nitrogen-dioxide and sulfuric-acid

Asthmatic individuals constitute a large sub-population that is often considered particularly susceptible to the deleterious effects of inhalation of airborne chemicals. However, for most such chemicals information on asthmatics is lacking and inter-individual assessment factors (AFs) of 3-25 have been proposed for use in the derivation of health-based guideline values.. To evaluate available information in attempt to determine whether a general difference in airway response during short-term exposure between healthy and asthmatic individuals can be identified, and whether current AFs for inter-individual variability provide sufficient protection for asthmatics.. After performing systematic review of relevant documents and the scientific literature estimated differential response factors (EDRF) were derived as the ratio between the lowest observed adverse effect levels for healthy and asthmatic subjects based on studies in which both groups were tested under the same conditions. Thereafter, the concentration-response relationships for healthy and asthmatic subjects exposed separately to four extensively tested chemicals (nitrogen dioxide, ozone, sulfuric acid, sulfur dioxide) were compared on the basis of combined data. Finally, a Benchmark Concentration (BMC) analysis was performed for sulfur dioxide.. We found evidence of higher sensitivity among asthmatics (EDRF > 1) to 8 of 19 tested chemicals, and to 3 of 11 mixtures. Thereafter, we confirmed the higher sensitivity of asthmatics to sulfuric acid and sulfur dioxide. No difference was observed in the case of ozone and nitrogen dioxide. Finally, our BMC analysis of sulfur dioxide indicated a ninefold higher sensitivity among asthmatics.. Although experimental data are often inconclusive, our analyses suggest that an AF of 10 is adequate to protect asthmatics from the deleterious respiratory effects of airborne chemicals.

Topics: Air Pollutants; Asthma; Databases, Factual; Humans; Nitrogen Dioxide; Ozone; Sulfur Dioxide; Sulfuric Acids

Experimental studies in man are an indispensable complement to epidemiological studies and experimental studies on animals. They aim at understanding the mechanisms of action of the main pollutants and at knowing their thresholds of triggering of the acute effects on the respiratory system. The studies made in man involve controlled exposure to different atmospheric pollutants, with measurement of the functional respiratory repercussions, studies of modification of the cells in broncho-alveolar lavage, as well as experimental protocols that combine inhalation of allergen and exposure to atmospheric pollutants by allergic subjects. The main results that are available are reported to distinguish those from normal subjects and those who are allergic. More recent protocols are based on exposure to concentrations that are close to atmospheric concentrations or those that are met in work places. The main data in the literature are reported in this journal and concern SO2 acid aerosols, dioxides of nitrogen, ozone and diesel particles. Pathogenic hypotheses concerning the undesirable effects of atmospheric pollutants on the respiratory system are considered.

Topics: Aerosols; Air Pollutants; Bronchoalveolar Lavage Fluid; Gasoline; Humans; Nitrogen Dioxide; Ozone; Respiratory Hypersensitivity; Sulfuric Acids

The mucociliary clearance system is a first line of defense against inhaled agents, and so its compromise can adversely affect health. The purpose of this paper is to provide a review of data on the effect of in vivo air pollutant exposures on the clearance of test particles from airways. Data from both animals and humans are compared whenever possible, so that estimates of human health effects may be made. Mechanisms of action are also discussed, presenting the view that for low level exposures, changes in secretions are probably responsible for most observed changes in clearance. The pollutants pertinent to this review are those that are common in the environment and most likely to have impacts on large numbers of people: sulfur oxides, sulfuric acid mist, O3, NO2, particulates, diesel exhaust, and cigarette smoke.

