Abstract  Environmental exposure of infants to perchlorate, thiocyanate, nitrate, might interfere with thyroid function. U.S. women with higher background perchlorate exposure have higher thyroid-stimulating hormone (TSH) and lower thyroxine (T4). There are no studies with individual measures of thyroid function and these goitrogens available in infants.

We examined the association of urinary perchlorate, nitrate, iodide, and thiocyanate with urinary T4 and TSH in infants and whether that association differed by sex or iodide status.

We used data and samples from the Study of Estrogen Activity and Development, which assessed hormone levels of full-term infants over the first 12 months of life. The study included 92 full-term infants between birth and 1 year of age seen up to four times. Perchlorate, thiocyanate, nitrate, and iodide were measured in 206 urine samples; TSH and T4 and were measured in urines and in 50 blood samples.

In separate mixed models, adjusting for creatinine, age, sex, and body mass index, infants with higher urinary perchlorate, nitrate or thiocyanate had higher urinary TSH. With all three modeled, children with higher nitrate and thiocyanate had higher TSH, but higher perchlorate was associated with TSH only in children with low iodide. Unexpectedly, exposure to the three chemicals was generally associated with higher T4.

The association of perchlorate exposure with increased urinary TSH in infants with low urinary iodide is consistent with previous findings. Higher thiocyanate and nitrate exposure were also associated with higher TSH in infants.

Abstract  The objective of this study was to explore whether magnesium levels (Mg) in drinking water modify the effects of nitrate on colon cancer risk. A matched case-control study was used to investigate the relationship between the risk of death from colon cancer and exposure to nitrate in drinking water in Taiwan. All colon cancer deaths of Taiwan residents from 2003 through 2007 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. Information on the levels of nitrate-nitrogen (NO3-N) and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's NO3-N and Mg exposure via drinking water. The results of our study show that there is a significant trend towards an elevated risk of death from colon cancer with increasing nitrate levels in drinking water. Furthermore, we observed evidence of an interaction between drinking water NO3-N and Mg intake via drinking water. This is the first study to report effect modification by Mg intake from drinking water on the association between NO3-N exposure and colon cancer risk.

Abstract  PM(2.5) nitrate (NO-(3)) and sulfate (SO=(4)) were measured continuously with R&P8400N and R&P8400S instruments, respectively, and compared with filter-based measurements at the Fresno Supersite from October, 2000 through December, 2005. NO-(3) concentrations were higher in winter than summer with a long-term decreasing trend. Correlations between 24-h average continuous and filter-based NO-(3) were greater than 0.96 in 4 out of 5 years. Continuous NO-(3) was generally lower than filter-based NO-(3) although the difference decreased over time, from -52% in 2001 to +13% in 2005. These differences were similar in winter (-23%) and summer (-19%) while the corresponding differences between ambient and instrument temperature were -12 and 0.7 degrees C, respectively. Neither seasonal nor long-term trends in NO-(3) can be explained by variations in ambient temperature, the difference between ambient and instrument temperature, or changes in aerosol chemical composition. There were no seasonal or long-term trends in SO=(4) concentrations, partially due to low concentrations observed in Fresno. Long-term variability in the performance of R&P8400 NO-(3) and SO=(4) instruments suggest that collocation with filter measurements is needed for long-term measurements.

Abstract  Despite many physiological similarities, humans and rats exhibit notably different susceptibilities to thyroid perturbation. Considerable research has recently been conducted on the thyroid-active chemical perchlorate, a chemical of emerging environmental and regulatory interest. While the data indicate humans and rats exhibit similar dose-response relationships in terms of acute inhibition of thyroidal iodide uptake, the two species appear to exhibit notable differences in terms of thyroid hormone response, the toxicologically significant consequence of iodide uptake inhibition. We analyzed dose-response data for changes in serum T(3), T(4), and TSH levels from studies in humans, rats, mice, and rabbits. We found that thyroid homeostasis in the rat appears to be strikingly more sensitive to perchlorate than any of the other species. Rats exhibited an increase in serum TSH at 0.1mg/kg-day whereas other species remained unresponsive even at doses of 10mg/kg-day. Less pronounced but consistent effects were seen with serum T(3) and T(4). These cross-species comparisons provide strong evidence that data obtained from rat studies should be critically evaluated for their relevance to humans. If rat data are used to develop toxicity criteria for perchlorate, we propose that this is an instance where an inter-species uncertainty factor less than one is supportable. DISCLOSURE STATEMENT: One of the authors (BDB) has been hired by Lockheed Martin Corporation as an expert in litigation involving perchlorate. A portion of the initial research presented in this paper was conducted in conjunction with her role in that matter.

