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Acute effects of nitrogen dioxide after accidental release.

OBJECTIVES: Following an accidental release of nitrogen dioxide from a railroad tank car containing nitrous tetroxide, the authors undertook a study of the health effects of the release, measuring the association between acute low level exposure and pulmonary symptoms. METHODS: The authors reviewed the records of three emergency departments, surveyed 80 emergency department patients, 552 community residents, 21 chemical plant workers, and 29 emergency workers, and conducted a case-control study. Pulmonary case status was defined as having an objective pulmonary finding noted on the emergency department record, reporting that the onset of symptoms was subsequent to the release, and being within the city limits at the time of the release. Self-reported case status was defined as reporting one or more symptoms consistent with exposure to nitrogen dioxide in the week after the release and having been within the city limits at the time of the release. Control subjects were survey respondents who reported no symptoms in the week after the release and had been within the city limits at the time of the release. Chemical exposure was characterized by proximity to, direction from, and being outdoors within one hour after the release. Duration of potential exposure was not measured. Logistic regression was used to estimate odds ratios and 95% confidence interval for symptoms by exposure level, adjusted for age, sex, smoking, and preexisting pulmonary conditions. RESULTS: Local emergency department visits increased fivefold in the week after the release. The most common complaints recorded in a systematic sample of 528 visits in the first 30 hours after the release were headache (31%), burning eyes (30%), and sore throat (24%). Objective pulmonary findings were recorded for 41 (5%) patients in the week before and 165 (4%) in the week after the release. The odds of being a pulmonary case increased by 40% for each quarter-mile increment in proximity to the release (odds ratio [OR] 1.4; 95% confidence interval [CI] 1.1, 1.7), while the odds of being a self-reported case increased by 20% for each quarter-mile increment in proximity (OR 1.2, 95% CI 1.1, 1.4). People who met the pulmonary case definition were 2.5 times (CI 1.3, 4.8) more likely than control subjects to have been outdoors and 6.4 times (CI 3.2, 12.6) more likely to report a preexisting pulmonary condition. Self-reported cases were 2.6 times (95% CI 1.8, 3.8) more likely than control subjects to have been outdoors and 1.9 times (95% CI 1.1, 3.1) more likely to report a preexisting pulmonary condition. CONCLUSIONS: Emergency department visits increased five-fold, but serious acute health effects were uncommon. People who met the pulmonary case definition were six times more likely to report pulmonary symptoms than those without preexisting conditions. This study was not designed to determine any potential long-term effects of exposure.

Accidents, Occupational↗

Effects of nitrogen dioxide on biochemical and physiological characteristics of soybean.

One month old soybean (Glycine max (L.) Merrill) cv. 'Williams' plants were exposed to nitrogen dioxide (NO2 at 0.1, 0.2, 0.3, and 0.5 microl liter(-1) and carbon filtered air (control), 7 h per day for five days, under controlled environment. Data were collected on net photosynthetic rate (PN), stomatal resistance (SR), and dark respiration rate (DR), immediately following the fifth day of exposure and 24 h after termination of exposure. Chlorophyll a (Ch a), chlorophyll b (Ch b), total chlorophyll (tot Ch) and foliar nitrogen (N) were measured before and after exposures. Growth characteristics--relative growth rate (RGR), net assimilation rate (NAR), leaf area ratio (LAR), and root shoot ratio (RSR) -- were computed for treated plants using standard growth equations. Increases of 18% and 23% in PN were observed immediately following exposure to 0.2 microl liter(-1) NO2 and after 24 h recovery period, respectively. With 0.5 microl liter(-1) NO2 treatment, reductions in PN of 23% and 50% were observed, immediately after exposure and following 24 h recovery, respectively. DR rates with 0.2 l liter(-1) treatment were higher than the control. Chlorophyll a and tot Ch showed significant reduction with 0.5 microl liter(-1) NO2 treatment. The percent reduction in Ch a and tot Ch with 0.5 microl liter(-1) NO2 were 45% and 47%, respectively. Increases in foliar nitrogen content after 0.2 and 0.3 microl liter(-1) NO2 treatments were 46% and 69%, respectively. Nitrogen dioxide at 0.5 microl liter(-1) reduced RGR and NAR by 47% and 51%, respectively. Leaf area ratio was 42% higher in 0.5 microl liter(-)1 NO2 treated plants, compared with the control; this increase was insufficient to compensate for the decrease in NAR resulting in a net decline in RGR. Nitrogen dioxide up to 0.2 microl liter(-1) increased PN and foliar-N content of soybean. With 0.5 microl liter(-1) NO2, significant decreases were observed in PN, leaf chlorophyll, foliar-N, NAR and RGR. Nitrogen dioxide up to 0.2 microl liter(-)1 has a favorable influence on overall growth characteristics of soybean; however, inhibitory effects were seen with NO2 treatment at 0.5 microl liter(-1).

