N-acetyltransferase 1 polymorphism increases cotinine levels in Caucasian children exposed to secondhand smoke: the CCAAPS birth cohort.

Cotinine is a proxy for secondhand smoke (SHS) exposure. Genetic variation along nicotine and cotinine metabolic pathways may alter the internal cotinine dose, leading to misinterpretations of exposure-health outcome associations. Caucasian children with available SHS exposure and hair cotinine data were genotyped for metabolism-related genes. SHS-exposed children had 2.4-fold higher hair cotinine (0.14±0.22 ng mg(-1)) than unexposed children (0.06±0.05 ng mg(-1), P<0.001). SHS-exposed children carrying the NAT1 minor allele had twofold higher hair cotinine (0.18 ng mg(-1) for heterozygotes and 0.17 ng mg(-1) for homozygotes) compared with major allele homozygotes (0.09 ng mg(-1), P=0.0009), even after adjustment for SHS dose. These findings support that NAT1 has a role in the metabolic pathway of nicotine/cotinine and/or their metabolites. The increased cotinine levels observed for those carrying the minor allele may lead to SHS exposure misclassification in studies utilizing cotinine as a biomarker. Additional studies are required to identify functional single-nucleotide polymorphism(s) (SNP(s)) in NAT1 and elucidate the biological consequences of the mutation(s).

Airway obstruction related to diacetyl exposure at microwave popcorn production facilities.

Obstructive lung diseases including bronchiolitis obliterans have been reported among microwave popcorn production employees. Butter flavourings including diacetyl have been associated with these findings. The present study was initiated at four microwave popcorn production plants to determine if exposure to diacetyl was associated with decrements in pulmonary function. Comprehensive diacetyl exposure assessment was undertaken for all job tasks. Spirometry was conducted for 765 full-time employees between 2005 and 2006. Outcomes included decrement in forced expiratory volume in one second (FEV(1)) % predicted, airway obstruction and persistent decline in FEV(1). Inclusion in the high-exposure group (mixers) prior to respirator use was associated with a significantly decreased FEV(1) % pred in non-Asian and Asian males at -6.1 and -11.8% pred, respectively, and an eight-fold increased risk for airway obstruction. Cumulative diacetyl exposure >or=0.8 ppm-yr caused similar results. No significant impact was seen in nonmixers or between current diacetyl exposure and persistent decline in FEV(1). Unprotected exposure as a mixer to butter flavouring including diacetyl resulted in decrements in FEV(1) (% pred) and increased airway obstruction. Control of employee exposure to butter flavouring additives is warranted in regard to both short-term peak and 8-h workday exposure.

Electron microscopy study of refractory ceramic fibers.

In epidemiological studies designed to identify potential health risks of exposures to synthetic vitreous fibers, the characterization of airborne fiber dimensions may be essential for assessing mechanisms of fiber toxicity. Toward this end, air sampling was conducted as part of an industry-wide study of workers potentially exposed to airborne fibrous dusts during the manufacture of refractory ceramic fibers (RCF) and RCF products. Analyses of a subset of samples obtained on the sample filter as well as on the conductive sampling cowl were performed using both scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to characterize dimensions of airborne fibers. Comparison was made of bivariate fiber size distributions (length and diameter) from air samples analyzed by SEM and by TEM techniques. Results of the analyses indicate that RCF size distributions include fibers small enough in diameter (< 0.25 microm) to be unresolved by SEM. However, longer fibers (> 60 microm) may go undetected by TEM, as evidenced by the proportion of fibers in this category for TEM and SEM analyses (1% and 5%, respectively). Limitations of the microscopic techniques and differences in fiber-sizing rules for each method are believed to have contributed to the variation among fiber-sizing results. It was concluded from these data that further attempts to characterize RCF exposure in manufacturing and related operations should include analysis by TEM and SEM, since the smallest diameter fibers are not resolved with SEM and the fibers of longer length are not sized by TEM.

Reliability and validity of chest radiograph surveillance programs.

