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PubMed2004

Designer ligands for beryllium.

We report the rational design of ligands that selectively bind beryllium. We selected two ligands to design Be based on binding polynulear species with a Be-O-Be motif: 2-hydroxyisophthalic acid (HIPA) and 2,3-dihydroxybenzoic acid (DHBA). All previous work has focused on BeL or BeL2 species. The HIPA and DHBA have extremely high binding constants of 17.5 and 18.4, respectively. These ligands outcompete chromotropic acid, which has one the highest binding constants for Be reported in the literature for a simple BeL species. The binding of the second Be to form the Be-O-Be motif is so strong that polynuclear species predominates in solution down to micromolar concentrations. Both ligands show a fluorescence response in the presence of beryllium, making them promising candidates for fluorescence-based sensors. In the case of HIPA, there is a fluorescence shift, and in the case of DHBA, the presence of beryllium turns on the fluorescence by removing two OH bonds that otherwise lead to nonradiative decay. The most dramatic result is that DHBA selectively binds Be in the presence of a metal cocktail containing a 50-fold excess of Al, Fe, Cr, Cu, Zn, Cd, and Pb. This is the first time that such selectivity for beryllium has been demonstrated.

Berylliosis↗

PubMed2006

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.

Beryllium↗

PubMed2000

Beryllium in food and drinking water--a summary of available knowledge.

In an overall evaluation of the situation published by IARC in 1993, beryllium and beryllium compounds are identified as carcinogens to humans. This prompted the initiation of this study on beryllium which reviews the situation up to 1998 on the aspects: properties and applications, toxicity, analytical procedures for food and drinking water, reference materials, occurrence in food and drinking water and estimates of daily dietary exposure. Special emphasis is put on analytical aspects and levels of beryllium in food and drinking water.

Beryllium↗

PubMed2002

Beryllium and lung cancer: a reanalysis of a NIOSH cohort mortality study.

This analysis is motivated by recent reviews on the carcinogenicity of beryllium by the International Agency for Research on Cancer, the U.S. Environmental Protection Agency, and the American Conference of Governmental Industrial Hygienists, and reconsideration by the National Toxicology Program on its classification of the carcinogenicity of beryllium. It reanalyzes data from a 1992 publication of a cohort mortality study conducted by the National Institute of Occupational Safety and Health (NIOSH) of workers employed in seven plants producing beryllium in the United States (Ward et al., 1992). That publication reported an increased risk of lung cancer in these workers and concluded that it is most likely due to occupational exposure to beryllium compounds. This present report uses: (1) an adjustment for smoking based on more germane estimates of the association between smoking and mortality from lung cancer; (2) computations of expected lung cancer rates based on alternative comparison populations; and (3) an overall combined estimate of the findings from the individual plants based on meta-analysis. Our findings indicate lower and generally not statistically significant standard mortality ratios that are not compatible with the interpretation of a likely causal association.

Beryllium↗

PubMed1985

Aerosol resuspension from fabric: implications for personal monitoring in the beryllium industry.

The fabric used for work clothing at an industrial site can significantly influence personal monitor (PM) exposure estimates because dust resuspension from clothing can increase the concentration at the sampler inlet. The magnitude of the effect depends on removal forces and on the interaction of the contaminant particles with work garments. Aerosol deposition and resuspension on cotton and Nomex aramid fabrics was evaluated at a beryllium refinery. Electrostatically charged cotton backdrops collected more beryllium than neutral controls, but electronegative Nomex backdrops did not. Moving fabrics collected more beryllium than did stationary controls. When contaminated fabrics were agitated, PMs mounted 2.5 cm in front of the fabric collected more beryllium than monitors above the fabric, positioned to simulate the nose or mouth. The difference between the air concentrations measured by these PMs increased with Be loading and tended to level off for highly contaminated fabric. Cotton resuspended a larger fraction of its contaminant load than Nomex. These results are consistent with current knowledge of the behavior of particles on fabric fibers. Aerosol resuspension from garments is an important consideration in assessing inhalation exposure to toxic dusts. A garment may attract and retain toxic particles. This contamination is then available for later resuspension.

Aerosols↗

PubMed2007

Exposure to beryllium and occurrence of lung cancer: a reexamination of findings from a nested case-control study.

