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PubMed2001

Beryllium sensitization, chronic beryllium disease, and exposures at a beryllium mining and extraction facility.

In this study, we examine beryllium sensitization, chronic beryllium disease (CBD), and workplace exposures at a beryllium mining (mine) and extraction facility (mill) in Delta, Utah. Historical airborne beryllium data collected between 1970-1999 included general area (GA), breathing zone (BZ), and personal lapel (LP) measurements and calculations of job-specific quarterly daily-weighted averages (DWVAs). We compared GA, BZ, and DWA data to airborne beryllium data from a mixed beryllium products facility and a beryllium ceramics facility located in Elmore, Ohio and Tucson, Arizona, respectively. At the Delta facility, jobs involving beryllium hydrolysis and wet-grinding activities had the highest air concentrations; annual median GA concentrations were less than 0.3 microg/m3 or both areas. Annual median GA sample concentrations ranged from 0.1-0.4 microg/m(-3) at Delta. These levels were generally lower than Elmore (0.1-1.0 microg/m3) and were comparable to the Tucson facility (0.1-0.4 microg/m3). Median BZ concentrations were higher, whereas DWAs were lower at the Delta facility than at the other two facilities. Among the 87 employees at the Delta facility, 75 participated in the medical survey; there were three persons sensitized, one with CBD. The individual with CBD previously worked at the Elmore facility for 10 years. Cumulative CBD incidence rates were significantly lower at the Delta facility: 0.3 percent compared to 2.0 percent for Elmore and 2.5 percent for the Tucson facility. Sensitization and CBD prevalence rates determined from cross-sectional surveys for the Delta facility were lower than but not significantly different from rates at the other two facilities. There was no sensitization or CBD among those who worked only at the mine where the only exposure to beryllium results from working with bertrandite ore. Although these results are derived from a small sample, this study suggests that the form of beryllium may affect the likelihood of developing CBD. Specifically, exposure to beryl and bertrandite ore dusts or to beryllium salts, in the absence of exposure to beryllium oxide particulates appears to pose a lower risk for developing CBD.

Adult↗

PubMed2005

Immunogenetic factors in beryllium sensitization and chronic beryllium disease.

Exposure to beryllium in the workplace can cause beryllium sensitization and chronic beryllium disease. Sensitization to beryllium can be detected in the laboratory using the beryllium lymphocyte proliferation test. It was shown that anti-HLA antibodies could block the beryllium-specific response in the beryllium lymphocyte proliferation test, thereby implicating HLA genes in chronic beryllium disease. A supratypic genetic marker, HLA-DPB1*E69, was found to be strongly associated with immunologic sensitization to beryllium and chronic beryllium disease in beryllium workers. However, there are 40 HLA-DPB1 gene variants that have E69 but that also have other DNA sequence variations. The purpose of the study was to evaluate the evidence for potential differential susceptibility that may be associated with the physical characteristics of HLA protein molecules for which different HLA-DPB1*E69 variants code; that is, do some HLA-DPB1*E69 variants convey higher risk of beryllium sensitization and chronic beryllium disease than others. To do this, two approaches were pursued: first, detailed analysis of the findings from the published literature was performed, and second, computational chemistry was used to seek clues concerning the physical properties of the HLA protein molecules for which these alleles code. Among the 40 HLA-DPB1 gene variants that code for E69, molecular epidemiological studies have suggested a risk hierarchy, where some variants appear to convey low to moderate risk of chronic beryllium disease (e.g., HLA-DPB1*0201, approximately 3-fold increased risk), some convey an intermediate risk (e.g., HLA-DPB1*1901, approximately 5-fold) and others convey high risk (e.g., HLA-DPB1*1701, >10-fold). Molecular modeling has been used to further investigate a potential mechanistic basis for these observations. We found a strong correlation between the hierarchical order of risk of chronic beryllium disease associated with specific alleles and the predicted surface electrostatic potential and charge of the corresponding isotypes. Therefore, when alleles were grouped by the relative negative charge on the molecules for which they code, the data suggest that those alleles associated with the most negatively charged proteins carry the greatest risk of beryllium sensitization and disease.

Berylliosis↗

PubMed2004

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.

Aerosols↗

PubMed2005

Frequency of beryllium-specific, TH1-type cytokine-expressing CD4+ T cells in patients with beryllium-induced disease.

