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  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  Growing evidence suggests that nitrite, acting via reduction to nitric oxide by deoxyhemoglobin, may play an important role in local control of blood flow during hypoxia. To investigate the effect of hypoxia (65 Torr arterial Po-2) on the kinetic properties of nitrite, a bolus injection of sodium nitrite (10 mg/kg iv) was given to normoxic or hypoxic newborn lambs, and the time course of plasma nitrite and methemoglobin (MetHb) concentrations was measured. The in vivo kinetics of nitrite disappearance from plasma were biphasic and were not affected by hypoxia. Changes in MetHb, a product of the nitrite-hemoglobin reaction, also did not differ with the level of oxygenation. Hypoxia potentiated the hypotensive effects of nitrite on pulmonary and systemic arterial pressures. The disappearance of nitrite from plasma was equivalent to the increase in MetHb on a molar basis. In contrast, nitrite metabolism in sheep blood in vitro resulted in more than one MetHb per nitrite equivalent under mid-and high-oxygenation conditions: oxyhemoglobin (HbO(2)) saturation = 50.3 +/- 1.7% and 97.0 +/- 1.3%, respectively. Under the low-oxygenation condition (HbO2 saturation = 5.2 +/- 0.9%), significantly less than 1 mol of MetHb was produced per nitrite equivalent, indicating that a significant portion of nitrite is metabolized through pathways that do not produce MetHb. These data support the idea that the vasodilating effects of nitrite are potentiated under hypoxic conditions due to the reduction of nitrite to nitric oxide by deoxyhemoglobin.

Abstract  Dose-dependent promotion effects of combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) on gastric carcinogenesis were examined in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 15 6-week-old F344 male rats were given 0.01% MNNG in their drinking water for 10 weeks to initiate carcinogenesis in the glandular stomach and a single intragastric administration of 100 mg/kg/bodyweight of MNNG by stomach tube at week 9 to initiate carcinogenesis in the forestomach. From week 11, they received either drinking water containing 0.05, 0.1 or 0.2% NaNO2 and a diet supplemented with 0.1 or 0.2% AsA in combination, each individual chemical alone or a basal diet until the end of week 42. In the forestomach, the incidence of hyperplasia was increased dose dependently by the treatment with NaNO2 alone. Incidences of neoplastic lesions were dramatically increased by the combined treatment with NaNO2 and AsA in a dose-dependent manner, but AsA itself had no effect. In the glandular stomach, only toxicity and regenerative changes were increased by the high-dose combination. In a second short-term experiment conducted for sequential observation, necrosis and strong inflammation were found in the forestomach epithelium shortly after commencing combined treatment with 1.0% AsA and 0.2% NaNO2, followed by hyperplasia, whereas there were no obvious effects in the glandular stomach. In addition, after a 4 h treatment with 1.0% AsA and 0.2% NaNO2, a slight increase in the 8-hydroxy-deoxyguanosine levels in the forestomach epithelium was observed by high-performance liquid chromatography and an electrochemical detection system, albeit without statistical significance. In vitro, electron spin resonance demonstrated nitric oxide formation during incubation with NaNO2 and AsA under acidic conditions. Thus, NaNO2 was demonstrated to exert promoter action in the forestomach, with AsA acting as a strong copromoter through cytotoxicity and regenerative cell proliferation, possibly mediated by oxidative DNA damage, but the combined treatment with NaNO2 and AsA had little influence on glandular stomach carcinogenesis.

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  We found high concentrations of nitrite/nitrate (166-1460 micromol/l) in 43 milk samples obtained from 32 women during postpartum days 1-8, which indicates enhanced mammary nitric oxide (NO) secretion. We detected adrenomedullin (AM) (2.7-20.7 pmol/l) only in 9 of the 43 samples using highly specific immunoradiometric assay. It is uncertain whether the entire adrenomedullin is actively secreted in human milk.

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  Nitrate inhibits the accumulation of iodide in thyroid gland. The aim of present study was to evaluate the influence of this ion on the iodine status of two risk population groups. Subjects of study were pregnant women and children aged between 3 and 6 years from two villages in Bulgaria with high- and low-nitrate levels in drinking water. The relative risk of thyroid disorders for the pregnant women living in the village with high-nitrate levels in drinking water expressed as an odds ratio was 5.294 (95% confidence intervals 1.003-27.939; P=0.0454) and was considered as significant. Statistically significant differences were found between the goiter rate in exposed and non-exposed pregnant women. The relative risk of thyroid dysfunction for the children exposed to a high-nitrate level, expressed as an odds ratio was 2.333 (95% confidence intervals 0.8491-6.412; P=0.1396) and was considered as not significant; the goiter prevalence in the exposed children was also not statistically different. The results of the study confirmed the role of high-nitrate level in drinking water as a risk factor for thyroid dysfunction in vulnerable population groups.

