Abstract  ABSTRACT While evidence suggests associations between maternal exposure to air pollution and adverse birth outcomes, pregnant women's exposure to household air pollution in developing countries is understudied. Personal exposures of pregnant women (n = 100) in Trujillo, Peru to air pollutants and their indoor concentrations were measured. The effects of stove-use related characteristics and ambient air pollution on exposure were determined using mixed-effects models. Significant differences in 48-hr kitchen concentrations of particulate matter (PM2.5), carbon monoxide (CO), and nitrogen dioxide (NO2) concentrations were observed across fuel-types (p < 0.05). Geometric mean PM2.5 concentrations were 112 μg/m (3) (CLs: 52, 242 μg/m(3)) and 42 μg/m(3) (21, 82 μg/m(3)) in homes were wood and gas were used respectively. PM2.5 exposure was at levels which recent exposure-response analyses suggest may not result in substantial reduction in health risks even in homes where cleaner burning gas stoves were used.

Abstract  BACKGROUND: The prevalence of Autistic Disorder (AD), a serious developmental condition, has risen dramatically over the past two decades but high-quality population-based research addressing etiology is limited. OBJECTIVES: We studied the influence of exposures to traffic-related air pollution during pregnancy on the development of autism using data from air monitoring stations and a land use regression (LUR) model to estimate exposures. METHODS: Children of mothers who gave birth in Los Angeles who were diagnosed with a primary AD diagnosis at ages 3-5 years during 1998-2009 were identified through the California Department of Developmental Services and linked to 1995-2006 California birth certificates. For 7,603 children with autism and 10 controls per case matched by sex, birth year, and minimum gestational age, birth addresses were mapped and linked to the nearest air monitoring station and a LUR model. We used conditional logistic regression, adjusting for maternal and perinatal characteristics including indicators of SES. RESULTS: Per interquartile range (IQR) increase, we estimated a 12-15% relative increase in odds of autism for O3 (OR = 1.12, 95% CI: 1.06, 1.19; per 11.54 ppb increase) and PM2.5 (OR = 1.15, 95% CI: 1.06, 1.24; per 4.68 μg/m3 increase) when mutually adjusting for both pollutants. Furthermore, we estimated 3-9% relative increases in odds per IQR increase for LUR-based NO and NO2 exposure estimates. LUR-based associations were strongest for children of mothers with less than a high school education. CONCLUSION: Measured and estimated exposures from ambient pollutant monitors and LUR model suggest associations between autism and prenatal air pollution exposure, mostly related to traffic sources.

Abstract  BACKGROUND: Prenatal and early life periods may be critical windows for harmful effects of air pollution on infant health. OBJECTIVES: We studied the association of air pollution exposure during pregnancy and the first year of life with respiratory illnesses, ear infections, and eczema during the first 12-18 months of age in a Spanish birth cohort of 2,199 infants. METHODS: We obtained parentally-reported information on doctor-diagnosed lower respiratory tract infections (LRTI), and parental reports of wheezing, eczema, and ear infections. We estimated individual exposures to nitrogen dioxide (NO2) and benzene with temporally-adjusted land use regression models. We used log-binomial regression models and a combined random-effects meta-analysis to estimate the effects of air pollution exposure on health outcomes across the four study locations. RESULTS: A 10-µg/m3 increase in average NO2 during pregnancy was associated with LRTI (RR = 1.05; 95% CI: 0.98, 1.12) and ear infections (RR = 1.18; 95% CI: 0.98, 1.41). The RRs for an interquartile range (IQR) increase in NO2 were 1.08 (95% CI: 0.97, 1.21) for LRTI and 1.31 (95% CI: 0.97, 1.76) for ear infections. Compared to NO2, the association for an IQR increase in average benzene exposure was similar for LRTI (RR = 1.06; 95% CI: 0.94, 1.19) and slightly lower for ear infections (RR = 1.17; 95% CI: 0.93, 1.46). Associations were slightly stronger among infants whose mothers spent more time at home during pregnancy. Air pollution exposure during the first year was highly correlated with prenatal exposure, thus we were unable to discern the relative importance of each exposure period. CONCLUSIONS: Our findings support the hypothesis that early life exposure to ambient air pollution may increase the risk of upper and lower respiratory tract infections in infants.