Abstract  The objective of this study was to (1) examine the relationship between nitrate (NO₃-N) levels in public water supplies and risk of death from childhood brain tumors (CBT) and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of NO₃-N on development of CBT. A matched cancer case-control study was used to investigate the relationship between the risk of death attributed to CBT and exposure to NO₃-N in drinking water in Taiwan. All CBT deaths of Taiwan residents from 1999 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 the 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 were collected from Taiwan Water Supply Corporation. The municipality of residence for CBT 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 ≤ 0.31 ppm, and the adjusted odds ration (OR) (95% confidence interval [CI]) for CBT occurrence was 1.4 (1.07-1.84) for individuals who resided in municipalities served by drinking water with a NO₃-N exposure > 0.31 ppm. No significant effect modification was observed by Ca and Mg intake via drinking water. Data suggest that exposure to NO₃-N in drinking water is associated with a higher risk of CBT development in Taiwan.

Abstract  Given that there was documented evidence of an association between diarrhea and high nitrate ingestion, the authors examined drinking water nitrate concentration and its possible correlation(s) with methemoglobin levels, cytochrome b(5) reductase activity, and recurrent diarrhea. In addition, the authors studied histopathological changes in the intestines of rabbits in an animal model. Five village areas were studied, and nitrate concentrations (expressed in mg of nitrate per liter of water) of 26, 45, 95, 220, and 459 existed in the respective villages. The study included 88 randomly selected children who were 8 yr of age or younger; they represented 10% of the total population of each of the areas. Detailed histories of recurrent diarrhea were noted, and medical examinations were conducted. Cytochrome b(5) reductase activity and methemoglobin levels were estimated biochemically. Collected data were analyzed statistically with Microsoft Excel software. In addition, the authors exposed rabbits to various levels of nitrate, and histopathological changes of the stomach and intestine (small and large) were evaluated. There was a strong relationship between nitrate concentration and recurrent diarrhea; 80% of the recurrent diarrhea cases were explained by nitrate concentration alone. In the rabbit intestines, lymphocytic infiltration and hyperplasia characterized the submucosa as nitrate concentrations increased.

Abstract  BACKGROUND: The present investigation was undertaken to better understand the production of nitric oxide (NO) in vivo as measured by alterations in plasma nitrite or nitrate in blood samples from studies in experimental animals or clinical studies in humans.

METHODS AND RESULTS: Plasma samples were taken from the aorta, the coronary sinus, a peripheral vein in the leg (skeletal muscle), or the right ventricle (mixed venous) in chronically instrumented conscious dogs. Plasma nitrite was converted to NO gas in an argon environment by use of hydrochloric acid, and plasma nitrate was converted first to nitrite with nitrate reductase and then to NO gas with acid. Standard curves were constructed, and the amount of nitrite and nitrate in plasma was determined. The primary metabolite was nitrate, whereas nitrate was approximately 10% of the total and remained constant. In the resting dog, the only vascular bed with a positive arterial-venous nitrate difference, evidence for production of NO, was the heart. Nitrate infusion into quietly resting dogs resulted in increases in plasma nitrate up to 38 +/- 3.4 mmol/L, increases in systemic arterial pressure, and a marked diuresis. The plasma half-life was calculated as 3.8 hours. The volume of distribution was calculated as 0.215 L/kg, or equivalent to the extracellular volume.

CONCLUSIONS: These studies indicate that nitrate is a reliable measure of NO metabolism in vivo but that because of the long half-life, nitrate will accumulate in plasma once it is produced. Because of the large volume of distribution (21% of body weight versus the 4% of body weight usually attributed to plasma volume, the compartment in which nitrate is measured), simple measures of plasma nitrate underestimate by a factor of 4 to 6 the actual production of nitrate or NO by the body. In disease states, such as heart failure, in which renal function and extracellular volume are altered, caution should be exercised when increases in nitrate in plasma as an index of NO formation are evaluated.

Abstract  BACKGROUND: It has long been known that nitrate combined with iodiduria < 100 micro gI(-)/l has a goitrogenic effect. The cause is a partial blockage of the sodium- iodide symporter together with a hindrance to iodide absorption in the intestine. 90% of the intake of nitrate is excreted in urine. Therefore nitraturia provides information about the population. The rare epidemiological studies of the influence of NO(3)(-) on goitre are limited to a small selection of older, regional samples. Our aim was to investigate the role of nitrate in the occurrence of goitre in Germany.