STUDY OBJECTIVES: Due to the lack of consensus in the literature in the use of posteroanterior (PA) vs PA with right and left oblique views as the optimum radiograph surveillance methodology to investigate pleural changes, a study was undertaken to evaluate the reliability, sensitivity, and specificity of these two approaches. DESIGN: Three experienced radiologist B readers used the 1980 International Labor Office classification system for pneumoconiosis to independently read chest radiographs of workers with individual identifiers masked. All radiographs were read first as a PA view only. Unknown to the B readers, each subject's PA was then matched to his or her corresponding right and left oblique views (film triad) and re-read several weeks later. SETTING AND PARTICIPANTS: The respiratory health of 652 workers exposed to refractory ceramic fiber was assessed as part of cross-sectional and longitudinal surveillance programs. MEASUREMENTS AND RESULTS: kappa Statistics for interreader and intrareader reliability between the PA view and film triad methods were calculated. Sensitivity, specificity, and positive predictive value were assessed by comparing the initial cross-sectional study to the longitudinal study. The film triad method had considerably higher interreader reliability (kappa = 0.59) compared to the PA-only method (kappa = 0.44). Results from the initial cross-sectional study were then compared to findings evaluated longitudinally. The film triad again was superior, demonstrating a positive predictive value of 73.7% compared to only 47.8% for the PA method. CONCLUSIONS: It is our recommendation that the film triad method be used in surveillance studies where both parenchymal and pleural changes are anticipated.

What is the potential measurement error in occupational exposure studies?

This paper demonstrates statistical methods that estimate measurement error from available industrial hygiene data. Errors in measuring a continuous exposure variable may arise when all individuals in a work area are assigned the same exposure. An example is when the mean of exposure measurements obtained on a sample of individuals is assigned to all workers with similar jobs. This may lead to inaccurate point and interval estimates in exposure-response modeling. A method of simulating the distribution of true (i.e., unobserved) individual exposures is described in order to estimate the mean and variance of measurement error. The minimum variance unbiased estimator approximates the mean of lognormally distributed exposure measurements. The distribution of true individual exposures is approximated by the distribution of simulated estimates of mean exposure. The methodology is illustrated by exposure data from work areas manufacturing refractory ceramic fiber (RCF) and RCF products. Results show that exposure is slightly underestimated in work areas with between 25 and 113 exposure measurements; measurement error variance averages about 1.3% of the total variance.

Potential significance of airborne fiber dimensions measured in the U.S. refractory ceramic fiber manufacturing industry.

BACKGROUND: To determine dimensions of airborne fibers in the U.S. refractory ceramic fiber (RCF) manufacturing industry, fibers collected through personal air sampling for employees at RCF manufacturing and processing operations have been measured. METHODS: Data were derived from transmission electron microscopy analyses of 118 air samples collected over a 20-year period. RESULTS: Characteristics of sized fibers include: diameter measurements of <60; 0.19 to 1.0 micron, m of which 75% are less than 0.6 micron and length ranging from < 0.6 to > 20 micron, with 68% of fibers between 2.4 and 20 micron. CONCLUSIONS: Exposures in RCF manufacturing include airborne fibers with dimensions (diameter < 0.1-0.4 micron, length < 10 micron) historically associated with biological effects in pleural tissues. Air sampling data and a review of studies relating fiber size to pleural effects in animals and humans support the belief that information on fiber dimensions is essential for studies with synthetic vitreous fibers.

Weight change and lung function: implications for workplace surveillance studies.

This study evaluated the relationship between weight change and longitudinal measurement of lung function among 361 men providing at least five pulmonary function tests. The men in this study were participants in a workplace pulmonary surveillance program for subjects with exposure to refractory ceramic fibers (RCFs). Occupational and environmental studies are generally designed to evaluate factors suspected of causing excess decline in lung function. Failure to adequately account for all significant factors may lead to erroneous conclusions regarding change in lung function. This study utilized two different statistical models to evaluate longitudinal changes in a cohort of RCF workers. What was unique to this study was the modeling of longitudinally measured initial weight, weight change, and longitudinal exposure before and during the period of observation. Results showed a strong relationship between weight gain and longitudinal loss in lung function that approximated forced vital capacity declines of 16 mL for every kilogram of weight gain per year in both models. This value is comparable or greater in magnitude and significance to other factors known to be inversely related to lung function, such as age and pack-years smoking to time of initial testing. In conclusion, weight gain was found to have a significant impact on longitudinal change in lung function. Therefore, weight gain becomes a very important variable that requires consideration whenever longitudinal studies of pulmonary function are conducted.

