Carol Rice

Chronic beryllium disease and sensitization at a beryllium processing facility.

We conducted a medical screening for beryllium disease of 577 former workers from a beryllium processing facility. The screening included a medical and work history questionnaire, a chest radiograph, and blood lymphocyte proliferation testing for beryllium. A task exposure and a job exposure matrix were constructed to examine the association between exposure to beryllium and the development of beryllium disease. More than 90% of the cohort completed the questionnaire, and 74% completed the blood and radiograph component of the screening. Forty-four (7.6%) individuals had definite or probable chronic beryllium disease (CBD), and another 40 (7.0%) were sensitized to beryllium. The prevalence of CBD and sensitization in our cohort was greater than the prevalence reported in studies of other beryllium-exposed cohorts. Various exposure measures evaluated included duration; first decade worked; last decade worked; cumulative, mean, and highest job; and highest task exposure to beryllium (to both soluble and nonsoluble forms). Soluble cumulative and mean exposure levels were lower in individuals with CBD. Sensitized individuals had shorter duration of exposure, began work later, last worked longer ago, and had lower cumulative and peak exposures and lower nonsoluble cumulative and mean exposures. A possible explanation for the exposure–response findings of our study may be an interaction between genetic predisposition and a decreased permanence of soluble beryllium in the body. Both CBD and sensitization occurred in former workers whose mean daily working lifetime average exposures were lower than the current allowable Occupational Safety and Health Administration workplace air level of 2 μg/m3 and the Department of Energy guideline of 0.2 μg/m3.

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 (FEV1) % predicted, airway obstruction and persistent decline in FEV1. Inclusion in the high-exposure group (mixers) prior to respirator use was associated with a significantly decreased FEV1 % 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 ≥0.8 ppm-yr caused similar results. No significant impact was seen in nonmixers or between current diacetyl exposure and persistent decline in FEV1. Unprotected exposure as a mixer to butter flavouring including diacetyl resulted in decrements in FEV1 (% 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.

Mortality of workers occupationally exposed to refractory ceramic fibers.

This study was prompted by refractory ceramic fibers (RCF) inhalation studies at high dose levels in animals that demonstrated positive effects for lung fibrosis, mesothelioma, and lung cancer. Current and former male workers employed between 1952 and 2000 at two RCF manufacturing facilities were followed to investigate a possible excess in mortality. The mortality analytic methods included: (1) standardized mortality ratios comparing this cohort to the general and state populations, and (2) a proportional hazards model that relates risk of death to the lifetime cumulative fiber-months/cc exposure among the RCF cohort, adjusted for age at hire and for race. There was no excess mortality related to all deaths, all cancers, or malignancies or diseases of the respiratory system including mesothelioma, but there was a statistically significant association with cancers of the urinary organs SMR = 344.8 (95% CL of 111.6, 805.4). The quality of the data for job history, exposure, and smoking history were very high. Although the cohort was relatively small and young with an average age of 51, the mean latency period was over 21 years. Because of these limitations, the preliminary findings warrant the continuation of this mortality registry for future analyses.

Cadmium and lung cancer mortality accounting for simultaneous arsenic exposure

Objectives Prior investigations identified an association between airborne cadmium and lung cancer but questions remain regarding confounding by arsenic, a well-established lung carcinogen. Methods A cadmium smelter population exhibiting excess lung cancer was re-analysed using a retrospective exposure assessment for arsenic (As), updated mortality (1940–2002), a revised cadmium (Cd) exposure matrix and improved work history information. Results Cumulative exposure metrics for both cadmium and arsenic were strongly associated making estimation of their independent effects difficult. Standardised mortality ratios (SMRs) were modelled with Poisson regression with the contribution of arsenic to lung cancer risk constrained by exposure–response estimates previously reported. The results demonstrate (1) a statistically significant effect of Cd independent of As (SMR=3.2 for 10 mg-year/m3 Cd, p=0.012), (2) a substantial healthy worker effect for lung cancer (for unexposed workers, SMR=0.69) and (3) a large deficit in lung cancer mortality among Hispanic workers (SMR=0.27, p=0.009), known to have low lung cancer rates. A supralinear dose-rate effect was observed (contribution to risk with increasing exposure intensity has declining positive slope). Lung cancer mortality was somewhat better predicted using a cadmium burden metric with a half-life of about 20–25 years. Conclusions These findings support an independent effect for cadmium in risk of lung cancer mortality. 1/1000 excess lifetime risk of lung cancer death is predicted from an airborne exposure of about 2.4 μg/m3 Cd.

