Abstract  One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.

Abstract  OBJECTIVES: Perchlorate, nitrate, and thiocyanate are well-known inhibitors of the sodium-iodide symporter and may disrupt thyroid function. This exploratory study investigated the association among urinary perchlorate, nitrate, and thiocyanate concentrations and parathyroid hormone (PTH) levels in the general U.S. population.

METHODS: We analyzed data on 4265 adults (aged 20 years and older) from the National Health and Nutrition Examination Survey in 2005 through 2006 to evaluate the relationship among urinary perchlorate, nitrate, and thiocyanate concentration and PTH levels and the presence of hyperparathyroidism cross-sectionally.

RESULTS: The geometric means and 95% confidence interval (95% CI) concentrations of urinary perchlorate, nitrate, and thiocyanate were 3.38 (3.15-3.62), 40363 (37512-43431), and 1129 (1029-1239) ng/mL, respectively. After adjusting for confounding variables and sample weights, creatinine-corrected urinary perchlorate was negatively associated with serum PTH levels in women (P = 0.001), and creatinine-corrected urinary nitrate and thiocyanate were negatively associated with serum PTH levels in both sex groups (P = 0.001 and P<0.001 for men, P = 0.018 and P<0.001 for women, respectively). Similar results were obtained from sensitivity analyses performed for exposure variables unadjusted for creatinine with urinary creatinine added as a separate covariate. There was a negative relationship between hyperparathyroidism and urinary nitrate and thiocyanate [odds ratio (95% CI) = 0.77 (0.60-0.98) and 0.69 (0.61-0.79), respectively].

CONCLUSIONS: A higher urinary concentration of perchlorate, nitrate, and thiocyanate is associated with lower serum PTH levels. Future studies are needed to determine the pathophysiological background of the observation.

Abstract  Models to assess dietary exposure of population groups to nitrates and nitrites should be based on the major sources of these substances in foods. Most models require the use of food consumption information and will, therefore, be flawed by the problems that exist with current dietary intake assessment methods. The Total Diet Study model would probably not provide representative coverage of the nitrites in processed meats. A nitrate/nitrite database model requires the gathering and compiling of published data and data from industry on the nitrate and nitrite content of foods. A nitrate/nitrite core food model requires the identification of the foods most responsible for nitrate/nitrite consumption in the U.S. and routine collection and analyses of these products. The large database model uses the database of a national food consumption survey and assigns nitrate and nitrite values to all the foods (based on available data and imputation). A processed meat production/consumption model focuses only on nitrites added to processed, cured meats. The nitrate/nitrite core food model is the preferred approach. Published by Elsevier Science Ltd.

Abstract  The effect of orally administered sublethal doses of 25. 50 and 100 mg/kg of sodium nitrite in drinking water ad lib. for 21 days on the immune response of Balb/c mice was investigated. The immunological parameters were examined at three phases: 1 day (phase A), 1 week (phase B) and 3 weeks (phase C) after the end of exposure to sodium nitrite. A significant decrease in dose-dependent manner was obtained in the following tests: lymphocyte percentages, concanavalin A (Con A)- and lipopolysaccharide (LPS)-induced lymphocyte proliferation assessed by the colorimetric MTT method, natural killer (NK) cell activity against WEHI-164 target cells, as well as IgM and IgG titers against injected sheep erythrocytes. Maximum suppressions were obtained in phase A after treatment with sodium nitrite at 100 mg/kg including lymphocyte count (17.5%), Con A-induced lymphocyte proliferation (40.1%), LPS-induced lymphocyte proliferation (31.4%), IL-2-stimulated NK cell activity (59.2%), unstimulated NK cell activity (59.6%), IgM titer (57.5%) and IgG titer (61.1%). On the other hand, a significant dose-dependent increase in neutrophil count (71.3%) in phase A and phagocytic activation (133%) in the first two phases was obtained using the nitroblue tetrazolium (NBT) assay in the presence of phorbol myristate acetate (PMA). It was found that the immunosuppressive effect of sodium nitrite is reversible after cessation of exposure. (C) 2001 Elsevier Science Ltd. All rights reserved.

Abstract  The concentrations of nitrate, nitrite, N-nitroso compounds and bacteria were measured in 96 samples of fasting gastric juice, pH 0.90-8.50, obtained from 56 individuals just before or at various times (8 days - 1 year) after gastric operation. The mean pH of the post-operative samples [4.66 +/- 0.39 (SEM)] was significantly higher than that of the pre-operative ones [3.29 +/- 0.33 (SEM)]. A positive correlation with pH was observed for the concentrations of total and nitrate-reducing bacteria (median values 5.0 X 10(5) organisms/ml and 9.2 X 10(4) organisms/ml, respectively, for samples with pH greater than or equal to 1.2 X 10(3) organisms/ml and 0 organisms/ml, respectively, for samples with pH less than or equal to 2.5) and nitrite [mean values 22.5 +/- 3.1 (SEM) microM and 3.20 +/- 0.5 (SEM) microM for samples with pH greater than or equal to 6.5 and pH less than or equal to 2.5, respectively]. No correlation with pH was seen for the concentrations of nitrate [mean value 0.48 +/- 0.06 (SEM) mM] or N-nitroso compounds [mean value 0.30 +/- 0.06 (SEM) microM]. The concentrations of bacteria and nitrite, although increased in hypochlorhydric individuals, were lower than those reported for corresponding individuals in other, primarily British, studies. It is suggested that the relatively low concentrations of nitrite observed in our hypochlorhydric population may account for the absence of elevated concentrations of N-nitroso compounds and that the latter phenomenon may be related to the relatively low frequency of gastric cancer in Greece.

