Experimental human exposure to carbon disulfide

Summary Six human volunteers were exposed to 10 and 20 ppm carbon disulfide at rest and to 3 and 10 ppm carbon disulfide under a 50 W level of physical exercise during four consecutive periods of 50 min. At the start of the experiments, at the end of the exposure periods and during the post-exposure period, urine was sampled and the concentration of 2-thiothiazolidine-4-carboxylic acid (TTCA) was determined. It was established that only a small percentage, ranging from 0.7 to 2.2% of the absorbed carbon sulfide was transformed into TTCA. The excretion rate of TTCA (mol TTCA h^–1) was found to be the best parameter in evaluating the respiratory uptake of carbon disulfide over a range of 37.9 to 163.3 mg CS₂ compared to the urinary concentration of TTCA (mole TTCA ml^–1) or the creatinine corrected concentration of TTCA (mmol TTCA mol^–1 creatinine). The total amount of TTCA (mol TTCA) excreted proved to be independent of the urinary flow (ml h^–1), the estimates of the individual fatty tissue content and the urinary pH. No correlation was found between the respiratory uptake of carbon disulfide (mg CS₂) and the excretion rate of TTCA within each exposure condition of 3, 10 or 20 ppm carbon disulfide, respectively.     

Toluene in alveolar air during controlled exposure to constant and to varying concentrations

Summary The concentratiuon of toluene in the alveolar air was measured in 20 males and 17 females exposed for 7 h either to a constant exposure to 100 ppm toluene or to a varying exposure with the same time-weighted average, but with peaks of 300 ppm every 30 min. Both exposure schedules included 50 to 100 W exercise in three 15-min periods. Repetitive measurements of the toluene concentrations in the alveolar air were made in two 30-min periods, one at rest and one including work. At rest the alveolar concentration increased rapidly in response to an increase in the inspiratory air concentration, while exercise delayed this increase by about 2 min, probably due to an altered distribution of toluene in the body. The average alveolar concentration was 16.5 ± 6.8 ppm (mean ±SD) at rest and 19.5 ± 5.3 ppm in the period including exercise while there was no difference between constant and varying exposure. The alveolar toluene concentration tended to be higher in females than in males both at rest and during exercise. Subjects exercising with an intensity of 100 W had 25% higher values at rest than those exercising at 75 W. The excretion of the metabolites hippuric acid and orthocresol in the last 3 h of exposure was correlated to the alveolar toluene concentration at rest but not during work. Besides this, body height and weight influenced the excretion rates, still leaving a large unexplained interindividual variation.     

Toluene in alveolar air during controlled exposure to constant and to varying concentrations

The concentration of toluene in the alveolar air was measured in 20 males and 17 females exposed for 7 h either to a constant exposure to 100 ppm toluene or to a varying exposure with the same time-weighted average, but with peaks of 300 ppm every 30 min. Both exposure schedules included 50 to 100 W exercise in three 15-min periods. Repetitive measurements of the toluene concentrations in the alveolar air were made in two 30-min periods, one at rest and one including work. At rest the alveolar concentration increased rapidly in response to an increase in the inspiratory air concentration, while exercise delayed this increase by about 2 min, probably due to an altered distribution of toluene in the body. The average alveolar concentration was 16.5 +/- 6.8 ppm (mean +/- SD) at rest and 19.5 +/- 5.3 ppm in the period including exercise while there was no difference between constant and varying exposure. The alveolar toluene concentration tended to be higher in females than in males both at rest and during exercise. Subjects exercising with an intensity of 100 W had 25% higher values at rest than those exercising at 75 W. The excretion of the metabolites hippuric acid and orthocresol in the last 3 h of exposure was correlated to the alveolar toluene concentration at rest but not during work. Besides this, body height and weight influenced the excretion rates, still leaving a large unexplained interindividual variation.     

