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PubMed2003

Beryllium in the environment: a review.

Beryllium is an important industrial metal because of its unusual material properties: it is lighter than aluminum and six times stronger than steel. Often alloyed with other metals such as copper, beryllium is a key component of materials used in the aerospace and electronics industries. Beryllium has a small neutron cross-section, which makes it useful in the production of nuclear weapons and in sealed neutron sources. Unfortunately, beryllium is one of the most toxic elements in the periodic table. It is responsible for the often-fatal lung disease, Chronic Beryllium Disease (CBD) or berylliosis, and is listed as a Class A EPA carcinogen. Coal-fired power plants, industrial manufacturing and nuclear weapons production and disposal operations have released beryllium to the environment. This contamination has the potential to expose workers and the public to beryllium. Despite the increasing use of beryllium in industry, there is surprisingly little published information about beryllium fate and transport in the environment. This information is crucial for the development of strategies that limit worker and public exposure. This review summarizes the current understanding of beryllium health hazards, current regulatory mandates, environmental chemistry, geochemistry and environmental contamination.

Beryllium↗
PubMed2004

Beryllium medical surveillance at a former nuclear weapons facility during cleanup operations.

Despite increasing need to remediate beryllium-contaminated buildings in industry, little is known about the magnitude of risk associated with beryllium abatement or the merits of beryllium medical surveillance for cleanup workers. We examined beryllium lymphocyte proliferation tests and reviewed medical evaluations on workers at a nuclear weapons facility during the process of decontamination and decommissioning. Of 2,221 workers, 19 (0.8%) were beryllium sensitized based on two or more abnormal beryllium lymphocyte proliferation tests. Eight of 19 sensitized individuals underwent full clinical evaluation, of whom two were diagnosed with chronic beryllium disease (CBD). Notably, seven beryllium sensitized and CBD cases were hired after the start of cleanup operations. Beryllium medical surveillance detects sensitization and CBD in cleanup workers. Exposure controls and medical surveillance need to be 'broad-based' to include all cleanup workers involved in beryllium-contaminated building remediation.

Adolescent↗
PubMed2003

Beryllium detection in human lung tissue using electron probe X-ray microanalysis.

Chronic berylliosis is an uncommon disease that is caused by the inhalation of beryllium particles, dust, or fumes. The distinction between chronic berylliosis and sarcoidosis can be difficult both clinically and histologically, as both entities can have similar presentations and exhibit nonnecrotizing granulomatous inflammation of the lungs. The diagnosis of chronic berylliosis relies on a history of exposure to beryllium, roentgenographic evidence of diffuse nodular disease, and demonstration of beryllium hypersensitivity by ancillary studies, such as lymphocyte proliferation testing. Additional support may be gained by the demonstration of beryllium in lung tissue. Unlike other exogenous particulates, such as asbestos, detection of beryllium in human lung tissue is problematic. The low atomic number of beryllium usually makes it unsuitable for conventional microprobe analysis. We describe a case of chronic berylliosis in which beryllium was detected in lung tissue using atmospheric thin-window energy-dispersive X-ray analysis (ATW EDXA). A woman with a history of occupational exposure to beryllium at a nuclear weapons testing facility presented with progressive cough and dyspnea and a nodular pattern on chest roentgenograph. Open lung biopsy showed nonnecrotizing granulomatous inflammation that was histologically indistinguishable from sarcoidosis. Scanning electron microscopy and ATW EDXA demonstrated particulates containing beryllium within the granulomas. This application of EDXA offers significant advantages over existing methods of beryllium detection in that it is nondestructive, more widely available, and can be performed using routine paraffin sections.

Adult↗
PubMed1977

[A study on the effects of beryllium addition upon biological and physical properties of dental cobalt-chromium alloys (author's transl)].

