Prevalence Of Chronic Beryllium Disease Research Articles

Low Prevalence of Chronic Beryllium Disease Among Workers at a Nuclear Weapons Research and Development Facility

To study the prevalence of beryllium sensitization (BeS) and chronic beryllium disease (CBD) in a cohort of workers from a nuclear weapons research and development facility. We evaluated 50 workers with BeS with medical and occupational histories, physical examination, chest imaging with high-resolution computed tomography (N = 49), and pulmonary function testing. Forty of these workers also underwent bronchoscopy for bronchoalveolar lavage and transbronchial biopsies. The mean duration of employment at the facility was 18 years and the mean latency (from first possible exposure) to time of evaluation was 32 years. Five of the workers had CBD at the time of evaluation (based on histology or high-resolution computed tomography); three others had evidence of probable CBD. These workers with BeS, characterized by a long duration of potential Be exposure and a long latency, had a low prevalence of CBD.

Physicochemical Characteristics of Aerosol Particles Generated During the Milling of Beryllium Silicate Ores: Implications for Risk Assessment

Inhalation of beryllium dusts generated during milling of ores and cutting of beryl-containing gemstones is associated with development of beryllium sensitization and low prevalence of chronic beryllium disease (CBD). Inhalation of beryllium aerosols generated during primary beryllium production and machining of the metal, alloys, and ceramics are associated with sensitization and high rates of CBD, despite similar airborne beryllium mass concentrations among these industries. Understanding the physicochemical properties of exposure aerosols may help to understand the differential immunopathologic mechanisms of sensitization and CBD and lead to more biologically relevant exposure standards. Properties of aerosols generated during the industrial milling of bertrandite and beryl ores were evaluated. Airborne beryllium mass concentrations among work areas ranged from 0.001 μg/m3 (beryl ore grinding) to 2.1 μg/m3 (beryl ore crushing). Respirable mass fractions of airborne beryllium-containing particles were < 20% in low-energy input operation areas (ore crushing, hydroxide product drumming) and > 80% in high-energy input areas (beryl melting, beryl grinding). Particle specific surface area decreased with processing from feedstock ores to drumming final product beryllium hydroxide. Among work areas, beryllium was identified in three crystalline forms: beryl, poorly crystalline beryllium oxide, and beryllium hydroxide. In comparison to aerosols generated by high-CBD risk primary production processes, aerosol particles encountered during milling had similar mass concentrations, generally lower number concentrations and surface area, and contained no identifiable highly crystalline beryllium oxide. One possible explanation for the apparent low prevalence of CBD among workers exposed to beryllium mineral dusts may be that characteristics of the exposure material do not contribute to the development of lung burdens sufficient for progression from sensitization to CBD. In comparison to high-CBD risk exposures where the chemical nature of aerosol particles may confer higher bioavailability, respirable ore dusts likely confer considerably less. While finished product beryllium hydroxide particles may confer bioavailability similar to that of high-CBD risk aerosols, physical exposure factors (i.e., large particle sizes) may limit development of alveolar lung burdens.

Vacuum sampling techniques for industrial hygienists, with emphasis on beryllium dust sampling

The U.S. Department of Energy (DOE) Chronic Beryllium Disease Prevention Program Rule, 10 CFR Part 850 became effective in 2000 in response to the prevalence of Chronic Beryllium Disease (CBD) in workers. The rule requires surface and air monitoring for beryllium to determine exposure levels and the evaluation of the effectiveness of controls used to minimize or eliminate that risk. The most common methods for surface sampling use wet or dry wipes. Wipe sampling techniques may be impractical for many surfaces common to most buildings such as cinder block, textured wall surfaces, fabric and carpet. Vacuum sampling methods have been developed for the evaluation of lead or pesticides on residential surfaces such as carpets, bare floors and window sills. However, the current vacuum methods may be impractical for many workplace situations such as sampling of protective clothing, complex facility structures, or equipment surfaces. Recent work using vacuum sampling for potential bio-terrorism agents such as anthrax spores may have significant application to industrial hygiene evaluations of the workplace and may be extendable for use in sampling of metals such as beryllium. Validated vacuum sampling methods that provide meaningful data would be of great value to industrial hygienists in identifying areas having surface contamination, evaluating existing controls and work practices and determining the potential of toxic material on surfaces to become airborne and present a potential risk to workers and the public. This article discusses various vacuum sampling methodologies and recommends harmonization of sampling methods.

