Clean Air Exposure Research Articles

Brain thiobarbituric acid-reactive substances in rats after short periods of ozone exposure

It has been proposed that molecules derived from reactions that occur between the ozone and the lung tissue mediate nonpulmonary effects caused by ozone exposure. Free radicals are among those proposed molecules that flow throughout the bloodstream to other organs producing lipid peroxidation. In order to elucidate on aspect of ozone toxicity mechanisms, we measured the thiobarbituric acid-reactive products (TBARS), as an index of lipid peroxidation, in a variety of brain regions in rats exposed to 1 ppm of ozone for 1, 3, 6, and 9 h. Another group exposed to 9 h of O 3 plus 3 h of clean-air exposure was also included. The results showed an important increase in TBARS content in all the studied structures. Such effect seems to be transient. These findings indicates that acute ozone exposure can produce cerebral peroxidation as it has been found in rats exposed chronically, suggesting an involvement of free radicals in brain effects of ozone exposure.

Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects: a brief communication.

Ambient exposure to nitrogen dioxide, a critical air pollutant in developed countries, is positively associated with cardiovascular mortality and morbidity. Although its cardiovascular effects are predominantly shown in patients with high risk of atherogenesis, no studies have elucidated whether daily exposure to nitrogen dioxide air pollution enhances atherogenic metabolisms, primarily in obese subjects who are susceptible to atherogenesis and subsequent cardiovascular diseases. We used male Otsuka Long-Evans Tokushima Fatty (OLETF) rats as obese subjects and Long-Evans Tokushima (LETO) rats as nonobese controls. The animals were continuously exposed to nitrogen dioxide at a concentration of 0, 0.16, 0.8, or 4.0 ppm from 8 weeks of age through 32 weeks. At 40 weeks of age, levels of body weight, triglyceride, and total cholesterol were significantly greater in the OLETF rats than in the LETO rats. A ratio of high-density lipoprotein (HDL) to total cholesterol was significantly smaller in the former than in the latter. In the LETO rats, nitrogen dioxide exposure significantly decreased only the levels of HDL as compared with clean air exposure. In the OLETF rats, however, nitrogen dioxide exposure at a concentration of 0.16 ppm significantly elevated triglyceride concentration and decreased the ratio of HDL to total cholesterol as well as the levels of HDL. Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects.

Exposure of Human Lung Cells to Inhalable Substances: A Novel Test Strategy Involving Clean Air Exposure Periods Using Whole Diluted Cigarette Mainstream Smoke

An experimental approach was established for the validation of an in vitro test system for complex environmental test atmospheres consisting of both gaseous substances and particulates. Smoke from two different cigarette types (generated by an automatic cigarette-smoking machine) was employed to assess both the sensitivity and the specificity of the system. The smoke was diluted with synthetic air and used to expose human lung cells grown on microporous membranes. Cells were exposed alternately to diluted cigarette smoke and pure synthetic air. The effect of diluted smoke was assessed without humidification, addition of CO 2, or any other physical or chemical modification of the smoke. The experimental setup included online monitoring of the gas phase (by analysis of CO concentration) and particulate phase (by light-scattering photometry). Replicate experiments confirmed a reproducible generation and dilution of the smoke and a smoke age of about 7 s at the time it came into contact with the cells. Experiments using human lung cells revealed that smoke from the two different cigarette types induced different levels of dose-dependent toxicity. A cell exposure of 6 min using 6 alternating smoke and synthetic air periods was sufficient to cause different effects as measured by intracellular glutathione content. The fact that the system could differentiate between two different types of cigarette smoke demonstrated its high sensitivity and specificity. The system offers new ways to test native complex gaseous and aerosol mixtures in vitro using short exposure times and very small amounts of test substances.