Topics: Air Pollutants; Animals; Cilia; Epithelium; Humans; Microscopy, Electron, Scanning; Mucus; Nitrogen Dioxide; Ozone; Respiratory Physiological Phenomena; Respiratory System; Smoking; Sulfur Dioxide; Sulfur Oxides; Sulfuric Acids

Inhalation toxicology experiments in whole animals have demonstrated a remarkable lack of toxicity of sulfuric acid in the form of respirable aerosols, especially in rats and nonhuman primates. Thus, much of the current experimental emphasis has shifted to the evaluation of the potential health effects of acid aerosols as components of mixtures. Rats have been concurrently exposed to mixtures of ozone or nitrogen dioxide with respirable-sized aerosols of sulfuric acid, ammonium sulfate, or sodium chloride, or to each pollutant individually. Their responses to such exposures have been evaluated by various quantitative biochemical analysis of lung tissue or wash fluids ("lavage fluid") or by quantitative morphological methods ("morphometry"). Such studies have mainly been performed in the acute time frame due to the inherent limitations of the most sensitive assays available and have generally involved exposures for 1 to 9 days, depending on the assays used. Good correlations were found between the most sensitive biochemical indicators of lung damage (protein content of lung lavage fluid or whole lung tissue and lung collagen synthesis rate) and the exposure concentration of oxidant gas present alone or in mixtures with acidic aerosols showing interactive effects. Synergistic interaction between ozone and sulfuric acid aerosol was demonstrated to occur at environmentally relevant concentrations of both pollutants by several of the analytical methods used in this study. Such interactions were demonstrated at concentrations of ozone as low as 0.12 ppm and of sulfuric acid aerosol at concentrations as low as 5 to 20 micrograms/m3.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acids; Administration, Inhalation; Aerosols; Air Pollutants; Animals; Atmosphere; Drug Synergism; Guinea Pigs; Hydrogen-Ion Concentration; Lung; Nitrogen Dioxide; Ozone; Proteins; Rats; Respiratory Tract Diseases; Sodium Chloride; Species Specificity; Sulfuric Acids

Rats were concurrently exposed to mixtures of ozone or nitrogen dioxide and respirable-sized aerosols of sulfuric acid, ammonium sulfate, or sodium chloride, or to each pollutant individually. Their responses to such exposures were evaluated by various quantitative biochemical analyses of lung tissue or lavage fluids, or by morphometric analyses. Such studies were performed in the acute time frame, generally involving exposures of from one to nine days, depending on the assays used. Correlations between the biochemical and morphometric results were examined over a wide range of pollutant concentrations in the exposure chambers. Good correlations were found between the most sensitive biochemical indicators of lung damage--the protein content of lung lavage fluid or whole lung tissue and the rate of lung collagen synthesis--and the morphometric estimation of volume density or volume percent of the centriacinar lung lesion characteristically observed in animals exposed to ozone. Synergistic interaction between ozone and sulfuric acid aerosol was demonstrated to occur at environmentally relevant concentrations of both pollutants by several of the analytical methods used. Such interactions were demonstrated at concentrations of ozone as low as 0.12 parts per million (ppm)2 and of sulfuric acid aerosol at concentrations as low as 5 to 20 micrograms/m3. The acidity of the aerosol is a necessary (and apparently a sufficient) condition for such a synergistic interaction between an oxidant gas and a respirable aerosol to occur. A hitherto unexpected synergistic interaction between nitrogen dioxide and sodium chloride aerosol was found during these studies; it is hypothesized that this was due to formation of their acidic (anhydride) reaction product, nitrosyl chloride, in the chambers during exposure to the mixture. Preliminary experiments treating exposed animals in vivo with various free-radical scavengers suggested that dimethylthiourea, a hydroxyl-radical scavenger, might be protective against effects of ozone on rat lungs. This observation might have mechanistic implications, but further studies will be necessary to determine the significance of these findings.

Topics: Aerosols; Air Pollutants; Ammonium Sulfate; Animals; Atmosphere Exposure Chambers; Bronchoalveolar Lavage Fluid; Collagen; Drug Synergism; Guinea Pigs; L-Lactate Dehydrogenase; Lung; Male; Nitrogen Dioxide; Ozone; Rats; Rats, Inbred Strains; Sulfuric Acids

Using surgical specimens from patients with lung tumor, alveolar apertures and alveolar sizes were quantitatively assessed using scanning electron microscopy. Compared with smoking habits, increased apertures, defined as alveolar destruction were observed in patients smoking more than 35 years, whereas alveolar size was increased in patients, with a 15-year smoking history. Experimental studies with exposure to NO2, O3 and H2SO4 mist showed that exposure of NO2 and H2SO4 could induce epithelial injury such as disappearance of cilia in the central airways.