OBJECTIVE: Our aim was to reanalyze a nested case-control study of beryllium and lung cancer because we identified analysis and study design issues that could have led to the elevated odds ratios obtained in the study. METHODS: We reanalyzed the data using nontransformed exposure metrics instead of log-transformed metrics used in the publication. We identified and examined effects on estimated odds ratios of imbalances between cases and controls caused by the control selection method. RESULTS: This reanalysis found no elevated odds ratios for any exposure variable. CONCLUSION: : Our conclusions differ from the authors' interpretation that the findings are due to a causal relationship between beryllium exposure and lung cancer. Our alternative explanation is that they may be due to methodological problems that could have been controlled by closer matching of controls to cases. CLINICAL SIGNIFICANCE: This study challenges conclusions made from a large case-control study concerning beryllium-lung cancer associations. Occupational medicine practitioners may want to integrate findings from this study into advice they give beryllium-exposed workers concerned about lung cancer.

Beryllium↗

PubMed1998

Development of a high-power water cooled beryllium target for use in accelerator-based boron neutron capture therapy.

In order for ABNCT (accelerator-based boron neutron capture therapy) to be successful, 10-16 kW or more must be dissipated from a target. Beryllium is well suited as a high-power target material. Beryllium has a thermal conductivity of 200 W/mK at 300 K which is comparable to aluminum, and it has one of the highest strength to weight ratios of any metal even at high temperatures (100 MPa at 600 degrees C). Submerged jet impingement cooling has been investigated as an effective means to remove averaged power densities on the order of 2 x 10(7) W/m2 with local power densities as high as 6 x 10(7) W/m2. Water velocities required to remove these power levels are in excess of 24 m/s with volumetric flow rates of nearly 100 GPM. Tests on a prototype target revealed that the heat transfer coefficient scaled as Re0.6. With jet-Reynolds numbers as high as 5.5 x 10(5) heat transfer coefficients of 2.6 x 10(5) W/m2K were achieved. With this type of cooling configuration 30 kW of power could be effectively removed from a beryllium target placed on the end of an accelerator. A beryllium target utilizing a proton beam of 3.7 MeV and cooled by submerged jet impingement could be used to deliver a dose of 13 RBE cGy/min mA to a tumor at a depth of 4 cm. With a beam power of 30 kW, 1500 cGy could be delivered in 14.2 min.

Beryllium↗

PubMed1978

Reversible respiratory disease in beryllium workers.

A medical and environmental survey was carried out in a beryllium extraction and processing plant in 1971, and a follow-up study was done in 1974. Peak air concentrations of beryllium of as much as 50 times the accepted peak limit value were found in the plant in 1971. Radiographic changes of interstitial disease were found in 31 workers, hypoxemia was found in 20, and in 11 workers a combination of hypoxemia and radiographic changes of interstitial disease was seen. Follow-up in 1974 showed that air concentrations had all decreased significantly, mainly because of improvements in engineering and ventilation in the plant. Improvement in hypoxemia and decreased alveolar-arterial O2 tension difference at rest ([A-a]DO2) were noted in 13 of the 20 men who had hypoxemia in 1971 and were available for follow-up. In addition, radiographic abnormalities of interstitial disease were reversed in some workers. Our results suggest that improvement in gas exchange and radiographic findings of interstitial disease occurs when peak air concentrations of beryllium are decreased. Our approach in combining environmental and medical screening in workers exposed to beryllium enabled us to identify persons with early changes, to detect reversible abnormalities, and to correlate air concentrations with the medical status of workers.

Adult↗

PubMedDate not supplied

Particle size distribution and respiratory deposition estimates of beryllium aerosols in an extraction and processing plant.

The mass size distribution of beryllium aerosols generated in the various operational areas of a typical extraction and processing plant was studied using an eight-stage impactor sampler. The total concentration of beryllium in the plant was found to be well below the threshold limit value. The mean value of mass median aerodynamic diameter of beryllium particles observed for various operations ranged from 5.0-9.5 microm. The alveolar deposition for various operational areas was estimated to be 3-5% for nasal breathing and 9-13% for oral breathing based on the International Commission on Radiological Protection (ICRP) human respiratory tract model. Deposition during oral breathing was higher than during nasal breathing by approximately a factor of two to three. This study on exposure characterization was useful for reducing the respirable fraction of beryllium aerosol by optimizing the capture velocity and improving the quality of other control measures.

Aerosols↗

PubMed2000

Government laboratory worker with lung cancer: comparing risks from beryllium, asbestos, and tobacco smoke.