Abstract  To show how remote-sensing products can be used to classify the entire CONUS domain into 'geographical regions' and 'chemical regimes', we analyzed the results of simulation from the Community Multiscale Air Quality (CMAQ) model version 4.7.1 over the Conterminous United States (CONUS) for August 2009. In addition, we observe how these classifications capture the weekly cycles of ground-level nitrogen oxide (NOx) and ozone (O-3) at US EPA Air Quality System (AQS) sites. We use the Advanced Very High Resolution Radiometer (AVHRR) land use dominant categories and the Global Ozone Monitoring Experiment-2 (GOME-2) HCHO/NO2 column density ratios to allocate geographical regions (i.e., "urban", "forest", and "other" regions) and chemical regimes (i.e., "NOx-saturated", "NOx-sensitive", and "mixed" regimes). We also show that CMAQ simulations using GOME-2 satellite-adjusted NOx emissions mitigate the discrepancy between the weekly cycles of NOx from AQS observations and that from CMAQ simulation results. We found geographical regions and chemical regimes do not show a one-to-one correspondence: the averaged HCHO/NO2 ratios for AVHRR "urban" and "forest" regions are 2.1 and 4.0, which correspond to GOME-2 'mixed' and "NOx-sensitive" regimes, respectively. Both AQS-observed and CMAQ-simulated weekly cycles of NOx show high concentrations on weekdays and low concentrations on weekends, but with one- or two-day shifts of weekly high peaks in the simulated results, which eventually introduces the shifts in simulated weekly-low O-3 concentration. In addition, whereas the high weekend O-3 anomaly is clearly observable at sites over the GOME-2 NOx-saturated regime in both AQS and CMAQ, the weekend effect is not captured at sites over the AVHRR urban region because of the chemical characteristics of the urban sites (approximate to GOME-2 mixed regime). In addition, the weekend effect from AQS is more clearly discernible at sites above the GOME-2 NOx-saturated regime than at other sites above the CMAQ NOx-saturated regime, suggesting that the GOME-2-based chemical regime classification is more accurate than CMAQ-based chemical classification. Furthermore, the CMAQ simulations using the GOME-2-derived NOx emissions adjustment (decreasing from 462 Gg N to 426 Gg N over the US for August 2009) show large reductions of simulated NOx concentrations (particularly over the urban, or NOx-saturated, regime), and mitigates the large discrepancies between the absolute amount and the weekly pattern of NOx concentrations of the EPA AQS and those of the baseline CMAQ.

Abstract  We have studied 26 asthmatic patients in whom deep inspiration induced a transient but marked bronchodilatation when carbachol-induced bronchoconstriction was present. Changes in bronchial tone were assessed by specific airway resistance measurements. Bronchodilatation after a slow inspiration (eight subjects) or a 10-second breath-hold at total lung capacity (13 subjects) was significantly less than that observed after either a fast inspiration or no breath-holding period. The magnitude of the bronchodilatation induced by a fast inspiration without breath-holding was directly and significantly related to the magnitude of the carbachol-induced bronchoconstriction in five subjects.

Abstract  Rationale: The role of air pollution exposure in the development of asthma, allergies, and related symptoms remains unclear, due in part to the limited number of prospective cohort studies with sufficiently long follow-ups addressing this problem. Objectives: We studied the association between traffic-related air pollution and the development of asthma, allergy, and related symptoms in a prospective birth cohort study with a unique 8-year follow-up. Methods: Annual questionnaire reports of asthma, hay fever, and related symptoms during the first 8 years of life were analyzed for 3,863 children. At age 8, measurements of allergic sensitization and bronchial hyperresponsiveness were performed for subpopulations (n = 1,700 and 936, respectively). Individual exposures to nitrogen dioxide (NO(2)), particulate matter (PM(2.5)), and soot at the birth address were estimated by land-use regression models. Associations between exposure to traffic-related air pollution and repeated measures of health outcomes were assessed by repeated-measures logistic regression analysis. Effects are presented for an interquartile range increase in exposure after adjusting for covariates. Measurements and Main Results: Annual prevalence was 3 to 6% for asthma and 12 to 23% for asthma symptoms. Annual incidence of asthma was 6% at age 1, and 1 to 2% at later ages. PM(2.5) levels were associated with a significant increase in incidence of asthma (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.10-1.49), prevalence of asthma (OR, 1.26; 95% CI, 1.04-1.51), and prevalence of asthma symptoms (OR, 1.15; 95% CI, 1.02-1.28). Findings were similar for NO(2) and soot. Associations were stronger for children who had not moved since birth. Positive associations with hay fever were found in nonmovers only. No associations were found with atopic eczema, allergic sensitization, and bronchial hyperresponsiveness. Conclusions: Exposure to traffic-related air pollution may cause asthma in children.