Topics: Adult; Aged; Aged, 80 and over; Air Pollutants; Animals; Humans; Microscopy, Electron, Scanning; Middle Aged; Nitrogen Dioxide; Ozone; Pulmonary Alveoli; Smoking; Sulfuric Acids; Time Factors

Research on human exposure to acidic aerosols and the health effects of such exposures has substantially strengthened the hypothesis that such aerosols are a causal factor for excesses in human mortality and morbidity that have been previously associated with crude exposure indices such as British Smoke, total suspended particulate matter, and sulfur dioxide. Research reported at this symposium also showed that combined exposures to acid aerosols and other ubiquitous air pollutants such as O3, NO2, HNO3, and SO2 produce greater effects in both humans and animals than exposures to each agent separately. The responses reported ranged from physiological functions to lung structure. Furthermore, some of the effects were cumulative with increasing duration of daily exposure and number of repetitive exposures. Critical areas for further research include better definition of the critical temporal parameters affecting exposure and response, effects of mixed pollutant exposures, and pathogenetic mechanisms for acid aerosol-induced chronic lung damage.

Topics: Acid Rain; Aerosols; Air Pollutants; Dose-Response Relationship, Drug; Humans; Nitrates; Nitric Acid; Nitrogen Dioxide; Ozone; Respiratory Tract Diseases; Risk Factors; Sulfur Dioxide; Sulfuric Acids

Effects of respirable aerosols of sulfuric acid, ammonium sulfate, sodium sulfite, and ammonium persulfate on lungs of rats are reviewed. The literature regarding interactions between ozone or nitrogen dioxide and acidic aerosols (ammonium sulfate, sulfuric acid) is discussed. An unexpected interaction between nitrogen dioxide and sodium chloride aerosol is also discussed. An attempt is made to identify bases for prediction of how and when acid aerosols might potentiate effects of inhaled gases.

Topics: Acid Rain; Aerosols; Air Pollutants; Ammonium Sulfate; Animals; Dose-Response Relationship, Drug; Formaldehyde; Lung; Nitrogen Dioxide; Ozone; Rats; Sodium Chloride; Sulfites; Sulfuric Acids

Under ambient conditions, sulfur and nitrogen oxides can react with photochemical products and airborne particles to form acidic vapors and aerosols. Inhalation toxicological studies were conducted, exposing laboratory animals, at rest and during exercise, to multicomponent atmospheric mixtures under conditions favorable to the formation of acidic reaction products. Effects of acid and ozone mixtures on early and late clearance of insoluble radioactive particles in the lungs of rats appeared to be dominated by the oxidant component (i.e., the mixture did cause effects that were significantly different from those of ozone alone). Histopathological evaluations showed that sulfuric acid particles alone did not cause inflammatory responses in centriacinar units of rat lung parenchyma (expressed in terms of percent lesion area) but did cause significant damage (cell killing followed by a wave of cell replication) in nasal respiratory epithelium, as measured by uptake of tritiated thymidine in the DNA of replicating cells. Mixtures of ozone and nitrogen dioxide, which form nitric acid, caused significant inflammatory responses in lung parenchyma (in excess of effects seen in rats exposed to ozone alone), but did not damage nasal epithelium. Mixtures containing acidic sulfate particles, ozone, and nitrogen dioxide damaged both lung parenchyma and nasal epithelia. In rats exposed at rest, the response of the lung appeared to be dominated by the oxidant gas-phase components, while responses in the nose were dominated by the acidic particles. In rats exposed at exercise, however, mixtures of ozone and sulfuric acid particles significantly (2.5-fold) elevated the degree of lung lesion formation over that seen in rats exposed to ozone alone under an identical exercise protocol.