Kinetics of tetrachloroethylene in volunteers; influence of exposure concentration and work load

Summary Six male volunteers were exposed for 4 h to 72 ppm tetrachloroethylene (PERC) at rest, to 144 ppm PERC at rest, and to 142 ppm PERC at rest combined with work load (2 times 30 min, 100 W). Minute volume and concentrations in exhaled air were measured to estimate the uptake. Concentrations of PERC and trichloroacetic acid (TCA) were determined in blood. Exhaled air was analysed for PERC; urine for TCA.The uptake/min decreased in the course of the exposure to 60 % of the initial uptake. The total uptake was influenced more by (lean) body mass than by respiratory minute volume or adipose tissue. During work load the uptake and minute volume increased to 3 fold the value at rest. In the post exposure period the quotient of the bloodconcentrations and exhaled air concentrations of PERC remained nearly constant at 23. Following exposure about 80–100 % of the uptake was excreted unchanged by the lungs, whereas till 70 h after exposure the amount of TCA excreted in urine represented about 1 % of the uptake.     

Interaction of ozone and cigarette smoke exposure

Possible interactions of ozone and cigarette smoke exposure have been tested in 2-hr chamber exposures of 26 male and 6 female subjects, all of whom were habitual smokers. Treatment conditions were air alone, air + cigarette smoking, ozone alone, and ozone + cigarette smoking. Ozone levels were increased progressively over four trials (0.37 ppm, 0.75 ppm, 0.50 ppm + intermittent exercise, and 0.75 ppm + intermittent exercise); exercise (50 W for 15 min alternating with 15-min rest) was intended to increase ventilation by a factor of 2.5. Ozone exposure reduced the carbon monoxide intake normally seen with smoking, as judged from smaller increments of blood carboxyhemoglobin readings. Ozone exposure alone gave rise to a decrease of lung function (forced vital capacity (VC), 1-sec forced expiratory volume, and maximum flow rates at 25 and 50% of VC), but the onset was slower and the response less dramatic than previously seen in nonsmokers, suggesting that the chronic effect of smoking may be to delay bronchial irritation by ozone. Smoking increased heart rate both at rest and during exercise, but this response was not materially influenced by simultaneous ozone exposure. It is concluded that over an acute 2-hr exposure, there is no appreciable interaction between cigarette smoking and responses to ozone.     

Kinetics of 1,1,1-trichloroethane in volunteers; Influence of exposure concentration and work load

Summary Six male volunteers were exposed for 4 h to 70 ppm 1,1,1-trichloroethane (methylchloroform, MC) at rest, to 145 ppm. MC at rest, and to 142 ppm MC at rest combined with work load (2 times 30 min, 100 W). Minute volume and concentration in exhaled air were measured to estimate the uptake. MC and its metabolites trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined as far as present in blood, exhaled air and urine. The uptake/min decreased in the course of exposure to 30 % of the initial uptake. The total uptake was more influenced by minute volume than by body weight or amount of adipose tissue. During work load the uptake increased to 2.3 fold and the minute volume to 3 fold the value at rest. In the post exposure period the quotients of the concentrations in blood and in exhaled air for MC and TCE remained nearly constant at 8.2 and 14,000, respectively. Following exposure about 60–80% of the amount taken up was excreted unchanged by the lungs, while until 70 h after exposure the amount of TCE and TCA excreted in urine represented about 2% and 0.5% of the uptake.     

Asthmatics' responses to 6-hr sulfur dioxide exposures on two successive days

Asthmatic volunteers (N = 14) aged 18 to 33 yr with documented sensitivity to sulfur dioxide (SO2) were exposed in a chamber to 0.6 ppm SO2 for 6-hr periods on 2 successive days. Similar exposures to purified air, 1 wk later or earlier, served as controls. Subjects exercised heavily (target ventilation rate 50 L/min) for 5 min near the beginning of exposure (early exercise) and for an additional 5 min beginning after 5-hr of exposure (late exercise). At all other times, they rested. Body plethysmographic measurements and symptom questionnaires were administered pre-exposure, after each exercise period, and hourly during rest. Bronchoconstriction and lower respiratory symptoms were observed during or immediately following exercise--to a slight extent with clean air, and to a more marked extent with SO2. Bronchoconstriction and symptoms were modestly less severe on the second day of SO2 exposure than on the first day, but there were no meaningful differences in response between early and late exercise periods on either day.     