Abstract  Several nasal nitric oxide (NO) measurement techniques have been described, but there is not a widespread measurement technique for measurement of nasal NO. In this study we evaluated the repeatability of one technique of nasal NO measurements using the nasal application of the NIOX system. METHODS: Three nasal NO measurements (NIOX Nitric Oxide Monitoring System, Aerocrine, Sweden) were made on a single occasion in 22 healthy subjects and 27 patients with asthma, aged 5-69 years. Nasal NO was sampled during breath hold from one nostril at a flow rate of 5 ml/s. RESULTS: The repeatability of nasal NO assessed by the coefficient of variation (CV) was 12.5% (95% Confidence interval (CI) 11.0-14.7%) for the total population. Healthy adults had a significantly better repeatability than healthy children (P<0.008). The mean NO level for the total population was 837 ppb. The mean NO levels in children were lower than in the adults (751 and 897 ppb, respectively). The mean breath hold length needed to obtain a steady NO plateau for all subject categories combined was 20.4+/-6.01 s. The average number of attempts needed to obtain three approved NO measurements was 5.4 (range 3-13) for the total population. There were no significant differences between the different subject categories. When using two measurements per session instead of three, the overall CV was 10.5% (95% CI 8.8-13.1%). Most subjects found the measurements easy to perform and all of them would accept to do the examination as a routine. CONCLUSIONS: Nasal NO measurements in NIOX may provide a useful reliable clinical tool to assess and monitor upper airways in different diseases, for example PCD and rhinitis, and are acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician.

Abstract  The Global Ozone Monitoring Experiment (GOME) is a new instrument aboard the European Space Agency's (ESA) Second European Remote Sensing Satellite (ERS-2), which was launched in April 1995. The main scientific objective of the GOME mission is to determine the global distribution of ozone and several other trace gases, which play an important role in the ozone chemistry of the earth's stratosphere and troposphere. GOME:measures the sunlight scattered from the earth's atmosphere and/or reflected by the surface in nadir viewing mode in the spectral region 240-790 nm at a moderate spectral resolution of between 0.2 and 0.4 nm. Using the maximum 960-km across-track swath width, the spatial resolution of a GOME ground pixel is 40 X 320 km(2) for the majority of the orbit and global coverage is achieved in three days after 43 orbits. Operational data products of GOME as generated by DLR-DFD, the German Data Processing and Archiving Facility (D-PAF) for GOME, comprise absolute radiometrically calibrated earthshine radiance and solar irradiance spectra (level 1 products) and global distributions of total column amounts of ozone and NO2, (level 2 products), which are derived using the DOAS aroach (Differential Optical Absorption Spectroscopy). (Under certain conditions and some restrictions, the operational data products are publically available from the European Space Agency via the ERS Helpdesk.) In addition to the operational data products, GOME has delivered important information about other minor trace gases such as OClO, volcanic SO2, H2CO from biomass burning, and tropospheric BrO. Using an iterative optimal estimation retrieval scheme, ozone vertical profiles can be derived from the inversion of the UV/VIS spectra. This paper reports on the GOME instrument, its operation mode, and the retrieval techniques, the latter with particular emphasis on DOAS (total column retrieval) and advanced optimal estimation (ozone profile retrieval). Observation of ozone depletion in the recent polar spring seasons in both hemispheres are presented. OClO observed by GOME under twilight conditions provides valuable information on the chlorine activation inside the polar vortex, which is believed to be responsible for the rapid catalytic destruction of ozone. Episodes of enhanced BrO in the Arctic, most likely contained in the marine boundary layer, were observed in early and late spring. Excess tropospheric nitrogen dioxide and ozone have been observed during the recent Indonesian fire in fall 1997. Formaldehyde could also clearly be identified by GOME and is known to be a by-product resulting from biomass burning.

