A recommended occupational exposure limit for formaldehyde based on irritation.

In recent years, several regulatory agencies and professional societies have recommended an occupational exposure limit (OEL) for formaldehyde. This article presents the findings of a panel of experts, the Industrial Health Foundation panel, who were charged to identify an OEL that would prevent irritation. To accomplish this task, they critiqued approximately 150 scientific articles. Unlike many other chemicals, a large amount of data is available upon which to base a concentration-response relationship for human irritation. A mathematical model developed by Kane et al. (1979) for predicting safe levels of exposure to irritants based on animal data was also evaluated. The panel concluded that for most persons, eye irritation clearly due to formaldehyde does not occur until at least 1.0 ppm. Information from controlled studies involving volunteers indicated that moderate to severe eye, nose, and throat irritation does not occur for most persons until airborne concentrations exceed 2.0-3.0 ppm. The data indicated that below 1.0 ppm, if irritation occurs in some persons, the effects rapidly subside due to "accommodation." Based on the weight of evidence from published studies, the panel found that persons exposed to 0.3 ppm for 4-6 h in chamber studies generally reported eye irritation at a rate no different than that observed when persons were exposed to clean air. It was noted that at a concentration of 0.5 ppm (8-h TWA) eye irritation was not observed in the majority of workers (about 80%). Consequently, the panel recommended an OEL of 0.3 ppm as an 8-h time-weighted average (TWA) with a ceiling value (CV) of 1.0 ppm (a concentration not to be exceeded) to avoid irritation. The panel believes that the ACGIH TLV of 0.3 ppm as a ceiling value was unnecessarily restrictive and that this value may have been based on the TLV Committee's interpretation of the significance of studies involving self-reported responses at concentrations less than 0.5 ppm. The panel concluded that any occupational or environmental guideline for formaldehyde should be based primarily on controlled studies in humans, since nearly all other studies are compromised by the presence of other contaminants. The panel also concluded that if concentrations of formaldehyde are kept below 0.1 ppm in the indoor environment (where exposures might occur 24 h/d) this should prevent irritation in virtually all persons. The panel could not identify a group of persons who were hypersensitive, nor was there evidence that anyone could be sensitized (develop an allergy) following inhalation exposure to formaldehyde. The panel concluded that there was sufficient evidence to show that persons with asthma respond no differently than healthy individuals following exposure to concentrations up to 3.0 ppm. Although cancer risk was not a topic that received exhaustive evaluation, the panel agreed with other scientific groups who have concluded that the cancer risk of formaldehyde is negligible at airborne concentrations that do not produce chronic irritation.

Upper respiratory tract environmental tobacco smoke sensitivity.

Some patients report rhinitis symptoms after exposure to environmental tobacco smoke (ETS), but objective assessments of this response have been lacking. Furthermore, the mechanism of this response is unknown. We assessed the frequency of ETS-related symptoms by administering a questionnaire to 77 healthy nonsmoking young adults who were participating in an unrelated study. Of the subjects 34% (26 of 77) reported one or more rhinitis symptoms (congestion, rhinorrhea, or sneezing) following ETS exposure. We then exposed 10 historically ETS-sensitive (ETS-S) and 11 historically ETS-nonsensitive (ETS-NS) subjects to 15 min of clean air followed by 15 min of sidestream tobacco smoke (CO concentration of 45 parts per million). At selected time points during these procedures we recorded symptoms, posterior nasal resistance, and spirometry and performed nasal lavages. ETS-S but not ETS-NS subjects reported significant (p less than 0.01) increases in nasal congestion, headache, chest discomfort or tightness, and cough following exposure to sidestream tobacco smoke. Rhinorrhea symptoms were greater and more prolonged in ETS-S subjects compared to ETS-NS subjects. Significant (p less than 0.01) increases in perception of odor and in eye, nose, and throat irritation occurred in both study groups, but ETS-S subjects reported significantly more nose and throat irritation. No significant changes in posterior nasal resistance occurred in the ETS-NS group but a significant increase occurred in the ETS-S subjects, with the resistance rising from 3.8 +/- 0.5 cm H2O/L/s (mean +/- SE) preexposure to a peak of 8.0 +/- 2.7 cm H2O/L/s 20 min after completion of the smoke exposure (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of nitrogen dioxide exposure on susceptibility to influenza A virus infection in healthy adults.