BACKGROUND: Beryllium sensitization is caused by exposure to beryllium in the workplace. A subset of beryllium-sensitized (BeS) subjects progress to chronic beryllium disease (CBD), a disorder characterized by a CD4+ T-cell alveolitis and granulomatous inflammation. Whether biomarkers are present in blood that would allow separation of CBD from beryllium sensitization without invasive pulmonary procedures is unknown. OBJECTIVE: The aim of this study was to determine whether the quantity of beryllium-specific T cells in blood of patients with CBD differs from that found in BeS subjects. METHODS: Beryllium-induced T-cell proliferation and T H 1-type cytokine secretion were determined in blood cells from 33 patients with CBD and 18 BeS subjects. RESULTS: We demonstrate here that patients with CBD have a significantly elevated number of IFN-gamma-producing and IL-2-producing beryllium-specific CD4+ T cells in blood compared with both BeS and normal control subjects. In contrast, no difference in beryllium-induced proliferation of blood T cells was seen between BeS patients and patients with CBD. Compared with the blood beryllium lymphocyte proliferation test, which detected beryllium-induced proliferation in 65% of BeS patients and patients with CBD, ELISPOT analysis detected IFN-gamma secretion in 80% of these subjects. Higher numbers of beryllium-specific cells in blood were also associated with the extent of alveolar inflammation, as measured by both bronchoalveolar lavage white blood cell and lymphocyte counts. CONCLUSION: The frequency of beryllium-specific T cells in the blood of beryllium-exposed subjects may be a useful biomarker that helps discriminate between beryllium sensitization and progression to CBD.

Adult↗

PubMed2004

Beryllium sensitization progresses to chronic beryllium disease: a longitudinal study of disease risk.

The blood beryllium lymphocyte proliferation test is used in medical surveillance to identify both beryllium sensitization and chronic beryllium disease. Approximately 50% of individuals with beryllium sensitization have chronic beryllium disease at the time of their initial clinical evaluation; however, the rate of progression from beryllium sensitization to chronic beryllium disease is unknown. We monitored a cohort of beryllium-sensitized patients at 2-year intervals, using bronchoalveolar lavage and repeated transbronchial lung biopsies to determine progression to chronic beryllium disease as evidenced by granulomatous inflammation in lung tissue. Fifty-five individuals with beryllium sensitization were monitored with a range of 2 to 5 clinical evaluations. Disease developed in 17 sensitized individuals (31%) within an average follow-up period of 3.8 years (range, 1.0-9.5 years). Thirty-eight of the 55 (69%) remained beryllium sensitized without disease after an average follow-up time of 4.8 years (range, 1.7-11.6 years). Progressors were more likely to have worked as machinists. We found no difference in average age, sex, race or ethnicity, smoking status, or beryllium exposure time between those who progressed to chronic beryllium disease and those who remained sensitized without disease. We conclude that beryllium sensitization is an adverse health effect in beryllium-exposed workers and merits medical follow-up.

Adult↗

PubMed1989

Maintenance of alveolitis in patients with chronic beryllium disease by beryllium-specific helper T cells.

Chronic beryllium disease is characterized by the accumulation of helper/inducer T cells, macrophages, and granulomas in the lungs. To evaluate the hypothesis that the proliferation of CD4+ (helper/inducer) T cells in the lungs of patients with this disorder is maintained by local activation of beryllium-specific T-cell clones, we studied T cells obtained from peripheral blood and by bronchoalveolar lavage in eight patients and five healthy controls. The proliferation of T cells in response to beryllium in vitro was confined to the CD4+ T cells from the patients and was dependent on the presentation of antigen in the presence of both major histocompatibility complex class II antigens and functional interleukin-2 receptors. T cells from the patients' lungs had a significantly greater response to beryllium than did T cells from their peripheral blood (stimulation index, 103 vs. 5; P less than 0.01). Lines and clones of cells developed from T cells from the patients' lungs showed dose-dependent proliferation in response to beryllium but did not respond to recall antigens or to other metals. Although all beryllium-specific T-cell clones were CD4+ and none were CD8+ (suppressor/cytotoxic), all beryllium-specific clones studied had different rearrangements of T-cell antigen receptors, suggesting that the response to beryllium involved T cells with diverse specificities for beryllium. We conclude that in patients with chronic beryllium disease, beryllium acts as a class II-restricted antigen, stimulating local proliferation and accumulation in the lung of beryllium-specific CD4+ (helper/inducer) T cells. Hence, chronic beryllium disease is a hypersensitivity disease in which beryllium is the specific antigen.