Abstract  The heterogeneous reaction of NO2 with water on the surface of laboratory systems has been known for decades to generate HONO, a major source of OH that drives the formation of ozone and other air pollutants in urban areas and possibly in snowpacks. Previous studies have shown that the reaction is first order in NO2 and in water vapor, and the formation of a complex between NO2 and water at the airûwater interface has been hypothesized as being the key step in the mechanism. We report data from long path FTIR studies in borosilicate glass reaction chambers of the loss of gaseous NO2 and the formation of the products HONO, NO and N2O. Further FTIR studies were carried out to measure species generated on the surface during the reaction, including HNO3, N2O4 and NO2+. We propose a new reaction mechanism in which we hypothesize that the symmetric form of the NO2 dimer, N2O4, is taken up on the surface and isomerizes to the asymmetric form, ONONO2. The latter autoionizes to NO+NO3-, and it is this intermediate that reacts with water to generate HONO and surface-adsorbed HNO3. Nitric oxide is then generated by secondary reactions of HONO on the highly acidic surface. This new mechanism is discussed in the context of our experimental data and those of previous studies, as well as the chemistry of such intermediates as NO+ and NO2+ that is known to occur in solution. Implications for the formation of HONO both outdoors and indoors in real and simulated polluted atmospheres, as well as on airborne particles and in snowpacks, are discussed. A key aspect of this chemistry is that in the atmospheric boundary layer where human exposure occurs and many measurements of HONO and related atmospheric constituents such as ozone are made, a major substrate for this heterogeneous chemistry is the surface of buildings, roads, soils, vegetation and other materials. This area of reactions in thin films on surfaces (SURFACE=Surfaces, Urban and Remote: Films As a Chemical Environment) has received relatively little attention compared to reactions in the gas and liquid phases, but in fact may be quite important in the chemistry of the boundary layer in urban areas.

Abstract  The effect of exposure to irritant air pollutants on the development of allergic airway disease is poorly understood. This study examines the effects of the lower respiratory tract irritant, NO2, on the outcome of ovalbumin (OVA)-induced allergic airway disease. Male and female C57Bl/6 mice were sensitized by weekly intraperitoneal (ip) OVA injections for 3 wk followed by daily 1-h OVA aerosol inhalation challenge for 3 or 10 d. Initially, mice were exposed daily for 3 d to air or 0.7 or 5 ppm NO2 for 2 h following each OVA aerosol challenge. OVA exposure resulted in pronounced lower airway inflammation, as evidenced by a significant increase in bronchoalveolar lavage (BAL) total cellularity and eosinophil levels. BAL eosinophil levels were significantly lower in OVA-NO2 compared to OVA-air animals. The reduction was similar at both NO2 exposure concentrations. In a subsequent study, sensitized animals were exposed for 3 or 10 d to aerosolized OVA followed by air or 0.7 ppm NO2. BAL eosinophils were again reduced at 3 d by OVA-NO2 exposure compared to OVA-air mice. At 10 d the eosinophilia was virtually abolished. This reduction in OVA-induced cellular inflammation by NO2 was confirmed by histopathological analysis. Contrary to expectations, exposure to NO2 during the aerosol challenge to OVA dramatically diminished the outcome of allergic disease in lungs as measured by airway cellular inflammation.

Abstract  BACKGROUND: Recent studies have suggested that exposure to air pollutants may enhance the airway responsiveness of susceptible individuals to inhaled allergen. METHODS: To investigate the effect of exposure to nitrogen dioxide (NO2) on nasal airways resistance (NAR) and inflammatory mediators in nasal lavage fluid, eight subjects with a history of seasonal allergic rhinitis, who were tested out of season, were exposed in a randomized single-blind, crossover study to either air or 400 ppb NO2 for 6 hours. The changes in NAR and eosinophil cationic protein (ECP), mast cell tryptase (MCT), neutrophil myeloperoxidase (MPO), and interleukin-8 (IL-8) in nasal lavage fluid before and after exposure were evaluated. Another group of eight subjects with a history of seasonal allergic rhinitis were also randomized to exposure to air or 400 ppb NO2 for 6 hours and then challenged with allergen, before evaluation for changes in NAR and changes in ECP, MCT, MPO, and IL-8 in nasal lavage fluid. RESULTS: Exposure to air or NO2 did not alter either NAR or the levels of ECP, MCT, MPO, or IL-8 in nasal lavage fluid. Allergen challenge after exposure to both air and NO2 significantly (p < 0.05) increased levels of MCT, but not MPO and IL-8 in the nasal lavage fluid. In addition, allergen challenge after exposure to NO2 but not air, significantly increased levels of only ECP in nasal lavage fluid (p < 0.05). CONCLUSIONS: These results suggest that acute exposure to NO2 at concentrations found at the curbside in heavy traffic during episodes of pollution, may "prime" eosinophils for subsequent activation by allergen in individuals with a history of seasonal allergic rhinitis.

