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Environmental Health Perspectives Aug 1981Beryllium, 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... (Review)
Review
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.
Topics: Animals; Beryllium; Humans; Lung Neoplasms; Neoplasms; Occupational Diseases
PubMed: 7023926
DOI: 10.1289/ehp.8140101 -
Environmental Health Perspectives Oct 1996This report is based on 30 deaths from chronic beryllium disease (CBD) in the United Kingdom with details of 19 autopsies. The majority were fluorescent lamp workers and... (Review)
Review
This report is based on 30 deaths from chronic beryllium disease (CBD) in the United Kingdom with details of 19 autopsies. The majority were fluorescent lamp workers and machinists who died from respiratory failure. There were no cases of lung cancer. The survival times ranged from less than 1 to 29 years and was longest in machinists. All of the workers showed interstitial pulmonary fibrosis with varying degrees of cystic change. The majority showed hyalinized, and a few active sarcoid-type, granulomas. Extrathoracic granulomas, as in a U.K. sarcoid autopsy series, were rare. A notable difference was the absence of myocardial involvement in CBD compared to an incidence of 20% in the sarcoid autopsies. The detection of beryllium in the criteria for diagnosis is emphasized and the cases classified as definite include 12 of 19 positive analysis, 6 of 19, negative or unavailable analysis. The remaining case was classified as dubious because, despite a positive analysis, granulomas were absent. The main differential diagnosis is sarcoidosis.
Topics: Autopsy; Berylliosis; Chronic Disease; Humans; Lung; Registries; United Kingdom
PubMed: 8933040
DOI: 10.1289/ehp.96104s5949 -
Journal of Immunology (Baltimore, Md. :... Oct 2018Metal-induced hypersensitivity is driven by dendritic cells (DCs) that migrate from the site of exposure to the lymph nodes, upregulate costimulatory molecules, and...
Metal-induced hypersensitivity is driven by dendritic cells (DCs) that migrate from the site of exposure to the lymph nodes, upregulate costimulatory molecules, and initiate metal-specific CD4 T cell responses. Chronic beryllium disease (CBD), a life-threatening metal-induced hypersensitivity, is driven by beryllium-specific CD4 Th1 cells that expand in the lung-draining lymph nodes (LDLNs) after beryllium exposure (sensitization phase) and are recruited back to the lung, where they orchestrate granulomatous lung disease (elicitation phase). To understand more about how beryllium exposures impact DC function during sensitization, we examined the early events in the lung and LDLNs after pulmonary exposure to different physiochemical forms of beryllium. Exposure to soluble or crystalline forms of beryllium induced alveolar macrophage death/release of IL-1α and DNA, enhanced migration of CD80 DCs to the LDLNs, and sensitized HLA-DP2 transgenic mice after single low-dose exposures, whereas exposures to insoluble particulate forms beryllium did not. IL-1α and DNA released by alveolar macrophages upregulated CD80 on immature BMDC via IL-1R1 and TLR9, respectively. Intrapulmonary exposure of mice to IL-1R and TLR9 agonists without beryllium was sufficient to drive accumulation of CD80 DCs in the LDLNs, whereas blocking both pathways prevented accumulation of CD80 DCs in the LDLNs of beryllium-exposed mice. Thus, in contrast to particulate forms of beryllium, which are poor sensitizers, soluble or crystalline forms of beryllium promote death of alveolar macrophages and their release of IL-1α and DNA, which act as damage-associated molecular pattern molecules to enhance DC function during beryllium sensitization.
Topics: Allergens; Animals; Berylliosis; Beryllium; CD4-Positive T-Lymphocytes; Cell Differentiation; Cell Movement; Cells, Cultured; Chronic Disease; Dendritic Cells; Enzyme-Linked Immunospot Assay; Humans; Hypersensitivity; Immunization; Lung; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid Differentiation Factor 88; Receptors, Interleukin-1 Type I; Toll-Like Receptor 9
PubMed: 30185516
DOI: 10.4049/jimmunol.1800303 -
Journal of Environmental Monitoring :... Jun 2006Control of workplace exposure to beryllium is a growing issue in the United States and other nations. As the health risks associated with low-level exposure to beryllium... (Review)
Review
Control of workplace exposure to beryllium is a growing issue in the United States and other nations. As the health risks associated with low-level exposure to beryllium are better understood, the need increases for improved analytical techniques both in the laboratory and in the field. These techniques also require a greater degree of standardization to permit reliable comparison of data obtained from different locations and at different times. Analysis of low-level beryllium samples, in the form of air filters or surface wipes, is frequently required for workplace monitoring or to provide data to support decision-making on implementation of exposure controls. In the United States and the United Kingdom, the current permissible exposure level is 2 microg m(-3) (air) and the United States Department of Energy has implemented an action level of 0.2 microg m(-3) (air) and 0.2 microg/100 cm(2) (surface). These low-level samples present a number of analytical challenges, including (1) a lack of suitable standard reference materials, (2) unknown robustness of sample preparation techniques, (3) interferences during analysis, (4) sensitivity (sufficiently low detection limits), (5) specificity (beryllium speciation) and (6) data comparability among laboratories. Additionally, there is a need for portable, real-time (or near real-time) equipment for beryllium air monitoring and surface wipe analysis that is both laboratory-validated and field-validated in a manner that would be accepted by national and/or international standards organizations. This paper provides a review of the current analytical requirements for trace-level beryllium analysis for worker protection and also addresses issues that may change those requirements. The current analytical state of the art and relevant challenges facing the analytical community will be presented, followed by suggested criteria for real-time monitoring equipment. Recognizing and addressing these challenges will present opportunities for laboratories, research and development organizations, instrument manufacturers and others.