The effect of NO2 exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, double-blind trial conducted in an environmentally controlled research chamber over 3 yr. Healthy, nonsmoking, young adult volunteers who were seronegative to influenza A/Korea/82 (H3N2) virus were randomly assigned to breathe either filtered clean air (control group) or NO2 for 2 h/day for 3 consecutive days. The NO2 concentrations were 2 ppm (Year 1), 3 ppm (Year 2), and 1 or 2 ppm (Year 3). Live, attenuated cold-adapted (ca) influenza A/Korea/82 reassortant virus was administered intranasally to all subjects immediately after the second exposure. Only one of the 152 volunteers had any symptoms; this person had a low grade fever. Pulmonary function measurements and nonspecific airway reactivity to methacholine were unchanged after NO2 exposure, virus infection, or both. Infection was determined by virus recovery, a fourfold or greater increase in serum or nasal wash influenza-specific antibody titers, or both. The infection rates of the groups were 12/21 (2 ppm NO2) versus 15/23 (clean air) in Year 1, 17/22 (3 ppm NO2) versus 15/21 (clean air) in Year 2, and 20/22 (2 ppm) and 20/22 (1 ppm) versus 15/21 (clean air) in Year 3. Each group exposed to 1 or 2 ppm NO2 in the last year became infected more often (91%) than did the control group (71%), but the differences were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute pulmonary response in healthy, nonsmoking adults to inhalation of formaldehyde and carbon.

Formaldehyde (HCHO) is a common chemical found in occupational and residential environments and has been suggested as a cause of asthmalike symptoms in some individuals. Clinical and animal studies suggest that HCHO adsorbed on respirable particles may elicit a greater pulmonary physiologic and inflammatory effect than gaseous HCHO alone. The purpose of this study was to determine if respirable carbon particles have a synergistic effect on the acute symptomatic and pulmonary physiologic response to HCHO inhalation. We randomly exposed 24 normal, nonsmoking, methacholine-nonreactive subjects to 2 h each of clean air, 3 ppm formaldehyde, 0.5 mg/m3 respirable activated carbon aerosol, and the combination of 3 ppm formaldehyde plus activated carbon aerosol. The subjects engaged in intermittent heavy bicycle exercise (VE = 57 l/min) for 15 min each half hour. Measures of response included symptom questionnaires, spirometry, body plethysmography, and postexposure serial peak flows. Formaldehyde exposure was associated with significant increases in reported eye irritation, nasal irritation, throat irritation, headache, chest discomfort, and odor. We observed synergistic increases in cough, but not in other irritant respiratory tract symptoms, with inhalation of formaldehyde and carbon. Small (less than 5%) synergistic decreases in FVC and FEV3 were also seen. We observed no HCHO effect on FEV1; however, we did observe small (less than 10%) significant decreases in FEF25-75% and SGaw which may be indicative of increased airway tone. Overall, our results demonstrated synergism, but the effect is small and its clinical significance is uncertain.

Susceptibility to virus infection with exposure to nitrogen dioxide.