Journal Article↗

Urinary hydroxyproline as a biomarker of effect after exposure to nitrogen dioxide.

A cross-sectional study was carried out on two groups of subjects differently exposed to nitrogen dioxide in order to test the urinary hydroxyproline ratio (UHP/mg/24 h/m(2)) as a biomarker of effect after exposure to this pollutant. UHP was determined in samples of 58 subjects divided into two groups comparable to as lifestyle and training. The first group was composed of 29 subjects who used to do jogging in urban areas polluted by nitrogen dioxide. The second group was made up of 29 subjects who used to do jogging in non-polluted countryside areas. The mean concentration of UHP of urban joggers was 25.02+/-9.21 mg/24 h/m(2), whereas in those training in the countryside it was 13.78+/-6.68 mg/24 h/m(2). Thus, UHP was higher in subjects training in areas polluted by nitrogen dioxide than in the subjects training in non-polluted areas.

Adolescent↗

Impaired regulation of surfactant phospholipid metabolism in the isolated rat lung after nitrogen dioxide inhalation.

Various drugs have been shown to stimulate surfactant phospholipid metabolism. Particularly beta-adrenergic agonists play an important role under physiologic conditions. For the first time we have studied whether nitrogen dioxide (NO2) inhalation alters beta-adrenergic regulation of surfactant phospholipid metabolism in the model of the isolated lung. Rats were continuously exposed in vivo to a 5 ppm NO2-containing atmosphere for 48 hr. The lungs were isolated and perfused in presence of the beta-adrenergic agonist dopexamine and surfactant metabolism was studied in three lung compartments: (1) lung lavage, (2) lung tissue, and (3) lavagable free alveolar cells. We found that (1) in normal rat lungs dopexamine increased the incorporation of palmitate and choline from the perfusate into lung lavage phospholipids. In nitrogen dioxide exposed rat lungs beta-adrenergic stimulation did not cause an increase in precursor incorporation. No significant difference in unstimulated precursor incorporation was found for normal and NO2-exposed rat lungs. (2) Lung tissue from rats exposed to NO2 showed a decreased precursor incorporation into disaturated phosphatidylcholine due to an augmented cellular pool size. (3) Lavagable alveolar cells showed an increased palmitate uptake after nitrogen dioxide inhalation and by beta-adrenergic stimulation. From these data we conclude that nitrogen dioxide inhalation impairs the beta-adrenergic regulation of surfactant phospholipid metabolism. Moreover these data underline the importance of beta-adrenergic agonists in surfactant metabolism.

Administration, Inhalation↗

Children's exposure to nitrogen dioxide in Sweden: investigating environmental injustice in an egalitarian country.

STUDY OBJECTIVE: Prior studies have shown that children are particularly sensitive to air pollution. This study examined whether children of low socioeconomic status suffered greater exposure to outdoor nitrogen dioxide than more affluent ones, both at their place of residence and at school, in a country with widespread state intervention for social equity. DESIGN: Local scale data on outdoor nitrogen dioxide obtained from a validated air pollution model were analysed, along with all school children accurately geocoded to their building of residence and school. PARTICIPANTS: All 29,133 children in grades one through nine (aged 7 to 15 years) residing and attending school in Malmö, Sweden, in 2001. MAIN RESULTS: Defining the socioeconomic status of children according to the mean income in their residential building, the spatial scan statistic technique allowed the authors to identify eight statistically significant clusters of low socioeconomic status children, all of which were located in the most polluted areas of Malmö. Four clusters of high socioeconomic status children were found, all of them located in the least polluted areas. The neighbourhood socioeconomic status better predicted the nitrogen dioxide exposure of children than the socioeconomic status of their building of residence. Exposure to nitrogen dioxide at the place of residence and school of attendance regularly increased as the socioeconomic status of a child's neighbourhood of residence decreased. CONCLUSIONS: Evidence of environmental injustice was found, even in a country noted for its egalitarian welfare state. Enforcement of environmental regulations may be necessary to achieve a higher level of environmental equity.