The effects of beryllium addition to a dental cobalt-chromium alloy on biological compatibility as well as physical properties were examined and the following results were obtained. 1. Slight, but significant depression of the rates of cell multiplication was obtained with the experimental groups, i.e., alloy with no beryllium added as well as alloys with beryllium of up to 3.0 per cent by weight, compared to control group, which contained no alloys, but a glass disk. Within the experimental groups no significant difference in the rates of cell multiplication was found between the alloys with beryllium addition ranging from zero up to 2.0% by weight. However, alloy with 3.0% beryllium yielded slight, but significant depression of the rates of cell multiplication. Pure beryllium metal revealed severe cytotoxicity. 2. Cell morphology of the experimental groups confirmed the above results of the rate of cell multiplication. 3. Increase of beryllium within the alloys resulted in increase of tensile strength as well as Rockwell hardness, while elongation and fusion temperature were brought down. 4. Metallographs of alloys and cast specimens confirmed the results of the mechanical properties. The more beryllium was added, the smaller was the alloy crystal observed. 5. Loss of beryllium in the alloy was found during such procedures as melting each metal for making up alloys and casting. It is considered that the present results will be able to lend suggestions to beryllium use in dentistry with regard to biological compatibility as well as physical properties.

Animals↗
PubMed1989

Pathologic and immunologic alterations in early stages of beryllium disease. Re-examination of disease definition and natural history.

Beryllium lung disease is a chronic granulomatous disorder in which a beryllium-specific immune response plays a central role. By using a measure of cellular immune response to beryllium salts, bronchoalveolar lavage (BAL), and lung biopsy, we have identified 12 new cases of beryllium disease. Each of these individuals had pathologic changes on biopsy, lymphocytic alveolitis on BAL, and positive BAL lymphocyte transformation tests (LTT) in response to beryllium sulfate. This group of patients was remarkable for its paucity of clinical findings. At initial evaluation, seven had no respiratory symptoms, and four had normal physical examinations. Five had no increase in interstitial markings on chest radiograph. In eight cases, flow rates and lung volumes were normal. Diffusing capacity for carbon monoxide was low in only one case, and oxygen exchange during exercise was normal in six of nine subjects studied. In addition to the 12 cases, we evaluated eight beryllium-exposed workers who had other (nonberyllium) lung diseases; two of these eight demonstrated beryllium sensitization based on BAL LTT. We conclude that use of fiberoptic bronchoscopy with transbronchial biopsy and BAL facilitates diagnosis of beryllium workers who have histopathologic and immunologic alterations consistent with chronic beryllium disease. These findings may precede frank clinical illness and physiologic impairment, having important implications for our understanding of the natural history of beryllium disease.

Adult↗
PubMed2001

Lung cancer case-control study of beryllium workers.

BACKGROUND: Cohort mortality studies have found elevated lung cancer mortality among beryllium-exposed workers, but none evaluated the association between beryllium exposure level and lung cancer risk. A nested case-control study of lung cancer within a beryllium processing plant was conducted to investigate the relationship between level of beryllium exposure and lung cancer. METHODS: Lung cancer cases were identified by mortality follow-up through 1992 of a cohort of male workers at a beryllium alloy production plant. Each of 142 lung cancer cases was age-race-matched to five controls. Calendar-time-specific beryllium exposure estimates were made for every job in the plant and were used to estimate workers' cumulative, average, and maximum exposures. The potential confounding effects of smoking were also evaluated. RESULTS: Lung cancer cases had shorter tenures and lower lifetime cumulative beryllium exposures than controls, but higher average and maximum exposures. However, after applying a 10- and 20-year lag, exposure metrics were higher for cases. Odds ratios in analyses lagged 20 years were significantly elevated for those with higher exposure compared to the lowest exposure category. Significant positive trends were seen with the log of the exposure metrics. Smoking did not appear to confound exposure-response analyses. CONCLUSION: Increased lung cancer among workers with higher lagged beryllium exposures and lack of evidence for confounding by cigarette smoking, provide further evidence that beryllium is a human lung carcinogen. Published 2001 Wiley-Liss, Inc.