Topics: Acid Rain; Aerosols; Air Pollutants; Animals; Cell Survival; DNA Replication; Male; Mucociliary Clearance; Nasal Mucosa; Nitric Oxide; Nitrogen Dioxide; Ozone; Pulmonary Alveoli; Rats; Rats, Inbred Strains; Smog; Sulfates; Sulfur Dioxide; Sulfuric Acids; Trachea

The research presented in the toxicology session of the Symposium on the Health Effects of Acid Aerosols significantly advances our understanding of the health effects of acid aerosols and clearly illustrates the importance of animal inhalation toxicology to risk assessment. The description of the effects of acid on airway mucus buffering capacity and viscosity helps explain some of the mechanisms responsible for the effects of sulfuric acid on mucociliary clearance and pulmonary function observed in man and animals. Several of the papers illustrate that other pollutants interact with sulfuric acid (H2SO4), causing concern about exposure risks and helping in elucidating the effects observed in epidemiology studies that have not yet been duplicated in a laboratory. For example, H2SO4 absorbed in zinc oxide (ZnO) particles appears to be about a log more potent than H2SO4 alone in causing pulmonary function decrements. Low levels of H2SO4 and O3 were found to be synergistic in increasing collagen synthesis, implying a risk in development of lung fibrosis. More complex mixtures containing H2SO4 cause a variety of interactions, depending upon the end points examined and the chemistry of the mixture. Other reports indicate that dose rate and length of exposure issues are critical to toxicological outcomes. Animal data on mucociliary clearance, which parallels that of human data, was extended to show that concentration of exposure was more important than time of exposure in eliciting a response, although time played a significant role. A recent chronic study showed that H2SO4 caused effects that also can occur in the development of chronic bronchitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Rain; Aerosols; Air Pollutants; Airway Resistance; Animals; Humans; Lung; Mucociliary Clearance; Nitrogen Dioxide; Ozone; Risk Factors; Sulfuric Acids

Clearance mechanisms are an integral part of pulmonary defense, serving to rid the lungs of inhaled particles that deposit upon airway surfaces. This is accomplished by mucociliary transport in conducting airways and to a large extent by alveolar macrophages in the respiratory region. This paper compares the effects of acute exposure to sulfuric acid (H2SO4), nitrogen dioxide (NO2), or ozone (O3) on mucociliary clearance in rabbits and on phagocytic activity of macrophages recovered by bronchopulmonary lavage from animals exposed in vivo. The possible toxicologic mechanisms underlying dysfunction of clearance mediated by these irritants is discussed in terms of response to a pure acid (H2SO4), a pure oxidant (O3), and a material (NO2) that is a direct oxidant but which may produce secondary oxidants and acids upon dissolution in lung fluids.

Topics: Air Pollutants; Animals; Bronchoalveolar Lavage Fluid; In Vitro Techniques; Lung; Male; Mucociliary Clearance; Nitrogen Dioxide; Ozone; Phagocytosis; Rabbits; Sulfuric Acids

Previously published data from the Ontario Air Pollution study are reviewed. It has been shown that there is a consistent association in summer between hospital admissions for respiratory disease in Southern Ontario, and daily levels of SO4, O3, and temperature. No association exists for a group nonrespiratory conditions. Multiple regression analyses are presented that show all environmental variables account for 5.6% of the variability in respiratory admissions and that if temperature is forced into the analysis first, it accounts for 0.89% of the variability only. Distribution plots of standardized residuals are presented. In June of 1983, there were an exceptional number of ozone episodes (defined as occasions when ozone was greater than 82 ppb for 3 or more hours in a calendar day) in this region. A separate analysis of hospital admissions for acute respiratory diseases for the month of June for several years shows no demonstrable excess in June of 1983; previously regional analyses have indicated that ozone is associated with increased levels in July and August over a 9-year period. It has also been found that daily SO4 data collected at one monitoring site in the center of the region are not correlated with respiratory admissions, whereas the SO4 values collected every sixth day, on different days of the week, at 17 stations in the region had the highest correlation with respiratory admissions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acid Rain; Aerosols; Air Pollutants; Carbon Monoxide; Cross-Sectional Studies; Humans; Nitrogen Dioxide; Ontario; Ozone; Respiratory Tract Diseases; Risk Factors; Sulfur Dioxide; Sulfuric Acids