The interaction between nitrogen dioxide (NO2) exposure and human susceptibility to respiratory virus infection was investigated in a placebo-controlled, randomized, blinded trial that was conducted in an environmentally controlled research chamber over a three-year period. Healthy, non-smoking volunteers, 18 to 35 years old, who were seronegative to influenza A/Korea/82 (H3N2) virus, were randomly assigned either to breathe filtered clean air (clean air group) or nitrogen dioxide (exposure group) for two hours a day for three consecutive days. The nitrogen dioxide concentrations were 2 ppm (Year 1), 3 ppm (Year 2), and 1 or 2 ppm (Year 3). Live, attenuated cold-adapted (ca) influenza A/Korea/82 reassortant virus was administered intranasally to all subjects after the second day of exposure. Only one of the 152 volunteers had any symptoms, and that subject had only a low-grade fever. No adverse changes in pulmonary function or nonspecific airway reactivity to methacholine were observed after 2 or 3 ppm nitrogen dioxide exposure, virus infection, or both. Infection was defined by virus recovery, a four-fold or greater increase in serum or nasal wash influenza-specific antibody titers, or both. The infection rates of the groups exposed to nitrogen dioxide and those breathing clean air were: 12/21 (2 ppm nitrogen dioxide) versus 15/23 (clean air) in Year 1; 17/22 (3 ppm nitrogen dioxide) versus 15/21 (clean air) in Year 2; and 20/22 (2 ppm nitrogen dioxide) and 20/22 (1 ppm nitrogen dioxide) versus 15/21 (clean air) in Year 3. Although the differences were not statistically significant, the groups exposed to 1 or 2 ppm nitrogen dioxide in the last year became infected more often (91 percent) than those breathing clean air (71 percent). The frequencies of infection in two of the four groups exposed to nitrogen dioxide were higher than the 56 to 73 percent infection rate observed in previous studies in healthy human volunteers with the same dose of ca-influenza A (H3N2) virus. Our findings suggest, but do not prove, that nitrogen dioxide alone may play a role in increasing the susceptibility of adults to respiratory virus infections.

Acute pulmonary response of asthmatics to 3.0 ppm formaldehyde.

Previous studies have failed to demonstrate bronchoconstriction in unselected asthmatics after brief (less than or equal to 1/2-h), controlled exposures to formaldehyde (HCHO). This study was designed to evaluate the acute pulmonary response to 3 ppm HCHO in nine nonsmoking asthmatic volunteers over a more relevant exposure duration (3 hrs). Pulmonary function, nonspecific airway reactivity and symptoms were assessed before and at intervals during the exposure. No significant changes in pulmonary function (FVC, FEV1, FEF25-27%, SGaw, or FRC) or airway reactivity were observed. There was a significant increase in nose/throat irritation at 30 min. (P less than 0.05) and in eye irritation at 60 min (P less than 0.05) and 180 min (P less than 0.01). These results suggest that individuals with asthma will not experience significant bronchoconstriction when exposed at rest to 3 ppm HCHO; however, most will experience eye and upper respiratory tract irritation.

Acute response to 3.0 ppm formaldehyde in exercising healthy nonsmokers and asthmatics.

Formaldehyde is an ubiquitous industrial and indoor air pollutant to which millions are daily exposed. Because of the paucity of scientific data concerning the inhalation toxicity of this compound in humans, we determined the symptoms and alterations in pulmonary function resulting from inhalation for 1 h of 3 parts per million formaldehyde in a controlled environmental chamber. The protocol consisted of randomized exposure of each subject to clean air or 3.0 ppm HCHO on 2 separate days. Twenty-two healthy normal subjects engaged in intermittent heavy exercise (VE = 65 L/min) and 16 asthmatic subjects performed intermittent moderate exercise (VE = 37 L/min). Symptoms and pulmonary function were assessed during the time course of exposure; nonspecific airway reactivity was assessed after exposure. Both groups exhibited similar, significant (p less than 0.01) increases in perceived odor, nose/throat irritation, and eye irritation throughout the exposure. The normal group had the following statistically significant (p less than 0.02) lower pulmonary functions after 55 min of exposure to formaldehyde as compared to clean air: 3.8% in FEV1, 2.6% in FVC, and 2.8% in FEV3. The asthmatic group showed no statistically significant decrements in pulmonary function. Five of 38 subjects studied had decrements in FEV1 greater than 10%. In conclusion, acute exposure to 3 ppm HCHO produced: consistent irritant symptoms in both normal and asthmatic subjects, small decreases in pulmonary function in normal subjects engaging in heavy exercise, and clinically significant responses (defined here as decrements in FEU1 greater than 10) in 13% of the study population.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary effects of sulfur dioxide and respirable carbon aerosol.

