Isocyanates in flexible polyurethane foams.
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Asthma↗
Biomedical subjects
R J Rando
Publications and source records attributed to R J Rando.
Cohort mortality study of North American industrial sand workers. I. Mortality from lung cancer, silicosis and other causes.
BACKGROUND: In 1997 a Working Group of the International Agency for Research on Cancer changed an earlier classification of crystalline silica as a human carcinogen from Group 2A to Group 1, though commenting that the carcinogenicity might vary with industrial circumstances and depend on additional factors affecting biological activity, including the distribution of its polymorphs. OBJECTIVE: We aimed to determine whether pure quartz exposure uncomplicated by the presence of other contaminating carcinogens, as experienced by workers in the production of high-grade industrial sand, was causally related to an increased risk of lung cancer. METHODS: A cohort of 2670 men employed before 1980 for 3 years or more in one of nine North American sand-producing plants and a large associated office complex was selected for study. Of the cohort, 2644 (99%) were traced through 1994, and certificated cause of death ascertained for 1025 (99%) of the 1039 men known to have died. Standardised mortality ratios (SMRs) were calculated for the main causes of death, using both US and state or provincial male mortality rates for reference. FINDINGS: The main analyses of deaths, 20 or more years after first employment against regional rates, gave the following SMRs: all causes 109, lung cancer 139, other malignancies 98, non-malignant respiratory disease 161, and nephritis/nephrosis 244. There were, in total, 37 deaths from silicosis or silico-tuberculosis, with one or more death at least in all nine production plants. Analyses failed to show any relation between lung cancer risk and duration of employment. The increased SMR for lung cancer was wholly due to high rates in four plants in two states, whereas no increase was found in the remainder of the cohort. CONCLUSION: In the absence of information on smoking histories and risk in relation to estimated exposure, the increased SMR for lung cancer (139), although statistically significant, cannot be attributed confidently to crystalline silica. An answer to the question of attributability must await the findings of the nested case-control study, in which level of exposure and smoking habits were ascertained for cases and matched controls. The strong indication in this cohort of excess mortality from non-malignant renal disease deserves further investigation.
Adult↗
Cohort mortality study of North American industrial sand workers. II. Case-referent analysis of lung cancer and silicosis deaths.
BACKGROUND: A cohort mortality study of 2670 men in nine North American industrial sand plants resulted in 83 deaths from lung cancer 20 or more years after hire (standardized mortality ratio 139) and 37 deaths from silicosis (including seven from silico-tuberculosis). The lung cancer excess was unrelated to duration of employment and not found in all plants. OBJECTIVES: The primary aim was to determine whether lung cancer risk among these employees was related to quantitative estimates of crystalline silica exposure, after allowance for cigarette smoking. A secondary aim was to do the same for silicosis mortality, partly as a means of validating the estimated levels of exposure. METHODS: A nested case-referent study was undertaken with cases matched with up to two controls on plant, age and date of first employment from men who survived the case. Exposures were estimated by linking work histories to a job-exposure matrix, undertaken separately. Cigarette smoking information was obtained from medical records and other sources, blind as to case-control status. Matched statistical analyses were conducted using conditional logistic regression. FINDINGS: Odds ratios for silicosis mortality were significantly related to cumulative silica exposures and tended to a relationship with category of average crystalline silica concentration, but inconsistently with length of employment. After accounting for a strong effect of cigarette smoking, odds ratios for lung cancer were related to cumulative crystalline silica exposure and to average silica concentration, but not to length of employment. CONCLUSION: These findings support a causal relationship between lung cancer and quartz exposure after allowance for cigarette smoking, in the absence of cristobalite or other known occupational carcinogens.
Aged↗
Cohort mortality study of North American industrial sand workers. III. Estimation of past and present exposures to respirable crystalline silica.