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.

Characterization of physicochemical properties of beryllium aerosols associated with prevalence of chronic beryllium disease.

Little is known about the physicochemical properties of beryllium aerosols associated with increased risk of beryllium sensitization and chronic beryllium disease (CBD). Such information is needed to evaluate whether airborne mass of beryllium is the appropriate metric of exposure or alternatively to provide a scientific basis for using information on particle size, surface area, and chemistry to support an improved exposure limit based on bioavailability through the inhalation and dermal routes of exposure. Thus, we used a suite of analytical techniques to characterize aerodynamically size-fractionated beryllium particles and powders that have been associated in epidemiological studies with higher prevalence of CBD. Aerosol particles were sampled from the ventilation systems of production lines for powders of beryllium metal and beryllium oxide and for ingots of copper-beryllium alloy. End product powders from the metal and oxide production lines were also collected. Particles released during production of beryllium metal were found to be complex, having heterogeneous composition, including reactive species such as fluorine. Powders from beryllium metal production were of high purity with only a minor component of beryllium oxide. Both particles and powders from oxide production were high-purity oxide. Particles released during production of copper-beryllium alloy were heterogeneous, being predominantly copper oxides. Thus, all particles and powders contain at least some beryllium in the form of beryllium oxide. These data justify efforts to thoroughly characterize beryllium aerosol properties when performing exposure assessments. The data also suggest that differences in particle chemical composition, size, number, and surface area may influence bioavailability of beryllium and contribute to risk of CBD. However, a scientific basis does not yet exist to replace mass as the current metric of exposure.

Is total mass or mass of alveolar-deposited airborne particles of beryllium a better predictor of the prevalence of disease? A preliminary study of a beryllium processing facility.

Cases of chronic beryllium disease (CBD) and beryllium (Be) sensitization continue to be identified among Be industry workers. The currently accepted method for measuring exposure, which involves measuring the total mass of airborne Be per cubic meter, shows an inconsistent dose-response relationship with the prevalence of CBD. This study was conducted to evaluate which Be aerosol characteristics other than total mass may be more informative in understanding the dose-response relationship between exposure to Be and disease. Personal (n = 53) and general (n = 55) area airborne Be samples were collected in five furnace areas at a Be manufacturing facility where prevalence rates of CBD and Be sensitization had been previously studied among 535 employees with significant Be exposure. In the five furnace areas, particle-size specific personal samples and area samples were collected using an Andersen impactor and a microorifice uniform deposit impactor (MOUDI), respectively. The calculated concentrations were expressed in terms of total mass per cubic meter, and in forms of mass, number, and surface area of particles less than 10 microm or less than 3.5 microm mass median aerodynamic diameter per cubic meter that are predicted to deposit in the alveolar region of the lung. Tests for linear trend of the relationships of the various exposure metrics to prevalence of CBD and sensitization demonstrated highly significant associations between mass concentration (MOUDI) of particles less than 10 microm, and less than 3.5 microm, predicted to deposit in the alveolar region of the lung and CBD (p = 0.0004 and 0.000003, respectively) and sensitization (p = 0.025 and 0.003, respectively). However, no statistically significant association was found between these two exposure metrics and personal (Andersen) samples. The number and surface area concentration (MOUDI) of alveolar-deposited particles (less than 10 microm) also showed significant relationships with CBD (p = 0.03 and 0.03, respectively). No other exposure parameters showed significant relationships with CBD or Be sensitization. These results suggest that the concentration of alveolar-deposited particles less than 10 microm or, more particularly, the concentration of alveolar-deposited particles less than 3.5 microm may be a more relevant exposure metric for predicting the incidence of CBD or sensitization than the total mass concentration of airborne Be.

