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Micellanized spectrophotometric method for the determination of beryllium using haematoxylin.

A simple and sensitized spectrophotometric method for the determination of trace amounts of beryllium has been described. The method is based on the formation of a ternary complex by the reaction of beryllium with haematoxylin in the presence of micellar medium (cationic surfactant, cetyltrimethylammonium bromide). The ternary complex of beryllium has a maximum absorbance at 592 nm and showed an excellent sensitivity (molar absorption coefficient of 7.07 x 10(4)L mol(-1)cm(-1) and the Sandell's sensitivity being 1.27 x 10(-4) microg cm(-2)) and reproducibility (within-day precision: R.S.D.<or=0.36%, n=5, between-day precision: R.S.D.<or=0.65%, n=5). Linearity was achieved over the range 0.01-0.1 microg mL(-1) of beryllium with a correlation coefficient of 0.9999. The effect of foreign substances on the determination has been examined. The proposed procedure has been applied to the determination of beryllium in water samples.

Beryllium↗

Beryllium: an easily scavenged metal ion in the environment.

This study was specifically aimed to determine the levels of beryllium in environmental samples near the vicinity of the beryllium metal plant (BMP). Air particulate samples collected at the BMP site, in the non-monsoon and monsoon seasons, showed an average beryllium concentration of 0.3 and 0.1 ng m(-3) respectively, where as rain water samples showed the beryllium values in the range of 0.01-0.2 ng ml(-1). The suspended particulate matter (dust load) at the site studied was 570 and 250 microg m(-3) in the non-monsoon and monsoon seasons respectively. The results obtained show that, in the environment, 80% of the total beryllium present is removed by rain.

Beryllium↗

Inhibition of myosin ATPase by beryllium fluoride.

Inhibition of the myosin subfragment 1 (S-1) ATPase activity by beryllium fluoride was studied directly in the presence of MgATP and following preincubation of samples with MgADP. In both cases, the rates of inhibition were very slow, with kapp = 0.5 and 58 M-1 s-1, respectively, in analogy to the rates of inhibition of myosin ATPase by vanadate [Goodno, C. C. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 2620-2624]. The very different rates of inhibition in the presence of MgATP and on preincubation with MgADP suggested that beryllium fluoride binds to the M.ADP state of myosin. The slow inhibition rates and the nonlinear dependence of the observed rates on beryllium fluoride concentration were consistent with a two-step inhibition process involving a rapid binding equilibrium to yield a collisional complex, M.ADP.BeF3-, and its slow isomerization into M++.ADP.BeF3-. A third, much slower, step was required to account for the conversion of the stable M++.ADP.BeF3- to a virtually irreversibly inhibited complex. Kinetic description of the inhibition pathway was derived from the observed rates of inhibition of myosin ATPase, information on the binding of beryllium fluoride to M.ADP, and measurements of epsilon ADP chase from M++.epsilon ADP.BeF3-. The isomerization rate and equilibrium constants were 1.4 x 10(-2) s-1 and 50, respectively, and the overall binding constant of beryllium fluoride to M.ADP was 5 x 10(5) M-1. The inhibitory complex showed a 16% enhancement to tryptophan fluorescence of S-1 and a reduced quenching of epsilon ADP by acrylamide. It is concluded that M++.ADP.BeF3- is analogous to the M++.ADP.Vi and M**.ADP.Pi states of myosin.

Adenosine Diphosphate↗

Beryllium concentrations in ambient air and its source identification. A case study.

Beryllium concentrations in atmospheric particulate and soil samples in and around a Beryllium Processing Facility (BPF) have been measured. The mean air concentration level of beryllium in and around the fence line of the BPF is 0.48 +/- 0.43 ng m(-3) (n = 397) and is mostly influenced by diurnal and seasonal changes. The observed air concentration levels were well below the prescribed ambient air quality (AAQ) standard of 10 ng m(-3). The soil concentration levels of beryllium in the study area were found to be in the range of 1.42-2.75 microg g(-1). The mass median aerodynamic diameter (MMAD) of beryllium aerosols in ambient air was found to be 6.9 microm. Source identification using the Enrichment Factor (EF) approach indicates soil as the predominant contributory source for air concentrations at the site.