Male reproductive effects of solvent and fuel exposure during aircraft maintenance.

Few studies have addressed the effects of mixed, low-level exposures to complex mixtures on a man's reproductive potential. In this prospective study, each subject was evaluated before first exposure and at 15 and 30 weeks after exposures had begun. A total of 50 men working on aircraft maintenance at an Air Force installation were included in the study. In addition, eight unexposed men were concurrently sampled. Industrial hygiene (IH) sampling and expired breath samples were collected for jet fuel as measured by total napthas, benzene--a component of jet fuel, 1,1,1-trichloroethane, methyl ethyl ketone, xylenes, toluene, and methylene chloride. Sperm production, structure, and function (sperm concentration, sperm motion, viability, morphology, morphometrics, and stability of sperm chromatin) were evaluated. Exposures were low. All mean IH measures were below 6 ppm, which is less than 10% of the Occupational Safety and Health Administration standard for all chemicals except benzene. Sheet metal workers had the highest mean breath levels for both total solvents (24 ppb) and fuels (28.3 ppb). For most sperm measures, mean values remained in the normal range throughout the 30 weeks of exposure. When jobs were analyzed by exposure groups, some adverse changes were observed. The paint shop group had a significant decline in motility of 19.5% at 30 weeks. Internal dose measures, however, did not show a significant association with spermatogenic changes.

Comparison of internal dose measures of solvents in breath, blood and urine and genotoxic changes in aircraft maintenance personnel.

Solvents and fuels are in widespread use both in civilian and military populations. 1,1,1-trichloroethane (TCA), xylene, toluene, methyl ethyl ketone (MEK) and methylene chloride are found in a variety of compounds including degreasing agents, paints, coatings, pesticides and paint strippers. Toluene and xylene are also found in fuels, which are complex mixtures of hundreds of agents. The purpose of this investigation was twofold. The first was to determine the optimum medium to measure internal dose of solvents comparing blood, urine and breath. The second was to determine if low level exposures were associated with genotoxic changes after a short-term exposure of fifteen or thirty weeks. To accomplish the first goal a pilot study was initiated involving eight volunteers who worked in aircraft maintenance including sheet metal, painting and assembly mechanic jobs. Industrial hygiene measurements were evaluated over 30 working days. Breath, blood and a 24-hour urine sample were collected twice to compare internal dose parameters. To achieve the second goal, 58 newly hired subjects were monitored prior to exposure and over 30 weeks to determine if there were genotoxic changes as a result of solvent and/or fuel exposure as measured by sister chromatid exchanges (SCEs) and micronuclei (MN). Exposure groups included workers involved in sheet metal (fuel cell) activities, painting, fueling operations and flight line. Results of the pilot study demonstrated that industrial hygiene air samples and internal breath measures taken on the same day were highly correlated for measuring TCA (r = 0.93) and toluene (r = 0.90) but was not as well correlated for the other compounds. Breath measures were more sensitive for measuring low level exposure than were either analytes in blood or 24-hour urine samples; these latter two measures were usually below the limit of detection. A small but statistically significant increase in the frequency of SCEs occurred after 30 weeks of exposure for sheet metal workers (p = 0.003) and for painters (p = 0.05). The MN frequency in the sheet metal workers initially showed a significant increase by 15 weeks, but by 30 weeks had decreased. Chance occurrence of exposures to other occupational or non-occupational agents can not be eliminated as a cause of the genotoxic results since between 58 and 93 total analytes could be found in the breath of some aircraft maintenance personnel.

An industry-wide pulmonary study of men and women manufacturing refractory ceramic fibers.