HLA class II DPB1 and DRB1 polymorphisms associated with genetic susceptibility to beryllium toxicity

Objectives Chronic beryllium disease (CBD) is a hypersensitivity granulomatous pulmonary disease caused by exposure to the metal beryllium (Be2+). Our objective was to extend current knowledge of the genetics of beryllium disease by examining all HLA-DPB1 and HLA-DPR1 gene polymorphisms and the interactions between them. Methods DNA-based typing of HLA-DPB1 and HLA-DRB1 loci at the allele level was performed on 65 CBD, 44 beryllium sensitised (BeS) but without CBD and 288 non-affected, beryllium exposed controls. Results The DPβE69 residue regardless of zygosity, but particularly if present on non-*0201 alleles, was of primary importance for the development of CBD and BeS, while other negatively charged residues DPβDE55, 56 and DPβDE84, 85 incrementally increased, although not independently, the risk. The DPβE69 positive alleles with charge −7 or −9 were associated with both CBD and BeS. The polymorphic residues DPβE69, DPβDE55, 56 and DPβDE84, 85 were responsible for the −9 charge and the first two residues for the −7 charge. Conclusions In the absence of DPβE69, DRβE71 is a risk factor for CBD and BeS. DPβE69 and DRβE71 are adjacent to other amino acids that are also negatively charged, suggesting that the positively charged Be2+ modifies the local environment of the epitopes in a way that promotes interactions between peptides and T cells and results in CBD. Finally, the protective effect of the DPB1*0201 positive haplotype may involve particular polymorphisms outside of the DPB1 gene.

ESTIMATION OF HISTORICAL AND CURRENT EMPLOYEE EXPOSURE TO REFRACTORY CERAMIC FIBERS DURING MANUFACTURING AND RELATED OPERATIONS

Abstract Refractory ceramic fibers (RCFs) have been produced in the United States since the early 1950s for use as a high temperature insulation material, or in the production of specialty products for insulation. Environmental data collected through 1991 have been assembled and used to reconstruct exposures at jobs in RCF manufacture or related operations. The algorithm incorporated consideration of the statistical distribution of the data, dates of implementation of engineering or process modifications potentially associated with a change in airborne fiber concentration, and the area in the facility (dust zone) where the sample was collected. Analysis of variance was used to test if differences between time periods within a dust zone were statistically significant. Time period was considered a fixed effect; the days of sample collection within a time period were considered a random, nested effect. Exposure estimates were constructed for 81 job tides in seven facilities for specified time periods. Overal...

An Asbestos Job Exposure Matrix to Characterize Fiber Type, Length, and Relative Exposure Intensity

The relationship between asbestos exposure and disease has been well documented, although questions persist as to variation in risk by the type and length of fiber. For a series of jobs with potential asbestos exposure, the primary fiber type (e.g., amosite, anthophylite, chrysotile, crocidolite, or tremolite) and fiber length were identified and the relative exposure intensity was estimated. The resulting job exposure matrix may be useful in epidemiological studies where asbestos is an exposure of interest.

ASSESSMENT OF POTENTIAL BIASES IN THE APPLICATION OF MSHA RESPIRABLE COAL MINE DUST DATA TO AN EPIDEMIOLOGIC STUDY

Systematic errors in exposure data will result in biased estimates of the exposure-response relationship derived from epidemiologic analyses. Thus, adjustment of exposure data to account for identified errors may provide for a more accurate assessment of effect. In preparing to apply respirable coal mine dust exposure data collected by the Mine Safety and Health Administration (MSHA) to a study of the pulmonary status of underground coal miners, an assessment of potential systematic errors was undertaken. Potential errors stemming from adjustment of controls during sampling, concentration-dependent sampling, truncation of sampling results, identified sampling equipment problems, and a disproportionate number of low concentration samples in mine operator-collected samples were identified and evaluated. Methods to account for these errors and adjust mean exposures by mine, occupation, and year are given.

HRCT/CT and associated spirometric effects of low Libby amphibole asbestos exposure.

Objective: Evaluate the relationship between cumulative fiber exposure and high-resolution or conventional chest computed tomography (HRCT/CT) changes and spirometry of workers with Libby amphibole asbestos exposure. Methods: Of the original 1980 cohort (n = 513), 431 were living and asked to participate. Images were evaluated for localized pleural thickening (LPT), diffuse pleural thickening (DPT), and parenchymal changes. Results: A total of 306 participants provided either HRCT/CT scans (n = 191) or chest radiographs (n = 115). Of the 191 with HRCT/CT, 52.9% had pleural changes and 13.1% had parenchymal changes. Those with LPT only, LPT and/or DPT, or DPT and/or parenchymal changes had mean 6.1, 8.0, and 18.0 loss in percent predicted forced vital capacity, respectively. Conclusions: Exposure to vermiculite containing amphibole fibers is associated with pleural and parenchymal HRCT/CT changes at low cumulative fiber exposure; these changes are associated with spirometric decrements.

Mortality patterns among Paducah Gaseous Diffusion Plant workers.

Objective: To determine whether Paducah Gaseous Diffusion Plant workers had mortality patterns that differed from the general US population and to investigate whether mortality patterns were associated with job title or workplace exposures. Methods: A retrospective occupational cohort mortality study was conducted on 6759 workers. Standardized mortality ratio analyses compared the cohort with the referent US population. Internal comparisons producing standardized rate ratios were conducted by job title, metal exposure, and cumulative internal and external radiation exposures. Results: Overall mortality and cancer rates were lower than the referent population, reflecting a strong healthy worker effect. Individual not significant standardized mortality ratios and standardized rate ratios were noted for cancers of the lymphatic and hematopoietic tissue. Conclusions: Although relatively low exposures to radiation and metals did not produce statistically significant health effects, no significant elevations for lymphatic and hematopoietic cancers were consistent with previous studies of nuclear workers.