Aerosols↗

Onsite direct-read system for semi-quantitative detection of traces of beryllium on surfaces.

The present work describes a simple and reproducible direct-read system for onsite monitoring of beryllium on surfaces of work areas. It is based on the colorimetric reaction of beryllium with active ingredients deposited in a swab. A color comparator consisting of beryllium color chart was designed to enable the semi-quantitative determination of beryllium in surface samples. The system provides a minimum detection limit of 0.01 microg sample(-1). Metals tested for any interference effect include Al(3+), Ba(2+), Cd(2+), Cu(2+), Co(2+), Cr(3+), Cr(6+), Fe(3+), Hg(2+), Mg(2+), Ni(2+), Pb(2+), Ti(4+) and UO(2)(2+). Validation of the system showed no significant effect from metal interferences on the quantification of beryllium.

Beryllium↗

Beryllium competitively inhibits brain myo-inositol monophosphatase, but unlike lithium does not enhance agonist-induced inositol phosphate accumulation.

Despite limiting side-effects, lithium is the drug of choice for the treatment of bipolar depression. Its action may be due, in part, to its ability to dampen phosphatidylinositol turnover by inhibiting myo-inositol monophosphatase. Beryllium has been identified as a potent inhibitor of partially purified myo-inositol monophosphatase isolated from rat brain (Ki = 150 nM), bovine brain (Ki = 35 nM), and from the human neuroblastoma cell line SK-N-SH (Ki = 85 nM). It is over three orders of magnitude more potent than LiCl (Ki = 0.5-1.2 mM). Kinetic analysis reveals that beryllium is a competitive inhibitor of myo-inositol monophosphatase, in contrast with lithium which is an uncompetitive inhibitor. Inhibition of exogenous [3H]inositol phosphate hydrolysis by beryllium (IC50 = 250-300 nM) was observed to the same maximal extent as that seen with lithium in permeabilized SK-N-SH cells, reflecting inhibition of cellular myo-inositol monophosphatase. However, in contrast with that observed with lithium, agonist-induced accumulation of inositol phosphate was not observed with beryllium in permeabilized and non-permeabilized SK-N-SH cells and in rat brain slices. Similar results were obtained in permeabilized SK-N-SH cells when GTP-gamma-S was used as an alternative stimulator of inositol phosphate accumulation. The disparity in the actions of beryllium and lithium suggest that either (1) selective inhibition of myo-inositol monophosphatase does not completely explain the action of lithium on the phosphatidylinositol cycle, or (2) that uncompetitive inhibition of myo-inositol monophosphatase is a necessary requirement to observe functional lithium mimetic activity.

Animals↗

Effects of asbestos and beryllium on release of alveolar macrophage enzymes.

Rabbit alveolar macrophages were exposed in culture medium to asbestos, beryllium sulfate, and beryllium oxide. The specific activities of the lysosomal hydrolases, acid phosphatase beta-N-acetylglucosaminidase and beta-glucuronidase plus the glycolytic enzyme, phosphohexose isomerase were determined in the medium, whole-cell homogenates, mitochondrial fractions, and supernatant. These hydrolases increased significantly in the medium but not in the mitochondrial fraction of cells exposed to dusts. Asbestos and beryllium sulfate were highly cytotoxic for alveolar macrophages in vitro and the data suggested that these agents were not associated with an increase in enzyme synthesis but rather a direct cytotoxic effect at the macrophage membrane level. For induction of enzyme release in vitro, a higher concentration of beryllium oxide was needed when compared with asbestos and beryllium sulfate. The cytotoxicity and enzyme release induced by these agents may represent an important nonspecific mechanism by which they induce inflammation and perhaps local proliferation of fibroblasts.

Acetylglucosaminidase↗

Tumor necrosis factor alpha gene expression in human monocytic THP-1 cells exposed to beryllium.