An industry-wide pulmonary morbidity study was undertaken to evaluate the respiratory health of employees manufacturing refractory ceramic fibers at five US sites between 1987 and 1989. Refractory ceramic fibers are man-made vitreous fibers used for high temperature insulation. Of the 753 eligible current employees, 742 provided occupational histories and also completed the American Thoracic Society respiratory symptom questionnaire; 736 also performed pulmonary function tests. Exposure to refractory ceramic fibers was characterized by classifying workers as production or nonproduction employees and calculating the duration of time spent in production employment. The risk of working in the production of refractory ceramic fibers and having one or more respiratory symptoms was estimated by adjusted odds ratios and found to be 2.9 (95 percent confidence interval 1.4-6.2) for men and 2.4 (95 percent confidence interval 1.1-5.3) for women. The effect of exposure to refractory ceramic fibers on forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), the ratio of the two (FEV1/FVC), and forced expiratory flow (liters/second) between 25 percent and 75 percent of the FVC curve (FEF(25-75)) was evaluated by multiple regression analysis using transformed values adjusted for height, by dividing by the square of each individual's height. For men, there was a significant decline in FVC for current and past smokers of 165.4 ml (p < 0.01) and 155.5 ml (p = 0.04), respectively, per 10 years of work in the production of refractory ceramic fibers. For FEV1, the decline was significant (p < 0.01) only for current smokers at 134.9 ml. For women, the decline was greater and significant for FVC among nonsmokers, who showed a decrease of 350.3 ml (p = 0.05) per 10 years of employment in the production of refractory ceramic fibers. These findings indicate that there may be important sex differences in response to occupational and/or environmental exposure.

Longitudinal estimates of pulmonary function in refractory ceramic fiber manufacturing workers.

Refractory ceramic fibers (RCF) are man-made vitreous fibers (MMVF) used in high-temperature industrial applications. Between 1987 and 1994, a prospective study evaluated pulmonary function of 361 male workers currently employed in RCF manufacturing and related operations for plausibility of a causal relationship between RCF exposure and pulmonary function changes. Workers included in the analysis provided at least five pulmonary function tests. The exposure-response relationship was modeled with two exposure variables: years in a production job, and cumulative fiber exposure (fiber-mo/cc). Comparison groups were nonproduction workers and workers with up to 15 fiber-mo/cc cumulative exposure. A statistically significant decrease in FVC was demonstrated among workers employed in production jobs more than 7 yr prior to initial test. A similar but nonstatistically significant result was demonstrated for FVC in workers with greater than 60 fiber-mo/cc cumulative exposure prior to initial pulmonary function test. Similar but nonstatistically significant results were obtained for FEV1. These findings, which primarily reflect workers employed before 1980, did not persist with analysis of follow-up production years and accumulated RCF exposure from initial pulmonary function test. Since longitudinal analyses are sensitive to influences that continue to affect annual decline during the study period, lower RCF exposure levels since the 1980s may be responsible for eliminating any further effect on pulmonary function.

Variability in the classification of radiographs using the 1980 International Labor Organization Classification for Pneumoconioses.

This study describes the extent of agreement in classification of chest radiographs using the International Labor Organization (ILO) classification among six readers from the United States and Canada. A set of 119 radiographs was created and read by three Canadian and three US readers. The two ratings of interest were profusion (scored from 0/- to 3/+) and pleural abnormalities consistent with pneumoconiosis (scored with the ILO system, then collapsed into a yes/no). We used a number of approaches to evaluate interreader agreement on profusion and pleural changes, determining concordance, observed agreement, kappa statistic, and a new measure to approximate sensitivity and specificity. This study found that five of six readers had good fair to good agreement for pleural findings and for profusion as a dichotomous variable (> or = 1/0 vs < or = 0/1) using the kappa statistic, while a sixth reader had poor agreement. We found that concordance, expressed as percent agreement, was higher for normal radiographs than for ones that showed disease, and describe the use of the kappa statistic to control for this finding. This analysis adds to the existing literature with the use of the kappa statistic, and by presenting a new measure for "underreading" and "overreading" tendencies.