BACKGROUND: Lung cancer and silicosis mortality were examined longitudinally and by a case-referent analysis in a cohort of workers selected from the North American industrial sand industry. Date of hire in the case-referent sub-cohort extended as far back as the second decade of the twentieth century. OBJECTIVE: The aim of this study component was to develop estimates of average and cumulative exposure to respirable crystalline silica for the 342 selected cases and referents. METHODS: Process and dust control histories were developed for each plant, and quantitative exposure data obtained from each of them and from a trade organization. An algorithm was developed to convert historical exposures reported in particle count concentrations to modern measures of mass concentration of respirable crystalline silica. Personal exposures were adjusted for use of protective equipment based on frequency of use and type of protection. FINDINGS: Between 1974 and 1998, a total of 14249 exposure measurements had been taken using a cyclone and membrane filter and gave an overall geometric mean of 42 microg/m3. The only exposure data identified earlier were based on approximately 500 samples collected across the industry between 1947 and 1955 using the Greenburg-Smith impinger, with analysis by microscopy. These data were converted to modern measures using a factor of 1 mppcf = 276 microg/m3 respirable dust and then adjusting for percentage silica. In general, the highest exposures occurred in bagging and bulk-loading operations and the lowest in wet processing of sand. CONCLUSIONS: There has been a substantial decline in exposure levels in this industry over time. The decline was rapid between the 1940s and 1970s and current exposures are, on average, less than 50 microg/m3. The use of personal protective equipment was judged to have had little impact on exposure before the 1970s.
Air Pollutants, Occupational↗
Occupational exposure of nonsmoking nightclub musicians to environmental tobacco smoke.
This study assessed environmental tobacco smoke (ETS) exposures of nonsmoking musicians in nightclub environments using total suspended particulate (TSP), the ultraviolet absorbing fraction of TSP (UVPM), gaseous nicotine, saliva nicotine, saliva cotinine, and perceived smokiness as exposure/dose indicators. Measured exposures were as high or higher than those of other occupational groups studied. TSP ranged from 110 to 1714 micrograms/m3 (mean 502, SD 390 micrograms/m3). UVPM (mean 221, SD 95 micrograms/m3) was associated with gaseous and saliva nicotine concentrations. Paired-sample variation was much higher for TSP than for UVPM. Correlation of TSP with UVPM, gaseous nicotine, and saliva nicotine was poor. Paired-sample gaseous nicotine results were similar, with exposures of 28.0 to 50.0 micrograms/m3 (mean 37.1, SD 6.9 micrograms/m3), and were high compared with previous studies. These results suggested that nightclub musicians may be exposed to higher concentrations of ETS than some other occupational groups. Saliva nicotine results were consistent with those previously reported with regard to the range of values, large variation observed, and increase in saliva nicotine levels observable after only a few hours of exposure. Saliva nicotine results could not be correlated with other measures of exposure and did not appear to be a reliable biological indicator of absorbed dose. Saliva cotinine levels were comparable to other occupational groups studied, but were lower than previous findings for bartenders and waitresses. Levels ranged from 1.7 to 5.0 ng/mL (mean 3.4, SD 0.9 ng/mL), and increased with number of exposures during the workweek, but did not correlate with other ETS indicators.
Adult↗
Bronchoprovocation tests in the diagnosis of isocyanate-induced asthma.
Over the past 25 years, investigators have continued to improve on the approach to providing nonirritant exposures for the accurate diagnosis of isocyanate-induced asthma. Although the technology used in testing has become more sophisticated and may be fairly considered the domain of the bioengineer, the chemist, and the industrial hygienist, the requirements of the physician have remained unchanged. The physician must observe the level of exposure closely and monitor the worker's symptoms and lung function. Direct physician involvement in the testing procedure remains critical to the worker's safety and for the accurate diagnosis of isocyanate-induced asthma.
Asthma↗
A transient model of mass transfer and kinetics in a passive vapor sampler.