Adolescent↗

Spin trapping of nitrogen dioxide and of radicals generated from nitrous acid.

Spin trapping of nitrogen dioxide radical by several nitrones has been studied. The reaction results in the formation of persistent acyl nitroxides, after the oxidation of the intermediate spin adducts having an -ONO group on C-2 atom. The intermediate is effectively detected when DEPMPO is used as the spin trap. The reaction between PBN or 5,7-di-tert-butyl-3,3-dimethyl indoline N-oxide with nitrous acid gives the corresponding acyl nitroxide only when oxygen is present in the reaction milieu. On the other hand, nitroso spin traps do not trap *NO2 confirming that the unpaired electron of nitrogen dioxide is localized on the oxygen atom.

Electron Spin Resonance Spectroscopy↗

Formation of N-nitrosomorpholine in mice treated with morpholine and exposed to nitrogen dioxide.

The possibility of N-nitrosomorpholine formation was investigated in mice treated with morpholine and then exposed to 45 p.p.m. nitrogen dioxide in an inhalation chamber for 2 h. Following this treatment, the mice were frozen and pulverized in liquid nitrogen and concentrated extracts from the powders of these animals were analyzed for N-nitrosomorpholine using a thermal energy analyzer interfaced to a gas chromatograph. The data indicate that nitrogen dioxide exposure causes the nitrosation of morpholine in vivo. Additional data show that significant levels of artifactually formed N-nitrosomorpholine are found in control animals that are treated with morpholine after exposure to nitrogen dioxide for 2 h unless a combination of L-ascorbic acid and d,1-alpha-tocopherol are used to inhibit nitrosation during the homogenization, extraction, and analysis of the samples. The need for both a lipid phase nitrosation blocker (d,1-alpha-tocopherol) and an aqueous phase nitrosation blocker (L-ascorbic acid) indicates that the nitrosation of morpholine occurs in both a lipid and an aqueous phase in vitro and therefore may occur in both a lipid and an aqueous environment in vivo. The data from this study also demonstrate the importance of adding suitable inhibitors of nitrosation, such as L-ascorbic acid and d,1-alpha-tocopherol to the extraction solution to prevent possible artifactual formation of N-nitrosomorpholine during the extraction and analysis of the samples.

Animals↗

Reactions of indoles with nitrogen dioxide and nitrous acid in an aprotic solvent.

The reaction of 2-phenyl- and 1-methyl-2-phenylindole with nitrogen dioxide or with nitrous acid (NaNO2-CH3COOH) in benzene leads mainly to the formation of the isonitroso and 3-nitroso indole derivatives, respectively. When reacted with nitrous acid, 1-methyl-2-phenylindole gives also the corresponding azo-bis-indole in good yields. The reaction of indole with nitrogen dioxide leads to 2-(indol-3-yl)-3H-indol-3-one as the main product together with small amounts of 2-(indol-3-yl)-3H-indol-3-oxime; whereas the major product obtained when the same indole is reacted with nitrous acid is represented by 2-(indol-3-yl)-3H-indol-3-oxime. The reaction of 3-alkyl substituted indoles with nitrogen dioxide is rather complex and results in the formation of different nitro indoles, whereas nitrosation is observed when nitrous acid is used. Crystal structures of 2-(indol-3-yl)-3H-indol-3-one and of 4-nitro-N-acetyltryptamine have been determined by X-ray analysis.

Magnetic Resonance Spectroscopy↗

The effects of ozone and nitrogen dioxide on lung function in healthy and asthmatic adolescents.

