Abstract  To identify occupational factors associated with non-Hodgkin's lymphoma (NHL).

A population-based case-control study was conducted in which incident cases of high-malignancy NHL (NHL(high)), low-malignancy NHL (NHL(low)), and chronic lymphocytic leukemia (CLL) were ascertained during the period 1986-1998 among men and women aged 15-75 years residing in six German counties; controls were drawn from population registries. Occupational histories were collected and agent-specific exposures were estimated via a job-exposure-matrix. Odds ratios were estimated by conditional logistic regression.

A total of 858 cases were included in these analyses. Agricultural workers [odds ratio (OR) = 2.67, 95% confidence interval (CI): 0.99, 7.21) and farmers (OR = 1.98, 95% CI: 0.98, 3.98] had elevated risk of NHL(high). Risk of NHL(low) was elevated among agricultural workers (OR = 2.46, 95% CI: 1.17, 5.16), and among blacksmiths, toolmakers, and machine tool operators (OR = 3.12, 95% CI: 1.31, 7.47). Workers in sales and construction had elevated risks of NHL(high) and NHL(low). Exposure to arsenic compounds, chlorophenols, diesel fuel, herbicides, nitrites/nitrates/nitrosamines, and organic dusts were associated with NHL(high) and NHL(low), while exhibiting little association with CLL. A positive monotonic trend in NHL(low) risk across tertiles of cumulative diesel fuel exposure was observed [P-value for test of linear trend (P) = 0.03].

These findings provide insights into several potential occupational risk factors for NHL and suggest some specific occupational agents for further investigation.

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 effects of methylnitrosourea (MNU) on the development of preimplantation mouse embryos were investigated in this study. ICR mice were treated intraperitoneally with single doses of 10, 20, and 30 mg MNU/kg body wt on day 0, 1, 2, or 3 of pregnancy. The uterine contents were examined on day 18 of pregnancy. The fetuses were examined for external and skeletal abnormalities. No significant differences were observed in the number of implantation sites between all the MNU-treated groups and controls. MNU treatment on day 2 or 3 of pregnancy caused dose-dependent significant increases in the incidence of abnormal fetuses over the control level, while treatment on day 0 or 1 failed to cause an increase of abnormalities. Cleft palate, exencephalus, and malformed vertebrae were the most common types of abnormalities. In the embryo transfer experiments, the frequency of fetal abnormalities induced when embryos were transferred from MNU-treated females to untreated pseudopregnant females was significantly higher than that induced when embryos were transferred from untreated females to MNU-treated or untreated pseudopregnant females. The results in the present study confirm and extend the previously proposed hypothesis that the direct effects of MNU on preimplantation embryos make a significant contribution to the induction of fetal malformations.

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.

Abstract  The relationship between nitrate levels in drinking water and colon cancer has been inconclusive. A matched case-control and a nitrate ecology study were used to investigate the association between colon cancer mortality and nitrate exposure from Taiwan's drinking water. All colon 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 sex, year-of-birth, and year-of-death. Each matched control was selected randomly from the set of possible controls for each case. Data on nitrate-nitrogen (NO3-N) level of drinking water throughout Taiwan have been 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 nitrate exposure via drinking water. The adjusted odds ratios for colon cancer death for those with high NO3-N levels in their drinking water, as compared to the lowest tertile, were 0.98 (0.84-1.14) and 0.98 (0.83-1.16), respectively. The results of the present study show that there was no statistically significant association between NO3-N in drinking water at levels in this study and risk of death from colon cancer.

Abstract  OBJECTIVE: To determine whether nitric oxide is synthesized in the breast and plays a role in lactation.

DESIGN: Concentrations of biopterin, neopterin, and the total concentration of nitrite plus nitrate, a marker for nitric oxide generation were measured in 242 samples of breast milk obtained from 39 women during postpartum days 1 to 30. The total concentration of nitrite plus nitrate was measured in 17 sets of breast milk and serum obtained from 17 women on postpartum day 4 or 5.

RESULTS: (1) The total concentration of nitrite plus nitrate rose and peaked just before an increase in the volume of milk secreted was observed. (2) The total concentration of nitrite plus nitrate in breast milk was not correlated with that in the serum. (3) High levels of neopterin and biopterin were found in breast milk. (4) The volume of breast milk on day 5 was correlated with the total concentration of nitrite plus nitrate observed in breast milk on days 1 to 3. (5) The total concentration of nitrite plus nitrate in the breast milk of the high secretors significantly exceeded that seen in the low secretors.

CONCLUSIONS: We suggest that nitric oxide is synthesized in the breast and may trigger lactation in humans.