A transient model of vapor contaminant diffusion and homogeneous reaction in a two-compartment passive sampler was formulated. The mathematical analysis considered finite reaction kinetics, bulk air boundary-layer effects, and the solubility of the vapor contaminant in the liquid absorbing/reacting medium. The model was evaluated using experimentally measured Cl2 uptake rates in a series of samplers of different dimensions containing a 0.1% aqueous sulfamic acid solution in the absorbing medium chamber. The theory predicts accurately the effects of sampler diameter, stagnant air chamber path length, and sampler orientation with respect to the flowing air on Cl2 uptake, with an average error of less than 10%. Chlorine uptake in a 33-mm diameter sampler with a 10.8-mm path length was found to be essentially independent of wind direction and varied by approximately 23% for wind speeds ranging from 5.1 to 203 cm s-1 (10-400 ft min-1). Calculations show that the sampler is sensitive to wind speed partly because of the Cl2 hydrolysis reaction, which produces HOCl and drops the vapor phase concentration of chlorine to near zero at the stagnant air/absorbing medium chamber interface, regardless of the rate of homogeneous reaction between HOCl and sulfamate anions. If the solubility of the vapor contaminant in the liquid absorbing medium were to obey Henry's Law (no hydrolysis reaction) and the homogeneous trapping reaction were sufficiently slow, then model calculations show that contaminant uptake could be controlled solely by reaction kinetics, although the sampling rates would be lower than those observed and predicted for the Cl2 case.
Air Pollutants, Occupational↗
Dichotomous sampling of vapor and aerosol of methylene-bis-(phenylisocyanate) [MDI] with an annular diffusional denuder.
A dichotomous sampler was developed for speciation of airborne methylene-bis-(phenylisocyanate) (MDI) into vapor and aerosol fractions. The sampler consisted of an impactor inlet and two sections of annular diffusional denuder, in series with a glass fiber filter. The denuders and filter were coated with N-4-nitrobenzyl-N-1-propylamine for collection and derivatization of MDI followed by high performance liquid chromatography analysis. The sampler was evaluated in the laboratory with test atmospheres of MDI over a range of 24 to 355 micrograms/m3 at an average temperature of 26 degrees C. The total amounts of MDI collected by the dichotomous sampler were not significantly different from a reference sampler over the entire range of MDI concentrations. The first denuder collected MDI vapor with an average efficiency of 91.6 +/- 5.2%, in comparison to a theoretical efficiency of 94.1%. MDI existed solely in the vapor state up to approximately 75 micrograms/m3 and was collected on the denuders. Above this, MDI partitioned into vapor and aerosol, and the device efficiently separated the sample into the vapor fraction, found on the denuders, and the aerosol fraction, which penetrated to the filter. While this work was done with condensation aerosol, appropriate modification of the sampler inlet should allow use of the device for sampling atmospheres containing larger aerosols.
Aerosols↗
Cotton dust and across-shift change in FEV1 as predictors of annual change in FEV1.
In this report of a 5-yr longitudinal study of workers employed at six cotton textile mills, exposure and across-shift FEV1 change were evaluated as possible predictors of the annual change in FEV1 for yarn manufacturing workers. A total of 611 workers had three repeatable spirometric tests, over at least 3 yr, and at least one (average of three) across-shift test, while always working the same shift. The "same shift" criterion controlled for the effect of diurnal variation. Average exposure was determined from measures of lint-free elutriated cotton dust in combination with job histories. This study found a significant association between the acute and chronic effects of cotton dust exposure. Both exposure and across-shift change proved to be significant predictors of annual change, and excess annual declines in FEV1 were predicted even for exposures of 200 micrograms/m3 and across-shift drops in FEV1 of 200 ml. These results suggest that, to prevent dust-related chronic decline in lung function, current smokers should be excluded from yarn manufacturing work and exposures should be reduced below 200 micrograms/m3, to approximately 100 micrograms/m3.
Acute Disease↗
Passive cigarette smoke-challenge studies: increase in bronchial hyperreactivity.