The aim of this project was to investigate whether or not well characterized groups of healthy adolescents and adolescents with asthma differed in their sensitivity to ozone and nitrogen dioxide at near ambient concentrations of these pollutants. The project was divided into three phases. In each phase, ten healthy and ten asthmatic adolescents were exposed via a mouthpiece to three different atmospheres (filtered air, ozone, and nitrogen dioxide, at either 0.12 or 0.18 ppm) on separate days at least one week apart. During Phase I, subjects at rest inhaled the test atmospheres at 0.12 ppm for two 30-minute periods. The following pulmonary functional values were measured before, during, and after exposure: peak flow, total respiratory resistance, thoracic gas volume at functional residual capacity, maximal flow at 50 and 75 percent of expired vital capacity (performed with both room air and a helium-oxygen mixture), and forced expiratory volume in one second. Pulmonary function was not consistently altered in either the asthmatic or the healthy nonasthmatic adolescents as a result of the exposures. As a result, the study was repeated with the addition of ten minutes of exercise to the 30-minute rest exposure period (Phase II). In Phase II, small but significant increases in total respiratory resistance to all test atmospheres were seen after exposure at 0.12 ppm during exercise in both healthy and asthmatic adolescents. However, the increase in resistance between the groups of subjects was not statistically different. On the basis of these results, Phase III was conducted at higher concentrations of the pollutants (0.18 ppm). In Phase III, statistically significant changes were seen in average total respiratory resistance values in both healthy and asthmatic adolescents exposed to 0.18 ppm ozone while exercising. Again, the difference between the groups was not significant. Small decreases in average forced expiratory volume were found in healthy subjects exposed to ozone and filtered air. After exposure to nitrogen dioxide there was a 3 percent decrease in the forced expiratory volume in one second in asthmatic subjects. This change was not significant. It is concluded that there were no differences in pulmonary function responses between asymptomatic, allergic asthmatic adolescents and healthy adolescents exposed to either ozone or nitrogen dioxide under the conditions of these studies. However, an increase in total respiratory resistance was observed in both asthmatic and healthy adolescent subjects after their exercise exposure to 0.18 ppm ozone.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

Validation tests of a new high uptake rate passive sampler for nitrogen dioxide measurements.

This study explains the main characteristics of a new passive sampler which is able to give reliable nitrogen dioxide measurements for short time sampling. The sampling rate was found to be on average 0.89 cm3 s(-1) for indoor sampling and 1.00 cm3 s(-1) for outdoor sampling. The detection limit was evaluated at 11 microg m(-3) for a one-hour measurement. In field conditions, the passive sampler measurements were in agreement with those of the chemiluminescent NOx monitors. Measurement uncertainties were estimated at 34% and 38% for laboratory tests in conditions corresponding respectively to indoor and outdoor measurements and were evaluated at 28 to 37% depending on the nitrogen dioxide concentration for field experiments. The effects of various factors on the passive sampler were determined in an exposure chamber. The sampling rate of the retained sampler version was not significantly influenced by wind speeds superior to 0.3 m s(-1). A decrease of the uptake rate is observed for high nitrogen dioxide doses. The sampling rate increases linearly with temperature (2% per degree C). The relative humidity has only a weak effect.

Air Pollutants↗

Influence of polyunsaturated fatty acid supplementation and membrane fluidity on ozone and nitrogen dioxide sensitivity of rat alveolar macrophages.

The phospholipid polyunsaturated fatty acid (PUFA) content and the membrane fluidity of rat alveolar macrophages were modified dose-dependently and in different ways. This was done to study the importance of both membrane characteristics for the cellular sensitivity toward ozone and nitrogen dioxide. Cells preincubated with arachidonic acid (20:4) complexed to bovine serum albumin (BSA) demonstrated an increased in vitro sensitivity versus ozone and nitrogen dioxide. The phenomenon was only observed at the highest 20:4 concentrations tested, whereas the membrane fluidity of the 20:4-treated cells already showed a maximum increase at lower preincubation concentrations. Hence it could be concluded that the increased ozone and nitrogen dioxide sensitivity of PUFA-enriched cells is not caused by their increased membrane fluidity, resulting in an increased accessibility of sensitive cellular fatty acid moieties or amino acid residues. This conclusion receives further support from other observations. These results strongly support the involvement of lipid oxidation in the mechanism(s) of toxic action of both ozone and nitrogen dioxide in an intact cell system.

Animals↗

Nitrate formation in rats exposed to nitrogen dioxide.