Four-hour individual and combined exposures to 1.0 ppm sulfur dioxide (SO2) and 0.5 mg/m3 (1.5 micron mass median diameter) activated carbon aerosol (ACA) were studied in 20 healthy nonsmoking subjects to determine if activated carbon as a "carrier" aerosol can augment the pulmonary response to SO2. Fifteen-minute exercise stints (VE = 35 liters/min) were performed at commencement and completion of each 4-hr period. Significant increases in nose or throat irritation occurred with the SO2 and SO2 + ACA exposures and in eye irritation with the SO2 + ACA exposure. Small, statistically significant decrements in spirometric function were observed following the first exercise (t = 17 min) for both the SO2 and SO2 plus ACA exposures; no significant changes were associated with the ACA exposure. Comparing function changes between the SO2 and the SO2 + ACA exposures demonstrated no statistically significant differences, thus a lack of SO2 response enhancement by the carbon aerosol. The determination that the activated carbon sorbed only 1% of the SO2 challenge concentration could explain the observed lack of SO2 response enhancement.

Acute pulmonary response to formaldehyde exposure in healthy nonsmokers.

The acute pulmonary response to three hours' exposure to 3 ppm formaldehyde (HCHO) during intermittent exercise was evaluated in nine healthy nonsmokers. The protocol consisted of clean air on the first day and HCHO on the second day with a 24-hour follow-up on the third day. Pulmonary function, nonspecific airway reactivity, and symptoms were assessed daily. Thirty minutes of HCHO exposure resulted in a 2% decrease in forced expiratory volume at one second (P less than .05) and a 7% decrease in forced midexpiratory flow rate 25%-75% (P less than .01); however, these effects were no longer present between 60 and 180 minutes. There was also a significant increase in odor (P less than .02), nose or throat irritation (P less than .01), and eye irritation (P less than .01) with exposure. No changes in pulmonary function or airway reactivity were observed 24 hours after exposure. Acute exposure to 3 ppm HCHO produced small, transient decreases in pulmonary function and mild to moderate eye and upper respiratory tract irritation.

Ozone response relationships in healthy nonsmokers.

Significant concentration responses were observed in FVC, FEV1, FEF25-75, SGaw, IC, and TLC in 20 healthy, nonsmoking volunteers exposed randomly to 0.00, 0.10, 0.15, 0.20, and 0.25 ppm O3. In addition, significant response changes for FVC, FEV1, and FEF25-75 were shown with time over the 2-h exposure. Intermittent, heavy exercise (VE, 68 L/min) lasting 14 min was employed every 30 min during exposure. Inspection of the concentration and time response curves suggests that the threshold for the group response is at or below 0.15 ppm O3. Six subjects experienced decreases greater than 5% in FEV1 or greater than 15% in SGaw at 0.15 ppm. This concentration is only slightly higher than the 1-h O3 National Ambient Air Quality Standard. A dose-related response was also seen for cough, nose and throat irritation, and chest discomfort. The work load, length of exposure, and individual sensitivity must be considered for establishing a safe O3 exposure level.

Pulmonary function adaptation to ozone in subjects with chronic bronchitis.

Twenty smokers with chronic bronchitis were exposed to 0.41 ppm ozone for 3 hr-day for 5 consecutive days and reexposed 4 days later to determine (1) if they are sensitive to ozone, (2) if they adapt, and (3) if the adaptation lasts longer than 4 days. There were significant decrements in forced vital capacity (FVC) and forced expiratory volume in 3 sec ( FEV3 ) on the first day of the 5-day repeated exposures and also on reexposure 4 days following cessation of the sequential exposures. Symptoms experienced were mild and did not predominate on any exposure days. These results suggest that individuals with chronic bronchitis adapt rapidly to ozone and lose this adaptive phenomenon within 4 days. The small decreases seen in FVC and FEV3 (less than or equal to 3%) appear to impose no more than minimal limitations on their daily activities.