Pharmacokinetics of trichloroethylene in volunteers,influence of workload and exposure concentration

Summary Four male volunteers inhaled for 4 h 70 and 140 ppm trichloroethylene (TRI) at rest and also at rest combined with exercise. To estimate the amount retained in the body (dose), minute volume and concentration in exhaled air were determined. Concentrations of TRI, trichloroethanol (TCE) and trichloroacetic acid (TCA) were determined in blood. Exhaled air was analysed for TRI and TCE; urine for TCE and TCA.During more than 60 h after exposure the concentration of TRI and TCE in blood and exhaled air were proportional to the dose, but the interindividual variation was large; workload increased the dose, but no influence was found on the distribution and metabolism. The total recovery was 67%; 10% as TRI by the lungs and in urine 39% as TCE and 18% as TCA.     

Effect of physical exertion on the biological monitoring of exposure to various solvents following exposure by inhalation in human volunteers: II. n-Hexane

This study evaluated the impact of physical exertion on two n-hexane (HEX) exposure indicators in human volunteers exposed under controlled conditions in an inhalation chamber. A group of four volunteers (two women, two men) were exposed to HEX (50 ppm; 176 mg/m(3)) according to several scenarios involving several periods when volunteers performed either aerobic (AERO), muscular (MUSC), or both AERO/MUSC types of exercise. The target intensities for 30-min exercise periods separated by 15-min rest periods were the following: REST, 50W AERO [time-weighted average intensity including resting period (TWAI): 38W], 50W AERO/MUSC (TWAI: 34W), 100W AERO/MUSC (TWAI: 63W), and 100W AERO (TWAI: 71W) for 7 hr (two 3-hr exposure periods separated by 1 hr without exposure) and 50W MUSC for 3 hr (TWAI: 31W). Alveolar air and urine samples were collected at different time intervals before, during, and after exposure to measure unchanged HEX in expired air (HEX-A) and urinary 2,5-hexanedione (2,5-HD). HEX-A levels during exposures involving AERO activities (TWAI: 38W and 71W) were significantly enhanced (approximately +14%) compared with exposure at rest. MUSC or AERO/MUSC exercises were also associated with higher HEX-A levels but only at some sampling times. In contrast, end-of-exposure (7 hr) urinary 2,5-HD (mean +/- SD) was not modified by physical exertion: 4.14 +/- 1.51 micromol/L (REST), 4.02 +/- 1.52 micromol/L (TWAI 34W), 4.25 +/- 1.53 micromol/L (TWAI 38W), 3.73 +/- 2.09 micromol/L (TWAI 63W), 3.6 +/- 1.34 micromol/L (TWAI 71W) even though a downward trend was observed. Overall, this study showed that HEX kinetics is practically insensitive to moderate variations in workload intensity; only HEX-A levels increased slightly, and urinary 2,5-HD levels remained unchanged despite the fact that all types of physical exercise increased the pulmonary ventilation rate.     

Effect of physical exertion on the biological monitoring of exposure of various solvents following exposure by inhalation in human volunteers: I. Toluene

Physical exertion (work load) has been recognized as one of several factors that can influence the kinetics of xenobiotics within the human body. This study was undertaken to evaluate the impact of physical exertion on two exposure indicators of toluene (TOL) in human volunteers exposed under controlled conditions in an inhalation chamber. A group of four volunteers (one woman, three men) were exposed to TOL (50 ppm) according to the following scenarios involving several periods during which volunteers were asked to perform either aerobic (AERO), muscular (MUSC), or both (AERO/MUSC) types of physical exercise (exercise bicycle, treadmills, pulleys). The target intensities (W) for each exercising period of 30 min--interspaced with 15 min at rest--were the following: REST, 50 W AERO (time-weighted average intensity [TWAI]: 46 watts); 50 W AERO/MUSC (TWAI: 38 watts) and 100 W AERO (TWAI: 71 watts) for 7 hours and 50 W MUSC for 3 hours (TWAI: 29 watts). Alveolar air and urine samples were collected at different time intervals before, during, and after exposure for the measurement of unchanged TOL in expired air (TOL-A) and urinary o-cresol (o-CR). Overall, the results showed that TOL-A measured during and after all scenarios involving physical activities were higher (approximately 1.4-2.0 fold) compared with exposures at rest. All scenarios involving physical exertion also resulted in increased end-of-exposure urinary o-CR (mean +/- SD): 0.9 +/- 0.1 mg/L (REST) vs. 2.0 +/- 0.1 mg/L (TWAI 46 watts). However, exposure at a TWAI of 71 watts did not further increase o-CR excretion (1.7 +/- 0.2 mg/L). This study confirms the significant effect of work load on TOL kinetics and showed that o-CR excretion increased proportionally with work load expressed as TWAI or with the estimated mean pulmonary ventilation during the period of exposure. This study also shows that exposure to TOL (50 ppm) involving a work load of around 50 W (light intensity) or lower is likely to produce urinary o-CR values that clearly exceed the current biological exposure index value for TOL.     