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

Abstract  Nitrites and nitrates are consumed nonchalantly in diet. Organic nitrates are also used as vasodilators in angina pectoris, but the therapy is associated with tolerance whose mechanism remains elusive. Previously, we found inorganic nitrate inhibited steroidogenesis in vitro. Because adrenocorticoids regulate water and electrolyte metabolism, tolerance may ensue from steroid deficiency. We have studied the effects of nitrite and nitrate on in vitro synthesis and in vivo blood levels of steroid hormones. In vitro, nitrite was more potent than nitrate in inhibiting human chorionic gonadotropin (hCG)-stimulated androgen synthesis by Mouse Leydig Tumor cells. At concentrations above 42 mM, nitrite completely inhibited androgen synthesis, and, unlike nitrate, the inhibition was irreversible by increasing hCG concentration. The cAMP production remained intact but reduced with both ions. The nitric oxide (NO) scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxy-3-oxide (c-PTIO) significantly increased hCG- or cAMP-stimulated androgen synthesis in all buffers, suggesting that NO is a chemical species directly involved in the nitrite/nitrate-induced inhibition. This is further supported by c-PTIO countering the inhibitory action of methylene blue on androgen synthesis. Rats given distilled water containing 50 mg/L NaNO(2) or NaNO(3) for 4 weeks drank significantly less daily. At the end, their blood corticosterone and testosterone levels were significantly decreased. The adrenocortical histology showed bigger lipid droplets, which are pathogonomic of impaired steroidogenesis. Nitrite and nitrate are metabolized to NO, which binds heme in cytochrome P450 enzymes, thereby inhibiting steroidogenesis. Therapeutic nitrates likewise may decrease adrenal (and gonadal) steroidogenesis. Cortisol deficiency would impair water excretion causing volume expansion, and aldosterone deficiency would cause sodium loss and raised renin. Paradoxically, volume expansion without sodium retention and raised renin has all been reported in tolerance.

Abstract  Rats were exposed to nitrate (NO3-) in drinking water, to phenylmercuryacetate (PMA) by gavage and to NO3- and PMA together during 4 different experiments. PMA impaired kidneys, NO3- thyroid gland, and NO3- and PMA together both organs. In the last case a synergistic effect on the thyroid gland was shown. The lowest effective concentration of NO3- was 40 mg/l. It resulted in histomorphological changes of the thyroid epithelial cells. That low effective dose of NO3- and possible synergistic effects should give a further impulse to take into consideration not only a low iodide intake but also goitrogenic environmental chemicals when evaluating the endemic goitre prevalence.

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  The objectives of this study were to (1) examine the relationship between nitrate levels in public water supplies and increased risk of death from rectal cancer and (2) determine whether calcium (Ca) and magnesium (Mg) levels in drinking water might modify the effects of nitrate on development of rectal cancer. A matched case-control study was used to investigate the relationship between the risk of death from rectal cancer and exposure to nitrate in drinking water in Taiwan. All rectal 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 (NO(3)-N), Ca, and Mg in drinking water was 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 level was <0.38 ppm, the adjusted odds ratio (OR) (95% CI) for rectal cancer occurrence was 1.15 (1.01-1.32) for individuals who resided in municipalities served by drinking water with a NO(3)-N exposure > or =0.38 ppm. There was no apparent evidence of an interaction between drinking water NO(3)-N levels with low Mg intake via drinking water. However, evidence of a significant interaction was noted between drinking-water NO(3)-N concentrations and Ca intake via drinking water. Our findings showed that the correlation between NO(3)-N exposure and risk of rectal cancer development was influenced by Ca in drinking water. This is the first study to report effect modification by Ca intake from drinking water on the association between NO(3)-N exposure and risk of rectal cancer occurrence. Increased knowledge of the mechanistic interaction between Ca and NO(3)-N in reducing rectal cancer risk will aid in public policymaking and setting threshold standards.

Abstract  Germfree and conventional-flora Sprague-Dawley rats were fed sodium nitrate or sodium nitrite in their drinking water (1,000 microgram/ml), and various organs, tissues, and sections of the intestinal tract were assayed for nitrate (NO3-) and nitrite (NO2-) by a spectrophotometric method. When fed NO3-, germfree rats had chemically detectable levels of NO3- (only) in the stomach, small intestine, cecum, and colon. Conventional-flora rats fed NO3- had both NO3- and NO2- in the stomach, but only NO3- in the small intestine and colon. When fed NO2-, germfree rats had both NO3- and NO2- in the entire gastrointestinal tract. Conventional-flora rats fed NO2- had both ions in the stomach and small intestine, but only NO3- in the large intestine. Conventional-flora rats fed NO3- or NO2- had lower amounts of these ions in the gastrointestinal tract than comparably fed germfree rats. Control (non-NO3- or NO2--fed) germfree and conventional-flora rats had trace amounts of NO3- (only) in their stomachs and bladders. These results, in conjunction with various in vitro studies with intestinal contents, suggest that NO3- or NO2- reduction is a function of the normal bacterial flora, whereas NO2- oxidation is attributable to the mammalian host. In addition, the distribution of these ions after their ingestion appears more widespread in the body than previously thought.