A comparison of exposures to refractory ceramic fibres over multiple work shifts.

As part of an ongoing, industry-wide study in the manufacture of refractory ceramic fibres (RCF), time weighted average (TWA) exposures have been collected at five facilities according to a standardised protocol. Work activities were grouped into dust zones (DZs). Persons to be sampled were randomly selected according to a protocol designed to assure that at least one sample was collected annually from each DZ; each work shift is also sampled at least annually. TWA exposures calculated over a sampling period of at least 360 min were included in the data set. DZs were combined into one of three groups (DZGs): fibre production; vacuum processes; other. The data were analysed to identify any differences by DZG between airborne fibre exposures, by the shift worked at each facility, and across all facilities. There were no statistically significant shift-related differences detected between airborne fibre exposures across the five RCF facilities when analysed as a group. Within four of the facilities, no shift-related differences were detected between airborne fibre exposures; however, at one facility, first and third shift exposures were statistically different. No documentation related to job activities was found to account for the observation. The data generally support the use of a single exposure estimate for each DZG in each of these facilities, regardless of shift worked. Researchers reconstructing exposure and not able to determine the shift worked by study subjects may find these results useful, but are cautioned that substantial differences in exposure across shifts may exist in other types of manufacturing.

Genotoxic changes after low-level solvent and fuel exposure on aircraft maintenance personnel.

Individuals may be exposed to solvent mixtures and fuel either at work or home, through air, water and food contamination. Few studies have addressed the genotoxic effects of mixed, low-level exposure to fuel and solvent. This was an optimally designed study where each subject was sampled prior to exposure and after 15 and 30 weeks while exposed, in a repeated measures design with each subject serving as his own control. Fifty men aged between 18 and 50, working on aircraft equipment operation and maintenance at a military installation were included. Eight unexposed men were concurrently sampled. Sister-chromatid exchanges (SCE) and micronuclei (MN) frequency were measured in conjunction with air sampling and expired breath analysis for jet fuel (JP-4), 1,1,1-trichloroethane, methyl ethyl ketone, xylenes, toluene and methylene chloride. Exposure levels measured by industrial hygiene were very low (all means <6 p.p.m.), <10% of the OSHA standard. Expired breath levels were also low, <25 p.p.b. A small but statistically significant increase in the frequency of SCE occurred after 30 weeks of exposure for sheet metal workers (P = 0.003) and for painters (P = 0.05). The MN frequency in the sheet metal workers initially showed a statistically significant increase, but by 30 weeks had decreased. Cigarette smoking, alcohol and caffeine use were not associated with changes from baseline for either MN or SCE. Smokers, however, had significantly higher values of SCEs at baseline than did nonsmokers. In summary, these findings suggest that small increases in SCEs in particular, may serve as a sensitive biologic indicator of low level hydrocarbon exposure in as much as statistically significant changes occurred in the highest exposed groups but not in the low or no exposure groups. Chance occurrence or exposures to other occupational or non-occupational agents cannot be eliminated as a cause of the study findings.

An early study of pulmonary asbestosis among manufacturing workers: original data and reconstruction of the 1932 cohort.

A cross-sectional prevalence survey of asbestosis, including all 1,140 employees of a diversified asbestos products manufacturer, was conducted in 1932 by Drs. Anthony J. Lanza and Frank V. Meriwether. Occupational histories were obtained from workers in order to identify job tasks with exposure to asbestos and other fibrogenic dusts. Abbreviated medical histories, physical examinations, fluoroscopy, and chest radiographs were performed. Radiographs were interpreted according to applicable criteria for pneumoconiosis, the presence of which was confirmed in 327 subjects (29%). Among those, 64% had previous exposure to dusts in addition to asbestos, coal being the leading non-asbestos exposure. Thirty-six percent of cases had prior exposure only to asbestos dust. The original conclusions do not survive. Contemporaneous related documents suggest that the original authors believed asbestosis to be a milder form of lung disease than silicosis. It was subsequently recommended that the company institute pre-employment physicals, including chest radiographs; not hire people with prior coal-dust exposure; warn workers against excessive exposure to asbestos dust; remove those with disease to less dusty areas; and begin periodic medical surveillance for pneumoconiosis. The study, which has never appeared in the medical or scientific literature, holds important lessons for those concerned with occupational health today and in the future.