Abstract  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.

Abstract  Red and processed meat intake is associated with increased risks of both colorectal adenoma and cancer. Processed meats contain nitrate and nitrite, precursors of N-nitroso compounds (NOCs); furthermore, meats cooked at high temperatures contain heterocyclic amines (HCAs) and polycyclic aromatic hydrocarbons (PAHs). Specific NOC, HCA and PAH are mutagens and animal carcinogens. We conducted a case-control study of 146 cases of colorectal adenoma, diagnosed at sigmoidoscopy or colonoscopy, and 228 polyp-free controls. We calculated odds ratios (ORs) [and 95% confidence intervals (CIs)] and found a 2-fold increased risk in the highest, compared with the lowest, quartile of processed meat intake (95% CI = 1.0-4.0). We estimated nitrate and nitrite intake from meat using published data from the literature as well as from actual measurements of meats analyzed recently. We evaluated the interaction of processed meat and nitrate plus nitrite intake with CYP2A6 activity, an enzyme able to metabolize some NOC to their carcinogenic form. Results for both methods of estimating nitrate and nitrite intake were similar; compared with the lowest, the highest quartile based on measured values was associated with a 2-fold elevated risk (95% CI = 1.0-3.9). Adjustment for the HCA 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) attenuated the association (OR = 1.6, 95% CI = 0.8-3.2), but other HCA and PAH had minimal effect. Higher CYP2A6 activity was not associated with risk and there was no evidence of an interaction of CYP2A6 activity with nitrate and nitrite intake. Our results suggest that nitrite and nitrate intake from processed meat intake increases the risk of colorectal adenoma after accounting for HCA and PAH.

Abstract  Findings from a recent large study suggest that perchlorate at commonly occurring exposure concentrations may decrease thyroid hormone levels in some women. Decreases in thyroid hormone seen with perchlorate exposure could be even greater in people with concomitant exposure to agents such as thiocyanate that may affect the thyroid by mechanisms similar to those of perchlorate.

We used data from the National Health and Nutrition Examination Survey to assess the impact of smoking and thiocyanate on the relationship between urinary per-chlorate and serum thyroxine (T(4)) and thyroid-stimulating hormone (TSH).

In women with urinary iodine levels < 100 microg/L, the association between the logarithm of perchlorate and decreased T(4) was greater in smokers [regression coefficient (beta) = -1.66, p = 0.0005] than in nonsmokers (beta = -0.54, p = 0.04). In subjects with high, medium, and low cotinine levels, these regression coefficients were -1.47 (p = 0.0002), -0.57 (p = 0.03), and -0.16 (p = 0.59). For high, medium, and low thiocyanate tertiles they were -1.67 (p = 0.0009), -0.68 (p = 0.09), and -0.49 (p = 0.11). Clear interactions between perchlorate and smoking were not seen with TSH or with T(4) in women with urinary iodine levels > or = 100 microg/L or in men.

These results suggest that thiocyanate in tobacco smoke and perchlorate interact in affecting thyroid function, and this effect can take place at commonly occurring perchlorate exposures. Agents other than tobacco smoke might cause similar interactions, and further research on these agents could help identify people who are particularly susceptible to perchlorate.

Abstract  The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and risk of death from brain cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the influence of nitrates on development of brain cancer. A matched cancer case-control study was used to investigate the relationship between the risk of death from brain cancer and exposure to nitrates in drinking water in Taiwan. All brain cancer deaths of Taiwan residents from 2003 through 2008 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 cancer cases by gender, year of birth, and year of death. Information on the levels of nitrate-nitrogen (NO₃-N), Ca, and Mg in drinking water was obtained 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 NO₃-N, Ca, and Mg exposure via drinking water. Relative to individuals whose NO₃-N exposure level was <0.38 ppm, the adjusted OR (95% CI) for brain cancer occurrence was 1.04 (0.85-1.27) for individuals who resided in municipalities served by drinking water with a NO₃-N exposure ≥ 0.38 ppm. No marked effect modification was observed due to Ca and Mg intake via drinking water on brain cancer occurrence.