Abstract  The clinical signs of acute nitrate toxicity vary according to species. In general, ruminant animals develop methemoglobinemia while monogastric animals exhibit severe gastritis. Nitrate ingestion has also been linked to impairment of thyroid function, decreased feed consumption, and interference with vitamin A and E metabolism. Hematologic changes seen with chronic high nitrate exposure include both compensatory increases in red blood cells and anemia, along with increased neutrophils and eosinophils. Unlike nitrate, nitrite is capable of inducing methemoglobinemia in a wide range of species, ie cattle, sheep, swine, dogs, guinea pigs, rats, chickens and turkeys. In rats, chronic nitrite exposure causes pathologic changes in a variety of tissues, alterations in motor activity and brain electrical activity, and alters gastric mucosal absorption. Nitrite affects the metabolism of sulfonamide drugs in animals such as the pig, guinea pig, and rat. The N-nitroso compound dimethylnitrosamine causes toxic hepatosis in cattle, sheep, mink, and fox. Nitrosamines have been reported in cows milk and been found to pass into the milk of goats under experimental conditions.

Abstract  BACKGROUND: Dietary nitrate increases saliva nitrite levels and swallowed saliva is the main source of nitrite entering the acidic stomach. In acidic gastric juice, this nitrite can generate potentially carcinogenic N-nitrosocompounds. However, ascorbic acid secreted by the gastric mucosa can prevent nitrosation by converting the nitrite to nitric oxide.

METHODS: To study the potential for N-nitrosocompound formation in a model simulating salivary nitrite entering the acidic stomach and the ability of ascorbic acid to inhibit the process. Concentrations of ascorbic acid, total vitamin C, nitrite, nitrosomorpholine, oxygen and nitric oxide were monitored during the experiments.

RESULTS: The delivery of nitrite into HCl containing thiocyanate resulted in nitrosation of morpholine, with the rate of nitrosation being greatest at pH 2.5. Under anaerobic conditions, ascorbic acid converted the nitrite to nitric oxide and prevented nitrosation. However, in the presence of dissolved air, the ascorbic acid was ineffective at preventing nitrosation. This was due to the nitric oxide combining with oxygen to reform nitrite and this recycling of nitrite depleting the available ascorbic acid. Further studies indicated that the rate of consumption of ascorbic acid by nitrite added to natural human gastric juice (pH 1.5) was extremely rapid with 200 micromol/l nitrite consumed 500 micromol/l ascorbic acid within 10 s.

CONCLUSIONS: The rapid consumption of ascorbic acid in acidic gastric juice by nitrite in swallowed saliva indicates that the potential for acid nitrosation will be maximal at the GO junction and cardia where nitrite first encounters acidic gastric juice. The high incidence of mutagenesis and neoplasia at this anatomical location may be due to acid nitrosation arising from dietary nitrate.

Abstract  The present study was undertaken to determine the effects of intake of inorganic nitrates in drinking water on thyroid gland activity and morphology in female rats. During 5 months of treatment, nitrates 50, 150 and 500 mg/L induced a significant dose-dependent decrease in bodyweight gain, compared with the control rats. At the end of the experiment, nitrates 150 and 500 mg/L induced hypertrophy of the thyroid gland, accompanied by an increase in the size of the thyroid follicles and hyposecretion of thyroid hormones T3 (triiodothyronine) and T4 (tetraiodothyronine). We concluded that a high nitrate intake in water influenced thyroid gland activity and morphology and might be considered to be a goitrogenic factor.

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  A subchronic oral toxicity study with potassium nitrite (KNO2) was carried out in rats. Groups of ten male and ten female 6-wk-old rats received KNO2 in the drinking-water (tap-water) at levels of 0, 100, 300, 1000 and 3000 mg/litre for a period of 13 wk. The potassium concentration in the nitrite solutions was equalized by adding potassium chloride (KCl) up to the potassium level of the 3000-mg KNO2/litre solution. An additional group of ten males and ten females received drinking-water supplemented with KCl only, at an amount resulting in a potassium concentration equivalent to that of the 3000-mg KNO2/litre solution. Body weight, food intake and food efficiency were decreased at 3000-mg/litre level in males, while liquid intake was decreased in males given 1000 and 3000 mg/litre and in females given 3000 mg/litre. There was significant increase in the methaemoglobin concentration in animals given 3000 mg/litre, while slight decreases in red blood cell variables occurred at the 1000- and 3000-mg/litre dose. No impaired renal function was observed in any of the test groups, although the relative weight of the kidneys and the plasma urea nitrogen level was increased at 3000 mg/litre. There was a slight decrease in plasma alkaline phosphatase activity at 3000 mg/litre. A small amount of nitrite was present in the saliva of the rats receiving 3000 mg/litre but there was no evidence of increased mutagenic activity in the urine of these rats. Interestingly, hypertrophy of the adrenal zone glomerulosa was observed in all test groups, the incidence and degree being dose related. It was concluded that in the study reported here the no-effect level is lower than 100 mg KNO2/litre in the drinking-water, which is equivalent to a level lower than 10 mg KNO2/kg body weight/day.

