Nitrate contamination of drinking water: relationship with HPRT variant frequency in lymphocyte DNA and urinary excretion of N-nitrosamines.

We studied peripheral lymphocyte HPRT variant frequency and endogenous nitrosation in human populations exposed to various nitrate levels in their drinking water. Four test populations of women volunteers were compared. Low and medium tap water nitrate exposure groups (14 and 21 subjects) were using public water supplies with nitrate levels of 0.02 and 17.5 mg/l, respectively. Medium and high well water nitrate exposure groups (6 and 9 subjects) were using private water wells with mean nitrate levels of 25 and 135 mg/l, respectively. Higher nitrate intake by drinking water consumption resulted in a dose-dependent increase in 24-hr urinary nitrate excretion and in increased salivary nitrate and nitrite levels. The mean log variant frequency of peripheral lymphocytes was significantly higher in the medium well water exposure group than in the low and medium tap water exposure groups. An inverse correlation between peripheral lymphocyte labeling index and nitrate concentration of drinking water was observed. Analysis of N-nitrosamine in the urine of 22 subjects by gas chromatography-mass spectrometry revealed the presence of N-nitrosopyrrolidine in 18 subjects. Analysis of the mutagenicity of well water samples showed that a small number of the well water samples were mutagenic in the Ames Salmonella typhimurium test after concentration over XAD-2 resin. In conclusion, consumption of drinking water, especially well water, with high nitrate levels can imply a genotoxic risk for humans as indicated by increased HPRT variant frequencies and by endogenous formation of carcinogenic N-nitroso compounds from nitrate-derived nitrite.     

Nitrate in public water supplies and risk of bladder cancer

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 (相似文献   

Drinking water nitrate and prevalence of methemoglobinemia among infants and children aged 1-7 years in Moroccan areas

ContextNitrate 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.MethodTwo 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).ResultsIn the exposed area, nitrate concentration was measured in 78 wells and ranged from 15.39 to 246.90 mg/l as NO₃⁻. Nitrate levels were higher than 50 mg/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 >50 mg/l were significantly more likely to have methemoglobinemia than those drinking well water with a nitrate concentration <50 mg/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 50 mg/l as NO₃⁻, and reached an abnormal level, when the nitrate concentration in water ranged between 50 and 90 mg/l as NO₃⁻. This last level was statistically similar to mean MetHb at nitrate level above 90 mg/l as NO₃⁻ (up to 246.9 mg/l as NO₃⁻). No association was observed between methemoglobinemia prevalence and gender. This is the first study about methemoglobinemia conducted in Morocco.     

Impact of nitrates in drinking water on cancer mortality in Valencia,Spain

The concentrations of nitrates in public drinking water in the Mediterranean coastal province of Valencia are not only the highest in Spain but also in the whole of Europe. Intensive agricultural practices involve a traditional and growing use of nitrogen fertilizers. This and the terrain — poorly consolidated and porous in areas — favors the accumulation of nitrates in underground aquifers, thereby perhaps accounting for this contamination. The possible conversion of nitrates to nitrites under certain conditions of gastric achlorhydria, followed by their transformation to nitrosamines — substances known to be carcinogenic in experimental models — has led to a number of epidemiological studies of the possible relationship between high nitrate levels in public drinking water and mortality due to different cancers. The aim of the present study was to analyze the relationship between different levels of exposure to nitrates in the drinking water of the 258 municipalities in the province of Valencia and mortality due to cancer of the stomach, bladder, prostate and colon in this population. The cancer mortality rate was found to rise with increasing exposure to nitrates in the case of gastric cancer in both sexes, and in prostate cancer. These same results were obtained on calculating relative risk for the different age groups associated with the consumption of drinking water containing different levels of nitrates. Thus, in populations with nitrate concentrations in excess of 50 mg/1, relative risk for gastric cancer in the 55–75 years age group was 1.91 and 1.81 for males and females, respectively (p<0.05). In the case of prostate cancer elevated relative risks were also encountered: 1.86 and 1.80 for the 55–75 and over 75 years age groups, respectively.     

Drinking water and dietary sources of nitrate and nitrite and risk of glioma

OBJECTIVE: Dietary nitrite has been associated with increased glioma risk; however, drinking water nitrate has not been extensively evaluated. METHODS: We conducted a population-based case-control study of adult glioma in Nebraska. Water utility nitrate measurements were linked to residential water source histories. We computed average nitrate exposure over a 20-year period. A food frequency questionnaire was used to assess dietary nitrate and nitrite. RESULTS: Increasing quartiles of the average nitrate level in drinking water were not significantly associated with risk (adjusted odd ratios: 1.4, 1.2, 1.3). Risk was similar among those with both higher and lower intakes of vitamin C, an inhibitor of N-nitroso compound formation. Dietary nitrite intake was not associated with risk. CONCLUSIONS: Our study does not support a role for drinking water and dietary sources of nitrate and nitrite in risk of adult glioma.     