Inhalation of ultrafine particles alters blood leukocyte expression of adhesion molecules in humans

Ultrafine particles (UFPs; aerodynamic diameter < 100 nm) may contribute to the respiratory and cardiovascular morbidity and mortality associated with particulate air pollution. We tested the hypothesis that inhalation of carbon UFPs has vascular effects in healthy and asthmatic subjects, detectable as alterations in blood leukocyte expression of adhesion molecules. Healthy subjects inhaled filtered air and freshly generated elemental carbon particles (count median diameter approximately 25nm, geometric standard deviation approximately 1.6), for 2 hr, in three separate protocols: 10 microg/m3 at rest, 10 and 25 microg/m3 with exercise, and 50 microg/m3 with exercise. In a fourth protocol, subjects with asthma inhaled air and 10 microg/m3 UFPs with exercise. Peripheral venous blood was obtained before and at intervals after exposure, and leukocyte expression of surface markers was quantitated using multiparameter flow cytometry. In healthy subjects, particle exposure with exercise reduced expression of adhesion molecules CD54 and CD18 on monocytes and CD18 and CD49d on granulocytes. There were also concentration-related reductions in blood monocytes, basophils, and eosinophils and increased lymphocyte expression of the activation marker CD25. In subjects with asthma, exposure with exercise to 10 microg/m3 UFPs reduced expression of CD11b on monocytes and eosinophils and CD54 on granulocytes. Particle exposure also reduced the percentage of CD4+ T cells, basophils, and eosinophils. Inhalation of elemental carbon UFPs alters peripheral blood leukocyte distribution and expression of adhesion molecules, in a pattern consistent with increased retention of leukocytes in the pulmonary vascular bed.     

Propylene glycol monomethyl ether occupational exposure. 3. Exposure of human volunteers

OBJECTIVE: Propylene glycol monomethyl ether (PGME) is a widely used additive in industrial and consumer products (paints, inks, diluents, cleaning products, cosmetics.). The aim of the present study was to determine uptake and disposition of PGME alpha-isomer in humans. METHOD: Six healthy male volunteers were exposed to PGME-alpha vapour (15, 50 and 95 ppm) with and without respiratory protection for 6 h including a 30-min break. Free PGME and total PGME (free and conjugated) were analysed in urine. The analytical method involved hydrolysis with HCl (only for the analysis of total PGME in urine), a solid phase extraction on LC-18 columns and a gas chromatograph-flame ionisation detector (GC/FID) analysis after derivatisation with trimethylsilylimidazole. RESULTS: End-exposure levels of free PGME in urine were found to reach 1.3 (+/-0.3), 4.4 (+/-1.6) and 7.9 (+/-2.5) mg/l for 15, 50 and 95-ppm exposure, respectively, without respiratory protection. End-exposure levels of total PGME in urine were found to reach 2.5 (+/-0.8), 6.2 (+/-1.6) and 10.3 (+/-2.3) mg/l for 15, 50 and 95-ppm exposure respectively. Levels of free PGME were also monitored in exhaled air (0.4 (+/-0.1), 1.4 (+/-0.4) and 2.9 (+/-0.9) ppm at the end of 15, 50 and 95-ppm exposure, respectively) and in blood (2.0 (+/-0.9), 4.9 (+/-2.3) and 11.8 (+/-2.4) mg/l at the end of 15, 50 and 95-ppm exposure, respectively). PGME is rapidly excreted in urine and in exhaled air; the half-lives were calculated to be approximately 3.5 h in urine and 10 min in exhaled air. PGME was below detection limits in breath (<0.1 ppm), in blood (<1 mg/l) and in urine (<1 mg/l) after dermal-only exposure to vapour. CONCLUSIONS: This study has demonstrated the relatively high pulmonary uptake compared with the dermal uptake. It has also shown the rapid excretion in urine (3.5 h) and in expired air (10 min). With regard to metabolism, this study has established the presence of conjugated PGME in urine.     