Topics: Accreditation; Beryllium; Laboratories; Occupational Exposure; Quality Control; Trace Elements
PubMed: 16767226
DOI: 10.1039/b601469k -
Environmental Health Perspectives Oct 1996The blood beryllium lymphocyte proliferation test (BeLPT) is an in vitro measure of the beryllium antigen-specific cell-mediated immune response. This response to... (Review)
Review
The blood beryllium lymphocyte proliferation test (BeLPT) is an in vitro measure of the beryllium antigen-specific cell-mediated immune response. This response to beryllium is now understood to play a central role in the immunopathogenesis of chronic beryllium disease (CBD). Although there remain some unresolved methodologic issues with testing, the blood BeLPT has already undergone sufficient development and field assessment to lead to a number of important conclusions: a) The BeLPT identifies beryllium sensitization and CBD earlier and better than any other clinical test presently available. b) The CBD cases identified with the blood test are clinically significant. c) A subset of the people identified by the BeLPT who do not yet have clinical disease will progress and require treatment with corticosteroids for impairing illness. d) The BeLPT can be used to improve clinical diagnostic accuracy and to correct mistaken diagnoses. e) The blood test can be used in screening large numbers of exposed workers because it is sensitive and specific and has high positive and negative predictive value for CBD. f) In every workforce studied to date, the BeLPT has identified beryllium sensitization and CBD that had been missed by conventional screening efforts. g) Worker populations that have been characterized using the BeLPT can help to elucidate the role of exposure genetics and dysregulated inflammation in the genesis of occupational lung disease.
Topics: Berylliosis; Beryllium; Chronic Disease; Humans; Lymphocyte Activation
PubMed: 8933041
DOI: 10.1289/ehp.96104s5953 -
Molecules (Basel, Switzerland) Apr 2021The aim of this article is to present results of theoretical study on the properties of C⋯M bonds, where C is either a carbene or carbodiphosphorane carbon atom and M...
The aim of this article is to present results of theoretical study on the properties of C⋯M bonds, where C is either a carbene or carbodiphosphorane carbon atom and M is an acidic center of MX2 (M = Be, Mg, Zn). Due to the rarity of theoretical data regarding the C⋯Zn bond (i.e., the zinc bond), the main focus is placed on comparing the characteristics of this interaction with C⋯Be (beryllium bond) and C⋯Mg (magnesium bond). For this purpose, theoretical studies (ωB97X-D/6-311++G(2df,2p)) have been performed for a large group of dimers formed by MX2 (X = H, F, Cl, Br, Me) and either a carbene ((NH2)2C, imidazol-2-ylidene, imidazolidin-2-ylidene, tetrahydropyrymid-2-ylidene, cyclopropenylidene) or carbodiphosphorane ((PH3)2C, (NH3)2C) molecule. The investigated dimers are characterized by a very strong charge transfer effect from either the carbene or carbodiphosphorane molecule to the MX2 one. This may even be over six times as strong as in the water dimer. According to the QTAIM and NCI method, the zinc bond is not very different than the beryllium bond, with both featuring a significant covalent contribution. However, the zinc bond should be definitely stronger if delocalization index is considered.
PubMed: 33920004
DOI: 10.3390/molecules26082275 -
Sangyo Eiseigaku Zasshi = Journal of... Mar 2021Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications... (Review)
Review
OBJECTIVES
Beryllium is primarily used in its metallic form, in alloys, or in beryllium oxide ceramics. Its physical and mechanical properties make it useful for many applications across a range of industries. Because beryllium is recognized as a sensitizing and carcinogenic agent, the management of occupational health for workers who may be occupationally exposed to beryllium has long been an important issue in the world. Under these circumstances, the U.S. Occupational Safety and Health Administration (OSHA) had published a rule in January 2017, to prevent the development of chronic beryllium disease and lung cancer. This rule strengthens the regulations governing the use of beryllium and its compounds. With the announcement of the OSHA rule in January 2017, the purpose of this study is to gain insight into the health problems and industrial hygiene associated with the use of beryllium and share the issues related to the management of occupational health for persons working with beryllium in Japan.
METHODS
We collected information regarding the beryllium industry, beryllium exposure, beryllium-induced health disorders, OSHA rule of January 2017, and regulations for beryllium use in Japan. After reviewing them, we discussed the issues concerning occupational health management of workers exposed to beryllium in Japan.
