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.     

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.     

Experimental human exposure to carbon disulfide

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. Every 5 min a sample was taken from the mixed exhaled air in which the concentration of carbon disulfide was determined. It was established that only an apparent steady state was reached during this exposure period. The retention values were established as 0.374 (SD = 0.106; n = 239) for exposure to 10 ppm carbon disulfide at rest and as 0.410 (SD = 0.103; n = 239) for exposure to 20 ppm carbon disulfide at rest. During exposure to 10 ppm and 3 ppm carbon disulfide, combined with a 50 W level of physical exercise, the retention values decreased to 0.286 (SD = 0.083; n = 239) and 0.277 (SD = 0.049; n = 239) respectively. Thereby, the measured individual retention values of carbon disulfide show considerable interindividual differences. The respiratory uptake of carbon disulfide (mg CS2) proved significantly influenced by the amount of body fat estimated from skinfold thickness measurements. The respiratory elimination of carbon disulfide in the exhaled air can be described by means of a two-exponential decay.     

Oral and oronasal breathing during continuous exercise produce similar responses to ozone inhalation

Breathing route has a profound effect on sulfur dioxide-induced pulmonary function response in human subjects. There is comparatively little evidence of the effects of oral, nasal, and oronasal breathing on ozone (O3)-induced responses in humans. In this study, six young adult males were exposed on five occasions to 0.40 parts per million (ppm) O3 while exercising continuously at one of two workloads (minute ventilation, VE, of approximately 30 and 75 l/min). The VE exposure time product was similar for all protocols. Four exposures were delivered randomly with a Hans-Rudolph respiratory valve attached to a silicone facemask, with breathing route effected with and without noseclip. A 2 x 2 analysis of variance revealed no statistically significant differences (p less than .05) across conditions in pulmonary function, exercise ventilatory pattern, or subjective symptoms responses. The fifth exposure, delivered via the same respiratory valve with mouthpiece, but without facemask, revealed significantly greater forced expiratory volume in 1 s (FEV1.0) impairment than that observed for the respiratory valve, facemask with noseclip exposure (-20.4% and -15.9%, respectively). The latter suggests partial O3 reactivity to the facemask and clean shaven facial surface of the subjects, although reduced oral scrubbing by mouthpiece-induced bypassing of the oral vestibule might account, in part, for this difference. Recent O3 uptake evidence from another laboratory, however, supports our conclusion that breathing route during moderate and heavy continuous exercise does not affect acute physiologic responses to 0.40 ppm O3.     

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.     

Toxicokinetics of inhaled 2-butoxyethanol (ethylene glycol monobutyl ether) in man

Seven male volunteers were exposed to 2-butoxyethanol at the Swedish occupational exposure limit (20 ppm or 0.85 mmol/m3) during light physical exercise (50 W) on a bicycle ergometer. The exposure took place in an exposure chamber and lasted 2 h. Expired air was collected at regular time intervals for estimation of the respiratory uptake of the solvent. Arterialized capillary blood and urine were sampled during and after the exposure period and analyzed for 2-butoxyethanol and its metabolite butoxyacetic acid. A new sensitive method for analyzing 2-butoxyethanol in biological specimens is described. 2-Butoxyethanol was derivatized with pentafluorobenzoyl chloride and analyzed by gas chromatography with electron capture detection. The respiratory uptake of 2-butoxyethanol averaged 10.1 mumol/min or 57% of the inspired amount. The concentration in blood reached a plateau level of 7.4 mumol/l. The apparent values of elimination half-time, mean residence time, total blood clearance, and steady-state volume of distribution were 40 min, 42 min, 1.2 1/min and 54 l, respectively. The amount of 2-butoxyethanol excreted in urine was less than 0.03% of the total uptake, while that of butoxyacetic acid ranged from 17 to 55%.     

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.     