Toxicokinetics of methyl tert-butyl ether (MTBE) and tert-amyl methyl ether (TAME) in humans, and implications to their biological monitoring

Healthy male volunteers were exposed via inhalation to gasoline oxygenates methyl tert-butyl ether (MTBE) or tert-amyl methyl ether (TAME). The 4-hr exposures were carried out in a dynamic chamber at 25 and 75 ppm for MTBE and at 15 and 50 ppm for TAME. The overall mean pulmonary retention of MTBE was 43 +/- 2.6%; the corresponding mean for TAME was 51 +/- 3.9%. Approximately 52% of the absorbed dose of MTBE was exhaled within 44 hr following the exposure; for TAME, the corresponding figure was 30%. MTBE and TAME in blood and exhaled air reached their highest concentrations at the end of exposure, whereas the concentrations of the metabolites tert-butanol (TBA) and tert-amyl alcohol (TAA) concentrations were highest 0.5-1 hr after the exposure and then declined slowly. Two consecutive half-times were observed for the disappearance of MTBE and TAME from blood and exhaled air. The half-times for MTBE in blood were about 1.7 and 3.8 hr and those for TAME 1.2 and 4.9 hr. For TAA, a single half-time of about 6 hr best described the disappearance from blood and exhaled air; for TBA, the disappearance was slow and seemed to follow zero-order kinetics for 24 hr. In urine, maximal concentrations of MTBE and TAME were observed toward the end of exposure or slightly (< or = 1 hr) after the exposure and showed half-times of about 4 hr and 8 hr, respectively. Urinary concentrations of TAA followed first-order kinetics with a half-time of about 8 hr, whereas the disappearance of TBA was slower and showed zero-order kinetics at concentrations above approx. 10 micro mol/L. Approximately 0.2% of the inhaled dose of MTBE and 0.1% of the dose of TAME was excreted unchanged in urine, whereas the urinary excretion of free TBA and TAA was 1.2% and 0.3% within 48 hr. The blood/air and oil/blood partition coefficients, determined in vitro, were 20 and 14 for MTBE and 20 and 37 for TAME. By intrapolation from the two experimental exposure concentrations, biomonitoring action limits corresponding to an 8-hr time-weighted average (TWA) exposure of 50 ppm was estimated to be 20 micro mol/L for post-shift urinary MTBE, 1 mu mol/L for exhaled air MTBE in a post-shift sample, and 30 micro mol/L for urinary TBA in a next-morning specimen. For TAME and TAA, concentrations corresponding to an 8-hr TWA exposure at 20 ppm were estimated to be 6 micro mol/L (TAME in post-shift urine), 0.2 micro mol/L (TAME in post-shift exhaled air), and 3 micro mol/L (TAA in next morning urine).     

Asthmatics' Responses to 6-Hr Sulfur Dioxide Exposures on Two Successive Days

Asthmatic volunteers (N = 14) aged 18 to 33 yr with documented sensitivity to sulfur dioxide (SO₂) were exposed in a chamber to 0.6 ppm SO₂ for 6-hr periods on 2 successive days. Similar exposures to purified air, 1 wk later or earlier, served as controls. Subjects exercised heavily (target ventilation rate 50 L/min) for 5 min near the beginning of exposure (early exercise) and for an additional 5 min beginning after 5-hr of exposure (late exercise). At all other times, they rested. Body plethysmographic measurements and symptom questionnaires were administered pre-exposure, after each exercise period, and hourly during rest. Bronchoconstriction and lower respiratory symptoms were observed during or immediately following exercise—to a slight extent with clean air, and to a more marked extent with SO₂. Bronchoconstriction and symptoms were modestly less severe on the second day of SO₂ exposure than on the first day, but there were no meaningful differences in response between early and late exercise periods on either day.     