Abstract  Halogen atoms and oxides are highly reactive and can profoundly affect atmospheric composition. Chlorine atoms can decrease the lifetimes of gaseous elemental mercury(1) and hydrocarbons such as the greenhouse gas methane(2). Chlorine atoms also influence cycles that catalytically destroy or produce tropospheric ozone(3), a greenhouse gas potentially toxic to plant and animal life. Conversion of inorganic chloride into gaseous chlorine atom precursors within the troposphere is generally considered a coastal or marine air phenomenon(4). Here we report mid-continental observations of the chlorine atom precursor nitryl chloride at a distance of 1,400km from the nearest coastline. We observe persistent and significant nitryl chloride production relative to the consumption of its nitrogen oxide precursors. Comparison of these findings to model predictions based on aerosol and precipitation composition data from long-term monitoring networks suggests nitryl chloride production in the contiguous USA alone is at a level similar to previous global estimates for coastal and marine regions(5). We also suggest that a significant fraction of tropospheric chlorine atoms(6) may arise directly from anthropogenic pollutants.

Abstract  BACKGROUND: The association of long-term air pollution and lung function has not been studied across adult European multi-national populations before. The aim of this study was to determine the association between long-term urban background air pollution and lung function levels, as well as change in lung function among European adults. METHODS:Forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and the ratio thereof (FEV1/FVC) were assessed at baseline and after 9 years of follow-up in adults from 21 European centres (followed-up sample 5610). Fine particles (PM(2.5)) were measured in 2000/2001 using central monitors. RESULTS: Despite sufficient statistical power no significant associations were found between city-specific annual mean PM(2.5) and average lung function levels. The findings also do not support an effect on change in lung function, albeit statistical power was insufficient to significantly detect such an association. CONCLUSIONS: The inability to refuse the null hypothesis may reflect (i) no effect of urban air pollution on lung function or (ii) inherent biases due to the study design. Examples of the latter are lack of individual-level air quality assignment, not quantified within-city contrasts in traffic-related pollution, or the heterogeneity of the studied populations and their urban environments. Future studies on long-term effects of air pollution on lung function could increase statistical power and reduce potential misclassification and confounding by characterizing exposure on the level of individuals, capturing contrasts due to local sources, in particular traffic.

Abstract  Multipollutant models are frequently used to differentiate roles of multiple pollutants in epidemiologic studies of ambient air pollution. In the presence of differing levels of measurement error across pollutants under consideration, however, they can be biased and as misleading as single-pollutant models. Their appropriate interpretation depends on the relationships among the pollutant measurements and the outcomes in question. In situations where two or more pollutant variables may be acting as surrogates for the etiologic agent(s), multipollutant models can help identify the best surrogate, but the risk estimates may be influenced by inclusion of a second variable that is not itself an independent risk factor for the outcome in question. In this paper, these issues will be illustrated in the context of an ongoing study of emergency visits in Atlanta. Emergency department visits from 41 of 42 hospitals serving the twenty-county Atlanta metropolitan area for the period 1993-2004 (n=10,206,389 visits) were studied in relation to ambient pollutant levels, including speciated particle measurements from an intensive monitoring campaign at a downtown station starting in 1998. Relative to our earlier publications, reporting results through 2000, the period for which the speciated data are now available is now tripled (six years in length). Poisson generalized linear models were used to examine outcome counts in relation to three-day moving average concentrations of pollutants of a priori interest (ozone, nitrogen dioxide, carbon monoxide, sulfur dioxide, oxygenated hydrocarbons, PM10, coarse PM, PM2.5, and the following components of PM2.5: elemental carbon, organic carbon, sulfate, water-soluble transition metals.) In the present analysis, we report results for two outcome groups: a respiratory outcomes group and a cardiovascular outcomes group. For cardiovascular visits, associations were observed with CO, 3 NO2, and PM2.5 elemental carbon and organic carbon. In multipollutant models, CO was the strongest predictor. For respiratory visits, associations were observed with ozone, PM10, CO and NO2 in single-pollutant models. In multipollutant models, PM10 and ozone persisted as predictors, with ozone the stronger predictor. Caveats and considerations in interpreting the multipollutant model results are discussed.