Adult↗

PubMedDate not supplied

Surface area of respirable beryllium metal, oxide, and copper alloy aerosols and implications for assessment of exposure risk of chronic beryllium disease.

The continued occurrence of chronic beryllium disease (CBD) suggests the current occupational exposure limit of 2 microg beryllium per cubic meter of air does not adequately protect workers. This study examined the morphology and measured the particle surface area of aerodynamically size-separated powders and process-sampled particles of beryllium metal, beryllium oxide, and copper-beryllium alloy. The beryllium metal powder consisted of compact particles, whereas the beryllium oxide powder and particles were clusters of smaller primary particles. Specific surface area (SSA) results for all samples (N=30) varied by a factor of 37, from 0.56 +/- 0.07 m(2)/g (for the 0.4-0.7 microm size fraction of the process-sampled reduction furnace particles) to 20.8 +/- 0.4 m(2)/g (for the </=0.4 microm size fraction of the metal powder). Large relative differences in SSA were observed as a function of particle size for the powder of beryllium metal, from 4.0 +/- 0.01 m(2)/g (for the particle size fraction >6 microm) to 20.8 +/- 0.44 m(2)/g (for the particle size fraction </=0.4 microm). In contrast, little relative difference in SSA (<25%) was observed as a function of particle size for the beryllium oxide powder and particles collected from the screening operation. The SSA of beryllium metal powder decreases with increasing particle size, as expected for compact particles, and the SSA of the beryllium oxide powders and particles remains constant as a function of particle size, which might be expected for clustered particles. These associations illustrate how process-related factors can influence the morphology and SSA of beryllium materials. To avoid errors in predicting bioavailability of beryllium and the associated risks for CBD, the mechanisms of particle formation should be understood and the SSA of beryllium particles should be measured directly.

Aerosols↗

PubMed1988

Proliferative response of bronchoalveolar lymphocytes to beryllium. A test for chronic beryllium disease.

STUDY OBJECTIVE: to ascertain whether measuring the proliferative response of bronchoalveolar lymphocytes to beryllium salts is useful for diagnosing chronic beryllium disease. DESIGN: prospective case series compared to normal volunteers and patients with sarcoidosis. SETTING: university referral center. PATIENTS: twenty-three consecutive beryllium workers were evaluated. Fourteen had chronic beryllium disease diagnosed on the basis of histologic evidence of a progressive pulmonary granulomatosis. Four had biopsy evidence of non-beryllium disease. Three had probable chronic beryllium disease but did not have lung biopsies. Two did not have biopsies and had basilar fibrosis on chest roentgenogram suggestive of non-beryllium lung disease. These patients were compared with 6 normal volunteers and 16 patients with sarcoidosis. MEASUREMENTS AND MAIN RESULTS: bronchoalveolar lavage was done and the proliferative response of the lung cells to two beryllium salts was tested. A positive proliferative test was defined as a stimulation index of more than five on two determinations. The sensitivity of this test was 100% in the 14 patients with definite chronic beryllium disease. The specificity of the test was also 100% among the normal volunteers and the 16 patients with sarcoidosis. The test was positive in none of the four patients with biopsy evidence of non-beryllium disease, none out of two patients with lower lobe fibrosis suggestive of non-beryllium disease, and all of three patients with probable chronic beryllium lung disease. CONCLUSIONS: the proliferative response of bronchoalveolar lymphocytes to beryllium appears to be a useful test for chronic beryllium disease.

Berylliosis↗

PubMed2001

Beryllium sensitization and disease among long-term and short-term workers in a beryllium ceramics plant.