Sprague-Dawley rats exposed to atmospheres containing low levels of nitrogen dioxide (NO2) for 24 hr had increased levels of nitrate in their urine on the day of exposure and on the 3 subsequent days. The total increase in urinary nitrate was linearly related to the nitrogen dioxide concentration administered. We recovered in urine 8.4 +/- 1.1 mumol nitrate/ppm NO2/24-hr exposure (slope +/- 95% confidence limits) for 185-g rats. Both the linearity and magnitude of this effect imply that reaction with respiratory tract water is not a major pathway of NO2 absorption in the lung. Instead, our observations support the hypothesis that the major interaction of NO2 in the lung is with readily oxidizable tissue components to form nitrite. We estimate that 9.6 mumol of nitrite is formed in the respiratory tract of the rat per ppm NO2 per 24-hr exposure. We also estimate that humans breathing air containing 0.1 ppm NO2 have about 3.6 mg of nitrite formed in their respiratory tract per day.

Absorption↗

Combined exposure to ozone and nitrogen dioxide.

A study of rats acutely exposed to ozone (0.5--2.0 ppm) or nitrogen dioxide (2--20 ppm) for 2 hr and sacrificed immediately thereafter shows little similarity in the individual biochemical effects of these pollutants. No evidence of nitrogen dioxide-induced lipid peroxidation was observed. Of interest is the finding that inhalation of nitrogen dioxide increases the extent to which concanavalin A agglutinates alveolar macrophages while ozone has exactly the opposite effect.

Air Pollutants↗

Postnatal effects of maternal exposure to nitrogen dioxide.

Pregnant albino rats were exposed to nitrogen dioxide in concentrations of 0.05, 0.10, 1 and 10 mg/m3 for 6 hr each day throughout gestation. Postnatal viability, growth, physical maturation, neuromotor development, and biochemical parameters indicative of NO2 oxidizing effects were studied in progeny up to the age of 3 months. It was found that although viability and physical development were little affected (only at 10 mg/m3), dose-dependent neurobehavioral deviations (such as disturbances in early neuromotor development, coordination deficits, retarded development of locomotion, reduced activity and reactivity) were induced by the lower exposures. The reduction in motor activity was found to persist into the postweaning period.

Animals↗

Scaling toxicity from laboratory animals to people: an example with nitrogen dioxide.

Published data on the toxicity of nitrogen dioxide (as a model compound) from five laboratory animal species were utilized to scale the relationship of dose and toxic effect to the human species. A minute volume of inspired air was used as a metabolic scaling factor, predicting a median lethality during the time of exposure of 174 ppm NO2 for a 1-h exposure for people. This work demonstrates a method of predicting effects in people when only data for laboratory animals exist. It also shows the value of planning toxicology studies that utilize several animal species, so that their data may be applied to forecasting the human condition.

Animals↗

Histopathological and histochemical studies of the skin of guinea pigs after long-term exposure to nitrogen dioxide.

Male guinea pigs were exposed to nitrogen dioxide (2 mg/m3) during 180 days (8 hours a day). Long-term exposure induced thickening of the corneal layer of the epidermis as well as inflammatory infiltrations in the proper skin. The following enzymes were estimated histochemically in skin samples of experimental and control animals: succinic dehydrogenase, NADH2-tetrazolium reductase, lactate dehydrogenase; alkaline phosphatase, acid phosphatase and adenosine triphosphatase. Chronic exposrue stimulated a decrease of NADH2-tetrazolium reductase in the epidermis and connective tissue components of proper skin and marked positive reaction of lactate dehydrogenase in epidermal cells and hair follicles. Increase of a diffuse reaction on adenosine triphosphatase in smooth muscles of the skin was found also in exposed animals.

Acid Phosphatase↗

Indoor air pollution and its effect on pulmonary function of adult non-smoking women: II. Associations between nitrogen dioxide and pulmonary function.

The association between nitrogen dioxide levels in homes and pulmonary function of 97 non-smoking adult women was investigated in a rural area in the Netherlands. The study population was a sub-sample of a longitudinal field study on chronic non-specific lung diseases which was started in 1965. Pulmonary function tests were performed at three-yearly intervals. NO2 was measured for one week in the winter in kitchen, living room and bedroom of each home. Cross-sectional analyses showed negative associations between NO2 exposure and several pulmonary function parameters as measured in the 1982 study. No significant association could be found between NO2 exposure and pulmonary function decline since the start of the study.

Adult↗