Air Pollutants, Occupational↗
PubMed2006

Proteomic analysis of beryllium-induced genotoxicity in an Escherichia coli mutant model system.

Beryllium is the second lightest metal, has a high melting point and high strength-to-weight ratio, and is chemically stable. These unique chemical characteristics make beryllium metal an ideal choice as a component material for a wide variety of applications in aerospace, defense, nuclear weapons, and industry. However, inhalation of beryllium dust or fumes induces significant health effects, including chronic beryllium disease and lung cancer. In this study, the mutagenicity of beryllium sulfate (BeSO(4)) and the comutagenicity of beryllium with a known mutagen 1-methyl-3-nitro-1-nitrosoguanidine (MNNG) were evaluated using a forward mutant detection system developed in Escherichia coli. In this system, BeSO(4) was shown to be weakly mutagenic alone and significantly enhanced the mutagenicity of MNNG up to 3.5-fold over MNNG alone. Based on these results a proteomic study was conducted to identify the proteins regulated by BeSO(4). Using the techniques of 2-DE and oMALDI-TOF MS, we successfully identified 32 proteins being differentially regulated by beryllium and/or MNNG in the E. coli test system. This is the first study to describe the proteins regulated by beryllium in vitro, and the results suggest several potential pathways for the focus of further research into the mechanisms underlying beryllium-induced genotoxicity.

Beryllium↗
PubMed1986

Ferritin and in vivo beryllium toxicity.

Beryllium (Be+2), a divalent metal ion, is toxic to both man and animal. Although the molecular basis for its toxicity is unknown, it is well established that micromolar concentrations of beryllium specifically inhibit certain enzymes. Previous in vitro studies have shown that the presence of ferritin, an iron-storage protein, reactivated these enzymes by sequestering beryllium (Price and Joshi, 1984). In the present study we demonstrate in vivo that beryllium and zinc are bound by ferritin in greater amounts than Pb+2, Cu+2, and Cd+2. Beryllium did not induce the synthesis of metallothionein. In animals pretreated with an iron salt (ferric ammonium citrate, 40 mg/kg body wt), liver ferritin was elevated approximately five times and the toxicity of intravenously injected beryllium was significantly attenuated. Excretion and deposition studies suggested that iron salt treatment resulted in a reduction of liver beryllium. Thus the protection against beryllium toxicity by ferric ammonium citrate may be due to increased production of ferritin which binds beryllium and its subsequent elimination in the feces.

Animals↗
PubMed1995

Effects of meso-2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate on beryllium-induced biochemical alterations and metal concentration in male rats.

The effects of two chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane 1-sulfonate (DMPS) on the mobilization, distribution, hepatic and hematopoietic toxicity of beryllium were compared in male rats exposed to beryllium. Animals were exposed to beryllium nitrate (0.5 mg/kg, orally, daily 5 days/week) for 21 days. Twenty-four hours after the last dose they were injected with a chelating agent (DMSA or DMPS) (25 or 50 mg/kg, twice daily for 5 days). The administration of DMSA and DMPS at a dose of 50 mg/kg marginally elevated the fecal excretion of beryllium. DMPS was effective in depleting beryllium from the liver, spleen and kidneys. However, DMPS (50 mg/kg) results in the redistribution of beryllium to blood. Beryllium-induced inhibition of hepatic alkaline phosphatase and hepatic adenosine triphosphatase (ATPase) were restored considerably with the chelating agents. Also, hepatic and renal histopathological lesions were less marked in rats treated with DMPS (50 mg/kg) compared with those treated with beryllium per se and DMSA. These effects were more prominent at the 50-mg/kg dose of chelating agents than at 25 mg/kg. These results suggest that treatment with DMPS has some beneficial effects in experimental beryllium intoxication.

Animals↗
PubMed1996

Possible health risks from low level exposure to beryllium.