OBJECTIVE: Workers at a beryllium ceramics plant were tested for beryllium sensitization and disease in 1998 to determine whether the plant-wide prevalence of sensitization and disease had declined since the last screening in 1992; an elevated prevalence was associated with specific processes or with high exposures; exposure-response relationships differed for long-term workers hired before the last plant-wide screening and short-term workers hired since then. METHODS: Current workers were asked to complete a questionnaire and to provide blood for the beryllium lymphocyte proliferation test (BeLPT). Those with an abnormal BeLPT were classified as sensitized, and were offered clinical evaluation for beryllium disease. Task- and time-specific measurements of airborne beryllium were combined with individual work histories to compute mean, cumulative, and peak beryllium exposures for each worker. RESULTS: The 151 participants represented 90% of 167 eligible workers. Fifteen (9.9% of 151) had an abnormal BeLPT and were split between long-term workers (8/77 = 10.4%) and short-term workers (7/74 = 9.5%). Beryllium disease was detected in 9.1% (7/77) of long-term workers but in only 1.4% (1/74) of short-term workers (P = 0.06), for an overall prevalence of 5.3% (8/151). These prevalences were similar to those observed in the earlier survey. The prevalence of sensitization was elevated in 1992 among machinists, and was still elevated in 1998 among long-term workers (7/40 = 18%) but not among short-term workers (2/36 = 6%) with machining experience. The prevalence of sensitization was also elevated in both groups of workers for the processes of lapping, forming, firing, and packaging. The data suggested a positive relationship between peak beryllium exposure and sensitization for long-term workers and between mean, cumulative, and peak exposure and sensitization for short-term workers, although these findings were not statistically significant. Long-term workers with either a high peak exposure or work experience in forming were more likely to have an abnormal BeLPT (8/51 = 16%) than the other long-term workers (0/26, P = 0.05). All seven sensitized short-term workers either had high mean beryllium exposure or had worked longest in forming or machining (7/55 = 13% versus 0/19, P = 0.18). CONCLUSIONS: A plant-wide decline in beryllium exposures between the 1992 and 1998 surveys was not matched by a decline in the prevalence of sensitization and disease. Similar to findings from other studies, beryllium sensitization/disease was associated with specific processes and elevated exposures. The contrast in disease prevalence between long-term and short-term workers suggests that beryllium sensitization can occur after a short period of exposure, but beryllium disease usually requires a longer latency and/or period of exposure. The findings from this study motivated interventions to more aggressively protect and test workers, and new research into skin exposure as a route of sensitization and the contribution of individual susceptibility.

Air Pollutants, Occupational↗

PubMed2005

Differences in dissolution behavior in a phagolysosomal simulant fluid for single-constituent and multi-constituent materials associated with beryllium sensitization and chronic beryllium disease.

Particle dissolution within macrophage phagolysosomes is hypothesized to be an important source of dissolved beryllium for input to the cell-mediated immune reaction associated with development of beryllium sensitization and chronic beryllium disease (CBD). To better understand the dissolution of beryllium materials associated with elevated prevalence of sensitization and CBD, single-constituent (beryllium oxide (BeO) particles sampled from a screener operation, finished product BeO powder, finish product beryllium metal powder) and multi-constituent (particles sampled from an arc furnace during processing of copper-beryllium alloy) aerosol materials were studied. Dissolution rates were measured using phagolysosomal simulant fluid (PSF) in a static dissolution technique and then normalized to measured values of specific surface area to calculate a chemical dissolution rate constant (k) for each material. Values of k, in g/(cm2 day), for screener BeO particles (1.3 +/- 1.9 x 10(-8)) and for BeO powder (1.1 +/- 0.5 x 10(-8)) were similar (p = 0.45). The value of k observed for beryllium metal powder (1.1 +/- 1.4 x 10(-7)) was significantly greater than observed for the BeO materials (p < 0.0003). For arc furnace particles, k (1.6 +/- 0.6 x 10(-7)) was significantly greater than observed for the BeO materials (p < 0.00001), despite the fact that the chemical form of beryllium in the aerosol was BeO. These results suggest that dissolution of beryllium differs among physicochemical forms of beryllium and direct measurement of dissolution is needed for multi-constituent aerosol. Additional studies of the dissolution behavior of beryllium materials in a variety of mixture configurations will aid in developing exposure-response models to improve understanding of the risk of beryllium sensitization and CBD.

Aerosols↗

PubMed2001

Beryllium sensitization and chronic beryllium disease at a former nuclear weapons facility.