METHODS: Using random samples from 3,059 clinically healthy persons of both sexes between 18 and 70 years old from all over Germany, we examined nitraturia and the prevalence of goitre or nodules, including the corresponding iodiduria. (Sonography: 7.5 MHz linear transducer; nitrate determination: isocratic ion chromatography; iodide determination: cerium-arsenite method.) Both the NO(3)(-) and the iodide excretion in spontaneous urine were measured in relation to 1 g creatinine. Statistical processing: Mann-Whitney U-Test, correlation analysis, multivariate linear regression analysis.

RESULTS: Median for nitraturia: 55.2 mg NO(3)(-)/g creatinine (men 61.5, women 51.5; p < 0.03). Significant increase in regional nitrate excretion from North to South and from East to West. No statistical connection between nitraturia, thyroid size and nodules. In the multivariate linear regression analysis relating to thyroid size/focal lesions, NO(3)(-) played the smallest part among the variables age, gender, body mass index, iodiduria, nitraturia. In the case of iodiduria with < 50 micro g I(-)/g creatinine (n = 71), there was a correlation between nitraturia and thyroid size (r = 0.18; p < 0.05). All persons with a nitraturia of > 60 mg NO(3)(-)/g creatinine (n = 1,166) evidenced a correlation with the thyroid size (r = 0.18; p < 0.01).

CONCLUSION: Since alimentary iodine shortage in Germany has been overcome to a large extent (iodiduria 100-200 micro gI(-)/l) and the nitrate content lies clearly below the WHO limit, the goitrogenic effect of nitrate is only of individual and not of epidemiological importance. The slight regional differences in NO(3)(-) excretion are the consequence of the nitrate content in drinking water and have no effect on the thyroid gland.

Abstract  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.

Abstract  Animal studies have shown that nitrate acts as an endocrine disrupter affecting the androgen production in adult males. This raises a concern for more severe endocrine disrupting effects after exposure during the sensitive period of prenatal male sexual development. As there are no existing studies of effects of nitrate on male sexual development, the aim of the study was to examine how in utero exposure to nitrate would affect male rat fetuses. Pregnant dams were dosed with nitrate in the drinking water from gestational day (GD) 7 to GD21 at the following dose levels 17.5, 50, 150, 450, and 900 mg/l. At GD21, fetuses were examined for anogenital distance, plasma thyroxine levels, testicular and plasma levels of testosterone and progesterone, and testicular testosterone production and histopathology. In addition, endocrine disrupting activity of nitrate and nitrite were studied in two in vitro assays, the H295R assay and T-screen. There were no consistent indications that nitrate induces anti-androgenic effects in male fetuses or that prenatal nitrate exposure affected the thyroid axis. However, a more comprehensive study with long-term exposure before and during pre- and postnatal development would be relevant to sufficiently address the concerns based on the indications for endocrine disrupting effects in adult animals.

Abstract  The relationship between nitrate levels in drinking water and bladder cancer development is controversial. A matched cancer case-control with nitrate ecology study was used to investigate the association between bladder cancer mortality occurrence and nitrate exposure from Taiwan drinking water. All bladder cancer deaths of Taiwan residents from 1999 through 2003 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 cancer case. Data on nitrate-nitrogen (NO3-N) levels in 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 for bladder cancer death for those with high nitrate levels in their drinking water were 1.76 (1.28-2.42) and 1.96 (1.41-2.72) as compared to the lowest tertile. The results of the present study show that there was a significant positive relationship between the levels of nitrate in drinking water and risk of death from bladder cancer.

Abstract  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 b5 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 NO3 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 b5 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.

Abstract  Sodium nitrite administered in the drinking water to Long-Evans rats during pregnancy and lactation severely affected erythropoietic development, growth, and mortality in their offspring. Pregnant rats were maintained throughout gestation on 0.5, 1, 2, or 3 g NaNO2/liter. There were no significant differences between treated and control litters at birth. Thereafter, pups of treated dams on 2 and 3 g NaNO2/liter gained less weight, progressively became severely anemic, and began to die by the third week postpartum. By the second week postpartum, hemoglobin levels, RBC counts, and mean corpuscular volumes of these pups were all drastically reduced compared to controls. Blood smears showed marked anisocytosis and hypochromasia. Gross chylous serum lipemia and fatty liver degeneration were noted. Histopathology demonstrated cytoplasmic vacuolization of centrilobular hepatocytes and decreased hematopoiesis in bone marrow and spleen. Administration of 1 g NaNO2/liter resulted in hematological effects but did not affect growth or mortality. NaNO2 (0.5 g/liter) was at or near the no observed effect level. Cross-fostering indicated that treatment during the lactational period was more instrumental in producing lesions than treatment during the gestational period. The data presented are consistent with the lactational induction of severe iron deficiency in the neonate.