The first case of chronic beryllium disease (CBD) at the Rocky Flats Environmental Technology Site (Rocky Flats) was diagnosed in a machinist in 1984. Rocky Flats, located 16 miles northwest of Denver, Colorado, is part of the United States Department of Energy (DOE) nuclear weapons complex. Research and development operations using beryllium began at Rocky Flats in 1953, and beryllium production operations began in 1957. Exposures could have occurred during foundry operations, casting, shearing, rolling, cutting, welding, machining, sanding, polishing, assembly, and chemical analysis operations. The Beryllium Health Surveillance Program (BHSP) was established in June 1991 at Rocky Flats to provide health surveillance for beryllium exposed employees using the Lymphocyte Proliferation Test (LPT) to identify sensitized individuals. Of the 29 cases of CBD and 76 cases of beryllium sensitization identified since 1991, several cases appear to have had only minimal opportunistic exposures to beryllium, since they were employed in administrative functions rather than primary beryllium operations. In conjunction with other health surveillance programs, a questionnaire and interview are administered to obtain detailed work and health histories. These histories, along with other data, are utilized to estimate the extent of an individual's exposure. Additional surveillance is in progress to attempt to characterize the possible risks from intermittent or brief exposures to beryllium in the workplace.

Berylliosis↗
PubMed2003

Beryllium: genotoxicity and carcinogenicity.

Beryllium (Be) has physical-chemical properties, including low density and high tensile strength, which make it useful in the manufacture of products ranging from space shuttles to golf clubs. Despite its utility, a number of standard setting agencies have determined that beryllium is a carcinogen. Only a limited number of studies, however, have addressed the underlying mechanisms of the carcinogenicity and mutagenicity of beryllium. Importantly, mutation and chromosomal aberration assays have yielded somewhat contradictory results for beryllium compounds and whereas bacterial tests were largely negative, mammalian test systems showed evidence of beryllium-induced mutations, chromosomal aberrations, and cell transformation. Although inter-laboratory differences may play a role in the variability observed in genotoxicity assays, it is more likely that the different chemical forms of beryllium have a significant effect on mutagenicity and carcinogenicity. Because workers are predominantly exposed to airborne particles which are generated during the machining of beryllium metal, ceramics, or alloys, testing of the mechanisms of the mutagenic and carcinogenic activity of beryllium should be performed with relevant chemical forms of beryllium.

Air Pollutants, Occupational↗
PubMed2003

Dissolved beryllium in rainfall, stream and shallow groundwaters in the Upper River Severn catchments, Plynlimon, mid Wales.

This paper examines the temporal changes in dissolved beryllium in deposition (rainfall and cloud water), stream water and groundwater for the upper River Severn catchments at Plynlimon in mid-Wales. There are two main themes to the study. Firstly, time series records are examined to see if anomalous behaviour occurred during 1996, when remarkably high concentrations were unexpectedly observed in the UK lowland rivers (Neal, Sci Total Environ, 2003). The results show (a) Beryllium concentrations in rainfall and stream water remained low throughout the period (mean 0.02 and 0.07 microg l(-1) in rainfall and stream water, respectively) and were often less than the lowest quotable value for a single determination (0.05 microg l(-1)). (b) Beryllium concentrations in the streams declined between 1983 and 1996 from a mean of approximately 0.07 to a mean of 0.04 microg l(-1). This was followed by a brief increase in the autumn of 1995 (up to values of approx. 0.2 microg l(-1) and a more sustained increase to approximately 0.12 microg l(-1) from 1997 to the end of monitoring late in 1998. (c) Rainfall concentrations of Beryllium were indistinguishable from zero throughout most of the monitoring period although concentrations increased late in the study in line with patterns observed in the stream when concentrations averaged approximately 0.08 microg l(-1). (d) Beryllium concentrations are much lower than observed in the UK lowlands where concentrations as high as 29 microg l(-1) were recorded. For the exceptionally high values occurring in the lowlands, there was the potential for environmental damage to aquatic organisms such as fish at levels greater than approximately 1 microg l(-1). There are no potential problems for the upper River Severn. Secondly, while Neal et al., [J Hydrol, 136 (1992) 33-49] provided information on the hydrogeochemistry of beryllium in the upper River Severn using available information at that time (rainfall, cloud water, stemflow, throughfall and stream water), there was no information available on groundwater chemistry. Since the publication of Neal et al. [J Hydrol, 136 (1992) 33-49], such information is now available and this paper makes up this shortfall. The results show that beryllium concentrations in groundwater are typically approximately 2-3 times higher than those found within the streams (mean 0.14 microg l(-1), range 0.06-1.56 microg l(-1)). This feature probably reflects the increased leaching of beryllium from the bedrock. The findings presented in this study combined with the earlier information of Neal et al. [J Hydrol, 136 (1992) 33-49] are used to provide an overview on dissolved beryllium for the upper River Severn, the most complete and extensive record for the UK.