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  BIOSIS COPYRIGHT: BIOL ABS. RRM FOOD ADDITIVE TOXICODYNAMICS ANEMIA

Abstract  In studies of the effect of diet on nitrosamine levels in selected human physiological fluids, volunteers were fed meals containing fish or beef (sources of precursor amines) or bacon (a source of preformed nitrosamines), in combination with spinach and vegetable juice to supply nitrite via possible reduction of nitrate. Blood, urine and gastric contents were sampled periodically for up to 4 hr after feeding. The results of the study indicated that traces of nitrosamines, usually N-nitrosodimethylamine, were present in many samples of blood, urine and gastric contents, even after an 8-hr fast. Eating the test meals led to a slight increase in nitrosamine levels in the blood and stomach contents in a few subjects. The data obtained from this study suggest that gastric formation of nitrosamine does not appear to be an important health factor in normal people, since the levels of nitrosamines found in physiological fluids are not markedly increased after eating.

Abstract  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.

Abstract  OEHHA is required to develop guidelines for conducting health risk assessments under the Air Toxics Hot Spots Program (Health and Safety Code Section 44360(b)(2)). OEHHA previously developed Technical Support Documents (TSDs) in response to this statutory requirement, including one in 2000 for exposure assessment. This revised draft TSD replaces the original TSD, and reflects new scientific knowledge developed since the previous guidelines were prepared. We have updated exposure parameters (e.g., inhalation rate, food consumption rate, etc.) based on the most recent data, including exposure factors for infants and children, in accordance with the mandate of the Children’s Environmental Health Protection Act (Senate Bill 25, Escutia, Chapter 731, Statutes of 1999, Health and Safety Code Sections 39669.5 et seq.). The revised document also updates the approach to assessing dermal exposure. A draft version of this TSD was released for public comment on November 7, 2011, and was discussed at public workshops in Oakland and Diamond Bar, CA in December 2011. The document was then revised to reflect public comments, and peer reviewed by the State’s Scientific Review Panel on Toxic Air Contaminants (SRP). It was initially presented to the SRP on April 5, 2012. A revised version of the document reflecting comments of the SRP was discussed at a second meeting held on June 25, 2012. At the latter meeting, the SRP approved the document describing the RELs and their derivation, subject to some additional editorial changes which have been incorporated into the final version.

Abstract  Iodine is a vital micronutrient required at all stages of life; fetal life and early childhood being the most critical phases of requirement. Diet is the sole source of iodine, which in turn is dependent upon the iodine content of water and soil. Iodine is metabolized in the human body through a series of stages involving the hypothalamus, pituitary, thyroid gland and blood. Recent advances in physiology and molecular science have revolutionized our understanding of iodine metabolism at the cellular and sub-cellular level. This in turn has improved our knowledge of Iodine Deficiency Disorders (IDD), their prevention, management and control. This article makes an attempt to revisit this important topic in light of recent advances and provides a comprehensive account of the subject.

Abstract  Although the goitre seems to be well defined at least from clinical point of view, it is virtually impossible to find the precise definition of the opposite side of what should be the normal thyroid as concerns its size, histological structure and namely the level of growth stimulation by the external factors (such as TSH) and intrinsic tissue growth factors. Theoretically, the normal thyroid should be able to cover the requirements of the organism for the hormone in a reasonably large range without being stimulated to grow by any external or internal factors. So far, the search for normal thyroid has been conducted by several ways: 1. by post mortem thyroid weight, 2. by palpation, 3. by ultrasound. As based on post mortem thyroid weight, until the middle of this century a typical thyroid gland was considered to be about 20-25 g with the accepted upper normal size of 30 g, while more recent studies in iodine replete population have reported mean weights of about 10 g and an upper normal size 20 g. According to several classifications for thyroid palpation the unpalpable thyroid should be allotted to the Grade 0 which is defined as "normal gland", "no goiter at all", "absence of goiter" etc. The first recommendation of normal thyroid volume for children and adolescents as estimated by ultrasound has been developed by Gutekunst and Teichert (1994). However, this was later challenged by the findings of considerable number of thyroid volumes which were higher than the upper limit of that recommendation as found in the countries with satisfactory values of urinary iodine (Delange et al. 1997). Nevertheless, recently it appeared that about 10-15 percent of adolescent thyroids show increased thyroid growth rate which significantly differs from the majority and which might be related to different tuning of molecular growth mechanism presumably of genetic origin (Tajtakova et al. 1998; Langer et al., in press). From, this follows that a certain number of enlarged thyroids apparently should not be included into a normal range.

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.