Experimental human exposure to toluene

Summary The relationship between the individual toluene uptake and the urinary hippuric acid excretion was studied under experimental conditions. Six healthy male subjects were exposed to various concentrations in inspired air (50, 100, 125, 150, and 200 ppm) at rest or under different levels of physical effort.The hippuric acid excretion near the end of the exposure appeared under all circumstances directly proportional to the time-weighted uptake rate of toluene. The correlation between respiratory uptake rate and the rate of metabolite excretion near the end of the exposure period proved not to be systematically influenced by personal factors such as body weight, amount of body fat, urine flow rate and urinary pH. The relatively pronounced differences in background excretion of hippuric acid and, perhaps, distribution phenomena of toluene between different tissues under heavy workload conditions, can partly explain the greater variability in metabolite excretions as compared to the individual uptake rates.The correlation between the individual uptake rate of toluene and the hippuric acid excretion proved substantially better when using the end exposure excretion rate as exposure parameter as compared with the end exposure hippuric acid concentration, even after correcting the latter for urine density.Reasonable biological limit values complying to an acceptable time-weighted toluene dose were found to be 3000–3500 mg/l and 2.0–2.5 mg/min, resp. for average hippuric acid concentrations and excretion rates in spot samples during the second half of a complete work shift.     

The relationship between exposure duration and sulfur dioxide-induced bronchoconstriction in asthmatic subjects

The purpose of this study was to determine the shortest duration of exposure to 1.0 ppm sulfur dioxide (SO2) sufficient to induce bronchoconstriction significantly greater than that observed with exposure to clean air (CA) in exercising SO2-sensitive asthmatics. Asymptomatic, nonmedicated, male asthmatics (n = 12) with airway hyperresponsiveness to both methacholine and SO2 were exposed in a chamber (20 degrees C, 40% relative humidity) for 0.0, 0.5, 1.0, 2.0 and 5.0 min to both CA and 1.0 ppm SO2 on separate days (10 exposures). Just prior to each exposure, subjects walked on a treadmill in CA for 5 min at a predetermined speed/elevation to elicit a target ventilation of about 40 L/min, i.e., a brisk pace up a slight incline. After this walk, subjects rapidly entered an adjoining exposure chamber containing either CA or SO2 and immediately walked at the same speed/elevation for the specified exposure duration. Subjects then rapidly exited the chamber. Specific airway resistance (SRaw) and ratings of respiratory symptoms associated with asthma [shortness of breath/chest discomfort (SB/CD) and wheezing (WHZ)] were measured prior to any exercise and following each exposure. Postexposure SRaw and symptom ratings increased with increased exposure duration in SO2; postexposure SRaw also was increased with increased exposure duration in CA but to a lesser extent. After adjusting for the CA response, significantly greater SO2-induced bronchoconstriction was observed for the 2.0 and 5.0 min exposures as indicated by substantially greater increases in SRaw and substantially higher ratings of respiratory symptoms. The authors conclude that with the above exposure conditions, on average, SO2-sensitive asthmatics exhibit significant bronchoconstriction at exposure durations of 2.0 min or more.     

Airway responses to 2.0 ppm nitrogen dioxide in normal subjects

Nitrogen dioxide (NO2) is a common indoor air pollutant. To characterize the acute respiratory responses to this gas, 18 nonsmoking normal subjects (mean age +/- standard deviation [SD] = 25 +/- 4 yr) were exposed to filtered air or 2 ppm NO2 gas for 1 hr in a 30-m3 environmental chamber on different days, typically 1 wk apart, in a double-blind randomized fashion. Lung function tests included forced vital capacity, forced expiratory volume in one second, partial expiratory flow at 40% of vital capacity (Vp40), functional residual capacity, and specific airway conductance, and were measured before and after exposure. Airway reactivity to methacholine inhalation was determined within 45 min of each exposure. The dose of methacholine in mg/ml to cause a 40% decrease in specific airway conductance (PD40) was measured. Airway reactivity to methacholine aerosol increased significantly after NO2, which is shown by a decrease in the concentration of methacholine; PD40 (AIR) = 101 +/- 44, PD40 (NO2) = 81 +/- 45 mg/ml, p = .003. No significant changes were noted in the lung function tests after NO2 exposure. These findings indicate that normal nonsmokers exposed to 2.0 ppm NO2 for 1 hr develop an increase in airway reactivity to methacholine aerosol, which is not associated with changes in lung volumes, flow rates, or respiratory symptoms.     