Abstract  BACKGROUND: Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons (PAHs). The authors comprehensively investigated the association between meat and meat components and bladder cancer.

METHODS: During 7 years of follow-up, 854 transitional cell bladder-cancer cases were identified among 300,933 men and women who had completed a validated food-frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. The authors estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat by using quantitative databases of measured values. Total dietary nitrate and nitrite were calculated based on literature values.

RESULTS: The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth quintile compared with first quintile, 1.22; 95% CI, 0.96-1.54; P(trend) = .07) and the HCA 2-amino-1 methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) (HR, 1.19; 95% CI, 0.95-1.48; P(trend) = .06) conferred a borderline statistically significant increased risk of bladder cancer. Positive associations were observed in the top quintile for total dietary nitrite (HR, 1.28; 95% CI, 1.02-1.61; P(trend) = .06) and nitrate plus nitrite intake from processed meat (HR, 1.29; 95% CI, 1.00-1.67; P(trend) = .11).

CONCLUSIONS: These findings provided modest support for an increased risk of bladder cancer with total dietary nitrite and nitrate plus nitrite from processed meat. Results also suggested a positive association between red meat and PhIP and bladder carcinogenesis.

Abstract  Objective: Methemoglobin formation caused by a liniment solution containing sodium nitrite (30 g/L and 140 g/L) was studied in rats with normal or abraded skin, by measuring the methemoglobin concentration before and after application of liniment solutions with differing nitrite concentration. Methods: Each liniment solution (120 mu L) was applied. Methemoglobin was measured for 180 minutes using a hemoximeter. Simul-taneously, arterial blood pressure and cutaneous blood flow was measured by laser Doppler flowmetry and a pressure transducer, Results: After the application of each liniment solution to normal skin, the methemoglobin concentration was not significantly modified depending on the time after application. Application of liniment solution to abraded skin (140 gn) resulted in a marked increase in methemoglobin concentration. A remarkable decrease in arterial blood pressure and subcutaneous blood flow were observed after application of liniment solution to abraded skin (140 gn). Conclusions: Each of these findings are characteristic of nitrite and they imply the percutaneous absorption of nitrite. Regardless of the nitrite concentration, the methemoglobin concentration was consistently higher in abraded skin than in normal skin.

Abstract  Methemoglobin (MHb) may arise from a variety of etiologies including genetic, dietary, idiopathic, and toxicologic sources. Symptoms vary from mild headache to coma/death and may not correlate with measured MHb concentrations, Toxin-induced MHb may be complicated by the drug's effect on other organ systems such as the liver or lungs. The existence of underlying heart, lung, or blood disease may exacerbate the toxicity of MHb. The diagnosis may be complicated by the effect of MHb on arterial blood gas and pulse oximeter oxygen saturation results. In addition, other dyshemoglobins may be confused with MHb. Treatment with methylene blue can be complicated by the presence of underlying enzyme deficiencies, including glucose-6-phosphate dehydrogenase deficiency. Experimental antidotes for MHb may provide alternative treatments in the future, but require further study.

Abstract  Protection of ground water for present and future use requires monitoring and understanding of the mechanisms controlling long-term quality of ground water. In this study, spatial and temporal trends in concentrations of nitrate and pesticides in ground water in the eastern San Joaquin Valley, California, were evaluated to determine the long-term effects of agricultural and urban development on regional ground-water quality. Trends in concentrations of nitrate, the nematocide 1,2-dibromo-3-chloropropane, and the herbicide simazine during the last two decades are generally consistent with known nitrogen fertilizer and pesticide use and with the position of the well networks in the regional ground-water flow system. Concentrations of nitrate and pesticides are higher in the shallow part of the aquifer system where domestic wells are typically screened, whereas concentrations are lower in the deep part of the aquifer system where public-supply wells are typically screened. Attenuation processes do not seem to significantly affect concentrations. Historical data indicate that concentrations of nitrate have increased since the 1950s in the shallow and deep parts of the aquifer system. Concentrations of nitrate and detection of pesticides in the deep part of the aquifer system will likely increase as the proportion of highly affected water contributed to these wells increases with time. Because of the time of travel between the water table and the deep part of the aquifer system, current concentrations in public-supply wells likely reflect the effects of 40- to 50-yr-old management practices.