Animals↗
PubMed1989

Determination of the oxide layer thickness on beryllium metal particles.

The hypothesis was tested that beryllium metal particles have a uniformly thick surface coating of beryllium oxide and that smaller particles should have a higher oxide fraction by mass because they have a higher surface to volume ratio. The mass fraction of oxygen, physical density, and specific surface area were determined for size-fractionated samples of respirable beryllium metal particles. The largest particles analyzed (count median diameter 4.6 microns with geometric standard deviation 1.6) contained 7% +/- 1% beryllium oxide by mass; had a physical density of 1.90 +/- 0.02 g/cm3; and had a specific surface area of 4.0 +/- 0.3 m2/g. The smallest particles analyzed (count median diameter 0.4 micron with geometric standard deviation 1.8) contained 31% +/- 3% beryllium oxide by mass; had a physical density of 2.00 +/- 0.17 g/cm3; and had a specific surface area of 20.8 +/- 2.1 m2/g. These shifts in density and oxide content with size and surface area are consistent with a beryllium metal core of density 1.84 +/- 0.02 g/cm3 (1.848 g/cm3 is theoretical); a beryllium oxide layer of density of 2.53 +/- 0.16 g/cm3 (3.025 g/cm3 is the perfect crystalline density); and an oxide layer thickness of 49 +/- 4 A for all particle sizes. These results indicate that the inhalation toxicity of beryllium metal particles may be similar to that of beryllium oxide formed at low temperatures.

Berylliosis↗
PubMed1994

Compartmentalized immune response reflects clinical severity of beryllium disease.

Although beryllium disease has been associated with a bronchoalveolar lavage (BAL) lymphocytosis and T cell-mediated immune response, we do not know if either the BAL cellular profile or the compartmentalized pulmonary response to the antigen reflect the severity of the disease. We studied 110 subjects divided into three groups of subjects: beryllium disease patients (n = 55), beryllium-sensitized patients without disease (n = 8), and control subjects (n = 47). Evaluation included completion of a respiratory symptom questionnaire, clinical examination, chest radiograph, spirometry, body plethysmographic lung volumes, and diffusing capacity (DLCO). In the patient groups, we performed maximal exercise testing with an indwelling arterial line. In addition, we examined BAL and performed blood and BAL beryllium lymphocyte transformation tests (BeLT) as measures of the beryllium-specific T cell-mediated response in these two compartments. In beryllium disease patients we correlated the BAL cellular constituents with clinical parameters indicative of disease severity. Beryllium disease patients exhibited elevated numbers of white cells and lymphocytes in BAL compared with both other groups; however, this lymphocytic alveolitis was significantly obscured in smokers. The BAL cellular constituents correlated with BAL BeLT but not with the blood BeLT. BAL cellular constituents also correlated with the radiographic profusion of small opacities, FEV1/FVC, DLCO, maximal achievable work load, VO2max, and measures of gas exchange at rest and at maximum exercise. We conclude that the lymphocyte-predominant pulmonary inflammatory response in beryllium disease is related to the magnitude of the localized response to antigen and that BAL cellularity, differential cell count, and BeLT reflect beryllium disease clinical severity.(ABSTRACT TRUNCATED AT 250 WORDS)

Berylliosis↗
PubMed1993

Epidemiology of beryllium sensitization and disease in nuclear workers.