Abstract  This article describes the governing equations, computational algorithms, and other components entering into the Community Multiscale Air Quality (CMAQ) modeling system. This system has been designed to approach air quality as a whole by including state-of-the-science capabilities for modeling multiple air quality issues, including tropospheric ozone, fine particles, acid deposition, and visibility degradation. CMAQ was also designed to have multiscale capabilities so that separate models were not needed for urban and regional scale air quality modeling. By making CMAQ a modeling system that addresses multiple pollutants and different spatial scales, it has a "one-atmosphere" perspective that combines the efforts of the scientific community. To implement multiscale capabilities in CMAQ, several issues (such as scalable atmospheric dynamics and generalized coordinates), which depend on the desired model resolution, are addressed. A set of governing equations for compressible nonhydrostatic atmospheres is available to better resolve atmospheric dynamics at smaller scales. Because CMAQ is designed to handle scale-dependent meteorological formulations and a large amount of flexibility, its governing equations are expressed in a generalized coordinate system. This approach ensures consistency between CMAQ and the meteorological modeling system. The generalized coordinate system determines the necessary grid and coordinate transformations, and it can accommodate various vertical coordinates and map projections. The CMAQ modeling system simulates various chemical and physical processes that are thought to be important for understanding atmospheric trace gas transformations and distributions. The modeling system contains three types of modeling components (Models-3): a meteorological modeling system for the description of atmospheric states and motions, emission models for man-made and natural emissions that are injected into the atmosphere, and a chemistry-transport modeling system for simulation of the chemical transformation and fate. The chemical transport model includes the following process modules: horizontal advection, vertical advection, mass conservation adjustments for advection processes, horizontal diffusion, vertical diffusion, gas-phase chemical reactions and solvers, photolytic rate computation, aqueous-phase reactions and cloud mixing, aerosol dynamics, size distributions and chemistry, plume chemistry effects, and gas and aerosol deposition velocity estimation. This paper describes the Models-3 CMAQ system, its governing equations, important science algorithms, and a few application examples.

Abstract  Aims: To investigate the chronic effects of air pollution caused mainly by automobiles in healthy adult females. Methods: Respiratory symptoms were investigated in 5682 adult females who had lived in the Tokyo metropolitan area for three years or more in 1987; 733 of them were subjected to pulmonary function tests over eight years from 1987 to 1994. The subjects were divided into three groups by the level of air pollution they were exposed to during the study period. The concentrations of nitrogen dioxide and suspended particulate matter were the highest in group 1, and the lowest in group 3. Results: The prevalence rates of respiratory symptoms in group 1 were higher than those in groups 2 and 3, except for wheezing. Multiple logistic regression analysis showed significant differences in persistent phlegm and breathlessness. The subjects selected for the analysis of pulmonary function were 94, 210, and 102 females in groups 1, 2, and 3, respectively. The annual mean change of FEV1 in group 1 was the largest (-0.020 l/y), followed by that in group 2 (-0.015 l/y), and that in group 3 (-0.009 l/y). Testing for trends showed a significant larger decrease of FEV1 with the increase in the level of air pollution. Conclusions: The subjects living in areas with high levels of air pollution showed higher prevalence rates of respiratory symptoms and a larger decrease of FEV1 compared with those living in areas with low levels of air pollution. Since the traffic density is larger in areas with high air pollution, the differences among the groups may reflect the effect of air pollution attributable to particulate matter found in automobile exhaust.

Abstract  Gaseous nitrogen dioxide (NO2) was found to induce umuC gene expression in Salmonella typhimurium carrying the umuC-lacZ fusion plasmid. The induction level of the umu operon responsible for inducible mutagenesis was measured by the level of beta-galactosidase in the cell, encoded by the fusion gene. NO2 gas was bubbled into bacterial suspensions at 10, 30 and 90 microliters/l for 30 min at a flow rate of 100 ml/min. Expression of the umuC gene varied with the concentration, flow rate and bubbling time of the NO2 gas. Although NO2 gas induces SOS functions, mutagenesis due to it was not detectable in Salmonella typhimurium TA100 and TA102. Nitric oxide gas (NO) did not induce any umuC gene expression.

