progression of parasite infestations following anti-parasite treatment. The study included 705 people living in a suburban zone in which the water table was polluted with nitrates of fecal origin. These individuals consumed either well water or water from springs. The overall prevalence of parasite infestation was 42.26%, but varied significantly with age (p < 0.001). Individuals who consumed well water were more frequently infested than those who consumed spring water, but the difference was not significant (p > 0.3). Giardia and Entamoeba coli were the most frequently isolated parasites, with Giardia predominating in the 0 to 9 year age-group. There was no significant correlation between the prevalence of the various parasites and indicators of water pollution (R2 = 0.0566 for nitrates and 0.1086 for fecal coliform bacteria). Similarly, no correlation was found with water pollution factors such as the depth of the water table (R2 = 0.027) and the distance between the wells and the latrines (R2 = 0.00007). Following specific treatment, the prevalence of parasite infestation fell to 30.81%. This indicates the limitations of drug treatment, which is always used alone to combat intestinal parasites, in the face of possible reinfestation.

The authors conducted a survey by mail of Wisconsin families who had their well water tested for nitrate to (a) assess their awareness and compliance with the state's health advisories for nitrate, (b) evaluate their reaction(s) to their test results, and (c) compare demographic differences between exposure levels. Owners of contaminated wells (i.e., > 12.9 mg/l nitrate-nitrogen) were more likely to have lived on a farm, had lower annual incomes, and had older and shallower wells than families whose wells were low in nitrate (i.e., < 2.0 mg/l nitrate-nitrogen). Most respondents were aware of the advisories for pregnant women and infants and, in accordance with these advisories, the majority of families with nitrate-contaminated drinking water took no remedial action. Given that many rural families consume nitrate-contaminated water daily, scientists should conduct additional research to determine whether chronic ingestion of nitrate-contaminated water poses a significant health threat to these families.

Ingestion of nitrates in drinking water has long been thought to be a primary cause of acquired infantile methemoglobinemia, often called blue baby syndrome. However, recent research and a review of historical cases offer a more complex picture of the causes of infantile methemoglobinemia. Gastrointestinal infection and inflammation and the ensuing overproduction of nitric oxide may be the cause of many cases of infantile methemoglobinemia previously attributed to drinking water nitrates. If so, current limits on allowable levels of nitrates in drinking water, which are based solely on the health threat of infantile methemoglobinemia, may be unnecessarily strict.

To obtain an indication of the nitrate-nitrogen levels in drinking water in rural areas of upstate New York and the number of infants at risk for methemoglobinemia, 419 wells supplying drinking water to farms were tested. Farmers were identified through two programs run by the New York State Department of Health. The farmers were asked to complete a short questionnaire about the type and size of their farm and their well and to collect the water sample. Overall, nitrates were detectable in 95% of the wells tested (concentration levels greater than 0.05 mg/L) and 15.7% had levels which exceeded 10 mg/L. Fifteen percent of the wells tested from farms where infants resided were also elevated. Wells which were shallow, dug or located on large farms, or springs were more likely to have elevated concentrations of nitrates., (Copyright 1999 Academic Press.)

Objectives: This small-area ecologic study in Yorkshire, northern England, examines the hypothesis that exposure to higher levels of nitrate in drinking water increases the risk of stomach, esophageal, or brain cancer in adults., Methods: Nitrate levels over the period 1990-95 and numbers of incident cancers from 1975-94 were available for 148 water supply zones, geographically defined areas each supplying water of homogeneous chemical composition to an average population of around 20,000., Results: No relationship was found between nitrate concentrations and the incidence of stomach or esophageal cancers. The incidence of cancer of the brain and central nervous system was found to be higher in areas with higher nitrate levels, with a relative risk of 1.18 (95 percent confidence interval = 1.08-1.30) in the quartile of the population with the highest average levels (mean 29.8 mg/l) compared with the lowest quartile (mean 2.4 mg/l). The increase in risk remained statistically significant (P < 0.01) after allowing for other covariates and for extra-Poisson variation in a regression model., Conclusions: This study does not support the hypothesis of an increased risk of stomach or esophageal cancer associated with higher nitrate levels in drinking water. The observed relationship with brain cancer requires confirmation in other studies, including those involving data on individuals.

The possible association between the risk of gastric cancer and the levels of calcium, magnesium, and nitrate in drinking water from municipal supplies was investigated in a matched case-control study in Taiwan. Records of gastric cancer deaths among eligible residents in Taiwan from 1987 through 1991 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by sex, year-of-birth, and year-of-death. Each matched control was selected randomly from the set of possible controls for each case. Data on calcium, magnesium, and nitrate levels in drinking water throughout Taiwan were obtained from the Taiwan Water Supply Corporation. The municipality of residence of the cases and controls was assumed to be the source of the subject's calcium, magnesium, and nitrate exposure via drinking water. The subjects were divided into tertiles according to the levels of calcium, magnesium, and nitrate in their drinking water. The results of the present study show that there is a significant positive association between drinking water nitrate exposure and gastric cancer mortality. The present study also suggests that there was a significant protective effect of calcium intake from drinking water on the risk of gastric cancer. Magnesium also exerts a protective effect against gastric cancer, but only for the group with the highest levels.