Abstract  The metabolic fate of a p.o. dose of 3.5 mmol 15N-labeled nitrate has been investigated in 12 healthy young adults. Samples of urine, saliva, plasma, and feces were collected over a period of 48 hr following administration of the dose. Subjects received either 60 mg of ascorbic acid, 2 g of ascorbic acid, or 2 g of sodium ascorbate per day. An average of 60% of the 15NO3- dose appeared in the urine as nitrate within 48 hr. Less than 0.1% appeared in the feces. The 15N label of nitrate was also found in the urine (3%) and feces (0.2%) in the form of ammonia or urea. The fate of the remaining 35% of the 15NO3- dose administered is unknown. No effect of ascorbic acid or sodium ascorbate on the nitrate and nitrite levels of plasma, saliva, urine, or feces was observed. A one-compartment pharmacokinetic model was used to describe the relationships between intake, plasma concentration, and urinary excretion of nitrate. The half-life of nitrate in the body was found to be approximately 5 hr, and its volume of distribution was about 30% of body weight. Daily endogenous biosynthesis of nitrate was estimated to be about 1 mmol/day.

Abstract  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.

Abstract  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/chromosome 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.

Abstract  BACKGROUND: Most studies of meat and colorectal adenoma have investigated prevalent events from a single screening, thus limiting our understanding of the role of meat and meat-related exposures in early colorectal carcinogenesis.

METHODS: Among participants in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who underwent baseline and follow-up sigmoidoscopy (n=17,072), we identified 1008 individuals with incident distal colorectal adenoma. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between meat and meat-related components and incident distal colorectal adenoma using multivariate logistic regression.

RESULTS: We observed suggestive positive associations for red meat, processed meat, haeme iron, and nitrate/nitrite with distal colorectal adenoma. Grilled meat (OR=1.56, 95% CI=1.04-2.36), well or very well-done meat (OR=1.59, 95% CI=1.05-2.43), 2-amino-1-methyl-6-phenyl-imidazo[4,5-b]pyridine (PhIP) (OR=1.75, 95% CI=1.17-2.64), benzo[a]pyrene (OR=1.53, 95% CI=1.06-2.20), and total mutagenic activity (OR=1.57, 95% CI=1.03-2.40) were positively associated with rectal adenoma. Total iron (diet and supplements) (OR=0.69, 95% CI=0.56-0.86) and iron from supplements (OR=0.65, 95% CI=0.44-0.97) were inversely associated with any distal colorectal adenoma.

CONCLUSION: Our findings indicate that several meat-related components may be most relevant to early neoplasia in the rectum. In contrast, total iron and iron from supplements were inversely associated with any distal colorectal adenoma.

Abstract  Ovarian cancer is a leading cause of cancer death among women in the United States and it has the highest mortality rate of all gynecologic cancers. Internationally, there is a five-fold variation in incidence and mortality of ovarian cancer, which suggests a role for environmental factors, including diet. Nitrate and nitrite are found in various food items and they are precursors of N-nitroso compounds, which are known carcinogens in animal models. We evaluated dietary nitrate and nitrite intake and epithelial ovarian cancer in the National Institutes of Health (NIH)-AARP Diet and Health Study, including 151 316 women aged 50-71 years at the time of the baseline questionnaire in 1995-1996. The nitrate and nitrite intake was assessed using a 124-item validated food frequency questionnaire. Through 31 December 2006, 709 incident epithelial ovarian cancer cases with complete dietary information were identified. Using Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs), women in the highest intake quintile of dietary nitrate had a 31% increased risk (95% CI: 1.01-1.68) of epithelial ovarian cancer, compared with those in the lowest intake quintile. Although there was no association for total dietary nitrite, those in the highest intake category of animal sources of nitrite had a 34% increased risk (95% CI: 1.05-1.69) of ovarian cancer. There were no clear differences in risk by histologic subtype of ovarian cancer. Our findings suggest that a role of dietary nitrate and nitrite in ovarian cancer risk should be followed in other large cohort studies.

Abstract  Supersedes PB89-192223. Sponsored by Environmental Protection Agency, Washington, DC. Criteria and Standards Div. cument deals with the drinking water health effects of Nitrate/Nitrite through the review of several studies. The studies include animal and humans. Physical and chemical properties are discussed. Carcinogenicity of the compound is reviewed and evaluated through various studies. Any existing guidelines and standards are presented.