Experimental human exposure to n-hexane

Summary The respiratory uptake rate of n-hexane showed considerable differences in six healthy male persons, exposed at rest to 360 mg/m³ and 720 mg/m³ of n-hexane in inspired air and to 360 mg/m³ under different levels of physical exercise. These differences could partly be explained by a positive correlation with the amount of body fat. At rest also a strong influence of the respiratory minute volume and respiratory frequency on the uptake rate could be proven. The average uptake rate remained virtually constant over a range of 20 to 60 W of continuous external physical load, indicating that under these circumstances the inspired n-hexane concentration alone predominantly determines the uptake rate.The respiratory elimination during the first hours after an exposure was also subject to important inter- and intraindividual fluctuations. The pulmonary ventilation rate at the moment of breath sampling had a pronounced influence on the measured exhaled concentration. On the other hand, there was no apparent effect of the amount of body fat. Generally, the correlation between the amount of n-hexane taken up and breath concentrations at different time intervals was rather poor.n-Hexane concentrations in peripheral venous blood reacted rapidly to changes in exposure conditions, but not in the same proportion as the uptake rate. The blood concentration proved more closely related to respiratory n-hexane retention than to the uptake rate, reflecting the state of saturation of different body tissues. At rest this parameter was clearly influenced by the amount of body fat. A decrease in relative blood perfusion of fatty tissue could explain why such relation was not found during exposure combined with physical effort.     

Air pollution is associated with increased level of exhaled nitric oxide in nonsmoking healthy subjects.

The authors sought to determine which air pollutant is responsible for the increase in exhaled nitric oxide observed in healthy subjects. Exhaled nitric oxide was measured in 16 nonsmoking healthy subjects on 14 workdays, during which there were varying air-pollution levels. Contamination of samples by ambient nitric oxide was excluded. The baseline value of exhaled nitric oxide, determined at times when outdoor air pollution was low, ranged from 7 to 43 ppb (mean = 28+/-5 ppb). The daily value of exhaled nitric oxide (range = 5-60 ppb) was associated positively with ambient carbon monoxide (r = .85) and nitric oxide (r = .81). Exposure during the morning hours to high levels of outdoor pollution was associated with increased exhaled nitric oxide (i.e., 50% above baseline), which persisted for up to 5 h (i.e., 32% above baseline). These results indicated that exhaled nitric oxide levels represent a useful biomonitor of individual exposure to air pollutants.     

Experimental human exposure to toluene

Summary Six healthy male subjects exposed to various concentrations of toluene in inspired air (50, 100, and 150 ppm) under controlled conditions of rest or physical exercise, showed markedly little differences in the rate of respiratory solvent uptake. On the whole the intra-individual variations proved as important as the between subjects variations. For a given level of physical exercise the lung clearance appeared most affected by fluctuations in respiratory minute volume. In our experimental group the uptake rate was not significantly influenced by the amount of body fat.Toluene concentrations in expired air (C_E) during the first 4 h after an exposure cannot be considered a reliable measure for the individual toluene uptake. This parameter appears to reflect the influence of a number of host factors which do not affect — or at least not in the same way — the toluene uptake by itself. As a consequence the observed variability of toluene in the expired air was always much greater than for the related lung clearances. The single most important factors explaining differences in respiratory solvent excretion, were the respiratory minute volume in the post-exposure period and, after exposures at rest, the amount of body fat.The mean excretion amounted to about 4 % of the total uptake within 24 H after the end of the exposure.     

Effect of individually diversified smoking habits on carbon monoxide retention in the respiratory tract of active smokers and validation of results based of environmental categories

Cigarette smoke, treated as smoke inhaled by active smokers, was generated using self-made smoking-machine and with application of formerly established parameters of individual smoking process. Carbon monoxide was analysed in generated smoke. It was concluded, that diversified smoking process is very individual (different volume and duration time of puff and intervals between puffs) and therefore influences levels of carbon monoxide in MS (from 3.5 to 17.5 mg/cigarette). Simultaneously, carbon monoxide was analysed in exhaled air by active smokers just after each puff. Difference between inhaled and exhaled dose of carbon monoxide was treated to calculated individual retention of carbon monoxide in active smoker's respiratory tract. Mean relative retention was 57.6% and differences between single values were lower than in the cases of CO levels in MS and absolute retention. Estimation of carbon monoxide inhaled doses was proceeded according to environmental standards. Forecasted blood concentration of HbCO after smoking of twenty cigarettes equals 2.3 to 10.4%. These results are similar to the situation that people would inhale air containing CO with concentration 1.2 to 5.5-times higher than limiting value.     