Balancing cost and precision in exposure assessment studies.

Because of the cost involved both for personnel and laboratory analyses, it is incumbent that industrial hygiene (IH) sampling plans be both precise and cost effective. The purpose of this paper is to describe a method of balancing two opposing objectives, increasing precision and decreasing the cost by manipulating the number and nature of IH sample collections. Data from a pilot study were used to obtain an optimum sampling scheme for exposure assessment. The design that obtains the highest precision while controlling costs serves as the model of choice. An approach is illustrated with data from an ongoing study examining health effects of workers exposed to solvents. It is shown that there is a large variation in precision for identical IH measurements, depending on the efficiency of the sampling schedule.

Refractory ceramic fibers activate alveolar macrophage eicosanoid and cytokine release.

Refractory ceramic fiber has been developed for industrial processes requiring materials with high thermal and mechanical stability. To evaluate the biological activity of this fiber, rat alveolar macrophages were exposed for < or = 24 h to 0-1,000 micrograms/ml of refractory ceramic fiber, crocidolite asbestos, silica (fibrogenic particles), or titanium dioxide (a nonfibrogenic particle), and eicosanoid, tumor necrosis factor-alpha (TNF), and lactate dehydrogenase release were measured. Particle dimensions were determined by electron microscopy. Radioactivity coeluting with leukotriene B4 (LTB4) and immunoreactive LTB4 and TNF release increased after refractory ceramic fiber and were similar in magnitude after asbestos but less than after silica. For example, the total [3H]eicosanoid release increased 3.9-fold after refractory ceramic fiber, 4.6-fold after asbestos, and 8.7-fold after silica. Refractory ceramic fiber and asbestos also have similar particle dimensions (diameter, length, and surface area). Inasmuch as macrophage-derived LTB4 and TNF are potent mediators in inflammatory events, including migration and activation of neutrophils, these findings suggest that refractory ceramic fiber can activate macrophages in vitro to release mediators relevant to in vivo findings of inflammation and fibrotic lung disease in laboratory animals.

Radon and man-made vitreous fibers.

Epidemiologic studies of miners have established a causal association between radon exposure and development of lung cancer. During the past decade the focus of attention has turned to the potential risks from exposure to radon in indoor air. Governmental involvement thus far has primarily been aimed at gathering further data and issuing voluntary guidelines for radon control in the indoor environment. The federal government's most recent risk assessment for exposure to indoor radon published in 1992 concluded that exposure to indoor radon results in 13,600 radon-induced lung cancer deaths in the United States each year. As public awareness of such environmental issues continues to grow, physicians will be faced with the need to respond to inquiries regarding potential health effects. Man-made vitreous fibers are silicate glass that have a noncrystalline structure. They have been in production for more than 100 years and are used in numerous applications in residential and commercial settings. The health risks from man-made vitreous fibers that are used in residential and commercial settings are limited to skin and occasional respiratory tract irritation under circumstances of improper installation or maintenance. When glass fiber contaminates an indoor environment, proper repair measures and thorough cleaning of the indoor environment will lead to resolution of any resultant irritant symptoms.

Indoor air quality medicolegal issues.

The regulatory and legal communities have begun only recently to address the medicolegal issues surrounding indoor air quality. No single governmental agency is responsible for indoor air quality issues. The focus of the federal government's indoor air quality programs is on the gathering and dissemination of information rather than on the regulation of indoor air pollution. State and local regulatory controls vary but may include antismoking ordinances, building codes, and contractor certification programs. Numerous lawsuits involving various parties and legal theories have been filed on the basis of illness allegedly related to indoor air quality. Further regulatory and legal review of indoor air problems will likely occur in the near future, particularly as a result of the characterization of environmental tobacco smoke as a class A carcinogen.