Degree and duration of bronchial hyperreactivity (BHR) after environmental tobacco smoke (ETS) inhalation was assessed in 31 smoke-sensitive subjects with asthma who exhibited lower airway symptoms on ETS exposure (group I) and 39 smoke-sensitive subjects without asthma who manifested only upper airway symptoms on cigarette-smoke exposure (group II). Subjects were challenged with ETS for 4 hours in a static-test chamber. The atmosphere was continuously monitored for airborne particulate levels (800 cpm), total suspended particulates (1266 +/- 283 micrograms/m3), and airborne nicotine levels (226 +/- 49 micrograms/m2). Methacholine challenges were performed before and serially after cigarette-smoke exposure, and the provocative dose causing a 20% fall in FEV1 was determined. Five of the 31 smoke-sensitive subjects with asthma and none of the smoke-sensitive subjects without asthma reacted to cigarette-smoke challenge (greater than or equal to 20% fall from baseline FEV1). Thirty-two percent (10/31) of the subjects with asthma demonstrated increased BHR at 6 hours, 29% (9/31) at 24 hours, and 13% (4/31) up to day 14 after ETS challenge. Of the subjects without asthma, 18% (7/39) demonstrated increased BHR at 6 hours, 10% (4/39) at 24 hours, and 8% (3/39) at 3 weeks. These studies demonstrated an increase in BHR after cigarette-smoke challenge in a number of study subjects (although they were clinically asymptomatic) and suggest that prolonged subclinical airway inflammation can occur in the absence of demonstrable change in airway caliber on exposure to ETS.
Adolescent↗
Assessment of multiple markers of environmental tobacco smoke (ETS) in controlled, steady-state atmospheres in a dynamic test chamber.
Controlled test atmospheres of sidestream and mixed mainstream/sidestream tobacco smoke were produced in a dynamic test chamber of 16.9 m3 volume. University of Kentucky 1R4F research cigarettes were automatically smoked by a Borgwaldt smoking machine. Different target levels of smoke were attained by varying the number of cigarettes being smoked (one or two cigarettes continuously) and dilution airflow through the chamber (1.6 to 7.4 m3/min). For each level, a "smoke index" was calculated as the number of cigarettes being smoked divided by the dilution flow rate. Ultraviolet light-absorbing particulate matter (UVPM); aerosol counts and size distribution; and concentrations of CO, NO2, NH3, formaldehyde, acetaldehyde, acrolein, and nicotine were determined in the test atmospheres and background dilution air. Parameters exhibiting the highest correlations with smoke index (r2 > 0.98) included UVPM, aerosol counts, formaldehyde, and acetaldehyde. The other parameters were also highly correlated with r2 > 0.9 in each case. Differences in concentration for sidestream and mixed mainstream/sidestream atmospheres were statistically significant for acetaldehyde, formaldehyde, and CO; in each case the level was higher in mixed mainstream/sidestream smoke. These results demonstrate the utility of employing multiple markers for assessment of environmental tobacco smoke levels and for dichotomizing the contributions of sidestream and mainstream smoke to these levels. The generation factors developed in this work can be used for estimating required ventilation rates for attainment of target air quality conditions in smoking rooms.
Air Pollutants↗
Abnormal lung function in polyurethane foam producers. Weak relationship to toluene diisocyanate exposures.