The prevalence of beryllium sensitization and chronic beryllium disease by job category was examined among individuals tested in the Rocky Flats Beryllium Health Surveillance Program. The program offered ongoing beryllium health surveillance for any current or former employee who believed they may have been exposed to beryllium at the Rocky Flats Environmental Technology Site. Of the 18,589 living individuals contacted, 7,573 requested participation and 6,614 (87.3%) eventually participated. Of this group, 78.2 percent were found to have verifiable job and building histories. The beryllium lymphocyte proliferation test was used to identify beryllium-sensitized individuals. Sensitization and chronic beryllium disease rates were analyzed with respect to gender, building work location(s), and length of employment at Rocky Flats. Several job categories and buildings were strongly associated with the 81 cases of chronic beryllium disease and the additional 154 cases of beryllium sensitization in this population. Beryllium sensitization was highest among beryllium machinists, 11.4 percent (odds ratio = 3.04, compared to the remainder of those tested, 95 % confidence interval = 1.48, 3.97) and health physics technicians, 11.9 percent (odds ratio = 2.87, 95% confidence interval = 1.12, 7.36). However, odds ratios were also increased among custodial employees, 5.64 percent (odds ratio = 1.30, 95% confidence interval = 0.92, 1.85) and other job titles that were thought to have only minimal potential for exposure to beryllium.

Berylliosis↗

PubMed2001

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.

Air Pollutants, Occupational↗

PubMed2001

Beryllium health effects in the era of the beryllium lymphocyte proliferation test.

The beryllium lymphocyte proliferation test (BeLPT) has revolutionized our approach to the diagnosis, screening, and surveillance of beryllium health effects. Based on the development of a beryllium-specific cell-mediated immune response, the BeLPT has allowed us to define early health effects of beryllium, including beryllium sensitization (BeS), and chronic beryllium disease (CBD) at a subclinical stage. The use of this test as a screening tool has improved our understanding of these health effects. From a number of studies it is apparent that BeS precedes CBD and develops after as little as 9 weeks of beryllium exposure. CBD occurs within 3 months and up to 30 years after initial beryllium exposure. Exposure-response variables have been associated with BeS/CBD, including work as a machinist, chemical or metallurgical operator, laboratory technician, work in ceramics or beryllium metal production, and years of beryllium exposure. Recent studies have found BeS and CBD in workplaces in which the majority of exposures were below the 2 microg/m3 OSHA time-weighted average (TWA). Ideally, the BeLPT would be used in surveillance aimed at defining other risk-related processes, determining exposure variables which predict BeS and CBD, and defining the exposure level below which beryllium health effects do not occur. Unfortunately, the BeLPT can result in false negative tests and still requires an invasive procedure, a bronchoscopy, for the definitive diagnosis of CBD. Thus, research is needed to establish new tests to be used alone or in conjunction with the BeLPT to improve our ability to detect early beryllium health effects.

Berylliosis↗

PubMed2006

Recombinant HLA-DP2 binds beryllium and tolerizes beryllium-specific pathogenic CD4+ T cells.

Chronic beryllium disease is a lung disorder caused by beryllium exposure in the workplace and is characterized by granulomatous inflammation and the accumulation of beryllium-specific, HLA-DP2-restricted CD4+ T lymphocytes in the lung that proliferate and secrete Th1-type cytokines. To characterize the interaction among HLA-DP2, beryllium, and CD4+ T cells, we constructed rHLA-DP2 and rHLA-DP4 molecules consisting of the alpha-1 and beta-1 domains of the HLA-DP molecules genetically linked into single polypeptide chains. Peptide binding to rHLA-DP2 and rHLA-DP4 was consistent with previously published peptide-binding motifs for these MHC class II molecules, with peptide binding dominated by aromatic residues in the P1 pocket. 9Be nuclear magnetic resonance spectroscopy showed that beryllium binds to the HLA-DP2-derived molecule, with no binding to the HLA-DP4 molecule that differs from DP2 by four amino acid residues. Using beryllium-specific CD4+ T cell lines derived from the lungs of chronic beryllium disease patients, beryllium presentation to those cells was independent of Ag processing because fixed APCs were capable of presenting BeSO4 and inducing T cell proliferation. Exposure of beryllium-specific CD4+ T cells to BeSO4 -pulsed, plate-bound rHLA-DP2 molecules induced IFN-gamma secretion. In addition, pretreatment of beryllium-specific CD4+ T cells with BeSO4-pulsed, plate-bound HLA-DP2 blocked proliferation and IL-2 secretion upon re-exposure to beryllium presented by APCs. Thus, the rHLA-DP2 molecules described herein provide a template for engineering variants that retain the ability to tolerize pathogenic CD4+ T cells, but do so in the absence of the beryllium Ag.