Nitrogen dioxide (NO2) and sulfuric acid (H2SO4) are important constituents of the gas-particle complex in ambient air. The purpose of this study was to examine the effects of combined exposures upon the clearance of insoluble tracer particles from the respiratory region of the lungs. Rabbits were the animal model, and were exposed for 2 h/day for 14 days to either 0.3 ppm NO2, 1 ppm NO2, or 500 microgram/m3 H2SO4 alone, or to mixtures of the low and high NO2 concentrations with acid. Inhaled singly, both concentrations of NO2 accelerated clearance while H2SO4 retarded it, compared to control. Exposure to the combination of 0.3 ppm NO2 plus H2SO4 resulted in a response which was not different from that due to the acid alone. However, exposure to 1 ppm NO2 plus H2SO4 resulted in a clearance pattern which differed from that of both NO2 and H2SO4, but was more similar to that of the latter.

Topics: Aerosols; Air Pollutants; Animals; Lung; Male; Nitrogen Dioxide; Rabbits; Sulfuric Acids

We examined interactions in rats between NO2 gas and respirable aerosols of sulfuric acid (H2SO4) or sodium chloride (NaCl). Rats were exposed for 1, 3, or 7 days to 5 ppm of NO2 gas, alone or in combination with 1 mg/m3 of H2SO4 or NaCl aerosols. The apparent rate of collagen synthesis by lung minces was measured after 7 days of exposure, and the protein content of whole lung lavage fluid was measured after 1 or 3 days of exposure. Responses from rats exposed to 5 ppm of NO2 alone were significantly different from controls by these assays. A synergistic interaction was demonstrated between 5 ppm of NO2 and 1 mg/m3 of either H2SO4 or NaCl aerosol as evaluated by measurement of the rate of lung collagen synthesis. A synergistic interaction was also demonstrated by the criterion of increased protein content of lung lavage fluid in rats exposed to 5 ppm of NO2 and 1 mg/m3 of H2SO4 aerosol after 1 day of exposure and between 5 ppm of NO2 and 1 mg/m3 of NaCl aerosol after 3 days of exposure. These observations with 5 ppm of NO2 alone and in combination with 1 mg/m3 of NaCl aerosol support the hypothesis that formation of nitrosyl chloride may contribute to a synergistic interaction between NO2 gas and NaCl aerosol. These results suggest that, in general, combinations of oxidant gases with respirable acidic aerosols or with acidogenic gases will demonstrate interactive effects on rat lungs. Such a hypothesis is testable and makes specific predictions about effects of inhalation of pollutant mixtures.

Topics: Acid Phosphatase; Aerosols; Animals; Collagen; Drug Synergism; Hexosaminidases; L-Lactate Dehydrogenase; Lung; Male; Nitrogen Dioxide; Ozone; Rats; Rats, Inbred Strains; Respiratory Insufficiency; Sodium Chloride; Solutions; Sulfuric Acids

Rabbits were exposed (2h/d) to atmospheres consisting of 0.5 mg/m3 (0.3 micron) H2SO4 plus NO2 at either 0.3 (low) or 1 ppm (high). Animals were sacrificed 24 h after 2, 6, or 13 exposures, and cells were recovered from the lungs by bronchopulmonary lavage. Exposure to high NO2 with acid resulted in an increase in neutrophils at all time points and an increase in phagocytic capacity of macrophages after two or six exposures. On the other hand, exposure to the low NO2 with acid resulted in depressed phagocytic capacity and mobility. The results were compared with those for NO2 or H2SO4 given alone.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cell Movement; Cell Survival; Drug Administration Schedule; Macrophages; Male; Nitrogen Dioxide; Phagocytosis; Pulmonary Alveoli; Rabbits; Sulfuric Acids