Oral and Oronasal Breathing During Continuous Exercise Produce Similar Responses to Ozone Inhalation

Breathing route has a profound effect on sulfur dioxide-induced pulmonary function response in human subjects. There is comparatively little evidence of the effects of oral, nasal, and oronasal breathing on ozone (O₃)-induced responses in humans. In this study, six young adult males were exposed on five occasions to 0.40 parts per million (ppm) O₃ while exercising continuously at one of two workloads (minute ventilation, [Vdot]_E, of ～ 30 and 75 1/min). The [Vdot]_E exposure time product was similar for all protocols. Four exposures were delivered randomly with a Hans-Rudolph respiratory valve attached to a silicone facemask, with breathing route effected with and without noseclip. A 2 × 2 analysis of variance revealed no statistically significant differences (p < .05) across conditions in pulmonary function, exercise ventilatory pattern, or subjective symptoms responses. The fifth exposure, delivered via the same respiratory valve with mouthpiece, but without facemask, revealed significantly greater forced expiratory volume in 1 s (FEV_1.0) impairment than that observed for the respiratory valve, facemask with noseclip exposure (-20.4% and -15.9%, respectively). The latter suggests partial O₃ reactivity to the facemask and clean shaven facial surface of the subjects, although reduced oral scrubbing by mouthpiece-induced bypassing of the oral vestibule might account, in part, for this difference. Recent O₃ uptake evidence from another laboratory,¹⁵ however, supports our conclusion that breathing route during moderate and heavy continuous exercise does not affect acute physiologic responses to 0.40 ppm O₃.     

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.     

Retention of styrene following controlled exposure to constant and fluctuating air concentrations

An experiment was designed to determine whether the respiratory retention of sytrene vapor, as estimated from measurements of end-exhaled air, was the same during periods of both constant and fluctuating exposure. Six human subjects were exposed to styrene inside an experimental chamber. A computer-controlled system was used to generate time-varying air concentrations of styrene over 4–5 h in both multistep sequences of constant exposure (four subjects exposed to 15–99 ppm. of styrene in 100-min steps) and fluctuating patterns representative of occupational exposures (two subjects exposed to mean concentrations of styrene of 50 ppm). In the latter case, lognormally distributed exposures, which fit one of two first-order autoregressive models, were generated at intervals of 2.5 min. It was found that the concentration of styrene in end-exhaled air was reduced by about half if the subject inhaled one to three breaths of clean air prior to sampling. This suggests that significant amounts of styrene were desorbed from the lining of the lungs during the initial exhalation. The retention of styrene vapor during constant exposures was 0.935 and was independent of the level. During each of the two sets of fluctuating exposure the retention of sytrene was also constant and was independent of both the variance and the autocorrelation coefficient. However, the retention of styrene during fluctuating exposure (estimates ranged from 0.957 to 0.973) was significantly higher than that observed during the constant exposures. It is speculated that the difference in retention between the constant and the fluctuating exposure regimens is related to non-steady-state behavior of styrene in the richly perfused tissues, as suggested by Opdam and Smolders (1986) regarding tetrachloroethylene exposure.     