Adenocarcinoma of the stomach and esophagus and drinking water and dietary sources of nitrate and nitrite

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.     

An ecologic study of nitrate in municipal drinking water and cancer incidence in Trnava District,Slovakia

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.     

High Nitrate Content in Drinking Water: Cytogenetic Effects in Exposed Children

The potential genotoxicity of nitrates and nitrites—contaminants of drinking water that have been implicated in carcinogenesis—was investigated in this study. Sister chromatid exchanges and frequency of chromatid/hromosome aberrations were studied in peripheral blood lymphocytes of 70 children who were 12–15 y of age. These children were permanent residents in geographical areas of Greece, where elevated concentrations of nitrates (i.e., 55.70–87.98 mg/l) existed in drinking water. The control group comprised 20 healthy children who resided in areas with very low nitrate concentrations (i.e., 0.7 mg/l). A significant increase in the mean number of chromatid/chromosome breaks was observed in children exposed to nitrate concentrations that exceeded 70.5 mg/l (p < .01), but there was no significant increase in the mean number of sister chromatid exchanges per cell. The results indicate that chronic administration of elevated concentrations of nitrate in drinking water has the capability of inducing cytogenetic effects.     

Nitrate, nitrite and N-nitrosamines

The major part of nitrate ingested by normal individuals from vegetables, water supplies, etc., is excreted unchanged. Where the stomach is colonised by bacteria however, as in achlorhydria, reduction to nitrite can occur with consequent methaemoglobinaemia. This problem is particularly marked in infants during the first few months of life if water supplies are rich in nitrate. Of greater potential importance to the majority of adults, however, is the formation within the body of N-nitroso compounds, the great majority of which are carcinogenic in experimental animals. A proportion of ingested nitrate is reduced microbiologically within the mouth to nitrite which then enters the acidic milieu of the normal stomach. Bacterial colonisation of the stomach occurs increasingly in old age, and is accompanied by the formation of increased levels of nitrite and N-nitroso compounds. Ascorbic acid is also ingested from many vegetables and is an inhibitor of the nitrosation process. Nevertheless, it is suggested that individuals with hypochlorhydria who may be particularly at risk from the formation of N-nitroso compounds in vivo should supplement their intake of this potentially protective agent.     

Risk of non-Hodgkin lymphoma and nitrate and nitrite from drinking water and diet

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.     

Municipal drinking water nitrate level and cancer risk in older women: the Iowa Women's Health Study

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.     

A Case-Control Study of Nitrate in Drinking Water and Non-Hodgkin's Lymphoma in Minnesota

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.     

Nitrate in Community Water Supplies and Risk of Childhood Type 1 Diabetes in Sardinia, Italy

We tested the hypothesis of an association between childhood type 1 diabetes (T1D) risk and nitrate concentration in drinking water in Sardinia, Italy, using Poisson regression analysis. Childhood T1D risk showed an inverse trend with increasing quartile of nitrate level in the total population and among men. A nitrate concentration in drinking water below 10 mg/l is unlikely to account for the spatial variation in childhood T1D incidence.     

Nitrate in public water supplies and the risk of colon and rectum cancers

BACKGROUND: Nitrate is a widespread contaminant of drinking water, but its potential health effects are unclear. In the body, nitrate is reduced to nitrite, which can react with amines and amides by nitrosation to form N-nitroso compounds, known animal carcinogens. N-nitroso compound formation is inhibited by certain nutrients, such as vitamin C, and increased by meat intake. METHODS: We investigated the association of nitrate in public water supplies with incident colon and rectum cancers in a case-control study conducted in Iowa from 1986 to 1989. Nitrate levels in Iowa towns were linked to the participants' water source histories. We focused our analyses on the period from 1960 onward, during which nitrate measurements were more frequent, and we restricted analyses to those persons with public water supplies that had nitrate data (actual or imputed) for greater than 70% of this time period (376 colon cancer cases, 338 rectum cancer cases, and 1244 controls). RESULTS: There were negligible overall associations of colon or rectum cancers with measures of nitrate in public water supplies, including average nitrate and the number of years with elevated average nitrate levels. For more than 10 years with average nitrate greater than 5 mg/L, the odds ratio (OR) for colon cancer was 1.2 (95% confidence interval [CI] = 0.9-1.6) and for rectum the OR was 1.1 (CI = 0.7-1.5). However, nitrate exposure (>10 years with average nitrate >5 mg/L) was associated with increased colon cancer risk among subgroups with low vitamin C intake (OR = 2.0; CI = 1.2-3.3) and high meat intake (OR = 2.2; CI = 1.4-3.6). These patterns were not observed for rectum cancer. CONCLUSIONS: Our analyses suggest that any increased risk of colon cancer associated with nitrate in public water supplies might occur only among susceptible subpopulations.     