Biosensing by insect olfactory receptor neurons

Action potentials of insect olfactory receptor neurons (ORN) were picked up with microelectrodes and amplified by a high-impedance amplifier connected to an oscilloscope, an audio amplifier, and an instrumentation amplifier. The amplified action potentials and odour exposure times were recorded on a DAT (digital audio tape) recorder for later analysis. This measurement of the stimulated action potential rates of the ORN of a blowfly ( Calliphora vicina) made it possible to estimate odour concentrations to which the ORNs of the antenna were exposed. Odours of 1,4-diaminobutane (14DAB), 1-hexanol (HX), and butanoic acid (BA) were used in the experiments to stimulate various ORNs, which discharged action potentials. Spontaneous and stimulated action potential rates were analysed by means of a time-to-voltage converter connected to a signal analyser. The estimated exposure concentrations of the 14DAB odour were between a few ppb (parts per billion) and about 100 ppm (parts per million) in air, those of BA odour between 20 ppm and almost 200 ppm, and those of HX odour about 8 ppm and 500 ppm. The 14DAB-sensitive ORN generated action potentials between 100 and 275 pps (pulses per second), the BA-sensitive ORN between 70 and 165 pps, and the HX-sensitive ORN between 115 and 300 pps. Higher exposure concentrations of each odour caused the cessation of action potential production because of adaptation and overloading of the sensor. This could be seen predominantly as a saturation of the corresponding ORN. The spontaneous action potential rate before, and after, each stimulus exposure was between 20 and 25 pps. Clean-air exposures typically sent action potentials at the same rate as the spontaneous activity of the ORN.

Body Burden Measurements and Models to Assess Inhalation Exposure to Methyl Tertiary Butyl Ether (MTBE)

Biomarkers of methyl tertiary butyl ether (MTBE) exposure and the partitioning of inhaled MTBE into the body were investigated in a human chamber study. Two subjects were exposed to an environmentally relevant nominal 5,011 µg/m3 (1.39 ppm) MTBE for 1 hour, followed by clean–air exposure for 7 hours. Breath and blood were simultaneously sampled, while total urine was collected at prescribed times before, during, and after the exposure. Mass–balance and toxicokinetic analyses were conducted based upon the time series measurement of multiple body–burden endpoints, including MTBE in alveolar breath, and MTBE and tertiary butyl alcohol (TBA) in venous blood and urine. The decay of MTBE in the blood was assessed by fitting the post–exposure data to a 2– or 3–exponential model that yielded residence times (τ) of 2–3 min, 15–50 min, and 3–13 h as measured by alveolar breath, and 5 min, 60 min, and 32 h as evaluated from venous blood measurements. Based on observations of lower than expected blood and breath MTBE during uptake and a decreasing blood–to–breath ratio during the post–exposure decay period, we hypothesize that the respiratory mucous membranes were serving as a reservoir for the retention of MTBE. The decay data suggest that 6–9% of the MTBE intake may be retained by this non–blood reservoir. The compartmental modeling was further used to estimate important parameters that define the uptake of inhaled MTBE. The first of these parameters is f, the fraction of Cair exhaled at equilibrium, estimated as 0.60 and 0.46 for the female and male subject, respectively. The second parameter is the blood–to–breath partition coefficient (P) estimated as ∼18. The product of these parameters provides an estimate of the blood concentration at equilibrium as 8–11 times the air concentration. Blood TBA lagged MTBE levels and decayed more slowly (τ = 1.5–3 h), providing a more stable indication of longer term integrated exposure. The concentration ranges of MTBE and TBA in urine were similar to that of the blood, ranging from 0.37 to 15 µg/L and 2 to 15 µg/L, respectively. In urine, MTBE and TBA by themselves bore little relationship to the exposure. However, the MTBE:TBA ratio followed the pattern of exposure, with peak values occurring at the end of the exposure (20– and 60–fold greater than pre–exposure values) before decaying back to pre–exposure levels by the end of the 7–h decay period. Urinary elimination accounted for a very small fraction of total MTBE elimination (<1%).

Formaldehyde exposure enhances inhalative allergic sensitization in the guinea pig

Formaldehyde (FA), a common indoor air pollutant, has been associated with increased prevalence rates of asthmatic symptoms among exposed individuals in epidemiologic surveys. We studied the influence of FA exposure on inhalative allergic sensitization in the guinea pig. Three groups of guinea pigs (n= 12 each) were exposed to clean air or two different FA concentrations (0.13 and 0.25 ppm) over 5 consecutive days. Exposure was followed by inhalation of 0.5% ovalbumin (OA) as sensitizing allergen. Three weeks later, specific bronchial provocation with OA was performed with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgGI (reaginic) antibodies were determined in serum. In a further six animals, the respiratory tract was examined histologically for signs of inflammation directly after the end of FA or clean air exposure. In the group exposed to 0.25 ppm FA, 10/12 animals were found to be sensitized to OA (positive reaction on specific provocation) vs. 3/12 animals in the control group (P<0.01). Furthermore, CA measurements of specific bronchial provocation and serum anti-OA-antibodies were significantly higher in the 0.25 ppm FA group than in controls (CA 0.35 vs. 0.09 ml median, P<0.01; anti-OA-IgC1 13 vs. <10 EU median, P<0.05), indicating enhanced sensitization. In the group exposed to 0.13 ppm FA, no significant difference was found compared to the control group. There was no sign of inflammation of the lower airways in FA-exposed guinea pigs other than mucosal edema, which was discovered by morphometry. We conclude that short-term exposure to a low concentration of FA (0.25 ppm) can significantly enhance sensitization to inhaled allergens in the guinea pig.