Occupational medicine physicians are frequently asked to establish cancer causation in patients with both workplace and non-workplace exposures. This is especially difficult in cases involving beryllium for which the data on human carcinogenicity are limited and controversial. In this report we present the case of a 73-year-old former technician at a government research facility who was recently diagnosed with lung cancer. The patient is a former smoker who has worked with both beryllium and asbestos. He was referred to the University of California, San Francisco, Occupational and Environmental Medicine Clinic at San Francisco General Hospital for an evaluation of whether past workplace exposures may have contributed to his current disease. The goal of this paper is to provide an example of the use of data-based risk estimates to determine causation in patients with multiple exposures. To do this, we review the current knowledge of lung cancer risks in former smokers and asbestos workers, and evaluate the controversies surrounding the epidemiologic data linking beryllium and cancer. Based on this information, we estimated that the patient's risk of lung cancer from asbestos was less than his risk from tobacco smoke, whereas his risk from beryllium was approximately equal to his risk from smoking. Based on these estimates, the patient's workplace was considered a probable contributing factor to his development of lung cancer.

Aged↗

PubMed1981

The carcinogenicity of beryllium.

Beryllium, some of its alloys, and a variety of its compounds have induced malignant tumors of the lung and osteogenic sarcoma in experimental animals. Three animal species, monkeys, rabbits, and rats, have been shown to be susceptible. Beryllium induces morphological transformation in mammalian cells and enhances viral transformation of mammalian cells. It has been shown to decrease fidelity of DNA synthesis. It has been recognized that exposure to compounds of this metal will, in some individuals, result in a chronic granulomatous disease of the lung. A series of overlapping recent human epidemiological studies have been suggestive of an increase in the incidence of lung cancer in populations occupationally exposed to beryllium. Such studies, together with animal and in vitro studies, argue for the strong presumption of a carcinogenic hazard to man in occupational beryllium exposures.

Animals↗

PubMed2006

Determination of beryllium in solid samples by flame atomic absorption spectrometry after preconcentration on activated carbon.

It is generally supposed that the preconcentration procedure is used for the determination of metal concentrations under the sensitivity of the measurement method. This study showed that preconcentration is also need for the beryllium (Be) concentration over the sensitivity of atomic absorption spectrometry. For this purpose, a simple and selective method for the determination of Be in solid samples is modified. The method is based on the preconcentration of the complexes of beryllium-acetylacetone plus morin, oxine, PAN and PAR on activated carbon at different pH values. The adsorbed beryllium was eluted with aqua regia and measured by flame atomic absorption spectrometry (FAAS). Recoveries of up to 85% were achieved. For removing chemical interferences and applying the method to Be determination in solid samples, the masking studies and reproducibility were examined. The detection limit was found to be 0.12 ng mL(-1). The relative sandard deviations (RSD) were found to be 8% for 60 mL of 10.0 ng mL(-1) using 10 replicate enrichment procedures. Beryllium concentrations in the studied solid samples were found in the range of 0.28 - 3.95 mg kg(-1).

Beryllium↗

PubMed1999

Identification of pathogenic T cells in patients with beryllium-induced lung disease.

Chronic beryllium disease (CBD) is caused by beryllium exposure and is characterized by granulomatous inflammation with accumulation of CD4+ T cells in the lung. We analyzed TCR beta-chain and alpha-chain genes expressed by these CD4+ T cells. In the lungs of individual patients, as well as among four of five CBD patients studied, different oligoclonal expansions within the Vbeta3 subset were found to express homologous or even identical CDR3 amino acid sequences. These related expansions were specific for CBD patients, were compartmentalized to lung, and persisted at high frequency in patients with active disease. Limiting dilution cloning and analysis of coexpressed TCR alpha-chain genes confirmed that these TCRs were selectively expanded by a common Ag involving beryllium. Overall, homologous TCR beta- and alpha-chains showed identical V regions and invariant charged residues within the CDR3 but considerable variability in TCRJ usage. Remarkably, CBD patients expressing nearly identical TCRs did not share common HLA-DRB1 or DQ alleles. These results implicate particular CD4+ cells in the pathogenesis of CBD and provide insight into how beryllium is recognized in human disease.

Amino Acid Sequence↗

PubMed2002

Role of chelating agents and antioxidants in beryllium induced toxicity.