A case-control study of nitrate in drinking water and non-Hodgkin's lymphoma in Minnesota

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 precursors of N-nitroso compounds in the drinking water and digestive system malignancy morbidity rates in Tashkent

The authors have studied a correlation between the intake of the precursors of N-nitroso compounds from drinking water in Tashkent residents and the digestive malignancy morbidity rates. With the average urban value of 4.1-6.6 mg/l, the drinking water levels of nitrates are found to vary in different administrative districts of Tashkent: the highest values (range 73-20.3 mg/l) are annually recorded in the Khamzin and Yakkasaray districts and the lowest ones (1.0-1.4 mg/l) in the Yunusabad, Shaikhantakhur, Mirzo-ulugbek, and Uchtepin districts. There is a direct average correlation (r = 0.5-0.6) between the intake of nitrates and the digestive malignancy morbidity rates in the majority of administrative districts of the city and a high one (r = 0.7-0.9) when the values are compared, by taking into account the 3-5 year delay effect.     

Cardiovascular mortality and calcium and magnesium in drinking water: an ecological study in elderly people

Background: Previous studies found relations between cardiovascular mortality and minerals in drinking water, but the major works considered water hardness or neglected the differences between adults and elderly. Drinking water is an important source of calcium in the elderly particularly because of increased needs and decreased consumption of dairy products. Methods: We collected informations about all deaths (14,311) occurring in 69 parishes of the South–West of France during 7 years (1990–1996). We obtained the causes of deaths from a special service of INSERM for each death, with age at death and sex. The exposure value was supplied by administrative source (DDASS) and by measurement surveys. We use an extra-Poisson variation model to take into account the heterogeneity of the population of these parishes. Results: A significant relationship was observed between calcium and cardiovascular mortality with a RR: 0.90 for non-cerebrovascular causes and RR: 0.86 for cerebrovascular (when calcium is higher than the second tercile: 94 mg/l). We found a protective effect of magnesium concentrations between 4 and 11 mg/l with a RR: 0.92 for non-cerebrovascular and RR: 0.77 for cerebrovascular mortality, as compared to concentrations lower than 4 mg/l. Conclusions: These findings strongly suggest a potential protective dose-effect relation between calcium in drinking water and cardiovascular causes. For magnesium, a U-shape effect is possible, especially for cerebrovascular mortality.     

Nitrite concentration in the saliva]

320 persons were tested on the nitrate content in saliva. In experiments were accounted the profession, age, sex, particularities of nourishment, drinking water, habits, diseases, taking medicines, vitamins, contact with toxic substances and so on (29 parameters). The average level of nitrates in saliva of estonians is 4.9 +/- 0.3 mg/l. The purity of teeth has the most significant influence on the nitrate content in saliva.     

Volatile N-nitrosamine formation after intake of nitrate at the ADI level in combination with an amine-rich diet.

Formation of nitrite from ingested nitrate can result in several adverse health effects and implies a genotoxic risk as a consequence of endogenous formation of carcinogenic N-nitroso compounds. We studied the formation of volatile N-nitrosamines after intake of nitrate at the acceptable daily intake (ADI) level in combination with a fish meal rich in amines as nitrosatable precursors. Twenty-five volunteers consumed this meal during 7 consecutive days; a diet low in nitrate was consumed during 1 week before and 1 week after the test week. Nitrate intake at the ADI level resulted in a significant rise in mean salivary nitrate and nitrite concentrations. Mean urinary nitrate excretion increased from 76 mg/24 hr in the first control week to 194 and 165 mg/24 hr in the test week, followed by a decline to 77 mg/24 hr in the second control week. The urine samples were analyzed for volatile N-nitrosamines, and both N-nitrosodimethylamine (NDMA) and N-nitrosopiperidine (NPIP) were detected in the samples. Mean urinary NDMA excretion significantly increased from 287 ng/24 hr in the control week to 871 and 640 ng/24 hr in the test week and declined to 383 ng/24 hr in the second control week. Excretion of NPIP was not directly related to the nitrate intake and composition of the diet. Nitrate excretion and NDMA excretion were significantly correlated, as well as salivary nitrate and nitrite concentration and NDMA excretion. We conclude that nitrate intake at the ADI level in combination with a fish meal containing nitrosatable precursors increases NDMA excretion in urine and thus demonstrates increased formation of carcinogenic N-nitrosamines.