A Comparison and Critique of Historical and Current Exposure Assessment Methods for Beryllium: Implications for Evaluating Risk of Chronic Beryllium Disease

The primary beryllium industry has generated a large amount of data on airborne beryllium concentrations that has been used to characterize exposure by task-specific activities, job category, individual worker, and processing area using a variety of methods. These methods have included high-volume breathing zone sampling, high-volume process sampling, high- and low-volume respirable and area sampling, real-time monitoring, and personal sampling. Many of the beryllium studies have used these air sampling methods to assess inhalation exposure and chronic beryllium disease (CBD) risk to beryllium; however, available data do not show a consistent dose-response relationship between airborne concentrations of beryllium and the incidence of CBD. In this article, we describe the air sampling and exposure assessment methods that have been used, review the studies that have estimated worker exposures, discuss the uncertainties associated with the level of beryllium for which these studies have reported an increased risk of CBD, and identify future investigative exposure assessment strategies. Our evaluation indicated that studies of beryllium workers are often not directly comparable because they (1) used a variety of exposure assessment methods that are not necessarily representative of individual worker exposures, (2) rarely considered respirator use, and (3) have not evaluated changes in work practices. It appears that the current exposure metric for beryllium, total beryllium mass, may not be an appropriate measurement to predict the risk of CBD. Other exposure metrics such as mass of respirable particles, chemical form, and particle surface chemistry may be more related to the prevalence of CBD than total mass of airborne beryllium mass. In addition, assessing beryllium exposure by all routes of exposure (e.g., inhalation, dermal uptake, and ingestion) rather than only inhalation exposure in future studies may prove useful.

Rocky Flats Beryllium Health Surveillance.

The Rocky Flats Beryllium Health Surveillance Program (BHSP), initiated in June 1991, was designed to provide medical surveillance for current and former employees exposed to beryllium. The BHSP identifies individuals who have developed beryllium sensitivity using the beryllium lymphocyte proliferation test (BeLPT). A detailed medical evaluation to determine the prevalence of chronic beryllium disease (CBD) is offered to individuals identified as beryllium sensitized or to those who have chest X-ray changes suggestive of CBD. The BHSP has identified 27 cases of CBD and another 74 cases of beryllium sensitization out of 4268 individuals tested. The distribution of BeLPT values for normal, sensitized, and CBD-identified individuals is described. Based on the information collected during the first 3 1/3 years of the BHSP, the BeLPT is the most effective means for the early identification of beryllium-sensitized individuals and to identify individuals who may have CBD. The need for BeLPT retesting is demonstrated through the identification of beryllium sensitization in individuals who previously tested normal. Posterior/anterior chest X-rays were not effective in the identification of CBD.

Novel in vitro method for identification of individuals at risk for beryllium hypersensitivity.

Beryllium-specific lymphocytes were generated by in vitro immunization of peripheral blood mononuclear cells (PBMC) from healthy unexposed individuals. Measurement of blastogenic responses of PBMC by [3H]thymidine uptake demonstrated that sensitization of PBMC with beryllium salts followed by stimulation with unrelated salts resulted in a negative response, whereas sensitization and restimulation of PBMC with beryllium salts produced a positive response. Flow cytometric and cell depletion analyses showed that all of the responding cells were CD4+ T cells. The in vitro immunization system was used to screen 52 human subjects for susceptibility to beryllium sensitization in vitro. The results show that of the 52 healthy unexposed subjects tested, only 1 (2%) was highly responsive, 4 subjects (8%) were moderately responsive, 20 subjects (39%) were low-level responders, and 27 subjects (52%) were nonresponders. The results showing 2% high-level responsiveness to beryllium sensitization in vitro correlate with the 1 to 5% prevalence of chronic beryllium disease in individuals sensitized to beryllium dust in vivo and thus support the thesis that the in vitro immunization system may permit the identification of individuals at risk for beryllium hypersensitivity.