We examined the epidemiology of chronic beryllium disease among a stratified, random sample (n = 895) of nuclear weapons workers using the blood beryllium lymphocyte transformation (BeLT) test and chest radiograph for case identification. Of 18 new cases of beryllium sensitization, 12 had beryllium disease, and three more developed pulmonary granulomas on lung biopsy over the succeeding 2 yr. Beryllium-sensitized cases did not differ from noncases in age, gender, race, ethnicity, smoking, most respiratory symptoms, spirometric or radiographic abnormalities, or job tenure. The six sensitized cases without initial disease differed from beryllium disease cases in having greater pack-years of smoking. Sensitization occurred among workers with inadvertent or bystander exposure, such as a secretary and security guard. However, beryllium sensitization risk was higher for machinists (4.7%) and for persons reporting measured overexposure (7.4%, odds ratio 5.1); exposure beginning before 1970 (3.6%, odds ratio 2.7); consistent beryllium exposure (3.4%); and sawing (4.7%) or band sawing (6.0%) of beryllium metal. We conclude that both individual susceptibility to sensitization and exposure circumstances are important in developing disease.

Adult↗
PubMed1996

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.

Berylliosis↗
PubMed1983

Hygienic and toxicological aspects of occupational and environmental exposure to beryllium.

As the production of missile, nuclear devices and electronics grew and modern industrial technologies emerged the risk of the occupational exposure to beryllium has become increasingly common and widespread. The environmental burden of beryllium is also on the increase, not only as a result of emissions from plants producing and processing beryllium, or its alloys and compounds, but also from burning coal of higher beryllium content in some localities. This article discusses primarily the hygienic and toxicologic aspects of beryllium and its threat to human health. The following topics are included in this review: occurrence, production and uses of beryllium; its metabolism and experimental toxicology; clinical toxicology and pathogenesis of berylliosis; hygienic and epidemiologic aspects of berylliosis; berylliosis treatment and prevention. Berylliosis is here characterized as a disease combining clinical manifestations of pneumosclerosis, allergy to beryllium and, in its granulomatous form, autoimmune reactions. Importantly, the available technical means and measures can ensure that the both occupational and environmental exposure to beryllium can be kept below the established MAC values. If occasionally impossible, special preventive measures should be adopted. It is essential that all persons with allergy be prophylactically excluded from work at risk of exposure to beryllium.

Animals↗
PubMed2004

Screening for beryllium disease among construction trade workers at Department of Energy nuclear sites.

BACKGROUND: To determine whether current and former construction workers are at significant risk for occupational illnesses from work at the Department of Energy's (DOE) nuclear weapons facilities, screening programs were undertaken at the Hanford Nuclear Reservation, Oak Ridge Reservation, and the Savannah River Site. METHODS: Medical examination for beryllium disease used a medical history and a beryllium blood lymphocyte proliferation test (BeLPT). Stratified and multivariate logistic regression analyses were used to explore the risk of disease by age, race, sex, trade, duration of DOE employment, reported work in buildings where beryllium was used, and time since last DOE site employment. RESULTS: Of the 3,842 workers included in this study, 34% reported exposure to beryllium. Overall, 2.2% of workers had at least one abnormal BeLPT test, and 1.4% were also abnormal on a second test. Regression analyses demonstrated increased risk of having at least one abnormal BeLPT to be associated with ever working in a site building where beryllium activities had taken place. CONCLUSIONS: The prevalence of beryllium sensitivity and chronic beryllium disease (CBD) in construction workers is described and the positive predictive value of the BeLPT in a population with less intense exposure to beryllium than other populations that have been screened is discussed. The BeLPT findings and finding of cases of CBD demonstrate that some of these workers had significant exposure, most likely, during maintenance, repair, renovation, or demolition in facilities where beryllium was used.

Berylliosis↗