Formaldehyde exposure enhances inhalative allergic sensitization in the guinea pig.

Formaldehyde (FA), a common indoor air pollutant, has been associated with increased prevalence rates of asthmatic symptoms among exposed individuals in epidemiologic surveys. We studied the influence of FA exposure on inhalative allergic sensitization in the guinea pig. Three groups of guinea pigs (n = 12 each) were exposed to clean air or two different FA concentrations (0.13 and 0.25 ppm) over 5 consecutive days. Exposure was followed by inhalation of 0.5% ovalbumin (OA) as sensitizing allergen. Three weeks later, specific bronchial provocation with OA was performed with body plethysmographic measurement of compressed air (CA). Furthermore, specific anti-OA-IgGl (reaginic) antibodies were determined in serum. In a further six animals, the respiratory tract was examined histologically for signs of inflammation directly after the end of FA or clean air exposure. In the group exposed to 0.25 ppm FA, 10/12 animals were found to be sensitized to OA (positive reaction on specific provocation) vs. 3/12 animals in the control group (P < 0.01). Furthermore, CA measurements of specific bronchial provocation and serum anti-OA-antibodies were significantly higher in the 0.25 ppm FA group than in controls (CA 0.35 vs. 0.09 ml median, P < 0.01; anti-OA-IgGl 13 vs. < 10 EU median, P < 0.05), indicating enhanced sensitization. In the group exposed to 0.13 ppm FA, no significant difference was found compared to the control group. There was no sign of inflammation of the lower airways in FA-exposed guinea pigs other than mucosal edema, which was discovered by morphometry. We conclude that short-term exposure to a low concentration of FA (0.25 ppm) can significantly enhance sensitization to inhaled allergens in the guinea pig.

Controlled exposures of young asthmatics to mixed oxidant gases and acid aerosol.

To help assess short-term respiratory responses to summertime air pollution, we exposed 24 asthmatic volunteers aged 11-18 in a chamber to respirable acid aerosol (mass median aerodynamic diameter 0.66 micron) plus 0.3 ppm nitrogen dioxide (NO2) plus 0.2 ppm ozone (O3). The aerosol contained available hydrogen ions (H-) at an average concentration of 2.6 mumol/m-, equivalent to 127 micrograms/m3 sulfuric acid (H2SO4); some H+ probably was in NH4HSO4 rather than H2SO4. The volunteers were exposed separately to O3/NO2 without acid and to clean air. Exposures lasted 90 min, including three 15-min exercise sessions with ventilation averaging 32 L/min, at 21 degrees C and 50% relative humidity. Asthma medications were withheld before and during exposures. Subjects gargled lemonade to minimize acid neutralization by oral ammonia (NH3). Exercise-induced bronchospasm was evident in all exposures. Differences in group mean lung function response among H2SO4/O3/NO2, O3/NO2, and clean-air exposures were not statistically significant. Individuals' measured oral NH3 concentrations or estimated inhaled doses of H2SO4 did not significantly predict their lung function changes. A few subjects showed unfavorable function changes during pollutant exposures, which might be chance occurrences or might indicate the existence of an acid-pollution-susceptible subgroup among young asthmatic subjects.

Age-related Changes in Electrocardiographic Responses to Trichloroethylene Inhalation in Conscious Rats.

Age-related effects of trichloroethylene (TRI) inhalation on heart rate (HR), its circadian rhythm, the incidence of spontaneous bradyarrhythmias (BA) and ventricular premature contractions (VPC) were examined in conscious rats, as was the dependence of arrhythmias on sleep-wakefulness. Indwelling electrodes were used for simultaneous electrocardiographic (ECG), electroencephalographic (EEG) and electromyographic (EMG) measurements in 2, 13, 20 and 26-month old rats. The rats were exposed for 8 hours to 300 ppm TRI followed by exposure to clean air for 7 days, after which they were exposed to 1,000 ppm for 8 hours. The polygraphic recordings were made during 8-hr exposures and for 28 hours thereafter. Control values for all physiological parameters were measured during 36-hr exposure to clean air. The exposure to TRI exacerbated an age-dependent decrease in HR and its circadian amplitude. Although the spontaneous BA incidence decreased with advancing age, the ratio of the number of BA episodes during the post-exposure period after TRI exposure to those during the corresponding period of clean-air exposure increased more pronouncedly for 20 and 26-month old rats than for 2 and 13-month old rats. The number of spontaneous VPC episodes increased for 20 and 26-month old rats but was not affected by the exposure to TRI. Gas chromatographic analysis of TRI and free trichloroethanol (TRI-OH) in the brain and blood of the TRI-exposed rats revealed the prolonged half-life of TRI and the delayed clearance of free TRI-OH from the tissues with advancing age. The age-related exacerbation of those ECG responses to TRI inhalation appears to be brought about in part by the age-related change in the pharmacokinetics of TRI and TRI-OH.