Sulfur dioxide and ammonium sulfate effects on pulmonary function and bronchial reactivity in human subjects.

The effect of exposures to 1 ppm sulfur dioxide (SO2) and 500 micrograms/m3 respirable ammonium sulfate [(NH4)2SO4] was studied in 20 nonsmoking subjects to determine if a response can be measured at these atmospheric levels and if the response is additive or synergistic. Four-hour separate and combined exposures were employed. Each subject acted as his or her own control and performed two light-to-moderate exercise stints (612 kg-m/min) for 15 minutes on each day's confinement in the environmental chamber. Pulmonary function tests (body plethysmography and spirometry) and bronchial reactivity to methacholine were performed to assess the response of these exposures. No significant changes in pulmonary function or bronchial reactivity were observed in the individual exposures [(NH4)2SO4 or SO2], the combined exposure [(NH4)2SO4 and SO2], or 24 hours post-exposure. This study design and the observed results did not demonstrate any readily apparent risk to healthy subjects with these exposures. Since no significant changes were measured, it was not possible to conclude if these two pollutants in combination produce an additive or synergistic response.

Pulmonary function and bronchial reactivity in human subjects with exposure to ozone and respirable sulfuric acid aerosol.

The effect of 0.3 ppm ozone with a subsequent exposure to 100 micrograms/m3 sulfuric acid aerosol was studied in 12 nonsmoking subjects to determine if preexposure to ozone would sensitize them to sulfuric acid aerosol. Pulmonary function and bronchial reactivity measurements were made after single and sequential exposures to these pollutants. No significant changes in pulmonary function or bronchial reactivity to methacholine were observed. However, a decrease in bronchial reactivity approaching significance occurred after the 4-h exposure to 100 micrograms/m3, 0.13 microns sulfuric acid aerosol. We conclude that there are no readily apparent risks from sequential exposures of nonsmokers to low concentrations of ozone and sulfuric acid aerosol during light-to-moderate exercise.

Duration of pulmonary function adaptation to ozone in humans.

The duration of pulmonary function adaptation subsequent to cessation of a 5-day repeated ozone (O3) exposure was studied in 24 nonsmoking human subjects. A three-week, 3 hr/day study was conducted. The subjects received filtered air on Week 1 and 0.4 ppm O3 on Week 2. During Week 3, 13 subjects were re-exposed to O3 on Friday and 11 were re-exposed to O3 on Tuesday. Spirometric measurements (FVC and FEV1) and bronchial reactivity to methacholine showed adaptation within 2-3 days of the repeated daily exposures (Week 2). Although the duration of adaptation seen with bronchial reactivity appears longer than 7-days, the FVC and FEV1 clearly demonstrated complete loss of adaptation by 7 days, with a trend toward significance by 4 days. We conclude, therefore, the loss of ozone adaptation in pulmonary function is a gradual phenomenon lasting less than 7 days following cessation of repeated daily exposures.

Adaptation in human subjects to the effects of inhaled ozone after repeated exposure.

Single exposures to low concentrations of ozone (0.4 to 0.5 ppm) have resulted in decrements in forced vital capacity and specific airway conductance. To establish whether adaptation might occur with repeated exposure, 14 normal human subjects were exposed on 5 consecutive days to 0.4 ppm of ozone for 3 hours per day in an environmental chamber. Measurements of forced vital capacity and specific airway conductance obtained after exposure to ozone were compared to corresponding control values obtained during the previous week, when the same subjects breathed filtered air in the environmental chamber for 3 hours per day on 5 consecutive days at the same time of day. The forced vital capacity was significantly lower than the control value on the first 3 days of exposure to ozone, but there was no significant difference on the fourth and fifth days. Specific airway conductance was significantly lower than the control value on the first and second days of exposure to ozone; no significant difference was noted on the third, fourth, or final day. All subjects were symptomatic on the first and second days of exposure to ozone. Symptoms resolved thereafter, with only one subject remaining symptomatic on the final day of exposure to ozone.