RESULTS
It has been reconfirmed that in recent years, the most serious health problem due to beryllium exposure is chronic beryllium disease caused by beryllium sensitization. Management of occupational health that emphasizes reduction of beryllium sensitization and early detection of beryllium-sensitized workers is important.
CONCLUSIONS
It was suggested that the following should be considered as the issues of management of occupational health of workers exposed to beryllium in Japan: (1) Collect epidemiologic data on health hazards from beryllium exposure in Japan. (2) Review the diagnostic items of special medical check-ups. (3) Review the definition of beryllium and its compounds in the Ordinance on Prevention of Hazards due to Specified Chemical Substances.
Topics: Berylliosis; Beryllium; Chronic Disease; Female; Humans; Japan; Lung Neoplasms; Male; Occupational Diseases; Occupational Exposure; Occupational Health; Workplace
PubMed: 32788509
DOI: 10.1539/sangyoeisei.2020-030-A -
Journal of the American Chemical Society Mar 2023The reactions of anionic aluminium or gallium nucleophiles {K[E(NON)]} (E = Al, ; Ga, ; NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di-butyl-9,9-dimethylxanthene) with...
The reactions of anionic aluminium or gallium nucleophiles {K[E(NON)]} (E = Al, ; Ga, ; NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di-butyl-9,9-dimethylxanthene) with beryllocene (BeCp) led to the displacement of one cyclopentadienyl ligand at beryllium and the formation of compounds containing Be-Al or Be-Ga bonds (NON)EBeCp (E = Al, ; Ga, ). The Be-Al bond in the beryllium-aluminyl complex [2.310(4) Å] is much shorter than that found in the small number of previous examples [2.368(2) to 2.432(6) Å], and quantum chemical calculations suggest the existence of a non-nuclear attractor (NNA) for the Be-Al interaction. This represents the first example of a NNA for a heteroatomic interaction in an isolated molecular complex. As a result of this unusual electronic structure and the similarity in the Pauling electronegativities of beryllium and aluminium, the charge at the beryllium center (+1.39) in is calculated to be less positive than that of the aluminium center (+1.88). This calculated charge distribution suggests the possibility for nucleophilic behavior at beryllium and correlates with the observed reactivity of the beryllium-aluminyl complex with -diisopropylcarbodiimide─the electrophilic carbon center of the carbodiimide undergoes nucleophilic attack by beryllium, thereby yielding a beryllium-diaminocarbene complex.
PubMed: 36786728
DOI: 10.1021/jacs.3c00480 -
Annals of Work Exposures and Health Oct 2019Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify...
OBJECTIVES
Peak beryllium inhalation exposures and exposure to the skin may be relevant for developing beryllium sensitization (BeS). The objective of this study was to identify risk factors associated with BeS to inform the prevention of sensitization, and the development of chronic beryllium disease (CBD).
METHODS
In a survey of short-term workers employed at a primary beryllium manufacturing facility between the years 1994-1999, 264 participants completed a questionnaire and were tested for BeS. A range of qualitative and quantitative peak inhalation metrics and skin exposure indices were created using: personal full-shift beryllium exposure measurements, 15 min to 24 h process-specific task and area exposure measurements, glove measurements as indicator of skin exposure, process-upset information gleaned from historical reports, and self-reported information on exposure events. Hierarchical clustering was conducted to systematically group participants based on similarity of patterns of 16 exposure variables. The associations of the exposure metrics with BeS and self-reported skin symptoms (in work areas processing beryllium salts as well as in other work areas) were evaluated using correlation analysis, log-binomial and logistic regression models with splines.
RESULTS
Metrics of peak inhalation exposure, indices of skin exposure, and using material containing beryllium salts were significantly associated with skin symptoms and BeS; skin symptoms were a strong predictor of BeS. However, in this cohort, we could not tease apart the independent effects of skin exposure from inhalation exposure, as these exposures occurred simultaneously and were highly correlated. Hierarchical clustering identified groups of participants with unique patterns of exposure characteristics resulting in different prevalence of BeS and skin symptoms. A cluster with high skin exposure index and use of material containing beryllium salts had the highest prevalence of BeS and self-reported skin symptoms, followed by a cluster with high inhalation and skin exposure index and a very small fraction of jobs in which beryllium salts were used. A cluster with low inhalation and skin exposure and no workers using beryllium salts had no cases of BeS.
CONCLUSION
Multiple pathways and types of exposure were associated with BeS and may be important for informing BeS prevention. Prevention efforts should focus on controlling airborne beryllium exposures with attention to peaks, use of process characteristics (e.g. the likelihood of upset conditions to design interventions) minimize skin exposure to beryllium particles, and in particular, eliminate skin contact with beryllium salts to interrupt potential exposure pathways for BeS risk.
Topics: Adult; Air Pollutants, Occupational; Benchmarking; Berylliosis; Beryllium; Cross-Sectional Studies; Female; Gloves, Protective; Humans; Inhalation Exposure; Male; Manufacturing and Industrial Facilities; Middle Aged; Occupational Exposure; Prevalence; Regression Analysis; Risk Factors; Skin; Young Adult
PubMed: 31504146
DOI: 10.1093/annweh/wxz064