Effect of Ozone Inhalation on the Response to Nasal Challenge with Antigen of Allergic Subjects

The effect of oxidant inhalation on allergic illness is of interest because allergic patients often report increased respiratory symptoms during episodes of poor air quality, and epidemiologic studies demonstrate an association between increased levels of the air pollutant ozone and exacerbations of asthma. The purpose of this study was to characterize the upper respiratory response to ozone inhalation in asymptomatic, allergic subjects and to determine whether ozone pre-exposure increased the acute response to nasal challenge with antigen in these subjects. A group of 12 asymptomatic subjects with a history of allergic rhinitis were exposed in a randomized, cross-over design, at rest, on each of 2 days, separated by 2 wk, to 4 h of clean air or 0.5 ppm ozone in an environmental chamber. Following the exposure period, subjects underwent nasal challenge with four doses of antigen (1 to 1,000 PNU ragweed or grass). Symptoms were rated and nasal lavage performed after each dose. Measurement of histamine and albumin concentration and TAME-esterase activity and determination of cell counts and differentials were performed. Exposure to ozone caused significant increases in upper and lower respiratory symptoms, a mixed inflammatory cell influx with a sevenfold increase in naval lavage neutrophils, a 20-fold increase in eosinophils, and a tenfold increase in mononuclear cells, as well as an apparent sloughing of epithelial cells. There was a significant increase in nasal lavage albumin concentration on the ozone exposure day and a small increase in nasal lavage histamine concentration on both the ozone and clean air exposure days. TAME-esterase activity showed no significant increase overall, but increased at least twofold in 5 of 12 subjects. (ABSTRACT TRUNCATED AT 250 WORDS)

Long-term exposure of dogs to a sulphite aerosol: III. Effect of lung clearance

Eight dogs were exposed to a sodium bisulphite aerosol during 290 days. Lung clearance was tested with moderately soluble and insoluble aerosol particles after a single inhalation. Three dogs showed significant changes in clearance rate of moderately soluble particles during the sulphite exposure compared to the clearance rate during clean air exposure. The results were confirmed by in vitro clearance measurements in alveolar macrophages.

Respiratory effects of 0.75 ppm sulfur dioxide in exercising asthmatics: Influence of upper-respiratory defenses

To determine the influence of mouthpiece breathing on respiratory responses to sulfur dioxide (SO 2), 23 young adult asthmatic volunteers were exposed in a chamber to 0.75 ppm SO 2 during heavy exercise, once with breathing unencumbered and once while they wore noseclips and mouthpieces. These conditions (more severe than in typical ambient exposures) were deliberately chosen to produce significant physiological and clinical responses. Similar exposures to clean air served as controls. Exposure studies were separated by 1-week intervals and order was randomized. The protocol consisted of 10 min on a bicycle ergometer (mean load 650 kg-m/min, mean ventilation 40 liter/min), preceded and followed by response testing (body plethysmography, symptom questionnaires, and forced expiratory function tests; the last were performed only postexposure). During clean-air exposures, specific airway resistance (SR aw) and symptoms increased significantly, but no meaningful differences between mouthpiece breathing and unencumbered breathing were observed. Exposures to SO 2 under these relatively severe conditions produced greater increases in SR aw than clean-air exposures regardless of the mode of breathing, but the excess increase was significantly greater with mouthpiece than with unencumbered breathing. Symptom changes and postexposure forced expiratory function showed qualitatively the same pattern of decrements with SO 2 as did SR aw, but the excess responses attributable to mouthpiece breathing did not attain statistical significance. Mouthpiece breathing can compromise upper-respiratory defenses against SO 2 to the extent that responses are greater than with more natural breathing. The mode of breathing should be taken in account when applying laboratory human exposure data to air-quality risk assessment.