Chronic beryllium disease, which results from occupational exposure to particulate beryllium, is characterized by the development of lung granulomas and progressive pulmonary fibrosis. Increased production of proinflammatory cytokines (e.g., tumor necrosis factor alpha and interleukin-1 beta) by pulmonary alveolar macrophages occurs in many chronic fibrotic lung diseases and is thought to contribute to the disease process. The purpose of the present study was to investigate cytokine production by human monocytic cells exposed to beryllium in vitro. The results indicated that such cells respond to beryllium ions in the presence of fluoride by accumulation of messenger ribonucleic acid for both tumor necrosis factor alpha and interleukin-1 beta. These findings suggest that inhaled beryllium may directly stimulate the production of these cytokines by alveolar macrophages in vitro.

Beryllium↗

Introduction to beryllium: uses, regulatory history, and disease.

Beryllium is an ubiquitous element in the environment, and it has many commercial applications. Because of its strength, electrical and thermal conductivity, corrosion resistance, and nuclear properties, beryllium products are used in the aerospace, automotive, energy, medical, and electronics industries. What eventually came to be known as chronic beryllium disease (CBD) was first identified in the 1940s, when a cluster of cases was observed in workers from the fluorescent light industry. The U.S. Atomic Energy Commission recommended the first 8-hour occupational exposure limit (OEL) for beryllium of 2.0 microg/m3 in 1949, which was later reviewed and accepted by the American Conference of Governmental Industrial Hygienists (ACGIH), the American Industrial Hygiene Association (AIHA), the American National Standards Institute (ANSI), the Occupational Safety and Health Administration (OSHA), and the vast majority of countries and standard-setting bodies worldwide. The 2.0 microg/m3 standard has been in use by the beryllium industry for more than 50 years and has been considered adequate to protect workers against clinical CBD. Recently, improved diagnostic techniques, including immunological testing and safer bronchoscopy, have enhanced our ability to identify subclinical CBD cases that would have formerly remained unidentified. Some recent epidemiological studies have suggested that some workers may develop CBD at exposures less than 2.0 microg/m3. ACGIH is currently reevaluating the adequacy of the current 2.0 microg/m3 guideline, and a plethora of research initiatives are under way to provide a better understanding of the cause of CBD. The research is focusing on the risk factors and exposure metrics that could be associated with CBD, as well as on efforts to better characterize the natural history of CBD. There is growing evidence that particle size and chemical form may be important factors that influence the risk of developing CBD. These research efforts are expected to provide data that will help identify a scientifically based OEL that will protect workers against CBD.

Berylliosis↗

Beryllium: a modern industrial hazard.

Beryllium exposure can cause a granulomatous lung disease in workers who develop a lymphocyte-mediated sensitization to the metal. Workers in diverse industries are at risk because beryllium's properties are critical to nuclear, aerospace, telecommunications, electronic, metal alloy, biomedical, and semiconductor industries. The occupational air concentration standard's failure to protect beryllium workers is driving many scientific and occupational health advances. These developments include study of bioavailability of different physicochemical forms of beryllium, medical surveillance to show effectiveness of skin protection in preventing sensitization in high-risk processes, gene-environment interaction, transgenic mice for use in experimental research, and risk-based management of industrial exposures in the absence of effective exposure-response information. Beryllium sensitization and disease prevention are paradigms for much broader public health action in both occupational and general population settings.

Air Pollutants, Occupational↗

Serum angiotensin converting enzyme activity in chronic beryllium disease.

Serum angiotensin converting enzyme (SACE) activity is used as a marker of sarcoidosis activity and severity, but in chronic beryllium disease (CBD) the studies of SACE give conflicting results. We examined SACE activity in 23 CBD patients, five patients with beryllium sensitization, and 25 beryllium-exposed control subjects. CBD patients underwent complete clinical evaluation, including physical examination, pulmonary function testing, exercise physiology testing, chest radiography, and bronchoscopy with bronchoalveolar lavage and biopsy. CBD SACE activity was systematically compared with these clinical markers of disease severity. Of CBD patients, 22% had elevated SACE activity. The test did not discriminate CBD patients from those in the beryllium-sensitized or beryllium-exposed groups. However, SACE activity in CBD correlated with the extent of pulmonary granulomatous inflammation as reflected by the symptom of breathlessness, the number of white cells in bronchoalveolar lavage (r = 0.44), the number of lavage lymphocytes (r = 0.58), the lavage lymphocyte percentage (r = 0.55), and the profusion of small opacities on chest radiograph (r = 0.41). The test-retest reliability of the assay was high (r = 0.84), as was the agreement between fresh and -70 degrees C frozen sera (r = 0.93). We conclude that SACE activity levels may reflect the extent of pulmonary granulomatous inflammation in CBD but that the test does not help discriminate disease from nondisease.