The pulmonary effects of ozone and nitrogen dioxide alone and combined in healthy and asthmatic adolescent subjects

Separate exposures to 0.12 ppm ozone (O3) or 0.18 ppm nitrogen dioxide (NO2) have not demonstrated consistent changes in pulmonary function in adolescent subjects. However, in polluted urban air, O3 and NO2 occur in combination. Therefore, this project was designed to investigate the pulmonary effects of combined O3 and NO2 exposures during intermittent exercise in adolescent subjects. Twelve healthy and twelve well-characterized asthmatic adolescent subjects were exposed randomly to clean air or 0.12 ppm O3 and 0.30 ppm NO2 alone or in combination during 60 minutes of intermittent moderate exercise (32.5 1/min). The inhalation exposures were carried out while the subjects breathed on a rubber mouthpiece with nose clips in place. The following pulmonary functional values were measured before and after exposure: peak flow, total respiratory resistance, maximal flow at 50 and 75 percent of expired vital capacity, forced expiratory volume in one second and forced vital capacity (FVC). Statistical significance of pulmonary function changes was tested by analysis of covariance for repeated measures. After exposure to 0.12 ppm O3 a significant decrease was seen in maximal flow at 50% of FVC in asthmatic subjects. After exposure to 0.30 ppm NO2 a significant decrease was seen in FVC also in the asthmatic subjects. One possible explanation for these changes is the multiple comparison effect. No significant changes in any parameters were seen in the asthmatic subjects after the combined O3-NO2 exposure or in the healthy subjects after any of the exposures.     

A dose-response study of healthy, heavily exercising men exposed to ozone at concentrations near the ambient air quality standard

Twenty-four healthy, well-conditioned young adult male volunteers, free of asthma or clinical respiratory allergies, were exposed to purified air containing ozone (O3) at 0.16, 0.14, 0.12, 0.10, 0.08, and 0.00 part per million (ppm). Exposures were separated by 2-week intervals, occurred in random order, and lasted 2 hours each. Temperature was 32 +/- 1 degree C and relative humidity was 38 +/- 3%, simulating Los Angeles area smog conditions. Subjects exercised 15 minutes of each half hour, attaining ventilation rates averaging 68 L/min (approximately 35 L/min per m2 body surface area). Lung function was measured pre-exposure and after 1 hr and 2 hr of exposure. Airway responsiveness to a cold-air challenge was measured immediately following the 2-hr exposure. Symptoms were recorded before, during, and for one-week periods following exposures. For the group as a whole, no meaningful untoward effects were found except for a mild typical respiratory irritant response after 2 hr exposure to 0.16 ppm O3. Two individual subjects showed possible responses at 0.14 ppm, and one of them also at 0.12 ppm. In comparison to some previous investigations, this study showed generally less response to O3. The comparative lack of response may relate to the favorable clinical status of the subjects, the pattern of exercise during exposure, or some other factor not yet identified.     

Transient decrease of exhaled nitric oxide after acute exposure to passive smoke in healthy subjects

Nitric oxide (NO) is produced and detected in the exhalate from the respiratory tract where it plays important regulatory functions. Exhaled nitric oxide (eNO) concentrations are reduced in active cigarette smokers between cigarettes and in nonsmoking subjects during short-term exposure to environmental tobacco smoke. In this study, the authors evaluated eNO before and after an acute exposure to environmental tobacco smoke in healthy, nonsmoking subjects (n = 12). Baseline eNO levels were measured by chemiluminescence at baseline (1 hr before exposure), shortly after the end of exposure, and 10 and 30 min after the end of exposure. Mean room air NO concentration increased from 3 ppb to 4 ppm (range, 560 ppb-8.5 ppm) during the exposure period. Carboxyhemoglobin levels were assessed before and after the exposure with spectrophotometry. All subjects had decreased eNO with exposure to environmental tobacco smoke (mean +/- standard error of the mean: 16.65 +/- 1.35 ppb to 13.86 +/- 1.33 ppb; p < .001). These concentrations remained significantly decreased at 10 min and recovered within 30 min. No modifications in airway resistance or increase in carboxyhemoglobin levels were observed. Exposure to environmental tobacco smoke transiently--but consistently--decreased eNO concentration in healthy, nonsmoking subjects, suggesting that second-hand smoke can directly affect NO in the airway environment.     