Abstract  BIOSIS COPYRIGHT: BIOL ABS. RRM FOOD ADDITIVE TOXICODYNAMICS ANEMIA

Abstract  Meat intake has been inconsistently associated with risk of non-Hodgkin lymphoma (NHL), a heterogeneous group of malignancies of the lymphoid tissue etiologically linked to immunomodulatory factors. In a large U.S. cohort, we prospectively investigated several biologically plausible mechanisms related to meat intake, including meat-cooking and meat-processing compounds, in relation to NHL risk by histologic subtype. At baseline (1995-1996), participants of the NIH-AARP Diet and Health Study completed a diet and lifestyle questionnaire (n = 492,186), and a subcohort (n = 302,162) also completed a questionnaire on meat-cooking methods and doneness levels. Over a mean of 9 y of follow-up, we identified 3611 incident cases of NHL. In multivariable Cox proportional hazards regression models, we found no association between intake of red meat, processed meat, fish, poultry, heme iron, nitrite, nitrate, animal fat, or protein and NHL risk. MeIQx (2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline) and DiMeIQx (2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline), heterocyclic amines formed in meats cooked to well done at high temperatures, were inversely associated with chronic lymphocytic leukemia/small lymphocytic lymphoma [n = 979; HR (95% CI) for the highest vs. lowest quintile of intake: 0.73 (0.55, 0.96) and 0.77 (0.61, 0.98), respectively]. In this large U.S. cohort, meat intake was not associated with NHL or any histologic subtypes of NHL. Contrary to findings in animal models and other cancer sites, meat-cooking and -processing compounds did not increase NHL risk.

Abstract  Previous epidemiologic studies of maternal exposure to drinking water nitrate did not account for bottled water consumption. The objective of this National Birth Defects Prevention Study (NBDPS) (USA) analysis was to assess the impact of bottled water use on the relation between maternal exposure to drinking water nitrate and selected birth defects in infants born during 1997-2005. Prenatal residences of 1,410 mothers reporting exclusive bottled water use were geocoded and mapped; 326 bottled water samples were collected and analyzed using Environmental Protection Agency Method 300.0. Median bottled water nitrate concentrations were assigned by community; mothers' overall intake of nitrate in mg/day from drinking water was calculated. Odds ratios for neural tube defects, limb deficiencies, oral cleft defects, and heart defects were estimated using mixed-effects models for logistic regression. Odds ratios (95% CIs) for the highest exposure group in offspring of mothers reporting exclusive use of bottled water were: neural tube defects [1.42 (0.51, 3.99)], limb deficiencies [1.86 (0.51, 6.80)], oral clefts [1.43 (0.61, 3.31)], and heart defects [2.13, (0.87, 5.17)]. Bottled water nitrate had no appreciable impact on risk for birth defects in the NBDPS.

Abstract  In India, especially in Rajasthan people drink water containing high level of nitrates and concentration up to 500 mg of nitrate ion per liter is not unusual. The ingested nitrate is converted to nitrite in the digestive system and absorb in blood causing methemoglobinemia. Methaemoglobin is not restricted to infants alone but it is prevalent in higher age groups also. The peak of methaemoglobin is observed at 45-95 mg/liter of nitrate concentration of water. Some recent studies have indicated the prevalence of a high percentage (40 – 82 %) of cases of acute respiratory tract infection with history of recurrence in children drinking high nitrate in water than that reported for areas of low nitrate concentration. Therefore an experimental study was conducted in 10 rabbits between three and half month to four month of age having weight ranging 1.310 kg to 10720 kg. Five groups A, B, C, and D & E were formed with two rabbits in each group. The control group A was administered water orally having 06 mg/liter .Group B to E (experimental groups ) were administered water orally having concentration of 100mg/liter,200mg/liter,400mg/liter & 500mg/liter of nitrate respectively for 120 days. During experimental period the difference in general behavior of rabbits were noted. After that rabbits were anaesthetized & sacrificed according to guidelines of ICMR and lungs were removed & processed for paraffin sections, hemotoxyllin and eosin staining was done for microscopic observations. During experimental period, the animals were lethargy on 75th day .The respiration rate & heart rate were increased with loss of weight. The microscopic study revealed epithelial hyperplasia and lymphoid aggregation in the respiratory parenchyma. In higher group the lungs were infiltrated with inflammatory cells in inter alveolar space with abundance of Type -2 pneumocytes in the alveolar epithelium.

Abstract  This manual offers current and practical approaches to nitrification prevention and response to a nitrification episode in chloraminated drinking water distribution systems.

Abstract  U.S. General Accounting Office. The Food and Drug Administration and the Department of Agriculture are faced with a dilemma regarding nitrite--a substance widely used to preserve, color, and flavor meats products. Using nitrite may pose a long-term cancer risk or other health problems. Not using it could increase risks from botulism food poisoning. Federal law provides that any additive to food shown to cause cancer must be eliminated from use. A substantial unresolved question about the safety of a food additive is also a basis for its removal from use. There is no acceptable chemical substitute for nitrite as a preservative. The validity of the study indicating that nitrite causes cancer has been questioned. Efforts are underway to resolve the questions. GAO's review was requested by seven members of the House of Representatives.