Abstract  Nitrogen dioxide induced SOS functions in Salmonella typhimurium and Escherichia coli K-12 and was mutagenic in Escherichia coli WP2. When a rabbit was administered aminopyrine intravenously and administered nitrogen dioxide by inhalation, N-nitrosodimethylamine was detected in its blood. Analysis was conducted with 15N-nitrosodimethylamine as an internal standard by a combination of capillary gas chromatography and mass spectrometry. Accompanying administration of cystamine increased the blood concentration of N-nitrosodimethylamine in the rabbit, suggesting inhibition of its metabolism. Concurrent sulfur trioxide inhalation increased N-nitrosodimethylamine formation in the rabbit.

Abstract  Nitric oxide (NO.) is a physiological messenger formed by several cell types. Reaction with O2 forms oxides that nitrosate amines at pH values near 7. We now report experiments in which NO. was added to intact human cells and to aerobic solutions of DNA, RNA, guanine, or adenine. TK6 human lymphoblastoid cells were mutated 15- to 18-fold above background levels at both the HPRT and TK gene loci. Xanthine and hypoxanthine, from deamination of guanine and adenine, respectively, were formed in all cases. NO. induced dose-responsive DNA strand breakage. Yields of xanthine ranged from nearly equal to about 80-fold higher than those of hypoxanthine. Yields of xanthine and hypoxanthine from nucleic acids were higher than those from free guanine and adenine. This was most pronounced for xanthine; 0.3 nmol/mg was formed from free guanine vs. 550 nmol/mg from calf thymus RNA. Nitric oxide added to TK6 cells produced a 40- to 50-fold increase in hypoxanthine and xanthine in cellular DNA. We believe that these results, plus the expected deaminations of cytosine to uracil and 5-methylcytosine to thymine, account for the mutagenicity of nitric oxide toward bacteria and mammalian cells.

Abstract  Male CD-1 mice were exposed to an nominal concentration of 20 p.p.m. of 15N-nitrogen dioxide (15NO2) for 6 h/day for 4 days and for 2 h on the day 5, and to 1 g morpholine/kg body wt by gavage daily for five consecutive days. N-Nitrosomorpholine (NMOR) was found in whole mice, stomachs, skins with hair, and remains. The sum of individual tissue concentrations measured separately was 3421 ng/tissue, where the average skin weighed 4.3 g, the average stomach weighed 1.0 g and the average remains weighed 22.2 g. The average whole mouse weighed 27.7 g and contained a total of 3903 ng of NMOR. The concentration of NMOR was highest in the skin, next highest in the stomach, and lowest in the remains. However, the total quantity of NMOR per tissue, while highest in the skin (83%), was next highest in the remains (14.8%) and lowest in the stomach (2.2%). GC-MS analysis served to distinguish between the NMOR of 15NO2 origin and that of other origin. All of the NMOR in the whole mouse homogenates was identified as 15NMOR. In the stomach 73% was identified as 14NMOR, representing 1.6% of the total NMOR in the mouse, and 27% as 15NMOR, representing 0.6% of the total NMOR in the mouse. N-Nitrosamine formation in vivo is discussed as a possibly ongoing mammalian process.

Abstract  Nitrogen dioxide (NO2) is a ubiquitous, pollutant gas that produces a broad range of pathological and physiological effects on the lung. Absorption of inhaled NO2 is coupled to near-interfacial reactions between the solute gas and constituents of the airway and alveolar epithelial lining fluid. Although alveolar surfactant imparts limited resistance to respiratory gas exchange compared with that contributed by either the pulmonary membrane or uptake in red blood cells, resistance to NO2 flux could have a significant effect on NO2 absorption kinetics. To investigate the effect of interfacial surfactant on NO2 absorption, we designed an apparatus permitting exposure of variably compressed monolayers. Our results suggest that compressed monolayers enriched in 1,2-dipalmitoyl-sn-3-glycero-phosphocholine present significant resistance to NO2 absorption even at surface tensions greater than those achieved in vivo. However, monolayers composed of pure unsaturated phospholipids failed to alter NO2 absorption significantly when compressed, in spite of similar reductions in surface tension. The results demonstrate that phospholipid monolayers appreciably limit NO2 absorption and further that monolayer-induced resistance to NO2 flux is related to physicochemical properties of the film itself rather than alterations within the aqueous and gas phases. On the basis of these findings, we propose that pulmonary surfactant may influence the intrapulmonary gas phase distribution of inhaled NO2.