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)     

Ratios of N-(2,3,4-trihydroxybutyl) valine and N-(2-hydroxy-3-butenyl) valine formed hemoglobin adducts in female mice inhalation exposure with 1,3-butadiene

1,3-Butadiene (BD) is a known rodent and probable human carcinogen (IARC, group 2A) or 'known to be a human carcinogen' (Department of Health and Human Services, 2000). Exposure to BD can occur either via petrochemical products or through the general environment. Adducts can be used as biomarkers for biological monitoring of carcinogen exposure. This study investigated the hemoglobin adducts in blood after inhalation exposure to BD in ICR female mice for three weeks (5 h/day x 5 days/week). During the inhalation exposure, the body weights of mice were significantly lower from day 9 onward for the 500 ppm BD group and from day 4 onward for the 1000 ppm BD group. On the 1st, 2nd and 3rd weeks after inhalation exposure, the concentrations of HB Val adducts were 1.8, 3.7 and 6.2 pmol/mg globin for the 500 ppm BD group, and 5.7, 7.4 and 16.0 pmol/mg globin for the 1000 ppm BD group. The concentrations of THB Val adducts were 32.0, 42.0 and 55.0 pmol/mg globin for the 500 ppm BD group, and 67.8, 72.7 and 83.5 pmol/mg globin for the 1000 ppm BD group. Their defined ratios were higher at the earlier exposure period and at the lower concentration. They were 17.8, 11.4 and 8.87 for the 500 ppm BD group, and 11.9, 9.8 and 5.2 for the 1000 ppm BD group, on the 1st, 2nd and 3rd weeks after inhalation exposure. THB Val and HB Val adducts appear to be the important hemoglobin adducts for monitoring BD exposure, with the latter being a more predictable biomarker than the former.     

Lack of bronchomotor response to up to 3 ppm formaldehyde in subjects with asthma

A study was undertaken to determine whether exposure to concentrations of formaldehyde occasionally encountered in polluted indoor air would cause bronchoconstriction in subjects with mild asthma. In seven subjects the increase in specific airways resistance (SR_aw) caused by inhalation of 1 ppm formaldehyde for 10 min was compared with the response caused by inhalation of formaldehyde-free air. Also, the increase in SR_aw caused by inhalation of 1 and 3 ppm formaldehyde during moderate exercise for 10 min was compared with the response caused by inhalation of formaldehyde-free air during exercise for 10 min. Inhalation of formaldehyde at rest and during exercise did not cause a significant increase in SR_aw in the subjects. It is concluded that brief exposure to these concentrations of formaldehyde, even in association with moderate exercise, is unlikely by itself to cause significant bronchoconstriction in most subjects with mild asthma.     

Nitrogen dioxide exposure in vivo and human alveolar macrophage inactivation of influenza virus in vitro

Epidemiologic studies have reported an increased incidence of respiratory infections and illness in association with elevated indoor levels of nitrogen dioxide (NO2). Animal exposure studies have found that brief exposures to peak levels of NO2 produce greater morbidity than continuous lower level exposure. In order to examine the effect of NO2 inhalation on human alveolar macrophages, normal volunteers were exposed sequentially to air or NO2, by double-blind randomization, in an environmental chamber. Two exposure protocols with comparable concentration x time products were used: (a) continuous 0.60 ppm NO2 (n = 9), and (b) background 0.05 ppm NO2 with three 15-min peaks of 2.0 ppm (n = 15). Inhalation of NO2 caused no significant changes in pulmonary function or airway reactivity in either exposure protocol. Alveolar macrophages obtained by bronchoalveolar lavage 3 1/2 hr after exposure to continuous 0.60 ppm NO2 tended to inactivate influenza virus in vitro less effectively than cells collected after air exposure (1.96 vs 1.25 log10 plaque-forming units on Day 2 of incubation, P less than 0.07). Four of nine subjects accounted for the observed impairment in virus inactivation; cells from these four subjects demonstrated an increase in interleukin-1 (IL-1) production after NO2 vs air, whereas the five remaining subjects decreased IL-1 production after NO2. In contrast, intermittent peak exposure did not alter the rate of viral inactivation or IL-1 production. This methodology has the potential to identify pollutant effects on mechanisms of respiratory defense in humans.