Adult↗

Mobilization and distribution of beryllium over the course of chelation therapy with some polyaminocarboxylic acids in the rat.

The efficacy of three common polyaminocarboxylic acids in the treatment of experimental beryllium intoxication was investigated in male rats. N-(2-hydroxyethyl) ethylene diamine triacetic acid (HEDTA) was more effective than calcium disodium ethylenediamine tetraacetic acid (CaNa2EDTA) in reducing the beryllium concentration of the blood, kidneys and spleen and reducing beryllium-induced inhibition of hepatic alkaline phosphatase activity. HEDTA was also most effective in reducing histopathological lesions in the liver and spleen. Compared to these two chelators, the third amino chelator, calcium trisodium diethylene triaminepenta acetic acid (CaNa3DTPA) produced severe deleterious effects in the liver and systemic toxicity. The results suggest that HEDTA is a promising chelator for beryllium toxicity while DTPA enhances the toxic manifestation of beryllium.

Animals↗

Proper use of beryllium-containing alloys.

BACKGROUND: To assist dentists in providing a safe and healthful workplace, the ADA Council on Scientific Affairs developed this advisory statement on the proper use of beryllium-containing alloys in the dental operatory and laboratory. OVERVIEW: Recommendations are made for reducing the potential risk of beryllium exposure for employees working in dental operatories or laboratories who fabricate or manipulate beryllium-containing alloys in dental prostheses. CONCLUSIONS AND PRACTICE IMPLICATIONS: The Council recommends that practitioners adhere to the Ocupational Safety and Health Administration's recommendations for reducing beryllium exposure in the dental operatory and laboratory. These include the recommendation that--where possible--practitioners use alloys that do not contain beryllium in the fabrication of dental prostheses.

Beryllium↗

Beryllium skin patch testing to analyze T cell stimulation and granulomatous inflammation in the lung.

Chronic beryllium disease (CBD) is characterized by granulomatous inflammation and the accumulation of CD4(+) T cells in the lung. Patch testing of CBD patients with beryllium sulfate results in granulomatous inflammation in the skin. We investigated whether the T cell clonal populations present in the lung of CBD patients would also be present in the involved skin of a positive beryllium patch test and thus mirror the granulomatous process in the lung. CBD patients with clonal TCR expansions in bronchoalveolar lavage (BAL) were selected for study. All three CBD patients studied had a positive response to beryllium sulfate application and a negative patch test to normal saline. Immunohistochemistry showed extensive infiltration with CD4(+) T cells and few, if any, CD8(+) T cells both at 3 days and at later times when granulomas were apparent. T cell infiltration early after skin testing appeared to be nonspecific with the TCR repertoire of infiltrating T cells being distinct from that present in BAL. At later times when granulomas were present, T cell clones in skin overlapped with those in BAL in all patients tested. Total TCR matches in skin and BAL were as high as 40% in selected Vbeta T cell subsets. Studies of peripheral blood T cells before and after patch testing provided evidence for mobilization of large numbers of pathogenic beryllium-reactive T cells into the circulating pool. These studies using skin patch testing provide new insight into the dynamics of T cell influx and mobilization during granulomatous inflammation.

Amino Acid Sequence↗

[Limits of beryllium detection with laser microprobe mass spectrometry (LAMMS)].