Exposures to toluene diisocyanate (TDI) were studied for effects on respiratory health of workers in two plants manufacturing polyurethane foams. Intensive personal monitoring was used to characterize job exposures. Of 4,845 12-min personal samples, 9% exceeded 5 ppb and 1% exceeded 20 ppb. Initial questionnaire and spirometry were obtained in 386 workers (88.7% of target population). Current smoking was associated with lower mean FEV1 and FEF25-75, but percent predicted (% pred) means were normal in all smoking categories. Multiple regression showed significant adverse effects of cumulative TDI exposure on initial level of FVC and FEV1 of current smokers, and an effect at borderline significance (p less than 0.063) on FEF25-75 over all smoking categories. Logistic regression showed that chronic bronchitis was more prevalent among those with higher cumulative exposures, after controlling for smoking, age, and sex. Methacholine (MCh) reactivity was associated with reduced airway function, -8.5% pred for FEV1 and -20.0% pred for FEF25-75. In 227 with adequate follow-up, the slopes of annual change were abnormal, for example, FEV1 of -67 ml/yr in current and -53 ml/yr in never smokers. Men had worse FEV1 declines than did women, -71 ml/yr versus -43 ml/yr. TDI exposure, lifetime or concurrent, had no significant effect on slopes, despite its demonstrated effects on initial level of lung function and on prevalence of chronic bronchitis.
Adult↗
Asthmatic responses to passive cigarette smoke: persistence of reactivity and effect of medications.
The present study assessed the persistence of cigarette-smoke reactivity and the effects of drug pretreatment on bronchial responsiveness to environmental tobacco smoke (ETS). Two groups of subjects were chosen for the study. Group I consisted of 15 atopic smoke-sensitive subjects with asthma, six of whom were defined "reactors" and nine "nonreactors" to ETS challenge. Group II consisted of 15 atopic subjects without asthma and with documented upper respiratory tract symptoms on exposure to ETS. All subjects were challenged for 2 to 6 hours with mechanically generated ETS in a static inhalation chamber. Five/six subjects in group I, who were previously demonstrated as reactors 24 months earlier, remained reactive within 1 to 2 hours of continuous ETS exposure. Pretreatment with albuterol, cromolyn, and a combination of albuterol and cromolyn 30 minutes before ETS exposure significantly diminished airway reactivity to ETS. All nine previous nonreactors in group I remained nonreactive despite rechallenge with ETS for up to 6 hours. Group II subjects challenged under identical conditions did not reveal a significant decline in FEV1 on challenge with ETS. These studies demonstrate the persistence of ETS reactivity during a 2-year period. Although cromolyn sodium and/or albuterol can protect against reactivity, mechanisms of ETS-induced airway reactivity remain unknown.
Adult↗
Exposure-related declines in the lung function of cotton textile workers. Relationship to current workplace standards.
To evaluate the effectiveness of the current workplace standards in preventing chronic health effects from cotton dust exposure, a 5-yr longitudinal study of a large multimill population of cotton textile and synthetic process workers, employed at a major U.S. textile company, was conducted. To control for and assess the effect of type of work area on annual change in lung function, we limited the analysis to those 1,817 subjects who, throughout their textile work history at the company, worked exclusively in cotton yarn manufacturing or slashing and weaving, or in synthetic textile mills. The expected effect of smoking on average annual change in lung function was demonstrated for both cotton and synthetic workers. Despite lower overall dust exposure, cotton yarn workers exhibited steeper annual declines in lung function than did workers in slashing and weaving; this difference persisted within each smoking category, indicating a dust potency effect. There were mill differences in annual change in lung function among cotton workers, potentially masking an exposure effect. A smoking-work area interaction persisted after adjusting for mill differences, with the largest annual declines observed in cotton yarn workers who smoke. A significant dose-response relationship was seen in cotton yarn manufacturing between annual declines in FEV1, FVC, and FEF25-75 and average exposure by mill, and the larger declines were found in mills using the highest percentage and lowest grade of cotton. Synthetic textile workers had larger declines than did cotton textile workers, which were not explained by smoking or duration of employment. Unrecognized and unmeasured causative exposures or selection bias could explain this result.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Persistence of toluene diisocyanate-induced asthma despite negligible workplace exposures.