Abstract  Nitrate and nitrite are precursors of N-nitroso compounds (NOC), probable human carcinogens that cause pancreatic tumors in animals. Disinfection by-products (DBP) exposures have also been linked with digestive system cancers, but few studies have evaluated relationships with pancreatic cancer. We investigated the association of pancreatic cancer with these drinking water contaminants and dietary nitrate/nitrite in a cohort of postmenopausal women in Iowa (1986-2011). We used historical monitoring and treatment data to estimate levels of long-term average nitrate and total trihalomethanes (TTHM; the sum of the most prevalent DBP class) and the duration exceeding one-half the maximum contaminant level (>½ MCL; 5 mg/L nitrate-nitrogen, 40 µg/L TTHM) among participants on public water supplies (PWS) >10 years. We estimated dietary nitrate and nitrite intakes using a food frequency questionnaire. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression and evaluated nitrate interactions with smoking and vitamin C intake. We identified 313 cases among 34,242 women, including 152 with >10 years PWS use (N = 15,710). Multivariable models of average nitrate showed no association with pancreatic cancer (HRp95vs. Q1  = 1.16, 95% CI: 0.51-2.64). Associations with average TTHM levels were also null (HRQ4vs. Q1  = 0.70, 95% CI:0.42-1.18). We observed no trend with increasing years of exposure to either contaminant at levels >½ MCL. Positive associations were suggested in the highest dietary nitrite intake from processed meat (HRp95vs. Q1  = 1.66, 95% CI 1.00-2.75;ptrend  = 0.05). We found no interactions of nitrate with known modifiers of endogenous NOC formation. Our results suggest that nitrite intake from processed meat may be a risk factor for pancreatic cancer.

Abstract  The effects of long-term concurrent administration of powdered fish meal and sodium nitrite were examined in F344 rats. A total of 600, 6-week-old rats were divided into 6 male and 6 female groups, each consisting of 50 animals. Rats in groups 1-3 and 7-9 were respectively fed diets supplemented with 64%, 32% and 8% (basal diet) fish meal, and simultaneously given 0.12% sodium nitrite in their drinking water. Groups 4-6 and 10-12 were respectively given 64%, 32% and 8% fish meal and tap water. At the 104th week, all surviving animals were killed and examined histopathologically, Treatment with fish meal dose-dependently increased the incidences and multiplicities of atypical tubules, adenomas and renal cell carcinomas in sodium nitrite-treated males. Females were less susceptible than males for renal tumor induction. In males given the 64% fish meal diet alone, the incidence and multiplicity of atypical tubules were also significantly increased as compared with the 8% fish meal alone case. Nephropathy was apparent in fish meal-treated groups in a clear dose-dependent manner, irrespective of the sodium nitrite treatment, and was more prominent in males than in females. Dimethylnitrosamine was found in the stomach contents after 4-week treatment with 64% fish meal plus 0.12% sodium nitrite, at a level twice that in the 8% fish meal plus 0.12% sodium nitrite group. The results clearly indicate that concurrent administration of fish meal and sodium nitrite induces renal epithelial tumors. Further studies are required to elucidate how nephropathy and nitrosamines produced in stomach contents may contribute to the observed renal tumor induction.

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  Trimorphamide [N-(1-formamido-2,2,2-trichloroethyl)morpholine], with an acute LD50 of 990 mg/kg, is a systemic fungicide under development. To examine its possible nitrosation in vivo, CFY rats were treated i.g. with 326 mg/kg trimorphamide, suspended in 40 mg/kg sodium nitrite. after 1 hour, another 40 mg/kg sodium nitrite was given i.g. and the animals were killed an hour later. The nitroso derivative was extracted by dichloromethane from the gastric content, after steam distillation. The samples were analysed by gas chromatography (GC) and mass spectrometry (MS). N-Nitrosomorpholine (NMOR) was identified by comparison with authentic samples, both by GC and MS, using retention times and electron impact mass spectra. Quantification was carried out by GC-MS-specific ion monitoring, using the m/e 116 peak. The yield of NMOR ws found to be 0.65%. By the use of the Ames test, NMOR formed in vivo proved to be strongly mutagenic for the strains TA 1535 and TA 100, both in presence and absence of S-9 fraction. Tumour-bearing animals, treated by sodium nitrite plus trimorphamide, are being analysed.

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.