Search for beryllium (Be) in tissues or urine in suspected beryllium disease is often disappointing due to inferior sensitivity of the methods employed. We evaluated the clinical use of laser microprobe mass spectrometry (LAMMS) for measurement of Be and detected the metal to a minimum concentration of 1 microM. We then investigated the biological relevance of this concentration. We looked at the alveolar macrophages in 7 patients subsequent to an incubation period of 24 h as well as peripheral blood mononuclear cells (PBMNC) and various cell lines with and without addition of beryllium sulfate (BeSO4). We also investigated skin biopsies of two patients 28 days after intracutaneous injections of BeSO4 (beryllium skin testing) and alveolar macrophages of A/J mice at various time intervals after a beryllium sensitisation protocol and a single intratracheal injection of BeSO4 (maximum interval: 15 weeks). Be was not defectable in native patient alveolar macrophages (AM), but in 6 of 7 cases after coincubation with BeSO4. There was no significant Be signal in any analysed PBMNC sample or cell line--even after coincubation with Be--or in the skin probes. Murine AM, however, had incorporated significant amounts of Be, which were detectable until the end of the experiments 15 weeks later. We conclude that concentrations of Be in acute disease (here, inoculation of Be in mice) exceed 1 microM and are thus detectable by LAMMS. On the other hand, concentrations in chronic processes (in this cosar, skin testing) are below the detection limits of LAMMS. Further results suggest compartmentalisation of the immune processes induced by Be because the alveolar macrophages were able to incorporate Be while PBMNC were not and because AM--at least in the animal experiments--seem to store Be intracellularly.

Adult↗

[Beryllium--underestimated occupational health hazard in Poland].

Beryllium is a metal used in different branches of industry. Inhalation is the most common way of exposure. Beryllium shows a high affinity to the lung tissue. It may act as toxic, carcinogenic and immunological agent. Chronic beryllium disease (CDB) is very difficult to diagnose because of its similarity to sarcoidosis. The lymphocyte proliferation assay is a very helpful test in CBD diagnosis. It seems reasonable to include this test into the body of the standard diagnostic procedures in workers exposed to beryllium. Early detection of hypersensitivity to beryllium, before CBD symptoms occur will allow to minimize adverse health effects.

Berylliosis↗

Comparative effectiveness of CaNa3DTPA and tiron along with alpha-tocopherol against beryllium-induced biochemical alterations in rats.

The therapeutic efficacy of chelating agents CaNa3DTPA (calcium trisodium diethylene triamine penta acetic acid) and Tiron (sodium-4,5-dihydroxy-1,3-benzene disulphonate) with and without antioxidant, alpha-Tocopherol was evaluated in the treatment of beryllium-induced toxicity in female albino rats. The animals were exposed to beryllium (as beryllium nitrate) at a dose of 1 mg/kg (ip) once a day for 28 consecutive days followed by chelation therapy by CaNa3DTPA (0.1 mM/kg, ip) and Tiron (471 mg/kg, ip) with and without alpha-Tocopherol (25 mg/kg, orally) for 5 consecutive days after toxicant administration. Tissue biochemistry revealed severe alterations in liver and kidney. A significant fall in total protein and glycogen contents, alkaline phosphatase, adenosine tri-phosphatase and succinic dehydrogenase level was noticed. On the contrary, an elevation in acid phosphatase was recorded. The significant rise in hepatic lipid peroxidation and decreased level of hepatic reduced glutathione showed toxicity due to beryllium. CaNa3DTPA with alpha-Tocopherol showed moderate therapeutic efficacy while Tiron in combination with alpha-Tocopherol exerted statistically more beneficial effects to reverse biochemical alterations in different variables altered due to beryllium intoxication.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

[Effect of beryllium salts on the activity of sarcoplasmic reticulum Ca2+,Mg2+-dependent ATP-ase].

In the presence of Mg2+ and Ca2+ ions beryllium compounds inhibit the Ca2+, Mg2+-dependent ATPase activity and the transport of Ca2+ in the sarcoplasmatic reticulum vesicles. The inhibition is reversible and concurrent with respect to the Mg2+ ions. In the absence of the Mg2+ ions an addition of beryllium compounds stimulates the ATPase activity, the dependence of the degree of its stimulation on the beryllium compounds concentration is characterized by a curve with a maximum. On the membranous Ca2+, Mg2+-dependent ATPase preparations beryllium compounds produce a stronger inhibiting effect than in the case of the purified enzyme, which is, apparently, due to their ability to influence the membranous structure. The hydrophobic spin probe method shows that beryllium compounds reduce the microviscosity of the lipid sections of the membrane.

Animals↗