Amino Acid Sequence↗

PubMed2006

Sensitization and chronic beryllium disease among workers in copper-beryllium distribution centers.

OBJECTIVE: Little is known about the risk of sensitization and chronic beryllium disease (CBD) among workers performing limited processing of copper-beryllium alloys downstream of the primary beryllium industry. In this study, we performed a cross-sectional survey of employees at three copper-beryllium alloy distribution centers. METHODS: One hundred workers were invited to be tested for beryllium sensitization using the beryllium blood lymphocyte proliferation test (BeLPT); a sensitized worker was further evaluated for CBD. Available beryllium mass concentration air sampling data were obtained for characterization of airborne exposure. RESULTS: One participant, who had exposure to other forms of beryllium, was found to be sensitized and to have CBD, resulting in a prevalence of sensitization/CBD of 1% for all tested. CONCLUSIONS: The overall prevalence of beryllium sensitization and CBD for workers in these three copper-beryllium alloy distribution centers is lower than for workers in primary beryllium production facilities.

Adult↗

PubMed2005

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 microg/m3 and the Department of Energy guideline of 0.2 microg/m3.

Aged↗

PubMed2005

Process-related risk of beryllium sensitization and disease in a copper-beryllium alloy facility.

BACKGROUND: Chronic beryllium disease (CBD), which primarily affects the lungs, occurs in sensitized beryllium-exposed individuals. At a copper-beryllium alloy strip and wire finishing facility we performed a cross-sectional survey to examine prevalences of beryllium sensitization and CBD, and relationships between sensitization and CBD and work areas/processes. METHODS: Current employees (185) were offered beryllium lymphocyte proliferation testing (BeLPT) for sensitization, clinical evaluation for CBD (if sensitized), and questionnaires. We obtained historical airborne beryllium measurements. RESULTS: Participation was 83%. Prevalences of sensitization and CBD were 7% (10/153) and 4% (6/153), respectively; this included employees with abnormal BeLPTs from two laboratories, four diagnosed with CBD during the survey, and one each diagnosed preceding and following the survey. Potential BeLPT laboratory problems were noted; one laboratory was twice as likely to have reported an abnormal result (P < 0.05, all tests), and five times as likely to have reported a borderline or uninterpretable result (P < 0.05, first blood draw and all tests). CBD risk was highest in rod and wire production (P < 0.05), where air levels were highest. CONCLUSIONS: Sensitization and CBD were associated with an area in which beryllium air levels exceeded 0.2 microg/m3, and not with areas where this level was rarely exceeded. Employees at this copper-beryllium alloy facility had similar prevalences of sensitization and CBD as workers at facilities with higher beryllium air levels.

Adult↗

PubMed1990

Clearance, translocation, and excretion of beryllium following acute inhalation of beryllium oxide by beagle dogs.

Beagle dogs inhaled radiolabeled beryllium oxide (7BeO) particles that were calcined at either 500 or 1000 degrees C, resulting in either high (mean of 50 micrograms/kg body wt) or low (mean of 17 micrograms/kg body wt) initial lung burdens (ILBs) of both preparations of BeO. Levels of beryllium in whole body, tissue, and excreta were measured by external gamma-ray counting. Dogs were euthanized in pairs at 8, 32, 64, and 180 days after exposure to determine beryllium distribution in tissues. Beryllium oxide calcined at 1000 degrees C was retained more tenaciously in the lungs (62% of the ILB retained at 180 days after exposure) than BeO calcined at 500 degrees C (14% of the ILB retained at 180 days after exposure). Most of the beryllium that was cleared from the lungs and not excreted was translocated to the tracheobronchial lymph nodes, skeleton, liver, and blood. More beryllium was translocated to the skeleton and liver at 180 days after inhalation of BeO prepared at 500 degrees C than at 1000 degrees C. The predominant mode of excretion at early times after exposure was through the feces, with urinary excretion assuming predominance at later times. These data are important for interpreting the toxic effects of beryllium in the exposed dogs. Furthermore, because little is known concerning the retention and clearance of inhaled beryllium in man, these results provide information that may be used to understand the disposition of beryllium in accidentally exposed humans.

Administration, Inhalation↗