Six polyurethane foam workers were shown to have TDI-induced asthma by specific inhalation challenge testing. All remained in the workplace in jobs with minimal TDI exposures. Mean and time-weighted average exposure concentration for the asthmatic group was 0.64 +/- 0.46 ppb, less than 5 percent of the permissible exposure limit and significantly less (p less than 0.01) than the mean TWA exposures occurring in the foam line and the finishing workers. Serial evaluation of the respiratory health of these six showed all persisted with respiratory symptoms, none had improvement in bronchial hyperresponsiveness to methacholine, and three had a greater than 15 percent decline in FEV1 on one of the days of spirometric testing over the five-year period from 1982 to 1986. Although we could not have predicted the outcome of asthma had these workers left the workplace and ceased isocyanate exposure entirely, occupational asthma persisted despite negligible ongoing TDI exposures.
Asthma↗
A diffusive sampler for personal monitoring of toluene diisocyanate (TDI) exposure; Part I: Design of the dosimeter.
A passive dosimeter for monitoring occupational exposure to toluene diisocyanate (TDI) was developed. The device is constructed from a 37-mm aerosol cassette. The collection medium used in the dosimeter is 0.5% sulfuric acid (H2SO4). Membranes of both the permeation and diffusion types were evaluated for use in the dosimeter. Microporous Teflon diffusion membranes exhibited superior performance in terms of surface effects and residual TDI and were chosen for use. Collected TDI is determined as toluenediamine by either colorimetry using a modification of the Marcali technique or fluorometry using fluorescamine reagent. A significant dependence on wind speed was minimized by use of a second microporous membrane as a wind screen. The mass transfer rate of TDI was found to be approximately 0.0152 micrograms/ppb.hr and was equivalent for the 2,4 and 2,6 isomers of TDI.
Air Pollutants, Occupational↗
A diffusive sampler for personal monitoring of toluene diisocyanate (TDI) exposure; Part II: Laboratory and field evaluation of the dosimeter.
A passive monitor for TDI which utilizes microporous Teflon diffusion membranes and a 0.5% sulfuric acid (H2SO4) absorbing medium was evaluated. The collection rate of TDI is proportional to exposure dose from 10 to at least 300 ppb.hr, and response is equivalent for 2,4- and 2,6-TDI. Collection rate is independent of humidity and normal atmospheric pressure variations, while temperature causes a decrease of 1.0% per degree centigrade. Negative interference caused by ambient nitrogen dioxide (NO2) is eliminated by addition of sulfamic acid (HSO3 NH2) to the collecting medium. N-ethylmorpholine is a positive interferent. Field testing of the sampler against a reference impinger technique indicated a positive bias when TDI is aerosolized.
Air Pollutants, Occupational↗
Role of inhalation challenge testing in the diagnosis of isocyanate-induced asthma.
Results of isocyanate challenge tests performed on 63 workers referred with a diagnosis of probable isocyanate asthma between 1974 and 1988 were reviewed. Thirty (48 percent) had an acute episode of asthma with a greater than 20 percent decline in FEV1 following subirritant exposure to isocyanates. No difference in the frequency or type of respiratory complaints between isocyanate reactors and nonreactors was found. No differences in lung function results were present when comparing smoking and ex-smoking reactors and nonreactors. In never-smokers with complaints consistent with isocyanate-induced asthma, the presence of obstructive lung disease increased the likelihood that isocyanate-induced asthma was present. Bronchial responsiveness to methacholine occurred in nearly all isocyanate reactors but predicted isocyanate-induced asthma in only 68 percent of the workers. In nearly all cases of challenge-confirmed toluene diisocyanate (TDI)-induced asthma, a 15-min exposure to 20 ppb of the commercial TDI mixture (80:20 2,4:2,6) provoked asthma. Conversely, in the absence of an asthmatic response following exposure to this dose for this duration, a second exposure at this concentration for a longer time would be reasonable to confirm the absence of isocyanate-induced asthma. Among workers employed in the production of polyurethane foam and confirmed to have TDI-induced asthma by inhalation challenge to the different TDI isomers, there appeared to be increased airway reactivity to the 2,6 isomer. This may have relevance to the frequency and intensity of respiratory symptoms that workers with TDI-induced asthma develop in differing industrial settings.
Adult↗