The biological response to ambient air pollution may be a function of specific combinations of pollutants. Groups of rabbits were exposed to NO2 (0.3 ppm or 1 ppm) with and without H2SO4 (0.5 mg/m3) for 2 hr/day for up to 14 days for assessment of effects upon mucociliary clearance of tracer particles from the tracheobronchial tree. Exposure to NO2 did not alter clearance, while exposure to H2SO4 produced a retardation toward the middle of the exposure series. The combination of 0.3 ppm NO2 with H2SO4 resulted in a speeding of clearance, while no change from control was seen with the mixture employing 1 ppm NO2 with acid. These results emphasize the importance of performing studies with pollutant mixtures, since it is not always possible to extrapolate responses from studies examining effects of individual pollutants.

Topics: Administration, Intranasal; Air Pollutants; Animals; Drug Interactions; Kinetics; Lung; Male; Mucociliary Clearance; Nitrogen Dioxide; Rabbits; Sulfuric Acids

Observations of high acidity (pH as low as 1.7) in fogwater collected in polluted areas have provoked concern for public health. Effects of exposure to acidic pollutants have not been studied under foggy conditions; thus there is no directly relevant information from which to estimate the health risk. Indirectly relevant information is available from numerous studies of volunteers exposed to "acid fog precursors" under controlled conditions at less than 100% relative humidity. The effect of fog in modifying responses to inhaled acidic pollutants is difficult to predict: depending on circumstances, fog droplets might either increase or decrease the effective dose of pollutants to the lower respiratory tract. Fog inhalation per se may have unfavorable effects in some individuals. Sulfur dioxide is known to exacerbate airway constriction in exercising asthmatics, at exposure concentrations attainable in ambient air. Nitrogen dioxide has shown little untoward respiratory effect at ambient concentrations in most studies, although it has been suggested to increase bronchial reactivity. Sulfuric acid aerosol has shown no clear effects at concentrations within the ambient range. At somewhat higher levels, increased bronchial reactivity and change in mucociliary clearance have been suggested. Almost no information is available concerning nitric acid.

Topics: Acids; Air Pollutants; Ammonium Sulfate; Humans; Humidity; Nitrates; Nitric Acid; Nitrogen Dioxide; Respiratory Tract Diseases; Sulfur Dioxide; Sulfuric Acids; Time Factors; Weather

There exist significant gaps in our understanding of human health effects from inhalation of pollutants associated with acid precipitation. Controlled clinical studies examine effects of criteria pollutants almost exclusively by assessing changes in lung mechanics. One constituent of acid precipitation, sulfuric acid aerosols, has been shown to induce bronchoconstriction in exercising extrinsic asthmatics at near ambient levels. These asthmatics may be an order of magnitude more sensitive to sulfuric acid aerosols than normal adults. More recently, a second component nitrogen dioxide has been observed to provoke changes in lung mechanics at progressively lower concentrations. To date, virtually no data exist from clinical exposures to acidic aerosols for subjects with chronic obstructive pulmonary disease.

Topics: Aerosols; Air Pollutants; Ammonium Sulfate; Asthma; Dose-Response Relationship, Drug; Humans; Lung; Nitrogen Dioxide; Physical Exertion; Sulfuric Acids

Problems associated with estimation of human exposure to ambient air pollutants are discussed. Ideally, we would prefer to have some indication of actual dose. For most pollutants this is not presently feasible. Specific problems discussed are adequacy of outdoor monitors; the need to correct for exposures and time spent indoors; the need to have particle size distributions described and the chemistry of the particles presented. These indicate the need to develop lightweight accurate and reliable personal monitors.

Topics: Acids; Air Pollutants; Ammonium Sulfate; Environmental Exposure; Humans; Missouri; Molecular Weight; Nitrogen Dioxide; Rain; Sulfates; Sulfuric Acids; Tennessee; Wisconsin