A study of respiratory effects from exposure to 2 ppm formaldehyde in healthy subjects

Formaldehyde (FA) is a common indoor air pollutant with irritative properties. It has been suggested that FA may produce physiologic alterations of the respiratory system. To study such responses, 15 nonsmoking, healthy subjects were exposed in a double blind, random manner to 0 and 2 ppm FA for 40 min in an environmental chamber. In addition, the same exposures were repeated on a separate day with the subjects performing moderate exercise (450 kpm/min) for 10 min. Exposures were carried out under controlled environmental conditions (temperature = 23 degrees C, relative humidity = 50%). Pulmonary function was measured before, during, and after exposures using partial and maximal flow-volume curves and airway resistance. Symptom diaries were given to the subjects; upper and lower airway symptoms were recorded for up to 24 hr following exposures. No significant bronchoconstriction was noted in this group. In 3 subjects, sequential measurements of peak flow over a 24-hr period following FA exposure failed to reveal any delayed airway response. On a separate day, 6 healthy subjects failed to demonstrate changes from their baseline responsiveness to methacholine after exposure to 2 ppm FA. Respiratory symptoms were, in general, confined to the upper airways and were mild to moderate in severity. We conclude that short exposures to 2 ppm FA do not result in acute or subacute changes in lung function among healthy individuals either at rest or with exercise. Subjective complaints following such exposures are confined to irritative phenomena of the upper airways.     

Pulmonary function, airway responsiveness, and respiratory symptoms in asthmatics following exercise in NO2

Two experiments were conducted to determine respiratory responses of persons with asthma performing intermittent moderate exercise while exposed to low concentrations of NO2. In the first, preliminary experiment, 13 male subjects, aged 19-35, with mild asthma were exposed on separate days in a chamber (natural breathing, 20 degrees C, 40% RH) to 0.30 ppm NO2 and to a control or "clean air" exposure (0.0 ppm NO2). Exposure included three 10-min periods of moderate treadmill exercise (VE = 44.5 liter/min), each followed by symptom measurement and pulmonary function testing. The average decrease in FEV1 following the initial 10 min exercise in 0.30 ppm was 11% which was significantly greater (p less than 0.05) than that observed in clean air (7%). Differences in FVC and SRaw were not significantly different at this time. Slight cough and dry mouth and throat were apparent only after the first exercise in NO2. After the second and third exercises, decreases in FEV1 and FVC and increases in SRaw were significantly greater in 0.30 than in 0.0 ppm NO2. Individual subject responses were variable. These results suggested that some asthmatics who perform moderate exercise while exposed to 0.30 ppm NO2 may experience bronchoconstriction and reduction in spirometric performance. Because of these preliminary findings, a more comprehensive, concentration-response experiment was conducted. Twenty-one male volunteers with mild asthma were exposed for 75 min with natural breathing to 0.0, 0.15, 0.30, and 0.60 ppm NO2. Exposure included three 10-min periods of moderate treadmill exercise (VE = 43 liter/min), each exercise followed by symptoms measurement and pulmonary function testing. In addition, airway responsiveness was measured two hr after each exposure by methacholine bronchial challenge testing. In the control exposures (0.0 ppm NO2), the exercise alone caused substantial decrements in pulmonary function. These decrements (as measured by decreases in FEV1 and FVC, and increases in SRaw) were not increased relative to the control exposure after any exercise session in any concentration of NO2. Furthermore, there was no overall group-averaged indication of a concentration-related effect of the NO2 on pulmonary function. Likewise, symptoms reported after NO2 exposure were not significantly different from those reported in clean air. Group-averaged airway responsiveness after exercise in NO2 was also not different from responsiveness after exercise in clean air. For only two subjects was there any indication of a concentration-related increase in airway responsiveness due to exposure to NO2.(ABSTRACT TRUNCATED AT 400 WORDS)