The present study was conducted to evaluate the therapeutic effectiveness of chelating agents [glutathione, 2,3 dimercapto propane sulfonic acid (DMPS) and D-penicillamine (DPA)] in combination with antioxidant (sodium selenite) in beryllium induced toxicity in female rats. A bolus dose of 50mg/kg-beryllium nitrate was administered singly followed by chelation therapy with GSH, DMPS + Se and DPA + Se at various durations of 1,3 and 7 days respectively. Results revealed a significant fall in the glycogen content, whereas, a marginal fall in the protein was also observed. The enzymatic activity of alkaline phosphatase and adenosine triphosphatase was depleted; on the contrary, there was a significant rise in the acid phosphatase and glucose-6-phosphatase pattern. A rise in the hepatic lipid peroxidation activity is a direct indication of oxidative damage resulting in free radical generation. The distribution of the metal by atomic absorption spectrophotometry revealed an increased concentration of beryllium in liver and kidney, followed by lung and uterus. The relative ability of three chelating agents to act as antagonists, for acute beryllium poisoning, have been examined in liver, kidney, lungs and uterus. The appreciable change in the beryllium concentration in various organs is duration dependent during the entire period being highly significant at 7 days regimen. Biochemical and distribution studies reveal that DPA + Se was the most effective therapeutic agent followed by DMPS + Se and GSH.

Animals↗

PubMedDate not supplied

[Safety criteria in working with metallic beryllium].

The concept of an acceptable risk was used to elaborate criteria required to analyze the safety of operations with metallic beryllium at dangerous industrial enterprises. To follow these criteria ensures the high level of beryllium work safety, follows the present-day tendency for the development of approaches to evaluating the safety of devices using toxically hazard substances. The criteria involve a human death risk due to the single entry of beryllium into the body during accidents, as well as the level of its chronic intake in different groups of subjects on secondary dust formation after an accident. The accident that occurred at the beryllium works, the industrial association "Ulbinsk Metallurgic Plant, in Ust-Kamenogorsk on September 12, 1990, has been analyzed by using the computer program "GAUSS". The results of calculations are in good agreement with those of observations.

Berylliosis↗

PubMed2005

[Determination of trace beryllium in geological samples by oxygen doped air-acetylene flame atomic absorption spectrometry].

A new method for the determination of trace beryllium in geological samples by oxygen-air-acetylene flame atomic absorption spectrometry is reported in the present paper. The optimum determination conditions were selected. When suitable amounts of 8-hydroxyquinoline are added, the interference effect from the coexisting elements can be minimized and the sensitivity for the determination of beryllium can be increased. The detection limit (k = 3) is 0.006 microg x mL(-1) for beryllium. The method has been applied to the determination of trace beryllium in geological standard samples, and the results are in good agreement with the certified values with a precision of 4.69% RSD( n = 8).

Acetylene↗

PubMed1977

[Behavior of various biochemical indices of liver efficiency and of selected blood serum electrolytes in workers exposed to beryllium].

In 30 workers being occupationally exposed to beryllium, examinations of biochemical indicators of liver efficiency were carried out: activity of alanine and asparagine aminotraspherase and basic phosphatases, cholinesterase, content of total protein and its fraction. Levels of electrolytes were determined: calcium, potassium, phosphorus, and magnesium. The above examinations were also carried out on 30 persons who have no contact with beryllium. The obtained results were subjected to statistical analysis. In 10 persons from the group exposed to beryllium one found lowering of the level of magnesium in blood serum, whereas in the control group the level of this electrolyte was correct in all persons. As to the results on the level of magnesium, in both groups high statistical significance was found (p less than 0,01). A dependence was found between the amount of workers and the lowered level of magnesium in blood serum and the duration of occupational exposure to beryllium. The comparison of the remaining results of examinations of both groups did not reveal any statistically significant differences or the differences were at the point of statistical significance.

Adult↗

PubMed1989

Cytochemical study of abnormal intranuclear structures rich in beryllium.

During prolonged intoxication with beryllium sulphate, intranuclear beryllium-rich structures (IBRS) develop mainly in the cells of the convoluted tubules of the kidney. These structures are constituted by the accumulation of dense granules approximately 20 nm in diameter. The present work shows: 1) by electron probe microanalysis that IBRS are rich in phosphorus and calcium, and 2) by high resolution ion microanalysis that the granules are rich in beryllium and proteins. Staining with thallium alcoholate and regressive staining with ethylenediaminetetraacetate (EDTA) seem to demonstrate the presence of ribonucleoproteins in the granules. But the richness in calcium and phosphorus makes it difficult to interprete cytochemical reactions based on thallium and lead because complexes can be formed between calcium and thallium or lead, and between phosphorus and lead. Extraction with EDTA and digestion with RNase carried out on floating slices fixed with glutaraldehyde and embedded in glycol methacrylate show that: 1) the positive response of IBRS to cytochemical techniques used seems due solely to calcium; 2) the RNase forms a stable complex with a constituent of the granules that could be the highly phosphorylated acidic protein that binds preferentially to beryllium described by Parker and Stevens.

Animals↗