Abstract  To determine if nitrogen dioxide (NO2), a gaseous free radical, modifies the protective antioxidant pool present in respiratory tract lining fluids, a random, double-blind study utilizing flexible fiberoptic bronchoscopy with bronchial and bronchoalveolar lavage was performed. Healthy, nonsmoking, asymptomatic subjects were exposed to filtered air and 2 ppm NO2 for 4 h on separate occasions. To examine the kinetics of the NO2-induced antioxidant reactions, 44 subjects were randomly assigned to one of three groups. Bronchoscopy was performed 1.5 h (group 1), 6 h (group 2) or 24 h (group 3) after each exposure. Reduced glutathione (GSH), uric acid, and ascorbic acid concentrations were determined in both bronchial and bronchoalveolar lavage fluid fractions. In addition, bronchoalveolar lavage fluid was screened for malondialdehyde as a marker of lipid peroxidation. Exposure to NO2 resulted in a rapid (1.5 h) loss of uric acid from the bronchial region, however by 6 h after exposure it had increased significantly above control uric acid concentration in this region. At 24 h after exposure, uric acid concentration had returned to the control level. A similar response of uric acid to NO2 was seen in the bronchoalveolar region. Ascorbic acid was also decreased in bronchial and bronchoalveolar lavage fluids 1.5 h after exposure to NO2, but returned to control values by 6 h. In marked contrast, significant increases in GSH concentration were seen at 1.5 and 6 h in bronchial lavage fluid after exposure to NO2, which subsequently returned to control levels by 24 h. No change in bronchoalveolar lavage fluid GSH concentration or malondialdehyde content was seen after NO2 exposure. These data support the view that antioxidants present in lung fluids react with, and hence modulate the impact of, NO2 on the lung.

Abstract  The authors investigated the association of early-life exposure to indoor air pollution with neuropsychological development in preschoolers and assessed whether this association differs by glutathione-S-transferase gene (GSTP1) polymorphisms. A prospective, population-based birth cohort was set up in Menorca, Spain, in 1997–1999 (n = 482). Children were assessed for cognitive functioning (McCarthy Scales of Children's Abilities) and attention-hyperactivity behaviors (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) at age 4 years. During the first 3 months of life, information about gas appliances at home and indoor nitrogen dioxide concentration was collected at each participant's home (n = 398, 83%). Genotyping was conducted for the GSTP1 coding variant Ile105Val. Use of gas appliances was inversely associated with cognitive outcomes (β coefficient for general cognition = –5.10, 95% confidence interval (CI): –9.92, –0.28; odds ratio for inattention symptoms = 3.59, 95% CI: 1.14, 11.33), independent of social class and other confounders. Nitrogen dioxide concentrations were associated with cognitive function (a decrease of 0.27 point per 1 ppb, 95% CI: –0.48, –0.07) and inattention symptoms (odds ratio = 1.06, 95% CI: 1.01, 1.12). The deleterious effect of indoor pollution from gas appliances on neuropsychological outcomes was stronger in children with the GSTP1 Val-105 allele. Early-life exposure to air pollution from indoor gas appliances may be negatively associated with neuropsychological development through the first 4 years of life, particularly among genetically susceptible children.

Abstract  One hundred and twenty female mice fed diets containing various levels of vitamin E were continuously exposed to 0.5 ppM, 1.0 ppM nitrogen dioxide (NO2), and filtered air for 17 months. Blood, lung, and liver tissues were assayed for glutathione peroxidase (GSH-peroxidase) activity. Exposure to 0.5 ppM NO2 did not affect blood and lung GSH-peroxidase activity; 1.0 ppM NO2 exposure however, caused suppression of the enzyme. A combination of vitamin E deficiency and 1.0 ppM NO2 exposure resulted in the lowest GSH-peroxidase activities in the blood and lung. High levels of vitamin E in the diet resulted in elevated GSH-peroxidase in the blood and lung. Liver GSH-peroxidase activity was unaffected by either dietary vitamin E or NO2 exposure.